References

International Commission on Radiological Protection. 1990 Recommendations of the International Commission on Radiological Protection. ICRP Publication 60. Oxford Pergamon Press, 1991. 2. International Commission on Radiation Units and Measurements. Determination of Dose Equivalents Resulting from External Radiation Sources. ICRU Report No. 39. Bethesda, MD ICRU, 1985. 3. Dillman LT. Radionuclide decay schemes and nuclear parameters for use in radiation-dose estimation. MIRD Pamphlet No. 4. J...

Lung Carcinoma

There have been numerous studies examining the accuracy of 18F -FDG PET in evaluating solitary pulmonary nodules 32,33 . Analysis of the published data has shown a high sensitivity (average 96 ) and accuracy (average 94 ) for determining malignancy (Figs. 16.2 and 16.3 2,8,34 . The specificity is also high but the variation is slightly greater and is dependent on the local prevalence of the known causes of false posi- Figure 16.2. Coronal sections of a 18F -FDG PET scan performed in a...

Componentbased Model for Normalization

Consider a tomograph where detectors are indexed using the coordinate system shown in Fig. 5.4. A general expression for the activity contained in a particular LOR joining a detector i in ring u and detector j in ring v can be written as follows A < X (p S R V AC DT ntrue uivj uivj uuivj uivj j uivj uivj luivj V-Lw where Auivj is the activity within the LOR, Puivj, Suivj and Ruivj are the prompt, scattered and random count rates respectively, ACuivj is the attenuation correction factor for...

Accelerating Drug Discovery

The second SNIDD symposium, which was held in October 2000 16 , discussed whether the use of PET can be implemented fast enough to compensate for the increased time and expense of these studies by decreasing the number of studies that must be completed. The goal of the second SNIDD conference was to discuss how the drug discovery process could be accelerated using well-established radiopharmaceuticals, such as 15O water for blood flow and 2- 18F -fluoro-2-deoxyglucose ( 18F -FDG) for glucose...

Annihilation Radiation

As this book is primarily concerned with positrons and their applications, we include a further classification for electromagnetic radiation which is neither x nor y Annihilation radiation is the energy produced by the positron-electron annihilation process. The energy of the radiation is equivalent to the rest mass of the electron and positron, as we saw in the section on Mass and Energy, above. The mechanism of positron decay is discussed in depth in the next section. Annihilation radiation,...

Attenuation Correction Using Coincidence Transmission Data

The most common approach has been to use a long-lived positron emitter, such as 68Ge-68Ga (68Ga is the positron emitter and 68Ge is its parent isotope with a half-life of 271 days), and measure the annihilation photons in coincidence as they pass through the body from an external source. A transmission scan typically takes 2-10 minutes to acquire and may be performed before or after the PET tracer is administered. However, it is not uncommon to perform transmission scans after tracer...

Attenuation Correction Using CT Data

With the advent of dual modality scanners capable of acquiring PET and CT data during the same imaging session, there has been considerable effort put into developing methods to make use of CT data for PET attenuation correction (Fig. 5.18c). The potential advantages of this approach arise because the statistical quality and spatial resolution of CT data is far superior to conventional transmission data used in PET, and because a whole body CT can be acquired in less than 1 minute using current...

Axial Block Profile Factors b aX and Axial Geometric Factors g

The axial block profile factors may be calculated from an acquisition of a central uniform right cylinder source. If scatter is not significant, the calculation is straightforward - the total counts Cu in each of the direct plane (i.e., ring difference 0) sinograms are computed, and the bUx are then given by where Cu is the mean value of the total counts in each sinogram. In 3D imaging, the amount of scatter can be large, and more importantly, the distribution can vary in the axial direction....

Labeling Strategies Biological Considerations

In order to address a given biological, pharmacological or medical question, the design of labeled tracer molecules need special consideration and there are a few points which need to be addressed (i) The labeling position must be considered since the metabolic pathway of the compound might have an impact on the interpretation of the PET data, (ii) Labeling in different positions in the molecule may give additional information. An illustration of this is nC-labeled L-DOPA and...

Cardiology and Cardiac Surgery

At present there are three major indications for PET scans using two physiological measurements in clinical practice. The two measurements are (i) to measure the myocardial perfusion using 13N -ammonia (or 82Rb from an on-site generator) and (ii) to measure myocardial viability (using 18F -FDG). There is increasing interest in a third measurement, cardiac innervation by studying myocardial receptors, which may have a greater role in the future. The three applications of these measurements are...

Characteristics of Scattered Radiation

When a positron annihilates in the body, there is a reasonable chance that one or both of the annihilation photons will scatter in the body or in the detector itself. At the energy of annihilation photons (0.511 MeV), the most likely type of interaction is Compton scattering in which the photon transfers some of its energy to loosely bound electrons and deviates from its initial path 35 . Since the coincidence LOR formed after one or both photons undergo Compton scattering is no longer colinear...

Chemistry of Technetium

Technetium is a second-row group-VII transition metal, with an electron configuration of Kr 5s24d5. The chemistry exhibited by Tc is vast as a result of the fact that it can occupy several different oxidation states (-1 to +7, although only +1 through +7 can exist in solution) and the large number of coordination geometries it can adopt 116 . These two factors mean that Tc can bind to a large number of donor ligands. However, this flexibility can cause problems in the design of Tc...

