Proton Magnetic Resonance Spectroscopic Imaging Research Articles

Radiation-induced bystander effect on the brain after fractionated spinal cord irradiation of aging rats

We investigated the influence of the so-called bystander effect on metabolic and histopathological changes in the rat brain after fractionated spinal cord irradiation. The study was initiated with adult Wistar male rats (n = 20) at the age of 9 months. The group designated to irradiation (n = 10) and the age-matched control animals (n = 10) were subjected to an initial measurement using in vivo proton magnetic resonance spectroscopy (1H MRS) and magnetic resonance imaging (MRI). After allowing the animals to survive until 12 months, they received fractionated spinal cord irradiation with a total dose of 24 Gy administered in 3 fractions (8 Gy per fraction) once a week on the same day for 3 consecutive weeks. 1H MRS and MRI of brain metabolites were performed in the hippocampus, corpus striatum, and olfactory bulb (OB) before irradiation (9-month-old rats) and subsequently 48 h (12-month-old) and 2 months (14-month-old) after the completion of irradiation. After the animals were sacrificed at the age of 14 months, brain tissue changes were investigated in two neurogenic regions: the hippocampal dentate gyrus (DG) and the rostral migratory stream (RMS). By comparing the group of 9-month-old rats and individuals measured 48 h (at the age of 12 months) after irradiation, we found a significant decrease in the ratio of total N-acetyl aspartate to total creatine (tNAA/tCr) and gamma-aminobutyric acid to tCr (GABA/tCr) in OB and hippocampus. A significant increase in myoinositol to tCr (mIns/tCr) in the OB persisted up to 14 months of age. Proton nuclear magnetic resonance (1H NMR)-based plasma metabolomics showed a significant increase in keto acids and decreased tyrosine and tricarboxylic cycle enzymes. Morphometric analysis of neurogenic regions of 14-month-old rats showed well-preserved stem cells, neuroblasts, and increased neurodegeneration. The radiation-induced bystander effect more significantly affected metabolite concentration than the distribution of selected cell types.

Downfield Proton MRSI at 3 Tesla: A Pilot Study in Human Brain Tumors.

To investigate the use of 3D downfield proton magnetic resonance spectroscopic imaging (DF-MRSI) for evaluation of tumor recurrence in patients with glioblastoma (GBM). Seven patients (4F, age range 44-65 and mean ± standard deviation 59.3 ± 7.5 years) with previously treated GBM were scanned using a recently developed 3D DF-MRSI sequence at 3T. Short TE 3D DF-MRSI and water reference 3D-MRSI scans were collected with a nominal spatial resolution of 0.7 cm3. DF volume data in eight slices covered 12 cm of brain in the cranio-caudal axis. Data were analyzed using the 'LCModel' program and a basis set containing nine peaks ranging in frequency between 6.83 to 8.49 ppm. The DF8.18 (assigned to amides) and DF7.90 peaks were selected for the creation of metabolic images and statistical analysis. Longitudinal MR images and clinical history were used to classify brain lesions as either recurrent tumor or treatment effect, which may include necrosis. DF-MRSI data were compared between lesion groups (recurrent tumor, treatment effect) and normal-appearing brain. Of the seven brain tumor patients, two were classified as having recurrent tumor and the rest were classified as treatment effect. Amide metabolite levels from recurrent tumor regions were significantly (p < 0.05) higher compared to both normal-appearing brain and treatment effect regions. Amide levels in lesion voxels classified as treatment effect were significantly lower than normal brain. 3D DF-MRSI in human brain tumors at 3T is feasible and was well tolerated by all patients enrolled in this preliminary study. Amide levels measured by 3D DF-MRSI were significantly different between treatment effect and tumor regrowth.

Proton Magnetic Resonance Spectroscopy versus Dynamic Contrast-Enhanced Magnetic Resonance Imaging in distinguishing recurrent brain tumors from brain radiation necrosis

Proton Magnetic Resonance Spectroscopy versus Dynamic Contrast-Enhanced Magnetic Resonance Imaging in distinguishing recurrent brain tumors from brain radiation necrosis

GABA decrease is associated with degraded neural specificity in the visual cortex of glaucoma patients

Glaucoma is an age-related neurodegenerative disease of the visual system, affecting both the eye and the brain. Yet its underlying metabolic mechanisms and neurobehavioral relevance remain largely unclear. Here, using proton magnetic resonance spectroscopy and functional magnetic resonance imaging, we investigated the GABAergic and glutamatergic systems in the visual cortex of glaucoma patients, as well as neural specificity, which is shaped by GABA and glutamate signals and underlies efficient sensory and cognitive functions. Our study shows that among the older adults, both GABA and glutamate levels decrease with increasing glaucoma severity regardless of age. Further, our study shows that the reduction of GABA but not glutamate predicts the neural specificity. This association is independent of the impairments on the retina structure, age, and the gray matter volume of the visual cortex. Our results suggest that glaucoma-specific decline of GABA undermines neural specificity in the visual cortex and that targeting GABA could improve the neural specificity in glaucoma.

