New Brain PET Abstract

Authors: Dean F. Wong, Olivier Rousset, Arman Rahmim, Anil Kumar, Hiroto Kuwabara, Ayon Nandi, Weiguo Ye, Mohab Alexander, James Brasic , Yun Zhou, Betsy McCaul, Gary Wand

Comparison of IV Amphetamine Induced 11C Raclopride Displacement between the HRRT and GE Advance PET: Implications for High Resolution/Sensitivity on Dopamine Release Measures

Psychostimulant induced displaced on 11C Raclopride, often interpreted as a measure of intrasynaptic dopamine release, is increasingly used as a novel tool for examining brain physiology and pathophysiology. The availability of brain dedicated high performance PET scanners such as the HRRT (High Resolution Research Tomograph) provides the promise of further enhancing these measurements currently being routinely carried out on non-PET CT vintage PET’s such as the HR+, and the GE Advance. Here we test the hypothesis that because of the 2 – 3 fold increase resolution and increase sensitivity of the HRRT compared to the GE Advance, that there could be an improvement in the quantification of binding potentials and even so called dopamine release measures following psychostimulant challenge. Such documentation is needed to help determine if the technical challenges of the increased number of slices (207) compared to 32 for the GE Advance), and the increase reconstruction time (as much as 15 hours for a 30 frame acquisition (over 90 minutes) is justified.

Methods: Healthy volunteers (age range 22 – 25, 2 males and 2 females) underwent 2 PET scans with IV 11C Raclopride each on the HRRT. Each received their first PET scan following and IV bolus of saline and 2 hrs an 15 minutes later received their 2nd PET scan following 0.3mg/kg intravenous amphetamine given 5 minutes before. All PET scans for carried out for 90 minutes and were reconstructed at the highest resolution (span 3) using the current Siemens/CPS/CTI reconstruction software carried out on a 32 node IBM cluster. Studies were acquired in list mode and reconstructed into 32 frames. Time activity curves were generated using MRI directed regions of interest using specialized software (IDEA Kuwabara, et al). Two sets of regional analysis were obtained; one using striatal sub-divisions including anterior and posterior caudate putamen and ventral striatum for a total of 10 sub-divisions (5 on each hemisphere). Also analysis were carried out using larger striatal sub-divisions including caudate putamen, etc. (Ayon fill in). Binding potentials were obtained using the modified simplified reference tissue method (Ichise, et al) method. Dopamine release was calculated as the percent change of baseline to post amphetamine.

All HRRT BP’s and DAR’s were compared to those using the same regional analysis in each case to 4 age, gender and racially matched normal volunteers studied on the GE Advance. There were no significant differences in specific activities mass injected between the HRRT and GE Advance groups (verify these 32 frames are also employed in the GE Advance study group as well).

Results: First a pair T test was obtained for each of the matched subjects and then pulled binding potentials were also tested for each of the following measures, the baseline binding potential (with saline 5 minutes earlier), the post amphetamine BP, and the percent change in BP (DAR). On average there was a trend for the HRRT baseline and post amphetamine BP’s to be higher in the HRRT vs. the GE Advance for the regional analysis with10 sub-division. Similarly, one left and right was pooled and the same results occurred. For the pooled analysis as well as for the pair of T tests both baseline and post amphetamine and BP’s were higher for the HRRT. However, the HRRT dopamine release (percent change in BP following amphetamine challenge) was borderline significantly lower for the pooled analysis (B=0.01) and then the paired analysis for 1 subject the DAR for the GE Advance was significantly higher than the HRRT but not significantly different in the other three cases.

This preliminary data set suggests that the relatively robust effect of 11C Raclopride displacement by IV amphetamine challenge can be measured in the HRRT successfully. Indeed binding potentials as expected by partial volume effects are significantly higher with HRRT vs. the GE Advance. However, the percent change in BP (DAR) may in fact not be higher or may be paradoxedly (spelling) lower. One reason for this may be the increase resolution and better resolution recovery arithmetically results in a lower percent change in BP evaluated with the HRRT. Future studies will include not only expanding the sample size (which already shows significant differences) but applying these comparisons where contrast is even greater between baseline and post challenge studies such as those high and low specific activities 11C Raclopride. Also, partial volume formal partial volume corrections are being developed for the HRRT which will allow direct comparison between the GE Advance and the HRRT under these conditions.

Grant Support: RR017219, DA00412, AA10158, AA12839, NS38927