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1

Nuclear Medicine Imaging


Peter F. Sharp and Keith A. Goatman

1.1 Introduction of radiopharmaceutical present. Such measure-


ments are made using the gamma- or beta-sample
In nuclear medicine clinical information is de- counting techniques discussed in Chapter 4.
rived from observing the distribution of a phar- The diagnostic information is provided by the
maceutical administered to the patient. By incor- action of the pharmaceutical; the role of the ra-
porating a radionuclide into the pharmaceutical, dioactivity is purely a passive one, enabling the
measurements can be made of the distribution of radiopharmaceutical to be localized. For this rea-
this radiopharmaceutical by noting the amount of son it is possible to use low levels of radioactivity
radioactivity present. These measurements may and so the potential hazard to the patient can be
be carried out either in vivo or in vitro. In vivo kept small (see Chapter 6).
imaging is the most common type of procedure
in nuclear medicine, nearly all imaging being car-
ried out with a gamma camera (see Section 1.3). 1.2 The Ideal
Nuclear medicine is intrinsically an imaging tech-
nique showing the body’s biochemistry, the par- Radiopharmaceutical
ticular aspect depending upon the choice of the
radiopharmaceutical. This is in contrast to other The specific features looked for in the ideal ra-
commonly used imaging procedures whose main diopharmaceutical are summarized in Table 1.1.
strengths are showing anatomy. It must be emphasized, however, that no single
Where a knowledge of the precise amount radiopharmaceutical actually has all these prop-
of activity present in an organ is required then erties. As the radionuclide label and the pharma-
positron emission tomography can provide this ceutical perform different functions, the particular
(see Chapter 3), although while its usage is in- features regarded as desirable for them can largely
creasing it still remains a specialized technique. be considered separately.
If an image of the distribution is not essential,
collimated scintillation probe detectors aligned
with the organ of interest may be used [1]. If
1.2.1 Radionuclides
the amount of radioactivity present is very low
then high-sensitivity whole body counters, con-
Half-life
sisting of heavily shielded probe detectors, are The half-life of the radionuclide determines how
necessary [2]. quickly the radioactivity will decay. Obviously, if
In vitro measurements are made on samples of the half-life is very short then the activity will have
material taken from the patient, such as breath, decayed to a very low level before imaging has
blood, urine, and feces, to determine the amount started. On the other hand, if it is too long then

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PRACTICAL NUCLEAR MEDICINE

Table 1.1. Ideal characteristics of a radiopharmaceutical Pharmaceutical Labeling


Half-life should be similar to the length of the test While the prime consideration in choosing a ra-
The radionuclide should emit gamma rays and there should dionuclide is that its manner of decay should be
be no charged particle emissions suitable for in vivo imaging, it must not be for-
The energy of the gamma rays should be between 50 and gotten that this material must be incorporated
300 keV
The radionuclide should be chemically suitable for incorpo-
into a pharmaceutical. Unfortunately all the ele-
ratingintoapharmaceuticalwithoutalteringitsbiological ments of biological interest, such as carbon, ni-
behavior trogen, and oxygen, do not have radioisotopes
The radionuclide should be readily available at the hospital meeting the criteria of Table 1.1. These particu-
site lar elements do, however, have radioisotopes that
Thepharmaceuticalshouldlocalizeonlyintheareaofinterest emit positrons. These positively charged electrons
The pharmaceutical should be eliminated from the body with annihilate with an electron to produce a pair of
a half-life similar to the duration of the examination 511 keV gamma rays. While the energy of these
The radiopharmaceutical should be simple to prepare gamma rays is such that the sensitivity of detec-
tion in the crystal of a standard gamma camera
will be low, nevertheless cameras are available that
the patient will remain radioactive for a consid- will do both single photon and positron imag-
erable time and in order to reduce the possibility ing, either by employing a high-energy collima-
of radiation damage the amount of activity ad- tor or, more commonly, by using coincidence
ministered will have to be kept low. Roughly, the electronics. The most effective way of imaging
half-life should be of a similar length to that of the positron emitting radiopharmaceuticals is, how-
examination, usually a few hours. ever, with specialized equipment, described in
Chapter 3.
Type and Energy of Emission Despite the potential problems, pharmacists
For imaging it is first necessary that the radiation and radiochemists have been very successful in
given off should be sufficiently penetrating to al- incorporating some of the most unlikely mate-
low it to be detected externally even though it may rial, such as the widely used radioisotope of tech-
need to pass through several centimeters of tissue. netium, into a large range of pharmaceuticals. This
This limits the choice to gamma rays or X-rays. problem will be considered in Chapter 7.
The energy of the radiation will also affect its abil-
ity to penetrate tissue: the higher the energy the
better it will be. However, the higher the energy
Production of Radionuclides
the more difficult it will be to stop the gamma ray Radionuclides can be produced from three
in the detector of the imaging device. In practice sources: the nuclear reactor, the cyclotron, or a
gamma rays with energies between 50 keV and 300 generator. It is not intended to go into detail about
keV are preferred, about 150 keV being ideal. the process of production of radioactive material
The radiation dose received by the patient must and the interested reader is recommended to read
also be considered. It is necessary to avoid those Ott et al [3].
radionuclides that have significant particulate (i.e. The reactor radionuclides are produced either
alpha and beta) emissions which, owing to their by introducing a target of stable material into the
short range, will simply increase radiation dose neutron flux found inside the reactor, or by sep-
without contributing to the image. As the purpose arating out fission products from the fuel rods
of radioactive decay is to redress an imbalance in or a uranium target. As neutron irradiation in-
the ratio of protons to neutrons in the nucleus, it creases the number of neutrons relative to the
is clear that simple gamma decay will be accompa- number of protons in the nucleus, it will produce
nied by the emission of a charged particle, usually radionuclides that decay predominantly by beta
a beta particle. There are, however, two decay pro- decay.
cesses that avoid this problem: isomeric transition The cyclotron produces a beam of charged par-
and electron capture. Particles will still be emitted, ticles, such as alpha particles or deuterons, which
namely Auger and conversion electrons, but at a is used to bombard a target material. The result-
considerably lower rate than the one per gamma ing radionuclide will have an excess of charge and
experienced with other modes of decay. so will decay either by emission of a positively
3