White Matter Metabolite Ratios Predict Cognitive Outcome in Pediatric Traumatic Brain Injury.

The prognostic ability of global white matter and gray matter metabolite ratios following pediatric traumatic brain injury (TBI) and their relationship to 12-month neuropsychological assessments of intelligence quotient (IQ), attention, and memory is presented. Three-dimensional proton magnetic resonance spectroscopic imaging (MRSI) in pediatric subjects with complicated mild (cMild), moderate, and severe TBI was acquired acutely (6-18 days) and 12 months post-injury and compared to age-matched typically developing adolescents. A global linear regression model, co-registering MRSI metabolite maps with 3D high-resolution magnetic resonance images, was used to identify longitudinal white matter and gray matter metabolite ratio changes. Acutely, gray matter NAA/Cr, white matter NAA/Cr, and white matter NAA/Cho ratios were significantly lower in TBI groups compared to controls. Gray matter NAA/Cho was reduced only in the severe TBI group. At 12 months, all metabolite ratios normalized to control levels in each of the TBI groups. Acute gray matter and white matter NAA ratios were significantly correlated to 12-month assessments of IQ, attention, and memory. These findings suggest that whole brain gray matter and white matter metabolite ratios reflect longitudinal changes in neuronal metabolism following TBI, which can be used to predict neuropsychological outcomes in pediatric subjects.

Is increased myocardial triglyceride content associated with early changes in left ventricular function? A 1H-MRS and MRI strain study.

Type 2 diabetes (T2D) and obesity induce left ventricular (LV) dysfunction. The underlying pathophysiological mechanisms remain unclear, but myocardial triglyceride content (MTGC) could be involved. This study aimed to determine which clinical and biological factors are associated with increased MTGC and to establish whether MTGC is associated with early changes in LV function. A retrospective study was conducted using five previous prospective cohorts, leading to 338 subjects studied, including 208 well-phenotyped healthy volunteers and 130 subjects living with T2D and/or obesity. All the subjects underwent proton magnetic resonance spectroscopy and feature tracking cardiac magnetic resonance imaging to measure myocardial strain. MTGC content increased with age, body mass index (BMI), waist circumference, T2D, obesity, hypertension, and dyslipidemia, but the only independent correlate found in multivariate analysis was BMI (p=0.01; R²=0.20). MTGC was correlated to LV diastolic dysfunction, notably with the global peak early diastolic circumferential strain rate (r=-0.17, p=0.003), the global peak late diastolic circumferential strain rate (r=0.40, p<0.0001) and global peak late diastolic longitudinal strain rate (r=0.24, p<0.0001). MTGC was also correlated to systolic dysfunction via end-systolic volume index (r=-0.34, p<0.0001) and stroke volume index (r=-0.31, p<0.0001), but not with longitudinal strain (r=0.009, p=0.88). Interestingly, the associations between MTGC and strain measures did not persist in multivariate analysis. Furthermore, MTGC was independently associated with LV end-systolic volume index (p=0.01, R²=0.29), LV end-diastolic volume index (p=0.04, R²=0.46), and LV mass (p=0.002, R²=0.58). Predicting MTGC remains a challenge in routine clinical practice, as only BMI independently correlates with increased MTGC. MTGC may play a role in LV dysfunction but does not appear to be involved in the development of subclinical strain abnormalities.

