Magnetic Resonance Spectroscopic Imaging Study Research Articles

N-Acetylaspartate and Choline Metabolites in Cortical and Subcortical Regions in Clinical High Risk Relative to Healthy Control Subjects: An Exploratory 7T MRSI Study.

N-acetylaspartate (NAA) and choline (Cho) are two brain metabolites implicated in several key neuronal functions. Abnormalities in these metabolites have been reported in both early course and chronic patients with schizophrenia (SCZ). It is, however, unclear whether NAA and Cho's alterations occur even before the onset of the disorder. Clinical high risk (CHR) individuals are a population uniquely enriched for psychosis and SCZ. In this exploratory study, we utilized 7-Tesla magnetic resonance spectroscopic imaging (MRSI) to examine differences in total NAA (tNAA; NAA + N-acetylaspartylglutamate [NAAG]) and major choline-containing compounds, including glycerophosphorylcholine and phosphorylcholine [tCho], over the creatine (Cre) levels between 26 CHR and 32 healthy control (HC) subjects in the subcortical and cortical regions. While no tCho/Cre differences were found between groups in any of the regions of interest (ROIs), we found that CHR had significantly reduced tNAA/Cre in the right dorsal lateral prefrontal cortex (DLPFC) compared to HC, and that the right DLPFC tNAA/Cre reduction in CHR was negatively associated with their positive symptoms scores. No tNAA/Cre differences were found between CHR and HC in other ROIs. In conclusion, reduced tNAA/Cre in CHR vs. HC may represent a putative molecular biomarker for risk of psychosis and SCZ that is associated with symptom severity.

Dorsolateral Prefrontal Cortex Glutamate/Gamma-Aminobutyric Acid (GABA) Alterations in Clinical High Risk and First-Episode Schizophrenia: A Preliminary 7-T Magnetic Resonance Spectroscopy Imaging Study.

Converging lines of evidence suggest that an imbalance between excitation and inhibition is present in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia (SCZ). Gamma-aminobutyric-acid (GABA) and, to a lesser extent, glutamate (Glu) abnormalities were reported in the DLPFC of SCZ patients, especially on the right hemisphere, by post-mortem studies. However, in vivo evidence of GABA, Glu, and Glu/GABA DLPFC abnormalities, particularly on the right side and the early stages of illness, is limited. In this preliminary study, we utilized 7-Tesla magnetic resonance spectroscopic imaging (MRSI) to investigate bilateral Glu/Creatine (Cre), GABA/Cre, and Glu/GABA in the DLPFC of sixteen first episode schizophrenia (FES), seventeen clinical high risk (CHR), and twenty-six healthy comparison (HC) subjects. FES and CHR had abnormal GABA/Cre and Glu/GABA in the right DLPFC (rDLPFC) compared with HC participants, while no differences were observed in the left DLPFC (lDLPFC) among the three groups. Furthermore, HC had higher Glu/GABA in rDLPFC compared to lDLPFC (R > L), whereas the opposite relationship (R < L) was observed in the DLPFC Glu/GABA of FES patients. Altogether, these findings indicate that GABA/Cre and Glu/GABA DLPFC alterations are present before illness manifestation and worsen in FES patients, thus representing a putative early pathophysiological biomarker for SCZ and related psychotic disorders.

Cerebellar GABA Change during Visuomotor Adaptation Relates to Adaptation Performance and Cerebellar Network Connectivity: A Magnetic Resonance Spectroscopic Imaging Study.