NUCLEAR MEDICINE IMAGING

charged particle (a positron) or by the capture of Selection of Pharmaceutical


a negative charge (electron capture). The latter, as
has been mentioned earlier, is a particularly use- The most important feature required of the phar-
ful decay process, as it has a gamma-to-beta ratio maceutical is that it should be taken up rapidly
greater than unity. and completely in the biological system of inter-
Obviously in most instances radionuclides pro- est. In practice most radiopharmaceuticals also lo-
duced by these two routes will be shipped to the calize in other parts of the body, and if these are
hospital from a central manufacturing site. This radiosensitive the amount of activity that can be
creates a problem, since short-lived radionuclides administered will be limited (see Chapter 6). Ac-
will decay significantly during transportation. For tivity in these other areas may also obscure that in
example, carbon-11 is a positron-emitting iso- the organ of interest. Tomographic imaging (see
tope with a half-life of only 20 minutes, which Chapter 2) has the advantage that it allows sepa-
severely restricts the distance between the cy- ration of the activity in organs that would be su-
clotron and the scanner. Fortunately the third perimposed in the conventional two-dimensional
mode of production, the generator, provides an planar image.
answer, at least for certain radionuclides. The gen- The length of time for which the radioactivity
erator will be discussed in Section 7.3.2, but ba- remains in the patient obviously influences the ra-
sically it depends upon the existence of a long- diation dose received. Not only does this depend
lived radionuclide which decays into the required upon the half-life of radioactive decay (τphysical )
short-lived radionuclide. All that is then needed but also upon the time taken for the radiophar-
is for this long-lived parent to be supplied in the maceutical to be excreted from the body, the bio-
form of a generator from which the short-lived logical half-life (τbiological ). The total residence time
daughter can be chemically extracted when re- of the radiopharmaceutical, τtotal , is given by
quired. This generator is the source of the radionu- 1 1 1
clide most commonly used in nuclear medicine, = + .
τtotal τphysical τbiological
technetium-99m, the parent material in this case
being molybdenum-99. It should be noted that although the physical
A list of commonly used radionuclides is given half-life is known accurately, the biological one
in Table 1.2 together with their mode of produc- may vary considerably, particularly in the presence
tion and characteristics of decay. of abnormal pathology. In seeking to minimize

Table 1.2. Characteristics of commonly used radionuclides


Mode of Type of Principal photon
Radionuclide production decaya emissions (keV) Half-life
Imaging tests
67 Ga Cyclotron EC 92, 182, 300, 390 78 h
123 I Cyclotron EC 160 13 h
131 I Reactor Beta 280, 360, 640 8 days
111 In Cyclotron EC 173, 247 2.8 days
113m
In Generator IT 391 100 min
81m
Kr Generator IT 191 13 s
99m
Tc Generator EC 140 6h
201
TI Cyclotron EC 68–80b 73.5 h
133
Xe Reactor Beta 81 5.3 days
Non-imaging tests
14
C Reactor Beta – 5760 years
51
Cr Reactor EC 323 27.8 days
54
Fe Reactor Beta 1100, 1300 45 days
42
K Reactor Beta – 14.3 days
a EC, electron capture; IT, isometric transition.
b Characteristic X-rays.
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PRACTICAL NUCLEAR MEDICINE

Figure 1.1. The gamma camera. The patient is lying between the detectors of this double-headed system. To the right of the camera is a rack
containing extra collimators. The technician is seated at the computer controlling data acquisition and image display.

radiation dose from a radiopharmaceutical it is analyzers to reject scattered radiation, control the
wise not to place too much reliance on biological detector and patient bed positions for SPECT
excretion, but to use a radionuclide with a reason- and whole body procedures, and display the im-
ably short physical decay time. age. A typical gamma camera image is shown in
Figure 1.2.
All gamma camera manufactures sell associ-
1.3 The Gamma Camera System ated computers and software to process and dis-
play the acquired images. The type of computer
1.3.1 Introduction and the operating system upon which the soft-
ware functions has, in the past, varied between
The gamma camera is the principal instrument manufacturers. This has led to a number of prob-
for imaging in nuclear medicine and is shown in lems, which has hindered the transfer of data be-
Figure 1.1. As can be seen, it consists of a large de- tween systems. However, in recent years, driven by
tector in front of which the patient is positioned. the demand for onscreen reporting of images by
Gamma cameras with more than one detector are clinicians and the need to transfer data to picture
now common, allowing a higher throughput of pa- archiving and communications systems (PACS),
tients by acquiring two or more views simultane- these problems have, in part, been overcome. The
ously. Every aspect of the modern gamma camera solution has been to develop an industry stan-
is under computer control, allowing the operator dard data format (DICOM) which, when used
to select the study acquisition time, or the num- with the correct software, will allow the free move-
ber of counts to be acquired, to set the pulse height ment of data between imaging systems. Although
5

NUCLEAR MEDICINE IMAGING

Figure 1.2. Gamma camera images of a bone study. Each spot


represents one detected gamma ray.

all manufacturers will promote their products as


being fully DICOM compliant, unfortunately a
number of specific problems remain.

1.3.2 Mode of Operation of the Gamma


Camera Figure 1.3. a Cross-section through the detector head of a gamma
camera. Gamma rays emitted from the patient pass through the
The basic principles of how a camera works are collimator to form an image in the scintillation crystal. The light
shown in Figure 1.3. The image of the distribution from this image is converted into electronic signals by the PMTs.
of the gamma-ray-emitting radiopharmaceutical b The signals from the camera head are processed to give the X
is produced in the scintillation crystal by a colli- and Y position signals and the Z energy signal. The Z signal goes
mator. The gamma rays, which are not visible to to a pulse height analyzer and, if it falls within the predetermined
the eye, are converted into flashes of light by the range of acceptable energy values, generates a signal which instructs
scintillation crystal. This light is, in turn, trans- the display system to record a gamma ray as having been correctly
detected at the X and Y location.
formed into electronic signals by an array of pho-
tomultiplier tubes (PMT) viewing the rear face
of the crystal. After processing, the outputs from ergy deposited in the crystal by the gamma ray.
the PMTs are converted into three signals, two of To improve their quality these signals then pass
which (X and Y) give the spatial location of the through correction circuits. The Z signal goes to a
scintillation while the third (Z) represents the en- pulse height analyzer (PHA), which tests whether
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PRACTICAL NUCLEAR MEDICINE

the energy of the gamma ray is within the range


of values expected for the particular radionuclide
being imaged. If the Z signal has an acceptable
value, then a signal is sent instructing the display
to record that there has been a gamma ray detected,
the position being determined by the X and Y sig-
nals. The individual elements of the system will
now be considered in more detail.