Microstructural and Metabolic Changes in Normal Aging Human Brain Studied with Combined Whole-Brain MR Spectroscopic Imaging and Quantitative MR Imaging

PurposeThis study aimed to detect age-related brain metabolic and microstructural changes in healthy human brains by the use of whole-brain proton magnetic resonance spectroscopic imaging (1H‑MRSI) and quantitative MR imaging (qMRI).MethodsIn this study, 60 healthy participants with evenly distributed ages (between 21 and 69 years) and sex underwent MRI examinations at 3T including whole-brain 1H‑MRSI. The concentrations of the metabolites N‑acetylaspartate (NAA), choline-containing compounds (Cho), total creatine and phosphocreatine (tCr), glutamine and glutamate (Glx), and myo-inositol (mI), as well as the brain relaxation times T2, T2’ and T1 were measured in 12 regions of interest (ROI) in each hemisphere. Correlations between measured parameters and age were estimated with linear regression analysis and Pearsonʼs correlation test.ResultsSignificant age-related changes of brain regional metabolite concentrations and tissue relaxation times were found: NAA decreased in eight of twelve ROIs, Cho increased in three ROIs, tCr in four ROIs, and mI in three ROIs. Glx displayed a significant decrease in one ROI and an increase in another ROI. T1 increased in four ROIs and T2 in one ROI, while T2’ decreased in two ROIs. A negative correlation of tCr concentrations with T2’ relaxation time was found in one ROI as well as the positive correlations of age-related T1 relaxation time with concentrations of tCr, mI, Glx and Cho in another ROI.ConclusionNormal aging in human brain is associated with coexistent brain regional metabolic alterations and microstructural changes, which may be related to age-related decline in cognitive, affective and psychomotor domains of life in the older population.

Gut and oral microbiome modulate molecular and clinical markers of schizophrenia-related symptoms: A transdiagnostic, multilevel pilot study

Although increasing evidence links microbial dysbiosis with the risk for psychiatric symptoms through the microbiome-gut-brain axis (MGBA), the specific mechanisms remain poorly characterized. In a diagnostically heterogeneous group of treated psychiatric cases and nonpsychiatric controls, we characterized the gut and oral microbiome, plasma cytokines, and hippocampal inflammatory processes via proton magnetic resonance spectroscopic imaging (1H-MRSI). Using a transdiagnostic approach, these data were examined in association with schizophrenia-related symptoms measured by the Positive and Negative Syndrome Scale (PANSS). Psychiatric cases had significantly greater heterogeneity of gut alpha diversity and an enrichment of pathogenic taxa, like Veillonella and Prevotella, in the oral microbiome, which was an accurate classifier of phenotype. Cases exhibited significantly greater positive, negative, and general PANSS scores that uniquely correlated with bacterial taxa. Strong, positive correlations of bacterial taxa were also found with cytokines and hippocampal gliosis, dysmyelination, and excitatory neurotransmission. This pilot study supports the hypothesis that the MGBA influences psychiatric symptomatology in a transdiagnostic manner. The relative importance of the oral microbiome in peripheral and hippocampal inflammatory pathways was highlighted, suggesting opportunities for probiotics and oral health to diagnose and treat psychiatric conditions.

1H magnetic resonance spectroscopic imaging of deuterated glucose and of neurotransmitter metabolism at 7 T in the human brain.

Impaired glucose metabolism in the brain has been linked to several neurological disorders. Positron emission tomography and carbon-13 magnetic resonance spectroscopic imaging (MRSI) can be used to quantify the metabolism of glucose, but these methods involve exposure to radiation, cannot quantify downstream metabolism, or have poor spatial resolution. Deuterium MRSI (2H-MRSI) is a non-invasive and safe alternative for the quantification of the metabolism of 2H-labelled substrates such as glucose and their downstream metabolic products, yet it can only measure a limited number of deuterated compounds and requires specialized hardware. Here we show that proton MRSI (1H-MRSI) at 7 T has higher sensitivity, chemical specificity and spatiotemporal resolution than 2H-MRSI. We used 1H-MRSI in five volunteers to differentiate glutamate, glutamine, γ-aminobutyric acid and glucose deuterated at specific molecular positions, and to simultaneously map deuterated and non-deuterated metabolites. 1H-MRSI, which is amenable to clinically available magnetic-resonance hardware, may facilitate the study of glucose metabolism in the brain and its potential roles in neurological disorders.

Is pre-radiotherapy metabolic heterogeneity of glioblastoma predictive of progression-free survival?

