S. Maramraju

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.

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.

Electromagnetic Interactions in a Shielded PET/MRI System for Simultaneous PET/MR Imaging in 9.4 T: Evaluation and Results

We previously integrated a magnetic resonance-(MR-) compatible small-animal positron emission tomograph (PET) in a Bruker 9.4 T microMRI system to obtain simultaneous PET/MR images of a rats brain and of a gated mouse-heart. To minimize electromagnetic interactions in our MR-PET system, viz., the effect of radiofrequency (RF) pulses on the PET, we tested our modular front-end PET electronics with various shield configurations, including a solid aluminum shield and one of thin segmented layers of copper. We noted that the gradient-echo RF pulses did not affect PET data when the PET electronics were shielded with either the aluminum- or the segmented copper-shields. However, there were spurious counts in the PET data resulting from high-intensity fast spin-echo RF pulses. Compared to the unshielded condition, they were attenuated effectively by the aluminum shield (~97%) and the segmented copper shield (~90%). We noted a decline in the noise rates as a function of increasing PET energy-discriminator threshold. In addition, we observed a notable decrease in the signal-to-noise ratio in spin-echo MR images with the segmented copper shields in place; however, this did not substantially degrade the quality of the MR images we obtained. Our results demonstrate that by surrounding a compact PET scanner with thin layers of segmented copper shields and integrating it inside a 9.4 T MR system, we can mitigate the impact of the RF on PET, while acquiring good-quality MR images.

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.

Preliminary Studies of a Simultaneous PET/MRI Scanner Based on the RatCAP Small Animal Tomograph

We are developing a scanner that will allow the simultaneous acquisition of high resolution anatomical data using magnetic resonance imaging (MRI) and quantitative physiological data using positron emission tomography (PET). The approach is based on the technology used for the RatCAP conscious small animal PET tomograph which utilizes block detectors consisting of pixelated arrays of LSO crystals read out with matching arrays of avalanche photodiodes (APDs) and a custom-designed ASIC. A version of the detector is being developed that will be constructed out of all nonmagnetic materials that can be operated inside the MRI field. We have demonstrated that the PET detector works inside the MRI field using 511 keV gamma rays, and have obtained MRI images with various detector components that show minimal distortion in the MRI image. We plan to improve on the image quality in the future using completely nonmagnetic components and by tuning the MRI pulse sequences. The combined result will be a highly compact, low mass PET scanner that can operate inside an MRI magnet without distorting the MRI image, and can be retrofitted into existing MRI instruments.

An MRI-compatible PET insert for whole body studies in rodents at high functional and anatomical resolution

The feasibility of performing high-resolution PET and high-field MRI simultaneously in rodents has been previously demonstrated in small-scale systems capable of imaging the rat brain and mouse. We are nearing completion of a larger scale PET system which will accommodate the whole rat and perform at 9.4 T with <2 mm PET resolution. The PET insert has inner/outer diameters of 13.5/20.6 cm, compact enough to fit within the gradient set of a Varian large-bore 9.4T MRI system while accommodating on the inside a commercial Insight birdcage coil for the rat. The resulting volume capable of simultaneous PET/MRI imaging is 7 cm in diameter and 5 cm axially. The 96 PET detectors are arranged in 4 rings of modular detector blocks, each with an array of 2 × 2 × 14 mm LYSO crystal coupled to a Hamamatsu APD array and read out by the RatCAP ASIC. Data acquisition is divided into 4 sectors, each handled by a local FPGA which communicates via Ethernet to the host PC. Offline data processing software is being developed to bin coincidences and determine physical corrections. Image reconstruction follows a listmode OSEM approach. The design of all hardware components is complete and prototypes of each have been fabricated. System integration is underway and initial performance of the system will be presented.

An MR compatible PET scanner based on RatCAP for small animal imaging at 9.4 T

Combining PET and MRI technology in order to obtain simultaneous functional information with anatomical precision in vivo is of tremendous interest in the field of molecular imaging. PET/MRI imaging provides perfect anatomical and temporal coregistration of PET and MR images, along with clear delineation of tissue boundaries. An MR compatible PET scanner based on Rat Conscious Animal PET (RatCAP) is developed for simultaneous acquisition of PET/MRI images of the rat brain in a 9.4 T microMRI scanner. The PET tomograph is housed in a segmented G10/copper case constructed with a copper coating thickness of 5 microns, to minimize the eddy currents and provide better RF shielding. Special RF coils were designed to fit inside the PET tomograph. A custom made G10 tube assembly was constructed for accurate positioning of the rat bed, RF coil and RatCAP. Simultaneous PET/MRI images of a rat striatum phantom were acquired in the 9.4 T microMRI with minimal interference between PET electronics and MRI. PET compatible RF quadrature coils are being constructed which are capable of providing rat brain images with improved SNR. The preliminary results show the feasibility of performing PET/fMRI studies of rat brain and exploring the possibility of acquiring simultaneous PET/MRI whole body mouse images in the 9.4 T.

Performance Enhancement of the RatCAP Awake Rat Brain PET System

The first full prototype of the RatCAP PET system, designed to image the brain of a rat while conscious, has been completed. Initial results demonstrated excellent spatial resolution, 1.8 mm FWHM with filtered backprojection and <1.5 mm FWHM with a Monte Carlo based MLEM method. However, noise equivalent countrate studies indicated the need for better timing to mitigate the effect of randoms. Thus, the front-end ASIC has been redesigned to minimize time walk, an accurate coincidence time alignment method has been implemented, and a variance reduction technique for the randoms is being developed. To maximize the quantitative capabilities required for neuroscience, corrections are being implemented and validated for positron range and photon noncollinearity, scatter (including outside the field of view), attenuation, randoms, and detector efficiency (deadtime is negligible). In addition, a more robust and compact PCI-based optical data acquisition system has been built to replace the original VME-based system while retaining the linux-based data processing and image reconstruction codes. Finally, a number of new animal imaging experiments have been carried out to demonstrate the performance of the RatCAP in real imaging situations, including an F-18 fluoride bone scan, a C-11 raclopride scan, and a dynamic C-11 methamphetamine scan.

A LSO Beta Microprobe for Measuring Input Functions for Quantitative Small Animal PET

A miniature scintillation beta microprobe has been developed to measure the input function in live rodents for use in longitudinal, quantitative PET studies. The probe consists of a small lutetium oxyorthosilicate (LSO) crystal measuring typically 0.3-0.6 mm diameter times 0.5-2 mm in length that is used to directly detect positrons in the blood or tissue. The probe has a sensitivity of 10-40 Hz/muCi/cc and is primarily sensitive to short range positrons emitted by labeled radiotracers in the blood. The sensitivity to gamma-ray background can be minimized using a variable threshold in the readout to discriminate between positrons and gammas. The probe was implanted in one of the tail veins of a Sprague-Dawley rat and the input function was measured for the injection of 0.8 mCi of FDG in the other tail vein. The probe exhibits a fast time response that is able to quickly and accurately measure the concentration of 18F circulating in the bloodstream. Additional tests were also carried out to study the probes sensitivity to gamma ray background.