Joel S. Karp

Benefit of Time-of-Flight in PET: Experimental and Clinical Results

Significant improvements have made it possible to add the technology of time-of-flight (TOF) to improve PET, particularly for oncology applications. The goals of this work were to investigate the benefits of TOF in experimental phantoms and to determine how these benefits translate into improved performance for patient imaging. Methods: In this study we used a fully 3-dimensional scanner with the scintillator lutetium-yttrium oxyorthosilicate and a system timing resolution of ∼600 ps. The data are acquired in list-mode and reconstructed with a maximum-likelihood expectation maximization algorithm; the system model includes the TOF kernel and corrections for attenuation, detector normalization, randoms, and scatter. The scatter correction is an extension of the model-based single-scatter simulation to include the time domain. Phantom measurements to study the benefit of TOF include 27-cm- and 35-cm-diameter distributions with spheres ranging in size from 10 to 37 mm. To assess the benefit of TOF PET for clinical imaging, patient studies are quantitatively analyzed. Results: The lesion phantom studies demonstrate the improved contrast of the smallest spheres with TOF compared with non-TOF and also confirm the faster convergence of contrast with TOF. These gains are evident from visual inspection of the images as well as a quantitative evaluation of contrast recovery of the spheres and noise in the background. The gains with TOF are higher for larger objects. These results correlate with patient studies in which lesions are seen more clearly and with higher uptake at comparable noise for TOF than with non-TOF. Conclusion: TOF leads to a better contrast-versus-noise trade-off than non-TOF but one that is difficult to quantify in terms of a simple sensitivity gain improvement: A single gain factor for TOF improvement does not include the increased rate of convergence with TOF nor does it consider that TOF may converge to a different contrast than non-TOF. The experimental phantom results agree with those of prior simulations and help explain the improved image quality with TOF for patient oncology studies.

Sex differences in regional cerebral glucose metabolism during a resting state

Positron emission tomography was used to evaluate the regional distribution of cerebral glucose metabolism in 61 healthy adults at rest. Although the profile of metabolic activity was similar for men and women, some sex differences and hemispheric asymmetries were detectable. Men had relatively higher metabolism than women in temporal-limbic regions and cerebellum and relatively lower metabolism in cingulate regions. In both sexes, metabolism was relatively higher in left association cortices and the cingulate region and in right ventro-temporal limbic regions and their projections. These results are consistent with the hypothesis that differences in cognitive and emotional processing have biological substrates.

Positron emission tomography

The developments in positron emission tomography (PET) are reviewed with an emphasis on instrumentation for clinical PET imaging. After a brief summary of positron imaging before the advent of computed tomography, various improvements are highlighted including the move from PET scanners with septa to fully 3D scanners, changes in the preferred scintillators, efforts to improve the energy discrimination, and improvements in attenuation correction. Time-of-flight PET imaging is given special attention due to the recent revival of this technique, which promises significant improvement. Besides technical instrumentation efforts, other factors which influenced the acceptance of clinical PET are also discussed.

Singles transmission in volume-imaging PET with a 137Cs source

The feasibility of a new method of attenuation correction in PET has been investigated, using a single-photon emitter for the transmission scan. The transmission scan is predicted to be more than a factor of ten faster with the singles method than the standard coincidence method, for comparable statistics. Thus, a transmission scan be completed in 1-2 min, rather than 10-20 min, as is common practice with the coincidence method. In addition, a potential advantage of using the single-photon source 137Cs, which has an energy of 662 keV, is that postinjection transmission studies can be performed using energy discrimination to separate the transmission from the emission data at 511 keV. In order to compensate for the energy difference of the attenuation coefficients at 662 keV compared to 511 keV, the transmission images are segmented into two compartments, tissue and lung, and known values (for 511 keV) of attenuation are inserted into these compartments. This technique also compensates for the higher amount of scatter present with the singles method, since it is not possible to use a position gate (based on collinearity of the source and two detector positions) as is commonly done with a positron-emitting source. We have demonstrated, with experimental phantom studies, that the singles transmission method combined with segmentation gives results equivalent both qualitatively and quantitatively to the coincidence method, but requires significantly less time.

