Whole-brain Magnetic Resonance Spectroscopic Imaging Research Articles

Brain metabolites are associated with sleep architecture and cognitive functioning in older adults.

Sleep deficits are a possible risk factor for development of cognitive decline and dementia in older age. Research suggests that neuroinflammation may be a link between the two. This observational, cross-sectional study evaluated relationships between sleep architecture, neuroinflammation and cognitive functioning in healthy older adults. Twenty-two adults aged ≥60 years underwent whole-brain magnetic resonance spectroscopic imaging (in vivo method of visualizing increased brain temperatures as a proxy for neuroinflammation), supervised laboratory-based polysomnography, and comprehensive neurocognitive testing. Multiple regressions were used to assess relationships between magnetic resonance spectroscopic imaging-derived brain temperature and metabolites related to inflammation (choline; myo-inositol; N-acetylaspartate), sleep efficiency, time and % N3 sleep and cognitive performance. Choline, myo-inositol and N-acetylaspartate were associated with sleep efficiency and cognitive performance. Higher choline and myo-inositol in the bilateral frontal lobes were associated with slower processing speed and lower sleep efficiency. Higher choline and myo-inositol in bilateral frontoparietal regions were associated with better cognitive performance. Higher N-acetylaspartate around the temporoparietal junction and adjacent white matter was associated with better visuospatial function. Brain temperature was not related to cognitive or sleep outcomes. Our findings are consistent with the limited literature regarding neuroinflammation and its relationships with sleep and cognition in older age, which has implicated ageing microglia and astrocytes in circadian dysregulation, impaired glymphatic clearance and increased blood-brain barrier integrity, with downstream effects of neurodegeneration and cognitive decline. Inflammatory processes remain difficult to measure in the clinical setting, but magnetic resonance spectroscopic imaging may serve as a marker of the relationship between neuroinflammation, sleep and cognitive decline in older adults.

A birdcage transmit, 24-channel conformal receive array coil for sensitive 31P magnetic resonance spectroscopic imaging of the human brain at 7 T.

Phosphorus (31P) magnetic resonance spectroscopic imaging (MRSI) can serve as a critical tool for more direct quantification of brain energy metabolism, tissue pH, and cell membrane turnover. However, the low concentration of 31P metabolites in biological tissue may result in low signal-to-noise ratio (SNR) in 31P MRS images. In this work, we present an innovative design and construction of a 31P radiofrequency coil for whole-brain MRSI at 7 T. Our coil builds on current literature in ultra-high field 31P coil design and offers complete coverage of the brain, including the cerebellum and brainstem. The coil consists of an actively detunable volume transmit (Tx) resonator and a custom 24-channel receive (Rx) array. The volume Tx resonator is a 16-rung high-pass birdcage coil. The Rx coil consists of a 24-element phased array composed of catered loop shapes and sizes built onto a custom, close-fitting, head-shaped housing. The Rx array was designed to provide complete coverage of the head, while minimizing mutual coupling. The Rx configuration had a mean reflection coefficient better than -20 decibels (dB) when the coil was loaded with a human head. The mean mutual coupling ( ) among Rx elements, when loaded with a human head, was -16 dB. In phantom imaging, the phased array produced a central SNR that was 4.4-fold higher than the corresponding central SNR when operating the 31P birdcage as a transceiver. The peripheral SNR was 12-fold higher when applying the optimized phased array. In vivo 3D 31P MRSI experiments produced high-quality spectra in the cerebrum gray and white matter, as well as in the cerebellum. Characteristic phosphorus metabolites related to adenosine triphosphate metabolism and cell membrane turnover were distinguishable across all brain regions. In summary, our results demonstrate the potential of our novel coil for accurate, whole-brain 31P metabolite quantification.

Brain Temperature as an Indicator of Cognitive Function in Traumatic Brain Injury Patients.

