T2 lesion location really matters: a 10 year follow-up study in primary progressive multiple sclerosis

Objectives: Prediction of long term clinical outcome in patients with primary progressive multiple sclerosis (PPMS) using imaging has important clinical implications, but remains challenging. We aimed to determine whether spatial location of T2 and T1 brain lesions predicts clinical progression during a 10-year follow-up in PPMS. Methods: Lesion probability maps of the T2 and T1 brain lesions were generated using the baseline scans of 80 patients with PPMS who were clinically assessed at baseline and then after 1, 2, 5 and 10 years. For each patient, the time (in years) taken before bilateral support was required to walk (time to event (TTE)) was used as a measure of progression rate. The probability of each voxel being ‘lesional’ was correlated with TTE, adjusting for age, gender, disease duration, centre and spinal cord cross sectional area, using a multiple linear regression model. To identify the best, independent predictor of progression, a Cox regression model was used. Results: A significant correlation between a shorter TTE and a higher probability of a voxel being lesional on T2 scans was found in the bilateral corticospinal tract and superior longitudinal fasciculus, and in the right inferior fronto-occipital fasciculus (p<0.05). The best predictor of progression rate was the T2 lesion load measured along the right inferior fronto-occipital fasciculus (p=0.016, hazard ratio 1.00652, 95% CI 1.00121 to 1.01186). Conclusion: Our results suggest that the location of T2 brain lesions in the motor and associative tracts is an important contributor to the progression of disability in PPMS, and is independent of spinal cord involvement

MRI investigation of the sensorimotor cortex and the corticospinal tract after acute spinal cord injury: a prospective longitudinal study

BACKGROUND: In patients with chronic spinal cord injury, imaging of the spinal cord and brain above the level of the lesion provides evidence of neural degeneration; however, the spatial and temporal patterns of progression and their relation to clinical outcomes are uncertain. New interventions targeting acute spinal cord injury have entered clinical trials but neuroimaging outcomes as responsive markers of treatment have yet to be established. We aimed to use MRI to assess neuronal degeneration above the level of the lesion after acute spinal cord injury. METHODS: In our prospective longitudinal study, we enrolled patients with acute traumatic spinal cord injury and healthy controls. We assessed patients clinically and by MRI at baseline, 2 months, 6 months, and 12 months, and controls by MRI at the same timepoints. We assessed atrophy in white matter in the cranial corticospinal tracts and grey matter in sensorimotor cortices by tensor-based analyses of T1-weighted MRI data. We used cross-sectional spinal cord area measurements to assess atrophy at cervical level C2/C3. We used myelin-sensitive magnetisation transfer (MT) and longitudinal relaxation rate (R1) maps to assess microstructural changes associated with myelin. We also assessed associations between MRI parameters and clinical improvement. All analyses of brain scans done with statistical parametric mapping were corrected for family-wise error. FINDINGS: Between Sept 17, 2010, and Dec 31, 2012, we recruited 13 patients and 18 controls. In the 12 months from baseline, patients recovered by a mean of 5·27 points per log month (95% CI 1·91–8·63) on the international standards for the neurological classification of spinal cord injury (ISNCSCI) motor score (p=0·002) and by 10·93 points per log month (6·20–15·66) on the spinal cord independence measure (SCIM) score (p<0·0001). Compared with controls, patients showed a rapid decline in cross-sectional spinal cord area (patients declined by 0·46 mm per month compared with a stable cord area in controls; p<0·0001). Patients had faster rates than controls of volume decline of white matter in the cranial corticospinal tracts at the level of the internal capsule (right Z score 5·21, p=0·0081; left Z score 4·12, p=0·0004) and right cerebral peduncle (Z score 3·89, p=0·0302) and of grey matter in the left primary motor cortex (Z score 4·23, p=0·041). Volume changes were paralleled by significant reductions of MT and R1 in the same areas and beyond. Improvements in SCIM scores at 12 months were associated with a reduced loss in cross-sectional spinal cord area over 12 months (Pearson's correlation 0·77, p=0·004) and reduced white matter volume of the corticospinal tracts at the level of the right internal capsule (Z score 4·30, p=0·0021), the left internal capsule (Z score 4·27, p=0·0278), and left cerebral peduncle (Z score 4·05, p=0·0316). Improvements in ISNCSCI motor scores were associated with less white matter volume change encompassing the corticospinal tract at the level of the right internal capsule (Z score 4·01, p<0·0001). INTERPRETATION: Extensive upstream atrophic and microstructural changes of corticospinal axons and sensorimotor cortical areas occur in the first months after spinal cord injury, with faster degenerative changes relating to poorer recovery. Structural volumetric and microstructural MRI protocols remote from the site of spinal cord injury could serve as neuroimaging biomarkers in acute spinal cord injury

Combining tractography and cortical measures to test system-specific hypotheses in multiple sclerosis

The objective was to test three motor system-specific hypotheses in multiple sclerosis patients: (i) corticospinal tract and primary motor cortex imaging measures differ between multiple sclerosis patients and controls; (ii) in patients, these measures correlate with disability; (iii) in patients, corticospinal tract measures correlate with measures of the ipsilateral primary motor cortex

Mapping Cortical Degeneration in ALS with Magnetization Transfer Ratio and Voxel-Based Morphometry