Improvement in Lesion Detection with Whole-Body Oncologic Time-of-Flight PET

Time-of-flight (TOF) PET has great potential in whole-body oncologic applications, and recent work has demonstrated qualitatively in patient studies the improvement that can be achieved in lesion visibility. The aim of this work was to objectively quantify the improvement in lesion detectability that can be achieved in lung and liver lesions with whole-body 18F-FDG TOF PET in a cohort of 100 patients as a function of body mass index, lesion location and contrast, and scanning time. Methods: One hundred patients with BMIs ranging from 16 to 45 were included in this study. Artificial 1-cm spheric lesions were imaged separately in air at variable locations of each patients lung and liver, appropriately attenuated, and incorporated in the patient list-mode data with 4 different lesion-to-background contrast ranges. The fused studies with artificial lesion present or absent were reconstructed using a list-mode unrelaxed ordered-subsets expectation maximization with chronologically ordered subsets and a gaussian TOF kernel for TOF reconstruction. Conditions were compared on the basis of performance of a 3-channel Hotelling observer signal-to-noise ratio in detecting the presence of a sphere of unknown size on an anatomic background while modeling observer noise. Results: TOF PET yielded an improvement in lesion detection performance (3-channel Hotelling observer signal-to-noise ratio) over non-TOF PET of 8.3% in the liver and 15.1% in the lungs. The improvement in all lesions was 20.3%, 12.0%, 9.2%, and 7.5% for mean contrast values of 2.0:1, 3.2:1, 4.4:1, and 5.7:1, respectively. Furthermore, this improvement was 9.8% in patients with a BMI of less than 30 and 11.1% in patients with a BMI of 30 or more. Performance plateaued faster as a function of number of iterations with TOF than non-TOF. Conclusion: Over all contrasts and body mass indexes, oncologic TOF PET yielded a significant improvement in lesion detection that was greater for lower lesion contrasts. This improvement was achieved without compromising other aspects of PET imaging.

Optimization of a fully 3D single scatter simulation algorithm for 3D PET

We describe a new implementation of a single scatter simulation (SSS) algorithm for the prediction and correction of scatter in 3D PET. In this implementation, out of field of view (FoV) scatter and activity, side shields and oblique tilts are explicitly modelled. Comparison of SSS predictions with Monte Carlo simulations and experimental data from uniform, line and cold-bar phantoms showed that the code is accurate for uniform as well as asymmetric objects and can model different energy resolution crystals and low level discriminator (LLD) settings. Absolute quantitation studies show that for most applications, the code provides a better scatter estimate than the tail-fitting scatter correction method currently in use at our institution. Several parameters such as the density of scatter points, the number of scatter distribution sampling points and the axial extent of the FoV were optimized to minimize execution time, with particular emphasis on patient studies. Development and optimization were carried out in the case of GSO-based scanners, which enjoy relatively good energy resolution. SSS estimates for scanners with lower energy resolution may result in different agreement, especially because of a higher fraction of multiple scatter events. The algorithm was applied to a brain phantom as well as to clinical whole-body studies. It proved robust in the case of large patients, where the scatter fraction increases. The execution time, inclusive of interpolation, is typically under 5 min for a whole-body study (axial FoV: 81 cm) of a 100 kg patient.

Design of a lanthanum bromide detector for time-of-flight PET

Recent improvements in the growth and packaging of lanthanum bromide (LaBr/sub 3/), in addition to its superb intrinsic properties of high light output, excellent energy resolution, and fast decay time, make it a viable detection material for a positron emission tomography (PET) scanner based on time-of-flight (TOF). We have utilized theoretical simulations and experimental measurements to investigate the design and performance of pixelated LaBr/sub 3/ Anger-logic detectors suitable for use in a TOF PET scanner. Our results indicate that excellent energy resolution can be obtained from individual as well as multicrystal arrays of LaBr/sub 3/ in a 4 mm/spl times/4 mm /spl times/ 30 mm geometry. Measured energy resolutions (at 511 keV) of 4.1% for a single crystal and an average of 5.1% for an array of 100 crystals have been achieved with our best samples. Both simulations and experimental measurements of an Anger-logic based detector consisting of the LaBr/sub 3/ crystal array coupled to a continuous light guide and seven photomultiplier tubes (PMTs), have resulted in the ability to clearly discriminate 511 keV interactions in each crystal. We have measured coincidence time resolutions for both 0.5% and 5.0% cerium-doped LaBr/sub 3/ and found that the higher level of Ce-doping yielded superior results with little to no degradation in light output or energy resolution. The time resolution for a single 5.0% Ce-doped LaBr/sub 3/ crystal (4 mm /spl times/ 4 mm /spl times/ 30 mm) coupled directly to a PMT was measured to be 275 ps full-width at half-maximum (FWHM). With an array of 100 crystals coupled to a light guide and seven PMT cluster an average time resolution of 290 ps FWHM was obtained by summing the signals from the PMT cluster. Ultimately, two 5.0% Ce-doped LaBr/sub 3/ Anger-logic detectors placed in coincidence yielded a time resolution of 313 ps FWHM.