Clinical Researchdiagnostic Question

Selected Physiological Pharmacokinetic Pathway or Molecular Target Tracer Molecule & Radiolabelling Position Radiochemical yield, spec.act. & purity In vivo and in vitro testing Max.administered dose of radioactivity - Formulated biological model Scanner spatial & temporal resolution, . . Corrections for attenuation scatter, random normalisation, sensitivity and field-of-view events and scanner dead time Scan protocol Blood and radiolabelled metabolite analysis Reconstruction method...

Colorectal Carcinoma

Staging of Primary Colorectal Cancer The diagnosis of colorectal cancer is principally based on colonoscopy and biopsy, with imaging being performed primarily to assist in initial surgical planning. There have been a number of studies examining the utility of PET for staging primary colorectal carcinoma. In one study of 16 patients with known or suspected primary or recurrent colon and rectal cancer studied with 18F -FDG PET and CT scans, PET detected all 12 sites of disease in bowel, whereas...

Compartmental Modeling Assumptions

The successful application of simple compartmental models to a complex biological system requires that many assumptions be true. These assumptions are typically not completely valid, so that successful use of these models depends upon whether errors in these assumptions produce acceptable errors in model measurements (see Error Analysis, below). Compartmental models, by their nature, assume that each compartment is well mixed, i.e., there are no concentration gradients within a single...

Conservation Laws

The principle of the conservation of fundamental properties comes from classical Newtonian physics. The concepts of conservation of mass and conservation of energy arose independently, but we now see that, because of the theory of relativity, they are merely two expressions of the same fundamental quantity. In the last 20-30 years the conservation laws have taken on slightly different interpretations from the classical ones previously they were considered to be inviolate and equally applicable...

Convolution and Deconvolution Approaches

Whereas the energy based methods derive information about the scatter distribution from auxiliary measurements, convolution based methods model it with an integral transformation of the projections recorded in the photopeak window. Initially, the method was developed for a ring type PET scanner operated in 2D mode 47 and the projected scatter distribution in a given slice took the following analytical form where punsc is the one dimensional projection of the true activity distribution and...

Copper bis thiosemicarbazones

One of the most commonly used Cu(II)-bis(thio-semicarbazone) is ( Cu PTSM), (Fig. 11.5). 62 64Cu PTSM is a highly lipophilic complex, and is used as a blood flow tracer. Following administration of 62 64Cu PTSM, tissue uptake is rapid, and the tracer is trapped in most major tissues such as the brain 77-80 , heart 77, 78, 81 , and tumors 82-85 . Tissue retention of 62 64Cu PTSM and other frzs(thiosemicar-bazone) derivatives is believed to result when the lipophilic complex diffuses across the...

Copper Radionuclides

A number of copper PET radionuclides can be produced on a biomedical cyclotron including 60Cu, 61Cu, 64Cu with half-lives of 23.4 min, 3.32 h, and 12.8 h respectively. 64Cu, 61Cu and 60Cu are produced at Washington University using a specially designed solid target holder 6, 7 . The isotopically enriched nickel targets are electroplated for irradiation, separated using ion exchange chromatography, and can then be recycled 7-9 . Large quantities of these Cu isotopes have been produced (yields of...

Copperlabeled Antibodies Proteins and Peptides

64Cu has labeled monoclonal antibodies (MAbs), proteins, and peptides for PET imaging. Copper is most commonly attached via macrocyclic ligands such as TETA acid), BAD N,N',N,N'-tetraacetic acid), CPTA Figure 11.5. Cu(II) bis(thiosemicarbazone) complexes, Cu PTSM and Cu ATSM. acid)) and DOTA acid). Schematic representations of these ligands are shown in Fig. 11.7. Direct labeling of Cu(I) to antibodies has also been attempted. Stannous tartrate was used to reduce disulfide groups, which then...

Count Rate Performance

Count rate performance refers to the finite time it takes the system to process detected photons. After a photon is detected in the crystal, a series of optical Figure 3.17. The energy spectra for single photons for a BGO PET system. The air and scatter measurements are of a 68Ge line source in air and in a 20 cm-diameter water-filled cylinder respectively, while the distributed source is for a solution of 18F in water in the same cylinder, to demonstrate the effect on energy spectrum of a...

Analytic Reconstruction by Rebinning

The high sensitivity of a PET scanner operated in 3D mode is directly related to the large number of sampled LORs, which is much larger than the number of reconstructed pixels NLOR > > P (by a factor proportional to Nr). We have already mentioned in the previous section that this data redundancy results in the non-uniqueness of the reconstruction filter. From the practical point of view, redundancy increases the data storage requirements and the computational load for reconstruction and...

Delayed Coincidence Channel Estimation

The most accurate (and currently the most commonly implemented) method for estimating random coinci dences is the delayed channel method. In this scheme, a duplicate data stream containing the timing signals from one channel is delayed for several times the duration of the coincidence window before being sent to the coincidence processing circuitry. This delay removes the correlation between pairs of events arising from actual annihilations, so that any coincidences detected are random. The...

Development of Modern Tomographs

To understand the current state of commercial PET camera design, and why, for example, the development of 3D PET on BGO ring detector systems was only relatively recent, it is instructive to briefly trace the development of full ring PET systems. One of the first widely implemented commercial PET cameras was the Ortec Figure 3.14. A schematic diagram of the block detector system, shown here as an 8 8 array of detectors, and the four PMTs which view the light produced is shown. The light shared...

Discrete Implementation of the FBP

The discrete implementation of Eqs. (12) and (13) using the measured samples of p(s, < j) described in the section on sinogram data and sampling, above (Eq. (5)), involves four approximations (i) The approximation of the kernel h(s) by an apodized kernel where w(v) is a low-pass filter which suppresses the high spatial frequencies, and will be discussed later in the section on the ill-posedness of the inverse X-ray transform. (ii) The approximation of the convolution integral by a discrete...

