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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5255_Библиотеки_им_академика_М_И_Перельмана
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Image Correction Techniques in SPECT and PET332
where the radionuclide image f(x,y) is first reconstructed without attenuation correction.
The denominator represents the multiplicative correction term for photon attenuation in
which M is the total number of projections used to acquire the radionuclide data and li is
the distance from the point (x,y) to the border of the object in the ith radionuclide projection.
When the object being imaged has an extended geometry, the correction term expressed in
equation- 3 overcompensates the image for photon attenuation which results in overcorrection
in some parts of the image and undercorrection in other parts. In these cases, the accuracy
of the photon attenuation correction can be improved using an iterative technique (referred
to as the “iterative Chang technique”) in which the initially corrected image fAC(x,y) is
reprojected mathematically to form a set of projection data that simulate the radionuclide
imaging process in a way that includes a priori information about the physical extent and
linear attenuation coefficient distribution of the object. The new estimated projections then
can be subtracted from the original measured projection data to calculate an error term that
can be backprojected using filtered backprojection reconstruction or other reconstruction
techniques, which then can be used to correct the radionuclide tomograms initially obtained
from filtered backprojection. In spite of its theoretical shortcomings, Chang’s method has
been used widely in multiple clinical applications and research studies. Other less popular
approaches have been described elsewhere (5) and will not be repeated here.
Since most anatomical regions are heterogeneous in their anatomical structure and
tissue composition, the radionuclide data inherently contain errors contributed by photon
attenuation. In addition, significant errors in the radionuclide image can be contributed by
other physical effects such as scattered radiation and the finite spatial resolution of the
imaging system (including the geometrical response of the collimator in the case of SPECT)
that are not accounted for in these reconstruction techniques. As discussed earlier, PET
images can be reconstructed using either analytic or iterative techniques, whereas nonuniform
attenuation correction for SPECT generally requires iterative reconstruction. Several different
iterative reconstruction methods have been developed and evaluated for radionuclide
imaging. Early techniques used additive correction terms in each iterative step to improve
computational speed and included the conjugate gradient weighted least squares (CG-WLS)
technique. However, most current reconstruction methods are based on the well-known
maximum likelihood expectation-maximization (ML-EM) method. This is an iterative
reconstruction technique that accounts for the Poisson statistical nature of the radionuclide
data, and that can incorporate other physical effects including a projector model that
accounts for the geometric response of the collimator. In addition, the ML-EM algorithm
has a positivity constraint (i.e., all reconstructed pixel values are non-negative), preserves
the integral number of counts in each iterative step, and converges monotonically to a
maximum likelihood solution.
Several methods have been devised to achieve accurate quantitative analysis of PET
studies. Significant attention has been devoted to optimizing computational performance
and to balancing conflicting requirements. Both approximate methods suitable for clinical
routine applications and more complicated approaches for research applications where
there is greater emphasis on accurate quantitative measurements have also been addressed
GSPant\Newbook\Final-2008\21-chp\332
Image Correction Techniques in SPECT and PET 333
(5).
Because attenuation correction in PET is relatively straightforward and its accuracy being
limited only by the noise (statistics) present in the acquired transmission scans, only two techniques
have materialized and both require the computation of the attenuation correction factors
(ACFs) through forward projection of the attenuation map at appropriate angles. To reduce
processing time and data storage requirements for 3-D PET data collection mode, it is often
convenient to work with pre-corrected data. This is the basis of the first approach where
data correction is carried out in projection space through multiplication of the ACFs by the
measured emission data by using the following expression:
AC
),(sp
The attenuation corrected projections ),(
AC
sL
sP
are then used to reconstruct the images
),(),(
dryxfspACF
),(
(4)
using either analytic or iterative reconstruction techniques. An attractive option is to produce a
smaller sinogram by pre-correcting the data and applying Fourier rebinning (FORE). However,
the data are no longer Poisson distributed. It has been shown that OS-EM yields suboptimal
images from such data. Alternatively, when an iterative algorithm (e.g. OS-EM) is used, the
ACFs can be used to provide proper statistical weighting to the data as is done in attenuationweighted OS-EM (AW-OSEM). This latter technique has better noise properties and is now part
of commercial software routinely used in many clinical PET facilities. A clinical whole-body
18
F-FDG scan reconstructed without and with attenuation correction is shown in figure 3. The
uncorrected image tends to depress the reconstructed activity at the center and might jeopardize
deep lesions detectability.
