Rameshwar Prasad

Advances in multimodality molecular imaging

Multimodality molecular imaging using high resolution positron emission tomography (PET) combined with other modalities is now playing a pivotal role in basic and clinical research. The introduction of combined PET/CT systems in clinical setting has revolutionized the practice of diagnostic imaging. The complementarity between the intrinsically aligned anatomic (CT) and functional or metabolic (PET) information provided in a “one-stop shop” and the possibility to use CT images for attenuation correction of the PET data has been the driving force behind the success of this technology. On the other hand, combining PET with Magnetic Resonance Imaging (MRI) in a single gantry is technically more challenging owing to the strong magnetic fields. Nevertheless, significant progress has been made resulting in the design of few preclinical PET systems and one human prototype dedicated for simultaneous PET/MR brain imaging. This paper discusses recent advances in PET instrumentation and the advantages and challenges of multimodality imaging systems. Future opportunities and the challenges facing the adoption of multimodality imaging instrumentation will also be addressed.

Performance Evaluation of the FLEX Triumph X-PET Scanner Using the National Electrical Manufacturers Association NU-4 Standards

The purpose of this work was to evaluate the performance characteristics of the preclinical X-PET subsystem of the FLEX Triumph PET/CT scanner based on the NU 4-2008 standards of the National Electrical Manufacturers Association (NEMA). Methods: The performance parameters evaluated include the spatial resolution, scatter fraction, count losses and random coincidences, sensitivity, and image-quality characteristics. The PET detector array consisted of 11,520 individual bismuth germanate crystals arranged in 48 rings and 180 blocks, with an axial field of view (FOV) of 11.6 cm and a inner ring diameter of 16.5 cm. The spatial resolution was measured with a small 22Na point source (diameter, 0.25 mm) at different radial offsets from the center. Sensitivity was calculated using the same source by stepping the source axially through the axial FOV of the scanner. Scatter fraction and counting-rate performances were determined using a mouse- and rat-sized phantom with an 18F line source insert. The NEMA image-quality phantom and rodent imaging were also performed to access the overall imaging capabilities of the scanner. Results: Tangential spatial resolution in terms of full width at half maximum varied between 2.2 mm at the center of the FOV and 2.3 mm at a radial offset of 2.5 cm. The radial spatial resolution varied between 2.0 at the center and 4.4 mm at a radial offset of 2.3 cm. The peak system absolute sensitivity was 5.9% at the center of the FOV. The absolute system sensitivity was 0.67 counts/s/Bq, and the relative total system sensitivity was 73.9%. The scatter fraction for the mouse-sized phantom was 7.9%, with a peak true counting rate of 168 kilocounts per second (kcps) at 0.3 MBq/mL and a peak noise-equivalent counting rate of 106 kcps at 0.17 MBq/mL. The rat-sized phantom had a scatter fraction of 21%, with a peak true counting rate of 93 kcps at 0.034 MBq/mL and a peak noise-equivalent counting rate of 49 kcps at 0.02 MBq/mL. Recovery coefficients for the image-quality phantom ranged from 0.13 to 0.88. Conclusion: The performance of the X-PET scanner based on the NEMA NU 4-2008 standards was fully characterized. The overall performance demonstrates that the X-PET system is suitable for preclinical research.

NEMA NU-04-based performance characteristics of the LabPET-8™ small animal PET scanner

The objective of this study is to characterize the performance of the preclinical avalanche photodiode (APD)-based LabPET-8™ subsystem of the fully integrated trimodality PET/SPECT/CT Triumph™ scanner using the NEMA NU 04 - 2008 protocol. The characterized performance parameters include the spatial resolution, sensitivity, scatter fraction, counts rate performance, and image quality characteristics. The PET system is fully digital using APD-based detector modules with highly integrated electronics. The detector assembly consists of phoswich pairs of LYSO and LGSO crystals with dimensions of 2×2×14 mm3 having 7.5 cm axial and 10 cm transverse field-of-view (FOV). The spatial resolution and sensitivity were measured using a small 22Na point source at different positions in the scanners FOV. The scatter fraction and count rate characteristics were measured using a mouse- and rat-sized phantoms fitted with 18F line source. The overall imaging capabilities of the scanner were assessed using the NEMA image quality phantom and laboratory animal studies. The NEMA-based radial and tangential spatial resolution ranged from 1.7 mm at the center of the FOV to 2.59 mm at a radial offset of 2.5 cm and from 1.85 mm at the center of the FOV to 1.76 mm at a radial offset of 2.5 cm, respectively. Iterative reconstruction improved the spatial resolution to 0.84 mm at the center of the FOV. The total absolute system sensitivity is 12.74% for an energy window of 250–650 keV. For the mouse-sized phantom, the peak noise equivalent count rate (NECR) is 183 kcps at 2.07 MBq/cc whereas the peak true count rate is 320 kcps at 2.5 MBq/cc with a scatter fraction of 19%. The rat-sized phantom had a scatter fraction of 31%, with a peak NECR of 67 kcps at 0.23 MBq/cc and a peak true count rate of 186 kcps at 0.27 MBq/cc. The average activity concentration and percentage standard deviation (%STD) are 126.97 kBq/ml and 7%, respectively. The performance of the LabPET-8™ scanner was characterized based on the NEMA NU 04 - 2008 standards. The all in all performance demonstrates that the LabPET-8™ system is able to produce high quality and highly contrasted images in a reasonable time, and as such it is well suited for preclinical molecular imaging-based research.

