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ADVANCES IN PET/CT IMAGING A TECHNOLOGISTS’ GUIDE Produced with the kind support of
Table of contents
Foreword 4
Andrea Santos
Introduction 6
David Bogović, Luca Camoni, Christelle Terwinghe, Agata Pietrzak
Chapter 1 Hardware updates 8
Igor Iskra
Chapter 2 Updates in reconstruction algorithms 22
Dimitris Visvikis, Michel Koole, Ian Armstrong, Christian Vanhove
Chapter 3 Diagnostic CT in the oncological PET applications and protocols 32
Ivana Zagar
Chapter 4 PET/CT artefacts and pitfalls 46
Tyler Middlebrooks
Chapter 5 Advanced radiopharmaceuticals 58
Guy Bormans, Frederik Cleeren
Chapter 6 Advances in neuroimaging 76
Donatienne Van Weehaeghe
Chapter 7 Novelties in cardiac imaging 88
Elisabetta Cerudelli
Chapter 8 New solutions in the oncology 104
Andrej Doma
Chapter 9 Radiomics 122
Florent Tixier
Imprint 131
EANM TECHNOLOGISTS’ GUIDE 3
ADVANCES IN PET/CT IMAGING
FOREWORD FOREWORD
Foreword
Positron emission tomography (PET) is one of the most promising areas
of current medicine, considering the constant evolution of the technical
equipment and the ongoing research into new and promising radiotracers
for the study of human physiology and pathology. Since the advent of the
hybrid imaging era, with computed tomography (CT) incorporated into
the PET scanner, PET imaging has undergone a great evolution in terms of
improved image quality and, consequently, better clinical output.
Nuclear medicine technologists are of the Technologists’ Guide, which this project. A special thank you goes to Angela Parker for her editing, reviewing
the professionals when it comes to the addressed the topic of hybrid imaging to the Physics Committee of the EANM, and support. Last but not least, I thank the
imaging process. in conventional nuclear medicine, the who have supported us throughout EANM Board and Executive Office for their
Acting as the link between the sciences European Association of Nuclear Medicine’s and made a valuable contribution to tireless efforts, which have made this series
that are the backbone of PET/CT imaging Technologist Committee (EANM-TC) has this Guide. I also gratefully acknowledge of publications possible. Advances in PET/
and the patient, we combine the necessary kept this year’s focus on hybrid imaging. the valuable content provided by our CT Imaging was only possible thanks to
theoretical background with practical skills This time, however, we have embarked overseas colleagues from the Society of the contributions of everyone mentioned
under the principle of best practice. To this on the topic of PET-CT imaging, inviting Nuclear Medicine and Molecular Imaging above. My most sincere thanks to you all!
end, an updated publication documenting specialists in each specific area to write – Technologist Section (SNMMI-TS). A
the advances in this imaging technique is about the advances in their field. special word of appreciation goes to the
of major importance in order to ensure I should like to express my tremendous editorial team who have dedicated their
that everyone is working at the same level. gratitude to all the authors who time to this publication: Agata, Luca, Andrea Santos
Following on from last year’s edition contributed their time and expertise to Christelle and David – thank you! and also Chair, EANM Technologists Committee
4 EANM TECHNOLOGISTS’ GUIDE EANM TECHNOLOGISTS’ GUIDE 5
ADVANCES IN PET/CT IMAGING ADVANCES IN PET/CT IMAGING
INTRODUCTION INTRODUCTION
Introduction
Every year, the Technologists Committee publishes a Technologists’
Guide to develop and improve the nuclear medicine specialists’
knowledge and personal skills in various aspects of nuclear medicine.
This year, together with an interdisciplinary group of specialists,
we decided to address the topic of “Advances in PET/CT Imaging”, outlining
recent advancements in radioisotope imaging with a special emphasis on
PET/CT techniques.
PET/CT study allows us to evaluate the the latest solutions that are improving advantages, utilities and applications, success of the process. We hope that this
aetiology of various diseases, and has technical and clinical study outcomes. not forgetting the method’s limitations latest edition of the Technologists’ Guide
therefore become an essential element This extensive guide encompassing and ways of avoiding their impact on the will be of benefit in helping our readers
of diagnostic management. The rapidly ten chapters provides the reader with eventual PET/CT dataset. update their personal skillsets.
evolving technology of medical imaging a wide range of information: from We believe that hybrid imaging is not
is permitting the constant improvement hardware and software updates, PET/ only a set of techniques and properties,
of existing solutions while simultaneously CT artefacts and pitfalls through but also and especially the interdisciplinary
eliminating the method’s limitations. radiopharmaceutical advancements to and qualified medical team, who have
Advances in PET/CT Imaging aims to the latest solutions in oncology and the a significant influence on diagnostic
provide a technical and clinical overview definition and applications of radiomics. management. The complexity of PET/CT David Bogović, Luca Camoni, Christelle
of PET/CT principles and applications, The contents guide readers through the study means that the technician’s extensive Terwinghe & Agata Pietrzak
highlighting recent innovations and long list of specific PET/CT characteristics, knowledge and experience is vital to the Editorial team
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U PDATES
by Igor Iskra
1
CHAPTER 1 CHAPTER 1
Positron emission tomography (PET) enables us to visualise molecular a transmission image was obtained using array of crystal elements was coupled
processes in the human body. Certain positron-emitting radionuclides an external source of 68Ga and enabling with four photomultiplier tubes (PMTs).