Figure 3. Sagital views of iterative reconstructions of a typical clinical 18F-FDG whole-body scan
GSPant\Newbook\Final-2008\21-chp\333
Image Correction Techniques in SPECT and PET334
without (left) and with (right) attenuation correction. The non-corrected image tends to depress
the reconstructed activity at the centre.
Partial volume effect correction strategies
The limited spatial resolution of PET causes an object to appear enlarged if its true size
is less than 2-3 times the system resolution. While the total reconstructed counts within the
object are conserved, the count density is decreased from the true value because the data
are “smeared” over a larger area. This characteristic is known as the partial volume effect
(6).
Attempts to compensate for partial volume effects date back to the time where they
were first pointed out as a serious limitation in quantitative analysis. Although the partial
volume phenomenon was first addressed in the context of “hot” objects in a “cold”
background, emphasizing on the apparent loss of radioactivity due to the small object size
with respect to the spatial resolution of the system, it became obvious that it was necessary
not only to account for activity “spilling-out” of the “hot” region, but that “spill-in” from
the surrounding usually “warm” area should also be accounted for in the regional
measurements. Several authors attempted some sort of partial volume correction (PVC) by
applying the recovery coefficients formulation.
PVC remains a priority for accurate image quantitation. The ability to compensate for
partial volume effects usually requires to: (i) characterize the PSF of the imaging system,
(ii) characterize the tissue components that participate in the uptake and metabolism of the
tracer, and (iii) characterize the resolution effects in terms of correction factors or maps.
Some correction methods require only the original emission data. These include methods
making all the necessary corrections for physical effects at the projection level. There has
also been a great deal of search for image processing tools that would restore, or at least
visually enhance, the noisy images obtained in emission tomography. Those can be
regrouped into the general class of filters used during image reconstruction (low-pass
filtering), and those used post-reconstruction for the purpose of restoration filtering.
Another approach that does not require additional data is based on the computation of
correction factors during mathematical modeling of kinetic data, such as regional cerebral blood
flow (CBF) measurement with PET, both in the heart and brain. A distinct class of correction
methods requires the definition of the various objects being imaged in addition to the
characterization of the scanner’s point-spread function (PSF). These include anatomy-based
post-reconstruction correction methods that make use of concomitant high-resolution structural
information from MR imaging or CT. These currently constitute the most popular methods and
are finding their way to the clinic. Finally, empirical methods based on the derivation of correction
factors from experiments with physical test objects remain an active way of characterizing
partial volume effects.
Those methods proved to be sufficiently accurate to be applied in a growing number of
research studies, if one considers that the number of publications related to the effect of the
application of PVC algorithms to research data has grown significantly in the past few years.
PVC is now a powerful and reliable tool that should become systematically used in research or
GSPant\Newbook\Final-2008\21-chp\334
Image Correction Techniques in SPECT and PET 335
clinical studies involving the use of emission tomography. It is expected that improvement
in all aspects of the prerequisite for accurate partial volume correction are still required,
especially for what concerns the quality of anatomo-functional mapping needed for accurate
quantitation of cell-specific function and metabolism.
Conclusions
In many situations, absolute quantification is desirable to obtain a truthful representation
of the biological process or metabolic function being imaged. In quantitative metabolic
imaging studies, there is always a tension between the desire for more data (e.g. MRI, CT,
blood samples, … etc), which ultimately improves the understanding of the process being
studied and the accuracy of the reported results, vs. logistic considerations, including cost,
time, imaging unit throughput and patients or healthy volunteers’ comfort. One must
consider what is logistically possible for the staffina busy clinical nuclear medicine facility
and what is tolerable by the patients and/or subjects. Likewise, accurate quantification
requires extensive technical and organizational efforts that may be unaffordable for a small
clinical department with limited scientific support. In the clinical setting, it has become
standard practice to use simplified imaging protocols compared to the often complex
methods developed for research using emission tomography.
