Perelman School of Medicine at the University of Pennsylvania

Physics and Instrumentation Group

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Time-of-Flight PET Systems

Improvement in lesion detection with whole-body oncologic time-of-flight PET.

El Fakhri G*, Surti S*, Trott C, Scheuermann J, Karp JS. (* joint first authors).

J Nucl Med, vol. 52, pp. 347-353, 2011.

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 patient's 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.


Impact of TOF PET on whole-body oncologic studies: a human observer detection and localization study.

Surti S, Scheuermann J, El Fakhri G, Daube-Witherspoon ME, Lim R, Abi-Hatem N, Moussallem E, Benard F, Mankoff D, JS Karp.

J Nucl Med, vol. 52, pp. 712-719, 2011.

Objectives Phantom studies have shown improved lesion detection with TOF PET. For the first time we now evaluate the benefit of fully-3D, TOF PET in clinical whole-body oncology using human observers to localize and detect lesions in realistic patient anatomic backgrounds.

Methods 100 patient studies with normal FDG uptake were chosen. 1-cm spheres were imaged in air at variable locations in the scanner FOV corresponding to lung and liver locations within each patient (4:1 local uptake). Sphere data were appropriately attenuated and merged with patient data to produce fused list data files. All list files were iteratively reconstructed with full corrections and with or without the TOF kernel. The images were presented to 4 clinicians to localize and report with a confidence level the presence/absence of a lesion. The data will be analyzed to calculate the probability of correct localization and detection, and the area under the LROC curve.

Results Initial results from a related study using a channelized hotelling observer (CHO SNR) show improved lesion detection for low uptake lesions and large patients (up to 14% gain). The human observer study is ongoing and will quantify the clinical impact of TOF PET on lesion detection and localization.

Conclusions In this study we evaluate the impact of TOF PET on lesion detection and localization by human observers in realistic human imaging settings. The conclusions will be derived for different BMI patients, varying scan times, and lesion locations.


The imaging performance of a LaBr3-based PET scanner.

Daube-Witherspoon ME, Surti S, Perkins A, Kyba CCM, Wiener R, Werner ME, Kulp R, Karp JS.

Phys Med Biol, vol. 55, pp. 45-64, 2010.

A prototype time-of-flight (TOF) PET scanner based on cerium-doped lanthanum bromide [LaBr3(5% Ce)] has been developed. LaBr3 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 LaBr3's point spread function. The LaBr3 TOF-PET scanner demonstrated the impact of superior timing and energy resolutions on image quality.


Experimental evaluation of a simple lesion detection task with time-of-flight PET.

Surti S, Karp JS.

Phys Med Biol, vol. 54, pp. 373-384, 2009.

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.


Benefit of time-of-flight in PET: Experimental and clinical results.

Karp JS, Surti S, Daube-Witherspoon ME, Muehllehner G.

J Nucl Med, vol. 49, pp. 462-470, 2008.

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.


Performance of Philips Gemini TF PET/CT scanner with special consideration for its time-of-flight imaging capabilities.

Surti S, Kuhn A, Werner ME, Perkins AE, Kolthammer J, Karp JS.

J Nucl Med, vol. 48, pp. 471-480, 2007.

Results from a new PET/CT scanner using lutetium-yttrium oxyorthosilicate (LYSO) crystals for the PET component are presented. This scanner, which operates in a fully 3-dimensional mode, has a diameter of 90 cm and an axial field of view of 18 cm. It uses 4 × 4 × 22 mm3 LYSO crystals arranged in a pixelated Anger-logic detector design. This scanner was designed to perform as a high-performance conventional PET scanner as well as provide good timing resolution to operate as a time-of-flight (TOF) PET scanner. Methods: Performance measurements on the scanner were made using the National Electrical Manufacturers Association (NEMA) NU2-2001 procedures to benchmark its conventional imaging capabilities. The scatter fraction and noise equivalent count (NEC) measurements with the NEMA cylinder (20-cm diameter) were repeated for 2 larger cylinders (27-cm and 35-cm diameter), which better represent average and heavy patients. New measurements were designed to characterize its intrinsic timing resolution capability, which defines its TOF performance. Additional measurements to study the impact of pulse pileup at high counting rates on timing, as well as energy and spatial, resolution were also performed. Finally, to characterize the effect of TOF reconstruction on lesion contrast and noise, the standard NEMA/International Electrotechnical Commission torso phantom as well as a large 35-cm-diameter phantom with both hot and cold spheres were imaged for varying scan times. Results: The transverse and axial resolution near the center is 4.8 mm. The absolute sensitivity of this scanner measured with a 70-cm-long line source is 6.6 cps/kBq, whereas scatter fraction is 27% measured with a 70-cm-long line source in a 20-cm-diameter cylinder. For the same line source cylinder, the peak NEC rate is measured to be 125 kcps at an activity concentration of 17.4 kBq/mL (0.47 μCi/mL). The 2 larger cylinders showed a decrease in the peak NEC due to increased attenuation, scatter, and random coincidences, and the peak occurs at lower activity concentrations. The system coincidence timing resolution was measured to be 585 ps. The timing resolution changes as a function of the singles rate due to pulse pileup and could impact TOF image reconstruction. Image-quality measurements with the torso phantom show that very high quality images can be obtained with short scan times (1–2 min per bed position). However, the benefit of TOF is more apparent with the large 35-cm-diameter phantom, where small spheres are detectable only with TOF information for short scan times. Conclusion: The Gemini TF whole-body scanner represents the first commercially available fully 3-dimensional PET scanner that achieves TOF capability as well as conventional imaging capabilities. The timing resolution is also stable over a long duration, indicating the practicality of this device. Excellent image quality is achieved for whole-body studies in 10–30 min, depending on patient size. The most significant improvement with TOF is seen for the heaviest patients.


Investigation of time-of-flight benefit for fully-3D PET.

Surti S, Karp JS, Popescu LM, Daube-Witherspoon ME, Werner M.

IEEE Trans Med Imaging, vol. 25, pp. 529-538, 2006.

The purpose of this paper is to determine the benefit that can be achieved in image quality for a time-of-flight (TOF) fully three-dimensional (3-D) whole-body positron emission tomography (PET) scanner. We simulate a 3-D whole-body time-of-flight PET scanner with a complete modeling of spatial and energy resolutions. The scanner is based on LaBr/sub 3/ Anger-logic detectors with which 300ps timing resolution has been achieved. Multiple simulations were performed for 70-cm long uniform cylinders with 27-cm and 35-cm diameters, containing hot spheres (22, 17, 13, and 10-mm diameter) in a central slice and 10-mm diameter hot spheres in a slice at 1/4 axial FOV. Image reconstruction was performed with a list-mode iterative TOF algorithm and data were analyzed after attenuation and scatter corrections for timing resolutions of 300, 600, 1000 ps and non-TOF for varying count levels. The results show that contrast recovery improves slightly with TOF (NEMA NU2-2001 analysis), and improved timing resolution leads to a faster convergence to the maximum contrast value. Detectability for 10-mm diameter hot spheres estimated using a nonprewhitening matched filter (NPW SNR) also improves nonlinearly with TOF. The gain in image quality using contrast and noise measures is proportional to the object diameter and inversely proportional to the timing resolution of the scanner. The gains in NPW SNR are smaller, but they also increase with increasing object diameter and improved timing resolution. The results show that scan times can be reduced in a TOF scanner to achieve images similar to those from a non-TOF scanner, or improved image quality achieved for same scan times.