Radial diffusivity as an imaging biomarker for early diagnosis of non-demented amyotrophic lateral sclerosis

Bao, Yijun; Yang, Li; Chen, Yan; Zhang, Biyun; Li, Haiqing; Tang, Weijun; Geng, Daoying; Li, Yuxin

doi:10.1007/s00330-018-5506-z

Cited by 14 publications

(18 citation statements)

References 73 publications

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“…Although several WM regions showed decreased AK values (data not shown), they did not reach statistical significance. Several previous DTI studies have provided results consistent with ours, in which no difference in axial diffusivity, a metric indicating the diffusion parallel to the axon, was found in ALS patients . Unfortunately, the specific reasons for the absence of diffusion axial measurement changes are not well understood for ALS at present .…”

Section: Discussionsupporting

confidence: 87%

“…RK specifically evaluates the radial diffusion perpendicular to the axon and is believed to reflect myelin integrity; thus, RK reduction may indicate the impairment of myelination in ALS. Consistently, demyelination in ALS has been demonstrated by postmortem studies and is also reflected by DTI measurements such as decreased FA and increased RD . In contrast, AK specifically evaluates the diffusion restriction along the axon (maximal diffusion direction) and could reflect axonal integrity.…”

Section: Discussionmentioning

confidence: 62%

“…Consistently, demyelination in ALS has been demonstrated by postmortem studies 5,23 and is also reflected by DTI measurements such as decreased FA and increased RD. 24 In contrast, AK specifically evaluates the diffusion restriction along the axon (maximal diffusion direction) and could reflect axonal integrity. Although several WM regions showed decreased AK values (data not shown), they did not reach statistical significance.…”

Section: Discussionmentioning

confidence: 99%

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Abnormal cerebral microstructures revealed by diffusion kurtosis imaging in amyotrophic lateral sclerosis

Huang

Zou

Xue

et al. 2019

Magnetic Resonance Imaging

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Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which cerebral structural impairment is a consistent feature. Purpose To investigate cerebral microstructural changes in ALS using diffusion kurtosis imaging (DKI) for the first time. Study Type Prospective. Subjects Eighteen ALS patients and 20 healthy controls. Field Strength/Sequence DKI images were obtained by a spin‐echo echo‐planar imaging sequence on a 3T MRI scanner, with three b‐values (0, 1000, and 2000 s/mm2) and 64 diffusion encoding directions. Assessment The revised ALS Functional Rating Scale (ALSFRS‐R) was administered to assess disease severity, and the symptom duration and disease progression rate were also recorded. Voxel‐based analysis was applied to examine the alteration of DKI metrics (ie, mean kurtosis metrics [MK], axial kurtosis [AK], and radial kurtosis [RK]) and the conventional diffusion metrics (ie, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity). Statistical Tests Student's t‐test, chi‐square test, and Pearson correlation analysis. Results ALS patients showed MK reductions in gray matter areas, including the bilateral precentral gyrus, bilateral paracentral lobule, and left anterior cingulate gyrus; they also showed decreased MK values in white matter (WM) in the bilateral precentral gyrus, bilateral corona radiata, bilateral middle corpus callosum, left occipital lobe, and right superior parietal lobule. The spatial distribution of the regions with reduced RK was similar to those with decreased MK. No significant AK difference was found between groups. The correlation analysis revealed significant associations between DKI metrics and clinical assessments such as ALSFRS‐R score and disease duration. Additionally, several WM regions showed between‐group differences in conventional diffusion metrics; but the spatial extent was smaller than that with reduced DKI metrics. Data Conclusion The reduction in DKI metrics indicates decreased microstructural complexity in ALS, involving both motor‐related areas and extramotor regions. DKI metrics can serve as potential biomarkers for assessing disease severity. Level of Evidence: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:554–562.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

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Abnormal cerebral microstructures revealed by diffusion kurtosis imaging in amyotrophic lateral sclerosis

Huang

Zou

Xue

et al. 2019

Magnetic Resonance Imaging

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“…Decreased FA and increased RD were the most pronounced ALS‐associated changes; colocalization of the affected WM‐tracts was evident in both contrasts. This is in line with prior TBSS studies with moderate‐to‐big sample sizes that also reported widespread differences—particularly in RD and FA contrasts—in case–control comparisons (Bao et al, 2018; Ben Bashat et al, 2011; Cardenas‐Blanco et al, 2014; Cirillo et al, 2012; de Albuquerque et al, 2017; Sarica et al, 2014; Zimmerman‐Moreno et al, 2016). However, some studies using smaller cohorts have reported that AD was the most profoundly altered DTI metric within their patient groups (Geraldo et al, 2018; Metwalli et al, 2010).…”

Section: Discussionsupporting

confidence: 86%

Disease aggressiveness signatures of amyotrophic lateral sclerosis in white matter tracts revealed by the D50 disease progression model

