Comparing IV amphetamine-induced 11C raclopride displacement between HRRT and GE advance PET: Implications for high resolution/sensitivity on dopmaine release measures

Dean Foster Wong, Olivier Rousset, Arman Rahmim, Anil Kumar, Hiroto Kuwabara, Ayon Nandi, Yun Zhou, Betsy McCaul, Gary S Wand

Research output: Contribution to journalArticle

Abstract

Background and aims: Psychostimulant-induced displacement of [11C]Raclopride (RAC), often interpreted as a measure of intrasynaptic dopamine release, is increasingly used as a novel tool for examining brain physiology and pathophysiology. Brain dedicated high-performance PET scanners such as the HRRT (High Resolution Research Tomograph, Siemens CPS/CTI) promise to enhance measurements carried out on non-PET CTs/PET-only like the Siemens HR+ and the GE Advance (GEA). Here we test the hypothesis that the 2?3 fold increase in spatial resolution and sensitivity of the HRRT over the GEA offers an improvement in the quantification of binding potentials (BPs) and dopamine release (DAR) measures following psychostimulant challenge. Such documentation may justify the technical challenges of increased slice number (207 vs 35 for the GEA) and reconstruction time (>15 hours for a 90-min, 30-frame acquisition). Methods: Healthy volunteers (age range 22 ? 25, 4 males, 2 females) underwent two 90-minute PET scans each with IV RAC on the HRRT: 1) Scan 1 following an IV bolus of saline, 2) Scan 2 (2.25 hrs later) following 0.3mg/kg IV amphetamine 5 minutes before tracer injection. Studies were reconstructed using the highest resolution (span 3), current Siemens/CPS/CTI reconstruction software, and a 32-node IBM cluster. Images were acquired in list mode and reconstructed to 30 frames. Time-activity curves were generated in the following regions of interest: anterior/posterior caudate and putamen, and ventral striatum. BPs were obtained using the modified simplified reference tissue method (Ichise, et al, 2002). DAR was calculated as the percent change of baseline to post-amphetamine BPs. All measures obtained on the HRRT were compared to 6 matched (for age, sex and race) subjects who completed amphetamine challenges on the GEA. Results: In each matched pair, we calculated percent increase in BP for HRRT vs. GEA. There was a significant increase in both baseline (range 9-27%, mean 16.0 + 6.7% SD) and post-amphetamine BPs (range 6-35%, mean 18.3 + 10.8% SD) across all regions; however, these BP increases between HRRT and GEA were not significantly different between saline and amphetamine scans. Specifically, BPs for the HRRT were higher than GEA BPs in anterior and posterior putamen and anterior caudate (p0.1). There was also no significant change in DAR between the two scanners (p>0.1). Conclusion: These preliminary data sets suggest that the HRRT can successfully measure the relatively robust effect of RAC displacement by IV amphetamine challenge. BPs, as expected by partial volume (PV) effects, were significantly higher with HRRT vs. the GEA. Although the contrast is lower in the post-amphetamine scans, the change in BP between the two scanners was not significantly different between the two scans. Future studies will not only expand the sample size but also apply these comparisons where contrast is even greater between baseline and post-challenge studies, i.e high and low specific activity RAC. Also, formal PV corrections are being developed for the HRRT as they have for the GEA to allow direct comparison between the GEA and the HRRT.

Original languageEnglish (US)
JournalJournal of Cerebral Blood Flow and Metabolism
Volume27
Issue numberSUPPL. 1
StatePublished - Nov 13 2007

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Raclopride
Amphetamine
Dopamine
Putamen
Brain
Documentation
Positron-Emission Tomography
Sample Size
Healthy Volunteers
Software
Injections
Research