1.3.3 Collimator
a As with all forms of electromagnetic radiation,
gamma rays are emitted isotropically. Simply us-
ing a detector would not result in an image, as
there would be no relationship between the po-
sition at which the gamma rays hit the detector
and that from which they were emitted from the
patient (Figure 1.4a).
In an optical system a lens is used to focus
the light but it is not possible to use it with
high-frequency radiation such as gamma rays. In-
stead a much cruder device must be employed, the
collimator. The most common type, the parallel-
hole collimator, is shown in Figure 1.5a. It con-
b sists of a lead plate through which runs an array
of small holes whose axes are perpendicular to the
Figure 1.4. a In the absence of collimation there is no relationship face of the collimator and parallel to each other.
betweenthepositionatwhichagammarayhitsthedetectorandthat Only those gamma rays that travel along a hole axis
from which it left the patient. b The parallel-hole collimator forms an will pass into the scintillation crystal, while those
image by excluding all gamma rays except those travelling parallel that approach the collimator at an oblique angle
to the hole’s axis.

a b

c d

Figure 1.5. Different types of collimator. The shaded area shows the field of view of the collimator. a The parallel-hole collimator; b the
converging collimator; c the diverging collimator; d the pinhole collimator.
7

NUCLEAR MEDICINE IMAGING

will hit the septa and be absorbed (Figure 1.4b). Table 1.4. Collimator specifications
Thus an image is formed by excluding all gamma Resolutiona Sensitivity Energyb
rays except the small number traveling in the pre- Type (mm) (cps MBq−1 ) (keV)
ferred direction perpendicular to the detector.
The two main parameters describing collimator Low-energy, high- 6.4 91 140
resolution
performance are spatial resolution and sensitivity.
Low-energy, general 8.3 149 140
Resolution is a measure of the sharpness of the im- purpose
age and is approximately equal to the minimum Low-energy, high- 14.6 460 140
separation needed between two structures if they sensitivity
are to be resolved. A more precise definition is Medium-energy, 10.8 140 280
given in Section 5.2.1. Typically the best spatial general purpose
resolution that can be achieved with a camera fit- High-energy, general 12.6 61 360
ted with a parallel-hole collimator is about 7 mm. purpose
Sensitivity is a measure of the proportion of those a Geometric resolution at 10 cm from collimator face.
gamma rays incident on the collimator that pass b 5% penetration of septa.
through to the detector; the higher the sensitiv-
ity, the greater the count rate recorded. Typically
the sensitivity for a parallel-hole collimator is only of a collimator, and a choice must be made de-
0.1% (hence 99.9% of photons are absorbed by the pending upon the type of investigation to be per-
collimator and do not reach the detector). The ef- formed. If the test requires high-resolution images
fectiveness of a collimator in producing an image and the amount of radioactivity in the patient is
in the scintillation crystal will depend upon the di- sufficiently high so that imaging times will not be
mensions of the collimator (Table 1.3). Note that unduly long, then the high-resolution design of
not all of these parameters are independent. For collimator can be employed. If, instead, the need
example, increasing hole diameter will reduce the is for a series of short-exposure images, as in a
number of holes in the collimator. dynamic imaging study, then resolution may be
The first point to note is that image resolu- sacrificed for increased sensitivity.
tion decreases with distance from the collimator. It is also necessary to have separate collima-
Therefore the resolution will be best for the organ tors for the different energy of radionuclides
that is closest to the collimator. Imaging must al- used: a low-energy (<140 keV), a medium-energy
ways be carried out with the relevant part of the (<260 keV), and a high-energy (<400 keV) col-
patient as close to the collimator as possible. Sec- limator. These differ in the thickness of the lead
ondly, the sensitivity of the parallel-hole collima- septa between the holes. In practice a department
tor is independent of the distance of the organ would have available a range of collimators for
from the collimator face. This is only true when different circumstances. A list of typical collima-
there is no attenuating material between organ and tors and their relative performance parameters is
collimator. In practice this is rarely the case, and shown in Table 1.4.
the normal exponential attenuation processes will While the parallel-hole collimator is used for
cause sensitivity to be dependent on distance. most studies, other designs of collimator are
There is a trade-off between collimator spa- available for more specialized applications. The
tial resolution and sensitivity; it is not possible to converging collimator has holes that point to a
optimize both the spatial resolution and sensitivity focal spot several centimeters in front of the face
of the collimator (Figure 1.5b). The value of this
Table 1.3. Factors affecting the performance of a parallel-hole hole geometry is that it will magnify the image
collimator of a small organ. Magnification will increase with
the distance from the collimator face, and so res-
Parameter that is increased Resolution Sensitivity olution will not deteriorate as rapidly as with the
Number of holes No change Increases parallel-hole collimator. Also, sensitivity increases
Hole diameter Worsens Increases with distance, so helping to compensate for the
Hole length Improves Decreases effect of attenuation. Unfortunately, the image
Septal thickness No change Decreases will be distorted, the back of an organ being mag-
Distance of object from Worsens No change
collimator nified to a different extent from that of the front,
and there will also be variations in resolution
8

PRACTICAL NUCLEAR MEDICINE

across the field of view as the hole geometry varies 1.3.4 Detector
from highly diverging near the edges to nearly
parallel at the center of the collimator. While the While the collimator modifies the gamma ray flux
converging collimator is rarely used these days, a so as to create an image, it is the function of the
variant of it, the fan-beam collimator, is used for detector assembly to convert the gamma rays into
cardiac and SPECT imaging (see Section 2.2.8). In a form that will, eventually, allow a visible image to
this collimator the holes in each row converge but be produced. This process takes place in two stages.
in the orthogonal direction they are parallel. Thus The first step is the conversion of the gamma rays
they focus to a line rather than a point. The diverg- into visible light by means of a scintillation crystal,
ing collimator is the opposite to the converging while in the second these scintillations are turned
collimator, having holes converging to a point into electrical signals by the PMTs. The proper-
behind rather than in front of the collimator. The ties of the ideal scintillation detector are given in
result is a collimator that can minify a large object Table 1.5.
so that it will fit into the smaller detector (Figure The scintillation crystal used in gamma cam-
1.5c). This collimator has the same disadvantages eras is made from sodium iodide with trace quan-
of image distortion and sensitivity varying across tities of thallium added, NaI(Tl). Its effectiveness
the field of view found with the converging colli- at stopping the gammas depends not only on its
mator. The need for such a collimator is rare with density but also on the thickness of crystal used
modern cameras, but a variation of this design in (see Figure 1.6).
which the holes diverge in one dimension only is
to be found in the so-called fish-tail collimators
Table 1.5. Desirable properties of the scintillation crystal
used with some whole-body scanning cameras.
This type of collimator increases the field of view, High efficiency for stopping gamma rays
so allowing the full width of the patient to be Stopping should be without scatter
imaged. The move to rectangular field of view de- High conversion of gamma ray energy into light
tectors has made this unnecessary in the modern Wavelength of light should match response of the PMTs
cameras. Crystal should be transparent to emitted light
A different concept of collimation is to be found Crystal should be mechanically robust
Length of scintillation should be short
in the pinhole collimator, which forms an image
in a way analogous to the optical pinhole camera.
It consists of a lead cone with a small hole of a few
millimeters in diameter at its apex (Figure 1.5d).
It constrains the detected gamma rays to those
passing through one particular point; thus each
elementary area on the detector sees only a small
area of the object and an image is produced in
the crystal. The ratio of the size of the image to
that of the object will depend upon the ratio of
the distance of the hole from the detector to that
of the organ from the hole. Its main use is to give
an enlarged image of a small organ. The organ
must be located near a body surface so that the
pinhole can be positioned close to it, the thyroid
gland being the organ most commonly imaged
in this way. As with all collimators, apart from
the parallel-hole type, there is image distortion.
For a thick object the magnification of the distant
posterior surface will be greater than that of the
anterior one. There is a variation in resolution and
sensitivity across an organ, and sensitivity falls off
quickly with increasing distance of the organ from Figure 1.6. The effectiveness of the crystal at stopping a gamma
the collimator. ray as a function of the gamma ray’s energy.
9

