Dysregulation of energy metabolism in multiple sclerosis measured in vivo with diffusion-weighted spectroscopy

Bodini, Benedetta; Branzoli, Francesca; Poirion, Émilie; García-Lorenzo, Daniel; Didier, Mélanie; Maillart, Élisabeth; Socha, J.; Bera, G.; Lubetzki, Catherine; Ronen, Itamar; Lehericy, Stéphane; Stankoff, Bruno

doi:10.1177/1352458517698249

Cited by 12 publications

(27 citation statements)

References 29 publications

(32 reference statements)

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“…Creatine-referenced N-acetyl aspartate has shown reductions relative to control in mixed or unspecified multiple sclerosis lesions (22–35), white matter (36), normal-appearing white matter (22, 24, 25, 30, 34, 37–46), and mixed tissue (47); in relapsing-remitting multiple sclerosis lesions (48–56), white matter (36, 54, 57–64), normal-appearing white matter (48, 50–52, 65–70), gray matter (54, 70), mixed tissue (54, 58, 63, 71–75), and spine (76); and in progressive multiple sclerosis lesions (50, 52, 77–79), white matter (36, 60, 62, 80), normal-appearing white matter (45, 46, 50, 52, 66, 69, 78, 79, 81, 82), gray matter (83), and mixed tissue (71, 73, 84–89). In addition, N-acetyl aspartate quantified as institutional units or relative to non-creatine references like water or phantom acquisitions has been shown to decrease in mixed or unspecified multiple sclerosis lesions (22, 29, 90–96), white matter (97, 98), normal-appearing white matter (22, 91, 94, 99–105), gray matter (94, 100, 103, 104, 106), mixed tissue (107, 108), spine (109–112), and whole-brain measures (113, 114); in relapsing-remitting lesions (50, 53, 96, 115–…”

Section: Potential Small-molecule Diagnostic Biomarkers Of Multiple Smentioning

confidence: 99%

“…The effect of multiple sclerosis on creatine concentrations in the central nervous system is still unclear, as creatine has been suggested to increase in mixed or unspecified multiple sclerosis lesions (92) and normal-appearing white matter (37); in relapsing-remitting multiple sclerosis lesions (137), normal-appearing white matter (50, 69, 137), and mixed tissue (123); and in progressive multiple sclerosis lesions (50), white matter (62), normal-appearing white matter (50, 69), and mixed tissue (84, 135). It has also demonstrated decreases, however, in unspecified and mixed multiple sclerosis lesions (94), normal-appearing white matter (105), and gray matter (103); in relapsing-remitting lesions (116); and in progressive gray matter (133) and mixed tissue (88).…”

Section: Potential Small-molecule Diagnostic Biomarkers Of Multiple Smentioning

confidence: 99%

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Quantifying the Metabolic Signature of Multiple Sclerosis by in vivo Proton Magnetic Resonance Spectroscopy: Current Challenges and Future Outlook in the Translation From Proton Signal to Diagnostic Biomarker

et al. 2019

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Proton magnetic resonance spectroscopy (1H-MRS) offers a growing variety of methods for querying potential diagnostic biomarkers of multiple sclerosis in living central nervous system tissue. For the past three decades, 1H-MRS has enabled the acquisition of a rich dataset suggestive of numerous metabolic alterations in lesions, normal-appearing white matter, gray matter, and spinal cord of individuals with multiple sclerosis, but this body of information is not free of seeming internal contradiction. The use of 1H-MRS signals as diagnostic biomarkers depends on reproducible and generalizable sensitivity and specificity to disease state that can be confounded by a multitude of influences, including experiment group classification and demographics; acquisition sequence; spectral quality and quantifiability; the contribution of macromolecules and lipids to the spectroscopic baseline; spectral quantification pipeline; voxel tissue and lesion composition; T1 and T2 relaxation; B1 field characteristics; and other features of study design, spectral acquisition and processing, and metabolite quantification about which the experimenter may possess imperfect or incomplete information. The direct comparison of 1H-MRS data from individuals with and without multiple sclerosis poses a special challenge in this regard, as several lines of evidence suggest that experimental cohorts may differ significantly in some of these parameters. We review the existing findings of in vivo 1H-MRS on central nervous system metabolic abnormalities in multiple sclerosis and its subtypes within the context of study design, spectral acquisition and processing, and metabolite quantification and offer an outlook on technical considerations, including the growing use of machine learning, by future investigations into diagnostic biomarkers of multiple sclerosis measurable by 1H-MRS.

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Section: Potential Small-molecule Diagnostic Biomarkers Of Multiple Smentioning

confidence: 99%

Section: Potential Small-molecule Diagnostic Biomarkers Of Multiple Smentioning

confidence: 99%

Quantifying the Metabolic Signature of Multiple Sclerosis by in vivo Proton Magnetic Resonance Spectroscopy: Current Challenges and Future Outlook in the Translation From Proton Signal to Diagnostic Biomarker

et al. 2019

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“…Work that has been done so far in disease implies that not only DW-MRS is possible to apply in clinical settings, but that the potential of added information to that obtained from DWI experiments justifies the effort. So far, DW-MRS has been applied to study cerebral ischemia in animal models (50, 80,81) and in humans (83,149), cerebral tumors in animals (58) and humans (83), normal aging (149,150), schizophrenia (147) and several studies in MS (63,139,151). Although valuable microstructural information can be obtained from combining simple DTI data and DW-MRS data acquired from a single volume, a significant effort should be invested in generating robust multivoxel DW-MRS data, as this will be essential for a spatially-resolved combination of data from the two modalities with significant gains for tissue microstructural characterization in healthy and more importantly for diseased conditions.…”

