Advances In Magnetic Resonance Spectroscopy Research Articles

Magnetic resonance spectroscopy studies in migraine

This review summarizes major findings and recent advances in magnetic resonance spectroscopy (MRS) of migraine. A multi database search of PubMed, EMBASE, and Web of Science was performed with variations of magnetic resonance spectroscopy and headache until 20th September 2021. The search generated 2897 studies, 676 which were duplicates and 1836 were not related to headache. Of the remaining 385 studies examined, further exclusions for not migraine (n = 114), and not MRS of human brain (n = 128), and non-original contributions (n = 51) or conferences (n = 24) or case studies (n = 11) or non-English (n = 3), were applied. The manuscripts of all resulting reports were reviewed for their possible inclusion in this manuscript (n = 54). The reference lists of all included reports were carefully reviewed and articles relevant to this review were added (n = 2).Included are 56 studies of migraine with and without aura that involve magnetic resonance spectroscopy of the human brain. The topics are presented in the form of a narrative review. This review aims to provide a summary of the metabolic changes measured by MRS in patients with migraine. Despite the variability reported between studies, common findings focused on regions functionally relevant to migraine such as occipital cortices, thalamic nuclei, cerebellum and cingulate. The most reproducible results were decreased N-acetyl-aspartate (NAA) in cerebellum in patients with hemiplegic migraine and in the thalamus of chronic migraine patients. Increased lactate (Lac) in the occipital cortex was found for migraine with aura but not in subjects without aura. MRS studies support the hypothesis of impaired energetics and mitochondrial dysfunction in migraine. Although results regarding GABA and Glu were less consistent, studies suggest there might be an imbalance of these important inhibitory and excitatory neurotransmitters in the migraine brain. Multinuclear imaging studies in migraine with and without aura, predominantly investigating phosphorous, report alterations of PCr in occipital, parietal, and posterior brain regions. There have been too few studies to assess the diagnostic relevance of sodium imaging in migraine.

P631. PTSD is Associated with Increased Myo-Inositol in the Aging Brain: A Magnetic Resonance Spectroscopy Study

PTSD is a disabling condition associated with increased risk for early onset of age-related conditions such as Alzheimer’s disease (AD) and dementia. Evidence suggests that PTSD is associated with elevated systemic levels of oxidative stress and inflammation, which may contribute to the early onset of neurodegeneration. Advances in magnetic resonance spectroscopy (MRS) make it possible to measure neurometabolites of oxidative stress and inflammation in the brain.

Neurometabolic Alterations in Motor Neuron Disease: Insights from Magnetic Resonance Spectroscopy.

Magnetic resonance spectroscopy (MRS) has contributed important academic insights in motor neuron diseases (MNDs), particularly in amyotrophic lateral sclerosis (ALS). Over the past three decades momentous methodological advances took place, including the emergence of high-field magnetic resonance imaging (MRI) platforms, multi-voxel techniques, whole-brain protocols, novel head-coil designs, and a multitude of open-source imaging suites. Technological advances in MRS are complemented by important conceptual developments in MND, such as the recognition of the importance of extra-motor brain regions, multi-timepoint longitudinal study designs, assessment of asymptomatic mutation carriers, description of genotype-associated signatures, and the gradual characterisation of non-ALS MND phenotypes. We have conducted a systematic review of published MRS studies in MND to identify important emerging research trends, key lessons from pioneering studies, and stereotyped shortcomings. We also sought to highlight notable gaps in the current literature so that research priorities for future studies can be outlined. While MRS remains relatively underutilised in MND compared to other structural, diffusivity and functional imaging modalities, our review suggests that MRS can not only advance our academic understanding of MND biology, but has a multitude of practical benefits for clinical and pharmaceutical trial applications.

Plug-and-play advanced magnetic resonance spectroscopy.