Drug Discovery in Oncology

The conventional paradigm of demanding proof of an anti-cancer drug's potency by demonstrating tumour shrinkage using conventional anatomical imaging is not consistent with the newer therapeutics, especially the chemostatic agents where the size of the tumour does not necessarily decrease in successful treatment. The use of proliferation marker agents such as 18F labelled fluorothymidine (FLT) and PET may show an earlier response 9 . Pharmaceutical companies now have the option of using...

Electrophilic Reactions with 18F Low Specific Activity

Fluorine is the most electronegative of all the elements. Fluorine exists as a colorless to pale yellow corrosive gas (F2) that reacts with many organic and inorganic substances. Fluorine is a powerful oxidizing agent and attacks both quartz and glass, making its handling problematic. The use of fluorine gas as a carrier in the production of 18F F2 leads to several orders of magnitude lower-specific-activity reaction products compared to methods using no-carrier added 18F fluoride obtained from...

Enzyme Catalyzed Reactions

Enzyme catalysis has been utilized in labeling synthesis, especially for the preparation of endogenous compounds. Enzyme catalysis has proved to efficiently prepare biomedically interesting compounds in high chemo-, regio-, and stereo-selectivity. The application in labeling synthesis with short-lived radionuclides is particularly rewarding since the small amounts of labeled substance makes it possible to achieve high yields and short reaction times with low enzyme concentrations. Enzyme...

Frequency of Measurement

The geometric factors do not normally change with time and need only be measured once. Depending on their nature, the misalignment factors may either be fixed, or may need to be re-measured as components are replaced. The time window alignment factors should be re-measured whenever detector components are replaced. The detector efficiency and block profile components can change with time, as photo-multiplier tube gains drift, and should be re-measured routinely (usually monthly or quarterly,...

Fully 3D Iterative Reconstruction

Axial and transaxial undersampling techniques were developed to reduce the data to a manageable size while hybrid algorithms were developed to achieve fast reconstruction for clinical PET scanners with limited computer resources. With sufficient CPU power and disk capacity these early approaches are not needed. The application of fully 3D iterative reconstruction methods then allows to overcome the limitations of the hybrid algorithms discussed in the previous section. We have seen that...

Ga68Ge Generator

The 68Ga 68Ge generator produces 68Ga as either 68Ga ethylenediaminetetraacetic-acid ( 68Ga EDTA) or 68Ga Cl3 in 1M HCl 30 . 68Ga has been used to label blood constituents, proteins, peptides, and antibodies (see section below on Gallium). There have been a limited number of patient studies using the 68Ga 68Ge generator. The most common use of 68Ga is in the form of 68Ga citrate, which upon administration produces 68Ga transferrin. This approach has been used to measure pulmonary transcapillary...

Galabeled Brain Imaging Agents

The work on gallium radiopharmaceuticals that can cross the blood-brain barrier (BBB) has been conducted for some time with only limited success. Species such as Ga THM2BED show low brain uptake immediately after injection, but have a very fast washout 71 . Ga EDTA has also been used to show BBB defects at the site of brain tumors and multiple sclerosis plaques 72-75 . The most promising gallium brain imaging ra-diopharmaceutical developed to date is that complexed with the small lipophilic S3N...

Gallium Labeling of Antibodies and Proteins

The monoclonal antibody antimyosin has been labeled with both 66Ga and 68Ga, via the bifunctional chelator DTPA, for the imaging of acute myocardial infarction 59 . The slow antigen-antibody reaction during the diffusion of antimyosin in necrotic myocardium requires several hours to equilibrate, therefore the longer-lived 66Ga would be more appropriate 59 . Twenty-nine hours after administrating 66Ga DTPA-antimyosin, the normal-to-infarcted myocardial ratio was 2.7, and this agent can be viewed...

Galliumcitratetransferrin

67Ga citrate has been used as a tumor imaging agent for over 30 years 38 . It was subsequently discovered that trans-chelation of gallium to the iron-binding protein transferrin was the actual tumor imaging agent 39 . Further work demonstrated that gallium is completely bound to transferrin as soon as 15 minutes after administration of 67Ga citrate 40 . The effectiveness of this radiopharmaceutical is such that it remains in use today in the clinical diagnosis of certain types of neoplasia,...

Gastric and Oesophageal Tumours

Although the detection of primary gastric and oesophageal tumours with 18F -FDG PET has been reported to be excellent, the identification of regional nodal metastases has been restricted by the presence of small volume disease in some lymph nodes (Fig. 16.8) 32 . Unsuspected distant disease may be detected by 18F -FDG PET in up to 20 of cases, and recurrent disease may also be evaluated more accurately than CT scan, which may represent the more appropriate clinical utility of this technique 32...

General Considerations for Fdgpetct Imaging Protocols

For oncology purposes a standard PET CT acquisition protocol, in essence, is a modern-day PET oncology imaging protocol, which consists of three steps (1) patient preparation and positioning, (2) transmission scan, and (3) emission scan. Additional CT scans, such as, e.g., a 3-phase liver CT, or a high-resolution lung scan could be requested by the reviewing physician, but generally these CT scans are not used for attenuation correction. While the clinical acquisition protocols of the PET CT...

Graphical Analysis

One increasingly common method applied to tracer kinetic data is that of graphical analysis 90,107-112 . The basic concept of this method is that after appropriate mathematical transformation, the measured data can be converted into a straight-line plot whose slope and or intercept has physiological meaning. This approach has advantages, since it is simple to verify visually the linearity of the data and it is simple to determine the slope and intercept by non-iterative linear regression...