Background and purposeAll glioblastoma subtypes share the hallmark of aggressive invasion, meaning that it is crucial to identify their different components if we are to ensure effective treatment and improve survival. Proton MR spectroscopic imaging (MRSI) is a noninvasive technique that yields metabolic information and is able to identify pathological tissue with high accuracy. The aim of the present study was to identify clusters of metabolic heterogeneity, using a large MRSI dataset, and determine which of these clusters are predictive of progression-free survival (PFS). Materials and methodsMRSI data of 180 patients acquired in a pre-radiotherapy examination were included in the prospective SPECTRO-GLIO trial. Eight features were extracted for each spectrum: Cho/NAA, NAA/Cr, Cho/Cr, Lac/NAA, and the ratio of each metabolite to the sum of all the metabolites. Clustering of data was performed using a mini-batch k-means algorithm. The Cox model and logrank test were used for PFS analysis. ResultsFive clusters were identified as sharing similar metabolic information and being predictive of PFS. Two clusters revealed metabolic abnormalities. PFS was lower when Cluster 2 was the dominant cluster in patients’ MRSI data. Among the metabolites, lactate (present in this cluster and in Cluster 5) was the most statistically significant predictor of poor outcome. ConclusionResults showed that pre-radiotherapy MRSI can be used to reveal tumor heterogeneity. Groups of spectra, which have the same metabolic information, reflect the different tissue components representative of tumor burden proliferation and hypoxia. Clusters with metabolic abnormalities and high lactate are predictive of PFS.

Associations between N-Acetylaspartate and white matter integrity in individuals with schizophrenia and unaffected relatives.

Compromised white matter has been reported in schizophrenia; however, few studies have investigated neurochemical abnormalities underlying microstructural differences. N-acetylaspartate (NAA) is used to synthesize myelin and is often reduced in persons with schizophrenia (PSZ) and their unaffected first-degree relatives (REL). Low levels of NAA could affect white matter by preventing the synthesis or repair of myelin. We used magnetic resonance spectroscopy and diffusion tensor imaging to investigate the relationship between NAA and white matter integrity in PSZ. REL were included to examine whether putative relationships are associated with symptom expression or illness liability. 52 controls, 23 REL and 25 PSZ underwent 7T proton magnetic resonance spectroscopy and/or 3T diffusion tensor imaging. NAA in the visual cortex and basal ganglia were measured and compared across groups. Diffusivity measures were compared across groups using tract-based spatial statistics and related to NAA concentrations. Visual cortex NAA was significantly reduced in PSZ compared to controls. White matter integrity did not differ between groups. Reduced cortical and subcortical NAA were associated with diffusivity measures of poor white matter microstructure. These data suggest that levels of neural NAA may be related to white matter integrity similarly across individuals with schizophrenia, those at genetic risk, and controls.

Hypothalamic neuroglial plasticity is regulated by anti-Müllerian hormone and disrupted in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common reproductive-endocrine disorder affecting between 5 and 18% of women worldwide. An elevated frequency of pulsatile luteinizing hormone (LH) secretion and higher serum levels of anti-Müllerian hormone (AMH) are frequently observed in women with PCOS. The origin of these abnormalities is, however, not well understood. We studied brain structure and function in women with and without PCOS using proton magnetic resonance spectroscopy (MRS) and diffusion tensor imaging combined with fiber tractography. Then, using a mouse model of PCOS, we investigated by electron microscopy whether AMH played a role on the regulation of hypothalamic structural plasticity. Increased AMH serum levels are associated with increased hypothalamic activity/axonal-glial signalling in PCOS patients. Furthermore, we demonstrate that AMH promotes profound micro-structural changes in the murine hypothalamic median eminence (ME), creating a permissive environment for GnRH secretion. These include the retraction of the processes of specialized AMH-sensitive ependymo-glial cells called tanycytes, allowing more GnRH neuron terminals to approach ME blood capillaries both during the run-up to ovulation and in a mouse model of PCOS. We uncovered a central function for AMH in the regulation of fertility by remodeling GnRH terminals and their tanycytic sheaths, and provided insights into the pivotal role of the brain in the establishment and maintenance of neuroendocrine dysfunction in PCOS. INSERM (U1172), European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement n° 725149), CHU de Lille, France (Bonus H).

Whole-brain MR spectroscopic imaging reveals regional metabolite abnormalities in perinatally HIV infected young adults.