Advanced MRS protocols improve data quality and reproducibility relative to vendor-provided protocols; however, they are challenging to incorporate into the clinical workflow and require local MRS expertise for successful implementation. Here, we developed an automated advanced MRS acquisition protocol at 3T to facilitate acquisition of high-quality spectroscopic data without local MRS expertise. First, a B0 shimming protocol was selected for automation by comparing 3 widely used B0 algorithms (2 vendor protocols and FAST(EST)MAP). Next, voxel-based B0 and B1 calibrations were incorporated into the consensus-recommended semi-LASER sequence and combined with an automated VOI prescription tool, a recently developed method for automated voxel prescription. The efficiency of collecting single-voxel data from a clinical cohort (N = 40) with the automated protocol (calibration time and fraction of usable datasets) was compared with the nonautomated semi-LASER protocol (N = 35) whereby all prescan calibrations were executed manually in the academic hospital setting with rotating MR technologists in the neuroradiology unit. A multi-iteration FAST(EST)MAP protocol resulted in narrower water linewidths than vendor's B0 shim protocols for data acquired from 6 brain locations (p < 1e-5) and was selected for automation. The automated B0 and B1 calibrations resulted in a time saving of ~4.5 minutes per voxel relative to the same advanced protocol executed manually. All spectra acquired with the automated protocol were usable, whereas only 86% of those collected with the manual protocol were usable and spectral quality was more variable. The plug-and-play advanced MRS protocol allows automated acquisition of high-quality MRS data with high success rate and consistency on a clinical 3T platform.

Glutamate, GABA and glutathione in adults with persistent post-concussive symptoms

Persistent post-concussive symptoms (PPCS) are debilitating and endure beyond the usual recovery period after mild traumatic brain injury (mTBI). Altered neurotransmission, impaired energy metabolism and oxidative stress have been examined acutely post-injury but have not been explored extensively in those with persistent symptoms. Specifically, the antioxidant glutathione (GSH) and the excitatory and inhibitory metabolites, glutamate (Glu) and γ-aminobutyric acid (GABA), are seldom studied together in the clinical mTBI literature. While Glu can be measured using conventional magnetic resonance spectroscopy (MRS) methods at 3 Tesla, GABA and GSH require the use of advanced MRS methods. Here, we used the recently established Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy (HERMES) to simultaneously measure GSH and GABA and short-echo time point resolved spectroscopy (PRESS) to measure Glu to gain new insight into the pathophysiology of PPCS. Twenty-nine adults with PPCS (mean age: 45.69 years, s.d.: 10.73, 22 females, 7 males) and 29 age- and sex-matched controls (mean age: 43.69 years, s.d.: 11.00) completed magnetic resonance spectroscopy scans with voxels placed in the anterior cingulate and right sensorimotor cortex. Relative to controls, anterior cingulate Glu was significantly reduced in PPCS. Higher anterior cingulate GABA was significantly associated with a higher number of lifetime mTBIs, suggesting GABA may be upregulated with repeated incidence of mTBI. Furthermore, GSH in both regions of interest was positively associated with symptoms of sleepiness and headache burden. Collectively, our findings suggest that the antioxidant defense system is active in participants with PPCS, however this may be at the expense of other glutamatergic functions such as cortical excitation and energy metabolism.

Monitoring the Neurotransmitter Response to Glycemic Changes Using an Advanced Magnetic Resonance Spectroscopy Protocol at 7T.

The primary excitatory and inhibitory neurotransmitters glutamate (Glu) and gamma-aminobutyric acid (GABA) are thought to be involved in the response of the brain to changes in glycemia. Therefore, their reliable measurement is critical for understanding the dynamics of these responses. The concentrations of Glu and GABA, as well as glucose (Glc) in brain tissue, can be measured in vivo using proton (1H) magnetic resonance spectroscopy (MRS). Advanced MRS methodology at ultrahigh field allows reliable monitoring of these metabolites under changing metabolic states. However, the long acquisition times needed for these experiments while maintaining blood Glc levels at predetermined targets present many challenges. We present an advanced MRS acquisition protocol that combines commercial 7T hardware (Siemens Scanner and Nova Medical head coil), BaTiO3 dielectric padding, optical motion tracking, and dynamic frequency and B0 shim updates to ensure the acquisition of reproducibly high-quality data. Data were acquired with a semi-LASER sequence [repetition time/echo time (TR/TE) = 5,000/26 ms] from volumes of interest (VOIs) in the prefrontal cortex (PFC) and hypothalamus (HTL). Five healthy volunteers were scanned to evaluate the effect of the BaTiO3 pads on distribution. Use of BaTiO3 padding resulted in a 60% gain in signal-to-noise ratio in the PFC VOI over the acquisition without the pad. The protocol was tested in six patients with type 1 diabetes during a clamp study where euglycemic (~100 mg/dL) and hypoglycemic (~50 mg/dL) blood Glc levels were maintained in the scanner. The new protocol allowed retention of all HTL data compared with our prior experience of having to exclude approximately half of the HTL data in similar clamp experiments in the 7T scanner due to subject motion. The advanced MRS protocol showed excellent data quality (reliable quantification of 11–12 metabolites) and stability (p > 0.05 for both signal-to-noise ratio and water linewidths) between euglycemia and hypoglycemia. Decreased brain Glc levels under hypoglycemia were reliably detected in both VOIs. In addition, mean Glu level trended lower at hypoglycemia than euglycemia for both VOIs, consistent with prior observations in the occipital cortex. This protocol will allow robust mechanistic investigations of the primary neurotransmitters, Glu and GABA, under changing glycemic conditions.