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

Cite this

@article{72aaaf4425304a3da3892e035f755210,
title = "Comparing IV amphetamine-induced 11C raclopride displacement between HRRT and GE advance PET: Implications for high resolution/sensitivity on dopmaine release measures",
abstract = "Background and aims: Psychostimulant-induced displacement of [11C]Raclopride (RAC), often interpreted as a measure of intrasynaptic dopamine release, is increasingly used as a novel tool for examining brain physiology and pathophysiology. Brain dedicated high-performance PET scanners such as the HRRT (High Resolution Research Tomograph, Siemens CPS/CTI) promise to enhance measurements carried out on non-PET CTs/PET-only like the Siemens HR+ and the GE Advance (GEA). Here we test the hypothesis that the 2?3 fold increase in spatial resolution and sensitivity of the HRRT over the GEA offers an improvement in the quantification of binding potentials (BPs) and dopamine release (DAR) measures following psychostimulant challenge. Such documentation may justify the technical challenges of increased slice number (207 vs 35 for the GEA) and reconstruction time (>15 hours for a 90-min, 30-frame acquisition). Methods: Healthy volunteers (age range 22 ? 25, 4 males, 2 females) underwent two 90-minute PET scans each with IV RAC on the HRRT: 1) Scan 1 following an IV bolus of saline, 2) Scan 2 (2.25 hrs later) following 0.3mg/kg IV amphetamine 5 minutes before tracer injection. Studies were reconstructed using the highest resolution (span 3), current Siemens/CPS/CTI reconstruction software, and a 32-node IBM cluster. Images were acquired in list mode and reconstructed to 30 frames. Time-activity curves were generated in the following regions of interest: anterior/posterior caudate and putamen, and ventral striatum. BPs were obtained using the modified simplified reference tissue method (Ichise, et al, 2002). DAR was calculated as the percent change of baseline to post-amphetamine BPs. All measures obtained on the HRRT were compared to 6 matched (for age, sex and race) subjects who completed amphetamine challenges on the GEA. Results: In each matched pair, we calculated percent increase in BP for HRRT vs. GEA. There was a significant increase in both baseline (range 9-27{\%}, mean 16.0 + 6.7{\%} SD) and post-amphetamine BPs (range 6-35{\%}, mean 18.3 + 10.8{\%} SD) across all regions; however, these BP increases between HRRT and GEA were not significantly different between saline and amphetamine scans. Specifically, BPs for the HRRT were higher than GEA BPs in anterior and posterior putamen and anterior caudate (p0.1). There was also no significant change in DAR between the two scanners (p>0.1). Conclusion: These preliminary data sets suggest that the HRRT can successfully measure the relatively robust effect of RAC displacement by IV amphetamine challenge. BPs, as expected by partial volume (PV) effects, were significantly higher with HRRT vs. the GEA. Although the contrast is lower in the post-amphetamine scans, the change in BP between the two scanners was not significantly different between the two scans. Future studies will not only expand the sample size but also apply these comparisons where contrast is even greater between baseline and post-challenge studies, i.e high and low specific activity RAC. Also, formal PV corrections are being developed for the HRRT as they have for the GEA to allow direct comparison between the GEA and the HRRT.",
author = "Wong, {Dean Foster} and Olivier Rousset and Arman Rahmim and Anil Kumar and Hiroto Kuwabara and Ayon Nandi and Yun Zhou and Betsy McCaul and Wand, {Gary S}",
year = "2007",
month = "11",
day = "13",
language = "English (US)",
volume = "27",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "Nature Publishing Group",
number = "SUPPL. 1",

}

TY - JOUR

T1 - Comparing IV amphetamine-induced 11C raclopride displacement between HRRT and GE advance PET