CT-Based Attenuation Correction on the FLEX Triumph Preclinical PET/CT Scanner

Positron Emission Tomography (PET) has emerged as a valuable molecular imaging modality for quantitative measurement of biochemical processes in vivo in the clinical and preclinical imaging domains. However, PET imaging suffers from various physical degrading factors including photon attenuation, which can be corrected using CT-based attenuation correction (CTAC) on combined PET/CT scanners. The attenuation map is calculated by converting CT numbers derived from low-energy polyenergetic x-ray spectra to linear attenuation coefficients at 511 keV. Generation of accurate attenuation maps is crucial for reliable attenuation correction of PET data and hence is a prerequisite for accurate quantification of biological processes. In this study, we implemented the CTAC procedure on the FLEX Triumph™ preclinical PET/CT scanner and evaluated tube voltage dependence for different kVps (40, 50, 60, 70, and 80). The quantitative impact of both bilinear and quadratic based energy-mapping methods on linear attenuation coefficients, attenuation maps and corrected PET images was assessed at different CT tube voltages. Attenuation maps were calculated from CT images of a cylindrical polyethylene phantom containing different concentrations of K2HPO4 in water. Correlation coefficients and best regression fit equations were calculated for both methods. Phantom and rodent PET/CT images were used to assess improvements in image quality and quantitative accuracy. It was observed that the slopes of the bilinear calibration curves for CT numbers greater than 0 HU increase with increasing tube voltage. In addition, higher correlation coefficients were obtained for the quadratic compared to the bilinear energy-mapping method. Tube voltage of 70 kVp produced the smallest relative error and higher correlation coefficient compared to other tube voltages. For low concentrations of K2HPO4, the mean relative difference (in %) between theoretical and calculated attenuation coefficients when using bilinear and quadratic energy-mapping methods are 1.39 ± 1.9 and 1.33 ± 1.8, respectively. They are 2.78 ± 1.3 and 2.5 ± 1.3, respectively, for high concentrations of K2HPO4 . As expected, higher activity concentrations were obtained for PET after attenuation correction. The increased PET signal for mouse tissues ranged between 21 and 31% for bilinear energy-mapping and between 21.8 and 35% for quadratic energy-mapping, whereas these varied from 40 to 51% and from 41 to 56%, respectively, for rat tissues. For biological tissues having a high atomic number such as bone, the quadratic energy-mapping method produced slightly improved results compared to the bilinear energy-mapping method. Phantom and rodent PET studies were successfully corrected for photon attenuation using the developed CTAC procedure.

Evaluation of scatter fraction and count rate performance of two small-animal PET scanners using dedicated phantoms

Positron Emission Tomography (PET) image quality deteriorates as the object size increases owing to increased detection of scattered and random events. The characterization of the scatter component in small animal PET imaging has received little attention owing to the small scatter fraction when imaging rodents. The purpose of this study is first to design and fabricate a dedicated cone-shaped phantom which can be used for measurement of object size dependent SF and noise equivalent count (NEC) rates and second, to evaluate those parameters for two small animal PET scanners, namely the X-PET™ and LabPET™-8 as function of radial offset, object size and lower energy threshold. Both scanners were modeled as realistically as possible using GATE Monte Carlo simulation platform. The simulation models were validated against experimental measurements in terms of sensitivity, SF and noise equivalent count rate (NECR). The dedicated phantom was designed and fabricated in-house using high-density polyethylene. The optimized dimensions of the cone-shaped phantom are 150 mm (length), 20 mm (minimum diameter), 70 mm (maximum diameter) and taper angle of 9°.The relative difference between simulated and experimental results for the LabPET™-8 scanner varied between 0.66% and 10% except for few results where it was below 16%. Depending on the radial offset from the axial centre for a central field of view (3–6 cm diameter), the SF for the cone-shaped phantom varied from 26.3 to 18.2% (X-PET™); 34.4 to 26.9% (LabPET™-8), 18.6 to 13.1% (X-PET™); 19.1 to 17.0% (LabPET™-8); 10.1 to 7.6% (X-PET™) and 9.1 to 7.3% (LabPET™-8) for lower energy thresholds of 250, 350 and 425 keV, respectively. The SF increases as the radial offset decreases, lower energy threshold (LET) decreases and object size increases. The SF values are higher for the LabPET™-8 compared to the X-PET™. The NECR increases as the radial offset increases and object size decreases. Maximum NECR was obtained at a LET of 350 keV for LabPET™-8 whereas 250 keV for X-PET™. High correlation coefficients (R2) for SF and NECR were observed between the cone-shaped phantom and an equivalent volume cylindrical (EVC) phantom for the three considered axial fields-of-view. A single cone-shaped phantom enables the assessment of effects of three factors, namely radial offset, energy threshold and object size on small animal PET imaging characteristics like SF and NECR. Hence, a cone-shaped phantom may be more suited for evaluation of object size-dependent SF and NECR instead of using various discrete phantoms of different size.