About

Muhammad G. Saleh, PhD, is an Assistant Professor of Radiology at the University of Pennsylvania's Perelman School of Medicine and a Senior Principal Scientist in the Radiology Research Group at the Children’s Hospital of Philadelphia. His research focuses on neurometabolic differentiation, brain chemistry, and neuroimaging techniques such as magnetic resonance spectroscopy. Dr. Saleh has contributed to understanding brain metabolism in various conditions, including hypersomnolence, HIV, autism, and the effects of aging on brain metabolites. His work involves advanced neuroimaging methods to investigate neural excitation-inhibition balance, brain susceptibility, and neurometabolite changes during early infancy, with a goal to improve diagnostic and therapeutic strategies in neurological and psychiatric disorders.

Research topics

• Computer Science
• Nuclear medicine
• Medicine
• Artificial Intelligence
• Physics
• Nuclear magnetic resonance
• Internal medicine
• Radiology

Selected publications

• Myo-inositol elevation as an in vivo marker of reactive gliosis in pediatric Friedreich ataxia: evidence from HERMES-edited MR spectroscopy

  NeuroImage Clinical · 2026-01-01

  articleOpen access

  • First in vivo measurement of glutathione (GSH) and γ-aminobutyric acid (GABA + ) in pediatric Friedreich ataxia (FRDA) using HERMES-edited MRS. • No significant group-level differences in GSH or GABA+, despite strong rationale for oxidative and inhibitory dysfunction in FRDA. • Significant reduction in the tNAA/mI ratio in FRDA, driven by elevated myo-inositol rather than reduced tNAA (tNAA not significant, p = 0.150). • Myo-inositol elevations are significant in both motor cortices (Bonferroni-corrected), with a trend in cerebellum (pcorr = 0.054). Friedreich ataxia (FRDA) is a rare neurodegenerative disorder caused by frataxin deficiency and is characterized by mitochondrial dysfunction, oxidative stress, and progressive motor dysfunction. Most in vivo MRS work in FRDA has focused on the cerebellum, brainstem/pons, and spinal cord, consistently reporting abnormalities in the neuronal marker N-acetylaspartate (NAA) and the glial metabolite myo-inositol (mI). To our knowledge, the NAA/mI ratio in the primary motor cortex has not been reported in FRDA, particularly in pediatric cohorts. Additionally, in vivo edited MRS measurements of the inhibitory neurotransmitter γ-aminobutyric acid (GABA+ (GABA + macromolecular contributions)) in FRDA have not yet been reported and GSH has been examined only rarely in FRDA and, to our knowledge, has not been studied in the motor cortex in either adult or pediatric cohorts. To assess GSH, GABA+, NAA, and mI across cerebellum and motor cortices in pediatric FRDA using HERMES-edited MRS. We acquired HERMES MRS data from 16 children with FRDA and 15 age-matched controls. Tissue-corrected metabolite estimates were obtained using LCModel and voxel-based tissue segmentation. Linear mixed models (LMMs) were used to evaluate group and region effects, with subject as a random effect. LMMs revealed no significant group differences in tissue-corrected GSH or GABA + . In contrast, the tNAA/mI ratio was significantly reduced in FRDA (p < 0.001), driven by elevated mI (p < 0.001), while tNAA did not differ between groups (p = 0.150). ROI-specific analyses showed higher mI in FRDA in both motor cortices after Bonferroni correction, with a non-significant trend in cerebellum (pcorr = 0.054). These findings support a model of early reactive gliosis in pediatric FRDA, indexed by elevated mI and occurring without statistically significant neuronal loss, (acknowledging that significant reductions in tNAA may require larger samples to resolve), and extend prior cerebellar-focused work to the primary motor cortex. While GSH and GABA + did not differ between groups, the observed mI elevations highlight myo-inositol as a practical in vivo biomarker of astrocytic activation and a candidate marker for disease progression in FRDA. Longitudinal studies are needed to confirm its sensitivity to clinical trajectory and therapeutic response.

