BME481 MEDICAL IMAGING

Dr. Betül Polat Budak BME481 Medical Imaging 1

 Lecture Contents:
• Introduction to Medical Imaging concepts
• Biomedical images: signals to pictures I: Ionizing Radiation
• Biomedical images: signals to pictures II: Non-ionizing Radiation
• Image quality
• Projection Radiography: X-rays
• Projection Radiography: CT
• Nuclear Imaging: Planar Scintigraphy
• Nuclear Imaging: PET and SPECT
• Ultrasound Imaging
• Magnetic Resonance Imaging
• Advanced and combined Techiques
• Wrap up and Closing remarks

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 Lecture 5

Projection Radiography: X-rays

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 Lecture 5 Part III
Projection Radiography: X-rays Contents
5.5 Radiation Dose and Radiogenic Risk

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 Radiation Dose and Radiogenic Risk

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 Radiation Dose and Radiogenic Risk
• Imaging with gamma- and X-rays has saved countless lives over the
past century, but medical radiation is a double-edged sword.
• Until recently, most of the ionizing radiation to which we are all
exposed was naturally occurring.
• It comes primarily from three sources: cosmic rays, which are highly
energetic protons and other particles bombarding Earth from outer
space, mostly from the Sun; radioactive materials in the soil and rocks
around us (primarily radium-226 coming from the decay of uranium-
238) and in our bodies (potassium-40) that emit gamma-rays; and
radon (Rn-222), a noble gas originating with the decay of radium in
the soil that then seeps into our basements.
• Our exposure to ionizing radiation has doubled over the past few
decades

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 Radiation health effects are caused by
damage to DNA
• The very photon-electron event that
removes a photon from the beam, and
thereby contributes to image formation,
also give rise to a high-energy photo- or
Compton electron. As it blazes through
tissue, this ejected electron dissipates its
considerable kinetic energy over a
millimeter or so by exciting and ionizing
hundreds or thousands of molecules lying
along its erratic path. In so doing, it may
directly or indirectly excite or ionize DNA
molecules, inducing chemical changes
that give rise to alterations of base
sequences or other damage.
• Radiogenic harm to DNA comes primarily
in two ways, known as direct and indirect
attack
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 Direct and indirect attack
• With direct attack on a DNA molecule, a fast electron passing nearby
will directly excite or ionize some part of a strand of DNA and leave it
in an unstable, chemically vulnerable excited state, DNA∗:
DNA + energy → DNA∗.
• Alternatively, the typical mammalian cell is 80–90% water, and in an
indirect attack, a high-speed electron transfers some of its kinetic
energy to a water molecule, commonly just splitting it into hydrogen
and hydroxyl free radicals, H• and OH•,
H2O + energy → H• + OH•,
• or any of a number of similar entities.

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 Sequence of events in the radiation
damage in cells.

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 Sequence of events in the radiation
damage in cells.
• Events tend to follow a well-defined general sequence.
• Fast Compton- or photoelectrons or free radicals attack a DNA
molecule, causing a structural transformation. If too many essential
cells in a tissue are killed or rendered non-functional, the irradiation
will lead to a deterministic health effect in the tissue as a whole.
Conversely, certain kinds of damage to the genetic material of one or
a few cells may result in a stochastic health effect, such as a cancer or,
if the affected cell is a germ cell, a transmitted genetic effect. Finally,
irradiation during rapid cell growth and organogenesis, as occurs in
humans approximately from weeks 3 to 11 weeks of gestation, may
also lead to congenital anomalies from changes in the growth
parameters of the affected cells.

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 Stochastic (probabilistic) radiogenic
health effects
• It is widely assumed (but not proven)
that even a small dose of ionizing
radiation can occasionally cause
genetic mutations that substantially
corrupt the information content of the
DNA of one or a few cells. Such a cell
transformation may turn on an
oncogene, or switch off the
suppression of one, resulting in
uncontrolled mitosis.
• Malfunctioning DNA can also lead to stochastic effects other than
carcinogenesis, such as genetic effects manifesting in one’s progeny or,
in the case of irradiation of the fetus, growth restriction, microcephaly,
mental retardation, and other congenital abnormalities.

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 Stochastic (probabilistic) radiogenic
health effects
• The word stochastic refers to events that occur randomly and
independently, for which it is only their probabilities of occurrence
that can be estimated.
• Radiogenic cancers and genetic errors are said to be stochastic, in the
sense that they are brought about by random collisions of high-energy
photons and electrons with atoms. Such health effects are not certain
to occur even at high exposures, but their probability of occurrence
does increase with dose, at least at higher doses (>0.1 Gy). It appears
that, unlike the case of cell killing or apoptosis, no critical number of
cells have to be transformed for this to occur, and it may (or may not)
be that there is no dose threshold below which there is no risk.