NUCLEAR MEDICINE IMAGING

Unfortunately, only a small fraction of the en- factor of 107 ) to give a sufficiently large current for
ergy lost by a gamma ray is converted into light, the subsequent electronics. Even with this signal
typically 10%, producing about 3000 light pho- amplification pre-amplifiers built into the PMT
tons at a wavelength of 410 nm for each 100 keV are necessary to ensure a sufficient signal-to-noise
of gamma ray energy absorbed. This wavelength, ratio.
however, matches quite closely that required by
the PMT. The length of each scintillation must be 1.3.5 Signal Processing
sufficiently short to avoid the overlap of light from
consecutive scintillations. In the NaI(Tl) crystal it Three types of signal processing are to be found in
takes about 0.8 µs to collect most of the light, and use at present. Analogue circuitry was used in cam-
this will obviously affect the maximum gamma ray eras exclusively until about the mid-1990s. Even
rate that the camera can handle without producing though so-called digital cameras have been mar-
a distorted image (see Section 1.3.8). keted since the mid-1980s, in practice they used
NaI(Tl) also suffers from the drawbacks of be- analogue circuits to produce the X, Y, and Z sig-
ing expensive to produce as a large crystal, frag- nals and digitized them prior to them entering the
ile and so needing protection from both thermal signal correction and display modules. Only since
and mechanical stresses, and hygroscopic, requir- the mid-1990s has truly digital signal processing
ing to be canned to prevent contact with moisture. been used in commercial cameras, with the signal
The latter requirement poses a problem since it from the individual PMTs being digitized.
is also necessary to ensure that the light emitted
in the scintillation is transmitted to the second Analogue Systems
part of the detector system, the PMT array. While
the front face and sides of the crystal are canned, The signals from the PMTs are processed to give
usually with aluminum sufficiently thin so as not the three signals required, X and Y providing spa-
to attenuate the incoming gamma rays unduly, tial information and Z the energy. The energy sig-
the rear crystal surface needs a transparent inter- nal is produced simply by summing the outputs
face between the crystal and PMTs. This is usually from all of the tubes, so measuring the total light
provided by a Pyrex optical plate or light guide produced by the scintillation. The spatial informa-
a few centimeters in thickness. Despite the obvi- tion is more difficult to produce. What is required
ous problems with using NaI(Tl), it has proved to is that the processed signal should be proportional
be the only satisfactory scintillation material for to the X or Y location of the scintillation. This is
gamma cameras. achieved by weighting the signals from each tube
While it is possible, at least in theory, to produce by passing the output from the PMTs through re-
an image from the scintillation in the crystal, the sistors or capacitors:
main advantage of first converting this image to 
wi oi
electrical signals is that pulse height analysis can i
X= 
be used to reduce the effect of scattered photons oi
on image quality. i
The PMTs are usually arranged in a close-
where wi is the weighting factor for the ith PMT
packed array to ensure that the smallest possible
and oi is the output signal. The value of the weight-
gaps are left between tubes. In recent years, the
ing factor is proportional to the spatial coordinate
shape of the crystal has changed from circular to
of the PMT, separate factors being used for the X
rectangular, as the latter is more suitable for imag-
and Y signals [4]. The divisor, which is equal to
ing the body. Typically, the crystal size is 60 ×
the energy of the gamma, is necessary to prevent
45 cm, giving a field of view of about 55 × 40 cm.
the X value being dependent upon the energy as
About 60 PMTs are needed to cover this rectan-
well as spatial location of the scintillation.
gular crystal. While PMTs with a photocathode
diameter of 3 inches are used mainly, it is also nec-
essary to use some 2 inch diameter tubes.
Digital Systems
The PMT not only converts light into an Modern camera systems now rely heavily on digital
electronic signal but also, as its name suggests, technology, both for correction of the spatial, en-
magnifies the electronic signal (typically by a ergy, and temporal information (see Section 1.3.8)
10

