Sudeepti Southekal

Small animal simultaneous PET/MRI: initial experiences in a 9.4 T microMRI

We developed a non-magnetic positron-emission tomography (PET) device based on the rat conscious animal PET that operates in a small-animal magnetic resonance imaging (MRI) scanner, thereby enabling us to carry out simultaneous PET/MRI studies. The PET detector comprises 12 detector blocks, each being a 4 × 8 array of lutetium oxyorthosilicate crystals (2.22 × 2.22 × 5 mm(3)) coupled to a matching non-magnetic avalanche photodiode array. The detector blocks, housed in a plastic case, form a 38 mm inner diameter ring with an 18 mm axial extent. Custom-built MRI coils fit inside the positron-emission tomography (PET) device, operating in transceiver mode. The PET insert is integrated with a Bruker 9.4 T 210 mm clear-bore diameter MRI scanner. We acquired simultaneous PET/MR images of phantoms, of in vivo rat brain, and of cardiac-gated mouse heart using [(11)C]raclopride and 2-deoxy-2-[(18)F]fluoro-D-glucose PET radiotracers. There was minor interference between the PET electronics and the MRI during simultaneous operation, and small effects on the signal-to-noise ratio in the MR images in the presence of the PET, but no noticeable visual artifacts. Gradient echo and high-duty-cycle spin echo radio frequency (RF) pulses resulted in a 7% and a 28% loss in PET counts, respectively, due to high PET counts during the RF pulses that had to be gated out. The calibration of the activity concentration of PET data during MR pulsing is reproducible within less than 6%. Our initial results demonstrate the feasibility of performing simultaneous PET and MRI studies in adult rats and mice using the same PET insert in a small-bore 9.4 T MRI.

Digital Coincidence Processing for the RatCAP Conscious Rat Brain PET Scanner

The RatCAP has been designed and constructed to image the awake rat brain. In order to maximize system performance, offline digital coincidence data processing algorithms including offset delay correction and prompt and delayed coincidence detection have been developed and validated. With offset delay correction using a singular value decomposition (SVD) technique, overall time resolution was improved from 32.6 to 17.6 ns FWHM. The experimental results confirm that the ratio of prompts to randoms was improved because a narrower timing window could be used. 18F-fluoride rat bone scan data were reconstructed using our fully 3-D ML-EM algorithm with a highly accurate detector response model created from Monte Carlo simulation.

A Simultaneous PET/MRI scanner based on RatCAP in small animals

The ability to acquire high resolution anatomical data as well as quantitative functional information in vivo is becoming an increasingly important factor in the diagnosis of disease. Simultaneous acquisition of PET and MRI data would provide essentially perfect co-registration between the two images which is particularly important for tissues whose position and shape can change between sequential scans. RatCAP is a complete 3D tomograph that is designed to image the brain of an awake rat. A special MRI coil composed of 2 saddle elements working in quadrature mode was mounted on a Delrin cylinder specifically designed to fit inside the RatCAP but allowing the rats head to be placed inside as well. Simultaneous PET/MRI images of the rat brain have been acquired in a 4 T MRI scanner using the RatCAP detector, with minimal effect on MRI images.

Results from prototype II of the BNL simultaneous PET-MRI dedicated breast scanner

At Brookhaven National Laboratory, we are developing a simultaneous PET-MRI breast imaging system. A prototype II version of the PET system has been constructed. This device consists of 24 detector blocks where each block consists of a 4 × 8 array of 2.2 × 2.2 × 15 mm3 LYSO crystal directly coupled to a 4 × 8 non-magnetic APD array. The scanner has an inner diameter of 100mm and an axial extent of 18mm. Resolution measurements were carried out for the prototype system to evaluate the depth of interaction effects. Average resolution less than 2mm FWHM was maintained throughout the field of view. The prototype PET system was operated unshielded inside the RF coil of the Aurora 1.5 T dedicated breast MRI machine. Artifact free MRI images with good SNR were obtained.

Statistical 3D image reconstruction for the RatCAP PET tomograph using a physically accurate, Monte Carlo based system matrix

This work describes a fully 3D statistical image reconstruction for the RatCAP (Rat Conscious Animal PET) using a Monte Carlo based system matrix. The RatCAP consists of 12 Iutetium oxyorthosilicate (LSO)-avalanche photodiode (APD) detector blocks arranged in a ring of 41.2 mm diameter. Due to the small ring diameter and low number of total lines of response (LORs), the size of a complete system matrix is small in comparison to a typical small animal scanner. This allows incorporation of an accurate, RatCAP-specific physical model with the inclusion of crystal penetration, Compton scattering in both rats brain and detector, attenuation and the realistic event positioning errors. The trade off between the statistical accuracy and the matrix computational time as it relates to the accuracy of image reconstruction will also be discussed.

