1
Introduction

A Concise History of Physics in Healthcare

With every advancement in science and technology, there have been curious minds trying to apply the knowledge learnt to the human body; attempting to understand the hidden secrets of nature. The following is a brief timeline of these significant milestones, that have helped shape medical physics that we know and love today:

BC Before Christ

AD Anno Domini

An interesting point to note is that physicists are not involved in clinical use, because as soon as a medical instrument/device is applied it becomes a doctors field and expertise

At the start of the twentieth century hospital physicists were mainly employed in radiotherapy and radiation protection. In the UK during 1932, only 10 - 12 hospital physicists existed and now this has grown to over 1500 physicists in 2010.

The reason for this exponential growth in numbers is the rapid advancement in new imaging and clinical measurement techniques briefly discussed above. As a result various bodies have been founded:

• Hospital Physicists’ Association (HPA) in 1943.
• Biological Engineering Society (BES) in 1960.
• Institute of Physics and Engineering in Medicine (IPEM) in 1995. It is a charity, learned society and professional body with over 4000 members. They strive to ‘promote for the public benefit the advancement of physics and engineering applied to medicine and biology and to advance public education in this section’

In 2000, medical physicists and clinical engineers were regulated as ‘clinical scientists’, and became a fully-fledged healthcare profession.

The Scope of Medical Physics

With the quick progression of medical physics a lot of new areas have arisen, and now medical physicists have a large range of responsibilities ranging from a more physics based to a more engineering based:

RADIOTHERAPY

Radiotherapy is the treatment of disease (usually cancer) using very high doses of X-ray or particle radiation. The particular role medical physics plays is to:

• Develop new types of treatment
• Plan for new equipment and facilities
• Plan patient treatments
• Check that the dose given by treatment machines is correct
• Make sure radiation is used safely
• Maintain treatment machines

X-Rays & CT Scans

Medical physics also has a large involvement in imaging using x-rays and computed tomography:

• Specify new equipment to meet emerging clinical needs
• Assess the perforce of imaging equipment
• Maximise performance for minimum radiation dose

Nuclear Medicine

In nuclear medicine, radioactive materials can be used to obtain images of tissue function, or in larger quantities, to treat disease. With medical physics helping to:

• Introduce new techniques into clinical practice
• Acquire and process patient images
• Assess the performance and safety of imaging equipment
• Calculate radiation doses

MAGNETIC RESONANCE IMAGING MRI

MRI is structural and functional imaging using magnetic fields and radio waves instead of ionising radiation. The particular role medical physics plays is to:

• Develop new imaging techniques
• Plan for new equipment and facilities
• Optimise imaging protocols for patients
• Assess the performance and safety of imaging equipment

Clinical Engineering

Clinical engineering focus on:

• Management of medical equipment
• Engineering of technology for rehabilitation and assistance
• Measurement of the physiological systems of the body

Research and Development

Medical physicists can also dedicate their time to research and development:

• Development and application of new diagnostic and therapeutic techniques
• A strong focus on translational research
• Carried out in universities, industry and the NHS, often in partnership
• Highly interdisciplinary

Some other areas of medical physics include ultrasound, radiation protection, lasers and optical imaging.

WORKING IN HEALTHCARE

There are three main fields that medical physics and clinical engineering can take you into:

1. The NHS

Most large hospitals have a ‘Medical Physics and Clinical Engineering’ department. You need:

• A good degree in physics/engineering/related subject
• Three year vocational training, with a salary, including an integrated MSc
• Registration with the Health and Care Professions Council as a Clinical Scientist
• Opportunities for advancement to consultant level posts

2. Academia

There are over 30 UK universities active in medical physics/engineering research, many with international reputations. You need:

• Good degree in physics/engineering/related subject
• Supervised research for PhD
• Fundamental research that improves our understanding of biological or physical processes
• Applied research that improves our ability to diagnose, model or treat disease
• Publish findings in peer-reviewed journals and present results to scientific conferences
• Teach the next generation of physicists and engineers
• Communicate the impact of findngs to the public

3. Industry

Many leading companies have large UK facilities, and there are many specialist UK companies with innovations, for example in lasers, ultrasound and medical devices.

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Biological effects & Radiation units

Learning Objectives

• Benefits and detriments of ionising radiation
• Development of radiation protection
• Quantities and units used in radiation protection
• Deterministic and stochastic effects of ionising radiation
• Quantitation of radiation risk
• Principles of radiation protection

Ionising Radiation

Benefits

In 1896 a German physics professor, William Röntgen, found a new kind of ray which he called the ‘x-ray’. There was an immediate worldwide excitement and Henri Becquerel quickly discovered radioactivity a year later. Then on 26 December 1898, Marie Curie and her husband Pierre announced the existence of a new element, which they name ‘radium’. They were fascinated by its effects on destroying tumour cells faster than the surrounding healthy cells. And within a few years systems were being devised to treat cancer.

Early Radiology

In the beginning radiographs were initially made onto glass photographic plates, film wasn’t introduced until 1918 thanks to George Eastman. Right from the start x-rays were used as a therapy, for ailments such as skin lesions.

Early Radiotherapy

Many early radiologists tested the strength of their radiotherapy machines by using their own arms. If their skin turned pink then this was estimated to be the correct ‘erythema dose’ as they called it. Unfortunately, unaware at the time a lot of them ended up developing leukaemia from exposing themselves to so much radiation.

Alternative Therapies

Soon people started to think that radiation was a ‘wonder cure’ for everything and a whole host of alternative therapies arose:

• Quack cures: a whole host of products were created including radium toothpaste and radium suppositories ‘for restoring sexual power’
• Radium bread: bread was even made with radium water
• Fluoroscopic shoe fitting: fluoroscopy screens were used to see if shoes were the right size
• Thermal spring, (Pammukule, Turkey) is thought to have healing powers

Detriments

However with the increased popularity of radiation, it was soon discovered that an excess of radiation would not cure cancer and other ailments but end up having a detrimental effect on human health.

Eyes irritation

One of the first warnings of possible adverse side effects came from Thomas Edison, William J. Morton and Nikila Tesla who all reported independently of one another, eye irritations from experimentation from x-rays and fluorescent substances.

Skin pain swelling burns

Elihu Thomson, an American physicist, deliberately exposed one of his little fingers to an x-ray tube for several days (half an hour a day) and ended up experiencing pain, swelling, stiffness, erythema and blistering.

Development of Radiation Protection

As it became more and more apparent that radiation is harmful when used incorrectly, safety measures were slowly introduced to try and reduce the harmful effects of radiation.

Protective Clothing 1920

People start to use protection such as lead clothing.

Regulations introduced 1921

British x-ray and Radium committee introduces regulations:

• No more than 7 working hours / day
• Sundays and 2 half days off per week
• As much leisure time as possible spent out of doors
• Annual holiday of 1 month or 2 fortnights
• Nurses in x-ray and radium departments should not work elsewhere

First International Congress of Radiology 1925

Is a meeting of radiologists, where they can exchange their ideas and harmonies the international standards and practice of radiology. With the first meeting in London in 1925, it is still running today with its 29th meeting in Buenos Aires in 2016.

Röntgen unit introduced 1931

The Röntgen (R) is the amount of radiation to produce a certain amount of ionisation in a given volume of air.

First dose limit 1934

First dose limit. ICRP recommends a tolerance dose limit of: 0.2 rad/day (~ 500 mSv/y)

Stochastic effects 1950

Reports of increases in leukaemia and other cancers from bomb survivors and therapy patients. Risk extrapolates to zero dose (no safe dose).

Quantities & Units of Radiation

As soon as it became understood that radiation is harmful when not used carefully, ways of measuring its dose were calculated and here are three different types:

1. Absorbed dose Gy

This reflects the amount of energy that radioactive sources deposit in medium (e.g. water, tissue, air) through which they pass. The absorbed dose can be calculated with the following equation:

Units are in Grey (Gy, mGy, cGy), 1 grey = 1 joule per kg. Different absorbed doses can lead different effects.

Bone marrow syndrome 1 - 10 Gy

With a radiation exposure 1 - 10 Gy, symptoms can include:

• Leucopenia (reduction in the number of white blood cells)
• Thrombocytopenia (lower platelet count)
• Haemorrhage (escape of blood from a ruptured blood vessel)
• Infections

A therapy for this amount of exposure is using symptomatic transfusions of leucocytes and platelets, bone marrow translation and growth stimulating factors. Prognosis is excellent to uncertain with survival rates ranging from 10% to 100%.

Gastrointestinal Problems 10 - 50 Gy

With a radiation exposure 10 - 50 Gy, symptoms can include:

• Diarrhoea (the shits)
• Fever (raised body temperature)
• Electrolytic imbalance (an imbalance of electrolytes such as sodium, potassium, urea etc)

Palliative care would be recommended, this may include controlling the diarrhoea and fever as well as replacing lost electrolytes. If you are lucky some morphine. Prognosis is very poor, survival rate is 10%.

Central nervous syndrome > 50 Gy

With a radiation exposure greater than 50 Gy, you can expect to see the following symptoms:

• Cramps (painful involuntary contraction of muscle)
• Tremor (involuntary shaking)
• Ataxia (impaired movement)
• Lethargy (lack of energy)
• Impaired vision
• Coma (a prolonged state of deep unconsciousness)

Symptomatic treatment would be advised to ease the above symptoms. Prognosis is hopeless, with the survival rate being 0%.

Lethal dose 50/30

Is the dose which would cause death to 50% of the population in 30 days. Its value is about 2-3 Gy for humans for whole body irradiation.

Relative Biological Effectiveness RBE

RBE is the ratio of biological effectiveness of one type of ionising radiation relative to another, given the same amount of absorbed energy. See the graph below for a few examples:

Note: LET stands for Linear Energy Transfer

2. Equivalent dose Sv

This is a measure of the radiation dose to tissue where an attempt has been made to allow for the different relative biological effects of different types of ionising radiation. It is used to assess how much biological damage is expected from an absorbed dose, as different types of radiation have different damaging properties. Equivalent dose is calculated with the following equation:

Equivalent dose is measured in Sieverts (Sv, mSv) but REM (Roentgen Equivalent in Man) is commonly used as well, where 1 Sv = 100 REM.

3. Effective dose Sv

This determines how dangerous an individual’s exposure to radiation can be, by taking into consideration not only the nature of the incoming radiation but also the sensitives of the body parts affected.

Effective dose is measure in Sieverts (Sv, mSv) and below are some common tissue weighting factors:

A Few Calculations

Here are a few example calculations using the above principles:

• Whole body absorbed dose of 5 Gy = Whole body effective dose of 5 Sv
• Thyroid absorbed dose of 5 Gy = Whole body effective dose of 5 x 0.04 = 0.2 Sv
• Thyroid, lung & heart absorbed dose of 5 Gy = (5x0.4) + (5x0.12) + (5x0.12) = 1.4 Sv

Biological Effects of Radiation

Ionisation is the process by which an atom or a molecule acquires a negative or positive charge by gaining or losing electrons to form ions, and this is often caused by radiation. Ionising radiation can have potentially disastrous effects on our body at a cellular level, causing radiochemical damage by either direct or indirect action:

1. Direct action

Direct action occurs when alpha particles, beta particles or x-rays create ions which physically break the sugar phosphate backbones or the weak hydrogen bonds holding together the base pairs of the DNA. However, heavy charged particles (alpha particles) have a greater probability of causing direct damage compared to the low charged particles (x-rays) which cause most of the damage by indirect effects.

2. Indirect action

Indirect action is when ionising radiation effects other biological molecules such as water. It can impair or damage cells indirectly by creating free radicals which are highly reactive due to the presence of unpaired electrons on the molecule.

Radical Formation

H₂O + Radiation H₂O⁺ + e^-

Free radicals may form compounds, such as hydrogen peroxide, which could initiate harmful chemical reactions within the cells.

Recombinant compounds

H₂O   OH   H₂O₂

Following these chemical changes cells may undergo a variety of different processes.

Reparation after exposure

Once damaged DNA usually usually repairs itself through a process called excision, this process has three main steps:

1. Endonucleases cut out the damaged DNA
2. DNA polymerase resynthesises the original DNA
3. DNA ligase repairs the sugar phosphate backbone

Unfortunately this method is not fool-proof and sometime DNA is incorrectly repaired. This can either lead to cell death or a mutation (either a substitution or a frameshift). And occasionally this could lead to the formation of cancer.

Forms of damage

With any exposure to radiation there is a risk that damage can occur and there are three main types:

• Genetic Damage
• Somatic Damage (formation of cancer)
• Teratogenic Damage (malformation of an embryo)

Classification of effects

The biological effects of radiation can be classified in two ways, deterministic and stochastic:

Deterministic direct effect

Deterministic effects describe a cause and effect relationship between radiation and some side-effects. They are also called non-stochastic effects to contrast their relationship with the chance-like stochastic effects, e.g. of cancer induction.

Deterministic effects have a threshold below which, the effect does not occur. The threshold may be very small and may vary from person to person. However, once the threshold has been exceeded, the severity of an effect increases with dose. Some examples of deterministic effects include:

• Skin erythema 2-5 Gy
• Irreversible skin damage: 20-40 Gy
• Hair loss: 2-5 Gy
• Sterility 2-3 Gy
• Cataracts: 5 Gy
• Lethality (whole body): 3-5 Gy
• Fetal abnormality: 0.1-0.5 Gy

Note: Doses given at absorbed dose

Stochastic occur by chance

Stochastic effects occur by chance. Cancer induction as a result of exposure to radiation occurs in a stochastic manner aS there is no threshold point and risk increases in a linear-quadratic fashion with dose. This is known as the linear-quadratic no threshold theory. Although the risk increases with dose, the severity of the effects do not; the patient will either develop cancer or they will not.

Determining Stochastic Risk

You can determine stochastic risk by creating epidemiological studies using risk data form:

• Occupational risk data such as dial painters, uranium miners, early radiologists
• Medical risk data such using fluoroscopy to diagnose TB, mammography (breast screening), therapy of ankylosing spondylitis (spinal arthritis), ringworm or artificial menopause.
• Fallout risk data from atomic bombs (Hiroshima and Nagasaki) and other nuclear disasters such as Chernobyl.

You can quantify this risk, for example the medical radiation risk (at 5% per Sv) in the table below:

Framework for Radiation Protection

The following are three fundamental principles of radiation protection, taken from the ICRP (International Commission on Radiological Protection) system:

Justification Radiation is harmful

The principle of justification requires that any decision that alters the radiation exposure situation should do more good than harm; in other words, the introduction of a radiation source should result in sufficient individual or societal benefit to offset the detriment it causes.

Optimisation Stochastic effects

The principle of optimisation requires that the likelihood of incurring exposures, the number of people exposed and the magnitude of their individual exposure should all be kept as low as reasonably achievable, taking into account economic and societal factors. In addition, as part of the optimisation procedure, the ICRP recommends that there should be restriction on the doses to individuals from a particular source and this leads to the concept of dose constraints.

Limitation Deterministic effects

The third principle of the ICRP’s system of protection is that of dose limitation. This principle requires that the dose to individuals from planned exposure situations, other than medical exposure of patients, should not exceed the appropriate limits recommended by the Commission.

