Magnetic Resonance Spectroscopy Technology Research Articles

AB006. The use of magnetic resonance spectroscopy in the differential diagnosis of paediatric intracranial tumours.

Despite different intracranial tumour subtypes varying largely in their prognoses and recommended treatment regimens, they can have markedly similar appearances on standard radiology, especially in paediatric patients where they tend to occur in the midline. There is a need for a non-invasive, accurate method of determining tumour diagnosis to help expedite treatment planning. Existing studies have found magnetic resonance spectroscopy (MRS) to have value in diagnosing intracranial tumours in adults. The aim of this study was to investigate whether MRS could be accurate in diagnosing and grading paediatric intracranial tumours. The hospital database was retrospectively searched for paediatric intracranial tumour patients ≤18 years that had 1.5 T MRS data available. Medical and demographic data were collected from existing records including MRS metabolites N-acetylaspartate (NAA), creatine (Cr), and choline (Cho), and final histopathologic diagnosis. MRS metabolites were then statistically compared against final histopathologic diagnosis. In total, 166 patients were included. In the overall cohort, the tumour to control tissue Cr ratio was significantly higher in grade 1 than grade 4 tumours (P=0.03), and tumour Cho/Cr was significantly higher in grade 4 than grade 1 tumours (P=0.004). When analyzing tumour subtypes, control tissue Cr was significantly higher in embryonal/germ cell tumours than glial tumours (P=0.044). Binary logistic regression models including MRS metabolite ratios and age, sex, and tumour location covariates could diagnose grade 4 tumours [area under the curve (AUC) =0.857], and grade 1 tumours (AUC =0.766) with reasonable accuracy. This study suggests that MRS has benefits in the non-invasive diagnosis of paediatric intracranial tumours, in particular, identifying low- and high-grade tumours. Future advances in MRS technology, and larger cross-sectional studies will be necessary to improve the clinical integration of MRS for accurate non-invasive paediatric intracranial tumour diagnosis.

Navigating Neural Landscapes: A Comprehensive Review of Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) Applications in Epilepsy.

This review comprehensively explores the evolving role of neuroimaging, specifically magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS), in epilepsy research and clinical practice. Beginning with a concise overview of epilepsy, the discussion emphasizes the crucial importance of neuroimaging in diagnosing and managing this complex neurological disorder. The review delves into the applications of advanced MRI techniques, including high-field MRI, resting-state fMRI, and connectomics, highlighting their impact on refining our understanding of epilepsy's structural and functional dimensions. Additionally, it examines the integration of machine learning in the analysis of intricate neuroimaging data. Moving to the clinical domain, the review outlines the utility of neuroimaging in pre-surgical evaluations and the monitoring of treatment responses and disease progression. Despite significant strides, challenges and limitations are discussed in the routine clinical incorporation of neuroimaging. The review explores promising developments in MRI and MRS technology, potential advancements in imaging biomarkers, and the implications for personalized medicine in epilepsy management. The conclusion underscores the transformative potential of neuroimaging and advocates for continued exploration, collaboration, and technological innovation to propel the field toward a future where tailored, effective interventions improve outcomes for individuals with epilepsy.

Recent advances in understanding brain cancer metabolomics: a review.

Regardless of the significant progress made in surgical techniques and adjuvant therapies, brain tumors are a major contributor to cancer-related morbidity and mortality in both pediatric and adult populations. Gliomas represent a significant proportion of cerebral neoplasms, exhibiting diverse levels of malignancy. The etiology and mechanisms of resistance of this malignancy are inadequately comprehended, and the optimization of patient diagnosis and prognosis is a challenge due to the diversity of the disease and the restricted availability of therapeutic options. Metabolomics refers to the comprehensive analysis of endogenous and exogenous small molecules, both in a targeted and untargeted manner, that enables the characterization of an individual's phenotype and offers valuable insights into cellular activity, particularly in the context of cancer biology, including brain tumor biology. Metabolomics has garnered attention in current years due to its potential to facilitate comprehension of the dynamic spatiotemporal regulatory network of enzymes and metabolites that enables cancer cells to adapt to their environment and foster the development of tumors. Metabolic changes are widely acknowledged as a significant characteristic for tracking the advancement of diseases, treatment efficacy, and identifying novel molecular targets for successful medical management. Metabolomics has emerged as an exciting area for personalized medicine and drug discovery, utilizing advanced analytical techniques such as nuclear magnetic resonance spectroscopy (MRS) and mass spectrometry (MS) to achieve high-throughput analysis. This review examines and highlights the latest developments in MRS, MS, and other technologies in studying human brain tumor metabolomics.