Improved Regional Activity Quantitation in Nuclear Medicine Using a New Approach to Correct for Tissue Partial Volume and Spillover Effects

We have developed a neσw method of compensating for effects of partial volume and spillover in dual-modality imaging. The approach requires segmentation of just a few tissue types within a small volume-of-interest (VOI) surrounding a lesion; the algorithm estimates simultaneously, from projection data, the activity concentration within each segmented tissue inside the VOI. Measured emission projections were fitted to the sum of resolution-blurred projections of each such tissue, scaled by its unknown activity concentration, plus a global background contribution obtained by reprojection through the reconstructed image volume outside the VOI. The method was evaluated using multiple-pinhole μSPECT data simulated for the MOBY mouse phantom containing two spherical lung tumors and one liver tumor, as well as using multiple-bead phantom data acquired on μSPECT and μCT scanners. Each VOI in the simulation study was 4.8 mm (12 voxels) cubed and, depending on location, contained up to four tissues (tumor, liver, heart, lung) with different values of relative 99mTc concentration. All tumor activity estimates achieved <; 3% bias after ~ 15 ordered-subsets expectation maximization (OSEM) iterations (×10 subsets), with better than 8% precision (≤ 25% greater than the Cramer-Rao lowσer bound). The projection-based fitting approach also outperformed three standardized uptake value (SUV)-like metrics, one of which was corrected for count spillover. In the bead phantom experiment, the mean ± standard deviation of the bias of VOI estimates of bead concentration were 0.9±9.5%, comparable to those of a perturbation geometric transfer matrix (pGTM) approach (-5.4±8.6%); however, VOI estimates were more stable with increasing iteration number than pGTM estimates, even in the presence of substantial axial misalignment between μCT and μSPECT image volumes.

Next Generation of Real Time Data Acquisition, Calibration and Control System for the RatCAP Scanner

RatCAP (Rat Conscious Animal PET) is miniature positron emission tomography scanner intended for neurological and behavioral study of small awake animal. The RatCAP system comprises of three distinct modules: rigid-flex technology based Printed Circuit Board (PCB) which houses the detector components and front end Application Specific Integrated Circuit (ASIC), Time to Digital Converter and Signal Processing module (TSPM) which receives and processes ASIC signals and transmits processed data over two Giga bit fiber optic links to PCI based data acquisition and control PCB (PACRAT). TSPM-3 is redesigned from previous versions to accommodate second generation front end ASIC and possible future two scanner expansion. ASICs programmable features are exploited using new additional TSPM electronics for scanner calibration and test. Designs of these three modules and corresponding firmware and software upgrades are complete. Results from fully integrated next generation RatCAP on the bench are presented.

The design and performance of the 2 nd -generation RatCAP awake rat brain PET system

The original prototype RatCAP PET scanner for conscious rat brain imaging has undergone a redesign of most major components resulting in a distinct 2nd -generation instrument. While maintaining the same field of view (38 mm diameter, 18 mm axial) and similar overall architecture, the new design allows for longer crystals to provide approximately a factor of 2 increase in coincidence sensitivity with a minimal increase in size and weight. The front-end electronics ASIC has been significantly upgraded, featuring programmable amplifier gains, lower noise, differential digital communication (LVDS), and selectable energy window modes and analog outputs for debugging. The rigid-flex circuit interconnecting the 12 blocks is now more mechanically stable and draws less power which minimizes APD gain shifts. The downstream time-stamp and signal processing module (TSPM) has been modified to be compatible with the new ASICs and further includes DACs for threshold control, twice as many inputs, and a doubling of data throughput capacity. The user interface and data acquisition software is in Labview, and data processing and image reconstruction software is being further developed to maximize imaging accuracy for quantitative neuroscience studies. Finally, a new mechanical support system has been constructed to improve the rats tolerance of the scanner. Preliminary data indicate improved energy and time resolution compared to the 1st-generation prototype and first images of the rat brain while conscious have been obtained.

The RatCAP conscious small animal PET tomography

The RatCAP is a small, head mounted PET tomograph designed and built to image the brain of an awake rat. It allows PET imaging studies to be carried out on laboratory rats without the use of anesthesia, which severely suppresses brain functions and affects many of the neurological activities that one would like to study using PET. The tomograph consists of a 4 cm diameter ring containing 12 block detectors, each of which is comprised of a 4 times 8 array of 2.2 times 2.2 times 5 mm3 LSO crystals read out with a matching APD array. The APDs are read out using a custom designed ASIC and VME readout system. We have successfully performed a system integration test with a partially instrumented tomograph ring. We present the recent progress towards a fully integrated system

A simultaneous PET/MRI breast scanner based on the RatCAP

We propose to develop a high resolution scanner for simultaneous PET and MRI breast imaging that is capable of providing highly sensitive and specific breast cancer examinations. The addition of high resolution positron emission tomography capability to an existing dedicated MRI system will give a device in which each of the modalities contributes its strengths to compensate for the weaknesses of the other. In this combined modality scanner, we have the anatomical information from the MRI to compensate for the somewhat poorer resolution in PET, and we have the predictive power of PET in identifying the type of lesion to overcome the high false positive rate of MRI. This device is based on the technical approach used in the RatCAP scanner with the innovation of detecting coincident events in separate rings of the RatCAP scanner. We are presenting the design and GATE simulations of the full breast imaging system and preliminary PET and MRI results from the prototype system.