Motor adaptation is crucial for performing accurate movements in a changing environment and relies on the cerebellum. Although cerebellar involvement has been well characterized, the neurochemical changes in the cerebellum underpinning human motor adaptation remain unknown. We used a novel magnetic resonance spectroscopic imaging (MRSI) technique to measure changes in the inhibitory neurotransmitter GABA in the human cerebellum during visuomotor adaptation. Participants (n = 17, six female) used their right hand to adapt to a rotated cursor in the scanner, compared with a control task requiring no adaptation. We spatially resolved adaptation-driven GABA changes at the cerebellar nuclei and cerebellar cortex in the left and the right cerebellar hemisphere independently and found that simple right-hand movements increase GABA in the right cerebellar nuclei and decreases GABA in the left. When isolating adaptation-driven GABA changes, we found that GABA in the left cerebellar nuclei and the right cerebellar nuclei diverged, although GABA change from baseline at the right cerebellar nuclei was not different from zero at the group level. Early adaptation-driven GABA fluctuations in the right cerebellar nuclei correlated with adaptation performance. Participants showing greater GABA decrease adapted better, suggesting early GABA change is behaviorally relevant. Early GABA change also correlated with functional connectivity change in a cerebellar network. Participants showing greater decreases in GABA showed greater strength increases in cerebellar network connectivity. Results were specific to GABA, to adaptation, and to the cerebellar network. This study provides first evidence for plastic changes in cerebellar neurochemistry during motor adaptation. Characterizing these naturally occurring neurochemical changes may provide a basis for developing therapeutic interventions to facilitate human motor adaptation.SIGNIFICANCE STATEMENT Despite motor adaptation being fundamental to maintaining accurate movements, its neurochemical basis remains poorly understood, perhaps because measuring neurochemicals in the human cerebellum is technically challenging. Using a novel magnetic resonance spectroscopic imaging method, this study provides evidence for GABA changes in the left compared with the right cerebellar nuclei driven by both simple movement and motor adaptation. Although right cerebellar GABA changes were not significantly different from zero at the group level, the adaptation-driven GABA fluctuations in the right cerebellar nuclei correlated with adaptation performance and with functional connectivity change in a cerebellar network. These results show the first evidence for plastic changes in cerebellar neurochemistry during a cerebellar learning task. This provides the basis for developing therapeutic interventions that facilitate these naturally occurring changes to amplify cerebellar-dependent learning.

Quantitative T1-relaxation corrected metabolite mapping of 12 metabolites in the human brain at 9.4 T

Magnetic resonance spectroscopic imaging (MRSI) is a non-invasive imaging modality that enables observation of metabolites. Applications of MRSI for neuroimaging have shown promise for monitoring and detecting various diseases. This study builds off previously developed techniques of short TR, 1H FID MRSI by correcting for T1-weighting of the metabolites and utilizing an internal water reference to produce quantitative (mmol kg−1) metabolite maps. This work reports and shows quantitative metabolite maps for 12 metabolites for a single slice. Voxel-specific T1-corrections for water are common in MRSI studies; however, most studies use either averaged T1-relaxation times to correct for T1-weighting of metabolites or omit this correction step entirely. This work employs the use of voxel-specific T1-corrections for metabolites in addition to water. Utilizing averaged T1-relaxation times for metabolites can bias metabolite maps for metabolites that have strong differences between T1-relaxation for GM and WM (i.e. Glu). This work systematically compares quantitative metabolite maps to single voxel quantitative results and qualitatively compares metabolite maps to previous works.

Active conductive head cooling of normal and infarcted brain: A magnetic resonance spectroscopy imaging study

Active conductive head cooling is a simple and non-invasive intervention that may slow infarct growth in ischemic stroke. We investigated the effect of active conductive head cooling on brain temperature using whole brain echo-planar spectroscopic imaging. A cooling cap (WElkins Temperature Regulation System, 2nd Gen) was used to administer cooling for 80 minutes to healthy volunteers and chronic stroke patients. Whole brain echo-planar spectroscopic imaging scans were obtained before and after cooling. Brain temperature was estimated using the Metabolite Imaging and Data Analysis System software package, which allows voxel-level temperature calculations using the chemical shift difference between metabolite (N-acetylaspartate, creatine, choline) and water resonances. Eleven participants (six healthy volunteers, five post-stroke) underwent 80 ± 5 minutes of cooling. The average temperature of the coolant was 1.3 ± 0.5°C below zero. Significant reductions in brain temperature (ΔT = –0.9 ± 0.7°C, P = 0.002), and to a lesser extent, rectal temperature (ΔT = –0.3 ± 0.1°C, P = 0.03) were observed. Exploratory analysis showed that the occipital lobes had the greatest reduction in temperature (ΔT = –1.5 ± 1.2°C, P = 0.002). Regions of infarction had similar temperature reductions to the contralateral normal brain. Future research could investigate the feasibility of head cooling as a potential neuroprotective strategy in patients being considered for acute stroke therapies.