Perinatally acquired HIV (PHIV) has been associated with brain structural and functional deficiencies, and with poorer cognitive performance despite the advent of antiretroviral therapy (ART). However, investigation of brain metabolite levels in PHIV measured by proton magnetic resonance spectroscopy (MRS) methods, is still limited with often inconclusive or contradictory findings. In general, these MRS-based methods have used a single voxel approach that can only evaluate metabolite concentrations in a few select brain anatomical regions. Additionally, most of the published data have been on children perinatally infected with HIV with only a few studies examining adult populations, though not exclusively. Therefore, this prospective and cross-sectional study aims to evaluate metabolite differences at the whole-brain level, using a unique whole-brain proton magnetic resonance spectroscopy imaging (MRSI) method, in a group of PHIV infected young adults (N = 28) compared to age and gender matched control sample (N = 28), and to find associations with HIV clinical factors and neurocognitive scores. MRSI data were acquired on a 3T scanner with a TE of 70 ms. Brain metabolites levels of total N-acetylaspartate (tNAA), total choline (tCho) and total creatine (tCre), as well as ratios of tNAA/tCre, tCho/tCre, and tNAA/tCho, were obtained from the whole brain level and evaluated at the level of gray matter (GM) and white matter (WM) tissue types and anatomical regions of interest (ROI). Our results indicate extensive metabolic abnormalities throughout the brains of PHIV infected subjects with significantly elevated levels of tCre and tCho, notably in GM regions. Decreases in tNAA and ratios of tNAA/tCre and tNAA/tCho were also found mostly in WM regions. These metabolic alterations indicate increased glial activation, inflammation, neuronal dysfunction, and energy metabolism in PHIV infected individuals, which correlated with a reduction in CD4 cell count, and lower cognitive scores. Our findings suggest that significant brain metabolite alterations and associated neurological complications persist in the brains of those with PHIV on long-term ART, and advocates the need for continued monitoring of their brain health.

Neurometabolite alterations in traumatic brain injury and associations with chronic pain.

Traumatic brain injury (TBI) can lead to a variety of comorbidities, including chronic pain. Although brain tissue metabolite alterations have been extensively examined in several chronic pain populations, it has received less attention in people with TBI. Thus, the primary aim of this study was to compare brain tissue metabolite levels in people with TBI and chronic pain (n = 16), TBI without chronic pain (n = 17), and pain-free healthy controls (n = 31). The metabolite data were obtained from participants using whole-brain proton magnetic resonance spectroscopic imaging (1H-MRSI) at 3 Tesla. The metabolite data included N-acetylaspartate, myo-inositol, total choline, glutamate plus glutamine, and total creatine. Associations between N-acetylaspartate levels and pain severity, neuropathic pain symptom severity, and psychological variables, including anxiety, depression, post-traumatic stress disorder (PTSD), and post-concussive symptoms, were also explored. Our results demonstrate N-acetylaspartate, myo-inositol, total choline, and total creatine alterations in pain-related brain regions such as the frontal region, cingulum, postcentral gyrus, and thalamus in individuals with TBI with and without chronic pain. Additionally, NAA levels in the left and right frontal lobe regions were positively correlated with post-concussive symptoms; and NAA levels within the left frontal region were also positively correlated with neuropathic pain symptom severity, depression, and PTSD symptoms in the TBI with chronic pain group. These results suggest that neuronal integrity or density in the prefrontal cortex, a critical region for nociception and pain modulation, is associated with the severity of neuropathic pain symptoms and psychological comorbidities following TBI. Our data suggest that a combination of neuronal loss or dysfunction and maladaptive neuroplasticity may contribute to the development of persistent pain following TBI, although no causal relationship can be determined based on these data.

Diffusion-weighted magnetic resonance imaging and magnetic resonance spectroscopy for non-invasive characterization of azoospermia: A prospective comparative single-center study.