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 The sievert (Sv) of equivalent dose
• “Dose” refers to ionizing radiation delivered to anything at all, animal,
vegetable, or mineral, and it is quantified in terms of grays. It has been
helpful to contrive several other entities that relate to the induction of
stochastic (not deterministic) health effects in human tissue. The two
most important of these are equivalent dose and effective dose, and
these both come in units known as sieverts (Sv)

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 linear energy transfer (LET)
• A number of parameters affect the response of cells or tissues to
irradiation. Some of these are their normal rate of cell turnover (i.e.,
frequency of mitosis), the degree of cell differentiation, the stage of
the cell cycle at the time of irradiation, and the presence of naturally
occurring or synthetic chemical radiation sensitizers (in particular,
oxygen) and protectors. The most important radiation-related factors
are the dose, the dose rate, and the pattern of the ionizations it
produces. In particular, when charged particles pass through matter,
whether they be Compton electrons or carbon-12 ions from a
specialized radiotherapy treatment machine, they leave trails of
ionizations behind them. The spatial rate at which they deposit their
energy along their paths, ΔE/Δx, is called the linear energy transfer
(LET).

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 High-LET and Low-LET radiation
• Compton and photoelectrons (and by extension, the gamma- and X-rays that
liberate them) are therefore said to be low-LET. When a low-LET particle
passes close to a DNA molecule, ionizations of the medium will tend to occur
at points so far apart that immediate damage will almost always be confined
to only one base or one sugar-phosphate strand.
• Protons and alpha particles, by contrast, are thousands of times heavier than
an electron and, with the same kinetic energy, move perhaps a hundred times
more slowly. They transfer energy to the medium in this particularly effective
fashion, and they are termed high-LET particles. High-LET radiation is much
more probable than low-LET to cause double-strand breaks and certain other
forms of complex damage in DNA that are resistant to complete cellular
repair.

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 Dose-risk assumption and estimates of
[Risk/Dose]
• it is estimated that we all have about
a 1 in 100 chance of dying from a
cancer induced by the 3 mSv/year of
natural background radiation.
Risk = [Risk/Dose] × [Dose].
• This essential linear, no-threshold
(LN-T) assumption underlies virtually
all of radiation protection at the
present time. It incorporates two
important points: first, the risk rate,
[Risk/Dose], is a constant and
independent, in particular, of the
dose. Second, the radiation risk is
linearly proportional to the dose,
[Dose], and there is no threshold
dose below which very low levels of
exposure are risk-free
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 Optimal dose for patient survival of
both the disease and the diagnosis
• Any diagnostic procedure that involves ionizing radiation must deposit
at least a little dose to provide a benefit, and sometimes more than a
little. But that possibly leads to an associated risk.
• Suppose that a patient presents with symptoms of a disease that is lethal if
untreated, and for which there is a reliable gamma- or X-ray imaging tool that can
reveal how to treat it properly. The probability of successfully detecting and
analyzing the lesion, thereby making it possible for the patient to ´Survive the
disease, Scure(D), is likely to be a sigmoidal function of patient dose, D . At too low
an exposure, noise will be too high, yet the use of very high doses won’t improve
things. (Indeed, with a screen-film system, say, too much dose to the IR will turn
the film entirely black.) The symbol S is adopted to emphasize the point that it
represents the probability of subsequent patient Survival of the illness.

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 Optimal dose for patient survival of
both the disease and the diagnosis
• At the same time, the probability that the patient will suffer a lethal radiation-
induced cancer from the diagnostic procedure itself is assumed to follow the linear
no-threshold dose response relationship; equivalently, the probability that the
patient will Survive the possibly deleterious effects of the diagnostic procedure
decreases from unity, falling off linearly and extremely slowly as Srad(D) = [1 – αD]
for some small α.
• The overall probability of patient well-being, Spatient(D), the likelihood that the
patient will survive both forms of harm (i.e., be cured of the disease and yet not
incur a radiogenic cancer during the diagnosis) is therefore given by the product of
the two independent probabilities, Spatient(D) = Scure(D) × Srad(D).
• This product passes through a maximum at some “optimal” exposure, Dopt, and,
if the objective is to cure the patient and do no irrevocable harm in the process,
then Dopt is the best amount of dose to employ. At lower exposures, the increased
risk from the disease would more than compensate for the reduced hazard of the
radiation itself, and the converse is true above Dopt.