Brain metabolite concentration in pain processing regions is linked with multidimensional morbidity in fibromyalgia - a voxel-wise 3D MR Spectroscopic Imaging study

Fibromyalgia is a multidimensional chronic pain syndrome. It is thought to result mainly from central nervous system dysfunction, but its working mechanism is not fully understood. In this study, we applied multi-slice magnetic resonance spectroscopy imaging (MRSI) to investigate the relationship between brain metabolite (e.g., combined glutamate and glutamine, Glx; myo-inositol, mIno; and combined N-acetylaspartate and N-acetylaspartylglutamate; tNAA) levels and the severity of multidimensional clinical/behavioral metrics (e.g., pain catastrophizing, clinical pain severity, and evoked pain sensitivity) in fibromyalgia patients (N=87). Fibromyalgia patients showed greater pain catastrophizing and hyperalgesia compared with age-matched healthy controls (N=40). In fibromyalgia patients, pain catastrophizing scale scores were positively correlated with Glx and tNAA levels in the insular cortex, and were negatively correlated with mIno levels in the posterior cingulate cortex (PCC). Clinical pain severity showed positive correlations with Glx levels in the insular and PCC, and with tNAA levels in the anterior middle cingulate cortex (aMCC), but negatively with mIno levels in the aMCC and thalamus. The level of tNAA in the insular cortex, MCC, PCC, and thalamus, were negatively correlated with evoked pain sensitivity. These results highlight the utility of MRSI in the understanding of molecular mechanisms underlying multidimensional aspects of fibromyalgia. This work was supported by the NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases grant R01-AR064367, National Center for Complementary and Integrative Health grants R01-AT007550, R61-AT009306, and P01-AT AT009965, and National Center for Research Resources grants P41-RR14075, S10-RR021110, and S10-RR023043). Development of MRSI pulse sequence and processing was funded by NIH/NCI grants K22CA178269 and R01CA211080.

P.525 The relationship between synaptic density marker SV2A and glutamate: a multimodal positron emission tomography and magnetic resonance spectroscopy imaging study

Recent studies using the mouse model of Alzheimer’s disease (AD) have shown that donepezil administration reduces brain amyloid-β (Aβ) accumulation. This study investigated whether donepezil administration can reduce brain Aβ accumulation in human patients with AD. Ten patients with AD underwent two 11C-Pittsburgh Compound B positron emission tomography sessions approximately one year apart to measure brain Aβ accumulation before and after donepezil treatment. Volumes-of-interest were placed on Aβ-preferred regions, and the standardized uptake value ratio (SUVR) was calculated considering the cerebellum as a reference region. Three and seven patients received 10 mg and 5 mg of donepezil, respectively. SUVR was significantly higher in the second than in the first session (P = 0.026). This study showed that one year of donepezil administration does not reduce brain Aβ accumulation in human patients with AD.

Advanced magnetic resonance spectroscopic neuroimaging: Experts' consensus recommendations.

