Suleman Surti

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.

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.

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.

NEMA NU 4-2008 Comparison of Preclinical PET Imaging Systems

The National Electrical Manufacturers Association (NEMA) standard NU 4-2008 for performance measurements of small-animal tomographs was recently published. Before this standard, there were no standard testing procedures for preclinical PET systems, and manufacturers could not provide clear specifications similar to those available for clinical systems under NEMA NU 2-1994 and 2-2001. Consequently, performance evaluation papers used methods that were modified ad hoc from the clinical PET NEMA standard, thus making comparisons between systems difficult. Methods: We acquired NEMA NU 4-2008 performance data for a collection of commercial animal PET systems manufactured since 2000: microPET P4, microPET R4, microPET Focus 120, microPET Focus 220, Inveon, ClearPET, Mosaic HP, Argus (formerly eXplore Vista), VrPET, LabPET 8, and LabPET 12. The data included spatial resolution, counting-rate performance, scatter fraction, sensitivity, and image quality and were acquired using settings for routine PET. Results: The data showed a steady improvement in system performance for newer systems as compared with first-generation systems, with notable improvements in spatial resolution and sensitivity. Conclusion: Variation in system design makes direct comparisons between systems from different vendors difficult. When considering the results from NEMA testing, one must also consider the suitability of the PET system for the specific imaging task at hand.

The imaging performance of a LaBr3-based PET scanner

A prototype time-of-flight (TOF) PET scanner based on cerium-doped lanthanum bromide [LaBr(3) (5% Ce)] has been developed. LaBr(3) has a high light output, excellent energy resolution and fast timing properties that have been predicted to lead to good image quality. Intrinsic performance measurements of spatial resolution, sensitivity and scatter fraction demonstrate good conventional PET performance; the results agree with previous simulation studies. Phantom measurements show the excellent image quality achievable with the prototype system. Phantom measurements and corresponding simulations show a faster and more uniform convergence rate, as well as more uniform quantification, for TOF reconstruction of the data, which have 375 ps intrinsic timing resolution, compared to non-TOF images. Measurements and simulations of a hot and cold sphere phantom show that the 7% energy resolution helps to mitigate residual errors in the scatter estimate because a high energy threshold (>480 keV) can be used to restrict the amount of scatter accepted without a loss of true events. Preliminary results with incorporation of a model of detector blurring in the iterative reconstruction algorithm not only show improved contrast recovery but also point out the importance of an accurate resolution model of the tails of LaBr(3)s point spread function. The LaBr(3) TOF-PET scanner demonstrated the impact of superior timing and energy resolutions on image quality.

Imaging performance of a-PET: a small animal PET camera

The evolution of positron emission tomography (PET) imaging for small animals has led to the development of dedicated PET scanner designs with high resolution and sensitivity. The animal PET scanner achieves these goals for imaging small animals such as mice and rats. The scanner uses a pixelated Anger-logic detector for discriminating 2 /spl times/ 2 /spl times/ 10 mm/sup 3/ crystals with 19-mm-diameter photomultiplier tubes. With a 19.7-cm ring diameter, the scanner has an axial length of 11.9 cm and operates exclusively in three-dimensional imaging mode, leading to very high sensitivity. Measurements show that the scanner design achieves a spatial resolution of 1.9 mm at the center of the field-of-view. Initially designed with gadolinium orthosilicate but changed to lutetium-yttrium orthosilicate, the scanner now achieves a sensitivity of 3.6% for a point source at the center of the field-of-view with an energy window of 250-665 keV. Iterative image reconstruction, together with accurate data corrections for scatter, random, and attenuation, are incorporated to achieve high-quality images and quantitative data. These results are demonstrated through our contrast recovery measurements as well as sample animal studies.

Optimizing the performance of a PET detector using discrete GSO crystals on a continuous lightguide

The authors are designing a new detector for PET using discrete 4/spl times/4/spl times/10 mm/sup 3/ GSO crystals on a continuous lightguide with 39 mm PMTs. The Light Response Function (LRF) of a detector is the amount of light received by a PMT as a function of the source position. It has to be controlled by a careful design of the lightguide in order to identify 4 mm crystals. The ideal LRF should be narrow with a linear variation over the PMT diameter. Simulations show that a 1.81 cm thick lightguide produces a narrow LRF with good crystal discrimination. However, the tails of this LRF are long. A further improvement can be achieved by using a 2.31 cm lightguide with 5 mm slots cut in its front surface. This results in a sharp edged, almost triangular, LRF. The slotted lightguide also minimizes the spatial dependence on varying depths of interaction of the gamma ray. The effect of varying slot depths was also investigated through the simulations. This was done while keeping the thickness of the lightguide continuous area constant. Experiments were performed and shown to be in general agreement with the simulations. The good spatial resolution and narrow LRF of such a detector will result in a high resolution PET scanner with good count rate capability.

Experimental evaluation of a simple lesion detection task with Time-of-Flight PET

A new generation of high-performance, time-of-flight (TOF) PET scanners have recently been developed. In earlier works, the gain with TOF information was derived as a reduction of noise in the reconstructed image, or essentially a gain in scanner sensitivity. These derivations were applicable to analytical reconstruction techniques and 2D PET imaging. In this work, we evaluate the gain measured in the clinically relevant task of lesion detection with TOF information in fully 3D PET scanners using iterative reconstruction algorithms. We performed measurements in a fully 3D TOF PET scanner using spherical lesions in uniform, cylindrical phantom. Lesion detectability was estimated for 10 mm diameter lesions using a non-prewhitening matched filter signal-to-noise-ratio (NPW SNR) as the metric. Our results show that the use of TOF information leads to increased lesion detectability, which is achieved with less number of iterations of the reconstruction algorithm. These phantom results indicate that clinically, TOF PET will allow reduced scan times and improved lesion detectability, especially in large patients.

Fundamentals of PET and PET/CT imaging

In this review, the fundamental principles of fluorodeoxyglucose (FDG) positron emission tomography (PET) and FDG PET/computed tomography (CT) imaging have been described. The basic physics of PET instrumentation, radiotracer chemistry, and the artifacts, as well as normal physiological or benign pathological variants, have been described and presented to the readers in a lucid manner to enable them an easy grasp of the fundamentals of the subject. Finally, we have outlined the current developments in quantitative PET imaging, including dual time point and delayed PET imaging, time‐of‐flight technology in PET imaging and partial volume correction, and global disease assessment with their potential of being incorporated into the assessment of benign and malignant disorders.