Hardware Approaches to Combined Imaging

An alternative to post hoc image fusion by software is, instead, to fuse the hardware from the two imaging modalities. While presenting a significant number of challenges, such an approach overcomes many of the difficulties of the software fusion methods. In the early nineties, Hasegawa and co-workers at the University of San Francisco developed the first device that could acquire both, anatomical (CT) and functional (SPECT) images, using a single, high-purity germanium detector for both...

Head and Neck Tumours

The presence of lymph node spread of head and neck tumours is associated with substantially worse prognosis, and clinical examination and imaging techniques (CT and MRI) detect fewer than 50 of involved lymph nodes, which may result in unnecessary neck surgery. In patients with head and neck tumours studied prior to initial surgery, the sensitivity and specificity of 18F -FDG PET in detecting nodal metastases has been reported ranging from 71 to 91 , and 88-100 , respectively (Fig. 16.7) 8,...

Historical Perspectives

Non-invasive technologies that image different aspects of disease should really be viewed, in almost all cases, as complementary rather than competing. When the sensitivity and specificity of one imaging technique for diagnosing or staging a specific disease is compared to that of another technique, it is usually to establish the superiority of one of the two techniques. In practice, however, such comparisons are of little real value because anatomical and functional imaging techniques have...

Image Acquisition

Registration algorithms perform better with images of approximately isotropic spatial resolution and cubic voxels. Conventional multislice MR images are not acquired with overlapping slices and the resulting missing data can cause some data corruption when resampled. As a result, true 3D MR image acquisition is preferred, in which Fourier encoding is applied along all three ordi-nates. MR images should be acquired so as to maximize contrast between anatomical structures of interest. While...

Image Formation in PET

Historically, PET systems have generally developed as circular rings. The earliest tomographs consisted of few detectors that rotated and translated to obtain a complete set of projection data, but soon full ring systems were developed. As PET uses coincidence detection, the detectors have to encompass 360 for complete sampling, unlike SPECT (single photon emission computed tomography) where 180 is sufficient. Today, PET systems use either full ring circular (or partial ring) configurations or...

Imaging Reporter Gene Expression with PET

Imaging therapeutic gene expression involves locating the tissues expressing a therapeutic gene of interest, as well as monitoring the magnitude and time variation of gene expression. Imaging can help to play a critical role in optimizing gene therapy. Two different strategies can be used to image therapeutic gene expression. The first approach involves direct imaging, where a labeled therapeutic protein substrate is used to image the specific expression of that protein. Direct imaging of the...

Intrinsic Detector Efficiencies euand Transaxial Block Profile b U

The intrinsic detector efficiencies are again usually computed from an acquisition of a central uniform right cylinder source, although planar or rotating line sources can also be used. Variance reduction may be effected using the fan-sum algorithm, which is essentially a simplified version of that used in randoms variance reduction. In the fan-sum algorithm, the fans of LORs emanating from each detector and defining a group A of opposing detectors are summed (see Fig. 5.11). It is assumed that...

Introduction

Positron emission tomography (PET) imaging is set to change the whole impact and role of Nuclear Medicine, not because it does everything better than conventional single photon imaging (planar and single photon emission computed tomography (SPECT)),but because it also has the impact and public relations of the fastest growing diagnostic speciality. PET is a powerful metabolic imaging technique utilising possibly the best radiopharmaceutical we have ever used 18F -fluorodeoxyglucose (FDG)....

Measurement of the Components

Although several components must be accounted for in component-based normalisation, they can be measured from just two separate scans using a relatively simple protocol. A typical protocol involves scanning a rotating rod source with nothing in the field of view and a uniform cylindrical source. Both scans are performed with low activity concentrations to minimise dead time effects and the scan times are quite long, typically several hours, to ensure adequate counting statistics. The rod scan...

Metal Artefacts

High-density implants, such as dental fillings, pacemakers, prostheses, or chemotherapy infusion ports may lead to serious artefacts in CT images 74, 75 . These CT artefacts have been shown to propagate through CT-based attenuation correction into the corrected PET emission images where artificially increased tracer uptake patterns may then be generated 76-78 . It is therefore recommended that PET images from PET CT are routinely correlated with the complementary CT, and that these PET data are...

Metal Mediated Reactions

Cyanation Reactions Using Hydrogen C cyanide Palladium-mediated coupling reactions have allowed formation of various carbon-carbon bonds that were previously difficult to make. One example is the synthesis of nC-labeled aromatic 26 and vinylic 27 nitriles via the palladium-mediated reaction of uC cyanide and an aromatic or vinyl halide (Fig. 10.6). Cross-Couplings Using 11C Methyl Iodide Palladium-mediated cross-coupling reactions are important in organic synthesis. The Stille reaction is a...

Model Identifiability

The first step in defining a model is to determine identifiability, meaning that the parameters of a model can be uniquely determined from measurable data. There is an extensive literature on this topic 16, 19, 71-77 , including studies with particular attention to PET applications 78-80 . In some cases, the structure of the model itself does not permit the unique definition of parameter values, even with noise-free data. One example of this is the case of high specific-activity studies with...

Monitoring Biochemical Changes in the Brain

The first symposium emphasised monitoring biochemical changes in the brain using PET and SPECT. This topic played a major role in the second symposium as well. Doudet reviewed the advantages and disadvantages of using 18F -FDG, a dopamine precursor ( 18F -DOPA), a tyrosine derivative (6-fluoro-m-tyro-sine,) and a number of radiolabelled substrates for the dopamine transporter to measure changes in Parkinson's disease 25 . She also reviewed the use of a radioligand for the vesicular monoamine...