Section: Multivoxel Dw-mrs and Dw-mrsimentioning

confidence: 99%

Insights into brain microstructure from in vivo DW-MRS

et al. 2018

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Many developmental processes, such as plasticity and aging, or pathological processes such as neurological diseases are characterized by modulations of specific cellular types and their microstructures. Diffusion-weighted Magnetic Resonance Imaging (DW-MRI) is a powerful technique for probing microstructure, yet its information arises from the ubiquitous, non-specific water signal. By contrast, diffusion-weighted Magnetic Resonance Spectroscopy (DW-MRS) allows specific characterizations of tissues such as brain and muscle in vivo by quantifying the diffusion properties of MR-observable metabolites. Many brain metabolites are predominantly intracellular, and some of them are preferentially localized in specific brain cell populations, e.g., neurons and glia. Given the microstructural sensitivity of diffusion-encoding filters, investigation of metabolite diffusion properties using DW-MRS can thus provide exclusive cell and compartment-specific information. Furthermore, since many models and assumptions are used for quantification of water diffusion, metabolite diffusion may serve to generate a-priori information for model selection in DW-MRI. However, DW-MRS measurements are extremely challenging, from the acquisition to the accurate and correct analysis and quantification stages. In this review, we survey the state-of-the-art methods that have been developed for the robust acquisition, quantification and analysis of DW-MRS data and discuss the potential relevance of DW-MRS for elucidating brain microstructure in vivo. The review highlights that when accurate data on the diffusion of multiple metabolites is combined with accurate computational and geometrical modeling, DW-MRS can provide unique cell-specific information on the intracellular structure of brain tissue, in health and disease, which could serve as incentives for further application in vivo in human research and clinical MRI.

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“…In this manner, DTS allows inferring more specific information on the underlying tissue microstructure than DTI and thus features improved pathologic specificity. The methodology has been applied to several pathologies such as acute cerebral ischemia ( Harada et al 2002 ; Zheng et al 2012 ), tumors ( Colvin et al 2008 ; Harada et al 2002 ), mitochondrial cytopathies ( Liu et al 2011 ), multiple sclerosis ( Bodini et al 2018 ; Wood et al 2012 ), systemic lupus erythematosus ( Ercan et al 2016 ), and migraine ( Zielman et al 2017 ).…”

Section: Introductionmentioning

confidence: 99%

In-vivo evaluation of neuronal and glial changes in amyotrophic lateral sclerosis with diffusion tensor spectroscopy

Reischauer

Gutzeit

Neuwirth

et al. 2018

NeuroImage: Clinical

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Diffusion tensor spectroscopy (DTS) combines features of magnetic resonance spectroscopy and diffusion tensor imaging and permits evaluating cell-type specific properties of microstructure by probing the diffusion of intracellular metabolites. This exploratory study investigates for the first time microstructural changes in the neuronal and glial compartments of the brain of patients with amyotrophic lateral sclerosis (ALS) using DTS. To this end, the diffusion properties of the neuronal metabolite tNAA (N-acetylaspartate + N-acetylaspartylglutamate) and the predominantly glial metabolites tCr (creatine + phosphocreatine) and tCho (choline-containing compounds) were evaluated in the primary motor cortex of 24 ALS patients and 27 healthy controls. Significantly increased values in the diffusivities of all three metabolites were found in ALS patients relative to controls. Further analysis revealed more pronounced microstructural alterations in ALS patients with limb onset than with bulbar onset relative to controls. This observation may be related to the fact that the spectroscopic voxel was positioned in the part of the motor cortex where the motor functions of the limbs are represented. The higher diffusivities of tNAA may reflect neuronal damage and/or may be a consequence of mitochondrial dysfunction in ALS. Increased diffusivities of tCr and tCho are in line with reactive microglia and astrocytes surrounding degenerating motor neurons in the primary motor cortex of ALS patients. This pilot study demonstrates for the first time that cell-type specific microstructural alterations in the brain of ALS patients may be explored in vivo and non-invasively with DTS. In conjunction with other microstructural magnetic resonance imaging techniques, DTS may provide further insights into the pathogenic mechanisms that underlie neurodegeneration in ALS.

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Dysregulation of energy metabolism in multiple sclerosis measured in vivo with diffusion-weighted spectroscopy

Cited by 12 publications

References 29 publications

Quantifying the Metabolic Signature of Multiple Sclerosis by in vivo Proton Magnetic Resonance Spectroscopy: Current Challenges and Future Outlook in the Translation From Proton Signal to Diagnostic Biomarker

Quantifying the Metabolic Signature of Multiple Sclerosis by in vivo Proton Magnetic Resonance Spectroscopy: Current Challenges and Future Outlook in the Translation From Proton Signal to Diagnostic Biomarker

Insights into brain microstructure from in vivo DW-MRS

In-vivo evaluation of neuronal and glial changes in amyotrophic lateral sclerosis with diffusion tensor spectroscopy

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