S. Krishnamoorthy

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.

A prototype CZT-based PET scanner for high resolution mouse brain imaging

One of the most challenging and potentially rewarding research applications of PET is imaging of the mouse brain. Although very high spatial resolution is required (< ~1 mm), there is a much wider variety of transgenic models in mouse compared to the rat. The solid state material CdZnTe (CZT) has long held promise for high resolution PET. Compared to scintillators, its limitations in time resolution and sensitivity can in some ways be compensated by its extremely high spatial and energy resolution, its compact geometry, and by sophisticated data processing techniques. Using such techniques, a time resolution of ~10 ns has been demonstrated for ~1 cm thick CZT pixel detectors, and this may be sufficient for mouse studies. The depth-of-interaction capability and high energy resolution can improve sensitivity by allowing detectors to be placed very close to the subject and by enabling both reconstruction of detector-scattered events and rejection of object-scattered events. A full-ring prototype scanner has been designed to demonstrate feasibility of the concept, consisting of 6 CZT pixel detectors in a novel geometry. The design of the detector, front-end electronics components, and data acquisition are presented, along with performance characterization of the custom-manufactured CZT detectors.

The RatCAP front-end ASIC

We report on the design and characterization of a new ASIC for the RatCAP, a head-mounted miniature PET scanner intended for neurological and behavioral studies of an awake rat. The ASIC is composed of 32 channels, each consisting of a charge sensitive preamplifier, a 5-bit programmable gain in the pole-zero network, a 3rd order bipolar semi-Gaussian shaper (peaking time of 80 ns), and a timing and energy discriminator. The energy discriminator in each channel is used to arm the zero-crossing discriminator and can be programmed to use either a low energy threshold or an energy gating window. A 32-to-1 serial encoder is embedded to multiplex into a single output the timing information and channel address of every event. Finally, LVDS I/O were integrated on chip to minimize the digital noise on the read-out PCB. The ASIC was realized in the TSMC 0.18 mum technology, has a size of 3.3 mm times 4.5 mm and a power consumption of 117 mW. The gate length of the N-channel MOSFET input device of the charge sensitive preamplifier was increased to minimize 1/f noise. This led to a factor 1.5 improvement of the ENC with respect to the first version of the ASIC. An ENC of 650 e-rms was measured with the APD biased at the input. In order to predict the achievable timing resolution, a model was derived to estimate the photon noise contribution to the timing resolution. Measurements were performed to validate the model, which agreed within 12%. The coincidence timing resolution between two typical LSO-APD-ASIC modules was measured using a 68Ge source. Applying a threshold at 420 keV, a timing resolution of 6.7 ns FWHM was measured. An energy resolution of 18.7% FWHM at 511 keV was measured for a 68Ge source.

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.

PET imaging of thin objects: measuring the effects of positron range and partial-volume averaging in the leaf of Nicotiana tabacum

INTRODUCTION PET imaging in plants is receiving increased interest as a new strategy to measure plant responses to environmental stimuli and as a tool for phenotyping genetically engineered plants. PET imaging in plants, however, poses new challenges. In particular, the leaves of most plants are so thin that a large fraction of positrons emitted from PET isotopes ((18)F, (11)C, (13)N) escape while even state-of-the-art PET cameras have significant partial-volume errors for such thin objects. Although these limitations are acknowledged by researchers, little data have been published on them. METHODS Here we measured the magnitude and distribution of escaping positrons from the leaf of Nicotiana tabacum for the radionuclides (18)F, (11)C and (13)N using a commercial small-animal PET scanner. Imaging results were compared to radionuclide concentrations measured from dissection and counting and to a Monte Carlo simulation using GATE (Geant4 Application for Tomographic Emission). RESULTS Simulated and experimentally determined escape fractions were consistent. The fractions of positrons (mean±S.D.) escaping the leaf parenchyma were measured to be 59±1.1%, 64±4.4% and 67±1.9% for (18)F, (11)C and (13)N, respectively. Escape fractions were lower in thicker leaf areas like the midrib. Partial-volume averaging underestimated activity concentrations in the leaf blade by a factor of 10 to 15. CONCLUSIONS The foregoing effects combine to yield PET images whose contrast does not reflect the actual activity concentrations. These errors can be largely corrected by integrating activity along the PET axis perpendicular to the leaf surface, including detection of escaped positrons, and calculating concentration using a measured leaf thickness.

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.

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.

The data acquisition system of the RatCAP conscious small animal PET tomograph

We describe the progress made in data acquisition system for the RatCAP tomograph. RatCAP is a small, head-mounted PET detector designed to image the brain of an awake rat. At its core, the tomograph consists of a number of LSO crystals read out with an array of APDs. The data are collected through a custom-designed ASIC, along with a custom VME board. We describe the design, implementation, and performance of a versatile VME-based data acquisition system which will be used to read out the VME board, as well as other off-the-shelf data acquisition electronics

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.