Monitoring Response of Tumour to Therapy

An emerging area of clinical utility of PET is in the monitoring of tumour response to therapy, principally with 18F -FDG. Accurate evaluation of response to both chemotherapy and radiation therapy, often prior to CT scan changes, have been reported in glioma, col-orectal, NSCLC, lymphoma, head and neck tumours, and soft tissue sarcomas 2, 8, 16, 17, 42, 61, 107 . The timing and reliability of 18F -FDG PET studies in predicting tumour response is the subject of numerous prospective studies. The...

Monte Carlo Simulation

Monte Carlo methods are frequently used to evaluate scatter correction techniques since this approach allows separation of the simulated scattered and un-scattered contributions to the projections which is not possible using phantom experiments. Furthermore, many Monte Carlo codes are able to simulate the scatter distribution for any specified emission and attenuation distribution and several different PET scanner geometries. As well as providing a powerful method of evaluating the accuracy of...

Multiple Energy Window Methods

The triple energy window (TEW) method is a straightforward extension of DEW which introduces a modification factor that accounts for source size and distribution dependencies in Rsc 45 .Under the assumption that Rsc > > Runsc, the TEW method can be written Robj and Rcalib are the ratios of counts in the two lower energy windows for the object being imaged and a calibration phantom respectively. The parameter b is a relaxation factor that controls the amount of feedback of the modification...

Multislice 2D Data

So far we have discussed data sampling for a single ring scanner located in the plane z z0. Multi-ring scanners are stacks of NR rings of detectors spaced axially by Az and indexed as r 0, , NR- 1 3 . The coincidences between two detectors belonging to the same ring r are organized in a direct sinogram p(s, < j, z rAz) as described in the previous section. This is the sinogram of the function f(x, y, z rAz) (Fig. 4.3). Multi-ring scanners also collect coincidences between detectors located in...

Noisefree data

Figure 4.6. 2D reconstruction of a mathematical phantom with the ML-EM algorithm (Nr 128,N 256,Nx Ny 256). The Poisson log-likelihood (left scale) and the square reconstruction error with regard to the reference image (right scale) are plotted versus the iteration number. The left plot is for ideal noise-free data. For the right plot, pseudo-random Poisson noise has been added for a total of 400,000 coincidences. The cost function increases monotonically in contrast with the error, which...

Oblique Sinograms

Some analytic algorithms use an alternative parameterization of the parallel projections, where the vari- Figure 4.8. A transverse and a longitudinal view of a multi-ring scanner. An LOR connecting a detector da in ring ra to a detector db in ring rb is shown, with the four variables (s, 0, Z,, 6) used for the oblique sinogram parameterization. The particular LOR represented has 0 0. able u in Eq. (53) is replaced by the axial coordinate u cos 9, the average of the axial coordinates of the two...

Occupational and Public Exposures

Healthcare Workers Within and Outside the PET Facility The radiation dose to a technologist performing a PET study is generally higher than for conventional nuclear medicine imaging 30-32 . Comparison of staff doses between PET facilities is not very informative because of the variability in clinical workload and scan procedures. With attention to shielding and protocols, it should be possible to maintain occupational exposure below approximately 6 mSv y1 in most circumstances 33 . Hand doses...

Other Performance Measures

In addition to the parameters described above (resolution, count rate, scatter, sensitivity), a number of other parameters are specified by bodies such as NEMA to assess PET scanner performance. These include accuracy of corrections for attenuation, scatter, randoms and dead time, and image quality assessments. Uniformity is another parameter that has been found to be useful to test. Energy resolution, though a major determinant of PET performance, has not been included in the latest NEMA PET...

Ovarian Carcinoma

Ovarian carcinoma is the leading cause of death among gynaecological tumours 99 . The treatment of ovarian carcinoma primarily consists of surgical resection followed by chemotherapy and or radiotherapy. Accurate staging is essential, particularly in the restaging of patients with elevated serum markers (CA-125). 18F -FDG PET has been shown to have high accuracy in detecting in ovarian carcinoma lesions greater than 1 cm in size, but the detection of micrometastatic disease (one of the most...

Parameter Estimation

The previous sections presented the mathematical techniques necessary to solve the model equations. Thus, with knowledge of the input function Ca(t), the model configuration, and its rate constants, the tissue concentration curve can be predicted mathematically. This section provides an overview of the inverse problem, i.e., given measurements of the tissue activity and the input function and a proposed model configu ration, one can produce estimates of the underlying rate constants. Many...

PET as a Tracer Method in Drug Development

The development of new drugs is a time consuming and expensive process. The costs are markedly increased the closer the drug proceeds towards market approval. This is especially clear when the process has reached the phase of clinical trials. During drug development a number of decisions have to be taken. At each point, adequate information must be available to give an optimal base for decision. The relevance of pre- Figure 10.8. Synthesis of 21-11C -progesterone and 1a-methyl-11C -mesterolone....

PET Radionuclides in Oncology

The short-lived radionuclides (radioisotopes) required for PET are produced in cyclotrons. In PET oncology clinical applications, the most commonly used positron-emitting tracer is 18F-fluoro-2-deoxy-glucose, or 18F -FDG 6 . The unique versatility of PET lies in the ability to study numerous physiologic and biochemical processes in vivo. The measurement of tissue blood flow, oxygen metabolism, glucose metabolism, amino acid and protein synthesis and nucleic acid metabolism have all been...

