1H Magnetic Resonance Spectroscopy Research Articles

Sequence building block for magnetic resonance spectroscopy on Siemens VE-series scanners.

We present a sequence building block (SBB) that embeds magnetic resonance spectroscopy (MRS) into another sequence on the Siemens VE platform without any custom hardware. This enables dynamic studies such as functional MRS (fMRS), dynamic shimming and frequency correction, and acquisition of navigator images for motion correction. The SBB supports nonlocalised spectroscopy (free induction decay), STimulated Echo Acquisition Mode single voxel spectroscopy, and 1D, 2D and 3D phase-encoded chemical shift imaging. It can embed 1H or X-nuclear MRS into a 1H sequence; and 1H-MRS into an X-nuclear sequence. We demonstrate integration into the vendor's gradient-recalled echo sequence. We acquire test data in phantoms with three coils (31P/1H, 13C/1H and 2H/1H) and in two volunteers on a 7-T Terra MRI scanner. Fifteen lines of code are required to insert the SBB into a sequence. Spectra and images are acquired successfully in all cases in phantoms, and in human abdomen and calf muscle. Phantom comparison of signal-to-noise ratio and linewidth showed that the SBB has negligible effects on image and spectral quality, except that it sometimes produces a nuclear Overhauser effect (NOE) signal enhancement for multinuclear applications in line with conventional 1H NOE pulses. Our new SBB embeds MRS into a host imaging or spectroscopy sequence in 15 lines of code. It allows homonuclear and heteronuclear interleaving. The package is available through the standard C2P procedure. We hope this will lower the barrier for entry to studies applying dynamic fMRS and for online motion correction and B0-shim updating.

Quantifying in vivo Mitochondrial Effciency at Rest and during Exercise in Human Skeletal Muscle

Introduction: Mitochondrial effciency provides an additional mechanism to fine-tune oxidative phosphorylation rate to match ATP demand in skeletal muscle with far-reaching consequences on exercise tolerance. However, the direct measurement of both oxygen consumption (VO2) and ATP production from the same region of the contracting muscle in vivo remains a technical challenge. Purpose: Using an innovative approach combining noninvasive phosphorus and proton magnetic resonance spectroscopy (31P/1H-MRS), the present study aimed to characterize skeletal muscle ATP synthesis rate and muscle VO2 at rest and during a graded dynamic plantar flexion exercise to determine mitochondrial effciency in the gastrocnemius muscle. Method: We assessed mitochondrial effciency in the gastrocnemius muscles of 12 healthy adults (21± 1 yrs.). 31P and 1H magnetic resonance spectroscopy (MRS) was performed using a whole-body 3T MR system (Skyra, Siemens) at rest and during a series of constant workloads coupled to brief transient ischemia to quantify both oxidative ATP synthesis (ATPox) rate and myoglobin-derived oxygen consumption (Mb-derived VO2). The MRS data were acquired with a dual-tuned 31P/1H surface coil with linear polarization positioned over the gastrocnemius muscle. Results: As expected, the end-exercise PCr concentration decreased from 29 ± 2 mM of WRmax to 18 ± 1 mM with increasing workload. Likewise, the end-exercise Mb oxygenation level declined linearly with increasing workload. As the exercise workload increased, the ATPox synthesis rate increased linearly (r2 = 0.45), whereas there was no significant change in Mb-derived VO2. At rest, the estimated P/O ratio in the gastrocnemius muscle was 1.95 ± 0.68, whereas non-physiological values were obtained during exercise. Conclusion: During exercise, Mb-derived VO2 was likely limited by O2 availability with the methodology employed (30-sec occlusion, spectrum time resolution of 10 sec), which precluded the accurate quantification of mitochondrial effciency. However, mitochondrial effciency calculated at rest is in agreement with previously documented values ex vivo and thus provides an additional parameter to evaluate mitochondrial function in vivo. This work was funded in part by National Heart, Lung, and Blood Institute Grant R00HL125756. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

2-Hydroxyglutarate as an MR spectroscopic predictor of an IDH mutation in gliomas.

