MRI DTI and PDFF as Biomarkers for Lower Motor Neuron Degeneration in ALS

Lichtenstein, Thorsten; Sprenger, Alina; Weiss, Kilian; Hokamp, Nils Große; Maintz, David; Schlamann, Marc; Fink, Gereon R.; Lehmann, Helmar C.; Henning, Tobias D.

doi:10.3389/fnins.2021.682126

Cited by 8 publications

(9 citation statements)

References 39 publications

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“…Previous studies on peripheral nerve repair have shown that the density and integrity of myelin increase during the process of nerve fiber regeneration, thereby resulting in higher FA and lower RD values ( Chen et al, 2017 ; Farinas et al, 2020 ; Zheng et al, 2021 ). Conversely, nerve anisotropy (FA) values decrease, and RD values increase during peripheral nerve degeneration in healthy older individuals or individuals with peripheral nerve disease because of decreased number of myelinated fibers ( Jeon et al, 2018 ; Lichtenstein et al, 2021 ). Therefore, FA and RD values are sensitive biomarkers to detect minor changes in the myelination of the peripheral nerves.…”

Section: Discussionmentioning

confidence: 99%

Performance of Single-Shot Echo-Planar Imaging in Diffusion Tensor Imaging in Rat Sciatic Nerve Compared With Readout-Segmented Echo-Planar Imaging

et al. 2022

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ObjectivesTo compare the performances of single-shot echo-planar imaging (SS–EPI) and readout-segmented echo-planar imaging (RS–EPI) for diffusion tensor imaging (DTI) of the rat sciatic nerve.MethodsEight healthy adult male Sprague-Dawley rats were anesthetized and scanned with a 3T MRI scanner using SS–EPI and RS–EPI DTI sequences. The image quality in terms of the morphology of the nerve, distortions of the nearby femur, muscles, and homogeneity of neuromuscular were evaluated and scored. The correlations between the DTI parameters including fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), apparent diffusion coefficient (ADC), and histopathological parameters were calculated by using the Pearson correlation coefficient and compared by the modified Fisher Z-transform, respectively.ResultsThe quality scores were higher for the images from the SS–EPI sequence compared with the RS–EPI sequence for characteristics such as sharpness of the sciatic nerve margin (P = 0.008), artifacts of the sciatic nerve (P = 0.008), and homogeneity of the neuromuscular region (P = 0.007), as well as the contrast-to-noise ratio (CNR) of DW images (P < 0.001). The correlation coefficients were higher for the FA and RD values from the SS–EPI sequence compared with those from the RS–EPI sequence. Furthermore, the correlation coefficients between FA and myelin thickness (P = 0.027), FA and diameter of the myelinated fiber (P = 0.036), as well as RD and myelin thickness (P = 0.05) were statistically higher for the SS–EPI sequence compared with those for the RS–EPI sequence.ConclusionDiffusion tensor imaging analysis of the rat sciatic nerve showed that the image quality from the SS–EPI sequence was significantly higher compared with that from the RS–EPI sequence. Furthermore, the FA and RD derived from the SS–EPI sequence are promising and sensitive biomarkers to detect the histopathological changes in the rat sciatic nerve.

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Section: Discussionmentioning

confidence: 99%

Performance of Single-Shot Echo-Planar Imaging in Diffusion Tensor Imaging in Rat Sciatic Nerve Compared With Readout-Segmented Echo-Planar Imaging

et al. 2022

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“…Previous studies on peripheral nerve repair have shown that the density and integrity of myelin increase during the process of nerve fiber regeneration, thereby resulting in higher FA and lower RD values (Chen et al, 2017;Farinas et al, 2020;Zheng et al, 2021). Conversely, nerve anisotropy (FA) values decrease, and RD values increase during peripheral nerve degeneration in healthy older individuals or individuals with peripheral nerve disease because of decreased number of myelinated fibers Lichtenstein et al, 2021). Therefore, FA and RD values are sensitive biomarkers to detect minor changes in the myelination of the peripheral nerves.…”