PET Scanner Calibration

Once the corrections for the various sources of bias described in this chapter have been applied to PET data, images can be reconstructed which are free of artefacts and which reflect the regional concentration of radiotracer in the body. In most clinical applications of PET this is sufficient as the images are interpreted visually without reference to the absolute voxel values. Indeed, this degree of quantification is sufficient in some types of kinetic research study also. For example,...

Precursor Production

The development of new precursors 9 is important for the development of new labeled substances. A number of precursors more or less routinely available from target-produced 11C carbon dioxide are shown in Fig. 10.2. The most frequently employed precursor is 11C methyl iodide 10 . There are two synthetic methods available converting 11C carbon dioxide to 11C methoxide followed by reaction with hydroiodic acid, or by a gas phase reaction where 11C methane is reacted with iodine. Methyl iodide is...

Radiation

Radiation can be classified into electromagnetic or particulate. Ionising radiation is radiation that has sufficient energy associated with it to remove electrons from atoms, thus causing ionisation. This is restricted to high-energy electromagnetic radiation (x and y radiation) and charged particles (a, P-, P+). Examples of non-ionising electromagnetic radiation include light, radio, and microwaves. We will concern ourselves specifically with ionising radiation as this is of most interest in...

Random and Deterministic Errors

In making the choices necessary to implement a tracer method, it is important to be aware of the many sources of error that affect the precision and accuracy of these physiological measurements 106 . A good understanding of what effects are more or less significant to a given tracer and to the biological question of interest is essential in designing a sensitive, reliable technique that is not overly complex. One aspect to consider is random errors, i.e., the effects of random statistical noise...

Randoms Correction Origin of Random Coincidences

Random coincidences, also known as accidental or chance coincidences, arise because of the finite width of the electronic time window used to detect true coincidences. This finite width allows the possibility that two uncorrelated single detection events occurring sufficiently close together in time can be mistakenly identified as a true coincidence event, arising from one annihilation. This is shown schematically in Fig. 5.1. The rate at which random coincidences occur between a detector pair...

Randoms Variance Reduction

Where randoms form a significant fraction of the acquired events, as is frequently the case in 3D imaging, it becomes desirable to obtain randoms estimates that are accurate but contain less noise than those obtained using the delayed channel method. Most delayed channel implementations allow the acquisition of separate datasets from the prompt and delayed coincidence channels - this allows the possibility of post-processing the randoms estimate to reduce noise, prior to subtraction from the...

Risk to the General Public

The United Kingdom annual dose limit for members of the general public is 1mSv and there is a recommendation that at any one exposure the dose should not exceed 30 of this 17 . Clearly, in a general waiting area there will not be just one PET patient, and an escort or carer could receive in excess of 0.3 Sv when taking into account the contribution from all the patients present. Ideally it is best to have a hot waiting room separate to the cold waiting room, and the planning arrangements in the...

Selection of Modelbased Methods

This chapter has presented an overview of modeling methods, from the most complex dynamic data acquisition with iterative parameter estimation to simplified methods including Patlak and Logan plots or single-scan techniques. Choosing the best approach is not simple, and other options are available when selecting a tracer method. In some studies, investigators normalize the physiological measurements. Instead of using the absolute values provided by a method, the results are scaled in some...

Sensitivity and Depth of Interaction

The sensitivity of a PET scanner represents its ability to detect the coincident photons emitted from inside the scanner FOV. It is determined by two parameters of the scanner design its geometry and the stopping efficiency of the detectors for 511 keV photons. Scanner geometry defines the fraction of the total solid angle covered by it over the imaging field. Small-diameter and large axial FOV typically leads to high-sensitivity scanners. The stopping efficiency of the PET detector is related...

Simulationbased Scatter Correction

Since the physics of photon interactions in matter is well understood, it is possible to model these processes and estimate the scatter contribution to projections given an accurate map of attenuation coefficients in the scattering medium and an initial estimate of the scatter-free radioactivity distribution. The scatter can be estimated analytically or numerically (for example, using Monte Carlo techniques). Punsc (s, z ) Pobs (s, z ) - k (s, z ) h(s, z ) Here, the projection data and the...

Sources of Dead Time

The degree to which a system suffers from dead time and the sources of dead time within a system are highly dependent on its design and architecture. We now describe three sources of dead time typically found in clinical PET scanners. A more detailed discussion of this topic can be found in 12 and 27 . Within a well-designed scintillation detector subsystem, the primary factor affecting the minimum time between separable events is the integration time, that is, the time spent integrating charge...

Specific Problems Related to PETCT

One of the most exciting technological advances in recent years is the clinical application of combined PET CT scanners. However, this new technology has come with its own particular set of artefacts and pitfalls. One of the biggest problems with PET CT imaging in a dedicated combined scanner is related to differ- Figure 14.12. Coronal CT attenuation corrected 18FDG scan demonstrating an apparent loss of activity at the level of the diaphragm (arrows) due to differences in breathing patterns...

Specificity of Gene Therapy

A major concern in the application of gene therapy is need to achieve controlled and effective delivery of genes to target cells or their surrounding matrix, and to avoid expression in non-target locations. Ex vivo approaches help to ensure that gene transfer is limited to cells of a particular organ. For example, gene transfer into bone marrow cells provides a means to introduce genes selectively into various blood cell types, including hematopoietic stem cells. Directing gene transfer and or...