The mutated enzyme isocitrate dehydrogenase (IDH) 1 and 2 has been detected in various tumor entities such as gliomas and can convert α-ketoglutarate into the oncometabolite 2-hydroxyglutarate (2-HG). This neuro-oncologically significant metabolic product can be detected by MR spectroscopy and is therefore suitable for noninvasive glioma classification and therapy monitoring.This paper provides an up-to-date overview of the methodology and relevance of 1H-MR spectroscopy (MRS) in the oncological primary and follow-up diagnosis of gliomas. The possibilities and limitations of this MR spectroscopic examination are evaluated on the basis of the available literature.By detecting 2-HG, MRS can in principle offer a noninvasive alternative to immunohistological analysis thus avoiding surgical intervention in some cases. However, in addition to an adapted and optimized examination protocol, the individual measurement conditions in the examination region are of decisive importance. Due to the inherently small signal of 2-HG, unfavorable measurement conditions can influence the reliability of detection. · MR spectroscopy enables the non-invasive detection of 2-hydroxyglutarate.. · The measurement of this metabolite allows the detection of an IDH mutation in gliomas.. · The choice of MR examination method is particularly important.. · Detection reliability is influenced by glioma size, necrotic tissue and the existing measurement conditions.. · Bauer J, Raum HN, Kugel H et al. 2-Hydroxyglutarate as an MR spectroscopic predictor of an IDH mutation in gliomas. Fortschr Röntgenstr 2024; DOI 10.1055/a-2285-4923.

Lonidamine Induced Selective Acidification and De-Energization of Prostate Cancer Xenografts: Enhanced Tumor Response to Radiation Therapy.

Prostate cancer is a multi-focal disease that can be treated using surgery, radiation, androgen deprivation, and chemotherapy, depending on its presentation. Standard dose-escalated radiation therapy (RT) in the range of 70-80 Gray (GY) is a standard treatment option for prostate cancer. It could be used at different phases of the disease (e.g., as the only primary treatment when the cancer is confined to the prostate gland, combined with other therapies, or as an adjuvant treatment after surgery). Unfortunately, RT for prostate cancer is associated with gastro-intestinal and genitourinary toxicity. We have previously reported that the metabolic modulator lonidamine (LND) produces cancer sensitization through tumor acidification and de-energization in diverse neoplasms. We hypothesized that LND could allow lower RT doses by producing the same effect in prostate cancer, thus reducing the detrimental side effects associated with RT. Using the Seahorse XFe96 and YSI 2300 Stat Plus analyzers, we corroborated the expected LND-induced intracellular acidification and de-energization of isolated human prostate cancer cells using the PC3 cell line. These results were substantiated by non-invasive 31P magnetic resonance spectroscopy (MRS), studying PC3 prostate cancer xenografts treated with LND (100 mg/kg, i.p.). In addition, we found that LND significantly increased tumor lactate levels in the xenografts using 1H MRS non-invasively. Subsequently, LND was combined with radiation therapy in a growth delay experiment, where we found that 150 µM LND followed by 4 GY RT produced a significant growth delay in PC3 prostate cancer xenografts, compared to either control, LND, or RT alone. We conclude that the metabolic modulator LND radio-sensitizes experimental prostate cancer models, allowing the use of lower radiation doses and diminishing the potential side effects of RT. These results suggest the possible clinical translation of LND as a radio-sensitizer in patients with prostate cancer.

Relating depressive and manic symptomatology to 1H-MRS spectra

BackgroundAlterations in neurochemical levels are potential biomarkers of affective disorders and offer a window into illness etiology. Much of the research done to date limits focus to few metabolites and relies on dichotomous diagnoses. Here, using 1H magnetic resonance spectroscopy (MRS), we generate profiles of association between depressive and manic symptom rating scales and numerous metabolites. MethodsMRS data were collected in 30 individuals (7 = major depressive disorder; 5 bipolar disorder and 18 unaffected individuals) in the right anterior cingulate cortex (ACC), insula and hippocampus. All participants were administered mania and depression symptom scales. ResultsSmall to medium relationships were observed between total choline (tCho), N-acetylaspartate (NAA), myo-inositol (mIns) and depressive and manic symptoms. Associations between NAA and mania (r = –0.47, p = 8.88×10−03) in the hippocampus, and tCho (r = –0.48, p = 8.79×10−03) and NAA (r = –0.44, p = 0.01) and mania in the ACC withstood multiple testing correction. ConclusionsElevated levels of choline-containing compounds (tCho) and reduced NAA measured in the ACC and hippocampus are associated with mania indexed dimensionally. These metabolites may represent potential in vivo biomarkers for bipolar disorder symptomatology that warrant follow-up.

Diffusion of brain metabolites highlights altered brain microstructure in type C hepatic encephalopathy: a 9.4 T preliminary study.