P022. Lactate concentration in breast cancer using advanced magnetic resonance spectroscopy

P022. Lactate concentration in breast cancer using advanced magnetic resonance spectroscopy

Editors' note: Meta-analysis of magnetic resonance spectroscopy in the diagnosis of hepatic encephalopathy

In their systematic review and meta-analysis of magnetic resonance spectroscopy (MRS) findings associated with hepatic encephalopathy (HE) due to cirrhosis, Zeng et al. observed a statistically significant increase in glutamine/glutamate metabolites with a decrease in myo-inositol and choline concentrations throughout the parietal, occipital, and basal ganglia regions among patients with HE vs those without HE. Of these metabolites, glutamine/glutamate presence in the parietal lobe was the most robust predictor of HE. In response to these findings, Dr. Gupta expresses concern as to the utility of advanced MRS imaging, given that HE remains a clinical diagnosis. The authors respond that MRS may be useful for earlier identification of mild or subclinical HE, which may lead to earlier, targeted treatment in patients at risk for later decompensation. In their systematic review and meta-analysis of magnetic resonance spectroscopy (MRS) findings associated with hepatic encephalopathy (HE) due to cirrhosis, Zeng et al. observed a statistically significant increase in glutamine/glutamate metabolites with a decrease in myo-inositol and choline concentrations throughout the parietal, occipital, and basal ganglia regions among patients with HE vs those without HE. Of these metabolites, glutamine/glutamate presence in the parietal lobe was the most robust predictor of HE. In response to these findings, Dr. Gupta expresses concern as to the utility of advanced MRS imaging, given that HE remains a clinical diagnosis. The authors respond that MRS may be useful for earlier identification of mild or subclinical HE, which may lead to earlier, targeted treatment in patients at risk for later decompensation.

Terminology and concepts for the characterization of in vivo MR spectroscopy methods and MR spectra: Background and experts' consensus recommendations.

With a 40‐year history of use for in vivo studies, the terminology used to describe the methodology and results of magnetic resonance spectroscopy (MRS) has grown substantially and is not consistent in many aspects. Given the platform offered by this special issue on advanced MRS methodology, the authors decided to describe many of the implicated terms, to pinpoint differences in their meanings and to suggest specific uses or definitions. This work covers terms used to describe all aspects of MRS, starting from the description of the MR signal and its theoretical basis to acquisition methods, processing and to quantification procedures, as well as terms involved in describing results, for example, those used with regard to aspects of quality, reproducibility or indications of error. The descriptions of the meanings of such terms emerge from the descriptions of the basic concepts involved in MRS methods and examinations. This paper also includes specific suggestions for future use of terms where multiple conventions have emerged or coexisted in the past.

Magnetic resonance spectroscopy of isocitrate dehydrogenase mutated gliomas: current knowledge on the neurochemical profile.

Magnetic resonance spectroscopy (MRS) may play a key role for the management of patients with glioma. We highlighted the utility of MRS in the noninvasive diagnosis of gliomas with mutations in isocitrate dehydrogenase (IDH) genes, by providing an overview of the neurochemical alterations observed in different glioma subtypes, as well as during treatment and progression, both in vivo and ex vivo. D-2-hydroxyglutarate (2HG) decrease during anticancer treatments was recently shown to be associated with altered levels of other metabolites, including lactate, glutamate and glutathione, suggesting that tumour treatment leads to a metabolic reprogramming beyond 2HG depletion. In combination with 2HG quantification, cystathionine and glycine seem to be the most promising candidates for higher specific identification of glioma subtypes and follow-up of disease progression and response to treatment. The implementation of advanced MRS methods in the routine clinical practice will allow the quantification of metabolites that are not detectable with conventional methods and may enable immediate, accurate diagnosis of gliomas, which is crucial for planning optimal therapeutic strategies and follow-up examinations. The role of different metabolites as predictors of patient outcome still needs to be elucidated.