Azoospermia affects about 15% of childless males. The differential diagnosis between subtypes of azoospermia is the initial step in its management. To investigate the role of diffusion-weighted magnetic resonance imaging and proton magnetic resonance spectroscopy in distinguishing obstructive azoospermia from non-obstructive azoospermia and predicting sperm retrieval together with histological alterations in men with non-obstructive azoospermia. This prospective comparative study involved 60 men with obstructive azoospermia (group A) and 60 men with non-obstructive azoospermia (group B). Scrotal proton magnetic resonance spectroscopy and diffusion-weighted magnetic resonance imaging were conducted for all participants to respectively evaluate testicular metabolites and normalized apparent diffusion coefficient 1 week before sperm retrieval. Apparent diffusion coefficient was significantly higher in group B as compared to group A (0.47±0.11vs. 0.29±0.05; and 0.46±0.14vs. 0.28±0.02) for the right and left testis, respectively. Conversely, testicular choline and lipids were significantly higher in group A as compared to group B. Normalized apparent diffusion coefficient, choline, and lipids at cut-off levels of 0.353, 0.31, and 0.725 could differentiate between obstructive azoospermia and non-obstructive azoospermia (area under the curve=0.963; confidence interval=0.939-0.986, area under the curve=0.985; confidence interval=0.974-0.997, and area under the curve=0.970; confidence interval=0.940-0.999, respectively). Regarding the prediction of sperm retrieval in the non-obstructive azoospermia group, choline levels had the highest area under the curve (0.923), and its cut-off level was 0.195. The normalized apparent diffusion coefficient was significantly lower in men with positive sperm retrieval as compared to men with unsuccessful retrieval. Finally, it was revealed that all magnetic resonance imaging parameters except creatine could independently predict testicular histology in men with non-obstructive azoospermia. The highest prediction was 95% in normal spermatogenesis, and the least prediction was 40% in spermatid arrest. Regression analysis was used to detect final predictors and extrapolate an equation that could be used to predict testicular pathology CONCLUSIONS: Normalized apparent diffusion coefficient and proton magnetic resonance spectroscopy are helpful in differentiating obstructive azoospermia from non-obstructive azoospermia and predicting sperm retrieval and related histological alterations in men with non-obstructive azoospermia.

Noninvasive 3-Dimensional 1 H-Magnetic Resonance Spectroscopic Imaging of Human Brain Glucose and Neurotransmitter Metabolism Using Deuterium Labeling at 3T : Feasibility and Interscanner Reproducibility.

Noninvasive, affordable, and reliable mapping of brain glucose metabolism is of critical interest for clinical research and routine application as metabolic impairment is linked to numerous pathologies, for example, cancer, dementia, and depression. A novel approach to map glucose metabolism noninvasively in the human brain has been presented recently on ultrahigh-field magnetic resonance (MR) scanners (≥7T) using indirect detection of deuterium-labeled glucose and downstream metabolites such as glutamate, glutamine, and lactate. The aim of this study was to demonstrate the feasibility to noninvasively detect deuterium-labeled downstream glucose metabolites indirectly in the human brain via 3-dimensional (3D) proton ( 1 H) MR spectroscopic imaging on a clinical 3T MR scanner without additional hardware. This prospective, institutional review board-approved study was performed in 7 healthy volunteers (mean age, 31 ± 4 years, 5 men/2 women) after obtaining written informed consent. After overnight fasting and oral deuterium-labeled glucose administration, 3D metabolic maps were acquired every ∼4 minutes with ∼0.24 mL isotropic spatial resolution using real-time motion-, shim-, and frequency-corrected echo-less 3D 1 H-MR spectroscopic Imaging on a clinical routine 3T MR system. To test the interscanner reproducibility of the method, subjects were remeasured on a similar 3T MR system. Time courses were analyzed using linear regression and nonparametric statistical tests. Deuterium-labeled glucose and downstream metabolites were detected indirectly via their respective signal decrease in dynamic 1 H MR spectra due to exchange of labeled and unlabeled molecules. Sixty-five minutes after deuterium-labeled glucose administration, glutamate + glutamine (Glx) signal intensities decreased in gray/white matter (GM/WM) by -1.63 ± 0.3/-1.0 ± 0.3 mM (-13% ± 3%, P = 0.02/-11% ± 3%, P = 0.02), respectively. A moderate to strong negative correlation between Glx and time was observed in GM/WM ( r = -0.64, P < 0.001/ r = -0.54, P < 0.001), with 60% ± 18% ( P = 0.02) steeper slopes in GM versus WM, indicating faster metabolic activity. Other nonlabeled metabolites showed no significant changes. Excellent intrasubject repeatability was observed across scanners for static results at the beginning of the measurement (coefficient of variation 4% ± 4%), whereas differences were observed in individual Glx dynamics, presumably owing to physiological variation of glucose metabolism. Our approach translates deuterium metabolic imaging to widely available clinical routine MR scanners without specialized hardware, offering a safe, affordable, and versatile (other substances than glucose can be labeled) approach for noninvasive imaging of glucose and neurotransmitter metabolism in the human brain.