PRACTICAL NUCLEAR MEDICINE

and for the analysis of image data. Since this Table 1.6. Factors affecting linearity and intrinsic resolution
requires the analogue signal to be digitized, there is Linearity Resolution
a strong case for having a completely digital cam-
era. Two general approaches are currently taken; Increasing crystal thickness Degrades Degrades
Increasing number of PMTs Improves Degrades
either to digitize the X, Y, and Z signals immedi- Increasing size of photocathode Degrades Improves
ately after these have been computed by analogue Improvingconversionefficiency No change Improves
circuitry or, in the latest generation of cameras, to of crystal
completely replace the analogue circuits, the sig- Improving PMT conversion No change Improves
nals from the PMTs being digitized before the X, Y, efficiency
and Z signals are computed. In the latter case each Increasing light guide thickness Improves Degrades
PMT has an analogue to digital converter located Using a higher-energy gamma No change Improves
after the preamplifier, and the signal position is ray
calculated from the centroid of the signals from a
group of PMTs, usually chosen to be those having
the strongest and hence least noisy signals. The Z The paucity of photons will also cause a similar
signal is calculated by summing the outputs from random variability in the energy signal. Typically
the group of tubes. the energy resolution of a gamma camera is about
10% (see Section 5.2.9).
Accuracy of Signal Processing To produce a high-quality image, both intrin-
sic resolution and spatial distortion must be con-
In order to reproduce the image that has been sidered. Unfortunately, altering the design of the
formed in the scintillation crystal the X and Y detector to increase the light received by each
signals must be proportional to the coordinates PMT and so improve resolution will often de-
of the scintillation. In other words the system grade linearity (Table 1.6). The solution is not
must demonstrate good spatial linearity. The de- necessarily to compromise, as the image can be
tector assembly must be constructed so that small corrected for poor linearity (see Section 1.3.8). In
changes in the position of the scintillation alter contrast intrinsic resolution cannot be corrected
significantly the relative strengths of the outputs as it is a random process, in which the correct
from the PMTs. value for the X and Y signals cannot be deter-
While the most obvious solution to optimize mined by some form of calibration. The detec-
the linearity would be to use a large number of tor assembly is thus designed to optimize intrinsic
PMTs, in practice this would degrade the image in resolution.
another way. The amount of light incident on the There are other problems which must be borne
array of tubes is very low, approximately 1000 pho- in mind when choosing a camera. An improve-
tons from a 140 keV gamma ray, producing about ment in intrinsic resolution may not produce a
25 electrons from the photocathode of each PMT, significant change in the total spatial resolution
which are then magnified to give the final output when the effect of collimator resolution is also
current. In practice the number of photoelectrons taken into account. Only when the resolution of
will vary randomly about this average value, a fea- the collimator is good, with objects close to the
ture found in the emission of all quanta including collimator face or when using a fine-resolution
gamma rays. So even if consecutive gamma rays collimator, will the improvement be perhaps
were to be stopped at exactly the same position in noticeable.
the crystal, the PMT outputs would not be identi- Caution must be exercised if the resolution has
cal, but would produce X and Y signals that varied been improved at the expense of other factors. In
randomly about the true value. The true image particular, the prospective purchaser may be faced
of the point would be blurred into a disk. This with a choice of crystal thickness, a 3/8 inch is com-
effect is referred to as the intrinsic resolution of monly used, but thicknesses between 1/4 up to 1
the camera. The total spatial resolution of a cam- inch are used, the higher values being for cam-
era thus consists of a combination of this intrinsic eras designed to also do PET imaging. While a
resolution and the collimator resolution, and is thinner crystal will improve intrinsic resolution it
given by also causes a decrease in sensitivity (Figure 1.6).
 1/2 It is debatable whether the overall result is an im-
Rtotal = R2collimator + R2intrinsic . provement in performance.
11

NUCLEAR MEDICINE IMAGING

1.3.6 Uniformity with a gamma ray of 140 keV those signals with
energies between 126 and 154 keV are judged to
Not only is it desirable that the camera perfor- be acceptable.
mance be optimized but also performance should While the scattered gamma rays are distinguish-
not vary significantly between different points in able by their lower energy, the spreading out of the
the crystal. Any variability is demonstrated most photopeak spectrum may mean that the energy
readily by the image of a uniform distribution of unscattered gammas overlaps that of scattered
of radioactivity, the so-called flood image. Areas ones. This overlap of the Compton and photopeak
of above- or below-average count density are in- spectrum means that a choice must be made be-
dicative of regions where the camera performance tween using a narrow window and so excluding a
has altered. The effect of variations in linearity large proportion of unscattered rays or accepting
and intrinsic resolution is to misposition gamma the presence of some scattered radiation in the im-
rays, putting them closer together or further apart age. Usually the latter is chosen, and with a 20%
than expected. Spatial variations in the value of window about 30% of the gamma rays in the image
the Z signal will result in local changes in the ap- will have been scattered.
parent sensitivity of the camera as a greater or When using radionuclides that emit gamma
smaller number of gammas are accepted by the rays at different energies, multiple window analyz-
pulse height analyzer. Digital correction circuitry ers need to be employed. Typically a maximum of
for linearity and the energy signal are found in all three sets of windows is available. In this instance,
modern cameras and will be discussed further in it is important to remember that scattered radia-
Section 1.3.8. tion from the higher-energy gammas may overlap
into the lower-energy photopeaks and this may
influence which gamma ray energies should be
1.3.7 Pulse Height Analysis selected.

The collimator is responsible for creating an im-


age out of the flux of gamma rays incident on it, 1.3.8 Correction Circuits
yet not all of these gamma rays will carry useful
image information. In particular, those rays that To improve image quality, real-time compensation
have been Compton scattered in the patient, and is provided for some of the defects in camera per-
so appear to come from another location, simply formance mentioned above. It is, however, only
reduce image contrast. Such rays can be identi- possible to correct where the cause of the distor-
fied by the fact that in being scattered they also tion is not random. So, while non-linearity can be
lose energy, the amount being dependent on the corrected, it is not possible to improve the intrinsic
angle through which they were deviated. As the spatial resolution of the camera.
scintillation detector allows the energy deposited
by the gamma ray in the crystal to be measured,
this information can be used to exclude scattered
Spatial Linearity
gamma rays. However, as has already been men- Spatial linearity correction is carried out by pre-
tioned, the gamma camera is limited in the accu- senting the camera with an image consisting of a
racy with which it can measure energy, with the series of parallel straight lines aligned with either
result that even in the absence of scatter the gamma the X or Y axis of the camera. The deviation be-
rays appear to have a range of energies. The width tween the true position of each point on the line,
of this so-called photopeak spectrum, measured at as calculated from a best-fit straight line, and the
half the maximum height, is about 10% of the true image of the line, is recorded and stored as a correc-
energy. The pulse height analyzer allows the oper- tion factor to be applied to subsequently acquired
ator to select only the signals from those gammas clinical images. To achieve the spatial resolution
in which the height of the Z signal, that is, gamma required to define the straight lines it is neces-
ray energy, has a certain value or range of values. If sary for the test pattern to be imaged without the
many useful gammas are not to be excluded from collimator, i.e. placed against the crystal and illu-
the image, a range of energies must be allowed minated with a flood source of gamma rays, usu-
through the PHA, and typically a window equal to ally from a point source of activity placed a long
20% of the peak energy value is used; i.e. for 99m Tc way from the camera. As this requires a phantom
12