The development of newer, faster and more robust algorithms remains an open research field
which requires further research and development efforts. In summary, quantitative analysis of
nuclear medicine images is an area of considerable research interest and many research groups
are very active in this field, leading the nuclear medicine community to forecast a promising
progress during the next few years.
References
1. Zaidi H. Ed. Quantitative analysis in nuclear medicine imaging. Springer, New York , 2006.
2. Novikov RG. An inversion formula for the attenuated x-ray transformation. Ark Mat 2004; 40: 145-
167.
3. Zaidi H and Koral KF. Scatter modeling and compensation in emission tomography. Eur J Nucl Med
Mol Imaging 2004; 31: 761–782.
4. Valk PE, Bailey DL, Townsend DW, et al. Eds. Positron Emission Tomography: Basic Science and
Clinical Science. Springer-Verlag, London.
5. Zaidi H and Hasegawa W. Determination of attenuation map in emission tomography. J Nucl Med
2003; 44: 291–315.
6. Rousset O, Rahmim A, Alavi A and Zaidi H. “Strategies for partial volume correction in PET”
PET Clinics 2007; 2: in press.
GSPant\Newbook\Final-2008\21-chp\335
Combined PET/CT: Clinical
Applications
Rakesh Kumar and Madhavi Chawla
Positron Emission Tomography (PET) is a functional diagnostic imaging technique,
which can accurately measure the in vivo distribution of a radiopharmaceutical with high
resolution. The ability of PET to study various biological processes opens up new possibilities
for both research and day-to-day clinical use. Addition of CT to PET improves the detection
efficiency and results in better localization of lesions. Therefore, PET-CT has shown better
specificity and sensitivity than either PET or CT alone. The most widely used radiotracer in
PET is Fluorine18-fluorodeoxyglucose (18F-FDG), an analogue of glucose. The uptake of
FDG is mediated by a family of structurally related glucose transporter proteins and is
similar to that of glucose (1). Subsequently, it is phosphorylated by the enzyme hexokinase
to FDG-6-phosphate (2). However, FDG-6-phosphate is biochemically trapped within the
cell since it is not a substrate for glucose-6-phosphate isomerase. Malignant cells are
characterized by an enhanced rate of glucose metabolism and express increased number of
glucose transporter proteins, such as Glut-1 and Glut-3. They also show increased levels of
hexokinase and phosphofructokinase activity, which promote glycolysis (2). In addition to
qualitative image display, it is possible to quantify specific uptake value normalized to the
injected dose, which is called “standardized uptake value” (SUV). The SUV provides an
approximate indicator that correlates with FDG metabolism in the tissue. SUV’s are calculated
according to the formula described below. A lesion with an SUV greater than 2.5 is normally
considered to have a high probability of malignancy.
SUV
33 6
)/(
gMBqactivityROIMean
)(/)(
gweightbodyMBqdoseInjected
Combined PET/CT : Clinical Applications 337
Both the PET and PET-CT have a very high sensitivity and a high negative predictive value
for lesion detection as compared to conventional morphological modalities like computed
tomography (CT), ultrasonography (USG) and magnetic resonance imaging (MRI). The role of
PET has already been established in initial staging, monitoring the response to therapy, and
management of various cancers. Being a functional technique, PET allows diagnosis of pathological
processes at a very early phase detecting changes at the molecular level. PET-CT provides better
characterization and localisation of lesions as compared to PET and CT alone. Unfortunately,
FDG is not a cancer specific agent and its uptake has been described in a number of nonneoplastic inflammatory lesions like sarcoidosis, tuberculosis, fungal infection, and abscesses
(3). This increased accumulation is probably related to an increased rate of glycolysis within the
activated inflammatory cells. The applications of PET and PET-CT in malignancies, cardiology
and neurology are discussed below.
Normal distribution and variants in distribution of FDG
FDG uptake in the thymus is commonly seen in some children, the cause being unclear, but
is likely to be related to physical and emotional stressors, which influence thymic metabolism.
Rebound thymic hyperplasia is seen in young patients following chemotherapy and enlargement
can persist for up to six months following completion.