Whether brain temperature noninvasively extracted by magnetic resonance imaging has a role in identifying brain changes in the later phases of mild to moderate traumatic brain injury (TBI) is not known. This prospective study aimed to evaluate if TBI patients in subacute and chronic phases had altered brain temperature measured by whole-brain magnetic resonance spectroscopic imaging (WB-MRSI) and if the measurable brain temperature had any relationship with cognitive function scores. WB-MRSI was performed on eight TBI patients and fifteen age- and sex-matched control subjects. Brain temperature (T) was extracted from the brain's major metabolites and compared between the two groups. The T of the patients was tested for correlation with cognitive function test scores. The results showed significantly lower brain temperature in the TBI patients (p < 0.05). Brain temperature derived from N-acetylaspartate (TNAA) strongly correlated with the 2 s paced auditory serial addition test (PASAT-2s) score (p < 0.05). The observation of lower brain temperature in TBI patients may be due to decreased metabolic activity resulting from glucose and oxygen depletion. The correlation of brain temperature with PASAT-2s may imply that noninvasive brain temperature may become a noninvasive index reflecting cognitive performance.

Whole-Brain Magnetic Resonance Spectroscopy Reveals Distinct Alterations in Neurometabolic Profile in Progressive Supranuclear Palsy.

Progressive supranuclear palsy (PSP) is an atypical Parkinsonian syndrome characterized by supranuclear gaze palsy, early postural instability, and a frontal dysexecutive syndrome. Contrary to normal brain magnetic resonance imaging in Parkinson's disease (PD), PSP shows specific cerebral atrophy patterns and alterations, but these findings are not present in every patient, and it is still unclear if these signs are also detectable in early disease stages. The aim of the present study was to analyze the metabolic profile of patients with clinically diagnosed PSP in comparison with matched healthy volunteers and PD patients using whole-brain magnetic resonance spectroscopicimaging (wbMRSI). Thirty-nine healthy controls (HCs), 29 PD, and 22 PSP patients underwent wbMRSI. PSP and PD patients were matched for age and handedness with HCs. Clinical characterization was performed using the Movement Disorder Society Unified Parkinson's Disease Rating Scale, PSP rating scale, and DemTect (test for cognitive assessment). In PSP patients a significant reduction in N-acetyl-aspartate (NAA) was detected in all brain lobes. Fractional volume of the cerebrospinal fluid significantly increased in PSP patients compared to PD and healthy volunteers. In PSP much more neuronal degeneration and cerebral atrophy have been detected compared with PD. The most relevant alteration is the decrease in NAA in all lobes of the brain, which also showed a partial correlation with clinical symptoms. However, more studies are needed to confirm the additional value of wbMRSI in clinical practice. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The Distribution of Major Brain Metabolites in Normal Adults: Short Echo Time Whole-Brain MR Spectroscopic Imaging Findings.

This prospective study aimed to evaluate the variation in magnetic resonance spectroscopic imaging (MRSI)-observed brain metabolite concentrations according to anatomical location, sex, and age, and the relationships among regional metabolite distributions, using short echo time (TE) whole-brain MRSI (WB-MRSI). Thirty-eight healthy participants underwent short TE WB-MRSI. The major metabolite ratios, i.e., N-acetyl aspartate (NAA)/creatine (Cr), choline (Cho)/Cr, glutamate + glutamine (Glx)/Cr, and myoinositol (mI)/Cr, were calculated voxel-by-voxel. Their variations according to anatomical regions, sex, and age, and their relationship to each other were evaluated by using repeated-measures analysis of variance, t-tests, and Pearson’s product-moment correlation analyses. All four metabolite ratios exhibited widespread regional variation across the cerebral hemispheres (corrected p < 0.05). Laterality between the two sides and sex-related variation were also shown (p < 0.05). In several regions, NAA/Cr and Glx/Cr decreased and mI/Cr increased with age (corrected p < 0.05). There was a moderate positive correlation between NAA/Cr and mI/Cr in the insular lobe and thalamus and between Glx/Cr and mI/Cr in the parietal lobe (r ≥ 0.348, corrected p ≤ 0.025). These observations demand age- and sex- specific regional reference values in interpreting these metabolites, and they may facilitate the understanding of glial-neuronal interactions in maintaining homeostasis.

Whole-Slab 3D MR Spectroscopic Imaging of the Human Brain With Spiral-Out-In Sampling at 7T.