PRACTICAL NUCLEAR MEDICINE

Scatter Correction
In many clinical studies a significant proportion of
the gamma rays in the image will be scattered. The
effect is to reduce the contrast since they will, ap-
proximately, form a uniform background, and to
defeat any attempts to quantify the amount of ra-
dioactivity in an organ. Since the amount of scat-
ter will vary within the image depending upon
the amount of tissue through which photons need
to pass before reaching the detector, any correc-
tion will need to be made on a pixel-by-pixel ba-
sis. Hence, as was mentioned in Section 1.3.7, the
use of the PHA alone is insufficient to remove the
scatter.
A number of techniques are offered by manu-
facturers to remove scatter. They are all based on
the removal of a fixed proportion of the photons
acquired in a pixel as it is obviously impossible, in
the absence of good energy resolution, to identify
Figure 1.7. Variation of the energy signal with the position of which particular gammas have been scattered. One
the scintillation in the crystal. At A, the two windows are situated class of techniques uses additional energy windows
symmetrically around the photopeak. At B, the calculated values either on either side of the photopeak window, or
for the energy signals are lower than at A and so more events are in a part of the spectrum that is known to include
accumulatedinwindow1than2,whileatCtheenergysignalishigher only scattered photons. The proportion of scatter
than at A and there are more events in window 2. Correction factors is then calculated from measurement of the num-
for the energy signals can be generated by comparing the number of ber of photons in the various windows [5].
gamma rays in the two windows. Knowing the energy of the detected photon and
the geometry of the scattering medium through
which it has passed, it is possible to predict the
manufactured to high tolerances, the generation likelihood that its X and Y coordinates are in er-
of new correction factors is usually done by the ror by a particular amount. A second correction
manufacturer’s service engineer. technique, employed commercially, uses a correc-
tion matrix based on the energy and geometry to
Energy predict the probability that, for each photon, the
The energy signal may also require correction, as recorded position was the true one [6]. The ad-
the calculated value is found to vary with the po- vantage of such a system is that there is no need
sition of the gamma ray across the detector. Shifts to use a pulse height window and so, in theory, all
in the position of the locally computed energy sig- photons can contribute towards the image. The
nal can be measured by comparing the number of disadvantages are that we do not know the actual
gamma rays whose energy falls inside two narrow energy of the photon, nor the scatter geometry.
windows, one set to each side of the average pho-
topeak value (Figure 1.7). Once again the amount
of correction required to ensure that the local sig-
Temporal Correction
nal matches the average value, i.e. that there are The typical nuclear medicine study requires the
equal numbers of gamma rays within each win- camera to process only a few tens of thousands of
dow, is stored in a correction matrix to be applied counts per second. There are some studies, how-
to the subsequent energy signals. This correction ever, cardiac first pass (see Section 9.5) being the
is acquired simply by imaging a flood source of main example, where the count rate can be very
radioactivity and can be performed regularly by high. The probability that successive pulses pass-
the user. Typically the average correction should ing through the camera’s electronic circuits will
yield a variation in the energy signal of less than overlap each other becomes unacceptably high.
0.2% across the detector. Such pulse pile-up results in incorrect X, Y, and Z
13

NUCLEAR MEDICINE IMAGING

signals being produced. Not only will this distort lem with modern systems), (ii) the total number of
the image, but the recorded energy of these events images to be acquired, (iii) the number of counts
will be higher than that of the individual pulses contained in each image, and (iv) the required
leading to them being rejected by the PHA; the de- temporal and spatial resolution.
tected count rate will no longer increase linearly, As modern systems can acquire and display
or indeed monotonically, with the amount of ac- static images with array sizes of up to 2048 × 2048
tivity in the camera’s field of view. The problem of pixels, image quality is comparable with that of
measuring pulse pile-up effects will be discussed analogue images. Each pixel is typically stored as
in Section 5.2.8. a 16 bit unsigned integer (allowing count values
The difficulty arises because the pulses coming to range from 0 to 65 535); more bits per pixel
out of the PMT preamplifiers have a finite length. would allow higher counts to be recorded, but at
Electronic pulse shaping can help to reduce the the expense of storage space, image transfer rate,
problem and digital arithmetic circuits should be and possibly processing time.
much faster than analogue ones. An online correc- The image data are mapped from the array of
tion circuit has been implemented using a tech- numbers, representing the number of gamma rays
nique known as pulse tail extrapolation [7]. The acquired at a specific spatial location, into a view-
circuit detects the overlap of two pulses by the able image by a look-up table which links the
failure of the signal to return to its baseline level number of gamma rays to a specific value of dis-
within a specified time. It then separates the two played image intensity. The first question to be ad-
pulses, the first pulse being without its tail which is dressed is how best to represent image intensity,
now mixed in with the second pulse. By examining both gray shades and colors having been used. The
the shape of the first pulse the correction circuit human eye can distinguish thousands of different
extrapolates the truncated tail to recreate its orig- colors, compared with only several tens of gray
inal shape. This extrapolated section is then sub- shades. The use of color to display intensity in-
tracted from the second pulse, so also restoring it formation, known as pseudo color, should there-
to its original shape. fore permit a much wider dynamic range to be re-
The effectiveness of correction circuits varies produced. For instance, the so-called “hot body”
considerably between manufacturers. An image of scale, first proposed for coding ultrasound images
a flood source often provides a simple test. The [8], uses a gradual variation in hue and intensity
prospective purchaser of a camera should check to increase the dynamic range of the display; the
that the correction facilities are usable for all op- scale changes from black, through shades of red, to
erations with the camera and that the correction white. Color scales can also make identification of
works for different radionuclides and for window specific ranges of pixel values easier, and are par-
settings of different energies. ticularly useful for parametric images, which are
discussed in Section 1.4.2.
1.3.9 Image Display However, there are several serious problems as-
sociated with color scales. Firstly, if the scale in-
Modern camera systems employ digital display cludes distinct perceptual color steps it can in-
systems. If the Z signal corresponding to a partic- troduce false edges and contours in the image,
ular detected gamma ray falls within the window greatly exaggerating small, and possibly insignifi-
that has been set on the PHA, then an enable signal cant, changes. Secondly, rather than enhancing the
is sent and the X and Y signals are recorded. dynamic range, poorly chosen color scales can de-
The most common form of image acquisition grade it and reduce image contrast. Finally, there is
is called matrix or frame mode. The camera’s field the issue as to whether the display device (whether
of view is divided into a regular matrix of pic- a screen or a hard-copy device) is actually capa-
ture elements or pixels. Each pixel is assigned a ble of reproducing all the colors in the color scale.
unique memory location in the computer. The Failing to do so can result in large portions of the
value stored in this location is the number of color scale being reproduced as the same color.
gamma ray events that have been detected in the The second question is how to map count
corresponding location on the camera face. The density to the chosen gray shades or colors. The
number, and hence the size, of the pixels used is simplest case is a linear relationship between the
of practical importance and depends on (i) the number of counts and the displayed intensity
available computer memory (unlikely to be a prob- (Figure 1.8a). Other transformations include
a b

c d

e f

Figure 1.8. Examples of different types of intensity mapping. a A linear mapped image; b the linear mapping scheme between input
(image counts) and output (displayed gray shade) intensity. c A histogram equalized image; d the histogram equalization mapping scheme.
e A contrast enhanced image; f the contrast mapping scheme.