Cardiac activity is variable ranging from no discernible activity above the background pool
activity to intense activity throughout the left ventricle myocardium. In the fasting state where
insulin levels are low, FDG uptake in cardiac muscle should be low. Myocardial uptake is
enhanced in the presence of high blood glucose levels, therefore cardiac activity is marked in the
post-prandial state. However, uptake can be variable even in the fasting state. Increased uptake
may be noted in the aorta and great vessels, particularly in artherosclerotic disease.
Glandular breasts show moderate activity, especially in premenopausal women and in women
taking estrogen pills, obscuring potential lesions in the breast.
Figure 1: PET image showing normal physiological distribution of 18F-FDG
Combined PET/CT : Clinical Applications338
Skeletal muscle is the most common site of physiological uptake, which is increased by both
voluntary and involuntary muscle activity. Muscle uptake is generally symmetrical but sometimes
can be asymmetrical, especially in torticollis and unilateral paralysis. Brown fat may also present
as foci of increased FDG uptake. With PET alone, it is difficult to interpret normal asymmetrical
FDG uptake in muscles and brown fat. However, with the advent of PET-CT, uptake in muscles
and brown fat rarely poses interpretation problems. To overcome false positives due to these
reasons, patients undergoing PET/PET-CT scan are advised to refrain from exercise, chewing
and talking immediately before and after injection of 18F-FDG. Mild sedation may also be
needed.
Uptake in the gastrointestinal tract is variable and is mainly due to smooth muscle activity
associated with peristalsis, bacterial uptake and due to metabolically active mucosa. Normal
mild FDG activity may be seen in the esophagus possibly due to swallowed saliva or smooth
muscle metabolism. Stomach is usually faintly seen. Intense FDG uptake may be noted in the
pyloric end of stomach due to contraction of these muscles. Uptake in the caecum and right
colon is usually higher than in other colonic segments and may be related to abundant lymphoid
tissue in this region.
Unlike glucose, FDG is filtered by the glomerulus and is not reabsorbed by the renal tubules.
So, significant activity may be displayed in any part of the urinary tract or surgical urinary
diversions such as ileal conduits. This activity in the urinary tract may interfere with the
interpretation of malignant tumors arising from kidneys, ureters, urinary bladder, cervix, ovary etc.
The liver, spleen and bone marrow normally show homogenous low-grade uptake. Bone
marrow and spleen normally show less intense uptake than the liver. Uptake in the bone marrow,
spleen and other reticuloendothelial organs may be significant after therapy with colony stimulating
factors.
Testicular uptake is normally seen and is symmetrically diffused. However, ovarian uptake is
not usually seen. Faint uterine activity is common. Uptake in the uterus has been reported during
menstruation and ovulation in pre-menopausal women and in relation to fibroids, but in practice it
is an uncommon finding. The normal distribution of 18F-FDG (Figure 1) is summarized in
table 1.
Combined PET/CT : Clinical Applications 339
Table 1: Summary of physiological 18F-FDG uptake
Region Distribution
Head Cerebral Cortex, cerebellum, thalami, basal ganglia: High uptakeWhite matter (low
uptake)
Neck Salivary glands at the base of the tongue,
Lymphatic tissue in Waldeyer’s ring, tonsils,
Muscles of mastication or larynx, trapezius and paraspinal muscles, esophagus,
Brown fat
Chest Thymus, Heart, Aorta, Lung, Respiratory muscles, Breasts- variable
Abdomen Stomach, Cecum and right colon, Reticuloendothelial system, Liver and Spleen:
Diffuse and low grade Urogenital system, Gonadal activity, Uterine endometrial
accumulation
Bone marrow Low uptake
Miscellaneous Sites of wounds, surgical incisions, osteotomy, prostheses, vessels
Clinical applications
PET in Oncology
Oncologic imaging involves lesion detection, characterization, evaluation of the extent, staging,
assessment of the response to therapy and restaging of malignant disease. Both structural and
functional imaging modalities are used for this purpose. Computed tomography (CT) was the
most commonly used imaging technique for the management of various malignancies till date.