Example Problem

Following a malfunction in the cooling circuit of an experimental nuclear reactor there was a catastrophic failure leading to an explosion. A monitoring station on the periphery of the reactor site at a distance of 100m from the reactor showed that the whole body absorbed dose to an individual at that point would have been 20 Gy from the initial radiation burst after the explosion. Other monitoring instruments indicated that the radiation in the burst was comprised 70% gammas and 30% neutrons.

Material vaporised during the explosion entered the atmosphere where it was distributed widely by the prevailing Westerly wind. Monitoring stations at 500m from the reactor recorded the absorbed dose to the lungs following inhalation of particulates from the plume. These particulates comprised 90% gamma-emitting isotopes and 10% alpha-emitting isotopes.

In the direction of the wind the total lung absorbed dose would have been 10 Gy. Individuals at the same distance from the reactor but at 900 to the wind direction would have received only 30% of this absorbed dose to the lungs. Individuals at 500m and in the opposite direction to the wind would receive no absorbed dose from particulates in the plume.

Make an estimate of the percentage increase in cancers expected in populations at distances of 1000, 2000 and 3000m from the reactor at the four cardinal points of the compass. Fully describe each step taken in reaching your answers.

You can assume that the inverse square law applies to both the initial radiation burst and the subsequent distribution of the plume. Also assume that the radiation weighting factor for neutrons is 2 and for alpha particles, 20. The only significant organ dose following inhalation is to the lungs.

Solution

Solution coming soon

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X-RAY DIAGNOSTIC IMAGING

Learning Objectives

• Production of x-rays
• Forming x-ray images
• Advanced imaging techniques
• Digital imaging

X-RAY TUBE

The Basics

A basic x-ray tube is formed of a cathode filament, an anode metal target enclosed in an evacuated glass bowl. There is also a shield which encloses this again, with only a small window to allow x-rays to pass through.

Current is applied through the filament, and there is thermionic emission of electrons from the filament. Then a high voltage is applied across that, causing electrons to flow across to the target leading to the emission of x-rays.

kV Control Circuit

The HV Rectifier ensures that there is always a positive voltage on the anode relative to the cathode. So in essence a sine wave is always positive (negative values are reflected back to positive values along x-axis), this is also called a full wave rectifier. In a half wave rectifier only the positive or negative values are rectified not both.

Modern X-Ray tubes

In modern x-ray tubes the anode rotates to prevent overheating as almost 99% of the energy required to produce x-rays is converted to heat. It is a very inefficient process. The whirring sound which you hear when having an x-ray is causing by the rotating anode, and the ‘clunk’ is the x-ray itself, the high voltage part of it. The cathode has one or more filaments (often two) to give a broad focus and a fine focus. This helps with the resolution of the x-ray tube.

If you overheat an anode, it can become significantly damaged, with concentric circles becoming apparent where the electrons are focused. And if the anode stops spinning but electrons are still ‘fired’ at it pitting can occur as well, effectively destroying the tube.

The tube housing encases the the x-ray tube. It is often made out of lead and it stops x-rays from being scattered in every direction. It contains a window from which they are emitted with a filter (often aluminium) blocking the lower energy x-rays as these do not help to form an image. Therefore reducing the amount of radiation the patient is exposed to.

Note: Photon energy is measured in kVp

Below the housing is a light-beam diaphragm which is co-incident with the x-ray beam. This shows the radiographer where the x-ray images be taken of the patient.

X-Ray Spectrum

The x-ray spectrum is formed from Bremsstrahlung (a continuous element) and a series of characteristic x-rays.

Note: In a diagnostic x-ray machine Bremsstrahlung is most important, radiographers are not really interested in the characteristic x-rays

1. Bremsstrahlung Radiation

Is the electromagnetic radiation produced by the deceleration of a charged particle after passing through the electric and magnetic fields of a nucleus. The kinetic energy that is lost by the charged particle is emitted as an electron.

2. Characteristic X-rays

Characteristic X-rays are produced when a material is bombarded with high-energy particles (electrons), some of the electrons surrounding the atom are ejected. These spaces created around the atom need to be filled. These outer electrons in higher shells cascade down to fill the vacancies causing emission of x-rays of characteristic of element.

For example, as electrons travel from the L shell to the K shell, creates a K-alpha x-ray. If an electron falls from the M to the K shell a K-beta x-ray is emitted.

Note: Innermost shell is K then L and Outermost shell is M

Tissue Attenuation

To form images, x-rays must attenuate in tissue. There are two iterations that happen at diagnostic energies, the Photoelectric effect and the Compton effect.

1. Photoelectric Effect Inner shell Z Dependent

The photoelectric effect is a form of interaction of X-ray or gamma photon with the matter. A low energy electron interacts with an electron in the atom and removes it from its shell. This is very likely if the electron is:

1. Tightly bound (as in k shell)
2. The energy of the incident photon is equal to or just greater than the binding energy of the electron in its shell

The electron that is removed is called a photoelectron; the incident photon is completely absorbed in the process; all photon energy is transferred to the electron.

Electron energy = Photon energy - Binding energy of electron

The photoelectric effect is related to:

• the atomic number (Z) of the attenuating medium
• the energy of the incident photon
• the physical density of the attenuating medium

Small changes in Z can have quite profound effects on the photoelectric effect, this has practical applications in the field of radiation protection. Hence materials with a high Z, e.g. lead (Z = 82) are useful shielding materials.

2. Compton Scatter Outer shell Z Independent

Compton scatter is one of the main causes of scattered radiation in a material. It occurs due to the interaction of the X-Ray or gamma photon with free electrons/loosely bound valence (outer) shell electrons. The resultant incident photon gets scattered (changes direction) and transfers energy to the recoil electron. The scattered photon will have a different wavelength and thus a different energy. The Klein-Nishina formula describes the compton effect and shows how energy and momentum are conserved.

The scattered x-rays therefore have a longer wavelength (and a lower energy) than those incident on the material. The Compton effect does NOT depend on the atomic number (Z) of the material, but does depend strongly on electron density.

Diagnostic Range Attenuation 30 - 120 Kev

The standard x-ray is a negative image with the bones in white representing a higher attenuation. Bone is significantly more attenuated at lower energies than the soft tissues (muscles and fat) which are represented by a grey colour. No attenuation leads to a black image, for example in the lungs or the gut (because they are full of air). This difference in attenuation gives the x-ray image. Radiating at a lower energy reduces photon attenuation and increases contrast.

Attenuation formula

$ n_x = n_0 e^{-\mu x} $

μ is the attenuation coefficient

Producing Images with X-rays

There are two properties that are most talked about which are contrast and sharpness (resolution).

1. Contrast

A ‘flat image’ is an image with little contrast and is often due to a high amount of attenuation. Radiating at lower kVs reduces attenuation (using photoelectric effect) and leads to higher contrast in the image.

2. Sharpness

This is partly a property of an X-ray tube. A larger filament leads to a worse image resolution, and bad image resolution often has a large penumbra (a region of ‘partial eclipse’ or geometric ‘unsharpness’). Also if the imaging plate is not directly beneath the object the penumbra increases. Inside the cathode, a large wire filament can be used within the focusing cup to produce a large focal spot; a small filament can be used for a small focal spot. However, there is a disadvantage to having a small penumbra (and high resolution image): electrons are concentrated on a small area, which is more damaging to the X-ray tube.

Scatter Problem

Scatter due to the Compton effect does not help image formation and adds a ‘fog’ to the image. You can prevent excessive scatter noise by using an anti-scatter grid, although this means there is a higher dose given to the patient; with an anti-scatter grid you need more X-rays to form a good image.

Contrast Agents

Contrast agents are used to improve images produced by X-ray, CT, MRI and ultrasound. These substances temporarily change the way x-rays or other tools interact with the body. When introduced to the body, contrast materials help to distinguish certain structures/tissues to allow diagnosis of medical conditions.

• Barium: has a very high Z value and is the most common contrast agent taken orally and rectally (barium enema). It is available in several forms including powder, liquid and tablet.
• Iodine is often used when we need a contrast agent in the blood, e.g. to monitor filtration of the agent out of the blood by the kidneys.
• Barium and air: in a double contrast study, the colon is first filled with barium, then drained so that only a thin layer of barium is left on the wall of the colon. When the colon is filled with air, this provides an extremely detailed view of the inner surface of the colon.

Moving Images Image intensifier

An image intensifier has a large area at the front and a small area at the back to minify the image and accelerate electrons to give you the energy enhancement sufficient to produce a good image on a screen. Examples of use include conventional fluoroscopy and a C-Arm image intensifier used in a cardiac/angiography room to look at problems in the heart.

How does it work?

The x-rays interact in a photocathode (caesium iodide) which changes them to electrons. The electrons are then accelerated across a voltage and are focused on output screen (phosphor).

An example of the use of an image intensifier is in combination with iodine contrast media to look at a beating heart, watching for any irregularities. Another use is in combination with barium and looking at swallowing in the oesophagus.

X-Ray Detector Technologies

Advances in technology has allowed us to move on from viewing X-ray on an analogue screen/film to digital ways of looking at X-Ray images. An old digital process was the use of Computed Radiography (CR) with imaging plates. However hospitals these days use Direct Digital Radiography (DDR) which is an instantaneous process as the imaging plates are now made up of diodes. With this process there is no need to wait for film to be developed or read CR plates.

Digital Processing

Digital images allow radiographers to enhance them by zooming, inverting, post processing, filter and edge enhancing. These allows them to manipulate the images allow them to see certain structures such as blood vessels more easily.

Digital Subtraction involves taking two images, one before contrast injection and one after. If you subtract one from the other you end up enhancing the structure you want to see more clearly. However a drawback is that there can’t be any movement between the two images.

Dual Energy X-Ray Absorptiometry DEXA

Dual-energy X-ray absorptiometry is a means of measuring bone mineral density (BMD). Two X-ray beams irradiate at different energy levels and are aimed at the patient’s bones. When soft tissue absorption is subtracted out, the BMD can be determined from the absorption of each beam by bone. Dual-energy X-ray absorptiometry is the most widely used and most thoroughly studied bone density measurement technology. It is a very low dose technique commonly used for people with osteoporosis.

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Basis of CT Imaging

Learning Objectives

• Understand the basic principles of CT scanning
• Understand the basic principles of CT image formation
• Understand the source of typical artefacts in CT imaging

What is Computed Tomography?

Computed Tomography (CT) is a radiography technique in which a three-dimensional image of a body structure is constructed by computer from a series of plane cross-sectional images made along an axis.

The word tomography is derived from Ancient Greek τόμος tomos, “slice, section” and γράφω graphō, “to represent, study”.

CT is a very widely used general diagnostic radiographic technique. However compared to a planar x-ray instead of just taking one image it takes as series of projections around an axis forming many different slices. More clinically useful information can be received with a CT scan but at the cost of giving the patient a higher dose.

Planar X-Rays vs CT

Planar radiography renders a 3D volume onto a 2D image. Conventional planar skull X-rays (SXR) were traditionally poor for head images due to lots of overlapping structures and skull dominating the projection making it hard to see any other information in the head. However with a sliced CT image one can clearly see the the ventricles in the brain. There are more problems with planar x-rays as well:

• Contrast in planar x-rays is very good for bone due to the differences in attenuation but is very hard to differentiate between softer tissues.
• Spatial relation as planar x-rays form a 2D image it is often hard to see where objects are spaced and where they lie in relation to each other. There is a loss of depth. Whereas in CT you can see small differences a lot clearer.

Tomographic Reconstruction

Is where different attenuation (or CT number) values are mapped out in order to form an image. It was developed by Johann Radon in 1917 and is related to Fourier Transforms.

Radon’s Theorem

Given an infinite number of one-dimensional projections taken at an infinite number of angles, you can reconstruct the original object perfectly

Basic Principles of CT Formation

CT Scanner design

The basic components of CT Scanner are:

• X-ray Tube: the source, which projects a fan beam
• X-ray detector: traditionally film, then Computed Radiogrpahy (CR), now Direct Radiography (DR).
• X-ray attenuator: the patient or thing to be x-rayed Motion: means to gather projection data from various angles, usually the x-ray tube and detector are connected together on slip rings.

First Generation CT Scanner

The first generation of CT Scanner had the following characteristics:

• Narrow pencil beam
• Single detector
• Translational and rotational movement around the patient
• Very Slow it took minutes per slice

Third Generation CT Scanner

The third (current) generation of CT scanner vastly improved upon the previous generations and had the following characteristics:

• Fan beam
• Multiple detectors
• Rotation only and no translation is required
• Much faster and is a fast as 0.5s per rotation

X-ray tube advances

CT is very demanding of X-ray tubes and generators as scans are required instantaneously (up to 700 mA) and sequences can take over 30 seconds. This requires a large heat capacity and fast cooling rates. Mechanical stresses due to tube rotation are very large as well and are over 15G for 0.5s rotation.

Flat Filtration

Filtration in the x-ray tube and housing absorbs low energy X-rays, which contribute to the patient dose but not to the image quality. Equivalent to as much as 13mm aluminium.

Beam shaping filter Bow-Tie

After normal filtration, another filter is present in a CT scanner and known as a bow-tie filter. The edges of the patient to be x-rayed are thinner and therefore have less attenuation. This bow-tie filter lessens the intensity of the x-ray beam at the edges (more intense beam at the centre) so the beam incident at the detectors is more constant and it also removes soft X-rays.

Detectors

These are a critical component as they record the intensity of the incident X-rays sending out a signal. There are many different types including:

• Xenon: Older variant uses pressurised Xenon gas, ionisation.
• Solid Sate: More common for CT imaging. In uses scintillation, photon capture, light-photo-diode-signal.

These detectors have to perform well and be efficient under lots of physical stress

Detector Arrangement

Detectors in 3rd generation scanners are arranged in an arc around the patient. There are approximately 600 to 900 elements in a detector bank which allows for good spatial information. Both the tube and the detectors rotate around the patient.

Helical CT Scanning

Helical Acquisition

To try and reduce dose and make scanning even faster, the table also moves while X-Ray tube and detector rotate during acquisition. A problem with this is that some gaps can form in the images of the patient, however these can be filled in with interpolation.

Helical Pitch

Is the speed of the table movement through the gantry defines the spacing of the helices.

EQUATION

$ Helical \ Pitch = \frac{Table \ Travel \ per \ Rotation}{X-ray \ beam \ Width} $

For Example: An increase in pitch increases the movement of the table, decreases the amount of time required however leads to more gaps between the images.

Helical Image Reconstruction

To reconstruct the data as normal, the CT scanner uses a combination of data 180° each side of a recon (reconstruction) position and interpolation. Interpolation averages data on either side of the reconstruction position to estimate the projection data at that point.

As a result, a interpolated helical scan is able to reduce artefacts due to changing structure in z-axis when moving the table. For any set reconstruction position, only one scan projection will be available at that point.

Note: Data at 180° at either side of the recon position is more commonly used than 360° on one side as z-axis interpolation distances are shorter. Also 180° interpolator makes use of the opposite (Anterior-Posterior & Positive-Anterior) views producing a second complementary spiral for interpolation

Advantages

A few advantages of helical scanning are:

• Speed: as there is no need to pause between scans for table movement, pitches greater than 1 are possible, pitches less than 1 are possible, reduced patient movement.
• More information but not exact!, arbitrary image position, can reconstruct overlapping images.

Disadvantages

A disadvantage is the broadening of the slice profile, however this can be overcome using a 180° interpolator at the expense of image noise.

