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198 Nuclear Medicine Physics

5.3.3.1.1 Brain PET

The development of scanners dedicated to brain studies, with better spatial

resolution, good sensitivity, and lower cost, has had a market in PET for

many years, especially in research. The ECAT 953B camera [56] appeared

in 1990; and, more recently, the HRRT (high-resolution research tomograph)

system has been developed, which has the best intrinsic spatial resolution

for studies in humans, about 2 mm [57]. Other systems have been developed

but not necessarily marketed and are used primarily in research. In PET,

these systems aim at maximizing spatial resolution by reducing the size of

crystals, while seeking to improve sensitivity by gaining in solid angle of

detection. One desirable feature is the ability to measure the DOI in PET, so

that the spatial resolution is more uniform in the ﬁeld of vision. The HRRT

camera was the ﬁrst commercial PET tomograph capable of measuring the

depth of interaction, through the joint use of two crystals in each detector

block, LSO and LYSO, in a technique called Phoswich. The different signal

produced by each scintillator can distinguish whether the interaction was on

the front or back of the detector, enabling improvement of the resolution at the

periphery of the ﬁeld of vision. The Phoswich arrangement using two crystals

can discriminate the depth information at two levels. The use of three or more

crystals increases complexity but would identify more levels of DOI. A viable

alternative, giving a greater number of levels of DOI, involves reading the

scintillation light at both ends of the crystal, for example, by using APDs (see

Section 5.1.3.2). The relationship between the readings of the two APDs can

distinguish the depth of interaction in the crystal with an accuracy of the order

of millimeters [58].

5.3.3.1.2 Animal PET

The growing importance of animal experimentation to help our understand-

ing of humans makes the development of systems dedicated to the study

of animals quite attractive. It offers testing methods for the better analysis

of both diseases and the behavior of normal tissues and organs, in addition

to trying out new therapies and techniques, such as in vivo observation of

gene expression. The ﬁrst commercial cameras dedicated to small animals

were produced in the late 1990s [59] and quickly became popular due to the

large number of research centers interested in their images. Nowadays, there

are dedicated animal testing cameras for all the main imaging techniques:

microPET, microSPECT, microCT, and microRMN. In these small cameras,

too, the smaller the area of detection the lower the price of components, and

increasing proximity to the subject enhances the sensitivity of the camera,

while it is possible to optimize the system in other ways, keeping the cost

relatively low. In this application, spatial resolution is essential and domi-

nates the other speciﬁcations (with the possible exception of sensitivity, which

should increase with the improvement of spatial resolution in order to main-

tain a sufﬁcient number of decays detected by a voxel and, thus, an adequate

Radiation Detectors and Image Formation 199

signal-to-noise ratio). This factor leads to the development of systems with

more radical solutions, such as the HIDAC system, which achieves better

spatial resolution, 0.95 mm [46], through nonconventional detectors in PET

(multiwire proportional chambers, which are not based on crystal scintilla-

tors). Indeed, the most successful attempts at approaching the physical limit

of spatial resolution are found in animal PET, where technical solutions exist

that can reach spatial resolutions close to a few tenths of millimeters [60,61].

5.3.3.1.3 Other Dedicated Systems

Several systems have been developed to observe speciﬁc organs, includ-

ing systems dedicated to mammography (PEM), where several groups are

actively researching this area; and there are several prototypes in develop-

ment [62,63]. Systems speciﬁcally designed for other organs are also being

developed [64], with the following characteristics in common: an important

clinical application, with a large number of patients able to justify a dedicated

and optimized system for the purpose; detection systems smaller than the tra-

ditional PET whole body systems, which can be placed closer to the patient,

in order to increase the solid angle and thus ensure good sensitivity at a low

cost; and high spatial resolution obtained with smaller individual crystals,

preferably able to measure the DOI. The best performance in sensitivity and

spatial resolution, for a lower cost, makes these systems particularly interest-

ing, whereas the fact that they are dedicated to a speciﬁc application improves

the functional aspects considered important. For example, a PEM system can

be optimally adapted to stereotactic systems to guide the biopsy, to conven-

tional mammography systems to aid the diagnosis with image fusion, and

to the geometric constraints of data acquisition (including the possibility of

inspecting the axillary region), among other possibilities.

5.3.3.2 PET/CT

The development of the ﬁrst PET or CT system with a conﬁguration similar

to current commercial systems began in 1995 with a prototype installed at

the University of Pittsburgh Medical Center that entered into clinical trials in

1998. This prototype had a PET camera and a CT camera in a tandem or in-line

conﬁguration, where the patient enters a CT tunnel followed by a PET tunnel

(Figure 5.42). This design was adopted, because it was simpler and more

modularthan anotheroption originally designed and testedin twoprototypes

[65]. In these prototypes, the two modalities were integrated in a single ring,

consisting of a partial ring of two PET detectors in coincidence, and the CT

component, with an x-ray source and detector, using the remaining space of

the ring [65]. This geometry with a unique rotating partial ring required the

development of electronics, sensors, and mechanics for a new type of camera

with integrated PET and CT. This forced the resolution of many technological

problems whose complexity was less advantageous than the option of simply

adding two existing and tested cameras and performing as few adjustments

200 Nuclear Medicine Physics

FIGURE 5.42

Some proposed PET camera geometries for systems designed for speciﬁc applications. (a) Tradi-

tional whole-body system (PET/CT), with indication of some coincidences detected. (b) Animal