Type C hepatic encephalopathy (HE) is a decompensating event of chronic liver disease leading to severe motor and cognitive impairment. The progression of type C HE is associated with changes in brain metabolite concentrations measured by 1H magnetic resonance spectroscopy (MRS), most noticeably a strong increase in glutamine to detoxify brain ammonia. In addition, alterations of brain cellular architecture have been measured ex vivo by histology in a rat model of type C HE. The aim of this study was to assess the potential of diffusion-weighted MRS (dMRS) for probing these cellular shape alterations in vivo by monitoring the diffusion properties of the major brain metabolites. The bile duct-ligated (BDL) rat model of type C HE was used. Five animals were scanned before surgery and 6- to 7-week post-BDL surgery, with each animal being used as its own control. 1H-MRS was performed in the hippocampus (SPECIAL, TE = 2.8 ms) and dMRS in a voxel encompassing the entire brain (DW-STEAM, TE = 15 ms, diffusion time = 120 ms, maximum b-value = 25 ms/μm2) on a 9.4 T scanner. The in vivo MRS acquisitions were further validated with histological measures (immunohistochemistry, Golgi-Cox, electron microscopy). The characteristic 1H-MRS pattern of type C HE, i.e., a gradual increase of brain glutamine and a decrease of the main organic osmolytes, was observed in the hippocampus of BDL rats. Overall increased metabolite diffusivities (apparent diffusion coefficient and intra-stick diffusivity-Callaghan's model, significant for glutamine, myo-inositol, and taurine) and decreased kurtosis coefficients were observed in BDL rats compared to control, highlighting the presence of osmotic stress and possibly of astrocytic and neuronal alterations. These results were consistent with the microstructure depicted by histology and represented by a decline in dendritic spines density in neurons, a shortening and decreased number of astrocytic processes, and extracellular edema. dMRS enables non-invasive and longitudinal monitoring of the diffusion behavior of brain metabolites, reflecting in the present study the globally altered brain microstructure in BDL rats, as confirmed ex vivo by histology. These findings give new insights into metabolic and microstructural abnormalities associated with high brain glutamine and its consequences in type C HE.

The relationship between oxidative stress markers and 1H-Magnetic resonance spectroscopy findings in obsessive compulsive disorder

IntroductionThe purpose of this study was to examine N-acetyl aspartate (NAA)/creatine (Cr) and glutamate, glutamine, and gamma-aminobutyric acid complex (Glx)/Cr levels in patients with obsessive compulsive disorder (OCD) and healthy controls’ orbitofrontal cortex (OFC) and caudate nucleus (CN) by proton magnetic resonance spectroscopy (1H-MRS) method and to investigate their relationship with oxidative stress markers glutathione peroxidase (GPx) and superoxide dismutase (SOD). MethodsThis study included patients with OCD (n = 25) and healthy controls (n = 25) ranging in age from 18 to 65. We used the ELISA method to evaluate serum SOD and GPx levels. Levels of NAA/Cr and Glx/Cr in the orbitofrontal cortex and caudate nucleus were measured using the 1H-MRS method. ResultsOur study did not detect statistically significant differences in the orbitofrontal cortex Glx/Cr and NAA/Cr levels between the OCD patients and the control group. OCD patients exhibited a decrease in NAA/Cr levels, consistent with impaired neuronal integration, and an increase in Glx/Cr levels, consistent with hyperactivation, in the caudate nucleus compared to the control group. We observed a negative correlation between NAA/Cr levels in the caudate nucleus and the levels of SOD and GPx. ConclusionsOur study is the first to assess CN and OFC together in OCD patients using 3 T MR, investigating the relationship between neurometabolite concentrations and oxidative stress parameters. The negative correlation we observed between NAA/Cr levels and SOD and GPx in the caudate nucleus suggests that increased oxidative stress in this brain region in OCD patients may contribute to impaired neuronal integration and functionality.

1H and 31P magnetic resonance spectroscopy reveals potential pathogenic and biomarker metabolite alterations in Lafora disease.

Lafora disease is a fatal teenage-onset progressive myoclonus epilepsy and neurodegenerative disease associated with polyglucosan bodies. Polyglucosans are long-branched and as a result precipitation- and aggregation-prone glycogen. In mouse models, downregulation of glycogen synthase, the enzyme that elongates glycogen branches, prevents polyglucosan formation and rescues Lafora disease. Mouse work, however, has not yet revealed the mechanisms of polyglucosan generation, and few in vivo human studies have been performed. Here, non-invasive in vivo magnetic resonance spectroscopy (1H and 31P) was applied to test scan feasibility and assess neurotransmitter balance and energy metabolism in Lafora disease towards a better understanding of pathogenesis. Macromolecule-suppressed gamma-aminobutyric acid (GABA)-edited 1H magnetic resonance spectroscopy and 31P magnetic resonance spectroscopy at 3 and 7 tesla, respectively, were performed in 4 Lafora disease patients and a total of 21 healthy controls (12 for the 1H magnetic resonance spectroscopy and 9 for the 31PMRS). Spectra were processed using in-house software and fit to extract metabolite concentrations. From the 1H spectra, we found 33% lower GABA concentrations (P = 0.013), 34% higher glutamate + glutamine concentrations (P = 0.011) and 24% lower N-acetylaspartate concentrations (P = 0.0043) in Lafora disease patients compared with controls. From the 31P spectra, we found 34% higher phosphoethanolamine concentrations (P = 0.016), 23% lower nicotinamide adenine dinucleotide concentrations (P = 0.003), 50% higher uridine diphosphate glucose concentrations (P = 0.004) and 225% higher glucose 6-phosphate concentrations in Lafora disease patients versus controls (P = 0.004). Uridine diphosphate glucose is the substrate of glycogen synthase, and glucose 6-phosphate is its extremely potent allosteric activator. The observed elevated uridine diphosphate glucose and glucose 6-phosphate levels are expected to hyperactivate glycogen synthase and may underlie the generation of polyglucosans in Lafora disease. The increased glutamate + glutamine and reduced GABA indicate altered neurotransmission and energy metabolism, which may contribute to the disease's intractable epilepsy. These results suggest a possible basis of polyglucosan formation and potential contributions to the epilepsy of Lafora disease. If confirmed in larger human and animal model studies, measurements of the dysregulated metabolites by magnetic resonance spectroscopy could be developed into non-invasive biomarkers for clinical trials.

