Using 7T MRI within a longitudinal clinical trial in patients with depression
Poster No:
540
Submission Type:
Abstract Submission
Authors:
Jen Evans1, Carlos Zarate1
Institutions:
1NIMH/NIH, Bethesda, MD
First Author:
Co-Author:
Introduction:
Ultra high field MRI promises potential improvements in the clinical realm which have yet to be fully realized. Higher signal, as compared to 1.5 or 3T, enables the use of higher acceleration factors, which in turn means higher spatial or temporal resolution which can translate to improved diagnostic specificity. On the flip side, many implants aren't evaluated at 7T which potentially means greater exclusion of patients from trials without additional expertise for safety evaluation. There is also an increased likelihood of negative patient reaction to the increased sensations and claustrophobia, especially in conditions with pre-existing anxiety such as depression. Here we detail the design and implementation and practical outcome of using 7T imaging within a double blind placebo drug trial in unmedicated patients with treatment resistant depression.
Methods:
9 participants with treatment resistant depression nominally completed 7T MRI scans at: Baseline, Day1, Day 21; repeated for each arm of the study (drug or placebo (PBO) for a total of 6 scans. There are nominally 3 functional MRI (fMRI) tasks: Rest (eyes closed) Mixed Gambles Task (MGT) (Tom, 2007),Monetary Incentive Delay (MID) task . Magnetic resonance spectroscopy (MRS (An, 2022)) was successfully acquired in a reduced number of participants
fMRI data was acquired using echo-planar imaging (EPI) sequence (2 mm cubic resolution, iPat: 3, multi-band: 3, echo times (TE): 13.4, 30.51, 47,62, 64,73 ms, TR: 2 s, flip angle (FA) 50°, 32 channel head coil). A high resolution anatomical scan (MP2RAGE, 0.75 mm cubic resolution, TE: 1.99 ms, TR: 4.3 s, inversion time (TI) 1: 0.84 s, FA: 5°;TI2: 2.37 s, FA: 6°) was also collected.
Data were processed in AFNI (Cox 1996) using afni_proc with preprocessing that included slice-timing and motion correction, processing to reduce physiological noise (RetroTS), and smoothing to 3mm. The EPI data were affine co-registered with the anatomical scan and subsequently non-linearly aligned to MNI152 space with the 2009 asymmetric template. Motion censoring set at 0.3mm and less than 15% of the entire timeseries.
fMRI data was acquired using echo-planar imaging (EPI) sequence (2 mm cubic resolution, iPat: 3, multi-band: 3, echo times (TE): 13.4, 30.51, 47,62, 64,73 ms, TR: 2 s, flip angle (FA) 50°, 32 channel head coil). A high resolution anatomical scan (MP2RAGE, 0.75 mm cubic resolution, TE: 1.99 ms, TR: 4.3 s, inversion time (TI) 1: 0.84 s, FA: 5°;TI2: 2.37 s, FA: 6°) was also collected.
Data were processed in AFNI (Cox 1996) using afni_proc with preprocessing that included slice-timing and motion correction, processing to reduce physiological noise (RetroTS), and smoothing to 3mm. The EPI data were affine co-registered with the anatomical scan and subsequently non-linearly aligned to MNI152 space with the 2009 asymmetric template. Motion censoring set at 0.3mm and less than 15% of the entire timeseries.
Results:
Figure 1 summarizes the individual outcomes for all scans and task types.
a) Resting state functional connectivity, including scans with high motion where artificially increased connectivity is expected are included for illustrative purposes Blank entries are where a scan was not done because of technical issues.
b) Box and whisker plot of GABA, glutamine, glutamate, glutathione, NAA, NAAG for each scan (baseline, day 1, day 21) and for both study arms where placebo are the white boxes and drug are the blue boxes. Individual participant data is represented by a dot. Given the longer acquisition time and sensitivity of the technique to motion a considerable amount of data was lost.
c) Average (mean) reaction time values and response counts (N) for each category in the MID task and scan time point (baseline, day1, day 21) for each arm of the study (placebo, drug). in_miss: incentivized miss, in_win: incentivized win, nin_miss: non-incentivitzed miss, nin_win: non-incentivized win.
d) MGT response and reaction time matrix pairs for each participant (rows) and scan session. The first matrix shows the participant's choice (red: strongly accept, pink: weakly accept, light blue: weakly reject, dark blue: strongly reject, and the second illustrates the reaction time with warmer colours indicating faster times.
a) Resting state functional connectivity, including scans with high motion where artificially increased connectivity is expected are included for illustrative purposes Blank entries are where a scan was not done because of technical issues.
b) Box and whisker plot of GABA, glutamine, glutamate, glutathione, NAA, NAAG for each scan (baseline, day 1, day 21) and for both study arms where placebo are the white boxes and drug are the blue boxes. Individual participant data is represented by a dot. Given the longer acquisition time and sensitivity of the technique to motion a considerable amount of data was lost.
c) Average (mean) reaction time values and response counts (N) for each category in the MID task and scan time point (baseline, day1, day 21) for each arm of the study (placebo, drug). in_miss: incentivized miss, in_win: incentivized win, nin_miss: non-incentivitzed miss, nin_win: non-incentivized win.
d) MGT response and reaction time matrix pairs for each participant (rows) and scan session. The first matrix shows the participant's choice (red: strongly accept, pink: weakly accept, light blue: weakly reject, dark blue: strongly reject, and the second illustrates the reaction time with warmer colours indicating faster times.
·Study summary
Conclusions:
The clinical trial was powered to detect clinical behavioral changes, as MRI effect sizes are smaller, the trial was not adequately powered to provide drug specific information for these data. However, we can gain insight into how the deep imaging approach can aid smaller clinical studies to provide information on each individual to guide future study design.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Modeling and Analysis Methods:
Activation (eg. BOLD task-fMRI)
fMRI Connectivity and Network Modeling
Methods Development 2
Keywords:
FUNCTIONAL MRI
HIGH FIELD MR
Psychiatric Disorders
1|2Indicates the priority used for review
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Provide references using APA citation style.
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