Steinbach

Gaur

Roediger

et al. 2020

Human Brain Mapping

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Numerous neuroimaging studies in amyotrophic lateral sclerosis (ALS) have reported links between structural changes and clinical data; however phenotypic and disease course heterogeneity have occluded robust associations. The present study used the novel D50 model, which distinguishes between disease accumulation and aggressiveness, to probe correlations with measures of diffusion tensor imaging (DTI). DTI scans of 145 ALS patients and 69 controls were analyzed using tract-based-spatial-statistics of fractional anisotropy (FA), mean-(MD), radial (RD), and axial diffusivity (AD) maps. Intergroup contrasts were calculated between patients and controls, and between ALS subgroups: based on (a) the individual disease covered (Phase I vs. II) or b) patients' disease aggressiveness (D50 value). Regression analyses were used to probe correlations with model-derived parameters. Case-control comparisons revealed widespread ALS-related white matter pathology with decreased FA and increased MD/RD. These affected pathways showed also correlations with the accumulated disease for increased MD/RD, driven by the subgroup of Phase I patients. No significant differences were noted between patients in Phase I and II for any of the contrasts. Patients with high disease aggressiveness (D50 < 30 months) displayed increased AD/MD in bifrontal and biparietal pathways, which was corroborated by significant voxel-wise regressions with D50. Application of the D50 model revealed associations between DTI measures and ALS pathology in Phase I, representing individual disease accumulation early in disease. Patients' overall disease aggressiveness correlated robustly with the extent of DTI changes. We recommend the D50 model for studies developing/validating neuroimaging or other biomarkers for ALS.

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“…However, previous studies have mostly focused on FA. Some studies used AD, RD, and MD values along with FA values to evaluate ALS (Supplementary Table S1) 14,[16][17][18][19][20][21][22][23][24] . However, most studies had a relatively small number of participants with wide diagnostic certainty according to the El Escorial criteria.…”

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confidence: 99%

Usefulness of diffusion tensor imaging findings as biomarkers for amyotrophic lateral sclerosis

Baek

Park

Kim

et al. 2020

Sci Rep

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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. However, no reliable biomarkers have been identified to represent the clinical status. This study aimed to investigate whether diffusion tensor imaging (DTI) findings are useful imaging biomarkers to indicate the clinical status of ALS patients. Ninety-six probable or definite ALS cases and 47 age-and sex-matched, normal controls were enrolled. Demographic and clinical data were collected at the time of DTI. DTI data were acquired using a 3-Tesla magnetic resonance imaging scanner and analysed by voxel-wise statistical analyses for fractional anisotropy, axial diffusivity, radial diffusivity, mean diffusivity, and mode of anisotropy. Compared with the healthy control group, the ALS group had significant differences in DTI scalars in the diffuse tracts of the brain, which was predominant in the corticospinal tract at the brainstem and cerebellar peduncle area. Furthermore, the DTI values correlated with the ALS functional rating scalerevised (ALSFRS-R) scores and the delta ALSFRS-R score representing the rate of disease progression. The subgroup analysis revealed a more severe and widespread brain degeneration was observed in rapidly progressive ALS. Therefore, our results suggest that DTI findings are useful as imaging biomarkers for evaluating the clinical severity and rate of disease progression in ALS. Amyotrophic lateral sclerosis (ALS) is a heterogeneous disease in many aspects, including clinical phenotypes and genetics 1. The identification of genes linking ALS with frontotemporal dementia (FTD) and the emerging concept of multisystem proteinopathies have changed the widely held belief that ALS affects only the motor neuron system 2,3. This heterogeneity has been recently emphasised, not only in the designing of clinical trials with stratification or enriched enrolment criteria but also in our understanding of the post-hoc analysis of responders and non-responders for the specific treatment. Therefore, stratification of patient groups according to clinical phenotypes (including diverse motor/psychological findings and genetic information) should be considered while designing clinical trials in heterogeneous ALS populations. In addition, objective biomarkers that can be used to reflect the disease status and predict prognosis could be valuable for the diagnosis and treatment of ALS and the design of clinical trials. With advances in brain imaging techniques, functional and microstructural changes in the central nervous system (CNS) have been investigated. Specifically, diffusion tensor imaging (DTI) is one of the most useful magnetic resonance imaging (MRI) techniques for examining microstructural changes in the CNS 4. Multiple DTI scalars extracted from raw DTI data reflect the various pathological changes. Fractional anisotropy (FA) is the most widely used scalar in DTI and indicates various characteristics of axon fibres, including the number and size of axon fibres, and the density of crossing fibres 5. Axial diffusivity (AD) has been s...

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Radial diffusivity as an imaging biomarker for early diagnosis of non-demented amyotrophic lateral sclerosis

Abstract: • Changes in RD were broader than those in FA in bilateral CST. • Involvement of extra-motor regions was uncovered by RD. • FA and RD in CST were related to ALSFRS-R scores.

Cited by 14 publications

References 73 publications

Abnormal cerebral microstructures revealed by diffusion kurtosis imaging in amyotrophic lateral sclerosis

Abnormal cerebral microstructures revealed by diffusion kurtosis imaging in amyotrophic lateral sclerosis

Disease aggressiveness signatures of amyotrophic lateral sclerosis in white matter tracts revealed by the D50 disease progression model

Usefulness of diffusion tensor imaging findings as biomarkers for amyotrophic lateral sclerosis

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