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interact with specific molecular pathways, thus giving us the opportunity attenuation correction. In 1974, to reduce The light produced in every scintillation
of imaging physiological or pathophysiological occurrences. PET scanners unwanted scattering effect, a hexagonal event, caused by the interaction between
use the principle of coincidence detection of annihilation photons, a array of sodium iodide scintillation the annihilation photon and the crystal
method in which two photons emerging from the same annihilation detectors was designed. This system element, was shared among all four
process are detected on opposite sides of a detector system. Of course, like was heavily shielded with the assembly photomultiplier tubes. The information
every diagnostic method, PET imaging has its own limitations and pitfalls, rotating around a transaxial plane, hence from the detector thus contained the
scattering and attenuation of photons by the tissue being the two most being known as positron emission coordinates of the scintillating element,
prominent ones. 1 2 transaxial tomography (PETT). This led determined from the light distribution,
to a commercial version of this design, and the energy of the incoming photon,
Coupling a PET scanner with a CT patient’s exposure to radiation. The idea known as the ECAT I (ECAT = emission determined from the total amount of
scanner is an efficient way to correct of using coincidence detection of positron computerised axial tomograph).4 5 produced light. 1 4
most of the imperfections of PET imaging. capture was born in the early 1950s. In The next step towards the modern Another problem in need of solving
“Low-dose” CT can greatly improve the 1953 a first paper was published on the PET-CT scanner was a configuration with was the small acceptance angle for
ability to obtain an exact anatomical application of coincidence detection for multi-ring geometry. This new design coincidence photon detection due to
localisation of pathophysiological localising brain tumours, describing a allowed better usage of scanners for PET the presence of the septa (2D mode).
processes in the patient. Furthermore, the pair of sodium iodide detectors placed quantification, but it also created some Retracting or totally removing the septa
correlation between the intensity of focal on opposite sides of the head. Then, in new problems, mainly by reducing the established a 3D mode of acquisition,
accumulation of radionuclide determined 1961, a ring of 32 sodium iodide-based spatial resolution. First, there was the improving sensitivity and enabling true
by the PET scanner and the degree of coincidence detectors was developed problem of size and spacing between the 3D reconstructions. The problem with the
morphological changes ascertained by and several other designs for coincidence detector elements. Another disadvantage 3D mode was an increased scatter fraction
the CT scanner is important in evaluating detectors emerged in the subsequent was the expensive and physically limiting (35% or even more), but several scatter
the pathological potential of certain years. 4 “one-to-one” coupling between the correction models were subsequently
focal changes. Lastly, “low-dose” CT is The first developmental breakthrough scintillation crystal and the photodetector. developed to compensate for this. 1
an irreplaceable tool for correcting the came in the early 1970s, with the first Lastly, the original designs included lead The last and most important step
attenuation of annihilation photons by the positron camera. Its unique design or tungsten shields between the detector towards modern PET-CT scanners was
tissue. 3 enabled smaller sodium iodide crystals rings, which severely reduced the overall the introduction of the CT scanner itself.
to be coupled with fewer and larger sensitivity. Nevertheless, the solutions In the early days, a PET scanner was often
photomultipliers, which resulted in to these problems yielded new designs equipped with some additional source of
HISTORICAL DEVELOPMENT OF reduced costs and improved spatial which laid the foundations for modern transmission scanning for the purpose of
PET-CT SCANNERS resolution. Shortly after that, the idea PET-CT scanners. 1 4 attenuation correction, as well as for regular
Since the advent of the first PET scanners, of a rotating positron camera emerged, The problem of ineffective coupling detector checks. 68Ge and 137Cs were the
the main developmental goals have been producing multiple plain images between the crystal and detector elements main radionuclides used. As mentioned
to improve the sensitivity and spatio- which were later back-projected onto was overcome by introducing the block before, the introduction of CT scanners in
temporal resolution and to reduce the tomographic images. In every projection detector concept. In this concept, an PET acquisition not only enabled better
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attenuation correction, but also paved stopping power for 511 keV photons, the real energy of the photons. Higher orthosilicate (LYSO), a derivate of LSO with
the way for other advanced features. A decay constant, light output and energy energy resolution means that the energy a small percentage of yttrium, is currently
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main pitfall of the early CT scanners used resolution. variance is smaller, therefore photons being used in the newest TOF-PET
in PET-CT acquisition was high radiation Stopping power is described as the whose energy is different from that of the scanners since it has slightly better light
exposure, which was later remedied by the inverse of the mean distance travelled incident photons, i.e. Compton-scattered output and energy resolution compared
advent of modern iterative reconstruction by photons before they deposit energy photons, will be less often detected. 1 7 8 to LSO.