The developmental trajectory of 1H-MRS brain metabolites from childhood to adulthood.

Human brain development is ongoing throughout childhood, with for example, myelination of nerve fibers and refinement of synaptic connections continuing until early adulthood. 1H-Magnetic Resonance Spectroscopy (1H-MRS) can be used to quantify the concentrations of endogenous metabolites (e.g. glutamate and γ -aminobutyric acid (GABA)) in the human brain in vivo and so can provide valuable, tractable insight into the biochemical processes that support postnatal neurodevelopment. This can feasibly provide new insight into and aid the management of neurodevelopmental disorders by providing chemical markers of atypical development. This study aims to characterize the normative developmental trajectory of various brain metabolites, as measured by 1H-MRS from a midline posterior parietal voxel. We find significant non-linear trajectories for GABA+ (GABA plus macromolecules), Glx (glutamate + glutamine), total choline (tCho) and total creatine (tCr) concentrations. Glx and GABA+ concentrations steeply decrease across childhood, with more stable trajectories across early adulthood. tCr and tCho concentrations increase from childhood to early adulthood. Total N-acetyl aspartate (tNAA) and Myo-Inositol (mI) concentrations are relatively stable across development. Trajectories likely reflect fundamental neurodevelopmental processes (including local circuit refinement) which occur from childhood to early adulthood and can be associated with cognitive development; we find GABA+ concentrations significantly positively correlate with recognition memory scores.

Iron-based compounds coordinated with phospho-polymers as biocompatible probes for dual 31P/1H magnetic resonance imaging and spectroscopy

In this work, we present the synthesis and evaluation of magnetic resonance (MR) properties of novel phosphorus/iron-containing probes for dual 31P and 1H MR imaging and spectroscopy (MRI and MRS). The presented probes are composed of biocompatible semitelechelic and multivalent phospho-polymers based on poly(2-methacryloyloxyethyl phosphorylcholine) (pMPC) coordinated with small paramagnetic Fe3+ ions or superparamagnetic maghemite (γ-Fe2O3) nanoparticles via deferoxamine group linked to the end or along the polymer chains. All probes provided very short 1H T1 and T2 relaxation times even at low iron concentrations. The presence of iron had a significant impact on the shortening of 31P relaxation, with the effect being more pronounced for probes based on γ-Fe2O3 and multivalent polymer. While the water-soluble probe having one Fe3+ ion per polymer chain was satisfactorily visualized by both 31P-MRS and 31P-MRI, the probe with multiple Fe3+ ions could only be detected by 31P-MRS, and the probes consisting of γ-Fe2O3 nanoparticles could not be imaged by either technique due to their ultra-short 31P relaxations. In this proof-of-principle study performed on phantoms at a clinically relevant magnetic fields, we demonstrated how the different forms and concentrations of iron affect both the 1H MR signal of the surrounding water molecules and the 31P MR signal of the phospho-polymer probe. Thus, this double contrast can be exploited to simultaneously visualize body anatomy and monitor probe biodistribution.

Preliminary study on early diagnosis of Alzheimer's disease in APP/PS1 transgenic mice using multimodal magnetic resonance imaging.