Correction to ‘ ORYX‐MRSI : A fully‐automated open‐source software for proton magnetic resonance spectroscopic imaging data analysis’

International Journal of Imaging Systems and TechnologyVolume 33, Issue 2 p. 770-770 CORRIGENDUMFree Access Correction to ‘ORYX-MRSI: A fully-automated open-source software for proton magnetic resonance spectroscopic imaging data analysis’ This article corrects the following: ORYX-MRSI: A fully-automated open-source software for proton magnetic resonance spectroscopic imaging data analysis Sevim Cengiz, Muhammed Yildirim, Abdullah Bas, Esin Ozturk-Isik, Volume 32Issue 4International Journal of Imaging Systems and Technology pages: 1068-1083 First Published online: May 17, 2022 First published: 27 January 2023 https://doi.org/10.1002/ima.22857AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat We regret to report a technical error in our manuscript entitled ‘ORYX-MRSI: A fully-automated open-source software for proton magnetic resonance spectroscopic imaging data analysis’. The volume of interest (VOI) for all the MR spectroscopic metabolites, other than the reference metabolite, are shifted in space by their respective chemical shift amounts as calculated by Equation 2 due to the chemical shift error. Even though there is a shift in the VOIs of different metabolites, it was incorrect to shift the metabolite maps along with their corresponding VOIs. This technical error has been corrected in the Oryx-MRSI source code, which has been updated on our laboratory's GitHub page. Currently, if the chemical shift correction is set to ‘on’, the corresponding VOIs for the metabolites are shifted in space by their respective chemical shift amounts, and the metabolite intensities are evaluated at their respective locations. Additionally, the metabolite ratios are evaluated only in the region that is located at the intersection of the corresponding metabolite VOIs. Moreover, the tissue fractions are calculated only once at the reference VOI. As a result, Figure 5 is not accurate after correction and hence should not be considered for further discussion. The authors thank Wolfgang Bogner, Ph.D. and Gilbert Hangel, Ph.D. for their careful reviews of the published manuscript and apologize for this error. REFERENCE 1Cengiz S, Yildirim M, Bas A, Ozturk-Isik E. ORYX-MRSI: a fully-automated open-source software for proton magnetic resonance spectroscopic imaging data analysis. Int J Imaging Syst Technol. 2022; 32: 1068- 1083. doi:10.1002/ima.22748 Volume33, Issue2March 2023Pages 770-770 ReferencesRelatedInformation

Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes and Chronic Kidney Disease

Background: Nonalcoholic fatty liver disease (NAFLD) is suggested as a risk factor for chronic kidney disease (CKD). The incidence of NAFLD is rising globally in parallel to the increasing incidences of obesity and type 2 diabetes. Diabetes remains the leading cause of CKD, but the co-existence of NAFLD, CKD, and type 2 diabetes is not well elucidated. Here, we evaluated the prevalence of NAFLD in patients with type 2 diabetes with and without CKD. Methods: This was a cross-sectional study including 50 patients with type 2 diabetes and CKD stages 3–5 (no dialysis), and 50 patients with type 2 diabetes without CKD. Liver fat content was estimated by proton magnetic resonance spectroscopy and magnetic resonance imaging proton density fat fraction. NAFLD was defined as liver fat fraction ≥5.6% according to guidelines. Results: Mean age was 72 ± 4.9 years in patients with CKD and 65.9 ± 7.8 years in patients without CKD (p < 0.0001). Three out of four participants were men. BMI was 28.6 ± 3.5 kg/m² and 27 ± 4.0 kg/m² in patients with and without CKD, respectively (p = 0.0087). NAFLD was identified in 22 (44%) patients with CKD and 19 (38%) patients without CKD (p = 0.6845). Median (IQR) liver fat fraction was 4.7% (3.0–8.5) and 4.1% (2.9–7.7) in patients with and without CKD, respectively (difference in geometric means 5.3%, 95% CI −23; 45, p = 0.7463). Conclusion: These findings do not support any association between NAFLD and CKD (stages 3–5) in patients with type 2 diabetes.

Replicability of proton MR spectroscopic imaging findings in mild traumatic brain injury: Implications for clinical applications