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 The effective dose
• The effective dose (ED) is widely
viewed as the least bad available
method to estimate the stochastic
risk for a person who is exposed
non-uniformly.
• Formerly known as the effective
dose equivalent, the ED is a risk-
weighted average over the local
doses to the various organs and
Tissues, as parameterized by the
index T.
• Effective dose accounts both for the
organ/tissue dose, DT, and the
ED = ෍ 𝑊𝑇𝐷𝑇
relative radiosensitivity of each, with
a tissue risk-weight of wT:

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 Representative doses for diagnostic
studies
• Although there are numerous sources of
guidance on estimated organ and
effective doses from various medical
procedures, two of the most useful at
present are the NCRP report no. 160,
and a series of reports prepared by the
NEXT program (Nationwide Evaluation
of X-ray Trends) managed by the Center
for Devices and Radiological Health
(CDRH) of the FDA and the Conference
of [state] Radiation Control Program
Directors (CRCPD).

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 Stochastic health effects in children

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 Stochastic health effects in children
• Infants and children are biologically different from adults, and they
require special care during all forms of imaging. For one thing, their
tissues are inherently more radiosensitive: they have relatively more
cells that are rapidly dividing, so there is greater opportunity for
uncorrected errors to arise and be propagated. Red bone marrow, for
example, is found throughout the neonate’s body, and it is a highly
radiosensitive tissue. Also, the cells of the young appear to be less
effective at repairing the mutations that may be caused by ionizing
radiation.

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 Deterministic health effects at
high doses
• Cell death is of no importance if only a few cells are so affected,
except in the early embryo. But, as a result of exposure to a high dose
of radiation above a tissue-specific threshold dose, adequate repair
may not take place; too large a fraction of the cells in the tissue may
undergo radiogenic acceleration of the normal physiological process
of apoptosis or be killed outright

Deterministic effects should almost never arise from diagnostic studies

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 Deterministic radiogenic health effects
• As has been verified numerous times in the
years since, tissues with cells that normally
undergo rapid proliferation or self-renewal are
commonly more sensitive at elevated doses (far
above the diagnostic range) to radiation-
induced cell killing and the resultant
deterministic effects.
• Rapidly dividing cells such as the epithelium of
the GI tract, skin and hair cells, erythroblasts,
spermatogonia, and lymphocytes are typically
highly sensitive due to the large fraction of
time spent in the M-phase of the cell cycle.
• And ionizing radiation depletes the supply of stem cells – it either kills them
outright or inhibits their mitosis – so that they can no longer replenish the tissue
at a rate sufficient to maintain its proper functioning.
• Cells with high metabolic activity, for example, exocrine glandular cells such as
those of the salivary, are also very radiosensitive. Muscle and nerve cells, by
contrast, are relatively resistant to radiation damage.

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 Teratogenic effects in the unborn
• Epidemiological studies indicate that the incidence of childhood
malignancies caused by irradiation in utero increases with dose, but
that the risk is small. The primary concern is with non-stochastic harm.
• In those few, higher-dose cases where teratogenic effects have arisen,
damage includes both congenital physical defects manifested as
growth-restriction and microcephaly, and a lowering of intelligence to
the point of severe mental retardation. Two primary determinants of
the extent of radiogenic damage in the womb, as learned largely from
studies on mice and rats and to some extent from the atomic bomb
survivors, are the dose received and the timing of the exposure.With
regard to radiation harm, gestation may be partitioned into three
distinct periods: preimplantation, organogenesis, and fetal. Pre-natal
death can be induced at any time by a sufficient dose, but the
threshold for this increases with embryonic/ fetal age.

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 Acute radiation syndrome
• This section has absolutely no application to the normal usage of
radiation in diagnosis or therapy, and hopefully you will never have cause
to turn to it, except out of general interest.
• It is possible that people may receive excessive whole-body irradiations
from, for example, an industrial accident.
• ARS consists of a complex of distinct deterministic effects caused by
radiation damage to specific organ systems, namely the bone marrow
(the most radiosensitive), the lining of the small bowel, the skin and, at
very high doses, the microvasculature that supports the nervous system.
A common set of symptoms including nausea, vomiting, diarrhea, and
headache, may manifest within minutes or not for days, and these can be
brief or long lasting. There follows a “latent” period during which the
patient may feel and appear healthy. But the same symptoms return after
that, along with new ones like loss of appetite, fatigue, fever, and, for the
most intensely exposed, seizures and coma. The severity and speed of
onset of the symptoms increase with the amount of damage caused,
which, in turn, increases with the dose imparted
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• A radiation safety program is built
on a solid philosophical
foundation, and consists of
personal actions and imaging
center activities that are guided,
or required, by the components of
the administrative structure.

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 Sources
• Medical Imaging For Health Professionals: Technologies And Clinical
Applications, First Edition. Edited By Raymond M. Reilly. © 2019 John
Wiley & Sons, Inc. Published 2019 By John Wiley & Sons, Inc
• Prince And Links, Medical Imaging Signals And Systems
• Fundamental Mathematics And Physics Of Medical Imaging
• Introduction To The Science Of Medical Imaging
• Introduction To Medical Imaging, Physics, Engineering And Clinical
Applications

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