Image reconstruction

The objective of CT image reconstruction is to determine how much attenuation of the narrow x-ray beam occurs in each voxel of the reconstruction matrix. These calculated attenuation values are then represented as grey levels in the 2D image of the slice.

Linear Attenuation Coefficient µ

All tissues or material has a linear attenuation coefficient which is summed along the path between the tube and the detectors, as well as varying with energy.

• High µ is for dense, high atomic number (z) materials. As the attenuation of X-rays is high, this gives a low signal to detectors
• Low µ is for low density, low atomic number (z) materials. Lower attenuation, higher signal to detectors

Note: µ relates to z (atomic number), ρ (physical density) and E (X-ray energy)

What is a CT image?

A map or array of picture elements (pixels) presenting a grey scale (pixel value) relating to the stored value which is the calculated result of the tomographic reconstruction of projection data relating to the attenuation in a volume cell (Voxel) in a patient. Each 2D pixel in a CT image represents average attenuation within a 3D voxel.

Data Acquisition

Many attenuation measurements are taken, with a sample at each detector position generating a profile. This gives view of a patient at one orientation; a projection. A number of projections are collected from views all around the patient. Different manufacturers have different combinations of detectors.

Filtered Back projection FBP

Back projection is a mathematical function that is applied to the attenuation data that you find, which reverses the process of measurement of projection data to reconstruct an image. Each projection is ‘smeared back’ across the reconstructed image. Consider each projection as an intensity map, where white is high attenuation (something ‘hard’) and dark is low attenuation (nothing there).

However the output back projection trans-axial image is blurry. The projection data needs to be processed before reconstruction. Kernels (mathematical filters) can be applied for different diagnostic purposes. Smoothing for viewing soft tissue and sharpening for high resolution imaging. This post-processing in combination with back-projection is known as filtered back projection.

CT Number HU

A normalised attenuation number using fixed reference points of water & air.

$ CT = \frac{\mu_{tissue} - \mu_{water}}{\mu_{water}} \times 1000 $

Hounsfield units are the standard units for CT number in medical imaging with water at 1000 HU and air at -1000 HU.

We can change the appearance of the image by varying the Window Level (WL) and Window Width (WW). This spreads a small range of CT numbers over a large range of grayscale values, making it easy to detect very small changes in CT number.

• Window Level (WL) is the CT number of mid-grey.
• Window Width (WW) is the number of HU from black to white.

CT imaging artefacts

Ring artefacts

This occurs in 3rd generation CT scanners. If one detector is out of calibration with the other detectors, this consistently gives erroneous readings at each projection. A circular artefact is presented.

Partial Volume effects

If an object is continuous is the z-axis the CT number is not affected by the z-sensitivity. If an object varies in z-axis (especially using helical scanning), the ‘partial volume effect’ will alter CT number. To solve this problem the pitch can be reduced.

Beam Hardening artefacts

As an x-ray beam passes through a material is becomes more attenuated and becomes ‘harder’ the further it travels. The peak energy of the x-ray beam starts moving higher up the spectrum, so becomes more penetrating and more intense at the detectors. This various artefacts to appear:

• Cupping: the central x-rays are hardened due to a decrease in attenuation rate compared to the edges. The beam is therefore more intense at the detectors.
• Streaks and dark bands: appear between dense objects. As the beam goes through both objects at some projections and one object for others. Beam passing through only one object is hardened less than those passing through both objects.

Metal artefacts

These are caused when density of material is beyond the normal range of a scanner computer (incomplete attenuation profiles). It is compounded by beam hardening, partial volume and aliasing. Filters can be applied to reduce the metal artefacts, but ideally metal objects are removed however this is not possible with implants!

Motion artefacts

If the object moves while the scanning takes place, misregistration artefacts appear as shading or streaking. To prevent this, the CT operator will tell a patient to hold their breath will scanning, to minimise any movement due to breathing.

5
Image Quality & Information Technology

Learning Objectives

• Understand what “good clinical image quality” means
• Learn about the three key technical IQ metrics (spatial resolution, contrast and noise), how these can be measured and the impact on Image Quality (IQ)
• Understand advantages and limitations of digital images
• Identify the contents of DICOM clinical image files and the typical size/archiving requirements
• Learn about the contrast limitations of the human visual system and the value of post-processing tools.
• Calculate the size of image files from given detector specs, data and image characteristics
• Apply the concept of Nyquist frequency to digital imaging problems.
• Overview of Information technologies (IT) in healthcare, including Picture Archive and Communication Systems (PACS) and Electronic Health Records (EHR).

Medical Imaging Modalities

There are many different imaging modalities:

• Ultrasound (US): Sound waves (mechanical energy), are very good at showing fluid (a dark echo will be seen).
• Computed Tomography (CT): Uses X-Rays at higher energies. Primarily provides information about the anatomy.
• Positron Emission Tomography - Computed Tomography (PET-CT): Positrons and gamma photons from PET, and X-rays from CT.
• Magnetic Resonance Imaging (MRI): uses magnetic fields and radio-frequency. Primarily provides information about the physiological.
• Positron Emission Tomography (PET): uses positrons and gamma photons. Primarily provides information about the physiological.
• Fluoroscopy: uses X-rays
• Mammography: uses X-rays at lower energies as breast is fat, soft tissue. Reduce energy to amplify photoelectric effect vs Compton scatter. Tomosynthesis is an advanced application of mammography to see images with less overlap of structure of the breast. Primarily provides information about the anatomy.
• Positron Emission Tomography - Magnetic Resonance (PET-MR): uses positrons and gamma photons from PET; magnetic fields and radio-frequency from MRI.

Image Quality IQ

Image Quality (IQ) is a general and subjective concept best described within the context of the specific task. An image with a good IQ has suitable characteristics for the intended use which could be screening, diagnostic, intervention or follow up.

Note: IQ does not mean aesthetically beautiful images!

For example in breast imaging, a high image quality enables detection and characterisation of:

• Micro-calcifications in clusters
• Nodules which are more dense than surrounding tissue
• Architectural distortions helps radiographers to how symmetric breasts are to each other
• Cysts, fluid
• Angiogenesis, the blood supply (shown by MRI)
• Increased glucose metabolism, important as often associated with cancer and other pathology (shown by PET)

Ideally with a high (100%) sensitivity (the ability to correctly identify the structures, the true positive rate) and a high (100%) specificity (the ability to correctly identify the structures without disease, the true negative rate).

Sensitivity Equation

$ Sensitivity = \frac{True \ Positive}{True \ Positive \ + \ False \ Negative} \times 100 $

Specificity Equation

$ Specificity = \frac{True \ Negative}{True \ Negative \ + \ False \ Positive} \times 100 $

Factors that affect IQ

Image quality is affected by information content, perception/interpretation and decisions by the observer:

Information content

• Tissue characteristics and pathology
• Radiographic technique (e.g. positioning, compression)
• Equipment specification (e.g. pixel size, dynamic range)
• Equipment performance (e.g. AEC setup, noose characteristics, etc)
• Post-processing (noise reduction, edge-enhancement)

Perception & Interpretation

• Viewing conditions (e.g. ambient light)
• Monitor specs (matrix size, pixel size, bit depth)
• Visual acuity

Observer decision criteria

• A priori knowledge
• Experience
• Personal Preference

Routine quality control aims to monitor equipment performance over time and compare it with a baseline/reference to ensure it adheres to the intended standards through the lifetime of the equipment.

ALARA / ALARP As Low As Reasonably Achievable/Practicable

Modalities involving ionising radiation require image quality to be complaint with ALARA/ALARP.

Digital Imaging Systems and Patient Dose

Analogue systems using film were sensitive to an upper and a low threshold. Too low a dose would result in the film being underexposed and too high a dose would result in the film being over exposed.

However digital systems (CR and DR) have wider dynamic range and are tolerant to sub-optimal exposure conditions. Therefore it is very hard for the operator to distinguish whether the machine is malfunctioning and potentially the patient could receive too little or too much radiation dose (dangerous!).

Digital Images

A digital image is an array of numbers assigned to each pixel or voxel. In a digital image the picture is broken down into discrete blocks. In a 2D system each block is termed a pixel (picture element) and in a 3D system each block is termed a voxel (volume element). A digital image is numerically described by:

Array Size 4 x 4 = 16 pixels

The array size determines the sampling frequency (pixels/mm). The higher the sampling frequency the better the representation of the object detail.

Bit Depth 2 bit = 2² = 4 possible pixel values

The bit depth determines the number of possible values that can be assigned to a pixel. Quoted as the number of bits allocated to the image, so the simplest image would be 1-bit = 2¹ = 2 possible values = black & white.

Terminology

The Human Visual System (HVS) is a little under 8-bit i.e. can distinguish ~200 Just Noticeable Differences (JND) in grey scale level. Medical imaging detectors and displays are typically 12-bit (i.e. 4096 grey levels) as post-processing tools manipulate and optimise the image for HVS.

Note: The representation of an object improves as the array size and bit depth are increased.

What is the image representation if the size is 2300 x 1900 at a 16 bit depth?

Image Size = 2300 x 1900 x 2 byte per pixel
Image Size = 8 740 000 bytes
Answer = 8.3 Mb

Digital image presentation

Digital images are normally viewed:

• Hardcopy (film) using a light box
• Medical Display (CRT or LCD) usually 3 MegaPixels upwards (5.9 MegaPixels for mammography)

Image processing tools

The same image at different window width and level settings show different information. Post processing may generate artefacts in the image (e.g. high level of edge enhancement may suggest that an implant is loose).

Compression and image data

Lossy compression can make a file a lot smaller, however it is required by law that medical images have a lossless compression (to avoid any degradation in quality that could cause a change in diagnosis).

DICOM format

Medical images are usually in the Digital Imaging and Communications in Medicine (DICOM) format. A DICOM file has two components:

1. Clinical information (signals with a clinical meaning)
2. Acquisition and image info (in the DICOM header)

All electronic detectors produce an analogue signal which varies continuously and which depends on the amount of radiation (or other form of energy) received by the detector. In most modern electronic imaging systems, the analogue system from the detector is transformed into a digital signal, that is a signal that has a discrete, rather than continuous values. During this transformation obviously some information is lost.

TYPICAL SIZE OF MEDICAL IMAGES

Technical descriptors of IQ

Spatial resolution, contrast and noise are the three key indicators of Image Quality. From these descriptors, Signal-to-Noise Ratio (SNR) and Contrast-to-Noise Ratio (CNR) can be derived. When measured under controlled conditions these can be very useful values.

Signal-to-Noise Ratio SNR

SNR shows how many times stronger the signal is compared to the noise (signal variations). If all the sources of non-random noise can be removed than then the dominant source of noise is random (Poisson) distribution.

$ SNR = \frac{signal}{noise} = \frac{signal}{\sqrt{signal}} = \sqrt{signal} $

Contrast-to-Noise Ratio CNR

CNR is a useful metric in medical imaging as it allows us to quantify subtle variations in signal between objects and their surrounding background.

$ CNR = \frac{ \vert signal_{obj} \ - \ signal_{bkgd} \vert }{noise_{bkgd}} $

Its best to have a high photoelectric absorption and low Compton scatter. Important requirements of an imaging system is that is has a high signal detection efficiency with a high SNR and a high CNR.

1. Spatial resolution

An ideal detector would produce an exact representation (sharp response) of the object irrespective of the spatial frequency. However in reality the response is more curved. Spatial resolution affects the visibility of detail in an image and the ability to detect small structures close to each other. Poor spatial resolution of the imaging system shows a blur in the image. Decreasing the pixel size improves the spatial resolution at the cost of more noise as there are less photons per area (unless you increase the dose to compensate for this).

Sampling frequency

Nyquist-Shannon’s Sampling Theorem states if you have a signal that is perfectly band limited to a bandwidth of f₀ (cycles/mm) then you can collect all the information there is in that signal by sampling it at discrete times, as long as your sample rate is greater than 2f₀ (samples/mm)

For example, if the maximum frequency in the object is 2cycles/mm then the sampling must be done at least 4 cycles/mm.

$ N_F = \frac{1}{2 \times Pixel \ Pitch} $

Where the pixel pitch is the distance between two adjacent pixels.

Under-sampling occurs at a sample rate below the Nyquist rate. This leads to misrepresentation of the signal, loss of information and generation of artefacts.

2. Contrast Z dependent

Contrast key to detect subtle signals and is determined by the relationship between the magnitude of the signal and the magnitude of the fluctuations in the signal (noise). It depends on the composition and thickness of an object as well as the properties of the detector such as noise.

3. Noise

An ideal imaging system would:

• Detect all X-rays
• Preserve all spatial information
• Absorb all energy from each x-ray
• No additional noise present in the system

However no such detector exists and noise is fashioned which prevents the visibility of small/low contrast details. Some sources of noise include:

• Gain calibration is where digital detectors can compare a raw image to reference values to compensate and produce a uniform image. This can produce electronic noise.
• Mottle (quantum noise) is determined by the stochastic (random) nature of X-ray production (a process we can’t control). Ideally X-ray systems operate in a quantum limited regime. i.e. where quantum noise is the limiting noise source and quantum noise decreases with increasing number of photons.
• Clutter (anatomic noise) is where the anatomy of the human body disrupts the region to be viewed. For example in chest radiography the detection of subtle lung nodules is limited by anatomic noise. Another example is the superimposition of breast tissue in mammography which degrades IQ and poses difficulty to lesion detection.
• Other sources include, electronics, detector structure/defects and quantisation (restricting the number of values of a system)

Noise can be reduced, but never eliminated completely. CNR provides valuable data to investigate drops in Image Quality.

Health Information technology HIT

HIT has changed the way healthcare is provided. It holds great promise towards improving healthcare quality, safety and costs. Some examples of IT in healthcare:

• Picture Archiving and Communication Systems (PACS)
• Electronic Health Record (EHR)
• Electronic prescription services
• Hospital Information Systems (HIS)
• Radiology Information Systems (RIS)
• Incident alert systems
• Patient registers
• NHSmail

Picture Archiving and Communication Systems PACS

There were some key milestones in the development of PACS:

• 1979: First digital data link between CT scanner and radiation treatment planning computer (Loma Linda University Medical Centre, California)
• 1993: PACS implemented in Hammersmith Hospital, UK
• 1993: DICOM 3.0 (originally ACR-NEMA 3.0) standard published
• 1996: The first filminess hospital in operation in the UK (Hammersmith Hospital)
• 1998: Integrating the Healthcare Enterprise (IHE) initiative established. …

PACS continue to develop, with technological advances making implementation similar and cheaper. Much current development focus on workflow and systems integration. At the moment, PACS typically comprises of:

• Data storage devices
• Image display devices
• Software
• Film printers and digitisers
• Computer networks

May have additional networks to the other IT systems (HIS, PAS, RIS)

Benefits of PACS

• Less physical space required
• Easy image access
• Safety
• Efficient data management
• Cost savings
• Environmental benefits
• Enables teleradiology

Challenges of PACS

• High capital investment and ongoing costs
• Integration with other (local and remote) IT
• Continuous user training
• Quality assurance
• Cost
• Specialised management/Technical skills

Electronic Health Record (EHR)

This is a record of important clinical information about the patient, and provides key performance indicators for the hospital or specialist unit (e.g. to support research, help planning new services):

• Consultation notes
• Hospital admission records and reasons
• Chronic health conditions (e.g. diabetes, asthma)
• Test results (x-ray, CT, MRI) and images
• Radiation dose received in imaging procedures
• Treatment received, medicines taken
• Adverse reactions to medications
• Hospital discharge records, follow-up appointments
• Lifestyle information (e.g. smoking)
• Personal details (NHS number, age, gender, address)

The EHR can be created, managed an consulted by authorised providers and staff across more than one health care organisation. It can bring together information from current and past doctors, emergency facilities, school and workplace clinics, pharmacies, laboratories and medical imaging facilities.