P-262 Magnetic Resonance spectroscopy of individual mammalian embryos and human microtissues

Abstract Study question Can magnetic resonance unravel the metabolic fingerprint of samples at the embryo scale? Summary answer We successfully utilized Magnetic Resonance Spectroscopy (MRS) on single mammalian embryos and microtissues and observed a diverse range of lipids in less than 1 hour. What is known already Non-invasive selection of the best embryo to transfer is one of the most significant challenges for ART professionals. The chemical sensitivity, resolving power, and, more importantly, the non-invasive nature of MRS makes it an excellent candidate to investigate the building blocks of complex organisms. Although MRS is a well-established technique for the biochemical profiling of large organisms, handling small samples like embryos and 3D cell cultures and spheroids alongside sensitivity issues has prevented its adoption for clinical and research applications. Our group has overcome these limitations with microchip-based sensors to leverage non-invasive MRS technology down to the embryo scale. Study design, size, duration A NASH in vitro model of liver microtissues was used first to detect lipid-based metabolic biomarkers over multiple time points in complex 3D cell cultures such as microtissues. We could discriminate between healthy and diseased human micro-livers based on their lipid content. Once the MRS data acquisition and analysis were set up using stimulated or control samples, we moved to the single early or late arrested bovine embryo analysis. The whole experiment lasted one month. Participants/materials, setting, methods Early or late arrested bovine embryos were obtained through IVF, cryopreserved and measured shortly after thawing. The microtissues were provided by InSphero AG (Schlieren, CH) and individually measured fresh in a time frame of 14 days based on 117 measurements. The micro-MRS device was loaded with culture medium and a single sample, then loaded into the MRS magnet. Measurements were performed for a total time of 50 min per embryo or 15 min per microtissue. Main results and the role of chance Micro-MRS efficiently identified four different biomarkers that were significantly differently expressed (p < 0.05) according to the biological state of microlivers simulating non-alcoholic fatty liver disease (NAFL). Three of these markers represent relative concentrations of lipid signatures from fully saturated, mono and poly-unsaturated fatty acids. In addition, we analyzed in vitro produced pre-implantation bovine embryos naturally arrested at different developmental stages. This choice arose from the necessity to analyze them at different and fixed developmental stages to investigate our technology discrimination potential. The spectra obtained from the embryos present up to 6 peak regions assignable to fatty acids as observed in microtissues. Furthermore, the amplitude of the peaks varies substantially within the same group, i.e., within the morulae and within the two 2-cell stage arrested embryos. Using both microtissues and mammalian embryos, we demonstrated that micro-MRS could be used to investigate variations in the lipid content of tiny samples non-invasively. Generally, the majority of the analytical assays used in lipid metabolism investigations rely on invasive/destructive methods such as histology and biopsies, which would hinder the continuation of embryonic development. A non-invasive in vivo assay like the one presented here would provide the means to reveal the role of embryonic lipids throughout development. Limitations, reasons for caution A vital step towards establishing MRS as a clinical and research tool is the reliable detection of a wide range of signals from cellular components. Our method is ready for R&D studies, while its clinical application requires further safety studies and protocol optimization. Wider implications of the findings A non-invasive quick assay would provide the means to reveal the role of embryonic lipids throughout development. Micro-MRS can further develop into a safe embryo assay for selection before embryo transfer. This would apply to both human and animal ART, whose success rate is relatively low. Trial registration number not applicable

Application of Medical Imaging Based on Deep Learning in the Treatment of Lumbar Degenerative Diseases and Osteoporosis with Bone Cement Screws.