Magnetic resonance spectroscopic imaging (MRSI) offers considerable promise for monitoring metabolic alterations associated with disease or injury; however, to date, these methods have not had a significant impact on clinical care, and their use remains largely confined to the research community and a limited number of clinical sites. The MRSI methods currently implemented on clinical MRI instruments have remained essentially unchanged for two decades, with only incremental improvements in sequence implementation. During this time, a number of technological developments have taken place that have already greatly benefited the quality of MRSI measurements within the research community and which promise to bring advanced MRSI studies to the point where the technique becomes a true imaging modality, while making the traditional review of individual spectra a secondary requirement. Furthermore, the increasing use of biomedical MR spectroscopy studies has indicated clinical areas where advanced MRSI methods can provide valuable information for clinical care. In light of this rapidly changing technological environment and growing understanding of the value of MRSI studies for biomedical studies, this article presents a consensus from a group of experts in the field that reviews the state-of-the-art for clinical proton MRSI studies of the human brain, recommends minimal standards for further development of vendor-provided MRSI implementations, and identifies areas which need further technical development.

Accuracy of Multi-echo Dixon Sequence in Quantification of Hepatic Steatosis.

ObjectiveToday, a biopsy is the gold standard in the diagnosis of non-alcoholic fatty liver. However, a biopsy is an invasive technique, limited to the sample taken, and it may lead to misdiagnosis. Therefore, novel noninvasive options are needed. The objective of this study was to investigate the accuracy of magnetic resonance (MR) Dixon sequence and elastography using magnetic resonance spectroscopy (MRS) as a reference in the quantification of hepatic steatosis.MethodsA total of 60 patients were included in the study. All patients underwent magnetic resonance imaging (MRI), MRS, and elastography in order to quantify hepatosteatosis. MRI and MRS imaging studies were performed using MR Dixon and high-speed T2-corrected multiple-echo 1H-MRS sequence (HISTO) sequences, respectively, in order to calculate proton density fat fraction (PDFF) values.ResultsThe mean MRI-PDFF value with the MRS region of interest (ROI) was found as 9.4% ± 12.1%. The mean MRS-PDFF was found as 8.9% ± 11.3%. No statistically significant difference was found between MRS-PDFF and MRI-PDFF values measured in ROI (p < 0.005). The correlation between MRS-PDFF and MRI-PDFF was examined with Spearman’s correlation analysis. Accordingly, there was an excellent correlation between MRS and MRI values measured in ROI (r ≥ 0.8, p < 0.001). Sensitivity, specificity, positive predictive value, and negative predictive value were calculated as 96%, 100%, 89.5%, and 92.6%, respectively, for MRI-PDFF in predicting hepatic steatosis for the same ROI localization with MRS. The optimum cut-off value of MRS-PDFF in predicting hepatic steatosis was found as 5.3% using the same ROI localization with MRS.ConclusionThe results of this study indicated an excellent correlation between MRI-PDFF and MRS-PDFF. The multi-echo Dixon MRI technique seems a promising alternative method in the detection of non-alcoholic fatty liver disease.

Age-related Brain Metabolic Changes up to Seventh Decade in Healthy Humans : Whole-brain Magnetic Resonance Spectroscopic Imaging Study.

To study brain metabolic changes under normal aging and to collect reference data for the study of neurodegenerative diseases. A total of 55 healthy subjects aged 20-70years (n ≥ 5 per age decade for each gender) underwent whole-brain magnetic resonance spectroscopic imaging at 3T after completing a DemTect test and the Beck depressions inventory II to exclude cognitive impairment and mental disorder. Regional concentrations of N-acetylaspartate (NAA), choline-containing compounds (Cho), total creatine (tCr), glutamine and glutamate (Glx), and myo-inositol (mI) were determined in 12brain regions of interest (ROIs). The two-sided t‑test was used to estimate gender differences and linear regression analysis was carried out to estimate age dependence of brain regional metabolite contents. Brain regional metabolite concentrations changed with age in the majority of selected brain regions. The NAA decreased in 8ROIs with arate varying from -4.9% to -1.9% per decade, reflecting ageneral reduction of brain neuronal function or volume and density in older age; Cho increased in 4ROIs with arate varying from 4.3% to 6.1%; tCr and mI increased in one ROI (4.2% and 8.2% per decade, respectively), whereas Glx decreased in one ROI (-5.1% per decade), indicating an inhomogeneous increase of cell membrane turnover (Cho) with altered energy metabolism (tCr) and glutamatergic neuronal activity (Glx) as well as function of glia cell (mI) in normal aging brain. Healthy aging up to the seventh decade of life is associated with regional dependent alterations of brain metabolism. These results provide areference database for future studies of patients.