Lactate concentration in breast cancer using advanced magnetic resonance spectroscopy

BackgroundPrecision medicine in breast cancer demands markers sensitive to early treatment response. Aerobic glycolysis (AG) upregulates lactate dehydrogenase A (LDH-A) with elevated lactate production; however, existing approaches for lactate quantification are either invasive or impractical clinically.MethodsThirty female patients (age 39–78 years, 15 grade II and 15 grade III) with invasive ductal carcinoma were enrolled. Lactate concentration was quantified from freshly excised whole tumours with double quantum filtered (DQF) magnetic resonance spectroscopy (MRS), and Nottingham Prognostic Index (NPI), LDH-A and proliferative marker Ki-67 were assessed histologically.ResultsThere was a significantly higher lactate concentration (t = 2.2224, p = 0.0349) in grade III (7.7 ± 2.9 mM) than in grade II (5.5 ± 2.4 mM). Lactate concentration was correlated with NPI (ρ = 0.3618, p = 0.0495), but not with Ki-67 (ρ = 0.3041, p = 0.1023) or tumour size (r = 0.1716, p = 0.3645). Lactate concentration was negatively correlated with LDH-A (ρ = −0.3734, p = 0.0421).ConclusionOur results showed that lactate concentration in whole breast tumour from DQF MRS is sensitive to tumour grades and patient prognosis.

Characterization of Carbonic Anhydrase In Vivo Using Magnetic Resonance Spectroscopy.

Carbonic anhydrase is a ubiquitous metalloenzyme that catalyzes the reversible interconversion of CO2/HCO3−. Equilibrium of these species is maintained by the action of carbonic anhydrase. Recent advances in magnetic resonance spectroscopy have allowed, for the first time, in vivo characterization of carbonic anhydrase in the human brain. In this article, we review the theories and techniques of in vivo 13C magnetization (saturation) transfer magnetic resonance spectroscopy as they are applied to measuring the rate of exchange between CO2 and HCO3− catalyzed by carbonic anhydrase. Inhibitors of carbonic anhydrase have a wide range of therapeutic applications. Role of carbonic anhydrases and their inhibitors in many diseases are also reviewed to illustrate future applications of in vivo carbonic anhydrase assessment by magnetic resonance spectroscopy.

Ischemic Heart Disease and Heart Failure: Advanced Magnetic Resonance Spectroscopy and Metabolic Imaging

Ischemic Heart Disease and Heart Failure: Advanced Magnetic Resonance Spectroscopy and Metabolic Imaging

Improved localization, spectral quality, and repeatability with advanced MRS methodology in the clinical setting.

To investigate the utility of an advanced magnetic resonance spectroscopy (MRS) protocol in the clinical setting, and to compare the localization accuracy, spectral quality, and quantification repeatability between this advanced and the conventional vendor-provided MRS protocol on a clinical 3T platform. Proton spectra were measured from the posterior cingulate cortices in 30 healthy elderly subjects by clinical MR technologists using a vendor-provided (point resolved spectroscopy with advanced 3D gradient-echo B0 shimming) and an advanced (semi-LASER with FAST(EST)MAP shimming) protocol, in random order. Spectra were quantified with LCModel using standard pipelines for the clinical and research settings, respectively. The advanced protocol outperformed the vendor-provided protocol in localization accuracy (chemical-shift-displacement error: 2.0%/ppm, semi-LASER versus 11.6%/ppm, point resolved spectroscopy), spectral quality (water linewidth: 6.1 ± 1.8 Hz, FAST(EST)MAP versus 10.5 ± 3.7 Hz, 3D gradient echo; P < 7e-6; residual water: 0.08 ± 0.12%, VAPOR versus 0.45 ± 0.50%, WET; P < 2e-5) and within-session repeatability of metabolite concentrations, particularly of low signal-to-noise ratio data with two to eight averages (test-retest coefficients of variance of metabolite concentrations, P < 0.01). Concentrations of J-coupled metabolites such as γ-aminobutyric acid and glutamate were biased when using the default pipeline with simulated macromolecules. The quality of MRS data can be improved using advanced acquisition and analysis protocols on standard 3T hardware in the clinical setting, which can facilitate robust applications in central nervous system diseases. Magn Reson Med 79:1241-1250, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

GABA System in Schizophrenia and Mood Disorders: A Mini Review on Third-Generation Imaging Studies.