techniques. 4 5 6 in the crystal, and it is proportional to Sodium iodide (NaI) was the first Instead of using LSO, some
the density and effective atomic number scintillator used in PET scanners. It is cheap manufacturers opted to replace BSO
of the material. Higher stopping power and has the highest light output, but it has with gadolinium orthosilicate (GSO),
MODERN PET-CT SCANNERS means that the electron will travel a very low effective density and a very long the main advantage of which is better
Although there are many specific shorter distance in a material because decay constant, so is no longer used today. energy resolution. Other materials such
scanner designs, every PET scanner it will interact more often with atoms in Bismuth germinate (BGO) was the as lanthanum (III) bromide (LaBr3) or LuAP
basically consists of three main parts: the material, therefore indirectly enabling main scintillator used in PET scanners (lutetium aluminium perovskite, LuAlO₃:Ce)
scintillation detectors, photodetectors and more effective detection of incident throughout the 1980s and 1990s. It has are currently being evaluated as possible
a computer. PET detectors are based on a photons. the highest known effective density of all new scintillators in PET scanners.1 4 7 9
process called scintillation in which high- The decay constant is determined by scintillators, but its low light output and
energy photons interact with scintillating the duration of the scintillation flash in the long decay constant became a problem Block detectors
crystals, creating a new electron either crystal. A shorter decay constant means with the widespread adoption of 3D As mentioned before, a block detector
by Compton scatter or by photoelectric that the scintillation material will be able acquisition mode. This resulted in a quest setup was one of the major breakthroughs
absorption. This new electron loses its to produce more individual scintillation to find new scintillators with a shorter in the development of modern PET
energy by passing through scintillation flashes in a certain period of time, thus decay constant, better light output and scanners. Instead of using “one-to-one”
material and exciting new electrons. 7 allowing more incident photons to be improved energy resolution. coupling between scintillators and
The excited electrons subsequently counted. Then came lutetium oxyorthosilicate photodetectors, this concept proposed
return to their original energy state by Light output can simply be described (LSO), a component originally used for using a block of scintillation crystals
releasing electromagnetic radiation in as the yield of scintillation photons nuclear well logging. It has a high light divided into an array of single-functioning
the form of light. This light is registered by produced by the incident photon. Higher output and high efficient density, but smaller elements, a few millimetres in
photodetectors and transformed into an light output means that the incident its main advantage is a very short decay size. This was achieved by mechanical
electrical signal with the specific energy photon will trigger the creation of more constant. LSO’s superior time resolution incision of channels in the primary crystal
and coordinates of the incident photon. scintillation photons, thus increasing has given PET scanners the ability to block, with channels being filled with
All the signals are then processed by the spatial and energy resolution. measure the time difference between opaque material. This opaque material
computer, creating a final image.1 7 Finally, energy resolution is the ability the arrivals of the two annihilation prevents so-called “cross-talk”, i.e. a
to accurately determine the energy of the photons. This is called “time of flight” (TOF), scatter of light between the elements. A
Scintillation crystals interacting photons. It depends on energy and it provides otherwise unavailable block is then usually coupled with four
Scintillation crystals are the most vital variance, which is the ratio between positioning information which enables photomultiplier tubes. The sharing of
part of any detector. Every scintillation the range of possible values of photon us to determine an annihilation point to light between the PMTs is converted to
material has four main characteristics: energy determined by the detector and within a few centimetres. Lutetium yttrium their relative signal output, which is then
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used to determine the crystal element analogue versions called avalanche exceptional light collection capability, PMTs.12in terms of physical performance
involved in interaction with the photon. photodiodes (APDs) and silicon which is due to their compact structure. and technical features. Particular attention
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There are also improved versions of block photomultipliers (SiPMs). APDs, working in Unlike the circular shape of PMTs, which has been given to evaluate the whole-
detectors constructed from two different Geiger mode, are generally not considered was responsible for the significant gaps body performance by sensitivity, spatial
scintillation materials with different decay an effective choice for TOF-PET scanners between them, SiMPs are square in shape, resolution, dead time, noise equivalent
constants (photoswitch), enabling better due to their significantly slower response which allows them to be packed more counting rate (NECR
determination of the depth of photon time. Analogue SiPMs use single photon tightly together. SiPMs mainly use “one-to- An alternative type of scanner geometry
interaction with the detector material. 4 7 avalanche diode (SPAD) arrays to detect one” coupling to crystals, which provides is the “partial-ring” setup, in which two
single scintillation photons, subsequently a much higher count rate capability and opposing matrices of crystal blocks
Photodetectors turning all the generated pulses into one improved spatial resolution.9 rotate around the patient. They are not
Photomultiplier tubes were the most analogue output signal. Like APDs, SiPMs perfectly opposed, thus achieving a
commonly used photodetectors in PET initially didn’t have TOF capability.10 11 PET-CT scanner geometry better transversal field of view during
scanners. PMTs are glass-enveloped In recent years a new group of solid- Most of the modern PET scanners have the rotation, but their general sensitivity
vacuum tubes with three main parts: a state detectors has emerged, called digital “full-ring” geometry, with their detectors is lower compared to “full-ring” scanners.