Metabolic imaging using proton magnetic resonance spectroscopic imaging (MRSI) has increased the sensitivity and spectral resolution at field strengths of ≥7T. Compared to the conventional Cartesian-based spectroscopic imaging, spiral trajectories enable faster data collection, promising the clinical translation of whole-brain MRSI. Technical considerations at 7T, however, lead to a suboptimal sampling efficiency for the spiral-out (SO) acquisitions, as a significant portion of the trajectory consists of rewinders. To develop and implement a spiral-out-in (SOI) trajectory for sampling of whole-brain MRSI at 7T. We hypothesized that SOI will improve the signal-to-noise ratio (SNR) of metabolite maps due to a more efficient acquisition. Prospective. Five healthy volunteers (28-38 years, three females) and a phantom. Navigated adiabatic spin-echo spiral 3D MRSI at 7T. A 3D stack of SOI trajectories was incorporated into an adiabatic spin-echo MRSI sequence with real-time motion and shim correction. Metabolite spectral fitting, SNR, and Cramér-Rao lower bound (CRLB) were obtained. We compared the signal intensity and CRLB of three metabolites of tNAA, tCr, and tCho. Peak SNR (PSNR), structure similarity index (SSIM), and signal-to-artifact ratio were evaluated on water maps. The nonparametric Mann-Whitney U-test was used for statistical testing. Compared to SO, the SOI trajectory: 1) increased the k-space sampling efficiency by 23%; 2) is less demanding for the gradient hardware, requiring 36% lower Gmax and 26% lower Smax ; 3) increased PSNR of water maps by 4.94 dB (P = 0.0006); 4) resulted in a 29% higher SNR (P = 0.003) and lower CRLB by 26-35% (P = 0.02, tNAA), 35-55% (P = 0.03, tCr), and 22-23% (P = 0.04, tCho), which increased the number of well-fitted voxels (eg, for tCr by 11%, P = 0.03). SOI did not significantly change the signal-to-artifact ratio and SSIM (P = 0.65) compared to SO. SOI provided more efficient MRSI at 7T compared to SO, which improved the data quality and metabolite quantification. 1 TECHNICAL EFFICACY STAGE: 2.

Reproducibility of whole-brain temperature mapping and metabolite quantification using proton magnetic resonance spectroscopy.

Assessing brain temperature can provide important information about disease processes (e.g., stroke, trauma) and therapeutic effects (e.g., cerebral hypothermia treatment). Whole-brain magnetic resonance spectroscopic imaging (WB-MRSI) is increasingly used to quantify brain metabolites across the entire brain. However, its feasibility and reliability for estimating brain temperature needs further validation. Therefore, the present study evaluates the reproducibility of WB-MRSI for temperature mapping as well as metabolite quantification across the whole brain in healthy volunteers. Ten healthy adults were scanned on three occasions 1 week apart. Brain temperature, along with four commonly assessed brain metabolites-total N-acetyl-aspartate (tNAA), total creatine (tCr), total choline (tCho) and myo-inositol (mI)-were measured from WB-MRSI data. Reproducibility was evaluated using the coefficient of variation (CV). The measured mean (range) of the intra-subject CVs was 0.9% (0.6%-1.6%) for brain temperature mapping, and 4.7% (2.5%-15.7%), 6.4% (2.4%-18.9%) and 14.2% (4.4%-52.6%) for tNAA, tCho and mI, respectively, with reference to tCr. Consistently larger variability was found when using H2 O as the reference for metabolite quantifications: 7.8% (3.3%-17.8%), 7.8% (3.1%-18.0%), 9.8% (3.7%-31.0%) and 17.0% (5.9%-54.0%) for tNAA, tCr, tCho and mI, respectively. Further, the larger the brain region (indicated by a greater number of voxels within that region), the better the reproducibility for both temperature and metabolite estimates. Our results demonstrate good reproducibility of whole-brain temperature and metabolite measurements using the WB-MRSI technique.