HDAC inhibition in glioblastoma monitored by hyperpolarized 13C MRSI

Vorinostat is a histone deacetylase (HDAC) inhibitor that inhibits cell proliferation and induces apoptosis in solid tumors, and is in clinical trials for the treatment of glioblastoma (GBM). The goal of this study was to assess whether hyperpolarized 13 C MRS and magnetic resonance spectroscopic imaging (MRSI) can detect HDAC inhibition in GBM models. First, we confirmed HDAC inhibition in U87 GBM cells and evaluated real-time dynamic metabolic changes using a bioreactor system with live vorinostat-treated or control cells. We found a significant 40% decrease in the 13 C MRS-detectable ratio of hyperpolarized [1-13 C]lactate to hyperpolarized [1-13 C]pyruvate, [1-13 C]Lac/Pyr, and a 37% decrease in the pseudo-rate constant, kPL , for hyperpolarized [1-13 C]lactate production, in vorinostat-treated cells compared with controls. To understand the underlying mechanism for this finding, we assessed the expression and activity of lactate dehydrogenase (LDH) (which catalyzes the pyruvate to lactate conversion), its associated cofactor nicotinamide adenine dinucleotide, the expression of monocarboxylate transporters (MCTs) MCT1 and MCT4 (which shuttle pyruvate and lactate in and out of the cell) and intracellular lactate levels. We found that the most likely explanation for our finding that hyperpolarized lactate is reduced in treated cells is a 30% reduction in intracellular lactate levels that occurs as a result of increased expression of both MCT1 and MCT4 in vorinostat-treated cells. In vivo 13 C MRSI studies of orthotopic tumors in mice also showed a significant 52% decrease in hyperpolarized [1-13 C]Lac/Pyr when comparing vorinostat-treated U87 GBM tumors with controls, and, as in the cell studies, this metabolic finding was associated with increased MCT1 and MCT4 expression in HDAC-inhibited tumors. Thus, the 13 C MRSI-detectable decrease in hyperpolarized [1-13 C]lactate production could serve as a biomarker of response to HDAC inhibitors.

The relationship between cortical glutamate and striatal dopamine in first-episode psychosis: a cross-sectional multimodal PET and magnetic resonance spectroscopy imaging study

SummaryBackgroundThe pathophysiology of psychosis is incompletely understood. Disruption in cortical glutamatergic signalling causing aberrant striatal dopamine synthesis capacity is a proposed model for psychosis, but has not been tested in vivo. We therefore aimed to test the relationship between cortical glutamate concentrations and striatal dopamine synthesis capacity, and psychotic symptoms.MethodsIn this cross-sectional multimodal imaging study, 28 individuals with first-episode psychosis and 28 healthy controls underwent 18F-DOPA PET (measuring striatal dopamine synthesis capacity), and proton magnetic resonance spectroscopy (measuring anterior cingulate cortex glutamate concentrations). Participants were recruited from first-episode psychosis services in London, UK and were required to be in the first episode of a psychotic illness, with no previous illness or treatment episodes. Exclusion criteria for all participants were: history of substantial head trauma, dependence on illicit substances, medical comorbidity (other than minor illnesses), and contraindications to scanning (such as pregnancy). Symptoms were measured using the Positive and Negative Syndrome Scale. The primary endpoint was the relationship between anterior cingulate cortex glutamate concentrations and striatal dopamine synthesis capacity in individuals with their first episode of psychosis as shown by imaging, examined by linear regression. Linear regression was used to examine relationships between measures.FindingsGlutamate concentrations showed a significant inverse relationship with striatal dopamine synthesis capacity in patients with psychosis (R2=0·16, p=0·03, β −1·71 × 10−4, SE 0·76 × 10−4). This relationship remained significant after the addition of age, gender, ethnicity, and medication status to the model (p=0·015). In healthy controls, there was no significant relationship between dopamine and glutamate measures (R2=0·04, p=0·39). Positive and Negative Syndrome Scale positive psychotic symptoms were positively associated with striatal dopamine synthesis capacity (R2=0·14, p=0·046, β 2546, SE 1217) and showed an inverse relationship with anterior cingulate glutamate concentrations (R2=0·16, p=0·03, β −1·71 × 10−4, SE 7·63 × 10−5). No relationships were seen with negative symptoms (positive symptoms, mean [SD] −18·4 (6·6) negative symptoms, mean [SD] −15·4 [6·1]).InterpretationThese observations are consistent with the hypothesis that cortical glutamate dysfunction is related to subcortical dopamine synthesis capacity and psychosis. Although the precise mechanistic relationship between cortical glutamate and dopamine in vivo remains unclear, our findings support further studies to test the effect of modulating cortical glutamate in the treatment of psychosis.FundingMedical Research Council, Wellcome Trust, Biomedical Research Council, South London and Maudsley NHS Foundation Trust, JMAS Sim Fellowship, Royal College of Physicians (Edinburgh) (SJ).