Objective To explore the application value of magnetic resonance spectroscopy (MRS) and GSI-energy spectrum electronic computed tomography (CT) medical imaging based on the deep convolutional neural network (CNN) in the treatment of lumbar degenerative disease and osteoporosis. Methods There were 56 cases of suspected lumbar degenerative disease and osteoporosis. A group of 56 subjects were examined using 1.5 TMR spectrum (MRS) and dual-energy X-ray absorptiometry (DXA) to collect the lumbar L3 vertebral body fat ratio (FF) and L1~4 vertebral bone mineral density (BMD) value. We divided the subjects into 2 groups with T value -2.5 as the critical point. Set T value > -2.5 as the negative group and T value ≤ -2.5 as the positive group. Pearson's method is used for FF-MRS and BMD correlation analyses. A group of all patients underwent GSI-energy spectrum CT scan, and X-ray bone mineral density (DXA) test results (bone density per unit area) were used as the gold standard to analyze the diagnosis of osteoporosis by the GSI-energy spectrum CT scan method value. Results The differences in FF and BMD between the negative group and the positive group were statistically significant (P < 0.01), and there was a highly negative correlation between the average value of FF and BMD. 30 cases were diagnosed as osteoporosis by DXA. The accuracy of GSI-energy spectrum CT medical imaging in diagnosing osteoporosis is 89.30%. The GSI-energy spectrum CT diagnosis of osteoporosis and DXA examination results have good consistency. Conclusion Based on the deep convolutional neural network (CNN) MRS technology, GSI-energy spectrum CT medical imaging is used in the clinical diagnosis and treatment of lumbar degenerative lesions and osteoporosis. It has a good advantage in assessing bone quality and has good consistency with DXA examination and has better application value high.

Usefulness of Magnetic Resonance Spectroscopy for the Initial Diagnosis of Mitochondrial DNA-Associated Leigh Syndrome

Purpose: Diagnosing Leigh syndrome (LS), a representative mitochondrial disease, remains challenging. Mitochondrial DNA (mtDNA)-associated LS, which is maternally inherited, has relatively well-known genetic variants. We evaluated the usefulness of brain magnetic resonance spectroscopy (MRS) for the initial diagnosis of mtDNA-associated LS using data from LS patients.Methods: The study involved LS patients who visited Gangnam Severance Hospital between 2006 and 2018. Based on patients’ clinical findings, genetic evaluations, brain magnetic resonance imaging, and brain MRS findings, 24 mtDNA-associated and 49 gene-negative LS patients were included in the current study. Lactate peaks and decreased N-acetyl aspartate (NAA) peaks in brain MRS were compared between both groups. Results: In total, 11 mtDNA mutation subtypes were detected. Our findings showed a higher proportion of brain MRS abnormalities in mtDNA-associated LS patients than in gene-negative LS patients, but no statistically significant differences were observed between the two groups (lactate peak, P=0.080; decreased NAA peak, P=0.115). Conclusion: Brain MRS is currently limited as an initial diagnostic test for mtDNA-associated LS. However, it may be a useful non-invasive test for the follow-up evaluation of mtDNA-associated LS treatment. Ultra-high-field MRS technology is expected in the future.

Magnetic Resonance Spectroscopy: Information and Efficiency of Diagnostics of Malignant Tumors (Review and Portfolio)

The potential field of magnetic resonance spectroscopy (MRS) application in the clinical practice of oncology is trivial: differential diagnosis of tumors, analysis of tumor malignancy degree, visualization of tumor response to chemotherapy, radiation therapy, and prediction of treatment outcome. The purpose of the work is to present, within the framework of infographics, the initial visual data of MRS of malignant tumors of various localizations for promising multiplatform systems of scientific visualization. Recall that scientific visualization deals with issues of accurate and understandable display of objects, processes and phenomena of scientific/practical interest. In the aspect of infographics, representative spectra of normal and tumor of brain tissues, auditory nerve, thyroid gland, lungs, mammary gland, pancreas, liver, kidneys, ovaries, uterus, prostate gland, muscles, and bones are presented. The main defined 1H-MPC tumor metabolites are described. Many tumors are overlapped in spectrum, and MRI results are best interpreted in conjunction with other imaging and histological analysis findings. The potential of MRS technologies can be fully realized only in superposition with artificial intellect.

Brain Gamma-Aminobutyric Acid (GABA) Concentration of the Prefrontal Lobe in Unmedicated Patients with Obsessive-Compulsive Disorder: A Research of Magnetic Resonance Spectroscopy.