PET. (c) Brain PET. (d) Positron emission mammography (PEM).

as necessary, especially mechanical ones, to allow the patient’s bed to enter the

two tunnels. Thus, PET or CT was born, combining two techniques with the

minimum of adaptation and, given its success, thereis now a trend in opposite

direction, with the development of dedicated new systems that optimize the

integration of two techniques, in terms of both software and hardware.

The ﬁrst commercial PET or CT system was introduced in 2000, and the

ﬁrst systems were installed in 2001 [66]. The success of PET or CT was huge;

and within a few years, the market for PET cameras had been replaced and

more than a dozen models had quickly emerged from various manufactur-

ers. The advantages of joining the morphological information of CT with the

functional information of PET in clinical practice were central to this success.

Additionally, there was the beneﬁt from using CT information to correct for

attenuation in PET with greater speed, lower noise, and better contrast. From

the perspective of the patient, PET or CT had the advantage of being able

Radiation Detectors and Image Formation 201

to acquire all data in a single and shorter study, thanks to the faster attenua-

tion correction. From the standpoint of the medical imaging service, reducing

the acquisition time of PET or CT both increased the number of studies and

facilitated the management of patients by halving the number of times they

have to come for examinations and the number of reports.

The rapid evolution of PET or CT has not yet been matched by an effective

and complete clinical validation of the advantages of PET or CT compared

with conventional PET alone or to PET coregistrated by software with CT

data acquired in another scanner [67]. Although many studies have been

carried out for different clinical applications, the information for an overall

assessment is still limited, partly for methodological reasons: it would be

difﬁcult to justify the systematic exposure of patients to multiple tests and a

higher dose of radiation for these studies. Apart from this, it is nevertheless

agreed that the observation of the function together with anatomy is a good

practice, improving the conﬁdence of physicians in assessing the status of the

patient. Whether this improvement is expressed in an actual clinical beneﬁt of

PET or CT relative to other options, thus offsetting the disadvantage of using

a higher dose of radiation than in PET alone or surpassing the advantage of

using existing cameras and software for coregistration and fusion, depends

on the characteristics of the speciﬁc clinical application; and more time is

needed for analysis. According to [66], a review of publications on PET or CT

suggested an incremental beneﬁt of PET or CT over PET in 10% of patients

analyzed. Some of the additional difﬁculties of such conclusions should be

noted: technology is rapidly changing, not only in terms of scanners and

software, which change the conditions of the comparison, but also with the

expected introduction of new and more speciﬁc radiopharmaceuticals, for

example, the clinical information available mainly refers to studies with FDG.

Although the integration of PET and CT in the ﬁrst PET or CT systems

attempted to minimize changes in the systems, several aspects had to be sub-

stantially modiﬁed. The patient table had to be redesigned, as it would have

to move more than usual because the tunnel was now wider. One of the prob-

lems found was related to the vertical deﬂection of the table due to the weight

of the patient and the larger extension outside the support as it entered the

tunnel, which caused coregistration errors between PET and CT data. One

solution was to move the table forward on rails instead of having a ﬁxed

base for it on the ﬂoor, so that the progression of the patient and, therefore,

the deﬂection was not signiﬁcant. Another concern was the use of CT data

for attenuation correction in PET. The CT data relate to the linear attenua-

tion coefﬁcient of tissues for photons emitted by the CT tube, with an energy

of about 70–140 keV, and not to the photons detected in PET, with 511 keV

(assuming there is no Compton interaction). Ways to convert the attenuation

coefﬁcient from CT to PET are discussed in Chapter 6. The difference between

the acquisition time for PET, typically several minutes, and for CT, of the

order of seconds, also generates artifacts: The movements of organs (heart,

lungs) cause greater blurring of the PET image relative to CT. This changes

202 Nuclear Medicine Physics

the shape of organs and leads to badly overlapped images and errors in atten-

uation correction. The resulting effect is the appearance of areas with wrong

attenuation correction factors, for example, in the diaphragm. Other artifacts

may arise due to metallic implants or other objects of higher density, causing

beam hardening in CT. This effect causes an increase of local values of the

attenuation coefﬁcient, leading to an excessive attenuation correction in the

region around the implant, which then appears to have greater activity than

it really does. Other artifacts include those due to the presence of contrast in

CT and the truncation of the patient, in some cameras that have a CT with a

smaller ﬁeld of view radius than that of PET [68]. These artifacts led to the

development of scanners with a larger ﬁeld of view radius for CT, with 70 cm

instead of the usual one of about 50 cm, to reduce the effects of truncation

of the CT image of the patient and the corresponding attenuation correction

errors (over-correction of attenuation within the patient, leading to overesti-

mation of the activity; the opposite situation in the region where there are no

attenuation coefﬁcients measured by CT [69]).