Third-generation neuroimaging research has been enriched by advances in magnetic resonance spectroscopy (MRS) measuring the concentration of important neurotrasmitters, such as the inhibitory amino acid GABA. Here, we performed a systematic mini-review on brain MRS studies measuring GABA concentration in patients affected by schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). We wondered whether multimodal investigations could overcome intrinsic technical limits of MRS giving a broader view of mental disorders pathogenesis. In SZ, unimodal studies gave mixed results, as increased, decreased, or unaltered GABA levels were reported depending on region, disease phase, and treatment. Conversely, multimodal results showed reduced level of glutamate, but not of GABA, in patients mirrored by in vitro biochemical findings revealing hippocampal reduction in glutamate signaling in SZ, and no deficits in GABA synthesis. Moreover, a mouse model confirmed the unique pathological characteristic of glutamate function in SZ. Unimodal studies in BD revealed again, inconsistent results, while no multimodal investigations including MRS on GABA exist. In MDD, unimodal studies could not differentiate patients from controls nor characterize high-risk subjects and remitted patients. However, a multimodal study combining functional magnetic resonance imaging and MRS revealed that cingulate cortex activity is related to glutamate, N-acetylaspartate levels and anhedonia in patients, and to GABA concentration in healthy subjects, improving the distinction between MDD and physiology. Overall, our results show that unimodal studies do not indicate GABA as a biomarker for the psychiatric disorders considered. Conversely, multimodal studies can widen the understanding of the link between psychopathology, genetics, neuroanatomy, and functional–biochemical brain activity in mental disorders. Although scarce, multimodal approaches seem promising for moving from GABA MRS unimodal-descriptive to causal level, and for integrating GABA results into a more comprehensive interpretation of mental disorder pathophysiology.

Advanced magnetic resonance spectroscopy and imaging techniques applied to brain development and animal models of perinatal injury

Magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) are widely used in the field of brain development and perinatal brain injury. Due to technical progress the magnetic field strength (B0) of MR systems has continuously increased, favoring 1H-MRS with quantification of up to 18 metabolites in the brain and short echo time (TE) MRI sequences including phase and susceptibility imaging. For longer TE techniques including diffusion imaging modalities, the benefits of higher B0 have not been clearly established. Nevertheless, progress has also been made in new advanced diffusion models that have been developed to enhance the accuracy and specificity of the derived diffusion parameters. In this review, we will describe the latest developments in MRS and MRI techniques, including high-field 1H-MRS, phase and susceptibility imaging, and diffusion imaging, and discuss their application in the study of cerebral development and perinatal brain injury.

Evaluation of epicardial and intra-myocardial fat in a patient with mitochondrial cardiomyopathy