Alzheimer's disease (AD) has an insidious onset and lacks clear early diagnostic markers, and by the time overt dementia symptoms appear, the disease is already in the mid-to-late stages. The search for early diagnostic markers of AD may open a critical window for Alzheimer's treatment and facilitate early intervention to slow the progression of AD. In this study, we aimed to explore the imaging markers for early diagnosis of AD through the combined application of structural magnetic resonance imaging (sMRI), resting-state functional magnetic resonance imaging (rs-fMRI), and 1H-magnetic resonance spectroscopy (1H-MRS) multimodal magnetic resonance imaging (MRI) techniques at the animal experimental level, with the aim to provide a certain reference for early clinical diagnosis of AD. First, sMRI scans were performed on 4-month-old amyloid beta precursor protein/presenilin 1 (APP/PS1) transgenic AD model mice and wild type mice of the same litter using a 7.0 T animal MRI scanner to analyze the differential brain regions with structural changes in the gray matter of the brain by voxel-based morphometry (VBM). Next, rs-fMRI scans were performed to analyze the differential brain regions between groups for local spontaneous brain activity and functional connectivity (FC) between brain regions. Finally, 1H-MRS scans were performed to quantify and analyze intergroup differences in the relative concentrations of different metabolites within regions of interest (cortex and hippocampus). Compared with wild type mice, the volume of the left hippocampus, and right olfactory bulb of APP/PS1 transgenic AD model mice were reduced, the functional activity of the bilateral hippocampus, right piriform cortex and right caudate putamen was reduced, the functional network connectivity of the hippocampus was impaired, and the relative content of N-acetylaspartate (NAA)in the hippocampus was decreased. In addition, this study found that imaging changes in olfactory-related brain regions were closely associated with AD diagnosis, and these findings may provide some reference for the early diagnosis of AD.

Mapping Changes in Glutamate with Glutamate-Weighted MRI in Forced Swim Test Model of Depression in Rats.

Chemical exchange saturation transfer with glutamate (GluCEST) imaging is a novel technique for the non-invasive detection and quantification of cerebral Glu levels in neuromolecular processes. Here we used GluCEST imaging and 1H magnetic resonance spectroscopy (1H MRS) to assess in vivo changes in Glu signals within the hippocampus in a rat model of depression induced by a forced swim test. The forced swimming test (FST) group exhibited markedly reduced GluCEST-weighted levels and Glu concentrations when examined using 1H MRS in the hippocampal region compared to the control group (GluCEST-weighted levels: 3.67 ± 0.81% vs. 5.02 ± 0.44%, p < 0.001; and Glu concentrations: 6.560 ± 0.292 μmol/g vs. 7.133 ± 0.397 μmol/g, p = 0.001). Our results indicate that GluCEST imaging is a distinctive approach to detecting and monitoring Glu levels in a rat model of depression. Furthermore, the application of GluCEST imaging may provide a deeper insight into the neurochemical involvement of glutamate in various psychiatric disorders.

Characterisation of paediatric brain tumours by their MRS metabolite profiles.

1H-magnetic resonance spectroscopy (MRS) has the potential to improve the noninvasive diagnostic accuracy for paediatric brain tumours. However, studies analysing large, comprehensive, multicentre datasets are lacking, hindering translation to widespread clinical practice. Single-voxel MRS (point-resolved single-voxel spectroscopy sequence, 1.5 T: echo time [TE] 23-37 ms/135-144 ms, repetition time [TR] 1500 ms; 3 T: TE 37-41 ms/135-144 ms, TR 2000 ms) was performed from 2003 to 2012 during routine magnetic resonance imaging for a suspected brain tumour on 340 children from five hospitals with 464 spectra being available for analysis and 281 meeting quality control. Mean spectra were generated for 13 tumour types. Mann-Whitney U-tests and Kruskal-Wallis tests were used to compare mean metabolite concentrations. Receiver operator characteristic curves were used to determine the potential for individual metabolites to discriminate between specific tumour types. Principal component analysis followed by linear discriminant analysis was used to construct a classifier to discriminate the three main central nervous system tumour types in paediatrics. Mean concentrations of metabolites were shown to differ significantly between tumour types. Large variability existed across each tumour type, but individual metabolites were able to aid discrimination between some tumour types of importance. Complete metabolite profiles were found to be strongly characteristic of tumour type and, when combined with the machine learning methods, demonstrated a diagnostic accuracy of 93% for distinguishing between the three main tumour groups (medulloblastoma, pilocytic astrocytoma and ependymoma). The accuracy of this approach was similar even when data of marginal quality were included, greatly reducing the proportion of MRS excluded for poor quality. Children's brain tumours are strongly characterised by MRS metabolite profiles readily acquired during routine clinical practice, and this information can be used to support noninvasive diagnosis. This study provides both key evidence and an important resource for the future use of MRS in the diagnosis of children's brain tumours.

Importance of 1H-MR spectroscopy of the brain to identify the minimal hepatic encephalopathy in different patients with liver cirrhosis: A prospective study.