The UK shows the biggest take-up of electronic health records in Europe. $2.1 billion (4% annual growth) was spent by the UK by the end of 2015 compared to $9.3 billion (7.1% annual growth) spent by the US.

Impact of EHR

The top 10 functions where doctors globally perceive a positive impact of EMR and HIE:

• Improved co-ordination of care across care settings/service boundaries
• Improved health outcomes
• Increased speed of access to health services
• Reduced number of unnecessary interventions/procedures
• Improved patient access to specialist health care services
• Reduction in medical errors
• Better access to quality data for clinical research
• Improved cross-organisational working processes
• Improved quality of treatment decisions
• Improved diagnostic decisions

However there are some challenges of implementing EHR. Potential of EHRs meets problems of implementation as they could distract from doctor-patient relationships, wasting valuable time and driving up costs (costly to maintain).

QUESTIONS

What does “good IQ” means in the context of medical images?
A good IQ has suitable characteristics for the intended use which could be screening, diagnostic, intervention or follow up.

What factors that influence IQ?…and perceived IQ?
Answer coming soon

What are the 3 key technical descriptors of IQ?
Answer coming soon

What are the main sources of noise in X-ray imaging? And their causes?
Answer coming soon

How can CNR be measured? What affects it?
Answer coming soon

How can the performance of a medical monitor be assessed?
Answer coming soon

What data is contained in a DICOM file?
Answer coming soon

How does image matrix size and bit depth affect image quality?
Answer coming soon

What differences are expected between an 12bit and a 8bit image?
Answer coming soon

How does SNR relates with the number of photons used to produce an X- ray image for an ideal x-ray imaging system?
Answer coming soon

What is spatial resolution and how can it be improved for a digital system?
Answer coming soon

Discuss advantages and limitations of digital imaging systems?
Answer coming soon

What are the 2 main functions of an Electronic Health Record (EHR)?
Answer coming soon

Give examples of impact of EHR on patient and the healthcare system.
Answer coming soon

What is PACS?
Answer coming soon

How can PACS affect workflow in the imaging department?
Answer coming soon

Discuss key requirements of a hospital PACS?
Answer coming soon

How could IT systems support the management of adverse incidents in a hospital setting?
Answer coming soon

Discuss the introduction of IT technologies in healthcare and how they can bring benefits to patients and the healthcare system?
Answer coming soon

PROBLEMS

In the plane of the detector what spatial frequency can be recorded by a 512 x 512 pixel digital fluoroscopy system with 150mm x 150mm receptors?

Detector size = 150mm x 150mm
Matrix size = 512 pxls x 512pxls
Pixel pitch (d) = 150mm/512 = 0.293 mm
Nyquist Frequency (Nf) = 1/2.d = 1 /2(0.293) = 1.71 l p/mm
Solution: 1.71 lp/mm

A grayscale chest radiograph is 35cm x 29cm in area and was digitised with a sampling frequency that preserves the inherent spatial resolution in the image which is approximately 5 lp/mm (line pairs per millimetre). Each sample was digitised with 16 bits.

(a) Determine the image array size (in pixels)
The minimum pixel size to preserve the frequency is calculated using the Nyquist theorem:
Nf=1/2p … p=1/(2x5 lp/mm) = 0.1 mm
Image array size (pixels) = 350/0.1 x 290/0.1 = 3500 pxl x 2900 pxl

(b) Calculate the memory (in Megabytes) required to store a chest radiograph composed of an antero-posterior (AP) and a lateral (L) view of the chest (i.e. 2 images)
Memory required for one image
= 3500 x 2900 x 2 = 20 300 000 bytes / 1024 bytes/kbytes
= 19 824 kbytes / 1024 kbytes/Mbytes
= 19.3 Mbytes
Memory required for AP + Lateral ~39 Mbytes

6
Nuclear Medicine

Learning Objectives

• Understand the basic physical and engineering principles of nuclear medicine.
• Be able to discuss the various technologies implemented in nuclear medicine.
• Be aware of the clinical implementation of nuclear medicine

Nuclear Medicine Imaging

Is functional molecular imaging, which takes advantage of molecular interactions in tissues and organs. Pharmaceuticals tagged with radionuclides are injected into patients. Radiopharmaceutical accumulates in the organ of interest. Then the imaging is performed and the pathway of the pharmaceutical is measured.

Compared to an X-ray, there are some fundamental differences:

• Nuclear medicine measures function not the structure of the anatomy
• Image contrast is due to the uptake not due to the attenuation
• Radiation source is inside the body and not the outside
• Radiation emission position and detection unknown
• Radiation emitted before, after and during imaging

Alpha, beta and gamma rays are involved in nuclear medicine. Alpha rays get stopped by paper, beta get stop by aluminium and mostly get stopped by lead.

What is radioactivity?

Radioactive materials are unstable and have insufficient binding energy to hold constituent particles together. With time the nucleus changes and the number of protons/neutrons change. These changes result in the emission of radiation. Decay probability is characteristic of the nucleus. Radioactivity is measured in Becquerels (disintegrations per second).

Half-life is the time required for half the atoms to decay. The activity is also reduced by half.

Radioactive Decay

A = A₀e^-λt

Where λ is the decay constant

If we have 100 MBq of Tc-99m, how much activity do we have after two hours given that the decay constant is λ = 3.21 x 10^-5 S^-1?

A = A₀e^-λt
A = 100e^{-3.21 x 10-5 x 7200}
A = 79.36 MBq

Radionuclides

The ideal characteristics of the radio-labeled chelator:

• X-ray or γ-ray type of radiation
• 120-180 keV of photon energy 79 keV (²⁰¹TI) to 360 keV (¹³¹I)
• Half-life depends on the uptake rate, and is normally hours only duration of hour long it is required.

Generation of Radionuclide

There are two main ways of producing radionuclides in hospitals, either through direct (nuclear reactor or cyclotron) or indirect (generators) means.

Many parent radionuclides go to a ‘metastable’ state through beta or alpha emission. Metastable daughter loses excess energy as a gamma photon to revert to ground state. Most common radionuclide in Nuclear Medicine is a metastable isotope Tc-99m (6.01 hour decay) which is the beta-emission ‘daughter’ of Mo-99 (66 hour decay).

A generator has an eluate (collection) vial at low pressure containing saline. A pressure difference draws saline into a column containing Mo-99 on Alumina beads. The saline washes off Tc-99m into eluate vial. Sodium Pertechnetate (NaTc0₄) ends up in the eluate. There is lead shielding all around the generator to protect the technicians. Special calibration equipment is used to determine whether the strength of the radioactivity is correct.

Which Radionuclide?

The organ/tissue of interest will determine the choice of radiopharmaceutical to be used.

Radionuclide Detection

Nuclear medicine scanners have advanced tremendously since their invention in 1950. A gamma camera is suspended above a patient obtaining a 2D image from a 3D distribution of radioactivity.

Scintillation Crystal

The scintillation crystal absorbs energy from incident gamma radiation giving out corresponding photons so we can detect the intensity of the radiation as light. Key properties of a scintillation crystal are:

• Attenuation coefficient
• Scintillation efficiency
• Speed
• Colour of light emission
• Physical properties
• Linear conversion of radiation energy into light energy.

Typical scintillator crystals are NaI(TI)

Photomultiplier Tube

The incident light photon from the scintillation crystals travels into the photomultiplier tube forcing electron emission from photocathode. The electron is focused onto first dynode which is at a higher potential than the focusing electrode causing the electrons to gain kinetic energy. The kinetic energy of the electrons is absorbed further in the dynode, freeing even more electrons in the process. This is repeated over 10-15 dynodes each at a higher potential. The pulse of charge is collected at the anode.

Photomultiplier tube size is 50 - 75mm

Collimators

Gamma rays are emitted in all directions from the patient, and in order to determine their location of origin a collimator is used. A collimator can be thought of a very tiny bunch of straws, and they have many different designs including parallel hole (most common), pin-hole, converging and fan-beam. The different designs stop the scattered photons in different ways depending on what imaging is required and many different factors have to be taken into account:

• Septal thickness (s): Photon Energy
• Hole length and width: Sensitivity vs Resolution, position of the source, type of scan and activity in the patient.
• Type of scan: Static or Dynamic
• Required resolution

However a collimator reduces the sensitivity of a detector system. The higher the resolution, the lower the sensitivity as more photons are absorbed by the collimator. Also collimators cannot avoid picking up scattered photons but these effects can be reduced by using energy discrimination of pulse height analysis. Without collimators intrinsic position calculation is ~3mm Full Width at Half Maximum (FWHM).

$ Energy \ Resolution = \frac{FWHM \ \times \ 100}{Peak \ Energy}\% $

Note: FWHM is full width of a peak at half its height.

Alternative Technologies

Scintillation detectors are bulky and have a relatively poor energy resolution. Recently some new Nuclear Medicine systems uses solid state semi-conductor detectors instead. These have a superior energy resolution, smaller and slim, costly are made up of substances such as Cadmium Zinc Telluride.

Avalanche Photodiode is an alternative to the photomultiplier tube, with a semiconductor detector sensitive to light photons. These are smaller, more compact, have a high quantum efficiency but are noisy and have a low timing resolution.

Image formation

X and Y position signals are converted to digital form with analogue to digital convertor. The address memory location is incremented. The final image is then displayed on a standard computer display. There are many different parameters which determine the characteristics of the output image:

• Energy e.g. 140 keV (+/- 10%)
• Pixel size = FWHM / (2 or 3)
• Matrix size = Detector size / Pixel size. Dynamic Imaging ( 64 x 64, 128 x 128 ) and Static Imaging ( > 256 x 256 )
• Pixel Depth 2⁸8 = 255 ~~~~ There are two main types of image acquisition:

1. Static Acquisition thyroid bone lung

The distribution of the radiopharmaceutical is fixed over the imaging period. The gamma camera is positioned over the area of interest for a fixed time and counts are accumulated. Multiple images from different angles can be acquired (e.g. anterior, posterior, oblique)

2. Dynamic Acquisition renogram GI bleed

Consecutive images are acquired over a period of time. The camera is in a fixed position allowing visualisation of the changing distribution of the radiopharmaceutical in the organ of interest.

Tomographic imaging

There are lots of limitations with planar images as they represent a 3D distribution of activity. Depth information does not exist and structures at different depths are superimposed. Loss of contrast in plane of interest is due to underlying and overlying structures. Tomographic images find a cross-section and can be more useful and prevent some of these limitations.

Single Photon Emission Computed Tomography SPECT

A set of angular projections of the activity distribution within the patient are acquired by rotating the gamma camera(s) around the patient. Images are reconstructed using filter back projection and iterative reconstruction. Some parameters that affect SPECT acquisitions include:

• Rotation speed (acquisition time at each angle)
• Number of angular samples
• Pixel size
• Rotation mode: step and shoot or continuous

Position Emission Tomography PET

This uses positron emission radionuclides (e.g. F-18, O-15, C-11). When these radionuclides interact with tissue they emit two 511 keV gamma rays. These gamma rays are emitted at 180° to each other and are detected in coincidence, improving the sensitivity. Just to compare a collimated single photon system has an absolute sensitivity of ~0.05% compared to ~0.5 - 5% of PET. The main application of PET is in oncology (study and treatment of tumours).

NM imaging limitations

Here is a list of limitations of nuclear medicine, with the main ones highlighted in bold:

• Scanner & Radiopharmaceutical
• Resolution
• Sensitivity
• Radiation Protection issues (before, during and after process)
• Patient motion
• Lengthy scans from 15mins - 1 hour
• Attenuation correction
• Localisation

Attenuation Correction

Two lesions with identical uptake but in different locations, will not have the same contrast. As the positrons emitting from one lesion will have to further than the other losing more energy and getting absorbed in the process. In order to resolve this a hybrid system is used, where SPECT/PET is used in combination with a low-dose CT. The information from SPECT/PET is overlaid the CT scan, showing exactly where in the body a disease is located.

Other NM Procedures

Nuclear medicine is involved in more than just imaging procedures.

Radionuclide Therapy

It is oral, intravenous or intra-cavity administration of unsealed radioactive source for the preferential delivery of radiation to tumours.

In therapy, Ɣ-emitters would not treat a tumour*, just pass straight through it. Therefore β-emitters, α-emmiters and Auger electrons are more desirable as their effects stay localised to the tumour. Therapy radionuclides have a longer half-life than imaging radionuclides, as you want them to stay active for longer (usually days) and keep treating the tumour until it goes away. Therapy radionuclides also have a high activity and a mild toxicity (Nephrotoxicity, Bone marrow toxicity)

*However some therapy radionuclides are also Ɣ-emitters so they can be imaged at the same time

An example of a radionuclide is I-131 which is used for thyroid carcinoma. It has a very high activity greater than 1100 MBq and can go up to 10-20 GBq. The patient is usually discharged when activity is below specific limits (usually 800 MBq). Patients are advised to drink plenty of water and usually have a scan just before discharge.

SIRT Selective Internal Radiation Therapy

SIRT is used in inoperable liver cancer. Glass micro skewers (the size of red blood cells) contain radioactive materials. These are implanted into a liver tumour via an intra-arterial catheter placed into the hepatic artery under fluoroscopic control by interventional radiologist. They are not metabolised or excreted and stay trapped permanently in the liver. They decay with a physical life of ⁹⁰Y. Its administered activity is about 3 GBq and delivers doses from 200 - 600 Gy.

Sentinel lymph node procedures SLN

The sentinel lymph nodes (SLN) are the first lymph node(s) to which cancer cells are likely to spread from the primary tumour. SLN biopsy is used to determine the extent or stage of cancer. Because SLN biopsy involves the removal of fewer lymph nodes than standard lymph node procedures, the potential for side effects is lower. The best practice is to use combined techniques of injecting blue dye and radioactive tracer. The procedure involves the injection of radioactive tracer ^99mTc-Nanocolloid. 40 MBq if injected the day before surgery (preferable). 20 MBq if injected on the day of surgery.

SLN procedures are mostly used for breast cancers

In Vitro Glomerular filtration

This is where adult patients are injected with 10ml (2 MBq) of Chromium (Cr-51), and three blood samples are taken 2, 3 and 4 hours post the injection. The samples are then centrifuged with causing the plasma to separate from the red blood cells. Here we are looking at the renal function so the plasma is then sampled and counted with gamma counter. If the counts decrease after every hour then that shows that the patient has good renal clearance.

7
Magnetic Resonance Imaging

Learning Objectives

• Nuclear Spin
• Magnetic Field and Magnetism
• Resonance Effect, Excitation, Signal Reception
• Image Formation (Gradients, k-space and spatial encoding)

Introduction

MRI is 30 000 times stronger than the Earth’s magnetic field. There are lots of advantages and disadvantages of MRI:

Nuclear Spin

An electron orbits the nucleus and is essentially a loop of current. This loop of current creates a perpendicular magnetic field known as a magnetic moment.