photocathode, dynodes and an anode. photon counters (DPCs). In this version covering a full 360° around the patient. 12
in terms of physical performance and
Their functioning is based on the of detectors, every detector module This setup provides optimum sensitivity, technical features. Particular attention
photoelectric effect, in which an emission consists of a 4 x 5 array of SiPM detector fewer image artefacts due to tracer, organ has been given to evaluate the whole-
of electrons is caused by interaction tiles, additionally divided into a 4 × 4 or patient motion, and excludes the need body performance by sensitivity, spatial
of light with photoelectric material. In matrix of silicon sensor chips. Each chip for additional calibrations since there are resolution, dead time, noise equivalent
PMTs, the photoelectric component is is a 2 × 2 matrix of digital photon counter no moving components.5 counting rate (NECR
called the photocathode. When electrons detectors called silicon pixels. In every Additionally, there are three different Axially, PET scanners today consist of 2
are emitted from the photocathode, pixel there are 3200 SPADs or microcells, types of detector surface structure. The to 5 rings of detector elements, compared
induced by scintillation photons, they are with every microcell functioning as an first type is the common block detector to several dozen in the earlier days. These
pulled towards the anode by the electric individual detector. The total count of all concept, in which there is a cylindrical rings can be separated by thin annular
potential generated. On their way to the photon–microcell interactions detected assembly of crystal blocks in a ring rings or septa made of photon-absorbing
anode, electrons collide with the dynodes, in a certain interval of time, initiated by structure several blocks deep. The second material like tungsten and used for
creating secondary electron emissions the arrival of the very first scintillation option is a curved crystal structure, in collimation. The presence or absence of
from the collision. The resulting electrical photon, is translated into a digital number which 6 bigger blocks of NaI crystals, septa determines the type of acquisition.
current is proportional to the number of proportional to the energy of the photon coupled with 48 PMTs each, are placed side If septa are present, then so-called “2D
initial scintillation photons, and is translated that induced the scintillation event. PET by side to achieve ring geometry. Finally, acquisition” is performed, since the septa
into an electrical signal. PMTs are therefore scanners equipped with DPCs show there is the PIXELAR module, consisting shield “out of plane” coincidence photons.
considered as analogue photodetectors, better image quality, improved lesion of a curved matrix made up of 628 (22 x Since the septa block a fairly large number
their main advantage being their lower detectability, and are reported to perform 29) GSO crystals attached to a continuous of true coincidences from ever reaching
sensitivity to temperature variations. 1 10 faster acquisitions with lower radiation light guide, in which ring geometry is the detector, this type of acquisition is
The development of modern solid- exposure.11 achieved by placing 28 of these modules characterised by reduced scattered and
state detectors started in the 1990s with The main advantage of SiPMs is their side by side and coupling them with 420 random coincidences, but it also has lower
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sensitivity. Another type of acquisition is on the vendor, although the basic - by measuring the changes in air because each gate can mix several tissue
so-called “full 3D acquisition”, performed elements of design are largely similar. PET temperature during respiration, either with positions. Researchers have suggested
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with or without retracted septa. In this scanners have “full-ring” geometry and are a sensor placed inside an oxygenation either selecting PET events from gated
situation coincidences are accepted integrated with CT scanners in a single mask or with a sensor placed close to the acquisitions or performing several PET
from all angles, thus providing higher device. The patient is positioned only patient’s nostrils: this mode of respiratory acquisitions (corresponding to a breath-
sensitivity. However, that also implies an once and the scans are acquired in close gating uses the fact that the air is warmer hold CT position
increase in random coincidences, higher sequence, enabling improved registration during exhalation; Cardiac PET-CT scanners also use
scatter fraction and loss of events due to accuracy and a single integrated scan. 4 5 - by using a spirometer placed close to an external ECG device for gating and
an increased count rate, and subsequently the patient’s nostrils or mouth: this mode detecting certain phases of the cardiac
increased dead time. It is worth mentioning Additional hardware for PET-CT studies of respiratory gating has not yet been used cycle, in the same way as in gSPECT.
that today’s commercial PET scanners are FDG PET-CT has an important role in clinical practice.