Liver cirrhosis patients commonly progress to minimal hepatic encephalopathy (MHE) with cognitive impairment and raised blood ammonia and proinflammatory cytokines levels. This study aims to identify the subjects of MHE in patients with liver cirrhosis by hydrogen 1 magnetic resonance (1H-MR) spectroscopy of the brain, serum proinflammatory cytokines, and neuropsychiatric tests. This prospective was carried out on 100 patients of liver cirrhosis without overt hepatic encephalopathy (HE) and compared with 100 healthy controls in a tertiary care hospital in Northeast India between September 2017 and October 2019. The psychometric hepatic encephalopathy score (PHES) neuropsychological tests, cranial MRIwith 1H-MR spectroscopy, and estimation of serum interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were done. The PHES scores and serum proinflammatory markers levels were correlated with the conventional and 1H-MR spectroscopy findings of the brain. The mean PHES score in the case group was -7.58±3.43 (standard deviation [SD]) and the control group was -3.41 ± 3.87 (SD). Patients with Child-Pugh class A (n = 8) had a PHES score of -8.7 ± 2.5 (SD), class B (n = 42) -7.62 ± 3.7 (SD), and class C (n = 50) had a score of -7.36 ± 3.3 (SD). The mean value of IL-6 and TNF-α in the case group was 219 ± 180 (SD) pg/mL and 99 ± 118 (SD) pg/mL and the control group was 67.4 ± 77 (SD) pg/mL and 57.5 ± 76 (SD) pg/mL. Globus pallidus T1-weighted hyperintensities on the visibility scale with a visibility score of 0 were observed in 39 cases, a score of 1 in 38 cases, and a score of 2 in 23 cases. Increased glutamate/glutamine/creatine (Glx/Cr) ratio was identified in the case group on MR spectroscopy as compared to the control (0.95 ± 0.24 vs. 0.31 ± 0.19, P < 0.0005), a decrease of myoinositol/creatine (mI/Cr) ratio (0.11 ± 0.13 vs. 0.30 ± 0.12, P < 0.0005), and increase choline/creatine (Cho/Cr) ratio (0.69 ± 0.26 vs. 0.61 ± 0.20, P < 0.0005). There was a statistically significant difference in Glx/Cr, mI/Cr and Cho/Cr ratio between the case and control groups with P < 0.0005. Predicting the development of MHE in established cases of liver cirrhosis using non-invasive modalities like PHES, IL-6, TNF-α levels, and 1H-MR spectroscopy plays an important role in further progression to overt HE and coma.

Longitudinal MRI and 1H-MRS study of SCA7 mouse forebrain reveals progressive multiregional atrophy and early brain metabolite changes indicating early neuronal and glial dysfunction.

SpinoCerebellar Ataxia type 7 (SCA7) is an inherited disorder caused by CAG triplet repeats encoding polyglutamine expansion in the ATXN7 protein, which is part of the transcriptional coactivator complex SAGA. The mutation primarily causes neurodegeneration in the cerebellum and retina, as well as several forebrain structures. The SCA7140Q/5Q knock-in mouse model recapitulates key disease features, including loss of vision and motor performance. To characterize the temporal progression of brain degeneration of this model, we performed a longitudinal study spanning from early to late symptomatic stages using high-resolution magnetic resonance imaging (MRI) and in vivo 1H-magnetic resonance spectroscopy (1H-MRS). Compared to wild-type mouse littermates, MRI analysis of SCA7 mice shows progressive atrophy of defined brain structures, with the striatum, thalamus and cortex being the first and most severely affected. The volume loss of these structures coincided with increased motor impairments in SCA7 mice, suggesting an alteration of the sensory-motor network, as observed in SCA7 patients. MRI also reveals atrophy of the hippocampus and anterior commissure at mid-symptomatic stage and the midbrain and brain stem at late stage. 1H-MRS of hippocampus, a brain region previously shown to be dysfunctional in patients, reveals early and progressive metabolic alterations in SCA7 mice. Interestingly, abnormal glutamine accumulation precedes the hippocampal atrophy and the reduction in myo-inositol and total N-acetyl-aspartate concentrations, two markers of glial and neuronal damage, respectively. Together, our results indicate that non-cerebellar alterations and glial and neuronal metabolic impairments may play a crucial role in the development of SCA7 mouse pathology, particularly at early stages of the disease. Degenerative features of forebrain structures in SCA7 mice correspond to current observations made in patients. Our study thus provides potential biomarkers that could be used for the evaluation of future therapeutic trials using the SCA7140Q/5Q model.

Metabolic alterations in the right anterior insula among patients with cirrhosis without overt hepatic encephalopathy: a magnetic resonance spectroscopy study.