14
15

NUCLEAR MEDICINE IMAGING

compression of parts of the scale to increase con- interest, but also how this distribution changes
trast over a specific count range (Figure 1.8b), and with time. In dynamic imaging the camera is set to
non-linear mappings, such as logarithmic, power acquire data either for a preset sequence of frames
law, square root or exponential [9]. Histogram (where the acquisition time for each frame can be
equalization is a non-linear intensity transform variable) or using list mode.
which has been applied to nuclear medicine im- In list mode acquisition image data are stored
ages [10] (Figure 1.8c). Count density is mapped as a list of the X and Y coordinates of each de-
such that each display intensity, gray shade or tected event along with regular timing data. Some
color, occurs approximately (due to digitization) systems also store the Z energy value, allowing
the same number of times in the image. Although post-acquisition energy window selection. In gen-
equalization theoretically maximizes image con- eral list mode acquisition requires more memory
trast, in practice it is rarely useful. A variation than matrix mode, since only the individual events
on this, adaptive histogram equalization [11], in- are stored whereas matrix mode requires the same
volves the application of histogram equalization amount of memory, irrespective of the number
in small sub-areas of the image, rather than glob- of counts in the image. However, some additional
ally to the whole image. However, it also tends to software and time information is required to for-
amplify image noise, an undesirable property for mat such data into suitable matrix mode images
nuclear medicine images. for display and subsequent processing.
One of the simplest ways of manipulating List mode is of particular value if very good
the displayed data is by thresholding (sometimes temporal resolution is required, or the required
known as windowing). For example, in bone imag- temporal resolution is not known in advance. It
ing the radiopharmaceutical is excreted into the has the advantage that several matrix mode stud-
bladder, giving an area of very high count density. ies with different frame times can be produced
In the absence of thresholding most of the display retrospectively from the original data.
levels will be used to display the bladder activ- Changes in the distribution of the radiophar-
ity rather than the bones. By applying an upper maceutical with time can be measured by draw-
threshold all areas having counts above a thresh- ing a region of interest (ROI) around the features
old value will be given the same maximum gray of interest seen in the study, using a cursor un-
shade. This leaves the remaining gray shades or der mouse control (sometimes this operation can
colors to be assigned to those counts found in the be automated as described in Section 1.6). The
bones. Similarly a lower threshold may be applied data acquisition system then plots time–activity
such that all low count density areas are given the curves (TACs) showing how the number of counts
same low gray shade. within the ROIs varies between image frames, i.e.
with time. Figure 1.9 shows an example TAC. This

1.4 Data Acquisition


1.4.1 Static Studies
Data are acquired for either some pre-selected ac-
quisition time or preset number of counts. The
former is effective if the count rate is known not
to vary significantly between patients and ensures
that patient throughput is predictable. However, if
there is an isolated area in the image containing a
high level of activity that is not of clinical interest,
as for example bladder activity in bone scans, then
preset counts may result in very few counts in the
areas of potential clinical interest.

1.4.2 Dynamic Studies


Figure1.9. Time–activitycurves.Thenumberofcountswithineach
In some clinical studies it is not simply the spatial ofthreeregionsofinterestisplottedonthey-axisasactivity.Thex-axis
distribution of the radiopharmaceutical that is of shows time elapsed after the start of dynamic image acquisition.
16

PRACTICAL NUCLEAR MEDICINE

technique is of particular value in renography (see can be analyzed as a time–activity curve, or para-
Chapter 11). metric images produced.

Parametric Images
Gated Imaging
While time–activity curves can be analyzed quan-
The assumption in nuclear medicine imaging is titatively, normally they are assessed visually. How-
that the structures being imaged do not themselves ever, TACs only show the average change in count
move during the imaging time. This is not gener- density within the ROI. In gated cardiac studies
ally true although, given the relatively poor spa- there is interest in how wall motion varies at differ-
tial resolution, the extent of this motion is usually ent locations in the left ventricle. One could draw
not sufficient to cause significant deterioration in a whole series of small ROIs but this would then
image quality. In the case of cardiac blood pool produce many TACs needing to be analyzed. In-
imaging (see Chapter 9), however, it is desirable stead each TAC is decomposed into a small num-
to capture images at a sufficiently high rate in or- ber of parameters. For gated cardiac images the
der to be able to view the changes in the blood parameters are the amplitude of the curve and the
image caused by the beating of the heart. phase, the time between maximum and minimum
Given that an average cardiac cycle is about 800 contraction (Figure 1.11a). Thus a TAC can be
ms in length, to acquire 16 images during the cy- generated from each pixel in the cardiac study, a
cle would need an exposure time per image of pair of parameters produced from each curve and
50 ms. With a typical count rate of a few tens of two new parametric images generated in which
thousands of counts per second each image frame the number of counts in a particular pixel is re-
would contain only a few hundred counts, far too placed by the parameter derived from its TAC
few to show any structure. The solution is to use (Figure 1.11b).
a physiological signal, in this case from the elec-
trocardiograph (ECG), to keep image acquisition
in phase with the beating heart so that data can be 1.5 Image Filtering
collected over many hundred cardiac cycles. The
principle is shown in Figure 1.10. In contrast to the mapping performed with look-
Data collected in this way can then be displayed up tables to produce a displayed image, image
in a cine loop, in which the frames are replayed in filtering alters the actual count density values.
rapid succession in a continuous loop. The data Filtering is used primarily to reduce the effect of

Figure 1.10. Multiple gated cardiac acquisition. In this example a dynamic study of the heart is performed. The start and end of each image is
indicated by the broken lines. Image acquisition starts with the arrival of the peak of the ECG and a dynamic study of seven images is collected.
With the arrival of the next peak, indicating the start of the next cardiac cycle, data are added to the original set of seven images. This continues
over several hundred cardiac cycles. At the completion of the study, each image represents the appearance of the heart at a particular point in
the cardiac cycle. Gated cardiac studies are discussed further in Chapter 9.
17

NUCLEAR MEDICINE IMAGING

where f (x, y) and g (x, y) are the original and fil-


tered images respectively, * represents the convolu-
tion operator, and w (s , t) are the filter coefficients
counts or kernel, which define the filter.
Linear filtering can also be performed in the
frequency domain by exploiting the convolution
theorem. This states that convolution in the spa-
tial domain is equivalent to multiplication in the
frequency domain (and likewise multiplication in
the spatial domain is equivalent to convolution
in the spatial domain). Hence the convolution
above may be performed by taking the Fourier
transforms of f (x, y) and w (x, y), applying
point-wise multiplication, and taking the inverse
Fourier transform of the result to obtain g (x, y),
a i.e.