not equipped with septa and thus acquire in evaluation of pulmonary lesions It is worth mentioning that nowadays,
data in this second acquisition mode. 14 and detection of occult intrathoracic in view of the significant practical CT SCANNER IMPROVEMENTS
12
in terms of physical performance and metastases. In contrast to CT, which limitations of hardware-based respiratory Over the years, the two main goals of CT
technical features. Particular attention covers only a part of one breathing gating, the emphasis is on software scanner development have been better
has been given to evaluate the whole- cycle, PET acquisition lasts substantially gating, Bayesian penalised likelihood image resolution and lower radiation
body performance by sensitivity, spatial longer through multiple breathing cycles. (BPL) PET reconstruction, and texture exposure to the patient. Alongside
resolution, dead time, noise equivalent Respiratory motion can thus cause a lot analysis. 13 14follow-up, and treatment better software solutions and image
counting rate (NECR). of motion and attenuation correction planning. For cancers located in the thorax reconstruction algorithms, upgrades in
artefacts on PET images. To eliminate or abdomen, the patient’s breathing hardware have been the main drivers of CT
PET-CT coupling this negative effect, respiratory gating is causes artifacts and errors in PET and CT scanner improvement. Nowadays, PET-CT
The first PET-CT scanner prototype performed. In this process, data collected images. Many different approaches for systems are equipped with up to 128-slice
emerged in 1998. The PET scanner was in each respiratory cycle is divided into artifact avoidance or correction have CT scanners, compared to the 16-slice
placed on the rear end of the CT scanner, “bins”, either by detecting a certain been developed; most are based on scanners in use as little as 15 years ago. 4 5 15
creating a single integrated assembly. The respiratory amplitude (amplitude-based gated acquisition and synchronization One other important area of
scanners rotated together at 30 rpm and gating) or a phase of the respiratory cycle between the respiratory signal and PET improvement is the development of new
the patient bed could be moved axially (phase-based gating). acquisition. The respiratory signal is usually acquisition modes. Conventional PET-CT
from the CT to the PET scanner so the Gating is usually performed using produced by an external sensor that tracks studies are performed in so-called “step-
corresponding images were accurately external sensors which track respiratory a physiological characteristic related to the and-shoot” mode, in which the patient bed
registered. However, the acquisition, motion. This can be accomplished in patient’s breathing. Respiratory gating is is moved between every step of image
reconstruction and operating systems several ways: a compensation technique in which time acquisition outside the initial axial FOV
were separate and image fusion was - by monitoring the displacement of the or amplitude binning is used to exclude range. An alternative mode is “continuous
performed by software. 5 abdominal wall using an elastic chest belt; the motion in reconstructed PET images. table motion” mode, in which the patient
Nowadays, PET and CT scanners are - by monitoring the displacement of Although this technique is performed table moves continuously throughout the
coupled through hardware fusion. The two infrared markers positioned on the in routine clinical practice, it fails to whole scanning process. Data is acquired
characteristics of scanners vary depending patient’s thorax; adequately correct for respiratory motion uninterruptedly while the patient is being
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moved through the gantry, resulting in effectively for this type of detection. 9 components and ambiguities regarding CONCLUSION
increased uniformity and sensitivity of Monolithic detector. One thin the indications for whole-body scans, Modern PET-CT scanners are currently
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acquisition. 16 block of crystal coupled with multiple which are still unclear. 17 18 undergoing rapid development. New
photodetectors can improve light designs and software improvements
transduction because of the larger crystal are aimed at ensuring better image
FUTURE INNOVATIONS volume and absence of inter-crystal resolution with lower radiation exposure
Improved ratio of deposited energy boundaries. 9 to the patient. New detector technologies
to light output of scintillators. Current using digital photon counters are set
Lu-based scintillation crystals have a to significantly improve the acquisition
somewhat non-linear light output in EXPLORER – A WHOLE-BODY process, enabling faster and more reliable
response to the energy deposited by the PET-CT SCANNER diagnostics.
interacting photon. In particular, this light Current PET-CT scanners only capture a
yield ratio decreases with decreasing small portion of the patient’s body inside
energy of photons. LuAP (lutetium the field of view (FOV). What is more, only VEREOS BIOGRAPH VI-
(PHILLIPS SION 600 DISCOVERY MI
aluminium perovskite, LuAlO3) and LuYAP 3–5% of the available signal is detected by PET-CT SCANNER EXPLORER
HEALTH- (SIEMENS (GE HEALTHCARE)
(lutetium-yttrium aluminium perovskite) scanners. These are the two main reasons CARE) HEALTHINEERS)
scintillator crystals have a superior light for the poor sensitivity of current whole-
yield ratio and hence superior energy body PET-CT scanners.