5.3.3.3 PET/MRI

The integration of PET and MRI (magnetic resonance imaging) is underway,

with several prototypes of cameras in development [70–73]. The marketing of

some of these systems is starting, at the moment only for animals, although

commercial clinical systems for the whole body are expected soon. A multi-

modal PET or MRI system has essentially the same advantages as a PET or CT

system; it integrates the functional and morphological information, ensuring

a good coregistration of the two types of information, with the beneﬁts that

result for the patient, clinic and service from doing a single study, as noted

in the previous section. However, there are also some notable differences: the

MRI has better contrast for different tissue types and a different ﬂexibility in

terms of other parameters measured, with the variants of magnetic resonance

spectroscopy (MRS) and functional nuclear magnetic resonance (fMRI). The

morphological information of MRI is, thus, of particular interest, for example,

not only in brain studies where it can easily distinguish between white and

gray matter (unlike CT) but also in other parts of the body, such as studies of

the pelvic and locomotor system. The MRS and fMRI can also provide addi-

tional functional information, complementary to PET. These modalities have

been the subject of intense research, especially in brain studies; and a wide

range of applications has already been developed, which would beneﬁt if they

could be simultaneously obtained with the information from PET. Although

there are software tools that facilitate the accurate fusion and coregistration

of the images, particularly in brain studies, they use data acquired at different

times and in different conditions. The ﬂexibility of MRI, especially if simul-

taneous with PET, can also, in principle, address a wider range of issues than

PET or CT, which is sequential in time in current systems. Basically, it is the

Radiation Detectors and Image Formation 203

possibility of developing new types of metabolic studies, correlating a vari-

ety of physiological variables that can be measured by fMRI and MRS, and

combining the excellent spatiotemporal resolution of MRI with the excellent

sensitivity and speciﬁcity of PET that enables us to predict great opportunities

for the study of biological systems in vivo, with the possibility of conducting

studies that have not been possible until now and of developing new clinical

applications in the short or medium term.

As with PET or CT, where the integration of modalities brought additional

beneﬁts such as CT attenuation correction, in PET or MRI, too, it is pos-

sible to correct for partial volume effects more easily and accurately. This

correction, discussed in Chapter 6, is of great interest in PET to quantify the

activity in small structures in absolute terms and with good precision. This

is useful in brain studies, for instance, where one intends to study the direct

action of drugs in the brain or to diagnose and study the development of

pathologies. However, this correction is rarely performed owing to the lack

of good quality anatomical information, inadequate acquisition or coregis-

tration, or simply because of the greater complexity of procedures involved.

These limitations disappear with PET or MRI systems, which could well serve

to improve the accuracy of the quantitative information provided by PET in

small structures.

Another advantage that may result from the simultaneous use of PET and

MRI is the fact that the magnetic ﬁeld can reduce the positron range, in

principle, reducing this limitation of PET physics and thereby improving the

spatial resolution of PET in the plane perpendicular to the magnetic ﬁeld.

This possibility has been mentioned several times [74,75], but it would require

very strong magnetic ﬁelds of the order of9Tormoretoachieve a signiﬁ-

cant effect with the most common radionuclides. This seems to be possible

in the medium term, with the ﬁrst signs that the studies on patients with

high ﬁelds (9.4 T) are safe and with the development of MRI scanners for

patients with ﬁelds above 11 T. With such high ﬁelds, the speciﬁcation of the

instrumentation becomes more difﬁcult to meet, so there is still a long way

to go.

Even though these advantages were known long ago, only now the ﬁrst PET

or MRI systems are appearing, mainly because their development poses more

important technical difﬁculties than PET or CT. The high magnetic ﬁelds of

MRI, its fast gradients, and high intensity of radio-frequency pulses interfere

with the electronic devices used in PET; and these, in turn, may inﬂuence

aspects of the MRI system such as the uniformity of the magnetic ﬁeld. The

PMTs used in PET detector blocks do not work in the ﬁelds of MRI and

must be replaced by other devices such as APDs (Avalanche PhotoDiodes).

This replacement of PMTs is beneﬁcial for PET, as APDs are smaller and

can help produce systems with better spatial resolution, while reducing the

size of the detection system, which can then enter the MRI ring in a device

usually known as PET insert (a system that is inserted when necessary to

acquire simultaneous PET or MRI, generally used for small animals). The

204 Nuclear Medicine Physics

shielding of the detectors and electronics is another concern of the groups that

are developing these systems, and it has been possible to develop scanners

where the interference between the PET electronics and MRI ﬁeld is reduced

to negligible values.

The ﬁrst PET or MRI systems for animals [70–73] and the brain [76,77]

are emerging and new and interesting applications are expected. It is not

clear how this technology will evolve in an environment dominated by PET

or CT [66], but it seems certain that the integration of imaging modalities

with important synergies between them that compensate for the additional

complexity of the systems will open up new paths that may lead to exciting

developments and discoveries in the coming years.

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