Effects of apodization smoothing and denoising on spectral fitting

PurposeVisual review of individual spectra in magnetic resonance spectroscopic imaging (MRSI) data benefits from the application of spectral smoothing; however, if this processing step is applied prior to spectral analysis this can impact the accuracy of the quantitation. This study aims to analyze the effect of spectral denoising and apodization smoothing on the quantitation of whole-brain MRSI data obtained at short TE. MethodsShort-TE MRSI data obtained at 3 T were analyzed with no spectral smoothing, following (i) Gaussian apodization with values of 1, 2, 4, 6, and 8 Hz, and (ii) denoising using principal component analysis (dnPCA) with 3 different values for the number of retained principal components. The mean lobar white matter estimates for four metabolites, signal-to-noise ratio (SNR), spectral linewidth, and confidence intervals were compared to data reconstructed using no smoothing. Additionally, a voxel-wise comparison for N-acetylaspartate quantitation with different smoothing schemes was performed. ResultsSignificant pairwise differences were seen for all Gaussian smoothing methods as compared to no smoothing (p<0.001) in linewidth and metabolite estimates, whereas dnPCA methods showing no statistically significant differences in these measures. Confidence intervals decreased, and SNR increased with increasing levels of apodization smoothing or dnPCA denoising. ConclusionMild Gaussian apodization (≤2 Hz at 3 T) can be applied with minimal (1%) errors in quantitation; however, smoothing values greater than that can significantly affect metabolite quantification. In contrast, mild to moderate dnPCA based denoising provides quantitative results that are consistent with the analysis of unsmoothed data and this method is recommended for spectral denoising.

No evidence of abnormal metabolic or inflammatory activity in the brains of patients with rheumatoid arthritis: results from a preliminary study using whole-brain magnetic resonance spectroscopic imaging (MRSI)

Introduction/objectivesMany individuals with rheumatoid arthritis (RA) report persistent fatigue even after management of peripheral disease activity. This study used whole-brain magnetic resonance spectroscopic imaging (MRSI) to investigate whether abnormal inflammatory activity in the central nervous system may be associated with such symptoms. We hypothesized that RA patients would show higher brain choline (CHO), myo-inositol (MI), and lactate (LAC), and higher brain temperature than healthy controls. We further hypothesized that the metabolite levels would be positively correlated with self-reported fatigue.MethodThirteen women with RA provided fatigue severity ratings and underwent whole-brain MRSI and a joint examination. Thirteen healthy controls (HC) provided comparison imaging and fatigue data. CHO, MI, LAC, and brain temperature in 47 brain regions were contrasted between groups using independent-samples t tests. Significant differences were determined using a false discovery rate (FDR)-adjusted p value threshold of ≤ 0.0023. Secondary analyses obtained correlations between imaging and clinical outcomes in the RA group.ResultsNo brain metabolic differences were identified between the groups. In the RA group, fatigue severity was positively correlated with CHO in several brain regions—most strongly the right frontal lobe (rs = 0.823, p < 0.001). MI was similarly correlated with fatigue, particularly in the right calcarine fissure (rs = 0.829, p < 0.001). CHO in several regions was positively correlated with joint swelling and tenderness.ConclusionsWe conclude that abnormal brain metabolites are not a common feature of RA, but may been seen in patients with persistent fatigue or disease activity after conventional treatment.Key Points• Whole-brain magnetic resonance spectroscopy revealed no metabolic abnormalities in the brain in patients with rheumatoid arthritis.• Brain choline levels were correlated with fatigue severity reported by RA patients and with peripheral joint swelling and tenderness.• Brain myo-inositol levels were similarly correlated with fatigue severity in RA patients.

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

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

Volumetric Spectroscopic Imaging of Glioblastoma Multiforme Radiation Treatment Volumes

Magnetic resonance (MR) imaging and computed tomography (CT) are used almost exclusively in radiation therapy planning of glioblastoma multiforme (GBM), despite their well-recognized limitations. MR spectroscopic imaging (MRSI) can identify biochemical patterns associated with normal brain and tumor, predominantly by observation of choline (Cho) and N-acetylaspartate (NAA) distributions. In this study, volumetric 3-dimensional MRSI was used to map these compounds over a wide region of the brain and to evaluate metabolite-defined treatment targets (metabolic tumor volumes [MTV]). Volumetric MRSI with effective voxel size of ∼1.0 mL and standard clinical MR images were obtained from 19 GBM patients. Gross tumor volumes and edema were manually outlined, and clinical target volumes (CTVs) receiving 46 and 60 Gy were defined (CTV46 and CTV60, respectively). MTVCho and MTVNAA were constructed based on volumes with high Cho and low NAA relative to values estimated from normal-appearing tissue. The MRSI coverage of the brain was between 70% and 76%. The MTVNAA were almost entirely contained within the edema, and the correlation between the 2 volumes was significant (r=0.68, P=.001). In contrast, a considerable fraction of MTVCho was outside of the edema (median, 33%) and for some patients it was also outside of the CTV46 and CTV60. These untreated volumes were greater than 10% for 7 patients (37%) in the study, and on average more than one-third (34.3%) of the MTVCho for these patients were outside of CTV60. This study demonstrates the potential usefulness of whole-brain MRSI for radiation therapy planning of GBM and revealed that areas of metabolically active tumor are not covered by standard RT volumes. The described integration of MTV into the RT system will pave the way to future clinical trials investigating outcomes in patients treated based on metabolic information.