crystals LYSO LYSO LSO LYSO
resolution. 9 EXPLORER is a PET-CT scanner prototype
Semiconductor detectors. These which can perform a whole-body PET scan
non-scintillating detectors use dense up to 40 times better than the currently 2.76 x 2.76 x 18.1 3.86 × 3.86 ×
crystal size 3.2 x 3.2 x 20 mm3 3.95 × 5.3 × 25 mm3
crystals which are capable of directly available scanners. It has 40 rings and is mm3 19 mm3
absorbing the interacting photon energy able to scan the whole body within 30
and converting it into electrical charge seconds. Its 564,480 LYSO crystals, 2.76 x photon detectors SiPM SiPM SiPM SiPM
detected by previously placed electrodes. 2.76 x 18.1 mm each, are arranged in 7 x
The materials used in these detectors are 6 arrays and coupled with SiPM. This PET
CdZnTe (CZT) and TlBr. 9 scanner has a diameter of 78.6 cm and an number of crystals 564 480 23 040 60 800 19 584
Using Cherenkov light to improve time axial length of 194 cm. EXPLORER is also
resolution. Cherenkov light is produced equipped with an 80-row, 160-slice CT
instantaneously when a 511 keV photon scanner. number of detectors 53 760 23 040 304 9 792
interacts with detector material, emitting This setup allows EXPLORER to
a small number of transient, high-energy, significantly increase acquisition sensitivity
in whole-body scans and to produce more CT slices 160 128 128 128
faster-than-light electrons. Lead-based
crystals, such as PbF2, show an excellent reliable images along with rapid scanning
time resolution of 70–90 ps. Also, it seems and lower radiation exposure. However,
that BGO scintillators could be used its main disadvantages are expensive Table 1. Comparison of some of the currently available PET-CT scanners 11 17 19 20 21
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11. Zhang J, Maniawski P, Knopp M V. 20. No Title. Accessed March 10, 2021. https://
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20 EANM TECHNOLOGISTS’ GUIDE
ADVANCES IN PET/CT IMAGINGUPDATES IN
RECONSTRUCTION
ALGORITHMS
by Dimitris Visvikis
Michel Koole
Ian Armstrong
Christian Vanhove
2CHAPTER 2 CHAPTER 2
Image reconstruction generates a volume of image data that reflects the used to reconstruct the 3D distribution of LOR (see Figure 1a), while in TOF-PET it
distribution and quantities of the injected radiopharmaceutical within the PET tracer in the body of the patient. depends on the time difference between
UPDAT ES IN R ECO N S TR UC TIO N ALGO R ITH MS
UPDATES IN R ECO N S TR UC TIO N ALGO R ITH MS
the patient. A reconstructed image typically consists of a 3-dimensional the arrival of two coincidence photons,
array of discrete elements referred to as voxels. When all appropriate as well as detector characteristics, and
corrections have been applied, the value for each voxel typically indicates TIME OF FLIGHT (TOF) it is applied as a Gaussian distribution
the radioactive concentration of the radiopharmaceutical within this voxel In TOF-PET the difference in time on the LOR (see Figure 1b). The centre
volume in units of Bq/ml. Since reconstruction starts from the raw or between the coincidence photons’ arrival of this Gaussian distribution along the
acquired PET data, a short overview of the process for PET data acquisition is measured and stored. For list-mode LOR is the length equivalent of the time
is given below. acquisition the time difference (Δt) is difference between the arrival of the two
stored event by event, while in sinogram coincidence photons, computed as s = c ·
mode the sinogram is divided into several Δt, with c representing the speed of light.
PET DATA ACQUISITION of a transaxial section through the patient. TOF-bins, each corresponding to a time The full width at half maximum (FWHM) of
For PET imaging, positron-emitting This matrix is called a sinogram, since all difference. In conventional PET image the Gaussian distribution is related to the
radioisotopes are required. When the LORs passing through a point at different reconstruction, the probability of an time resolution of the detector.
positron is emitted, it travels for a few angles correspond to a sinusoid curve. This annihilation event is constant along the
millimetres through the body until it also explains the term sinogram. However,
interacts with a free electron, resulting in before the detected events are stored in a
an annihilation event which produces two sinogram, coincidence events can also be
back-to-back gamma photons with energy stored in a list as individual events in the
of 511 keV each. These photons are emitted order in which they are detected (1). This
in almost opposite directions, defining a is called list mode, but it should be noted
line along which the annihilation event that list-mode acquisition is not always
must have occurred. Since PET is based available on the PET system, or it needs to
on the coincident detection of these two be deliberately selected as the acquisition
opposite gamma photons along this line mode. List-mode acquisition provides
of response (LOR), a pair of detectors is more flexibility, however, as additional
needed. Clinical PET systems use a full information such as photon energy,
ring of detectors surrounding the patient, detection timing and detection location
which also explains the superior sensitivity can be stored as well (2). Based on this
of PET. If the two back-to-back gamma information, list-mode data can then be
photons are detected within a certain short used to generate sinograms. In addition,
time window (typically 4 ns depending on list-mode data also allow for retrospective
the PET system settings), it is assumed that rebinning of dynamic raw PET data into
they originate from the same annihilation sinograms corresponding to different time
event. These coincidence events are stored frames, where the frame duration can be
in a matrix which represents the number chosen after data acquisition is completed.