Mitochondrial cardiomyopathy is one of the main manifestations in patients with primary mitochondrial respiratory chain disease characterized by mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) and carries a similar prognosis. The phenotype frequently includes hypertrophic cardiomyopathy; dilated cardiomyopathy and left ventricular (LV) non-compaction are rarely present [ [1] Bates M.G. Bourke J.P. Giordano C. d'Amati G. Turnbull D.M. Taylor R.W. Cardiac involvement in mitochondrial DNA disease: clinical spectrum, diagnosis, and management. Eur Heart J. 2012; 33: 3023-3033 Crossref PubMed Scopus (147) Google Scholar ]. Cardiac magnetic resonance imaging (MRI) with gadolinium-based contrast agents has been widely used for evaluating the morphology and function of the left ventricle and injured myocardial tissue [ [2] Okayama S. Uemura S. Soeda T. et al. Clinical significance of papillary muscle late enhancement detected via cardiac magnetic resonance imaging in patients with single old myocardial infarction. Int J Cardiol. 2011; 146: 73-79 Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar ]. Cine imaging with a standard steady state free precession sequence has been validated for accurate evaluation of epicardial fat [ [3] Nelson A.J. Worthley M.I. Psaltis P.J. et al. Validation of cardiovascular magnetic resonance assessment of pericardial adipose tissue volume. J Cardiovasc Magn Reson. 2009; 5: 15 Crossref Scopus (81) Google Scholar ], which is associated with coronary atherosclerosis and LV systolic dysfunction [ [4] Khawaja T. Greer C. Chokshi A. et al. Epicardial fat volume in patients with left ventricular systolic dysfunction. Am J Cardiol. 2011; 108: 397-401 Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar ]. Recent advances in magnetic resonance spectroscopy (MRS) have enabled noninvasive measurement of intra-myocardial triglyceride content [ [5] Nakae I. Mitsunami K. Yoshino T. et al. Clinical features of myocardial triglyceride in different types of cardiomyopathy assessed by proton magnetic resonance spectroscopy: comparison with myocardial creatine. J Card Fail. 2010; 16: 812-822 Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar ], which is increased and associated with LV diastolic dysfunction in patients with diabetes mellitus [ 6 McGavock J.M. Lingvay I. Zib I. et al. Cardiac steatosis in diabetes mellitus: a 1H-magnetic resonance spectroscopy study. Circulation. 2007; 116: 1170-1175 Crossref PubMed Scopus (464) Google Scholar , 7 Rijzewijk L.J. van der Meer R.W. Smit J.W. et al. Myocardial steatosis is an independent predictor of diastolic dysfunction in type 2 diabetes mellitus. J Am Coll Cardiol. 2008; 52: 1793-1799 Abstract Full Text Full Text PDF PubMed Scopus (423) Google Scholar ].

Description of the Intermediate Length Scale Structural Motifs in Sodium Vanado-phosphate Glasses by Magnetic Resonance Spectroscopies

For the first time, the local and medium range orders in sodium vanado-phosphate glasses have been investigated by advanced magnetic resonance spectroscopy methods. One- and two-dimensional 31P/51V magic angle spinning nuclear magnetic resonance techniques (31P(51V) REAPDOR and 51V(31P) D-HMQC) have been used to monitor the formation of P–O–V5+ bonds and to provide the first accurate description of the intermediate length scale structural motifs in these glasses. The structural model has been completed by the investigation of the chemical environment of the V4+ ions (produced through the partial reduction of V5+ during the melting stage of the glass preparation) using standard continuous wave and advanced pulsed electron paramagnetic resonance techniques (HYSCORE). Finally, the combination of both sets of data leads to the first complete and precise structural model of the alkali vanado-phosphate glass system.

Individual Differences in Subconscious Motor Control Predicted by GABA Concentration in SMA

Subliminal visual stimuli affect motor planning, but the size of such effects differs greatly between individuals. Here, we investigated whether such variation may be related to neurochemical differences between people. Cortical responsiveness is expected to be lower under the influence of more of the main inhibitory neurotransmitter, GABA. Thus, we hypothesized that, if an individual has more GABA in the supplementary motor area (SMA)--a region previously associated with automatic motor control--this would result in smaller subliminal effects. We measured the reversed masked prime--or negative compatibility--effect, and found that it correlated strongly with GABA concentration, measured with magnetic resonance spectroscopy. This occurred specifically in the SMA region, and not in other regions from which spectroscopy measurements were taken. We replicated these results in an independent cohort: more GABA in the SMA region is reliably associated with smaller effect size. These findings suggest that, across individuals, the responsiveness of subconscious motor mechanisms is related to GABA concentration in the SMA.

Research Applications of Magnetic Resonance Spectroscopy to Investigate Psychiatric Disorders

Advances in magnetic resonance spectroscopy (MRS) methodology and related analytic strategies allow sophisticated testing of neurobiological models of disease pathology in psychiatric disorders. An overview of principles underlying MRS, methodological considerations, and investigative approaches is presented. A review of recent research is presented that highlights innovative approaches applying MRS, in particular, hydrogen MRS, to systematically investigate specific psychiatric disorders, including autism spectrum disorders, schizophrenia, panic disorder, major depression, and bipolar disorder.