Section: Discussionmentioning

confidence: 99%

Peripheral Nerve Imaging

2022

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Frontiers is more than just an open-access publisher of scholarly articles: it is a pioneering approach to the world of academia, radically improving the way scholarly research is managed. The grand vision of Frontiers is a world where all people have an equal opportunity to seek, share and generate knowledge. Frontiers provides immediate and permanent online open access to all its publications, but this alone is not enough to realize our grand goals. Frontiers Journal SeriesThe Frontiers Journal Series is a multi-tier and interdisciplinary set of open-access, online journals, promising a paradigm shift from the current review, selection and dissemination processes in academic publishing. All Frontiers journals are driven by researchers for researchers; therefore, they constitute a service to the scholarly community. At the same time, the Frontiers Journal Series operates on a revolutionary invention, the tiered publishing system, initially addressing specific communities of scholars, and gradually climbing up to broader public understanding, thus serving the interests of the lay society, too. Dedication to QualityEach Frontiers article is a landmark of the highest quality, thanks to genuinely collaborative interactions between authors and review editors, who include some of the world's best academicians. Research must be certified by peers before entering a stream of knowledge that may eventually reach the public -and shape society; therefore, Frontiers only applies the most rigorous and unbiased reviews. Frontiers revolutionizes research publishing by freely delivering the most outstanding research, evaluated with no bias from both the academic and social point of view. By applying the most advanced information technologies, Frontiers is catapulting scholarly publishing into a new generation.

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“…The MRI protocol was based on a protocol already established in studies of patients with chronic inflammatory demyelinating polyneuropathy or amyotrophic lateral sclerosis [ 14 , 19 ]. The well-established protocol was extended by a quantitative T2 mapping sequence.…”

Section: Methodsmentioning

confidence: 99%

“…Muscle MRI can be supplemented by nerve diffusion tensor imaging (DTI), revealing information about nerve damage and regeneration [14][15][16][17][18]. Previous studies in other neuromuscular and neuropathy disorders found a decreased fractional anisotropy (FA) in the sciatic nerve compared to controls [14,19]. So far, studies in SMA patients only investigated the FA in muscle tissue showing increased values compared to healthy controls but did not investigate nerve structures themselves [9,20].…”

Section: Introductionmentioning

confidence: 99%

MRI correlates of motoneuron loss in SMA

et al. 2022

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Background Magnetic resonance imaging (MRI) is currently explored as supplemental tool to monitor disease progression and treatment response in various neuromuscular disorders. We here assessed the utility of a multi-parametric magnetic resonance imaging (MRI) protocol including quantitative water T2 mapping, Dixon-based proton density fat fraction (PDFF) estimation and diffusion tensor imaging (DTI) to detect loss of spinal motor neurons and subsequent muscle damage in adult SMA patients. Methods Sixteen SMA patients and 13 age-matched controls were enrolled in this prospective, longitudinal study. All participants underwent MRI imaging including measurements of Dixon-based PDFF and DTI of the sciatic nerve. SMA patients furthermore underwent measurements of muscle water T2 (T2w) of the biceps femoris muscle (BFM) and quadriceps femoris muscle (QFM). Ten participants returned for a second scan six months later. MRI parameter were correlated with clinical data. All patients were on nusinersen treatment. Results There were significantly higher intramuscular fat fractions in the BFM and QFM of SMA patients compared to healthy controls at baseline and after 6 months. Furthermore, T2 values significantly correlated positively with intramuscular fat fractions. The Hammersmith functional motor scale significantly correlated with the QFM’s intramuscular fat fractions. DTI scans of the sciatic nerve were not significantly different between the two groups. Conclusion This study demonstrates that, water T2 mapping and Dixon-based PDFF estimation may distinguish between adult SMA patients and controls, due to massive intramuscular fat accumulation in SMA. More extensive long-term studies are warranted to further evaluate these two modalities as surrogate markers in SMA patients during treatment.

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MRI DTI and PDFF as Biomarkers for Lower Motor Neuron Degeneration in ALS

Cited by 8 publications

References 39 publications

Performance of Single-Shot Echo-Planar Imaging in Diffusion Tensor Imaging in Rat Sciatic Nerve Compared With Readout-Segmented Echo-Planar Imaging

Performance of Single-Shot Echo-Planar Imaging in Diffusion Tensor Imaging in Rat Sciatic Nerve Compared With Readout-Segmented Echo-Planar Imaging

Peripheral Nerve Imaging

MRI correlates of motoneuron loss in SMA

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