  PublisherDOI

• Myo-Inositol Elevation as an In Vivo Marker of Reactive Gliosis in Pediatric Friedreich Ataxia: Evidence from HERMES-Edited MR Spectroscopy

  SSRN Electronic Journal · 2025-01-01

  preprintOpen access
  PublisherDOI

• Proton Magnetic Resonance Spectroscopy for Pediatric Neuroimaging: Key Concepts for Practice

  Seminars in Ultrasound CT and MRI · 2025-04-01

  reviewOpen accessSenior author
  PublisherOA PDFDOI

• Spectrally Edited Glutamate Associated with Autism Traits

  Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2025-09-16

  article1st authorCorresponding

  Motivation: This study examines the relationship between Autism Spectrum Disorder (ASD) severity, measured by the Social Responsiveness Scale (SRS), and brain levels of excitatory glutamate and inhibitory GABA. Goal(s): Explore whether these chemicals are associated with the severity of ASD. Approach: Using the MEGA-PRESS sequence, we measured Glu and GABA levels in the temporal cortices of typically developing children and children with ASD. We later correlated Glu and GABA levels (separately) with the SRS scores. Results: The ASD group negatively correlated with SRS scores, suggesting Glu as a potential correlate of ASD severity ratings. Impact: Brain glutamate plays a role in language comprehension, which differs in ASD. This study found that MRS-derived glutamate levels are associated with SRS scores, implying that glutamate is a potential marker for communication deficits in ASD.

  PublisherDOI

• Age-related Changes in Brain Metabolites in Early Infancy: A Cross-Sectional Analysis of the First HBCD Data Release

  Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2025-09-16

  article

  Motivation: Neurometabolite concentration changes in the first few months after birth have not been studied in a large cohort. Goal(s): To assess early neurochemical development in a large cohort of 0-8 month-old infants by analyzing all available data in the first MRS data release of the HEALthy Brain and Child Development study ("HBCD"). Approach: Linear combination modeling will quantify 14 neurometabolites in this cross-sectional population. Statistical analyses will test for significant relationships between metabolite levels, birth-age and gestational age. Impact: Identifying changes in neurochemical levels in the first few months after birth in a large cohort for the first time will help deepen our understanding of the various roles these chemicals play in neurodevelopment.

  PublisherDOI

• GABA (gamma-aminobutyric acid) levels in dorsal anterior cingulate cortex are negatively associated with food motivation in a pediatric sample

  Scientific Reports · 2024-10-22 · 1 citations

  articleOpen access

  Food motivation varies between individuals, affecting body weight and risk for eating disorders. Prior neuroimaging studies in youth and adults have revealed functional and structural alterations in the anterior cingulate cortex [ACC] in those with obesity and disordered eating but have not investigated their neurochemical underpinnings. In a sample of 37 children aged 4 to 13 years old, we used Magnetic Resonance Spectroscopy [MRS] to assess levels of γ-aminobutyric acid [GABA] - the major inhibitory neurotransmitter in the human brain - quantified relative to creatine in a 27-ml voxel including the dorsal ACC. We used the CEBQ to assess trait food motivation. In analyses adjusting for age, lower GABA+/Cr levels in the dorsal ACC were associated with higher trait enjoyment of food. Higher enjoyment of food scores were in turn associated with higher energy intake during an ad libitum test meal and during a postprandial task assessing intake in the absence of hunger, and higher body weight. Our results indicate a role for GABA function in the dorsal ACC in determining individual variation in food motivation in children.

  PublisherOA PDFDOI

• Edited MRS of the Infant Brain on 28 Scanners

  Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2024-11-26

  article

  Motivation: The Healthy Brain and Child Development (HBCD) study is a longitudinal, multi-vendor, multi-site study of early brain development, which will enroll ~7,500 infants. HBCD includes MRS within the imaging protocol. Goal(s): The goal of this abstract is to present HBCD MRS pilot data, and identify any vendor and site differences in MRS data quality and measured metabolite concentrations. Approach: HBCD pilot MRS data were successfully acquired on 28 scanners, and analyzed using Osprey 2.5.0, to examine vendor and site differences. Results: ANOVA results show minimal vendor and site differences which is encouraging for such a large-scale multi-site, multi-vendor study. Impact: HBCD is an NIH-funded multicenter study of brain development across the first decade of life. It is the largest ever study to incorporate MRS. In this abstract, we present in vivo data demonstrating MRS performance across vendor and site.