Characterisation of tissue-type metabolic content in secondary progressive multiple sclerosis: a magnetic resonance spectroscopic imaging study

Proton magnetic resonance spectroscopy yields metabolic information and has proved to be a useful addition to structural imaging in neurological diseases. We applied short-echo time Spectroscopic Imaging in a cohort of 42 patients with secondary progressive multiple sclerosis (SPMS). Linear modelling with respect to brain tissue type yielded metabolite levels that were significantly different in white matter lesions compared with normal-appearing white matter, suggestive of higher myelin turnover (higher choline), higher metabolic rate (higher creatine) and increased glial activity (higher myo-inositol) within the lesions. These findings suggest that the lesions have ongoing cellular activity that is not consistent with the usual assumption of ‘chronic’ lesions in SPMS, and may represent a target for repair therapies.

Acupuncture therapy in treating migraine: results of a magnetic resonance spectroscopy imaging study.

BackgroundAcupuncture has been proven to be effective as an alternative therapy in treating migraine, but the pathophysiological mechanisms of the treatment remain unclear. This study investigated possible neurochemical responses to acupuncture treatment.Patients and methodsProton magnetic resonance spectroscopy imaging was used to investigate biochemical levels pre- and post-acupuncture treatment. Participants (N=45) included subjects diagnosed with: 1) migraine without aura; 2) cervicogenic headache; and 3) healthy controls. Participants in the two patient groups received verum acupuncture using acupoints that target migraine without aura but not cervicogenic headache, while the healthy controls received a sham treatment. All participants had magnetic resonance spectroscopy scans before and after the acupuncture therapy. Levels of brain metabolites were examined in relation to clinical headache assessment scores.ResultsA significant increase in N-acetylaspartate/creatine was observed in bilateral thalamus in migraine without aura after the acupuncture treatment, which was significantly correlated with the headache intensity score.ConclusionThe data demonstrate brain biochemical changes underlying the effect of acupuncture treatment of migraine.

Altered brain high-energy phosphate metabolism in mild Alzheimer's disease: A 3-dimensional 31P MR spectroscopic imaging study.

In Alzheimer's disease (AD), defects in essential metabolic processes for energy supply and phospholipid membrane function have been implicated in the pathological process. However, post-mortem investigations are generally limited to late stage disease and prone to tissue decay artifacts. In vivo assessments of high energy phosphates, tissue pH and phospholipid metabolites are possible by phosphorus MR spectroscopy (31P–MRS), but so far only small studies, mostly focusing on single brain regions, have been performed. Therefore, we assessed phospholipid and energy metabolism in multiple brain regions of 31 early stage AD patients and 31 age- and gender-matched controls using 31P–MRS imaging. An increase of phosphocreatine (PCr) was found in AD patients compared with controls in the retrosplenial cortex, and both hippocampi, but not in the anterior cingulate cortex. While PCr/inorganic phosphate and pH were also increased in AD, no changes were found for phospholipid metabolites. This study showed that PCr levels are specifically increased in regions that show early degeneration in AD. Together with an increased pH, this indicates an altered energy metabolism in mild AD.