Design evaluation of A-PET: A high sensitivity animal PET camera

In recent years it has been shown that PET is capable of obtaining in vivo metabolic images of small animals. These serve as models to study the development and progress of diseases within humans. Imaging small animals requires not only image resolution better than 2 mm, but also high sensitivity in order to image ligands with low specific activity or radiochemical yields. Toward achieving these goals, we have developed a discrete 2 /spl times/ 2 /spl times/ 10 mm/sup 3/ GSO Anger-logic detector for use in a high resolution, high sensitivity, and high count-rate animal PET scanner. This detector uses relatively large 19 mm diameter photomultiplier tubes (PMT), but nevertheless achieves good spatial and energy resolution. The scanner (A-PET) has a port diameter of 21 cm, transverse field-of-view of 12.8 cm, axial length of 11.6 cm, and operates in 3-D volume imaging mode. The absolute coincidence sensitivity is 1.3% for a point source. Due to the use of large PMTs in an Anger design, the encoding ratio (number of crystals/PMT) is high, which reduces the complexity and leads to a cost-effective scanner. Simulation results show that this scanner can achieve high NEC rates for small cylindrical phantoms due to its high sensitivity and low dead-time. Initial measurements show that our design goals for spatial resolution and sensitivity were realized in the prototype scanner.

Dedicated PET scanners for breast imaging.

We have used computer simulations to compare two designs for a PET scanner dedicated to breast imaging with a whole-body PET scanner. The new designs combine high spatial resolution, high sensitivity, and good energy resolution to detect small, low-contrast masses. The detectors are position sensitive NaI(Tl) scintillators. The first design is a ring scanner surrounding the breast and the second consists of two planar detectors placed on opposite sides of the breast. We have employed standard performance measures to compare the different designs: contrast, percentage standard deviation of the background, and signal-to-noise ratios of reconstructed images. The results of the simulations show that both of the proposed designs have better lesion detectability than a whole-body scanner. The results also show that contrast is higher in the ring breast system but that the noise is lower in the planar breast system. Overall, the ring system yields images with the best signal-to-noise ratios, although the planar system offers practical advantages for imaging the breast and axilla.

Three-dimensional image reconstruction for PET by multi-slice rebinning and axial image filtering

A fast method is described for reconstructing volume images from three-dimensional (3D) coincidence data in positron emission tomography (PET). The reconstruction method makes use of all coincidence data acquired by high-sensitivity PET systems that do not have inter-slice absorbers (septa) to restrict the axial acceptance angle. The reconstruction method requires only a small amount of storage and computation, making it well suited for dynamic and whole-body studies. The method consists of three steps: (i) rebinning of coincidence data into a stack of 2D sinograms; (ii) slice-by-slice reconstruction of the sinogram associated with each slice to produce a preliminary 3D image having strong blurring in the axial (z) direction, but with different blurring at different z positions; and (iii) spatially variant filtering of the 3D image in the axial direction (i.e. 1D filtering in z for each x-y column) to produce the final image. The first step involves a new form of the rebinning operation in which multiple sinograms are incremented for each oblique coincidence line (multi-slice rebinning). The axial filtering step is formulated and implemented using the singular value decomposition (SVD). The method has been applied successfully to simulated data and to measured data for different kinds of phantom (multiple point sources, multiple discs, a cylinder with cold spheres, and a 3D brain phantom).