Quantum Spin Stern-Gerlach Experiment

The Stern-Gerlach experiment is where silver atoms are fired out and pass through a non-uniform magnetic field to a screen. Originally the classical theory predicted random orientation of angular momentum of silver atoms when they reached the screen. However quantum theory predicted the opposite, that the silver atoms land in two discrete orientations (now known as spin up, spin down). The results of the experiment agreed with quantum prediction not the classical one. The quantum property causing the deflection of silver atoms is known as the inartistic angular momentum or spin.

Nuclei with non-zero spin

The following are a group of nuclei with no nuclear spin:

Not only is Hydrogen extremely sensitive to magnetic fields but it is also the most abundant element in the human body (as well as the planet!).

in vivo biomedical nuclei

Hydrogen Nucleus

The most common isotope of hydrogen (1H) is simply a single proton. It is the most sensitive to external magnetic fields (42.56 MHz T^-1), therefore almost all biomedical MRI makes use of 1H nuclei. Other nuclei are studied in MR Spectroscopy.

Magnetisation

In the presence of an external magnetic fields, the spins tend to align either parallel or anti parallel, with a small bias towards the parallel (low-energy) state.

Note: How magnetisation is sensitive to temperature, easier to increase the magnetic field than keep the patient cool

Because of this slight bias, the patient will have a net magnetisation (very small). If all these magnetisation elements are added together they become the ‘bulk’ magnetisation vector.

As you can see, the degree of magnetisation is tiny, but at just 20 ppm (protons per million) this is enough to make detailed images of the body.

Static Magnetic field

Clinical MRI scanners have field strength of 1.5 T or 3 T usually. The Earth’s magnetic field is ~50 µT. Ferromagnetic objects can become missiles at 0.3 mT and active implants such as pacemakers can fail at 0.5 mT.

Resonance

Precession

This is where, like the Earth’s axis, each spin is tilted slightly away from the bore’s magnetic field. This leads to a precession around the bore axis at the Larmor frequency. This natural frequency is defined by field strength and is also known as the resonant frequency.

Excitation

A second temporary (B1) magnetic field is turned on perpendicular to the main B field. This short pulse at the resonant (Larmor) frequency flips the M (magnetisation) vector into the transverse plan towards the higher energy anti-parallel state. The degree of the flip angle, α, is defined by the length and amplitude of the pulse.

Longitudinal and Transversal Magnetisation

The flipped M vector now has two components, M_z (still exists, but can go to zero) and M_xy transverse magnetisation (which didn’t exist before). This movement of transverse magnetisation produces the change in magnetic field. However now M_z and M_xy want to return to their original state, a process known as relaxation.

Relaxation

The relaxation of the two Mz and Mxy components are separate, and during the process causes induced current in the RF coil.

Note: usually the same RF coil produces the pulse and picks up the change in magnetic field, although they can be different

T1 longitudinal spin-lattice

M_z wants to return to the parallel state, its full peak to M₀. This is an interaction of the hydrogen spin with the lattice surrounding it. Depending on the lattice structure around the spin, the relaxation happens at different exponential rates. Relaxation of M_z tends to 63% ($ 1-\frac{1}{e} $). Different tissue types have different T1 values with fat having the fastest rate, then Muscle, with Blood being the slowest.

EQUATION SHOULD BE KNOWN!

$ M_z = M_0(1-e^{\frac{-t}{T_1}}) $

T2 transverse spin-spin

M_xy wants to disappear through decoherence or dephasing. M_xy is at a maximum when the flip angle is at 90° This is a result of spin-spin interaction, i.e. hydrogen nuclei with other hydrogen nuclei. Again different tissue types have different T2 values with M_xy starting at 37% ($\frac{1}{e} ​$).

$ M_{xy}(t) = M_{xy}(0) e^{\frac{-t}{T_2}} $

T1 & T2 Values

Notice that T2 is largely insensitive to field strength. CSF takes the longest time to relax because it is the most liquid, having free movement and little time for interaction with the lattice or with other spins

RF Reception

Faraday’s law means that a fluctuating magnetic field will induce currents. Receiving RF coils are tuned to the expected signal from the rotating M vector. Electronic components (ADC, bandpass filtering, gain etc) digitise signal for image formation.

RF Coils and Excitation

Any electrically-conductive material exposed to RF will have currents induced, leading to resistive heating. Heating of the body is measured in W/kg, aka SAR (Specific Absorption Rate). MR scanner estimates SAR for every sequence and this is limited by FDA/IEC regulations

At 3T effects can occur in current loops as small as 30cm, such as the touching of arms and or legs with the body. Therefore patients are advised to touch their body parts together. Otherwise, the patients may get burnt at the point of contact as there is an increase in resistance at that point, causing the skin to warm up.

Imaging

Gradients

While the main magnetic field of the scanner (B₀) cannot change, we can add additional, smaller magnetic fields with changing electrical fields. As you may remember from physics, a changing electrical field produces a magnetic field; this is the basis of electromagnets. Each MR scanner has 3 sets of spatial encoding electrical coils to produce magnetic fields in the x, y, and z directions. These coils can be adjusted to produce not a constant field but a gradient, in other words a magnetic field that changes in strength depending on your position.

These magnetic fields are much weaker than B0 and vary linearly across the x, y, or z direction. They can even be turned on in combinations to create a linear gradient in any arbitrary direction, ‘tilted’ in space. By the Larmor equation, f = γ * B, so that if the magnetic field varies across space, the precession frequency of the protons will vary as well.

Slice Selection

The thickness of the slice is determined by the intersection of the gradient and the bandwidth. A region of spins are excited by an RF pulse. The thinner the slices the less signal you receive resulting in worse image quality. A bit like when you cut an onion in two it becomes a bit see through, there is not enough there.

Filling K-Space

The white plots in the middle of the K space (frequency domain) are low frequency, and slowly varying. There is conjugate symmetry in the K space matrix.

K Matrix size: 256 x 256 = 256 samples and 256 phase-encoding steps. Fourier Transform of K-space returns matrix in image space of exact same size. For a fixed field of view, increasing the matrix size increases the resolution.

Safety procedures noise

Time-varying magnetic fields induce currents in electrically conductive materials. This can lead to nerve stimulation. The Control of Noise at Work Regulations (2005) require that hearing protection is available if staff noise exposure exceeds 80 dB(A). Groups of particular concerns are children and neonates, the foetus, unconscious patients, and those with pre-existing hearing problems.

Localisation is performed by spatially varying the phase and frequency of a frequency-selected slice.

Pulse sequence

A pulse sequence is a series of RF and gradient field pulses used to acquire an MR image. Altering pulsed fields timing and strength, results in changes to the information content of the resulting image. Different pulse sequences are designed to encode different kinds of information into NMR signal.

Free Induction Decay FID

This is a sinusoidal wave which oscillates a Lamor frequency. The signal received from the RF coil is a function of the precession and decay of the transverse magnetisation. Measuring T2 from the FID is difficult due to the technical limitations. The transverse magnetisation is ‘refocused’ in order to produce an echo.

LEARN THIS BLOODY FUCKER!

$ M_{xy}(t) = M_0 exp(iw_0 t) \dot exp \bigg( \frac{-t}{T_2} \bigg) $

The signal received from the RF coil is a function of the precession and decay of the transverse magnetisation. Measuring T2 from the FID is difficult due to the technical limitations. The transverse magnetisation is ‘refocused’ in order to produce an ‘echo’.

Gradient Echo T2

The spin (RF) echo refocuses relaxation due to inhomogeneity but not spin-spin interactions. Gradient echo uses the gradient not, NOT RF, to refocus FID but cannot undo the effect of inhomogeneity. The transverse magnetisation is ‘refocused’ in order to produce an ‘echo’.

GRE Pulse Sequence

Echo is produced by inverting the FE gradient. Flip angle usually less than 90, leads to faster imaging and reduced SAR (Specific Absorption Rate). Sensitive inhomogeneity, can be plus or negative depending on the context.

Contrast in Gradient Echo

The echo time (TE) represents the time from the center of the RF-pulse to the center of the echo. For pulse sequences with multiple echoes between each RF pulse. The repetition time (TR) is the length of time between corresponding consecutive points on a repeating series of pulses and echoes.

Important Points

• Major MRI components (Static coils, gradient coils, RF coils), their roles and safety considerations
• Origin of the MRI signal, why we sue a certain nuclei, why we excite it and how we get image formation
• Spin echo and gradient echo. The differences in between them and about inversion recovery and why we use that. Signal suppression
• How to calculate acquisition in time and how to speed it up
• SNR and how to speed it up.

Problems

Which equation describes the Larmor frequency of a magnetic moment exposed to an external magnetic field?
$f = 2 \pi \gamma B_0$

What mathematical technique is required to transform a signal from the time domain into the frequency domain?
Fourier Transform

Which of these is NOT an advantage of MRI over CT?

• Excellent soft tissue contrast
• No use of ionising radiation
• Can image in arbitrary planes
• Good visualisation of skeletal structure (solution)

Which nuclei is the primary nuclei studied in biomedical MRI
1H

At what field strength to ferromagnetic objects become a missile risk?
3mT

Which tissue has a very long T1 relaxation time?
CSF

What risks are associated with the RF coils?
Heating of the body

What is the image size of an MRI slice if the K-Space matrix is 128x128?
128x128

What impact on SNR does halving the slice thickness (delta z) have on the SNR?
It halves the SNR, but increases spatial resolution in the z direction.

In an axial conventional spin echo image of the brain, the skull fat is brightest, followed by the white matter, followed by the gray matter. The CSF is dark. What weighting does this image have?
T1

Generally, how is the SNR different in SE (Spin Echo) vs GRE (Gradient Echo)?
SNR is higher than in GRE.

8
Ultrasound Imaging

Learning Objectives

• Describe the fundamental interactions of sound with tissues
• Explain the difference between reflection and scattering
• Calculate the amplitude and power, reflection and transmission coefficients, when supplied with appropriate acoustic impedance values
• Explain the origin of speckle in ultrasound images
• Describe the basic modes of operation of an ultrasound scanner and the information they provide
• Have a basic understanding of the key factors affecting spatial and temporal resolution
• Calculate the Doppler shift associated with scattering from a moving target and calculate the speed of a target given a measured Doppler shift
• Describe and explain a range of common artefacts that affect ultrasound imaging and be able to provide techniques for avoidance.
• Explain the potential biohazards of ultrasound imaging and describe the indices that are used to guard against these.

Introduction

Ultrasound imaging is transmission of high frequency sound into the body. It involves the detection of echoes and signal processing, leading to the parametric display of returning echoes.

Ultrasound has widespread medical applications as it is safe (non-ionising radiation), relatively cheap and portable and versatile. It is particularly useful for imaging soft tissues especially in the context of preclinical studies, to see the anatomy and/or function.

Resolution is proportional to frequency, as the higher the frequency, the higher the resolution. Also penetration into the body is proportional to the frequency, lower frequencies penetrate deeper into the body.

Note: There are also many industrial (non-medical) applications

The standard ultrasound is same size as a filing cabinet but it is on wheels. They have lots of controls as they lots of parameters that can be tweaked for the particular area than is to be scanned. The ultrasound scanner clinical transducer is the instrument that is used to produce and receive the ultrasound signal. The thickness of the active element is 0.4mm and produces a frequency of around 5.4 MHz.

There are many different modes of Ultrasound Imaging:

• B-Mode (brightness) is a 2D map of echo intensity (strengthen of the sound)
• Colour Doppler is a 2D map of instantaneous mean velocity of blood (how fast blood is moving towards or away from the scanner)
• Power Doppler is a 2D map of backscattered power in signals from moving blood. (if there is more blood, there is more of a substance)
• Spectral Doppler is a full spectral analysis of signals from fixed region.

Sound waves

Sound waves are a form of mechanical energy (vibration) that propagates due to the motion of particles in the medium. The density and elasticity are the fundamental physical properties that determine how sound waves propagate.

Robert Hooke discovered that stress is proportional to strain (Hooke’s Law). Using this is relation to ultrasound:

$ \beta $ is the bulk elastic modulus, $ \frac{\Delta V}{V_0} $ is the fractional volume change

$ \frac{\rho - \rho_0}{\rho_0} $ is the relative change in density

As as sound wave propagates, energy is lost and At boundaries between different materials, it can be reflected, refracted, or scattered. Remember that sound rarely travels through completely homogeneous media.

Interactions with Tissues

Acoustic Impedance

Acoustic impedance is the ratio of push (local pressure) variable to flow (how fast particles are moving) variable.

Specific Acoustic Impedance

$ Z_{sp} = \frac{p}{v} $

where Z_sp is the Acoustic Impedance, p is the press and v is the particle velocity. Note how similar this equation is to $ R = \frac{V}{I} $

Characteristic Acoustic Impedance

$ Z_{sp} = \frac{p}{v} = Z_{ch} = \rho_0 c_0 $

Special case of infinite plane wave. Where c₀ is the speed of sound

Pulse reflection and transmission

Pulse waves are required for range finding. The length of the pulse affects the resolution, sensitivity and total energy derived.

At a boundary between two media, the pulse wave splits into transmitted and reflected components with power being conversed across the boundary.

Power Coefficients

$ r = \bigg( \frac{Z_2 - Z_1}{Z_2 + Z_1} \bigg)^2 \quad t = \frac{Z_1}{Z_2} \bigg( \frac{2Z_2}{Z_2 + Z_1} \bigg)^2 $

Amplitude Coefficients

$ R = \frac{Z_2 - Z_1}{Z_2 + Z_1} \quad T = \frac{2Z_2}{Z_2 + Z_1} $

Rayleigh Scattering speckle

Scattering occurs when there are small inhomogeneities in wavelength as well as a possible local variation in density, elasticity and speed. This ends up causing the ‘speckle’ artefact in an ultrasound image. It is highly dependent on size and frequency.

There are many objects or particles per resolution cell. The random arrangement gives rise to incoherent scattering or specie noise. Speckle is a random, deterministic, interference pattern that is an inherent characteristic of coherent imaging. Its texture does not correspond to underlying structure, and the interference effect is superimposed on average scattering magnitude.

Attenuation

Signal loss

When sound passes through tissue some of the energy it possess’ is lost due to scattering and absorption. Absorption is the conversion of wave energy to heat, and is dependent on frequency.

Attenuation coefficient μ

The lost of energy is characterised using an Attenuation coefficient, in a logarithm scale with units in dB.cm^-1.MHz^-1. Note that it is frequency dependent, the higher the frequency the more energy you lose.

Time gain compensation TGC

Sound is attenuated as it propagates (depth), the ultrasound machine automatically calculates the attenuation coefficient and adjusts the brightness on the display so it is an even image (i.e. not darker with the increase in depth).

Image Formation

Echo location

Echo location is the timing of echoes providing depth information.

Transducers: The Piezoelectric Effect

The Piezoelectric effect is how we generate the sound pulses in the machine. In some materials, when a potential difference is varied across them, the material will vary in thickness. This can be used to generate a high frequency vibration. Mechanical distortion leads to the imbalance of distribution of electric charge (the reverse effect is also true). As a result, the electric field is proportional to the strain.