BackgroundIn recent years, a large number of neuroimaging studies found that the Cortico-Striato- Thalamo-Cortical circuit (CSTC), including the prefrontal lobe, a significant part of CSTC, has disturbance metabolically in patients with Obsessive-Compulsive Disorder (OCD).AimExplore the correlation between the neuro-metabolic features and clinical characteristics of OCD patients using magnetic resonance spectroscopy technology.Methods88 patients with OCD who were not received medication and outpatient treatment for 8 weeks and 76 health controls were enrolled, there was no significant difference in gender, age or education level between the two groups. SIEMENS 3.0T MRI scanner was used to measure the spectral wave of Orbito Frontal Cortex (OFC) and Anterior Cingulate Cortex (ACC) of participants, setting mega-press sequences. Meanwhile, the concentrations of gamma-aminobutyric acid (GABA), glutamine/glutamate complex (Glx) and N-Acetyl Aspartate (NAA) were measured relative to concentration of water, on the ACC and OFC of participants, for statistical analysis via LC model version 6.3 software. The concentration of metabolic substances of the OCD group compared to the healthy control group was analyzed using two sample t-test. The correlation between substance concentration and scores on the scales, including Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Anxiety scale (HAMA) and Hamilton Depression scale (HAMD) was carried out using the Pearson correlation method.ResultsCompared with healthy controls, the GABA/W and NAA/W concentration in individuals with OCD are significantly decreased (p=0.031, t=2.193, p=0.002, t=3.223). Also, the concentration of GABA/W had a trend of decrease in the ACC. The GABA/W of the OFC had a negative correlation with Y-BOCS-O, Y-BOCS-C and Y-BOCS-T scores (p=0.037, r=0.221; p=0.007, r=0.283; p=0.014, r=0.259).ConclusionsThese results support that GABA concentration in the OFC area of patients with OCD is significantly decreased and the concentration in the ACC has a trend of decreasing. All of these indicate that there is a relationship between the GABA concentration and the psychopathology of OCD.

Radiologic Imaging Techniques for the Diagnosis and Management of Invasive Fungal Disease

Invasive fungal diseases (IFDs) are an important cause of morbidity and mortality, especially in immunocompromised patients. Prompt antifungal therapy is essential for favorable outcomes, but clinical signs and symptoms are nonspecific and mycologic confirmation is often not possible. Radiographic testing is an important adjunct to the diagnosis and management of IFDs. Early imaging has been associated with improved survival, particularly in neutropenic patients with fungal pneumonia or acute invasive fungal sinusitis. This review summarizes common radiologic appearances of IFDs of the lung, sinus, and brain. The advantages and limitations of computed tomography (CT) and magnetic resonance (MR) imaging are discussed as are recent developments in nuclear medicine and proton MR spectroscopy technology.

Anatomical, functional and molecular biomarker applications of magnetic resonance neuroimaging.

MRI and magnetic resonance spectroscopy (MRS) along with computed tomography and PET are the most common imaging modalities used in the clinics to detect structural abnormalities and pathological conditions in the brain. MRI generates superb image resolution/contrast without radiation exposure that is associated with computed tomography and PET; MRS and spectroscopic imaging technologies allow us to measure changes in brain biochemistry. Increasingly, neurobiologists and MRI scientists are collaborating to solve neuroscience problems across sub-cellular through anatomical levels. To achieve successful cross-disciplinary collaborations, neurobiologists must have sufficient knowledge of magnetic resonance principles and applications in order to effectively communicate with their MRI colleagues. This review provides an overview of magnetic resonance techniques and how they can be used to gain insight into the active brain at the anatomical, functional and molecular levels with the goal of encouraging neurobiologists to include MRI/MRS as a research tool in their endeavors.

3.0 T MRI arterial spin labeling and magnetic resonance spectroscopy technology in the application of Alzheimer's disease

The purpose of this study was to investigate the changes in the cerebral blood flow (CBF) and spectrum variables in the posterior cingulate region of patients with AD under the detection of arterial spin labeling (ASL) and magnetic resonance spectroscopy (MRS). A total of 20 AD patients (8 males and 12 females; mean age, 64.84±8.82years) and 20 healthy controls (9 males and 11 females; mean age, 64.94±7.93years) were included in this study for analysis. All images were obtained using a 3.0-T MR imager and an 8-channel head array receiving coil. MRS measurements were conducted exploring variables of metabolite ratios. Statistical analyses were conducted with the SPSS 11.0 statistical software package. Findings in the present study revealed a significant difference in the mean MMSE scores between the AD group and the healthy control group (16.21±4.01 vs. 27.35±1.01, P<0.01). Compared with the healthy control group, CBF in the bilateral frontal region showed a significant decrease in the AD group (right frontal: 83.5±7.2 vs. 110±11.5, P<0.05; left frontal: 85.6±8.1 vs. 108.7±12.2, P<0.05, respectively), and a similar association was also observed in the TL, TPJ, parietal, and hippocampal regions (all P<0.05). MRS imaging in the posterior cingulate region showed a significant reduction in the NAA/Cr ratio in the AD group (1.43±0.1 vs. 1.49±0.0, P<0.05). Additionally, we found that the MI/Cr and Cho/Cr ratios were higher than normal controls in patients with AD (all P<0.05). Our results suggested that 3D ASL detection combined with MRS in studying AD could show the regional hypo-perfusion with the decrease of CBF and the abnormal metabolic changes of the posterior cingulate cortex.