PurposeProton magnetic resonance spectroscopy (1H MRS) offers biomarkers of metabolic damage after mild traumatic brain injury (mTBI), but a lack of replicability studies hampers clinical translation. In a conceptual replication study design, the results reported in four previous publications were used as the hypotheses (H1-H7), specifically: abnormalities in patients are diffuse (H1), confined to white matter (WM) (H2), comprise low N-acetyl-aspartate (NAA) levels and normal choline (Cho), creatine (Cr) and myo-inositol (mI) (H3), and correlate with clinical outcome (H4); additionally, a lack of findings in regional subcortical WM (H5) and deep gray matter (GM) structures (H6), except for higher mI in patients’ putamen (H7). Methods26 mTBI patients (20 female, age 36.5 ± 12.5 [mean ± standard deviation] years), within two months from injury and 21 age-, sex-, and education-matched healthy controls were scanned at 3 Tesla with 3D echo-planar spectroscopic imaging. To test H1-H3, global analysis using linear regression was used to obtain metabolite levels of GM and WM in each brain lobe. For H4, patients were stratified into non-recovered and recovered subgroups using the Glasgow Outcome Scale Extended. To test H5-H7, regional analysis using spectral averaging estimated metabolite levels in four GM and six WM structures segmented from T1-weighted MRI. The Mann-Whitney U test and weighted least squares analysis of covariance were used to examine mean group differences in metabolite levels between all patients and all controls (H1-H3, H5-H7), and between recovered and non-recovered patients and their respectively matched controls (H4). Replicability was defined as the support or failure to support the null hypotheses in accordance with the content of H1-H7, and was further evaluated using percent differences, coefficients of variation, and effect size (Cohen’s d). ResultsPatients’ occipital lobe WM Cho and Cr levels were 6.0% and 4.6% higher than controls’, respectively (Cho, d = 0.37, p = 0.04; Cr, d = 0.63, p = 0.03). The same findings, i.e., higher patients’ occipital lobe WM Cho and Cr (both p = 0.01), but with larger percent differences (Cho, 8.6%; Cr, 6.3%) and effect sizes (Cho, d = 0.52; Cr, d = 0.88) were found in the comparison of non-recovered patients to their matched controls. For the lobar WM Cho and Cr comparisons without statistical significance (frontal, parietal, temporal), unidirectional effect sizes were observed (Cho, d = 0.07 – 0.37; Cr, d = 0.27 – 0.63). No differences were found in any metabolite in any lobe in the comparison between recovered patients and their matched controls. In the regional analyses, no differences in metabolite levels were found in any GM or WM region, but all WM regions (posterior, frontal, corona radiata, and the genu, body, and splenium of the corpus callosum) exhibited unidirectional effect sizes for Cho and Cr (Cho, d = 0.03 – 0.34; Cr, d = 0.16 – 0.51). ConclusionsWe replicated findings of diffuse WM injury, which correlated with clinical outcome (supporting H1-H2, H4). These findings, however, were among the glial markers Cho and Cr, not the neuronal marker NAA (not supporting H3). No differences were found in regional GM and WM metabolite levels (supporting H5-H6), nor in putaminal mI (not supporting H7). Unidirectional effect sizes of higher patients’ Cho and Cr within all WM analyses suggest widespread injury, and are in line with the conclusion from the previous publications, i.e., that detection of WM injury may be more dependent upon sensitivity of the 1H MRS technique than on the selection of specific regions. The findings lend further support to the corollary that clinic-ready 1H MRS biomarkers for mTBI may best be achieved by using high signal-to-noise-ratio single-voxels placed anywhere within WM. The biochemical signature of the injury, however, may differ and therefore absolute levels, rather than ratios may be preferred. Future replication efforts should further test the generalizability of these findings.

Proton magnetic resonance spectroscopy (MRS) in individuals with internet gaming.

Various comorbid psychiatric diagnoses, including attention deficit hyperactivity disorder (ADHD), have been reported in individuals with internet gaming disorder (IGD). Prior research has shown alterations in brain metabolites, including N-acetylaspartate (NAA), and combined glutamate and glutamine in patients with ADHD that were similar to those observed in patients with IGD. We hypothesized that the decreased NAA levels in the IGD group would be associated with a history of ADHD. Forty adults participated in this study. Participants were classified as having a high risk for IGD if they had a total score higher than 21 on the IGD Scale-short form. Proton magnetic resonance spectroscopy (1H-MRS) and high-resolution structural magnetic resonance imaging (MRI) data were acquired using a 3 Tesla Siemens Prisma scanner system. Levels of NAA within the right prefrontal cortex were lower in the IGD group than those observed in the control group. In a multiple linear regression analysis, internet addiction test scores and history of ADHD were shown to predict increased game play. In addition, history of ADHD predicted lower levels of NAA within the right prefrontal cortex. The preliminary results of current study suggest a mediating effect of ADHD on the severity of internet game play as well as the levels of NAA within the dorsolateral prefrontal cortex (DLPFC). The inclusion of ADHD in IGD research is important and deserving of further consideration.