T2 - Implications for high resolution/sensitivity on dopmaine release measures

AU - Wong, Dean Foster

AU - Rousset, Olivier

AU - Rahmim, Arman

AU - Kumar, Anil

AU - Kuwabara, Hiroto

AU - Nandi, Ayon

AU - Zhou, Yun

AU - McCaul, Betsy

AU - Wand, Gary S

PY - 2007/11/13

Y1 - 2007/11/13

N2 - Background and aims: Psychostimulant-induced displacement of [11C]Raclopride (RAC), often interpreted as a measure of intrasynaptic dopamine release, is increasingly used as a novel tool for examining brain physiology and pathophysiology. Brain dedicated high-performance PET scanners such as the HRRT (High Resolution Research Tomograph, Siemens CPS/CTI) promise to enhance measurements carried out on non-PET CTs/PET-only like the Siemens HR+ and the GE Advance (GEA). Here we test the hypothesis that the 2?3 fold increase in spatial resolution and sensitivity of the HRRT over the GEA offers an improvement in the quantification of binding potentials (BPs) and dopamine release (DAR) measures following psychostimulant challenge. Such documentation may justify the technical challenges of increased slice number (207 vs 35 for the GEA) and reconstruction time (>15 hours for a 90-min, 30-frame acquisition). Methods: Healthy volunteers (age range 22 ? 25, 4 males, 2 females) underwent two 90-minute PET scans each with IV RAC on the HRRT: 1) Scan 1 following an IV bolus of saline, 2) Scan 2 (2.25 hrs later) following 0.3mg/kg IV amphetamine 5 minutes before tracer injection. Studies were reconstructed using the highest resolution (span 3), current Siemens/CPS/CTI reconstruction software, and a 32-node IBM cluster. Images were acquired in list mode and reconstructed to 30 frames. Time-activity curves were generated in the following regions of interest: anterior/posterior caudate and putamen, and ventral striatum. BPs were obtained using the modified simplified reference tissue method (Ichise, et al, 2002). DAR was calculated as the percent change of baseline to post-amphetamine BPs. All measures obtained on the HRRT were compared to 6 matched (for age, sex and race) subjects who completed amphetamine challenges on the GEA. Results: In each matched pair, we calculated percent increase in BP for HRRT vs. GEA. There was a significant increase in both baseline (range 9-27%, mean 16.0 + 6.7% SD) and post-amphetamine BPs (range 6-35%, mean 18.3 + 10.8% SD) across all regions; however, these BP increases between HRRT and GEA were not significantly different between saline and amphetamine scans. Specifically, BPs for the HRRT were higher than GEA BPs in anterior and posterior putamen and anterior caudate (p0.1). There was also no significant change in DAR between the two scanners (p>0.1). Conclusion: These preliminary data sets suggest that the HRRT can successfully measure the relatively robust effect of RAC displacement by IV amphetamine challenge. BPs, as expected by partial volume (PV) effects, were significantly higher with HRRT vs. the GEA. Although the contrast is lower in the post-amphetamine scans, the change in BP between the two scanners was not significantly different between the two scans. Future studies will not only expand the sample size but also apply these comparisons where contrast is even greater between baseline and post-challenge studies, i.e high and low specific activity RAC. Also, formal PV corrections are being developed for the HRRT as they have for the GEA to allow direct comparison between the GEA and the HRRT.

AB - Background and aims: Psychostimulant-induced displacement of [11C]Raclopride (RAC), often interpreted as a measure of intrasynaptic dopamine release, is increasingly used as a novel tool for examining brain physiology and pathophysiology. Brain dedicated high-performance PET scanners such as the HRRT (High Resolution Research Tomograph, Siemens CPS/CTI) promise to enhance measurements carried out on non-PET CTs/PET-only like the Siemens HR+ and the GE Advance (GEA). Here we test the hypothesis that the 2?3 fold increase in spatial resolution and sensitivity of the HRRT over the GEA offers an improvement in the quantification of binding potentials (BPs) and dopamine release (DAR) measures following psychostimulant challenge. Such documentation may justify the technical challenges of increased slice number (207 vs 35 for the GEA) and reconstruction time (>15 hours for a 90-min, 30-frame acquisition). Methods: Healthy volunteers (age range 22 ? 25, 4 males, 2 females) underwent two 90-minute PET scans each with IV RAC on the HRRT: 1) Scan 1 following an IV bolus of saline, 2) Scan 2 (2.25 hrs later) following 0.3mg/kg IV amphetamine 5 minutes before tracer injection. Studies were reconstructed using the highest resolution (span 3), current Siemens/CPS/CTI reconstruction software, and a 32-node IBM cluster. Images were acquired in list mode and reconstructed to 30 frames. Time-activity curves were generated in the following regions of interest: anterior/posterior caudate and putamen, and ventral striatum. BPs were obtained using the modified simplified reference tissue method (Ichise, et al, 2002). DAR was calculated as the percent change of baseline to post-amphetamine BPs. All measures obtained on the HRRT were compared to 6 matched (for age, sex and race) subjects who completed amphetamine challenges on the GEA. Results: In each matched pair, we calculated percent increase in BP for HRRT vs. GEA. There was a significant increase in both baseline (range 9-27%, mean 16.0 + 6.7% SD) and post-amphetamine BPs (range 6-35%, mean 18.3 + 10.8% SD) across all regions; however, these BP increases between HRRT and GEA were not significantly different between saline and amphetamine scans. Specifically, BPs for the HRRT were higher than GEA BPs in anterior and posterior putamen and anterior caudate (p0.1). There was also no significant change in DAR between the two scanners (p>0.1). Conclusion: These preliminary data sets suggest that the HRRT can successfully measure the relatively robust effect of RAC displacement by IV amphetamine challenge. BPs, as expected by partial volume (PV) effects, were significantly higher with HRRT vs. the GEA. Although the contrast is lower in the post-amphetamine scans, the change in BP between the two scanners was not significantly different between the two scans. Future studies will not only expand the sample size but also apply these comparisons where contrast is even greater between baseline and post-challenge studies, i.e high and low specific activity RAC. Also, formal PV corrections are being developed for the HRRT as they have for the GEA to allow direct comparison between the GEA and the HRRT.

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