G (u, v) = F (u, v)W(u, v)

where F (u, v), G (u, v) and W(u, v) follow the


usual convention that the capitalized form of
a variable indicates the Fourier transform (fre-
quency domain form) of the lower case spatial
domain function. For larger filter kernels the over-
head necessary to calculate the Fourier transform
using a fast Fourier transform (FFT) is easily out-
b weighed by the computational complexity of con-
volution.
Figure 1.11. a The time–activity curve shows the variation in the The modulation transfer function (MTF) of the
amount of radioactivity in the left ventricle of the heart during a gamma camera demonstrates how effectively it re-
cardiac cycle. Such a curve is measured for each image pixel and the produces information at different spatial frequen-
length of time to the curve minimum, the phase, and the difference
between maximum and minimum activity, the amplitude, are mea- cies (see Section 5.2.1). This shows why gamma
sured. b Parametric images. These show the resulting images of the camera images appear blurred; the MTF decreases
amplitude and phase values for a normal cardiac study. rapidly with increasing spatial frequency and con-
sequently fine detail is not recorded. In contrast,
noise on image interpretation and analysis. It can the image noise, due primarily to counting statis-
also, to a certain extent, improve image resolution tics, is independent of frequency (and is known
by compensating for the degradation produced as “white noise” by analogy to the energy spec-
mainly by the gamma camera collimator. Image trum of white light). The ratio of the useful
filtering can be broadly categorized into linear and image information to the noise, the signal-to-
non-linear techniques. noise ratio (SNR), therefore decreases with in-
creasing spatial frequency. The overall image SNR
can be improved quite simply by attenuating the
1.5.1 Linear Filtering higher spatial frequencies, which are predomi-
nantly (or entirely) noise. The simplest solution
In linear filtering each pixel is replaced with a (usu-
is to apply a “low-pass filter”, which attenuates
ally weighted) linear combination of its surround-
high-frequency components without affecting the
ing pixels. It may be implemented using convolu-
lower-frequency ones. This is particularly impor-
tion, given by
tant in SPECT imaging where the “ramp filter”
g (x, y) = f (x, y) ∗ w (x, y) required by filtered back-projection also accen-
 a b tuates the noise at high frequencies (see Section
= f (x − s , y − t)w (s , t) 2.2.2). Care should be taken when designing the
s =−a t=−b low-pass filter to ensure that artifacts are not
18

PRACTICAL NUCLEAR MEDICINE

generated by the filter which may be mistaken for noise level is given by the ratio of the regional
abnormalities. standard deviation and mean. In one such filter
Filters may also be designed that restore some a median filter has been combined with a local
of the image resolution lost due to the MTF of the averaging filter and is claimed to be effective for
gamma camera. The simplest approach is to de- smoothing noisy images containing strong edges.
sign a filter whose frequency response is equal to
the inverse of the camera MTF, a process known
as inverse filtering. If F (u, v) and G (u, v)are the 1.6 Automated Image Analysis
Fourier transforms of the true image and the
blurred image respectively, then given the MTF, Automated image analysis has the potential, al-
H(u, v), the blurred image is given by though yet to be fully realized, to increase through-
put, ensure consistency, and improve accuracy.
G (u, v) = F (u, v)H(u, v). One technique is to make a “normal” or “tem-
Restoration appears to be straightforward, by plate” image to which all patient images may be
simple algebra: aligned and compared to detect abnormal features.
The normal image is usually created from a sam-
G (u, v) ple of studies assessed to be clinically normal; the
F (u, v) = . images are registered and the normal inter-subject
H(u, v)
variations estimated. This approach has been used
In practice this does not work as it is evident that as the basis for the automated detection of ab-
frequencies that are absent in the image cannot normalities in SPECT heart images [12]. Princi-
be restored by the filter. Inverse filters emphasize pal component analysis has been used to extract
the higher spatial frequencies, which are predomi- significant modes of variation from such sets of
nantly noise, and thus tend to obscure the true im- normal images [13].
age. Therefore any practical resolution restoration Another use for the normal template is the au-
filter needs to employ some form of constraint to tomatic location of regions of interest within an
control the noise level in the resulting image. Three image. Once regions have been drawn on the tem-
such methods are Wiener filtering, Metz filtering, plate image (perhaps using higher resolution mag-
and constrained least squares filtering. netic resonance images or X-ray CT images as a
guide), they may be applied automatically to all
1.5.2 Non-linear Filters subsequent images, either by registering the im-
age to the template and applying the ROIs, or by
The most common non-linear filter is probably using the inverse mapping to align the ROIs with
the median filter, which replaces each pixel by the the image.
median value of its surrounding neighborhood. More recently, statistical parametric mapping
Since it is not possible to apply Fourier analysis to (SPM) has been used to tackle this problem [14].
non-linear filters, it is difficult to predict the ef- Image data are registered and spatially normal-
fect of the median filter on the spatial frequency ized to a standard stereotactic space. A statistical
content of images. However, in general the median comparison can then be made between groups of
filter behaves like a low-pass filter which preserves images on a pixel or voxel basis. This approach
some edge detail. It is of limited effectiveness for was originally intended for PET and functional
noisy nuclear medicine images (which do not con- MRI brain studies, but has been used by a num-
tain sharp edges) as it can introduce false edge ber of groups with SPECT images. It has the ad-
structure and contours to the image and suppress vantage of making no a priori assumptions about
specific spatial frequencies in the image. the size and location of any differences between
A problem with all the preceding filters is that groups of images. However, assessment of an in-
they assume that there is one filter that is best for dividual, as compared to a group of patients, is
the whole image. Yet regions with higher numbers difficult.
of counts will have a higher SNR, and therefore Interest in multimodality imaging [15], to com-
require less smoothing than regions with fewer bine the functional information from nuclear
counts. Adaptive filters attempt to estimate the re- medicine and the anatomical information from
gional noise level and apply an appropriate degree another modality, has encouraged the develop-
of smoothing. For instance, one estimate of the ment of multimodality registration algorithms
19

NUCLEAR MEDICINE IMAGING

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