Contributions of magnetic resonance spectroscopy to understanding development: Potential applications in the study of adolescent alcohol use and abuse

A growing body of research has documented structural and functional brain development during adolescence, yet little is known about neurochemical changes that occur during this important developmental period. Magnetic resonance spectroscopy (MRS) is a well-developed technology that permits the in vivo quantification of multiple brain neurochemicals relevant to neuronal health and functioning. However, MRS technology has been underused in exploring normative developmental changes during adolescence and the onset of alcohol and drug use and abuse during this developmental period. This review begins with a brief overview of normative cognitive and neurobiological development during adolescence, followed by an introduction to MRS principles. The subsequent sections provide a comprehensive review of the existing MRS studies of development and cognitive functioning in healthy children and adolescents. The final sections of this article address the potential application of MRS in identifying neurochemical predictors and consequences of alcohol use and abuse in adolescence. MRS studies of adolescent populations hold promise for advancing our understanding of neurobiological risk factors for psychopathology by identifying the biochemical signatures associated with healthy brain development, as well as neurobiological and cognitive correlates of alcohol and substance use and abuse.

Metabolic imaging of mild traumatic brain injury

Traumatic brain injury results in a metabolic cascade of changes that occur at the molecular level, invisible to conventional imaging methods such as computed tomography or magnetic resonance imaging. Non-invasive metabolic imaging tools such as single photon emission computed tomography (SPECT), positron emission tomography (PET), and magnetic resonance spectroscopy (MRS) are the ideal methods for providing insight to these changes by measuring regional cerebral blood flow, glucose metabolism, and brain metabolite concentrations, respectively, after mild traumatic brain injury (mTBI). The purpose of this review is to provide an overview of the different methodologies and provide an up-to-date summary of recent findings with SPECT, PET, and MRS technologies, specifically after mTBI, as defined by standardized criteria. Given that the different physiological and pathological responses are heterogeneous, efforts will be made to separate studies at different time points after injury (acute, subacute, and chronic stages) as well as to the different types of mTBI such sports-related head injury where repetitive head injuries are much more common and may present a unique signature.

In Vivo Clinical Measures of Intermediary Metabolism Are Inadequate

The heart derives most of its energy via mitochondrial oxidative metabolism. The heart's fuels or energy substrates include fatty acids, lactate, glucose, and ketones. Substrate concentrations vary during the day, driven mainly by postprandial status. Entry into mitochondrial oxidation requires metabolism to acetyl-coenzyme A (CoA), the fuel of the tricarboxylic acid (TCA) cycle. Acetyl-CoA oxidation generates reduced Nicotinamide adenine dinucleotide (NADH), which drives oxidative phosphorylation, the reduction of O2 to H2O, and, ultimately, the synthesis of ATP, which is essential for myocardial mechanics. The heart uses this highly regulated series of enzyme-catalyzed reactions to convert chemical energy into mechanical energy.1 Metabolism and function in the heart are inextricably linked. Article see p 201 The pathological states of the heart, such as ischemia, hypertrophy, and failure, modify metabolism. Available technologies to measure intermediary metabolism have been inadequate. Magnetic resonance spectroscopy (MRS) can be used to spatially map or at least locally measure metabolism in vivo. Measurement of endogenous triglycerides in patients using 1H MRS has demonstrated that cardiac steatosis precedes the onset of type 2 diabetes mellitus and left ventricular systolic dysfunction.2 In the failing human heart and in preclinical heart failure models, 31P MRS has shown that flux through the creatinine kinase reaction is altered.3,4 Also, ATP and phosphocreatine are reduced after myocardial infarction due to myocyte loss.5 Myocardial energy substrate can be measured with 13C MRS. It has the chemical specificity, but its inherently low sensitivity limits the spatial and temporal resolution necessary for clinical application. In isolated hearts, 13C MRS has to be used with labeled substrate molecules to define TCA cycle kinetics. The metabolites of the TCA cycle have not been measured directly in these experiments. The content of the TCA cycle metabolites is …