of detected events along different angles Once generated, sinogram data are Figure 1: Probability distributions during (a). conventional image reconstruction, (b). TOF-PET image
reconstruction
24 EANM TECHNOLOGISTS’ GUIDE EANM TECHNOLOGISTS’ GUIDE 25
ADVANCES IN PET/CT IMAGING ADVANCES IN PET/CT IMAGINGCHAPTER 2 CHAPTER 2
RECONSTRUCTION takes into account the Poisson statistics An accelerated variant of MLEM, ordered convert a measured count rate to activity
After acquisition of PET data, the next of radioactive decay and the statistical subsets expectation maximisation (OSEM) concentration, and the attenuation and
UPDAT ES IN R ECO N S TR UC TIO N ALGO R ITH MS
UPDATES IN R ECO N S TR UC TIO N ALGO R ITH MS
step is to reconstruct an estimate of the in nature of the measurement process. Since (5), is currently the most commonly used time-of-flight differences of the two 511
vivo tracer distribution. There are different this approach is iterative, it starts from an iterative reconstruction algorithm in PET keV gamma rays. The exceptions are
approaches to reconstruct the PET data. initial estimate and updates the previous clinical imaging. OSEM accelerates the corrections for scattered and random
On the one hand, there is an analytical estimate of the reconstructed image until convergence of MLEM by performing coincidences; these are typically added
approach with filtered back-projection the new estimate is very close the previous updates based on part of the measured on to the estimated sinograms that are
(FBP), which consists in back- projecting one, meaning that the reconstruction is data only, so that it approximates the generated using the forward projection.
the sinogram data across the imaging no longer improved and convergence MLEM solution but in a much shorter Since accurate modelling of the
matrix. However, simple back-projection is reached. To update the previous computation time and with less memory PET system response during iterative
of the measured data results in a blurred estimate, iterative reconstruction utilises requirement. This technique divides reconstruction results in a reconstructed
version of the original image. The blurring is a probability matrix, commonly referred the measured PET data into several PET image with much better quantitative
minimised by applying a filter to sinogram to as the system matrix. This matrix defines subsets, following a specific order. During properties and homogeneous resolution,
data before back-projection to amplify the probability that a 511 keV gamma-ray reconstruction, each update is based iterative reconstruction provides clear
the high frequencies representing fast- pair originating from a particular voxel on the projection data belonging to a advantages over the older method of FBP
varying intensity changes such as edges, location within the reconstructed image specific subset only, while a different reconstruction. However, it is not without
hence the name filtered back-projection. would give rise to a particular line of subset is selected for the next update. This disadvantages. Due to computational
Although FBP is a very fast technique with response in a sinogram. An initial estimate accelerated convergence using subsets limitations, the system matrix is unlikely
limited memory requirements, it does not of the reconstructed image is created allows the OSEM algorithm to generate to perfectly model the system response
take into account the statistical nature and, from here, estimated sinograms are PET images in clinically relevant times for the forward and back projection
of radioactive decay, nor does it make generated from the system matrix values – (6). Unlike MLEM, where one iteration operations. This may place data in
allowance for the characteristics of the PET a process referred to as forward projection. corresponds to one update, one OSEM erroneous locations, which manifests as
system (3). These estimated sinograms are compared iteration corresponds to a cycle in which noise. What is more, PET measurements are
For these reasons, along with the general with the acquired sinograms and a ratio all subsets have been used to update generally very noisy. This in combination
increase in memory and computation is calculated at each sinogram pixel. The the reconstruction. In OSEM, the number with the discrete spatial sampling of
power, FBP is no longer the reconstruction ratios are then transposed back into the of updates therefore corresponds to the both sinograms and the reconstructed
technique of choice, and iterative reconstructed image – a process referred number of iterations multiplied by the image volume means that the process is
methods represent the current state of to as back-projection – and the estimate of number of subsets. ill-conditioned, the main consequence
the art in clinical PET reconstruction. The the reconstructed image is updated. This The system matrix is the critical being that the noise in the reconstructed
most widely-used iterative reconstruction process repeats in a series of loops referred component in iterative reconstruction, image increases as more iterations are
algorithm is maximum likelihood to as iterations, and the estimate of the as this is where most of the physical performed. Noise in an image that is fully
expectation maximisation (MLEM) (4). The activity distribution in the reconstruction aspects of the PET measurement are converged will be so significant that the
principle behind MLEM is to estimate the image converges until it represents the modelled. This includes modelling of image is unlikely to be of any clinical use.