Inside an ultrasound probe, there are hundreds of wires connected up to hundreds of independent transmitters and receivers in a linear array. Thos is desirable, as you want to make it possible for the operator to ‘steer’ the sound. A circular wavefront can then be formed to focus the beam, by firing of small ultrasound pulses from the different transmitters at different times. This manipulation of the beam is known as beamforming.

Axial Resolution

The transducer has a natural resonant frequency, however at this frequency the pulse is long. This is undesirable in ultrasound, so they are dampened to create shorter pulses. This dampening however is inefficient and energy is wasted. Ideally, pulse length (T_p) would be equal to the wavelength, however due to physical limitations it is always longer than a single wavelength. A larger frequency and a larger bandwidth improves resolution.

The range resolution ($ \Delta r $), which is the ability to distinguish two scatterers at different depths behind each other, is inversely proportional to the frequency.

$ \Delta r = \frac{cT_p}{2} $

T_p is the length of pulse in time, c is the speed of sound, $ \Delta r is the range resolution $

Lateral Resolution

In the horizontal (lateral) direction a higher frequency, larger aperture and tighter focus all contribute to an improvement in resolution.

Temporal Resolution

Is the precision of ultrasound with respect to time, and is represented by the following equation:

$ T = N.\frac{2d}{c} $

T = time per frame, N = liens per frame, d = depth, c = $ \sqrt{ \frac{\beta}{\rho_0}} $ = speed of sound

Imaging Moving Targets

In ultrasound, the doppler effect occurs twice, the moving target receives and transmits the sound wave. The change in frequency is negative as the velocity towards the original source reduces separation and increases frequency:

c = speed of sound, V = target velocity, f = frequency

There is no Doppler effect when a target is moving perpendicular to the sound direction. Only the component of the target velocity along the axis of the wave direction contributes to the Doppler Shift.

Example Doppler Shift Calculation

If Ultrasound f = 5 MHz, Blood velocity = 0.5 m/s, Angle = 45°, Sound speed = 1540 m/s.

Note: We will be able to hear this sound, and sometimes doctors use this in their diagnosis.

Limitations

Unfortunately there are many common artefacts in Ultrasound, however fortunately most of these can be avoided by moving the transducer:

• Shadowing/Pseudo Enhancement: signal loss/gain: non-uniform attenuation
• Reverberation: multiple repetitions (often due to parallel tissues bouncing the sound back and forth). Comet tails
• Mirror Images: misplaced echoes
• Side Lobe Interference: low contrast, misplaced echoes

Ultrasound Contrast Agents

Ultrasound contrast agents are designed so more scattering occurs, so more pulses are reflected and received. The problem is that Blood on an Ultrasound is dark/black. Microbubble contrast agent, a few micrometers in diameter, can provide a non-linear response to ultrasound. For example this can be helpful to visualise tumours in a liver.

The dangers of Ultrasound

• The tissues in the body could heat up due to the energy from the Ultrasound pulse, potentially damaging the tissue.
• A medium could tear apart in a low pressure environment.

Thermal mechanisms

The intensity of a plane travelling wave:

Energy lost per unit area, per unit distance and time:

Assume all energy is absorbed as heat. The heat energy, assuming no heat is lost via conduction, convention or radiation is represent by:

$ \rho $ is the density, C is the specific heat capacity, and $ \Delta T $ is the change in temperature. Remember that I is the energy per unit time: $ \frac{dQ}{dt} = \mu I $

However heat is transported away via tissue perfusion.

Acoustic Cavitation

Acoustic cavitation is the formation, motion and effects of acoustically driven cavities in fluids. It involves the tearing apart of the medium due to low pressure (i.e boiling).

Inertial (Transient) Cavitation

Inertial cavitation refers to the sudden collapse of a cavity in the compression phase. It is governed by the inertia of the surrounding medium. Acoustic shock wave, High temperatures ~1kK, production of light. It is a very localised effect and free radicals are created.

Non-Inertial (Stable) Cavitation

Non-Inertial cavitation refers to stable oscillation of a cavity during isolation. This includes effects associated with motion of the surface and gas diffusion.

Ultrasound ‘safety’ indexes

These are two guidelines which a clinician uses which air on the side of caution:

Thermal Index TI

The thermal index is intended as a measure of an ultrasound beam’s thermal bioeffects.

$ TI = \frac{W}{W_{deg}} $

$ W_{deg} $ is the acoustic power required to raised temperature by 1°C (steady state), $ W $ is the current power output. Note TI is not an indication of actual temperature rise. Different models are used to calculate TI for soft tissue, bone (at focus), and cranial bone

Mechanical Index MI

The MI indicates the possibility of mechanical damage to the tissues as a result of cavitation. It is based on the analysis of pressure required to initiate inertial cavitation. It is a most basic level this index gives an idea of changes in acoustic pressure level with output power. Above 0.7 there is a theoretical risk of cavitation.

$ MI = \frac{P_{-ve}}{\sqrt{f}} $

$ P_{-ve} $ is the peak negative acoustic pressure. $ f $ is the ultrasound frequency. MI is not a probability. Pressure is derated by assumed attenuation in tissue.

Questions

1. What do the following ultrasound imaging modes display: B-mode, Colour Doppler, Power Doppler, Spectral Doppler?
2. What key physical properties of a medium influence the propagation of a sound?
3. Use the definition of, power and amplitude, reflection and transmission coefficients to determine the relative pressure amplitude and power of the various wave components arising after a an ultrasound wave is incident on a boundary between air and water?
4. What is Speckle?
5. What does time gain compensation refer to in ultrasound imaging?
6. What limits the frame rate (temporal resolution) of an ultrasound scanner?
7. Why is there an angle in Doppler shift equation?
8. If you increase the ultrasound frequency, what happens to the Doppler shift? (all other things being equal).
9. Why does shadowing occur in Ultrasound Images?
10. Can you name and describe the origin of two other image artefacts?
11. What are side-lobes, and how can they contribute to image artefacts?
12. What would you use as an Ultrasound contrast agent and why?
13. Describe 2 main possible bio-effects of ultrasound imaging. How are monitored.

9
Cardiography

Learning Objective

• Basic Function of the Heart
• Physiological Measurements
• Heart Electrical Stimulators
• Basic Electrical Safety

Heart

Basic Function

The heart is the pump station of the body and is responsible for circulating blood throughout the body. It is about the size of a clenched fist and sits in the chest cavity between the two lungs. Its walls are made up of muscle that can squeeze or pump blood out every time that organ “beats” or contracts.

Fresh, oxygen-rich air is brought to the lungs through the trachea or every time that you take a breath. The lungs are responsible for delivering oxygen to the blood, and the heart circulates the blood to the lungs and different parts of the body.

The heart beats’ about 100,000 times in one day and about 35 million times in a year. During an average lifetime, the human heart will beat more than 2.5 billion times. The body has about 5-6 litres of blood around it three times every minute. In one day, the blood travels a total of 19,000km. The heart pumps about 1 million barrels of blood during an average lifetime - thats enough to fill more than three super tankers!

Functional Anatomy of the Heart

The human heart consists of four “chambers” - two atrial and two ventricular cavities which are separated by muscle walls and valves. The main function of the heart is to be a pump but actually it acts as a double pump - right and left. The right pump sends blood into lungs for oxygenation. The left pump supplies the whole body with oxygenated blood (it is more powerful). Together with muscle cells, the heart wall contains specialised cells which form a network allowing an electrical impulse to spread through the heart.

Blood Circulation through the Heart

1. Blood returns in the heart from system circulation to the right atrium (through the vena cava)
2. From the right atrium it travels to the right ventricle (through the tricuspid valve)
3. From the right ventricle it is ejected to the lungs (through the pulmonary artery)
4. From the lungs the oxygenated blood returns to the atrium (through the pulmonary vein)
5. From the left atrium it goes to the left ventricle (through the mitral valve)
6. From the left ventricle the oxygenated blood is ejected to the system circulation (through the aorta)

Excitatory and Conductive System of the Heart

The heart is composed of three major types of cardiac muscle: atrial muscle, ventricular muscle and specialised excitatory and conductive fibres. The atrial and ventricular muscles are very similar to skeletal muscle by its structure but the duration of contraction is much longer.

The heart structure includes a specific system for generating rhythmical impulses to cause rhythmical contraction of the heart muscle. The conductive system delivers these impulse rapidly throughout the heart muscle.

Heart Excitation and Contraction

1. The sinoatrial (SA) node includes self-excitatory pacemaker cells. They generate pulses at a rate of ~70/min.
2. These pulses propagate through the atria, but can not go to the ventricles.
3. The atrioventricular (AV) node is between the atria and ventricles and has an intrinsic frequency of 50 pulse per min.
4. However AV node can be triggered at a higher frequency - i.e. normally it follows the pace of the SA node
5. Pulse propagation from the AV node to the ventricles is made through specialised conduction system
6. This system provides the pulse at relatively high speed to the ventricles (through the Purkinje fibres)
7. From the inner wall of the ventricles the many activated fibres create a wave front which propagates through the ventricular mass toward the outer wall of the muscle and causes contraction (pumping).
8. After each activation, de-activation occurs and the muscles are ready for a new activation pulse.

Formation of an action potential

1. Neurons communicate through nerve action potentials (impulses) based on electric current of ions
2. Generation of action potential depends on: ion channels in cell membrane & resting membrane potential
3. In the rest the cell is polarised - its membrane has internal negative potential (~approx. -70 mV) in respect to the extracellular space (inside there are mainly PO₄^3- ions, and outside mainly Na⁺ ions; K⁺ ions flow-in-out)
4. An external stimulus can open some ion channels in cell membrane (N.B. Na channels open first) allowing Na⁺ ions to enter the cell thus making it positive (up to +30 mV) - action potential (Depolarisation)
5. Some time after opening of Na channels, the K channels open (increased membrane permeability for K), and K⁺ ions flow out, restoring the initial negative polarisation inside the cell (Repolarisation)
6. The impulse from one cell stimulates the channels in the adjacent cell, this way propagating the stimulus.
7. The size of the impulse is independent of the strength of the stimulus. After the repolarisation the cell has a refractory period, during which it restores its ionic balance and cannot be stimulated again.

An action potential (AP) is a rapid change in the membrane potential during which the potential rapidly depolarises and repolarises. The potential reverses and the membrane becomes positive inside. AP provides long-distance transmission of information through the nervous system. Half or more of all smooth muscle contraction is initiated not by actions potentials nut by stimulatory factors acting directly on the smooth muscle contractile machinery. The two types of non-nervous and non-action potential stimulating factors most often are:

1. Local tissue factors: lack of oxygen in the local tissue and an excess of carbon dioxide causes smooth muscle contraction
2. Various hormones: most of the circulating hormones in the body affect smooth muscle contraction (these include serotonin, histamine, epinephrine, oxytocin).

There are two major differences between the membrane properties of the cardiac and skeletal muscle:

1. The action potential of skeletal muscle is caused by sudden opening of large numbers of “fast sodium channels”. In cardiac muscle, the action potential is caused by the opening of two types of channels: “fast sodium channels”, which are the same as in skeletal muscle, and “slow calcium-sodium channels”, which are much slower.
2. Immediately after the onset of the action potential the permeability of the cardiac muscle membrane for potassium decreases about five times. This process does not occur in skeletal muscle. The decreased potassium permeability greatly decreases the outflow of potassium ions during the action potential plateau and thereby prevents early recovery.

The duration of the plateau ensures cardiac contraction which lasts 20 to 50 times longer than in skeletal muscle. The refractory period of atrial muscle is much shorter than for the ventricles (about 0.15 second) and the relative refractory period is another 0.03 second. Therefore, the rhythmic rate of contraction of the atria can be much faster than that of the ventricles.

The surface of cardiac muscle is oppositely polarised compared with inside cells

Physiological Measurements

After imaging, physiological measurements are among the most important diagnostic methodologies used in health care.

Electrocardiogram ECG

The body fluids are good conductors, fluctuations in potential that represent the algebraic sum of the action potentials of myocardial fibres can be recorded from the surface of the body. The rocked of these potential fluctuations during the cardiac cycle is called ECG.

The phase of ECG formation, based on the changes of the summary potential (vector) of the cardiac surface. The bulk electrical activity of the heart produces a reasonable sized signal on the body surface, which can be measured by connecting electrodes to the skin. The recorded waveform and amplitude (1 mV) depends greatly on the position of the electrodes.

The P wave is caused by the atrial depolarisation prior to contraction.

The QRS complex (~ 1mV amplitude) is caused by currents generated when the ventricles depolarise prior to contraction. Therefore, both P wave and the components of the QRS complex are depolarisation waves.

The T wave is caused by currents generated as the ventricles recover from the state of depolarisation.

Registration of the ECG

The yellow electrodes are attached to the left arm and the red electrodes to the right arm, green to the left leg and black to the right leg (ground electrode).

Horizontal and vertical calibration is made using a grid printed or display. The horizontal lines are the voltage, 10 small divisions upward or downward represent 1 mV. The vertical calibration lines represent the time, with each 2.5 cm representing a second. The standard speed is 25 mm/s.

ECG abnormalities

There are many different heart abnormalities that can be picked up with an ECG:

• Arrhythmia is the change of the normal sinus rhythm due to defects in conduction of the cardiac impulse.
• Heart block is when the conduction system between the atria and ventricles fails.
• Bradycardia is the slowing of the heart rate
• Tachycardia is an elevated heart rate

Other ECG leads

The electrical activity of heart forms isopotential lines over the body surface, which assume various positions of ECG leads (with different signal waveforms).

Blood Pressure

As blood is pumped out of the left ventricle into the arteries the pressure in the aorta rises, the higher level being the systolic pressure. At the end of the left ventricular contraction, blood flows away from the heart so the aortic pressure falls. When the aortic valve closes, a notch appears on the pressure waveform. The lowest pressure is just before the next heartbeat, and is the diastolic pressure. The rate at which pressure falls depends on the systemic vascular resistance (SVR).

MAP - Mean Arterial Pressure, CO - Cardiac Output, SVR - Systemic Vascular Resistance, CVP - Central Venous Pressure

Mean Arterial Pressure (MAP) is the average pressure in a cardiac cycle. It is not the value halfway between systolic and diastolic pressures because the diastole lasts longer than systole (470 vs 330 ms).

Blood Pressure Measurement

In 1904 Korotkoff described the sounds that blood made as it moved intermittently through an artery when measuring blood pressure. The artery distal to the cuff is listened to using a stethoscope (auscultation method).

1. The first sound appear (is hear in the stethoscope) when the cutoff pressure falls below the peaks of blood pressure and blood can flow intermittently in the artery (systemic pressure)
2. As the cuff pressure drops below the diastolic pressure, blood flows continuously, the artery walls no longer close and the sounds of intermittent blood flow (heard in the stethoscope) disappear

Auscultatory Method

Measuring the ABP (arterial blood pressure) using the auscultatory enables the doctor to find a few different variables:

Systolic Pressure (SP) is the maximum pressure reached during peak ventricular ejection. Normal values at rest - between 100 and 140 mm Hg.

Diastolic Pressure (DP) is the minimum pressure reached during ventricular relaxation. Normal values at rest - between 60 and 90 mm Hg.