Synthesis of Compounds Labeled with 11C

The labeling synthesis can be divided into two areas of chemistry, nC-hetereo (N, O, and S) and nC-C bond-forming reactions. The first application of nC methyl iodide was an alkylation on a sulfur nucleophile in the synthesis of nL- uC methionine 16 as is presented in Fig. 10.3. Later, the general utilization of nC methyl iodide in alkylation reactions with N-, O- and S-nucle-ophiles such as amines, amides, phenolates, carboxy-lates and thiolates became the most common way of introducing 11C in...

Synthetic Considerations

Several aspects apart from those in conventional synthesis have to be considered when planning syntheses of compounds labeled with short-lived P+-emitting nu-clides. For example, the time factor, radiation protection, labeling position and specific radioactivity are points which need consideration. Furthermore, in production of tracers for in vivo human applications the final product has to be sterile, endotoxin-free and dissolved in an appropriate physiological vehicle. The whole procedure has...

Technical Issues for Gene Therapy

Gene therapy can be achieved either by ex vivo or in vivo methods (Fig. 18.1). Technically, ex vivo methods are simpler with regard to DNA delivery, but these methods often require minor surgery to harvest cells, which are then replaced after introduction of gene(s) ex vivo. With in vivo gene therapy protocols, it is desirable to have highly efficient target-specific vectors while minimizing risk. Each disease has its own specific requirements such as target tissues, the amount of gene product...

The Cornerstone of Tomographic Reconstruction The Central Section Theorem

Tomographic reconstruction relies on Fourier analysis. Recall that the Fourier transform of a function f(x,y) is defined by J dxdyf(x,y)exp(-2ni(xvx + yvy)) (6) and is inverted by changing the sign of the argument of the complex exponential (F-1F )(x, y) f (x, y) J dVx dVy F(Vx ,Vy )exp(2ni(xVx +yVy)) We use Vx and Vy to denote the frequencies associated to x and y respectively, and denote the Fourier transform of a function, e.g., f, by the corresponding upper case character, e.g., F. These...

The CT and PET Components

The choice of the level of CT and PET performance depends to some extent on the applications envisaged. As with the prototype, the design described here is targeted primarily at PET whole-body oncology, although potential cardiac applications are not excluded. Since the PET scanner performance is the limiting factor in terms of statistical image quality, spatial resolution, and scan duration, the highest possible PET performance is obviously indicated. This consideration influenced the...

The Filtered Backprojection Algorithm

The FBP algorithm is the standard algorithm of tomography. It is equivalent to the direct Fourier reconstruction in the limit of continuous sampling, but its discrete implementation differs. The FBP inversion explicitly combines Eqs. (11), (10) and (7). Straight-forward manipulations involving changing from Cartesian (vx, vy) to polar (v, 0) coordinates lead to a two-step inversion formula (Fig. 4.4) Figure 4.4. Illustration of 2D filtered backprojection. The top row shows a brain section and...

The Illposedness of the Inverse Xray Transform

Like many problems in applied physics, the inversion of the x-ray transform is an ill-posed problem the solution f defined by Eqs. (11), (10) and (7) does not depend continuously on the data p(s, < j). Concretely, this means that an arbitrarily small perturbation of p due to measurement noise can cause an arbitrarily large error on the reconstructed image f. We refer to Bertero and Boccacci 20 and Barrett and Myers 7 for an introduction to the concept of ill-posedness and its implication in...

The Modeling Process

Once a radioactive tracer has been selected for evaluation, there are a number of steps involved in developing a useful model and a model-based method. Figure 6.1 gives an overview of this process. Based on prior information of the expected in vivo behavior of the tracer, a complete model can be specified. Such a model is usually overly complex and will have many more parameters than can be determined from PET data due to the presence of statistical noise. Based on initial modeling studies, a...

The Reprojection Algorithm

The 3D FBP algorithm is valid only for non-truncated parallel projections. In almost all PET studies, the tracer distribution extends axially over the whole FoV of the scanner, and the only non-truncated parallel projections are those with 6 0. For sampled data, the equality 6 0 is replaced by 6 < 60 for some small maximum oblicity angle 60, which corresponds typically to the maximum ring difference d2Dmax incorporated in a 2D acquisition. The standard analytic reconstruction algorithm for...

The Structural Misalignment Factors muvj

The effects of structural misalignment are not easy to predict. They can often be determined by examining data used for calculating the transaxial geometric factors after normalisation for all other known components. On the GE Advance (GE Medical Systems, Milwaukee,WI), this process reveals high-frequency non-uniformities which are consistent in every sinogram, regardless of ring difference. These non-uniformities are correlated with rotational misalignments of the block modules, which extend...

The Transaxial Geometric Factors g

Rotating transmission sources, planar sources and scanning line sources have all been used to generate data for calculating the transaxial geometric factors e.g., 16,22,25,26 . Once the data have been collected, an analytic correction is applied to compensate for non-uniform illumination of the LORs by the source. The data are then corrected for variations in detector efficiency and block profile. For systems where crystal interference is not expected to be a problem, the transaxial geometric...

Timeofflight Measurement

Good timing resolution of a PET detector, besides helping reduce the number of random coincidences, can also be use to estimate the annihilation point between the two detectors by looking at the difference in arrival times of the two photons. For this, an extremely fast scintillator, such as BaF2, is needed. In Fig. 2.24, point P marks an annihilation point which is located a distance d from the point which is exactly halfway (distance d) between the two detectors. A photon moving along PA will...