We investigated metabolic alterations in the right anterior insula (rAI) in cirrhotic patients and determined its association with patients' cognitive dysfunction. In this study, 31 healthy controls (HCs) and 32 cirrhotic patients without overt hepatic encephalopathy participated. Both blood ammonia level and Child-Pugh score were measured. The psychometric hepatic encephalopathy score (PHES) was used to evaluate cognitive function. 1H-magnetic resonance spectroscopy (MRS) data located in the rAI were recorded on a commercially available 3T magnetic resonance imaging scanner. The ratios of metabolites were measured, including N-acetylaspartate (NAA)/total creatine (tCr), glutamate plus glutamine (Glx)/tCr, myo-inositol (mI)/tCr, and total choline (tCho)/tCr. We adopted the non-parametric Mann-Whitney U-test for intergroup comparison of metabolic ratios. To determine the association between metabolite concentration and clinical parameters, we performed Spearman correlation analyses. Patients with cirrhosis performed worse on PHES in comparison with HCs (P < 0.001). Patients with cirrhosis had significantly decreased mI/tCr (0.87 ± 0.07 vs. 0.74 ± 0.19, P = 0.025) and increased Glx/tCr (1.79 ± 0.17 vs. 2.07 ± 0.29, P < 0.001) in the rAI. We did not observe any significant between-group differences in tCho/tCr and NAA/tCr. The blood ammonia level was correlated with Glx/tCr (r = 0.405, P = 0.022) and mI/tCr (r = -0.398, P = 0.024) of the rAI. In addition, PHES was negatively correlated with Glx/tCr of the rAI (r = -0.379, P = 0.033). Metabolic disturbance of the rAI, which is associated with ammonia intoxication, might account for the neural substrate of cirrhosis-related cognitive dysfunction to some extent.

Interhemispheric reactivity of the subthalamic nucleus sustains progressive dopamine neuron loss in asymmetrical parkinsonism

Parkinson's disease (PD) is characterized by the progressive and asymmetrical degeneration of the nigrostriatal dopamine neurons and the unilateral presentation of the motor symptoms at onset, contralateral to the most impaired hemisphere. We previously developed a rat PD model that mimics these typical features, based on unilateral injection of a substrate inhibitor of excitatory amino acid transporters, L-trans-pyrrolidine-2,4-dicarboxylate (PDC), in the substantia nigra (SN). Here, we used this progressive model in a multilevel study (behavioral testing, in vivo 1H-magnetic resonance spectroscopy, slice electrophysiology, immunocytochemistry and in situ hybridization) to characterize the functional changes occurring in the cortico-basal ganglia-cortical network in an evolving asymmetrical neurodegeneration context and their possible contribution to the cell death progression. We focused on the corticostriatal input and the subthalamic nucleus (STN), two glutamate components with major implications in PD pathophysiology. In the striatum, glutamate and glutamine levels increased from presymptomatic stages in the PDC-injected hemisphere only, which also showed enhanced glutamatergic transmission and loss of plasticity at corticostriatal synapses assessed at symptomatic stage. Surprisingly, the contralateral STN showed earlier and stronger reactivity than the ipsilateral side (increased intraneuronal cytochrome oxidase subunit I mRNA levels; enhanced glutamate and glutamine concentrations). Moreover, its lesion at early presymptomatic stage halted the ongoing neurodegeneration in the PDC-injected SN and prevented the expression of motor asymmetry. These findings reveal the existence of endogenous interhemispheric processes linking the primary injured SN and the contralateral STN that could sustain progressive dopamine neuron loss, opening new perspectives for disease-modifying treatment of PD.

State of the art in the diagnostic evaluation of osteomyelitis: exploring the role of advanced MRI sequences-a narrative review.

Osteomyelitis, a severe bone infection caused mainly by pyogenic organisms, poses diagnostic challenges due to its non-specific magnetic resonance imaging (MRI) manifestations. Conventional MRI, though the imaging modality of choice, often exhibits signal abnormalities with overlapping differential diagnoses, potentially leading to overestimation of infection extent and duration. To address these limitations, advanced MRI sequences, including dynamic contrast-enhanced (DCE) MRI, 1H magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI), and Dixon techniques have emerged as promising alternatives. This narrative review explores the potential role of these sequences in aiding the differential diagnosis of osteomyelitis. We used the PubMed database to search for relevant articles using the MeSH keywords: (osteomyelitis) AND (advanced MRI sequences) and we manually selected the most suitable studies to include in our review. Articles outside of original studies were also included. Only records in English or French were considered. In particular, DWI is useful for characterizing fluid collections, distinguishing bone infarcts, and bacterial skull base osteomyelitis from neoplastic lesions. Moreover, DWI assists in differentiating diabetic foot osteomyelitis (DFO) from Charcot neuro-osteoarthropathy, facilitates the diagnosis of pediatric acute osteoarticular infections, and aids in distinguishing osteomyelitis from Modic I degenerative changes. Additionally, DWI proves valuable in monitoring spinal infections and distinguishing pedal osteomyelitis from other conditions, even in patients with renal impairment. DCE-MRI enhances MRI specificity by assessing contrast uptake over time, providing valuable insights into inflammatory microenvironments. It aids in detecting DFO, differentiating it from acute Charcot arthropathy, and distinguishing osteomyelitis from neuropathic arthropathy. Moreover, DCE-MRI shows potential in assessing response to antibiotic therapy in spinal infections. Dixon acquisition improves image quality and facilitates the detection of bone marrow abnormalities, aiding in the differentiation of diabetic foot from osteomyelitis. It also assists in distinguishing osteomyelitis from neuropathic arthropathy and provides valuable information in evaluating the diabetic foot. Proton MR spectroscopy, a well-established modality, offers metabolic information that can differentiate malignant from benign lesions. The role of advanced MRI techniques in evaluating osteomyelitis remains to be fully defined, and further research is required to explore its potential utility in this context. In conclusion, the incorporation of advanced MRI sequences has shown promise in improving the differential diagnosis of osteomyelitis. Future investigations exploring combinations of these techniques and their clinical applications hold significant potential to enhance diagnostic accuracy and patient outcomes.

