Reliability of neurometabolite detection with two‐dimensional localized correlation spectroscopy at 3T

et al. 2019

Ther Adv Neurol Disord

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Background: We have applied in vivo two-dimensional (2D) localized correlation spectroscopy (2D L-COSY), in treated relapsing relapsing-remitting multiple sclerosis (RRMS) to identify novel biomarkers in normal-appearing brain parenchyma. Methods: 2D L-COSY magnetic resonance spectroscopy (MRS) spectra were prospectively acquired from the posterior cingulate cortex (PCC) in 45 stable RRMS patients undergoing treatment with Fingolimod, and 40 age and sex-matched healthy control (HC) participants. Average metabolite ratios and clinical symptoms including, disability, cognition, fatigue, and mental health parameters were measured, and compared using parametric and nonparametric tests. Whole brain volume and MRS voxel morphometry were evaluated using SIENAX and the SPM LST toolbox. Results: Despite the mean whole brain lesion volume being low in this RRMS group (6.8 ml) a significant reduction in PCC metabolite to tCr ratios were identified for multiple N-acetylaspartate (NAA) signatures, gamma-aminobutyric acid (GABA), glutamine and glutamate (Glx), threonine, and isoleucine/lipid. Of the clinical symptoms measured, visuospatial function, attention, and memory were correlated with NAA signatures, Glx, and isoleucine/lipid in the brain. Conclusions: 2D L-COSY has the potential to detect metabolic alterations in the normal-appearing MS brain. Despite examining only a localised region, we could detect metabolic variability associated with symptoms.

Section: Introductionmentioning

confidence: 99%

2D in-vivo L-COSY spectroscopy identifies neurometabolite alterations in treated multiple sclerosis

Quadrelli

Ribbons

et al. 2019

Ther Adv Neurol Disord

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“…In line with another study, these metabolic variations between different times of the day could be attributed to biological factors rather than hardware‐related imperfections. As expected, our in vitro measurements exhibited very low CV values and did not show time of the day effects for any of the metabolites. Circadian rhythms in the adult human brain are complex and influenced by sleep/wake cycles .…”

Section: Discussionmentioning

confidence: 99%

“…The diurnal effects of lipids in this study may be explained by the fact that lipid metabolism in the brain is influenced by food intake . Since a 2D L‐COSY sequence without outer volume suppression pulses was used, a minimal, yet reproducible, extravoxel lipid contamination was tolerated . More important, the lipid/MM peak at 0.90 ppm along the diagonal could well be a composite peak that has a reasonable contribution from macromolecules, as well as valine and leucine to a lesser extent due to the absence of any related cross‐peaks and their naturally occurring low concentrations .…”

Section: Discussionmentioning

confidence: 99%

“…33 Since a 2D L-COSY sequence without outer volume suppression pulses was used, a minimal, yet reproducible, extravoxel lipid contamination was tolerated. 22 More important, the lipid/MM peak at 0.90 ppm along the diagonal could well be a composite peak that has a reasonable contribution from macromolecules, 34 as well as valine and leucine to a lesser extent due to the absence of any related cross-peaks and their naturally occurring low concentrations. 5 Macromolecules are large hydrophilic molecules that originate from cytosolic proteins and their levels in healthy brain is age-dependent and varies between different brain regions.…”

Section: Discussionmentioning

confidence: 99%

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Diurnal variability of cerebral metabolites in healthy human brain with 2D localized correlation spectroscopy (2D L‐COSY)

