David Schlyer

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.

Fast Uptake and Long-Lasting Binding of Methamphetamine in the Human Brain: Comparison with Cocaine

Methamphetamine is one of the most addictive and neurotoxic drugs of abuse. It produces large elevations in extracellular dopamine in the striatum through vesicular release and inhibition of the dopamine transporter. In the U.S. abuse prevalence varies by ethnicity with very low abuse among African Americans relative to Caucasians, differentiating it from cocaine where abuse rates are similar for the two groups. Here we report the first comparison of methamphetamine and cocaine pharmacokinetics in brain between Caucasians and African Americans along with the measurement of dopamine transporter availability in striatum. Methamphetamines uptake in brain was fast (peak uptake at 9 min) with accumulation in cortical and subcortical brain regions and in white matter. Its clearance from brain was slow (except for white matter which did not clear over the 90 min) and there was no difference in pharmacokinetics between Caucasians and African Americans. In contrast cocaines brain uptake and clearance were both fast, distribution was predominantly in striatum and uptake was higher in African Americans. Among individuals, those with the highest striatal (but not cerebellar) methamphetamine accumulation also had the highest dopamine transporter availability suggesting a relationship between METH exposure and DAT availability. Methamphetamines fast brain uptake is consistent with its highly reinforcing effects, its slow clearance with its long-lasting behavioral effects and its widespread distribution with its neurotoxic effects that affect not only striatal but also cortical and white matter regions. The absence of significant differences between Caucasians and African Americans suggests that variables other than methamphetamine pharmacokinetics and bioavailability account for the lower abuse prevalence in African Americans.

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.

System performance simulations of the RatCAP awake rat brain scanner

The capability to create high quality images from data acquired by the Rat Conscious Animal PET tomograph (RatCAP) has been evaluated using modified versions of the PET Monte Carlo code Simulation System for Emission Tomography (SimSET). The proposed tomograph consists of lutetium oxyorthosilicate (LSO) crystals arranged in 12 4 /spl times/ 8 blocks. The effects of the RatCAPs small ring diameter (/spl sim/40 mm) and its block detector geometry on image quality for small animal studies have been investigated. Since the field of view will be almost as large as the ring diameter, radial elongation artifacts due to parallax error are expected to degrade the spatial resolution and thus the image quality at the edge of the field of view. In addition to Monte Carlo simulations, some preliminary results of experimentally acquired images in both two-dimensional (2-D) and 3-D modes are presented.

A prototype Anger-type detector for PET using LSO and large-area APDs

Spatial resolution in positron emission tomography has steadily improved over the years, but remains substantially worse than in other imaging modalities, currently at ~2 mm for the most popular commercial tomographs. This is a serious limitation particularly for imaging mice, which have great potential in preclinical PET research because of their compatibility with genetic manipulation. A novel gamma-ray detector design which can achieve high resolution and sensitivity and also facilitates depth of interaction measurement has been developed. It consists of a slab of LSO and arrays of large-area avalanche photodiodes (APDs) on both sides which are used in a light sharing (Anger-type) scheme. A fully instrumented prototype detector has been constructed comprising a 10 mm thick LSO crystal and an array of 7 square APDs (each 11 mmtimes11 mm in area) optically coupled to each side. Preliminary measurements carried with a collimated source mounted on a computer controlled X-Y translational stage demonstrate a resolution of ~2.5 mm FWHM between the center of two APDs. Optimization of electronics noise factors is critical to improving detector performance

An intracerebral beta microprobe for studying radiotracer kinetics in freely moving animals

A scintillation microprobe has been developed to directly measure the positron decay activity from radiotracers in live animals. The probe consists of a small LSO crystal coupled to an optical fiber which is read out with a photomultiplier tube operated in a single photon counting mode. Positron conversions in the crystal are detected with high efficiency due to the excellent stopping power and high light output of LSO, and allows for the direct determination of the positron emitter concentration in a localized region of tissue. The probe can be used in the study of chemical kinetics and the development of new radiotracers in awake and freely moving animals.

Noninvasive high-resolution detection of the arterial and venous input function through a PET wrist scanner

In order to assess the kinetics of radiotracer accumulation in tissue, the amount of radioactivity in the blood must be quantitatively measured as an input function to the kinetic model. Due to safety and comfort issues with invasive determination of the input function, a non-invasive method for arterial measurement of blood radioactivity is investigated using a wrist scanner. A prototype consisting of two detector pairs of LSO and APD detector arrays is used to obtain planar images of an anatomically correct wrist phantom. The spatial resolution and sensitivity of the prototype is determined. The results showed the detector was able to discriminate the arterial and venous flows from each other when using planar coincidence images.

Quantitation Of The Human Basal Ganglia with Positron Emission Tomography

The accurate measurement of the concentration of a radioisotope in small structures with PET requires a correction for quantitation loss due to the partial volume effect and the effect of scattered radiation. To evaluate errors associated with measures in the human basal ganglia (BG) we have built a unilateral model of the BG that we have inserted in a 20 cm cylinder. The recovery coefficient (RC = measured activity/true activity) for our BG phantom has been measured on a CTI tomograph (model 931-08/12) with different background concentrations (contrast) and at different axial locations in the gantry. The BG was visualized on 4 or 5 slices depending on its position in the gantry and on the contrast used. The RC was 0.75 with no background (contrast equal to 1.0). Increasing the relative radioactivity concentration in the background increased the RC from 0.75 to 2.00 when the contrast was {minus}0.7 (BG < Background). The RC was also affected by the size and the shape of the region of interest (ROI) used (RC from 0.75 to 0.67 with ROI size from 0.12 to 1.41 cm{sup 2}). These results show that accurate RC correction depends not only on the volume of the structure but also on its contrast with its surroundings as well as on the selection of the ROI. They also demonstrate that the higher the contrast the more sensitive to axial positioning PET measurements in the BG are. These data provide us with some information about the variability of PET measurements in small structure like the BG and we have proposed some strategies to improve the reproducibility. 18 refs., 3 figs., 5 tabs.