The diagnostic challenge of lack of choline level elevation on 1H-MR spectroscopy in grade II-III gliomas.

The accurate diagnosis of brain tumour is very important in modern neuro-oncology medicine. Magnetic resonance spectroscopy (MRS) is supposed to be a promising tool for detecting cancerous lesions. However, the interpretation of MRS data is complicated by the fact that not all cancerous lesions exhibit elevated choline (Cho) levels. The main goal of our study was to investigate the lack of Cho lesion /Cho ref elevation in the population of grade II-III gliomas. 89 cases of gliomas grade II and III were used for the retrospective analysis - glioma (astrocytoma or oligodendroglioma) grade II (74 out of 89 cases [83%]) and III (15 out of 89 cases [17%]) underwent conventional MRI extended by MRS before treatment. Histopathological diagnosis was obtained either by biopsy or surgical resection. Gliomas were classified to the group of no-choline elevation when the ratio of choline measured within the tumour (Cho lesion ) to choline from NABT (Cho ref ) were equal to or lower than 1. Significant differences were observed between ratios of Cho lesion /Cr lesion calculated for no-choline elevation and glial tumour groups as well as in the NAA lesion /Cr lesion ratio between the no-choline elevation group and glial tumour group. With consistent data concerning choline level elevation and slightly lower NAA value, the Cho lesion /NAA lesion ratio is significantly higher in the WHO II glial tumour group compared to the no-choline elevation cases ( p < 0.000). In the current study the results demonstrated possibility of lack of choline elevation in patients with grade II-III gliomas, so it is important to remember that the lack of elevated choline levels does not exclude neoplastic lesion.

Brain glutathione may be associated with white matter hyperintensities in patients with cardiovascular disease

AbstractBackgroundWhite matter hyperintensity (WMH) is a marker of age‐related cerebrovascular damage and is correlated with cognitive impairment; ischemia and inflammatory mechanisms have been proposed to be involved in its pathogenesis. These processes are associated with oxidative stress (OS), which may impair cellular function and affect antioxidant balance; however, the role of central antioxidant responses is still unclear.MethodPatients (age 55‐85) with ≥2 vascular risk factors or a previous vascular event were assessed at baseline for an exercise rehabilitation program. All participants completed the Montreal Cognitive Assessment (MoCA). Baseline WHM severity was determined using the standardized Canadian Dementia Imaging Protocol and semiautomatic protocols. Brain glutathione (GSH) at baseline was obtained in the anterior cingulate (AC) and occipital region (OC) using 1H magnetic resonance spectroscopy (MEscher–GArwood Point Resolved Spectroscopy). Spectroscopic analysis was completed using the Gannet toolkit (vers. 3.1) in Matlab (vers. 2020b).ResultOf 30 participants (mean age: 66.2 ± 7.42 SD; 80% male) currently enrolled, brain volumetric measurements were completed for 25 participants. Lower MoCA score was associated with greater total WMH volume, controlling for age (b[SE] = ‐0.017 [0.005], t(22) = ‐3.24, p = 0.004); this relationship remained significant when controlling for years of education separately (b[SE] = ‐0.016 [0.006], t(22) = ‐2.86, p = 0.01). Correcting for cerebrospinal fluid volume, lower AC‐GSH level was associated with higher deep WMH volume in the medial middle frontal (MMF) region of interest (b[SE] = ‐0.056 [0.023], t(23) = ‐2.38, p = 0.026), but not with MMF paraventricular WMH volume. After controlling for age, the model was no longer significant (F (2, 22) = 2.87, p = 0.078). No significant associations were found between OC‐GSH and occipital lobe WMH.ConclusionAs expected, total white matter hyperintensity volume was associated with poorer global cognition. In the medial middle frontal (MMF) region of interest, higher deep WMH was associated with lower GSH levels, suggesting altered brain antioxidant levels may be associated with the presence or formation of WMH. Recruitment is ongoing, and additional participants are needed to reinforce findings and to control for confounders in the analysis.