Danny F. Newport

Simultaneous PET-MRI: a new approach for functional and morphological imaging

Noninvasive imaging at the molecular level is an emerging field in biomedical research. This paper introduces a new technology synergizing two leading imaging methodologies: positron emission tomography (PET) and magnetic resonance imaging (MRI). Although the value of PET lies in its high-sensitivity tracking of biomarkers in vivo, it lacks resolving morphology. MRI has lower sensitivity, but produces high soft-tissue contrast and provides spectroscopic information and functional MRI (fMRI). We have developed a three-dimensional animal PET scanner that is built into a 7-T MRI. Our evaluations show that both modalities preserve their functionality, even when operated isochronously. With this combined imaging system, we simultaneously acquired functional and morphological PET-MRI data from living mice. PET-MRI provides a powerful tool for studying biology and pathology in preclinical research and has great potential for clinical applications. Combining fMRI and spectroscopy with PET paves the way for a new perspective in molecular imaging.

MicroPET II: design, development and initial performance of an improved microPET scanner for small-animal imaging

MicroPET II is a second-generation animal PET scanner designed for high-resolution imaging of small laboratory rodents. The system consists of 90 scintillation detector modules arranged in three contiguous axial rings with a ring diameter of 16.0 cm and an axial length of 4.9 cm. Each detector module consists of a 14 x 14 array of lutetium oxyorthosilicate (LSO) crystals coupled to a multi-channel photomultiplier tube (MC-PMT) through a coherent optical fibre bundle. Each LSO crystal element measures 0.975 mm x 0.975 mm in cross section by 12.5 mm in length. A barium sulphate reflector material was used between LSO elements leading to a detector pitch of 1.15 mm in both axial and transverse directions. Fused optical fibre bundles were made from 90 microm diameter glass fibres with a numerical aperture of 0.56. Interstitial extramural absorber was added between the fibres to reduce optical cross talk. A charge-division readout circuit was implemented on printed circuit boards to decode the 196 crystals in each array from the outputs of the 64 anode signals of the MC-PMT. Electronics from Concorde Microsystems Inc. (Knoxville, TN) were used for signal amplification, digitization, event qualification, coincidence processing and data capture. Coincidence data were passed to a host PC that recorded events in list mode. Following acquisition, data were sorted into sinograms and reconstructed using Fourier rebinning and filtered hackprojection algorithms. Basic evaluation of the system has been completed. The absolute sensitivity of the microPET II scanner was 2.26% at the centre of the field of view (CFOV) for an energy window of 250-750 keV and a timing window of 10 ns. The intrinsic spatial resolution of the detectors in the system averaged 1.21 mm full width at half maximum (FWHM) when measured with a 22Na point source 0.5 mm in diameter. Reconstructed image resolution ranged from 0.83 mm FWHM at the CFOV to 1.47 mm FWHM in the radial direction, 1.17 mm FWHM in the tangential direction and 1.42 mm FWHM in the axial direction at 1 cm offset from the CFOV. These values represent highly significant improvements over our earlier microPET scanner (approximately fourfold sensitivity increase and 25-35% improvement in linear spatial resolution under equivalent operating conditions) and are expected to be further improved when the system is fully optimized.

Performance Evaluation of the Inveon Dedicated PET Preclinical Tomograph Based on the NEMA NU-4 Standards

The Inveon dedicated PET (DPET) scanner is the latest generation of preclinical PET systems devoted to high-resolution and high-sensitivity murine model imaging. In this study, we report on its performance based on the National Electrical Manufacturers Association (NEMA) NU-4 standards. Methods: The Inveon DPET consists of 64 lutetium oxyorthosilicate block detectors arranged in 4 contiguous rings, with a 16.1-cm ring diameter and a 12.7-cm axial length. Each detector block consists of a 20 × 20 lutetium oxyorthosilicate crystal array of 1.51 × 1.51 × 10.0 mm elements. The scintillation light is transmitted to position-sensitive photomultiplier tubes via optical light guides. Energy resolution, spatial resolution, sensitivity, scatter fraction, and counting-rate performance were evaluated. The NEMA NU-4 image–quality phantom and a healthy mouse injected with 18F-FDG and 18F− were scanned to evaluate the imaging capability of the Inveon DPET. Results: The energy resolution at 511 keV was 14.6% on average for the entire system. In-plane radial and tangential resolutions reconstructed with Fourier rebinning and filtered backprojection algorithms were below 1.8-mm full width at half maximum (FWHM) at the center of the field of view. The radial and tangential resolution remained under 2.0 mm, and the axial resolution remained under 2.5-mm FWHM within the central 4-cm diameter of the field of view. The absolute sensitivity of the system was 9.3% for an energy window of 250–625 keV and a timing window of 3.432 ns. At a 350- to 625-keV energy window and a 3.432-ns timing window, the peak noise equivalent counting rate was 1,670 kcps at 130 MBq for the mouse-sized phantom and 590 kcps at 110 MBq for the rat-sized phantom. The scatter fractions at the same acquisition settings were 7.8% and 17.2% for the mouse- and rat-sized phantoms, respectively. The mouse image-quality phantom results demonstrate that for typical mouse acquisitions, the image quality correlates well with the measured performance parameters in terms of image uniformity, recovery coefficients, attenuation, and scatter corrections. Conclusion: The Inveon system, compared with previous generations of preclinical PET systems from the same manufacturer, shows significantly improved energy resolution, sensitivity, axial coverage, and counting-rate capabilities. The performance of the Inveon is suitable for successful murine model imaging experiments.