Truncation Artefacts

Spiral CT technology currently offers a transverse field-of-view of 50 cm, and thus falls short 10 cm less than the corresponding transverse PET field-of-view (Table 8.3). This difference may lead to truncation artefacts in the CT images 80 and to a systematic bias of the recovered tracer distribution when scanning obese patients, or when positioning patients with their arms down (Fig. 8.7). If not corrected for truncation, CT images appear to mask the reconstructed emission data with the...

Use of Knockout Mice in Drug Discovery

Imaging can save considerable time in pre-clinical studies. Multi-drug resistance (MDR) in cancer chemotherapy is mediated by P-glycoprotein. Monitoring the effectiveness of modulators is an important area of imaging. Piwnica-Worms and Marmion presented a case study that used knockout mice to decide whether 99mTc -Q complexes would be effective as probes for P-glycoprotein. The 99mTc -Q complexes tested in MDR 1a ab knockout mice showed enhancement of initial brain uptake but no significant...

Validation and Quantifying Registration Accuracy

Registration algorithms, especially automated ones, involve a large number of computations that may be opaque to the user. Registration accuracy is the metric used to determine the quality of a specific registration. Any registration method must be sufficiently accurate for the application envisaged and sufficiently robust to be clinically useful. No algorithm is 100 robust so any clinical protocol must have the means to detect failure with close to 100 reliability. Registration accuracy is...

[18Ffptztp in vitro and rat studies

We have been working extensively with a muscarinic agonist based on a series first proposed by Sauerberg et al. 40 of Novo Nordisk as potential drugs to treat Alzheimer's disease. These ligands contain a thiadia-zolyl moiety attached to various heterocycles, including tetrahydropyridine. Two of these compounds, xanomeline and butylthio-TZTP, demonstrated M1 selectivity and have been labelled with 11C and studied with PET 41 . Another compound, (P-TZTP), is M2 selective. In the in vitro...

[18Ffptztp studies in nonhuman primates

This section summarises the PET studies performed with 18F -FP-TZTP in monkeys. These experiments were used to develop the methodology and analysis techniques for human studies. They also demonstrated the in vivo specific binding of 18F -FP-TZTP and demonstrated its sensitivity to synaptic acetylcholine levels. PET studies were performed in isoflurane-anesthetized rhesus monkeys to assess the in vivo behaviour of 18F -FP-TZTP 14 . Control studies (n 11) were performed first to characterise...

Whole Body Imaging in Oncology

Presently whole-body FDG imaging protocols for oncology applications takes full advantage of the recent developments in tomographs and image reconstruction. For most extra-cranial malignancies, the goal is to image the entire torso, from skull base to pelvis within one hour or less of scanner time, and in fact with recent developments in PET tomograph detector technology and combined PET CT tomographs, imaging of the entire torso in under 30 minutes is becoming routine. The brain is usually not...

Impact of Radioactivity Outside the Field of View

Scanner design has traditionally included significant lead end-shields to restrict the majority of single photons emitted from outside the axial field of view of the scanner from having direct line-of-sight trajectories to the detectors. Single photons from outside the field of view will not form a true coincidence, but will increase the number of events the detector has to process leading to increased dead time and random coincidences. Some true coincidences from scattered photons may be...

Validation of Physiological Measures

In the process of developing and selecting a suitable model formulation and methodology, it is important to perform validation studies which prove that the parameter estimates produced by a model are correct. These studies determine the precision and accuracy of model estimates, verify the legitimacy of the model assumptions, and help choose between various approaches. Such an evaluation invariably must be done in animals because of constraints on experimental design, scan duration, and...

Scatter Fraction

Scatter fraction is defined as that fraction of the total coincidences recorded in the photopeak window which have been scattered. The scattering may be of either, or both, of the annihilation photons, but it is predominantly scattering of one photon only. Scattering arises from a number of sources (i) scattering within the object containing the radionuclide, (ii) scattering off the gantry components such as lead septa and side shields, (iii) scattering within the detectors. A number of methods...

Dual Energy Window Methods

There have been two distinct approaches to the use of dual energy windows for scatter estimation. The dual energy window (DEW) method uses an energy window set below the photopeak and abutting it 41 (Fig. 5.15a) while the estimation of trues method (ETM) uses an energy window whose lower level discriminator is set above 511 keV and which overlaps the upper portion of the photopeak window 42 (Fig. 5.15b). These methods both make use of measurements in the auxiliary energy window to estimate the...

Radiolabeling Studies Using 94mTc

The first technetium complex to give consistently high uptake and slow washout in myocardial tissue was the technetium(I) cationic complex Tc(tbi)6 + 117 . In this complex, the Tc(I) oxidation state is stabilized by the back-bonding isonitrile ligands, which adopt an octahedral geometry around the technetium. In an effort to improve the heart-to-non-target organ ratios, the isonitrile ligand was functionalized. This led to the development of the complex technetium-methoxy-isobutylisonitrile...

Positron Decay

There are two methods of production of positrons by pair production, and by nuclear transmutation. Pair production will be discussed in the following section. Positron emission from the nucleus is secondary to the conversion of a proton into a neutron as in with in this case a neutrino is emitted. The positron is the antimatter conjugate of the electron emitted in P-decay. The general equation for positron decay from an atom is where Q is energy. The atom X is proton-rich and achieves stability...

Melanoma

The role of 18F -FDG PET in the initial staging of low-risk (< 1 mm thickness) and intermediate-risk (1-3 mm thickness) melanoma is limited, due to the low prevalence of metastatic disease (particularly in low-risk melanoma), and the often small size of metastatic deposits in nodes involved with metastatic spread 72,73 . Malignant melanoma can spread widely and unpredictably throughout the body, and median survival after the appearance of distant metastases is approximately six months 74 ....