In vivo magnetic resonance spectroscopy of cancer

Magnetic resonance (MR) methods provide anatomical, physiological and metabolic assessment of the cancer non- invasively. In vivo MR spectroscopy (MRS) provides information on endogenous metabolites present in tissues which is useful not only for diagnosis but also for monitoring the tumor response to therapy. Technical developments in field of in vivo MRS have resulted in mapping spatial distribution of metabolites (spectroscopic imaging), improvement in spectral sensitivity and resolution, and determination of absolute concentration of metabolites. The localized proton MRS first reported two decades ago has now emerged as a non-invasive methodology, to be used in clinical settings for the evaluation of brain and other tumors. The method has shown tremendous potential in the assessment of cancer of different organs, notably, in brain, breast and prostate cancers. Recent developments in MRS technology has made possible to expand its application to other malignancies such as musculoskeletal system, head and neck, and liver. In this review we briefly summarize the potential applications of MRS in diagnosis, staging, monitoring treatment, guiding biopsies and prediction of malignancy in brain, breast and prostate cancers. We also present briefly the current status and limitations of the applications of MRS in musculoskeletal system and liver, as two examples.

Intramyocellular lipids versus intramyocellular triglycerides

Ren et al. recently reported an elegant study of measuring lipid contents of human muscle in vivo using proton magnetic resonance spectroscopy (MRS) techniques (1). The intramyocellular (IMCL) and extramyocellular lipid proton resonances appear as two almost completely resolved peaks for both the methylene and methyl groups of the acyl chains. The methyl resonance peak is used for the quantification of IMCL, in absolute terms. This allows direct comparisons with the results in the literature that are mostly in the absolute terms. The technical advancements shall facilitate the noninvasive investigation of muscle lipids that has been very active for nearly two decades since the initial application by Schick et al. (2). In the report, the authors equated IMCL to IMCL triglycerides (imcTG). This is worth discussion. As MRS quantifies lipids based on the amounts of methylene or methyl protons, the results should reflect TG and phospholipids as well as other fatty acid-containing lipids (3). Cytosolic lipids also include diglycerides, acylcarnitines, and nonesterified fatty acids at substantial levels, especially the latter, with distinct functions (4,5). Lactate methyl resonance peak also overlaps with the lipid methylene resonance (6,7). To measure TG, it is sometimes assumed that cellular phospholipids produce broad peaks that are lost in the background (8). However, no specific tests seem to have been done in this regard to erase the concern and ensure that the resonances are largely free of interference from non-TG lipids. In fact, in most MRS studies this concern is not explicitly addressed. Therefore, it is uncertain whether these resonances can be attributed to imcTG. For this reason, the term IMCL seems more appropriate. However, this term is confused with imcTG in that IMCL is usually studied either as an energy source during exercise (9,10) or as a factor related to insulin resistance (11,12), to which only is imcTG relevant. After more than a decade of such “acclimation,” IMCL seems to have been construed to be almost synonymous with imcTG. Cellular phospholipids are often more abundant than imcTG, a small lipid pool as local energy source (13). In addition to plasma membrane phospholipids, some intracellular phospholipids are in close proximity to or in direct contact with imcTG droplets such as those of mitochondrial membrane as shown by electron microscope (14). Therefore, it seems logical to speculate that MRS may over-estimate imcTG by including non-TG lipids. For instance, IMCL concentration has been reported to be as high as 1.76–2.2% ± 1.1% (IMCL protons as % of water protons) for soleus muscle of obese and healthy lean humans, respectively (15,16). This translates into a TG concentration of 29.3 mmol/kg wet weight after taking into account the differences in the number of protons (62 vs. 2, Ref. 17) and molecular weight of TG (assuming 750) and water molecules, and assuming a muscle water content of 76% (Ref. 18). This is nearly four times higher than the imcTG concentration measured biochemically at 2.1–2.7 mmol/kg wet weight in vastus lateralis of normal and healthy lean humans, (19,20), even after taking into consideration the difference in imcTG concentration between soleus and vastus lateralis (assuming 3:1). There are higher values of imcTG measured biochemically but they are likely contaminated by adipocytes (21). For this reason, we place more confidence on the lower values achieved by using careful dissection techniques (22). Nonetheless, IMCL of soleus and tibialis anterior reported by Ren et al. (1,23) are in the expected range. However, IMCL reported for quadriceps or gastrocnemius are often overestimates (23,24). Interestingly, Howald et al. reported underestimation of tibialis anterior lipids by MRS (14). Although their MRS result is in the expected range for this less oxidative muscle, the results from biochemical and electron microscope (EM) measurements (6.5 and 5.9 mmol/kg ww, respectively) for the same muscle are unrealistically as high as that for oxidative soleus muscle. Therefore, an underestimation by MRS could not be established. It is not clear what caused these overestimations. In particular, it is not known whether non-TG lipids contributed to the methylene and methyl resonances based on which IMCL is quantified. After nearly two decades of active use of the MRS technique, this fundamental question remains unclear. As MRS increasingly becomes a major research tool in the investigation of tissue lipid metabolism, clarifying this issue is critical to better understand the quantitative relation-ship between IMCL and imcTG so that informed comparisons can be made between them. The significance and usefulness of MRS technology to the studies of tissue lipids as related to insulin resistance and sports medicine will depend on the extent that it can reliably probe the relevant lipid pools.