Whole-brain magnetic resonance spectroscopic imaging measures are related to disability in ALS.

To demonstrate the sensitivity of a recently developed whole-brain magnetic resonance spectroscopic imaging (MRSI) sequence to cerebral pathology and disability in amyotrophic lateral sclerosis (ALS), and compare with measures derived from diffusion tensor imaging. Whole-brain MRSI and diffusion tensor imaging were undertaken in 13 patients and 14 age-similar healthy controls. Mean N-acetylaspartate (NAA), fractional anisotropy, and mean diffusivity were extracted from the corticospinal tract, compared between groups, and then in relation to disability in the patient group. Significant reductions in NAA were found along the course of the corticospinal tracts on whole-brain MRSI. There were also significant changes in fractional anisotropy (decreased) and mean diffusivity (increased) in the patient group, but only NAA showed a significant relationship with disability (r = 0.65, p = 0.01). Whole-brain MRSI has potential as a quantifiable neuroimaging marker of disability in ALS. It offers renewed hope for a neuroimaging outcome measure with the potential for harmonization across multiple sites in the context of a therapeutic trial.

Application of volumetric MR spectroscopic imaging for localization of neocortical epilepsy

The aim of this study was to evaluate volumetric proton magnetic resonance spectroscopic imaging (MRSI) for localization of epileptogenic foci in neocortical epilepsy. Twenty-five subjects reporting seizures considered to be of neocortical origin were recruited to take part in a 3-T MR study that included high-resolution structural MRI and a whole-brain MRSI acquisition. Using a fully automated MRSI processing protocol, maps for signal intensity normalized N-acetylaspartate (NAA), creatine, and choline were created, together with the relative volume fraction of grey-matter, white-matter, and CSF within each MRSI voxel. Analyses were performed using visual observation of the metabolite and metabolite ratio maps; voxel-based calculation of differences in these metabolite maps relative to normal controls; comparison of average grey-matter and white-matter metabolite values over each lobar volume; and examination of relative left-right asymmetry factors by brain region. Data from 14 subjects were suitable for inclusion in the analysis. Eight subjects had MRI-visible pathologies that were associated with decreases in NAA/creatine, which extended beyond the volume indicated by the MRI. Five subjects demonstrated no significant metabolic alterations using any of the analysis methods, and one subject had no findings on MRI or MRSI. This proof of principle study supports previous evidence that alterations of MR-detected brain metabolites can be detected in tissue areas affected by neocortical seizure activity, while additionally demonstrating advantages of the volumetric MRSI approach.

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The aim of this study was to evaluate volumetric proton magnetic resonance spectroscopic imaging (MRSI) for localization of epileptogenic foci in neocortical epilepsy.Twenty-five subjects reporting seizures considered to be of neocortical origin were recruited to take part in a 3-T MR study that included high-resolution structural MRI and a whole-brain MRSI acquisition. Using a fully automated MRSI processing protocol, maps for signal intensity normalized N-acetylaspartate (NAA), creatine, and choline were created, together with the relative volume fraction of grey-matter, white-matter, and CSF within each MRSI voxel. Analyses were performed using visual observation of the metabolite and metabolite ratio maps; voxel-based calculation of differences in these metabolite maps relative to normal controls; comparison of average grey-matter and white-matter metabolite values over each lobar volume; and examination of relative left–right asymmetry factors by brain region.Data from 14 subjects were suitable for inclusion in the analysis. Eight subjects had MRI-visible pathologies that were associated with decreases in NAA/creatine, which extended beyond the volume indicated by the MRI. Five subjects demonstrated no significant metabolic alterations using any of the analysis methods, and one subject had no findings on MRI or MRSI.This proof of principle study supports previous evidence that alterations of MR-detected brain metabolites can be detected in tissue areas affected by neocortical seizure activity, while additionally demonstrating advantages of the volumetric MRSI approach.