Pulse Pressure (PP) is the difference between the systolic and diastolic pressure. PP = SP - DP

Heart Electrical Stimulators

Programmable Pacemaker

Cardiac Pacemaker is an electric stimulator that produces periodic small electrical pulses to the heart (as from the AV and/or SA nodes). The stimulus aims to generate heart contraction (atrial and/or ventricular)

Approximately 500,000 new pacemakers are implemented each year and other 100,000 are replaced

There are two main types of pacemakers:

1. Competitive

This is a fixed rate (asynchronous) pacemaker.

2. Non-competitive

This is split into another two types, depending on the location. There are ventricular pacemakers that are either R-wave inhibited (demand) or R-wave triggered. And there are Atrial pacemakers that are usually P-wave triggered.

How a Pacemaker works

A Pacemaker has to work in synchrony with the heart natural pace, or to fully replace it. If it works in synchrony it has to detect the main heart rhythm (R wave) and, if R wave is there to inhibit the internal timer, but if it is different from the expected one, to generate a stimulus pulse (Feedback 1). The amplitude and duration of the stimulus electrical pulse can change to deliver the needed effect.

The pulse parameters depend on the the battery of the pacemaker. Feedback 2 constantly monitors the battery output and modifies the pulse parameters to deliver the needed effect. The pacemaker has to be protected from external strong electrical fields/pulses (e.g. Defibrillator). A number of leads (electrodes) deliver the pulse to the heart (same leads measure the heart activity).

Electrodes (either unipolar of bipolar) deliver a 1 millisecond pulse with 10 mA amplitude to the heart. The lead must survive constant flexing (30 - 40 million cycles per year) in warm, corrosive saline medium, therefore it is made out of platinum with 10% iridium alloy.

External pacemakers are for temporary arrhythmias and internal pacemakers are implanted for more permanent conditions.

The electrodes have a tissue resistance of ~500 Ω. Therefore using the P = I²R equation:

1 sec x 50mW will give average consumption of 50 μW per second (at 60 bpm). 10 mA flows for 1 msec - what gives an average of 10 μA per second.

The battery capacity (mAh) has to supply these 10 μAs for a number of years. Useful battery capacity divided to pulse charge 10 μAs will give the useful period of function (usually more ~ 10 years). This period depends on the type of use and the type of battery (i.e. lithium iodine cell).

Defibrillator

A defibrillator is an electrical device that produces a strong electrical pulse to heart aiming at re-establishing a more normal cardiac rhythm.

Atrial Fibrillation is where the ventricles still function but with an irregular rhythm.

Ventricular Fibrillation is very dangerous as the pumping function of ventricles stops.

Defibrillators deliver large electric shocks to the heart aiming to restore a normal sinus rhythm: total stop of the heart which inhibits fibrillation in hope that the heart will re-start in an orderly rhythm. The position of the electrodes is crucial for this to work.

The resistance of the skin/electrodes is ~50 Ω and the current through the chest is ~ 50 A. Pulse duration is ~ 4 msec.

Block Diagram of a Defibrillator

Inside the fibrillator is a capacitor which discharges itself over the heart.

There are three main types of defibrillators:

• Direct (during surgery) - max output ~ 50 J
• Cardioversion (synchronised clock across the chest for atrial fibrillation) ~20-200 J
• Emergency (ventricular fibrillation) - first pulse of ~200 J followed by higher E.

Implanted defibrillators (max 30 J) has a battery that is sufficient for ~ 100 shocks.

Basic Electrical Safety

A macro shock is where a high current passes through the body with a small component passing through the heart. A micro shock is a low value current passing directly through the heart.

Physiological effects of electricity

Tissue heating > x.10 kHz

This results at all frequencies if the power density is high enough.

Neuromuscular stimulation from x Hz to x kHz

Alternating current stimulates muscles directly. Ventricular fibrillation threshold is high for short impulses (e.g. 2 A for 200 msec) but fails dramatically for pulse durations approaching 1/3 of the cardiac cycle). Stimulation can occur through the skin:

• 1 mA: threshold of sensation
• ~ 6 mA: Let-go current is the maximal current at which the subject can withdraw voluntarily (before muscle paralysis)
• 18 - 22 mA: respiratory arrest
• 75 - 400 mA: ventricular fibrillation
• 1 - 6 A: sustained myocardial contraction
• Greater than 10 A: burns

Direct heart stimulation - ventricular fibrillation threshold is very low (~60 μA at 50 Hz)

Electrolysis very low freq

This takes places at electrode-tissue interfaces (even at d.c.). If a current of 0.1 mA d.c. passes through an electrode to jelly to skin for ~x minutes it can causes an ulcer.

Leakage Current

In hospital electrical devices a ground wire takes leakage current proportionally to the difference of resistance ground/heart (in the case 10,000 times more μA). However if the ground wire is broken all 100 μA leakage current will go through the heart and a micro-shock occurs at 60 μA (50 Hz).

Earth Leakage Circuit Breaker ELCB

It monitors the balance of incoming and outgoing current flows (from Live and Neutral) and interrupts the circuits if an imbalance is detected.

10
Non-Laser Optical Radiation

Learning Objectives

• What is Non-Ionising Radiation
• Sources of non-laser optical equipment in healthcare (phototherapy and dosimetry)
• The body that advises on Non-Ionising Radiation (NIR) protection
• The hazards of NIR
• UK Regulations
• Examples of Exposure Calculation

Non-Ionising Radiation NIR

NIR is radiation that does not produce ionisation. In healthcare the term is largely used to indicate both electromagnetic radiation and ultrasound (mechanical energy). Usually the wavelengths are greater than 100nm.

Electromagnetic radiation is made by quanta, i.e. photons. Each photon carries a finite energy (E) dependent upon the frequency (v) of the EM wave.

where λ is 100 nm, h = 6.626x10^-34 Js (Planck’s constant), C = 3x10⁸ ms^-1 (speed of light)

The minimum energy required for ionisation is about 12 eV. Photons need v < 100nm to have such energy.

There are two types of NIR, laser and non-laser radiation:

• Laser or Coherent: EM waves ‘phase-linked’ and same wavelength.
• Non-coherent: waves do not move in phase and have a different frequency.

Non-Laser Optical Radiation 100nm - 3mm

This is broad band optical radiation, produced by spontaneous incoherent emissions of excited materials (i.e. Gas, Semiconductors junctions).

Phototherapy Equipment

Phototherapy units exploit UV light (mostly fluorescent tubes) to treat skin diseases such as psoriasis. They work by interacting with the immune system and mechanisms of skin regeneration.

Different wavelengths have different penetrations in the skin and are more suitable for different diseases. The cabins are the most common Phototherapy units, or there are treatment beds for longer treatments. Hand and Foot units are used for partial disease or to top up radiation. The hands and feet are often used to exposure to NIR (from the sun) so need a higher dosage. There is also a comb unit if a disease is present on the scalp of a patient’s head.

Examination lights use both UV and visible lights. They can use a variety of light sources: UV compact fluorescent tubes, halogen and LED lights. The region of emission will depend on the specific source used.

Therapeutic sources that exploit the specific interaction of blue light with either the body or the materials (dentistry). They can used fluorescent, halogen or LED sources.

Other typical non-laser sources include Infra-red used in Gate analysis

UV Phototherapy Sources

Ultraviolet (UV) light is used to treat skin diseases. There are different spectra available. A dermatology consultant will recommend the use of one of them after assessing the patient. The starting treatment dose is chosen on the basis of the patient’s skin type or a test dose or (better) both. Phosphor coating on materials can be selected to obtain different spectral outputs.

Phototherapy lamps

Typical phototherapy lamps emit the following spectra:

• UVB: 280 - 315 nm (older, rarely used now)
• Narrowband UVB (TL01): 311 nm (newer technique, less hazardous, lower risk of cancer)
• UVA: 315 - 400 nm
• UVA1: 340 - 400 nm (newer technique, higher waves, higher doses)

The longer the wavelength of UV light the further it penetrates into the skin

The light dose for patients exposed to a UV phototherapy source (D), is estimated in terms of radiant energy received for unitary surface and measured in Jm^-2 (or often in practice as mJcm^-2). The dose (D) can be calculated by the knowledge of a source irradiance (E) and patient exposure time (T).

Dose

$ D = ET $

D (Jm^-2), E (Wm^-2), T (s)

International Commission on NIR Protection ICNIRP

This is a non-profit independent body that disseminates information and advice on potential on potential health risk linked to non ionising radiation (NIR). It has a main commission of 14 scientific experts with 4 standing committees (7 members):

• Epidemiology
• Biology
• Physics
• Optics

ICNIRP daily limits

H_eff = 30 Jm^-2 in 8hr (eye, skin)
H_UVA = 10⁴ Jm^-2 in 8hr (eye - lens)

(ICNIRP - 2010)

Hazards of NIR

Optical radiation can undergo transmission, reflection, refraction, diffraction, adsorption, scattering. UV photons above the ionisation energy can disrupt atoms and molecules. UV photons below the ionisation energy are strongly absorbed in producing electron transitions.

Exposure to UV can affect either the skin or the eyes. UV radiation produces photochemical damages. The photons absorbed have enough energy to induce modifications into the molecules.

Skin Hazard

• Erythema
• Elastosis
• Skin Cancer

Ocular Hazard

• Conjunctivitis
• Photokeratitis
• Cataractogenesis

Visible light Hazards

Exposure to intense visible light can cause retinal damage. The hazard is highest at those wavelengths the photoreceptors of the retina are most sensitive to 450-550 nm.

UK Regulations on UV equipment

Health and Safety at Work Act 1974 HSW 1974

It shall be the duty of every employee while at work to take responsible care for the health and safety of himself and of other persons who may be affected by his acts or omissions at work.

Personal Protective Equipment at Work Regulations 1992 PPEWR 1992

European Directive on Artificial Optical Radiation 2006/25/EC AORD 2006

This refers to the ICNIRP guidelines on exposure: - Wavelength dependency of the hazards - Maximum exposure for specific bands of emissions

The Control of Artificial Optical Radiation at Work Regulations 2010 AORR 2010

The employer must eliminate or reduce any risk related to exposure to optical radiation. Staff exposure to non-coherent optical radiation must be below Exposure Limit Values (ELVs) specified in Annex I of the AORD.

Action Spectra

The wavelength dependency of the optical hazard is described by hazard Action Spectra (AS). The ICNIRP adopts 2 spectra for UV, one for blue light damage and one for thermal damage.

Maximum Exposure Time

$ MET = \frac{b}{E} $

MET is Maximum Exposure Time (s), b is the guideline limit (Jm^-2), and E is the Exposure produced by the unit (mWm^-2)

Questions

Non-laser optical equipment uses what time of radiation and what are the range of emissions?
Broadband radiation wth emissions between 100nm - 3mm

Name four typical non-laser optical sources in healthcare
Phototherapy UV lights, diagnostic lights, blue light units and infrared thermometry

Who is the body that advises on NIR hazards?
ICNIRP

What are the organs exposed to NIR optical radiation?
Skin and Eyes

What is the specific UK regulation on UV?
The Control of Artificial Optical Radiation at Works 2010 is the specific UK regulation

11
Laser Optical Radiation

Learning Objectives

• The physics and different modes of operation of lasers
• Laser classification
• Quantifying laser hazards
• Protective eyewear
• Laser interactions

Introduction

We are interested in the following portion of the electromagnetic spectrum, regarding lasers:

Lasers created from an artificial optical coherent radiation source were first invented in 1960 by Maiman. LASER is an acronym for:

• Light
• Amplification by
• Stimulated
• Emission of
• Radiation

The basic components of a laser are:

• Laser medium: this determines the wavelength of the laser emitted and can be solid, liquid or gas
• Energy source: this gives energy to the laser medium which in turn emits light photons.
• Optical feedback: allows the light photons to interact (possibly many times) with the laser medium

Basic Laser Physics

Atoms in the losing material exist initially in the ground state with energy A.

Stimulated Absorption

An energy source source provides energy to the lazing material and *raises atoms from the ground state (A) to an excited state (A)** by a process called stimulated absorption. The energy required is A* - A, and the value of this depends entirely on the lasing material and determines the wavelength of the laser.

Population Inversion

The majority of the atoms in the lasing material are in the excited state.

Spontaneous Emission

Atoms spontaneously decay back to the ground state, emitting photons with random phase & direction.

Stimulated Emission

The “trigger photon” from spontaneous emission (with energy A* - A) encounters excited atoms from the lasing material. The excited atom is forced to emit a photon with identical direction & phase (i.e. wavelength) than the “trigger photon” leading to amplification.

Laser Design

A lasing material is encased between two mirrors inside a laser cavity. An energy source excites the lasing material that emits photons. A back mirror is fully reflective & a front mirror is partially transmitting to allow photons to exit the laser cavity. The laser beam can only emerge when the shutter is opened (i.e. foot/hand switch activated). Beam delivery device directs the beam to its final destination. A cooling system is also required to maintain output level.

Beam Delivery System

The laser energy is transferred to the treatment site in one of two ways:

1. Articulated Arm

This hollow articulated arm has mirrors (highly polished stainless steel) at elbows. The beam alignment is crucial.

2. Optical Fibres

This uses reflections to trap the light inside (total internal reflection). Light rays can travel along glass or plastic fibres. The laser will lose it’s coherence (this has no significance for treatment purposes).

Laser Light Properties

Lasers have many different useful properties:

• Monochromatic (i.e. one frequency): all the light is emitted in a very narrow band of wavelengths.
• Coherent: all the light waves emitted from the laser are in the same phase (same wavelength and same frequency)
• Directional: laser light emitted is highly directional as it tends to diverge slowly.
• Intense: laser beams tend to have a high intensity, with some lasers up to x100 brighter than the sun.

Modes of operation

When treating a patient then the method of laser light delivery is very important:

• Continuous: Laser light is continuously pumped and continuously emits light.
• Pulsed: Laser is operated in short pulses which may be predefined or operator dependent. Typical pulse duration is 0.25 s to 10 μs.
• Q-Switched: Laser medium is pumped but the “trigger photons” that cause stimulated emission are prevented from entering the laser medium. Continued pumping leads to population inversion and gain saturation. At gain saturation, the “trigger photons” are allowed to enter the lasing medium resulting in emission of a giant pulse. Typical pulse duration is 5 - 40 ns.

Measuring Laser Output

Laser outputs tend to take into account the area of the beam as this is key to the effect the beam has on the surface. There are two main types of lasers, continuous and pulsed:

Continuous wave laser

For a continuous wave laser, power ($ \frac{energy}{time} $) is the most useful measurement, and its units are Watts (W). Irradiance takes into account the area of this power and it is measured in W/cm²

Pulsed laser

For a pulsed laser, energy is the most useful measurement, and its units are Joules (J). Radiant exposure (dose) takes into account the area of this energy and is measured in J/cm².

Radiant Exposure (J/cm²) = Irradiance (W/cm²) x time

Interactions

Some of the properties become important when treating a patient.

Transmission

If no chromophore (an atom or group whose presence is responsible for the colour of a compounds) all photons will pass through the tissue without any effect. There will be total transmission. Selection of proper chromophore in or near the target is the first important step.

Reflection

This occurs at all interfaces of media, such as air, water, skin surface. Skin reflects 4% to 7% of visible light. To reduce reflection have firm contact with skin, light guide, US jelly, holding hand-piece perpendicular to the skin surface.