Is there Evidence for Neurotoxicity in the Prodromal and Early Stages of Schizophrenia?

Retrospective and prospective studies in schizophrenia have identified a period of time, termed the prodromal period, that precedes the first episode of frank psychosis by a variable length of time (days–years) and is characterized by subthreshold psychotic symptoms. Importantly, both the prodromal phase and the early stages of the schizophrenia illness are associated with significant loss in social and intellectual abilities (Yung et al, 2005), as well as gray matter volume (Cahn et al, 2006; Pantelis et al, 2003). In addition, patients' response to antipsychotic medication decreases from first to subsequent episodes (Agid et al, 2011). It has been hypothesized that a neurobiological process might underlie this early progressive deterioration. In order to gain insight into this period, researchers have identified and followed subjects at ‘ultra high risk', either because of a strong family history of schizophrenia or because of the presence of subthreshold symptoms. In addition, studies of first-episode subjects have become more common, in part because they lack the confounding effect of antipsychotic medication treatment. In this issue of Neuropsychopharmacology, de la Fuente-Sandoval et al (2011) use 1H magnetic resonance spectroscopy (MRS) to obtain glutamate measurements in the caudate nucleus of antipsychotic-naive prodromal subjects, antipsychotic-naive first-episode psychosis subjects, and matched healthy control subjects. These investigators report that the high-risk and first-episode groups showed higher levels of glutamate than controls, without differences between ultra high risk and first episode. These findings are noteworthy for several reasons. Few studies have compared ultra high-risk and first-episode populations cross-sectionally. Because only 15–35% of high-risk subjects transition to psychosis, the interpretation of purely cross-sectional studies is somewhat ambiguous. Yet, in this study, the identification of the same pattern of high glutamate levels in the high-risk and first-episode populations provides stronger support for the relevance of this abnormality. Clearly, prospective studies of ultra high-risk populations are needed to address whether the degree of this early abnormality is predictive of the illness. Nevertheless, this study suggests that high levels of glutamate measured in the precommissural dorsal-caudate nucleus, a region with prominent projections throughout the cortical mantle, could induce cortical neuronal toxicity leading to a progressive functional and intellectual deterioration. Because there is preliminary evidence that stable medicated subjects either do not show a difference or evidence a decrease in glutamate levels compared with normal subjects (de la Fuente-Sandoval et al, 2011; Reid et al, 2010), it is tempting to hypothesize that a time-limited neurotoxic process may characterize the prodromal period and the early stages of the illness. Although more research is needed in this area, this suggests the possibility of curtailing functional deterioration by intervening therapeutically during the early stages. Importantly, this study provides strong clues as to the nature of these interventions, as well as specific targets, that is, glutamate level, to monitor treatment intervention. This study also points towards potential prediction algorithms to identify those who might, or might not, go on to develop the illness. These data need to be considered in light of a recent study that reported increased striatal 18F-dopa uptake, which reflects increased presynaptic dopaminergic function, in another group of ultra –high-risk subjects (Howes et al, 2009). These data parallel findings of increased presynaptic dopamine function in psychotic and first-episode subjects. Do glutamatergic and dopaminergic dysfunctions coexist in the prodromal period, and is one the consequence of the other? In the caudate, both glutamatergic and dopaminergic afferents synapse on the same dendritic spines and shafts of medium-sized GABA-ergic projection neurons, providing an ideal anatomical arrangement for interactions between these neurotransmitters (Sesack, 2010). Alternatively, because of the use of different operational definitions of the at-risk population, the studies of Howes et al (2009) and de la Fuente-Sandoval et al (2011) may have enrolled slightly different populations. Nevertheless, these studies emphasize the need for prospective multimodal brain imaging of the prodromal period. The stakes are high. Any breakthrough in the neurobiology of the prodromal period could dramatically impact the life of subjects with schizophrenia. Finally, the study of de la Fuente-Sandoval et al (2011) re-emphasizes the role of MRS technology for the non-invasive investigation of the brain's neurochemistry. It needs to be remembered that there are a number of limitations to this technique, such as factors that can confound measurements, including but not limited to age, nicotine and substances of abuse, and psychotropic medications (Licata and Renshaw, 2010). Thus, more than ever, caution will need to be exercised when matching populations. Nonetheless, with the introduction of more powerful magnets (that is, 7T), MRS will acquire greater precision and become an even more important tool to characterize, in vivo, key elements underlying the neuropathology of psychiatric conditions, especially with regard to glutamate, and to assess novel treatment strategies.