Pathogenesis of Primary Orthostatic Tremor: Current Concepts and Controversies.

BackgroundOrthostatic tremor (OT), a rare and complex movement disorder, is characterized by rapid tremor of both legs and the trunk while standing. These disappear while the patient is either lying down or walking. OT may be idiopathic/primary or it may coexist with several neurological conditions (secondary OT/OT plus). Primary OT remains an enigmatic movement disorder and its pathogenesis and neural correlates are not fully understood.MethodsA PubMed search was conducted in July 2017 to identify articles for this review.ResultsStructural and functional neuroimaging studies of OT suggest possible alterations in the cerebello-thalamo-cortical network. As with essential tremor, the presence of a central oscillator has been postulated for OT; however, the location of the oscillator within the tremor network remains elusive. Studies have speculated a possible dopaminergic deficit in the pathogenesis of primary OT; however, the evidence in favor of this concept is not particularly robust. There is also limited evidence favoring the concept that primary OT is a neurodegenerative disorder, as a magnetic resonance spectroscopic imaging study revealed significant reduction in cerebral and cerebellar N-acetyl aspartate (NAA) levels, a marker of neuronal compromise or loss.DiscussionBased on the above, it is clear that the pathogenesis of primary OT still remains unclear. However, the available evidence most strongly favors the existence of a central oscillatory network, and involvement of the cerebellum and its connections.

Detecting neuronal dysfunction of hand motor cortex in ALS: A MRSI study

Background: Although hand motor cortex (HMC) has been constantly used for identification of primary motor cortex in magnetic resonance spectroscopy (MRS) studies of amyotrophic lateral sclerosis (ALS), neurochemical profiles of HMC have never been assessed independently. As HMC has a constant location and the clinic–anatomic correlation between hand motor function and HMC has been established, we hypothesize that HMC may serve as a promising region of interest in diagnosing ALS.Patients and methods: Fourteen ALS patients and 14 age- and gender-matched healthy controls (HC) were recruited in this study. An optimized magnetic resonance spectroscopic imaging (MRSI) method was developed and for each subject bilateral HMC areas were scanned separately (two-dimensional multi-voxel MRSI, voxel size 0.56 cm3). N-acetyl aspartate (NAA)–creatine (Cr) ratio was measured from HMC and the adjacent postcentral gyrus.Results: Compared with HC, NAA/Cr ratios from HMC and the postcentral gyrus were significantly reduced in ALS. However, in each group the difference of NAA/Cr ratios between HMC and the postcentral gyrus was not significant. Limb predominance of HMC was not found in either ALS or HC. In ALS, there was a significant difference in NAA/Cr ratio between the most affected HMC and the less affected HMC. A positive relationship between NAA/Cr ratio of HMC and the severity of hand strength (assessed by finger tapping speed) was demonstrated.Conclusion: Neuronal dysfunction of HMC can differentiate ALS patients from HC when represented as reduced NAA/Cr ratio. Postcentral gyrus could not serve as normal internal reference tissue in diagnosing ALS. Asymmetrical NAA/Cr ratios from bilateral HMC may serve as a promising diagnostic biomarker of ALS at the individual level.