activity distribution that would most likely real activity distribution within the patient. the geometric efficiency of the PET There are three mitigating strategies to
produce the sinograms that have been In MLEM, the number of updates also detector, the position-dependent spatial reduce noise in reconstructed images. The
acquired by the PET system. As such, it corresponds to the number of iterations. resolution, the calibration factor used to first strategy is to stop the reconstruction
26 EANM TECHNOLOGISTS’ GUIDE EANM TECHNOLOGISTS’ GUIDE 27
ADVANCES IN PET/CT IMAGING ADVANCES IN PET/CT IMAGINGCHAPTER 2 CHAPTER 2
process before convergence in order amplification in the image by penalising
to prevent excessive image noise highly varying activity values between
UPDAT ES IN R ECO N S TR UC TIO N ALGO R ITH MS
UPDATES IN R ECO N S TR UC TIO N ALGO R ITH MS
amplification. Although the degree of neighbouring voxels. More recently, the Figure 2. Partial volume
noise is kept to an acceptable level, approach was introduced as a clinical effects. On the left there
this approach can produce an image reconstruction approach which makes are no partial volume
with reduced quantitative properties as use of a prior relative difference to effects, resulting in sharp
convergence is not fully reached and not reduce noise amplification during image representation of a lesion.
all necessary corrections are fully applied. reconstruction (9). Basically, it penalises On the right, partial volume
The second approach is to perform a small relative differences between effects due to the limited
sufficient number of updates to ensure neighbouring activity values as these spatial resolution of a PET
that the full image is close to convergence are assumed to be noise, while larger system cause signal spread.
and all appropriate corrections have been differences are attributed to edges and are
applied. A filter is then applied to the therefore preserved. Unlike a conventional A limited spatial resolution leads to partial small tumour lesions (typically < 15mm)
reconstructed PET image to reduce the OSEM reconstruction, which needs the volume effects, which, as pointed out by will look larger but less aggressive in PET
noise levels (7). A Gaussian full width half number of iterations and subsets to be Soret et al (11, 12), are a major confounding imaging because partial volume effects
maximum (FWHM) filter is generally used specified, a BPL reconstruction only needs factor in PET imaging that cannot be will spread the signal of a small hot lesion,
for this purpose. The FWHM determines one tuneable parameter to be set which ignored because it can severely affect resulting in voxel values that will be lower
how many neighbouring voxels are used controls the strength of the penalty to image quality and image quantification. than the actual maximum value (Figure 2).
to calculate the smoothed image, so that preserve edges. Furthermore, no filter for Partial volume effects typically refer to Because these voxel values (i.e. radioactive
a larger FWHM corresponds to a higher post-smoothing the reconstructed image two different phenomena: (1) the image concentration) are often used to follow up
degree of smoothing. and increasing image quality is necessary blurring introduced by the finite spatial treatment response, these partial volume
The final approach is to constrain as full convergence is reached without resolution of the PET imaging system, effects can lead to misinterpretation of the
the amplification of noise during the increasing noise (10). and (2) image sampling into voxels so measured data. Furthermore, the apparent
reconstruction process using the that individual voxels contain different larger lesion size can lead to problems
maximum a posteriori approach (8). This tissue types where the measured voxel when lesion contouring is derived from
approach basically assumes that not all RESOLUTION MODELLING intensity is mostly a weighted average the PET data, resulting in a lesion that is
reconstructions are equally likely, but that In recent years, there have been multiple of different tissue intensities included in larger than the real metabolically active
prior assumptions can be made about hardware and software advances in PET/ each voxel (13). It is important to note lesion. The spatial resolution in the
the reconstructed image. These prior CT to improve image quality, small lesion that even imaging systems with perfect reconstructed images determines how far
assumptions correspond to a penalty detectability and quantification accuracy. spatial resolution would still be hampered the signal of small hot lesions spreads. A
term which is taken into account when However, the two main limitations of PET by partial volume effects due to image better spatial resolution will result in less
updating the image – a process referred compared to CT and MRI are its relatively sampling into voxels. For this reason, partial spread, whereas a lower spatial resolution
to as penalisation or regularisation, which low spatial resolution and generally low volume effects not only affect PET, but are will introduce a larger amount of spread.
results in a Bayesian penalised likelihood signal-to-noise ratio. In this section we also of concern in image modalities with Consequently, a better spatial resolution
(BPL) reconstruction algorithm. In general, will focus on advances in reconstruction better spatial resolution, such as MRI or CT will result in fewer partial volume effects.
this penalty term is used to reduce noise algorithms to improve spatial resolution. (11). As a result of partial volume effects,
28 EANM TECHNOLOGISTS’ GUIDE EANM TECHNOLOGISTS’ GUIDE 29
ADVANCES IN PET/CT IMAGING ADVANCES IN PET/CT IMAGINGCHAPTER 2 CHAPTER 2
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