Introduction of positron emission tomography (PET) has improved the management of these
patients significantly as it provides information about the functional status of the disease. Since
glucose metabolism is increased many fold in malignant tumors, PET images show preferential
higher uptake in malignant tumors as compared to normal cells. Recent addition of CT to PET
has further improved the value of PET as PET-CT provides functional and structural information
in the same setting. In addition CT also provides attenuation correction factors (ACF) for PET
images. PET and PET-CT with 18F-FDG is now the standard of care in the initial staging,
monitoring the response to the therapy and restaging of lung cancer, colorectal cancer, lymphoma,
melanoma, esophageal cancer, head and neck cancer, breast cancer etc.
Solitary Pulmonary Nodule (SPN)
Conventional imaging modalities such as chest radiography and CT have secured an essential
role in solitary pulmonary nodules (4). However, these anatomic imaging techniques are limited
in their ability to differentiate benign from malignant nodules. 18F-FDG PET can provide additional
information and complement structural imaging techniques in the evaluation of such disorders
and has been successfully used as a non-invasive diagnostic test for SPN’s in order to differentiate
benign lesions from malignancy (5). Interpretation can be performed visually or semi quantitatively.
Combined PET/CT : Clinical Applications340
In the visual interpretation of 18F-FDG PET images, generally focal intense uptake of 18F-FDG
greater than the blood pool activity is considered ‘positive’ for malignancy while, lesions that are
hypointense to the mediastinum, are considered benign (Figure 2). Quantitative assessment can
be made by the use of the standardized uptake value (SUV). In general, SUV over 2.5 is
generally considered as characteristic of malignancy. False positives are seen in patients with
active granulomatous infection like tuberculosis, sarcoidosis, histoplasmosis or coccidioidomycosis.
Delayed PET images taken several hours after 18F-FDG injection (dual time point imaging),
along with routine one-hour imaging protocol (6) has shown better results, with malignant
nodules showing increased 18F-FDG uptake over time. False Negatives are seen with low-grade
tumors like bronchoalveolar carcinoma and bronchial carcinoid (7). In addition, small lesions
can be missed on PET imaging due to partial volume effect.
Figure 2: CT, PET and PET-CT Coronal and axial images showing intense 18F-FDG uptake in
solitary pulmonary nodule suggestive of malignancy
Lung Cancer
Computed tomography is usually the imaging modality of choice to define the extent of the
primary tumor and to assess tumor involvement of pleural surfaces and thoracic wall (8). PET
alone may be useful to determine T stage in cases where the nodule is small and clearly confined
to the pulmonary parenchyma (Figure 3). For higher levels of T staging it is not useful because
of inferior resolution. It is, however, useful to evaluate additional pulmonary nodules in the same
lobe and to identify malignant pleural effusion, the presence of 18F-FDG uptake in the pleural
space being a bad prognostic sign compared to benign effusion (9).
Combined PET/CT : Clinical Applications 341
Figure 3: CT, PET and PET-CT images showing intense FDG uptake in left lung (primary lung
cancer)
Mediastinoscopy, CT and MRI are used for assessing the involvement of lymph nodes. The
main limitation of CT and MRI is a size criterion of 1 cm for diagnosis of tumor involvement,
which results in many false positive and false negative results for detection of lymph node
metastases. Since 18F-FDG PET imaging depends on increased metabolism of the malignant
cells, it can be used successfully to identify malignant nodes (Figure 3). PET and PET-CT are
also very effective in detecting distant metastases (10). A typical scan extends from the orbits or
base of skull through the pelvis, covering the most common sites of metastatic disease, i.e. lung,
liver, brain, adrenals, and bone etc (Figure 4). 18F-FDG PET has particularly an important role
for detecting adrenal metastases in lung cancer patients thus eliminating the need for biopsy of
benign enlarged adrenal glands in these patients (11). Overall, PET is able to detect the sites of
disease, which may not be apparent by standard imaging strategies in 10-14% of cases and
therefore can change management in many patients (12). It is also an accurate imaging modality
in order to rule out metastasis in cases of false positive or indeterminate findings on anatomical
imaging.
Figure 4: CT, PET and PET-CT images showing focal areas of intense FDG uptake in multiple
mediastinal lymph nodes and liver and bone suggestive of metastasis in a patient of lung cancer.
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