  PublisherDOI

• Neurochemical Predictors of Generalized Learning Induced by Brain Stimulation and Training

  Journal of Neuroscience · 2024-03-26 · 7 citations

  articleOpen access

  Methods of cognitive enhancement for humans are most impactful when they generalize across tasks. However, the extent to which such "transfer" is possible via interventions is widely debated. In addition, the contribution of excitatory and inhibitory processes to such transfer is unknown. Here, in a large-scale neuroimaging individual differences study with humans (both sexes), we paired multitasking training and noninvasive brain stimulation (transcranial direct current stimulation, tDCS) over multiple days and assessed performance across a range of paradigms. In addition, we varied tDCS dosage (1.0 and 2.0 mA), electrode montage (left or right prefrontal regions), and training task (multitasking vs a control task) and assessed GABA and glutamate concentrations via ultrahigh field 7T magnetic resonance spectroscopy. Generalized benefits were observed in spatial attention, indexed by visual search performance, when multitasking training was combined with 1.0 mA stimulation targeting either the left or right prefrontal cortex (PFC). This transfer effect persisted for ∼30 d post intervention. Critically, the transferred benefits associated with right prefrontal tDCS were predicted by pretraining concentrations of glutamate in the PFC. Thus, the effects of this combined stimulation and training protocol appear to be linked predominantly to excitatory brain processes.

  PublisherOA PDFDOI

• Simultaneous Measurements of GABA, Glx and GSH in the Thalamus in Patients with Mild Traumatic Brain Injury: A Preliminary Study

  Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2024-08-14

  article

  In this study, we report the preliminary results of simultaneous measurements of GABA, Glx (glutamate + glutamine), and GSH in the thalamus using HERMES in the mTBI patients. HERMES was acquired in the thalamus for patients in acute, subacute, and chronic stages, and control subjects as reference using optimized acquisition and processing. Metabolite fitting were performed in Gannet with spectral alignment. The results demonstrate that HERMES can maintain the spectral and fitting quality in the mTBI patients versus the control subjects. Differences in the metabolite levels warrant accruing a larger number of patients for a more definite evaluation.

  PublisherDOI

• Edited MRS of Glutamate

  Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2024-11-26

  article1st authorCorresponding

  Motivation: Spectral editing methods are widely used to measure &amp;gamma;-aminobutyric acid (GABA), which also co-edits glutamate (Glu) at 2.34 ppm in the sum spectrum (sum=ON+OFF). However, the co-detection of Glu at 2.34 ppm has not been assessed. Goal(s): We demonstrate the co-editing of Glu without glutamine using HERMES of GABA and glutathione. Approach: Simulations of HERMES and 1D J-resolved of Glu, glutamine, and GABA, followed by in vivo experiments on 137 participants. Results: Simulations and in vivo experiments show a Glu-edited signal without overlapping glutamine and GABA signals from both methods. In vivo quantification of Glu show that the two methods are significantly correlated. Impact: Our study demonstrates a purer measurement of Glu using HERMES without needing a separate acquisition. HERMES provides an opportunity to study Glu/GABA/glutathione concurrently to understand their relationships under homeostasis or drug interventions that might affect the glutamatergic/GABAergic/antioxidant systems.

  PublisherDOI

Recent grants

• Neurometabolic profile of tobacco smoking in HIV-infected Individuals

  NIH · $747k · 2021–2026

• Neurometabolic profile of tobacco smoking in HIV-infected Individuals

  NIH · $347k · 2021–2023

Frequent coauthors

• Richard A.E. Edden

  121 shared

• Mark E. Mikkelsen

  Weill Cornell Medicine

  81 shared

• Georg Oeltzschner

  71 shared

• Kimberly L. Chan

  The University of Texas Southwestern Medical Center

  70 shared

• Michael Dacko

  University Medical Center Freiburg

  61 shared

• Jamie Near

  University of Toronto

  60 shared

• Helge J. Zöllner

  Johns Hopkins Medicine

  58 shared

• Thomas Lange

  University Medical Center Freiburg

  55 shared

Labs

• Muhammad G. Saleh LaboratoryPI

Education

• PhD in Biomedical Engineering, Human Biology

  University of Cape Town

  2016