Optimization and performance evaluation of the microPET II scanner for in vivo small-animal imaging

MicroPET II is a newly developed PET (positron emission tomography) scanner designed for high-resolution imaging of small animals. It consists of 17,640 LSO crystals each measuring 0.975 x 0.975 x 12.5 mm3, which are arranged in 42 contiguous rings, with 420 crystals per ring. The scanner has an axial field of view (FOV) of 4.9 cm and a transaxial FOV of 8.5 cm. The purpose of this study was to carefully evaluate the performance of the system and to optimize settings for in vivo mouse and rat imaging studies. The volumetric image resolution was found to depend strongly on the reconstruction algorithm employed and averaged 1.1 mm (1.4 microl) across the central 3 cm of the transaxial FOV when using a statistical reconstruction algorithm with accurate system modelling. The sensitivity, scatter fraction and noise-equivalent count (NEC) rate for mouse- and rat-sized phantoms were measured for different energy and timing windows. Mouse imaging was optimized with a wide open energy window (150-750 keV) and a 10 ns timing window, leading to a sensitivity of 3.3% at the centre of the FOV and a peak NEC rate of 235,000 cps for a total activity of 80 MBq (2.2 mCi) in the phantom. Rat imaging, due to the higher scatter fraction, and the activity that lies outside of the field of view, achieved a maximum NEC rate of 24,600 cps for a total activity of 80 MBq (2.2 mCi) in the phantom, with an energy window of 250-750 keV and a 6 ns timing window. The sensitivity at the centre of the FOV for these settings is 2.1%. This work demonstrates that different scanner settings are necessary to optimize the NEC count rate for different-sized animals and different injected doses. Finally, phantom and in vivo animal studies are presented to demonstrate the capabilities of microPET II for small-animal imaging studies.

Performance evaluation of the microPET-Focus - F120

microPETreg-Focus-F120 is the latest model of dedicated small animal PET scanners from CTI-Concorde Microsystems LLC, (Knoxville, TN). This scanner, based on the geometry of the microPET-R4, takes advantage of several detector modifications to the coincidence processing electronics that improve the image resolution, sensitivity, and counting rate performance as compared to the predecessor models. This work evaluates the performance of the Focus-F120 system and shows its improvement over the earlier models. In particular, the spatial resolution is shown to improve from 2.32 to 1.69 mm at 5 mm radial distance and the peak absolute sensitivity increases from 4.1% to 7.1% compared to the microPET-R4. The counting rate capability, expressed in noise equivalent counting rate (NEC-1R), was shown to peak at over 800 kcps at 88 MBq for both systems using a mouse phantom. For this small phantom, the NECR counting rate is limited by the data transmission bandwidth between the scanner and the acquisition console. The rat-like phantom showed peak NEC-1R value at 300 kcps at 140 MBq. Evaluation of image quality and quantitation accuracy was also performed using specially designed phantoms and animal experiments

Cardiac PET imaging in mice with simultaneous cardiac and respiratory gating

Gating firmware and software were developed for the microPET II small animal scanner. The measured cardiac and respiratory signals were collected and converted to TTL gating signals by a Biopac MP150 data acquisition system and sent to microPET II through two BNC connectors on the front panel. During acquisition, the coincidence monitor takes the average of the last eight gate input cycles and inserts this into the list mode data stream on the falling edge of the gating pulse. This value is then used to determine the current time interval of the next gate cycle when the list mode data are sorted into sinograms. The gating firmware and software were validated by an experiment using a rotating point source. Mouse heart (18F-FDG) and bone (18F(-)) imaging was performed with simultaneous cardiac and respiratory gating. It was clearly demonstrated that the contractile function of the mouse heart can be studied by cardiac-gated imaging with microPET II. The left ventricular volumes at different times of the cardiac cycle were measured and the ejection fraction was calculated. In the bone scan, no detectable movement caused by heart contraction was observed. Respiratory motion was more subtle with virtually no motion for more than 75% of the respiratory cycle. The motion of the mouse heart and bones in the thorax caused by respiration was less than 1 mm. It appears with the current resolution of PET, and the small fraction of the respiratory cycle in which motion occurs, that respiratory gating is probably not necessary for most mouse cardiac studies.

