An advanced technique for rapid magnetic resonance proton spectroscopic imaging (1H-MRSI) will be employed in a drug challenge study in healthy volunteers to spatially map and measure acute changes in the brain chemicals GABA, glutamate and glutamine after administration of a drug. Three condition will be tested in a double-blind fashion, i)depressant, ii)stimulant, iii)placebo. It is hypothesized that unique and reproducible spatial and directional metabolic response patterns will be observed, unique to each condition within the brain.
Proton magnetic resonance spectroscopy (1H MRS) is a powerful tool for assessing neurochemistry non-invasively in vivo. However, the primary shortcoming in most studies is the lack of spatial coverage afforded by the typical single-voxel design. Limits on participant tolerance and financial resources restrict single-voxel studies to an examination of one or two carefully chosen voxels per scan, thus inadequately addressing the question of focal vs. global pathophysiology. A secondary shortcoming is that most studies report on either GABA or glutamate-glutamine (Glu-Gln) due to the technically demanding spectral-editing techniques that must be implemented in order to resolve and quantify those metabolites with any accuracy. 1H MRS imaging (MRSI) can partially overcome these limitations by providing a global picture of brain chemistry rather than just the focal snapshot afforded by the single-voxel design. However, the scan time necessary for collecting enough data for adequate spatial resolution and signal-to-noise, particularly if also using specialized spectral-editing techniques, is still too lengthy. We recently developed a method that combines Spectroscopic Imaging with the MEGAPRESS-based difference-editing acquisition for optimal GABA detection as well as for optimal detection of Glu and Gln. This MEGACSI sequence will permit us to obtain the maximum amount of neurochemical information in a clinically sound scan time, while using the current state-of-the-art MRS editing methods for optimal detection of GABA, Glu, and Gln.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
7
Alprazolam, gel-capsule, 1mg, single-dose, 1-day
Dextroamphetamine, gel-capsule, 20mg, single-dose, 1-day
Placebo, gel-capsule, single-dose, 1-day
McLean Imaging Center, McLean Hospital
Belmont, Massachusetts, United States
Left Thalamus: Percent Change in GABA Levels After an Acute Drug Challenge
The primary goal of this study is to assess the efficacy of an advanced spectroscopic imaging protocol in detecting changes in the levels of brain GABA in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100\*(later timepoint - earlier timepoint) / earlier timepoint
Time frame: from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)
Left Basal-Ganglia: Percent Change in GABA Levels After an Acute Drug Challenge
The primary goal of this study is to assess the efficacy of an advanced spectroscopic imaging protocol in detecting changes in the levels of brain GABA in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100\*(later timepoint - earlier timepoint) / earlier timepoint
Time frame: from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)
Left Temporal: Percent Change in GABA Levels After an Acute Drug Challenge
The primary goal of this study is to assess the efficacy of an advanced spectroscopic imaging protocol in detecting changes in the levels of brain GABA in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100\*(later timepoint - earlier timepoint) / earlier timepoint
Time frame: from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)
Parieto-Occipital: Percent Change in GABA Levels After an Acute Drug Challenge
The primary goal of this study is to assess the efficacy of an advanced spectroscopic imaging protocol in detecting changes in the levels of brain GABA in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100\*(later timepoint - earlier timepoint) / earlier timepoint
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Time frame: from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)
Right Thalamus: Percent Change in GABA Levels After an Acute Drug Challenge
The primary goal of this study is to assess the efficacy of an advanced spectroscopic imaging protocol in detecting changes in the levels of brain GABA in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100\*(later timepoint - earlier timepoint) / earlier timepoint
Time frame: from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)
Right Basal-Ganglia: Percent Change in GABA Levels After an Acute Drug Challenge
The primary goal of this study is to assess the efficacy of an advanced spectroscopic imaging protocol in detecting changes in the levels of brain GABA in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100\*(later timepoint - earlier timepoint) / earlier timepoint
Time frame: from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)
Right Temporal: Percent Change in GABA Levels After an Acute Drug Challenge
The primary goal of this study is to assess the efficacy of an advanced spectroscopic imaging protocol in detecting changes in the levels of brain GABA in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100\*(later timepoint - earlier timepoint) / earlier timepoint
Time frame: from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)