Key clinical benefits of neuroimaging at 7 T

The growing interest in ultra-high field MRI, with more than 35.000 MR examinations already performed at 7T, is related to improved clinical results with regard to morphological as well as functional and metabolic capabilities. Since the signal-to-noise ratio increases with the field strength of the MR scanner, the most evident application at 7T is to gain higher spatial resolution in the brain compared to 3T. Of specific clinical interest for neuro applications is the cerebral cortex at 7T, for the detection of changes in cortical structure, like the visualization of cortical microinfarcts and cortical plaques in Multiple Sclerosis. In imaging of the hippocampus, even subfields of the internal hippocampal anatomy and pathology may be visualized with excellent spatial resolution. Using Susceptibility Weighted Imaging, the plaque-vessel relationship and iron accumulations in Multiple Sclerosis can be visualized, which may provide a prognostic factor of disease. Vascular imaging is a highly promising field for 7T which is dealt with in a separate dedicated article in this special issue. The static and dynamic blood oxygenation level-dependent contrast also increases with the field strength, which significantly improves the accuracy of pre-surgical evaluation of vital brain areas before tumor removal. Improvement in acquisition and hardware technology have also resulted in an increasing number of MR spectroscopic imaging studies in patients at 7T. More recent parallel imaging and short-TR acquisition approaches have overcome the limitations of scan time and spatial resolution, thereby allowing imaging matrix sizes of up to 128×128. The benefits of these acquisition approaches for investigation of brain tumors and Multiple Sclerosis have been shown recently. Together, these possibilities demonstrate the feasibility and advantages of conducting routine diagnostic imaging and clinical research at 7T.

Spectral Quantification for High-Resolution MR Spectroscopic Imaging With Spatiospectral Constraints

To obtain reliable spectral estimation from magnetic resonance spectroscopic imaging (MRSI) data. The proposed method takes advantage of prior knowledge: 1) along the spectral dimension in the form of spectral bases, and 2) along the spatial dimensions in the form of spatial regularizations (e.g., smoothness or transform sparsity) and jointly estimates parameters from all the voxels. Simulation and in vivo studies have been performed to demonstrate the performance of the proposed method. A Cramér-Rao-bound-based analysis is also provided. Incorporation of both spatial and spectral constraints can significantly improve spectral quantification of MRSI data. The proposed method is expected to be useful for various quantitative MRSI studies.

Metabolic Abnormalities in the Hippocampus of Patients with Schizophrenia: A 3D Multivoxel MR Spectroscopic Imaging Study at 3T.

Schizophrenia is well-known to be associated with hippocampal structural abnormalities. We used 1H-MR spectroscopy to test the hypothesis that these abnormalities are accompanied by NAA deficits, reflecting neuronal dysfunction, in patients compared with healthy controls. Nineteen patients with schizophrenia (11 men; mean age, 40.6 ± 10.1 years; mean disease duration, 19.5 ± 10.5 years) and 11 matched healthy controls (5 men; mean age, 33.7 ± 10.1 years) underwent MR imaging and multivoxel point-resolved spectroscopy (TE/TR, 35/1400 ms) 1H-MRS at 3T to obtain their hippocampal GM absolute NAA, Cr, Cho, and mIns concentrations. Unequal variance t tests and ANCOVA were used to compare patients with controls. Bilateral volumes from manually outlined hippocampal masks were compared by using unequal variance t tests. Patients' average hippocampal GM Cr concentrations were 19% higher than that of controls, 8.7 ± 2.2 versus 7.4 ± 1.2 mmol/L (P < .05); showing no differences, concentrations in NAA were 8.8 ± 1.6 versus 8.7 ± 1.2 mmol/L; in Cho, 2.3 ± 0.7 versus 2.1 ± 0.3 mmol/L; and in mIns, 6.1 ± 1.5 versus 5.2 ± 0.9 (all P > .1). There was a positive correlation between mIns and Cr in patients (r = 0.57, P = .05) but not in controls. The mean bilateral hippocampal volume was ∼10% lower in patients: 7.5 ± 0.9 versus 8.4 ± 0.7 cm3 (P < .05). These findings suggest that the hippocampal volume deficit in schizophrenia is not due to net loss of neurons, in agreement with histopathology studies but not with prior 1H-MR spectroscopy reports. Elevated Cr is consistent with hippocampal hypermetabolism, and its correlation with mIns may also suggest an inflammatory process affecting some cases; these findings may suggest treatment targets and markers to monitor them.