Magnetic Resonance Imaging

Al‐iedani

Lea

et al. 2019

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Background Two‐dimensional localized correlation spectroscopy (2D L‐COSY) is a research tool that has been applied to evaluate in vivo metabolic activity in many neurological and oncological disorders. Circadian mediators such as brain temperature, hydration, and osmotic regulation have been claimed to change metabolic profiles. Purpose To evaluate the diurnal variability of neuro‐metabolites with 2D L‐COSY in healthy subjects using a 3 T scanner. Study Type Crossover. Population/Phantom Ten healthy subjects and magnetic resonance spectroscopy‐high definition (MRS‐HD) sphere or “Braino.” Field Strength/Sequence: 3 T/2D L‐COSY MRS. Assessment In vivo 2D L‐COSY measurements were performed on ten healthy subjects (5 M/5F, mean age 36.1 ± 7.7 years) repeatedly at three timepoints (0700, 1200, and 1700) on the same day. in vitro evaluations were performed in a similar fashion as in vivo on Braino containing selected brain metabolites at physiological concentrations and pH. 2D L‐COSY was acquired from a 27 cm3 voxel located in the posterior cingulate cortex. A total of 75 resonances were included in the analysis and spectral peak volumes were normalized to creatine. Statistical Test One‐way repeated measured analysis of variance with Bonferroni post‐hoc adjustment using SPSS software. Results In vitro data showed no statistically significant differences between different scans (P > 0.12). in vivo results showed statistically significant diurnal variations (P ≤ 0.05, F > 3.88) for 22 resonances. Bonferroni post‐hoc testing showed there was statistically significant increases in metabolite ratios between 0700 and 1700 and these include different moieties of N‐acetylaspartate, creatine, choline, myo‐inositol, lipids, fucose, glutathione, and homocarnosine. Data Conclusion 2D L‐COSY can detect diurnal physiological variability in neuro‐metabolite levels. Thus, time of the day should be considered when planning MRS studies to avoid confounding results. Level of Evidence: 1 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019;50:592–601.

“…MR 2D L‐COSY allows unambiguous detection of several coupled metabolites simultaneously, even at low concentrations 12 . We have shown previously that MR 2D L‐COSY is a reliable technique that can be applied to unravel biochemical footprints of MS in normal‐appearing white matter (NAWM) of patients with relapsing‐remitting MS (RRMS) 13, 17 . In addition to standard spectroscopic methods that have been used so far to study the major high concentration metabolites, such as NAA and glutamate, MR 2D L‐COSY has potential to identify a larger number of metabolites including those with low concentration that may be responsible for fatigue development in MS.…”

Section: Introductionmentioning

confidence: 99%

Biochemical Correlations with Fatigue in Multiple Sclerosis Detected by MR 2D Localized Correlated Spectroscopy

Journal of Neuroimaging

Al‐iedani

Ribbons

et al. 2021

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BACKGROUND AND PURPOSE Fatigue is the common symptom in patients with multiple sclerosis (MS), yet its pathophysiological mechanism is poorly understood. We investigated the metabolic changes in fatigue in a group of relapsing‐remitting MS (RRMS) patients using MR two‐dimensional localized correlated spectroscopy (2D L‐COSY). METHODS Sixteen RRMS and 16 healthy controls were included in the study. Fatigue impact was assessed with the Modified Fatigue Impact Scale (MFIS). MR 2D L‐COSY data were collected from the posterior cingulate cortex. Nonparametric statistical analysis was used to calculate the changes in creatine scaled metabolic ratios and their correlations with fatigue scores. RESULTS Compared to healthy controls, the RRMS group showed significantly higher fatigue and lower metabolic ratios for tyrosine, glutathione, homocarnosine (GSH+Hca), fucose‐3, glutamine+glutamate (Glx), glycerophosphocholine (GPC), total choline, and N‐acetylaspartate (NAA‐2), while increased levels for isoleucine and glucose (P ≤ .05). Only GPC showed positive correlation with all fatigue domains (r = .537, P ≤ .05). On the other hand, Glx‐upper, NAA‐2, GSH+Hca, and fucose‐3 showed negative correlations with all fatigue domains (r = –.345 to –.580, P ≤ .05). While tyrosine showed positive correlation with MFIS (r = .499, P ≤ .05), cognitive fatigue was negatively correlated with total GSH (r = –.530, P ≤ .05). No correlations were found between lesion load or brain volumes with fatigue score. CONCLUSIONS Our results suggest that fatigue in MS is strongly correlated with an imbalance in neurometabolites but not structural brain measurements.