Performance Evaluation of the microPET®—FOCUS-F120

microPETreg-Focus-F120 is the latest model of dedicated small animal PET scanners from CTI-Concorde Microsystems LLC, (Knoxville, TN). This scanner, based on the geometry of the microPET-R4, takes advantage of several detector modifications to the coincidence processing electronics that improve the image resolution, sensitivity, and counting rate performance as compared to the predecessor models. This work evaluates the performance of the Focus-F120 system and shows its improvement over the earlier models. In particular, the spatial resolution is shown to improve from 2.32 to 1.69 mm at 5 mm radial distance and the peak absolute sensitivity increases from 4.1% to 7.1% compared to the microPET-R4. The counting rate capability, expressed in noise equivalent counting rate (NEC-1R), was shown to peak at over 800 kcps at 88 MBq for both systems using a mouse phantom. For this small phantom, the NECR counting rate is limited by the data transmission bandwidth between the scanner and the acquisition console. The rat-like phantom showed peak NEC-1R value at 300 kcps at 140 MBq. Evaluation of image quality and quantitation accuracy was also performed using specially designed phantoms and animal experiments

Fast iterative image reconstruction of 3D PET data

For count-limited PET imaging protocols, two different approaches to reducing statistical noise are volume, or 3D, imaging to increase sensitivity, and statistical reconstruction methods to reduce noise propagation. These two approaches have largely been developed independently, likely due to the perception of the large computational demands of iterative 3D reconstruction methods. The authors present results of combining the sensitivity of 3D PET imaging with the noise reduction and reconstruction speed of 2D iterative image reconstruction methods. This combination is made possible by using the recently-developed Fourier rebinning technique (FORE), which accurately and noiselessly rebins 3D PET data into a 2D data set. The resulting 2D sinograms are then reconstructed independently by the ordered-subset EM (OSEM) iterative reconstruction method, although any other 2D reconstruction algorithm could be used. The authors demonstrate significant improvements in image quality for whole-body 3D PET scans by using the FORE+OSEM approach compared with the standard 3D Reprojection (3DRP) algorithm. In addition, the FORE+OSEM approach involves only 2D reconstruction and it therefore requires considerably less reconstruction time than the 3DRP algorithm, or any fully 3D statistical reconstruction algorithm.

SPMD cluster-based parallel 3D OSEM

This study empirically compares two approaches to parallel 3D OSEM that differ as to whether calculations are assigned to nodes by projection number or by transaxial plane number. For projection space decomposition (PSD), the forward projection is completely parallel, but backprojection requires a slow image synchronization. For image space decomposition (ISD), the communication associated with forward projection can be overlapped with calculation, and the communication associated with backprojection is more efficient. To compare these methods, an implementation of 3D OSEM for three PET scanners is developed that runs on an experimental, 9-node, 18-processor cluster computer. For selected benchmarks, both methods exhibit speedups in excess of 8 for 9 nodes, and comparable performance for the tested range of cluster sizes.

Evaluation of transmission methodology and attenuation correction for the microPET Focus 220 animal scanner

An accurate, low noise estimate of photon attenuation in the subject is required for quantitative microPET studies of molecular tracer distributions in vivo. In this work, several transmission-based measurement techniques were compared, including coincidence mode with and without rod windowing, singles mode with two different energy sources ((68)Ge and (57)Co), and postinjection transmission scanning. In addition, the effectiveness of transmission segmentation and the propagation of transmission bias and noise into the emission images were examined. The (57)Co singles measurements provided the most accurate attenuation coefficients and superior signal-to-noise ratio, while (68)Ge singles measurements were degraded due to scattering from the object. Scatter correction of (68)Ge transmission data improved the accuracy for a 10 cm phantom but over-corrected for a mouse phantom. (57)Co scanning also resulted in low bias and noise in postinjection transmission scans for emission activities up to 20 MBq. Segmentation worked most reliably for transmission data acquired with (57)Co but the minor improvement in accuracy of attenuation coefficients and signal-to-noise may not justify its use, particularly for small subjects. We conclude that (57)Co singles transmission scanning is the most suitable method for measured attenuation correction on the microPET Focus 220 animal scanner.