MUSCLE RESEARCH WORK WITH BRITTON CHANCE FROMIN VIVOMAGNETIC RESONANCE SPECTROSCOPY TO NEAR-INFRARED SPECTROSCOPY

Britton Chance has pioneered magnetic resonance spectroscopy (MRS) and near-infrared (NIR) spectroscopy (NIRS) as noninvasive methods for measuring muscle metabolism in vivo from the late 1970s. This review honoring Britton Chance will highlight the progress that has been made in developing and utilizing MRS and NIRS technologies for evaluating skeletal muscle O2dynamics and energetics. Adaptation of MRS and NIRS technology has focused on the validity and reliability of the measurements and extending the methods in physiological and clinical research. Britton Chance has conducted MRS and NIRS research on elite athletes and a number of chronic health conditions, including patients with chronic heart failure, peripheral vascular disease, and neuromuscular myopathies. As MRS and NIRS technologies are practical and useful for measuring human muscle metabolism, we will strive to continue Chance's legacy by advancing muscle MRS and NIRS studies.

Advanced In Vivo Heteronuclear MRS Approaches for Studying Brain Bioenergetics Driven by Mitochondria.

The greatest merit of in vivo magnetic resonance spectroscopy (MRS) methodology used in biomedical research is its ability for noninvasively measuring a variety of metabolites inside a living organ. It, therefore, provides an invaluable tool for determining metabolites, chemical reaction rates and bioenergetics, as well as their dynamic changes in the human and animal. The capability of in vivo MRS is further enhanced at higher magnetic fields because of significant gain in detection sensitivity and improvement in the spectral resolution. Recent progress of in vivo MRS technology has further demonstrated its great potential in many biomedical research areas, particularly in brain research. Here, we provide a review of new developments for in vivo heteronuclear 31P and 17O MRS approaches and their applications in determining the cerebral metabolic rates of oxygen and ATP inside the mitochondria, in both animal and human brains.

Proton magnetic resonance spectroscopic imaging as a cancer biomarker for pediatric brain tumors (Review)

Magnetic resonance (MR) techniques offer a non-invasive, non-irradiating yet sensitive approach to diagnose and monitor cancer, which encompasses diverse processes affecting various aspects of pathophysiology. Techniques such as MR spectroscopy (MRS) have been developed and applied to monitor the metabolic aspects of cancer. Given that cancer is such a variable disease, biomarkers identified using MRS represent a promising advance and may suggest appropriate therapy, especially when diagnostic biopsies are not feasible. This article will focus on proton MRS, which appears to be the most promising MR method and is complementary to existing diagnostic methods that may be used to characterize and monitor cancer processes. We further focus on applying the MRS technology to pediatric brain tumors, the leading cause of pediatric cancer mortality.