Scattering

This occurs predominantly from inhomogeneities in structures whose size is similar to the wavelength or slightly larger i.e. collagen fibres. It is the inverse function of wavelength. A shorter wavelength equates to greater scattering. The greater the scattering, the less depth of penetration and more possibility of absorption.

Other

Other factors also have a bearing on the depth of penetration. In tissues, more scattering occurs when a small spot size is used. With a large spot size, photons hit each other and are recollected and redirected downward increasing the depth of penetration.

Classification

A laser manufacturer is responsible for assigning all laser products to one of seven general hazard classes defined in BS EN 60825-1:2007:

Access to areas in which Class 3B or Class 4 lasers are used must be marked with warning signs.

Accesible Emission Limit

This determines the classification of a laser or laser product. It depends on how much access an individual has under normal operating conditions, for example:

• Open beam laser - full access - maximum hazard
• CD player - no access
• Laser printer - no access

Quantifying Laser Hazards

Maximum Permissible Exposure MPE

Maximum exposure level to laser radiation that (in normal circumstances) should not injure the eye or skin. Data and equations are given in BS EN 60825-1:2007

It is at a different value for the skin and the eyes. MPE can be stated in two ways discussed earlier:

• Watts per metre squared (W/m²) is termed ‘Irradiance’
• Joules per metre squared (J/m²) is termed ‘Radiant Exposure’

If the exposure time is known then its possible to convert between the two

Determining MPE

For example, imagine a diode laser with a wavelength of 689 nm. It has a power output of 4 mW, a beam diameter of 3mm and is a continuous wave. First the area of the beam is calculated:

From this the irradiance at the laser exit (neglecting divergence) can be calculated:

A more complicated calculation is irradiance to the eyes. The limiting aperture over which the average irradiance for an eye exposure would be 7mm. First the area of the eye aperture is found:

Then the average irradiance to the eye is calculated:

The diode laser emits in the visible range at 689 nm so the blink reflex response needs to be taken into account. At this value the MPE is 18 t^0.75 C₆ Jm^-2. This values is found from a table when t is blink response time of 0.25 s and C₆ is the correction factor (this is 1 for our purposes).

Combining all these values the MPE at the cornea works out to be 6.36 Jm^-2 or 25.3 Wm^-2. These MPE values are clearly exceeded by our previous calculations of 103.9 Wm^-2 therefore safety eyewear would be required.

Note: if the laser is invisible, then you can’t use the blink response time of 0.25 s. In this case, 10 seconds is generally used instead.

Nominal Ocular Hazard Distance NOHD

This is the distance from laser aperture at which it would be safe to view the laser without safety glasses, when the laser output is below the MPE level. This can range from ‘cm’ to hundreds of metres and depends on the output level and type of laser. As the beam size gets larger, the area that the power is divided over gets bigger and so the irradiance gets smaller. At a certain distance, the irradiance will equal the MPE and this is called the Nominal Ocular Hazard Distance (NOHD).

Determining NOHD

In order to determine NOHD the following equation is used:

$ NOHD \ (m) \ = \ \frac{\sqrt{\frac{4 \times Power}{\pi \times MPE} \ - \ aperture \ diameter }}{Divergence} $

Radiant power (W), Aperture diameter (m), Divergence (radians), Maximum Permissible Exposure level (Wm^-2)

Protective Eyewear

Persons standing at a distance closer than the NOHD should wear adequate protective eyewear. It is designed to reduce worst case accidental viewing conditions to a ‘safe’ level (blink reflex applies). Protection level is reduced when beams are focused to small spot sizes (as encountered in medical applications)

Optical Density

This represents a measure of the transmission of an optical medium for a given wavelength. It is a logarithmic scale:

OD5 results in a reduction in transmission by 10⁵ (100 000 times). OD5 is usually high enough as it reduces a 100 W laser beam to 1 mW.

Note: the optical density fails to explain how long it will offer protection for

BS EN 207(2009)

This takes into account both optical density & damage threshold of a material. This guarantees protection from direct beam for only 5 secs or 50 pulses under specific test conditions. L-number indicates protection level and this varies with mode of operation and wavelength.

D - Continuous, I - Pulsed, R - Q switched (v. short powerful pulses)

Laser Interactions

Biological Effects

The interactions that lasers have with biological tissues depend on three main parameters:

• Wavelength Laser radiation needs to be absorbed in tissue to have any effect
• Pulse Duration
• Output Power

The location and level of absorption of laser radiation is strongly wavelength dependent. The interaction effects can be roughly grouped into the following processes:

Photochemical UV blue end

Photochemical damage can occur for lower irradiance that are not high enough to cause thermal damage (i.e. too small to cause a temperature rise). Examples include skin tanning, psoriasis treatment, new born jaundice treatment, sunburn, skin cancer and cataracts.

Thermal

Above a critical tissue temperature, proteins are de-natured and thermally induced damage occurs. At temperatures of 60°C, coagulated tissue becomes necrotic. Once temperatures are greater than 100°C, water in the tissue begins to boil. Further temperature increases lead to carbonisation.

Carbonisation should be avoided since the tissue will die at lower temperatures and it reduces the visibility of a target during surgery. To avoid carbonisation, the tissue is usually cooled using water or gas. Examples of thermal effects include coagulate, cut & burn and heat.

Photoablation thin layers of tissue are removed

On the surface of a tissue such as the cornea for UV and far IR wavelengths, thermo-mechanical effects lead to ablation of material. The heated material is rapidly removed from the rest of the material which is hardly affected by the process.

The depth of tissue removal is determined by the pulse energy. Advantages of this procedure are the precision of etching and the fact that no thermal damage is caused to the surrounding tissue.

UV photons (typically Excimer lasers) provide enough energy for this mechanism to occur. An example of photoablation is vision correction surgery.

Thermomechanical

This occurs when tissue is heated very rapidly. Rapid thermal expansion and vaporisation of liquid leads to mechanical shock waves. Cells rupture explosively.

For ultrashort pulses, a very high temperature plasma may also be formed. This leads to shockwave generation & ablation (a process called photodisruption). Examples of thermomechanical effects include kidney stone removal and removal of fibrous tissue growth which can form after cataract surgery.

Eye Hazards

The eye is the most vulnerable to laser hazards. Injuries can occur at much lower power levels than for the skin and are typically more serious than skin effects:

UVA lens

The lens the pre-dominant absorbed of UV-A although a small amount is absorbed by the cornea. The effectiveness of UV to induce photochemical damage decreases with increasing wavelength. Thermal damage is the main concern here.

UVB cornea lens

UV-B light penetrates deeper into the eye and both the cornea and the lens are at risk. Levels encountered in accidental laser exposure are typically well above the threshold causing permanent damage to the lens.

UVC cornea

The absorption depth is very shallow and all light is absorbed in the surface of the cornea. Exposures above the threshold for damage for short pulses can result in ablation of the cornea .i.e. Excimer lasers.

If the peak irradiance is not high enough for photoablation, inflammation can occur. The injury can take take several hours to develop.

Retinal Damage 400nm - 1400nm

Between 400 nm and 1400 nm wavelengths, the retina is at risk. Transmission is higher in young persons (~380 nm) compared to adults. Concern from widespread use of LEDs emitting in the near UV range. Retinal damage will be permanent.

Infra-red Radiation

Near IR is transmitted to the retina. Mid-range IR affects the cornea and penetrates the aqueous humour. The far IR is absorbed by the cornea.

The cornea is damaged at an irradiance level lower than that necessary to acutely affect the lens. Below 1400nm, injuries can be superficial and will heal within a couple of days. Above 1400nm injuries will be deeper and permanent (well above threshold)

Eye Protection is required to all lasers of class 3R and above.

Skin Hazards

Risk of skin injury is secondary to eye damage. Skin injuries are not as significant and will usually heal, even after penetrating damage that may lead to infections. Damage to the skin may be thermal or photochemical, known simply as a ‘burn’ or a ‘sunburn’. Burn generally means a thermal injury. Sunburn generally means a photochemically induced erythema. Effects on the skin will depend on:

• Power
• Wavelength
• Spot Size
• Duration of Exposure
• Blood Circulation
• Heat Conduction of Exposed Skin

Skin Injuries can vary greatly in severity with a severe thermal injuries possibly damaging the underlying muscle and major blood vessels.

Associated Hazards

Not direct hazards from laser light but the hazards from the equipment that create it, and these include:

• Electrical
• Mechanical
• Chemical
• Fire and Explosion
• Noise
• Temperature & Humidity
• Smoke/Vapour/Fumes

Examples of Laser Applications

• Tattoo Removal: Modern lasers are more gentle and effective at removing tattoos with less chances of scarring.
• Laser Skin Resurfacing
• Ophthalmic Treatments: such as laser vision correction (LASIK treatment)
• Dentistry
• Tongue tumour
• Endovenous Laser Treatment (EVLT)

12
Radiotherapy

Learning Objectives

• Cancer Basics
• Fractionation
• The use of photons in radiotherapy
• Special techniques in radiotherapy
• Role of physicists in radiotherapy

Radiotherapy is the treatment of cancer with ionising radiation.

What is cancer?

The abnormal, uncontrolled growth of cells that ultimately forms a tumour. As the tumour grows, some abnormal cells can break off and spread via the blood and lymph system to other parts of the body. This is known as a metastatic spread.

Stages of Cancer

Cancer is initiated by a genetic mutation that affects the cell growth mechanism. Internal or external agents can promote the growth of that particular cancer. Cancer then progresses and becomes more aggresive

Cancer Treatments

Treatments for cancer can include surgery, chemotherapy, hormone therapy, immunotherapy and radiotherapy.

Chemotherapy

Chemotherapy is where drugs are used to kill rapidly dividing cells. However cancer cells are not the only cells which are quickly dividing, other cells such as Red and White Blood Cells are also killed during treatment. As a result this lowers the immune system of patients, making them prone to infections. Another side effect is hair loss.

Hormone Therapy

Some cancer cells are hormone receptive (e.g. breast cancer). Drugs such as Tamoxifen can bind to these receptor sites on the cancer cells, preventing their further division.

Immunotherapy

Tumour cells bind to T-cells to deactivate them. Immunotherapy drugs specifically block tumour cells from deactivating the T-cells, so the T-cells will kill the cancer cell.

Ionising Radiation Treatment

If an ionisation treatment is applied during mitosis (as the cell is dividing), this is the most effective phase in the cell cycle to damage the cell.

Cancer cells cope less with an increase in radiation dose than normal cells, as cancer cells are more often in metaphase.

Fractionation

This is a form of radiotherapy where multiple small doses of radiation are used at intervals to take advantage of the fact that normal cells recover faster (and are less damaged by radiation) than cancer cells.

Fractionation has an enhanced effect on cancer cells. The common mode of delivery is around 30 fractions over 6 weeks. Hyperfractionation is an experimental technique using even more fractions.

Radiation Dose Gray

A prescription is given in cGy (centiGray) which is related to former unit, rad (where 100 rad = 1 Gy). Usual doses are given in 10’s Gy in fractions of 1-2 Gy. Accuracy is critical (needs to be above 3%). A typical radiotherapy treatment could be 50 Gy.

Photons

X or gamma rays are predominantly used in radiotherapy. Their penetration increases with energy, and have interactions that include photoelectric absorption, compton scatter and pair production.

Depth Dose Characteristics

The ionisation is greatest not at the surface of the skin but at a slight depth. This slight depth is known as the build up. The higher the energy the longer it takes to ‘build up’ the number of electrons so the depth is deeper.

Plotting tank

Is a large size motorised 3D water phantom for automatic dose distribution measurement of radiation therapy beams. Inside a plotting tank, there is an ionisation chamber to accurately measure the detection and measurement of certain types of ionising radiation; X-rays, gamma rays and beta particles.

Treatment Planning

A treatment is planned to maximise the dose to the tumour and minimise the dose to the surrounding tissue. The parameters than a radiotherapist can change is the penetration, the number of fields, the field size and the field shape. It is usually computerised.

In order to plan a treatment, imaging is often used to locate the tumour. Tumour localisation and beam positioning can be found using a CT simulator. Fluoroscopy and beam positioning can be used to stimulate a treatment.

Single Field Treatment Plan

This is an unsatisfactory treatment plan, as there is a dose gradient across a tumour, and a higher dose is given to the normal tissue above it.

Parallel Opposed Treatment Plan

This is a more accurate, where the same field is given from both sides. However again it is not sufficient to provide a cure because it causes too much damage to normal tissue. It is used almost always in palliative treatment.

External Beam Radiation Therapy

With more beams, the treatment begins to become more accurate and effective than the single/parallel field treatments. However there are still come complexities with treatment. For example, the rectum is next to the prostate, but it is extremely sensitive to radiation. So to avoid any unwanted effects the beam is modified using:

• Collimators
• Filters (beam flattening)
• Wedges
• Compensators

Treatment Delivery

Treatment can be delivered using a variety of techniques:

• Gamma therapy: originally used Radium 226, more recently caesium 137. The problem with gamma is that it has to be changed every few years and so these machines are no longer used.
• Superficial x-ray: (approx 300 keV) is used to treat cancers on or near the skin surface.
• Linear Accelerators: (Linac) these are x-ray devices, using 5 - 25 MeV. It has almost replaced cobalt external beam machines. See below for a cross-section of a linear accelerator.

Alignment

Patient set-up is crucial, with alignment as simulated. Patient’s are often given skin tattoo’s to align them with a laser as accurately as on the simulator. A cast is used for head and neck to prevent the patient from moving. The latest systems are even synchronised to breathing.

Special Techniques

Portal Imaging

This is imaging during therapy. The alignment of the beam is confirmed with the tumour site. This allows modifications to the position etc. on the fly if the tumour volume changes during treatment.

Intensity Modulated Radiation Therapy IMRT

This involves treating irregular shaped tumours. Detailed planning is required. It uses a multileaf and dynamic collimator, which aids in beam shaping/accuracy. Tomotherapy scans a tumour while it is being treated by radiotherapy.

Gamma Knife

This is used to combat brain tumour. It consists of multiple small beams (60+). Complex planning is involved.

Total Body Irradiation TBI

TBI is used in leukaemia treatment. It destroys malignant bone arrow, which is replaced by a transplant of matched donor marrow. The set up is designed for uniform irradiation, lung dose is critical (10 Gy dose).

External Beam Radiotherapy EBRT

External beam radiotherapy (EBRT) or teletherapy is the most common form of radiotherapy (radiation therapy). The patient sits or lies on a couch and an external source of ionizing radiation is pointed at a particular part of the body.

Brachytherapy

Brachytherapy is a form of radiotherapy where a sealed radiation source is placed inside or next to the area requiring treatment. Brachytherapy is commonly used as an effective treatment for cervical, prostate, breast, and skin cancer and can also be used to treat tumours in many other body sites.

Role of Physicists

Physicists are heavily involved in treatment planning, identify problems and providing solutions. During treatment planning they lease with the oncologist and determine the best ‘set-up’. Physicists calculate the point dose and discuss this with the oncologist.

They look at the beam output, field uniformity, beam alignment (radiation/light), interlocks (doors, wedges etc). They measure all field sizes to ensure beam data is correct, beam outputs (all energies, photons and electrons) and other safety features. This process can take months.

Physicists are also commissioned for room design and protection. For example in a radiotherapy bunker, shielding, scattering and safety features all have to be calculated.