7T 1H-MRS of the anterior cingulate in patients with psychosis spectrum and mood symptoms
Eric Petersen1, Sanjeev Chawla2, Andrew Crow1, Theodore Satterthwaite1, Raquel E Gur1, Ruben C Gur1, Ravi Prakash Reddy Nanga2, Hari Hariharan2, Mark Elliott2, Ravinder Reddy2, and David R Roalf1

1Psychiatry, University of Pennsylvania, Philadelphia, PA, United States, 2Radiology, University of Pennsylvania, Philadelphia, PA, United States


Data from 12 typically developing (TD), 10 clinical high risk for psychosis (CHR), 6 psychosis (PSY) and 4 mood disorder (MD) participants who underwent 1HMRS at 7T. Short TE single voxel spectra (SVS) were obtained using a custom-modified PRESS sequence from the anterior cingulate gyrus. Data quality was high and tissue contribution within the acquisition voxel was similar across diagnostic groups. NAA, Creatine, Choline, GSH and Glu were significantly lower in PSY as compared to TD. CHR showed an intermediate pattern for all brain neurometabolites, except GSH, which was elevated as compared to TD. MD patients, in general, showed higher concentrations of NAA, Cho, GSH and Glu as compared to TD.


Precise etiological mechanisms for neurodevelopmental disorders such as psychosis and depression are yet to be established, but structural and functional magnetic resonance imaging document significant disruption of several neuronal processes.1 Here, we use 1HMRS, the primary method for measurement of in vivo neurometabolites, at 7T in a diverse clinical sample to better understand alterations in brain neurochemistry that may underline previously reported structural and functional dysfunction. Alterations in brain glutamate (Glu) are of particular interest given its ubiquity and involvement in high-order functions and neuronal metabolism. Changes in brain Glu appear related to the course of psychosis2 and depression.3 The presence and magnitude of Glu dysfunction depends on patient subgroup (chronic SZ, high risk individuals or first episode patients), brain region (cingulate vs. hippocampus) and medication status (never treated vs. chronically treated). 1HMRS findings in clinical high risk (CHR) are even less consistent.2,4 Meta-analytic results indicate that CHR individuals show elevated Glx only within the medial frontal cortex,2 whereas individual studies indicate lower,5-9 higher,8-14 and no difference15-17 in Glu (or Glu/Gln) in several brain regions. Thus, the role and time course of Glu changes, particularly early in the course, remain unclear. We aimed to compare patterns of brain metabolites in TD, CHR, PSY and MD using ultra-high field (7Tesla) 1HMRS.


7T Acquisition: Short TE single voxel spectra (SVS) were obtained using a previously employed18 custom-modified Point-RESolved Spectroscopy (PRESS) sequence19,20 with the following acquisition parameters: averages = 8 (water reference)/128 (water suppressed), TE = 23ms and TR = 3000ms. The SVS acquisition voxel was centered over the anterior cingulate gyrus. Acquisition time was 36 seconds for water reference spectrum and 6 min 48s for water suppressed spectrum. Water suppression is achieved with variable power RF pulses with optimized relaxation delays (VAPOR21) prior to SVS acquisition. Chemical shift artifacts for Glu and NAA are minimized by setting water acquisition spectrum excitation and refocusing pulses in resonance with the water peak at 4.7ppm, and for water suppressed spectrum, the excitation and refocusing pulses are set in resonance with the Glu peak at 2.35ppm. Pulse amplitudes are calibrated before measurement to reduce B1 inhomogeneity by acquiring six localized STimulated Echo Acquisition Mode (STEAM) water spectra at fixed reference voltage and varying flip angle from 0º to 180º with a step size of 30º. The sin3 dependence of the amplitudes is then used to estimate the reference voltage of the transmitter.22 Cramer Rao lower bounds and spectral analysis were performed using LC Model.


Data quality was high and tissue contribution within the acquisition voxel was similar across diagnostic groups. NAA, Creatine, Choline, GSH and Glu were significantly lower in PSY compared to TD (ps < 0.05). CHR showed intermediate levels between PSY and TD for all brain neurometabolites, except GSH, which was elevated compared to TD. MD patients, in general, showed significantly higher concentrations of NAA, Creatine, Choline GSH, Glx and Glu as compared to PSY; these levels were nominally higher than TD and CHR .


The current 1HMRS findings coupled with our recent results in glutamate chemical exchange saturation transfer (GluCEST)23 at 7T MRI, provide convergent evidence that brain Glu is lower in PSY as compared to TD and the CHR show an intermediate pattern. Moreover, the dissociation between PSY (lower) and MD (higher) in brain Glu provides insight into specific alterations that are likely related to the clinical course of each disorder. These data suggest that disruption of brain Glu, and other neurometabolites, may be valid markers of incipient and early stage dysfunction of psychopathology.


This project was supported by the National Institute of Mental Health MH089983, MH089924, MH087626, K01MH102609; NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation, the Dowshen Program for Neuroscience at the University of Pennsylvania; and the Life Span Brain Institute (LiBI)—a collaboration between the University of Pennsylvania School of Medicine and Children’s Hospital of Philadelphia.


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Figure 1. (A) Single voxel 1HMRS was acquired in the anterior cingulate cortex using a high-resolution MP2RAGE for localization. (B) An example spectra from one participant. Data were analyzed using LCModel.

Table 1. Participant characteristics and quality assurance data for the SVS sample

Figure 2. Metabolite concentrations from the anterior cingulate. Psychosis spectrum and Mood patients show divergent patterns.

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)