Pathological and imaging data indicate that amyotrophic lateral sclerosis (ALS) is a multisystem disease involving several cerebral cortical areas. Advanced quantitative magnetic resonance imaging (MRI) techniques enable to explore in vivo the volume and microstructure of the cerebral cortex in ALS. We studied with a combined voxel-based morphometry (VBM) and magnetization transfer (MT) imaging approach the capability of MRI to identify the cortical areas affected by neurodegeneration in ALS patients. Eighteen ALS patients and 18 age-matched healthy controls were examined on a 1.5T scanner using a high-resolution 3D T1 weighted spoiled gradient recalled sequence with and without MT saturation pulse. A voxel-based analysis (VBA) was adopted in order to automatically compute the regional atrophy and MT ratio (MTr) changes of the entire cerebral cortex. By using a multimodal image analysis MTr was adjusted for local gray matter (GM) atrophy to investigate if MTr changes can be independent of atrophy of the cerebral cortex. VBA revealed several clusters of combined GM atrophy and MTr decrease in motor-related areas and extra-motor frontotemporal cortex. The multimodal image analysis identified areas of isolated MTr decrease in premotor and extra-motor frontotemporal areas. VBM and MTr are capable to detect the distribution of neurodegenerative alterations in the cortical GM of ALS patients, supporting the hypothesis of a multi-systemic involvement in ALS. MT imaging changes exist beyond volume loss in frontotemporal cortices

Structural magnetic resonance imaging findings and histopathological correlations in motor neuron diseases—A systematic review and meta-analysis

OBJECTIVES The lack of systematic evidence on neuroimaging findings in motor neuron diseases (MND) hampers the diagnostic utility of magnetic resonance imaging (MRI). Thus, we aimed at performing a systematic review and meta-analysis of MRI features in MND including their histopathological correlation. METHODS In a comprehensive literature search, out of 5941 unique publications, 223 records assessing brain and spinal cord MRI findings in MND were eligible for a qualitative synthesis. 21 records were included in a random effect model meta-analysis. RESULTS Our meta-analysis shows that both T2-hyperintensities along the corticospinal tracts (CST) and motor cortex T2$^{*}$-hypointensitites, also called "motor band sign", are more prevalent in ALS patients compared to controls [OR 2.21 (95%-CI: 1.40-3.49) and 10.85 (95%-CI: 3.74-31.44), respectively]. These two imaging findings correlate to focal axonal degeneration/myelin pallor or glial iron deposition on histopathology, respectively. Additionally, certain clinical MND phenotypes such as amyotrophic lateral sclerosis (ALS) seem to present with distinct CNS atrophy patterns. CONCLUSIONS Although CST T2-hyperintensities and the "motor band sign" are non-specific imaging features, they can be leveraged for diagnostic workup of suspected MND cases, together with certain brain atrophy patterns. Collectively, this study provides high-grade evidence for the usefulness of MRI in the diagnostic workup of suspected MND cases. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020182682

Comprehensive Evaluation of Corticospinal Tract Metabolites in Amyotrophic Lateral Sclerosis Using Whole-Brain 1H MR Spectroscopy

Changes in the distribution of the proton magnetic resonance spectroscopy (MRS) observed metabolites N-acetyl aspartate (NAA), total-choline (Cho), and total-creatine (Cre) in the entire intracranial corticospinal tract (CST) including the primary motor cortex were evaluated in patients with amyotrophic lateral sclerosis (ALS). The study included 38 sporadic definite-ALS subjects and 70 age-matched control subjects. All received whole-brain MR imaging and spectroscopic imaging scans at 3T and clinical neurological assessments including percentage maximum forced vital capacity (FVC) and upper motor neuron (UMN) function. Differences in each individual metabolite and its ratio distributions were evaluated in the entire intracranial CST and in five segments along the length of the CST (at the levels of precentral gyrus (PCG), centrum semiovale (CS), corona radiata (CR), posterior limb of internal capsule (PLIC) and cerebral peduncle (CP)). Major findings included significantly decreased NAA and increased Cho and Cho/NAA in the entire intracranial CST, with the largest differences for Cho/NAA in all the groups. Significant correlations between Cho/NAA in the entire intracranial CST and the right finger tap rate were noted. Of the ten bilateral CST segments, significantly decreased NAA in 4 segments, increased Cho in 5 segments and increased Cho/NAA in all the segments were found. Significant left versus right CST asymmetries were found only in ALS for Cho/NAA in the CS. Among the significant correlations found between Cho/NAA and the clinical assessments included the left-PCG versus FVC and right finger tap rate, left -CR versus FVC and right finger tap rate, and left PLIC versus FVC and right foot tap rate. These results demonstrate that a significant and bilaterally asymmetric alteration of metabolites occurs along the length of the entire intracranial CST in ALS, and the MRS metrics in the segments correlate with measures of disease severity and UMN function

Spinal Cord Imaging in Amyotrophic Lateral Sclerosis: Historical Concepts—Novel Techniques

Amyotrophic lateral sclerosis (ALS) is the most common adult onset motor neuron disease with no effective disease modifying therapies at present. Spinal cord degeneration is a hallmark feature of ALS, highlighted in the earliest descriptions of the disease by Lockhart Clarke and Jean-Martin Charcot. The anterior horns and corticospinal tracts are invariably affected in ALS, but up to recently it has been notoriously challenging to detect and characterize spinal pathology in vivo. With recent technological advances, spinal imaging now offers unique opportunities to appraise lower motor neuron degeneration, sensory involvement, metabolic alterations, and interneuron pathology in ALS. Quantitative spinal imaging in ALS has now been used in cross-sectional and longitudinal study designs, applied to presymptomatic mutation carriers, and utilized in machine learning applications. Despite its enormous clinical and academic potential, a number of physiological, technological, and methodological challenges limit the routine use of computational spinal imaging in ALS. In this review, we provide a comprehensive overview of emerging spinal cord imaging methods and discuss their advantages, drawbacks, and biomarker potential in clinical applications, clinical trial settings, monitoring, and prognostic roles

Clinically Feasible Microstructural MRI to Quantify Cervical Spinal Cord Tissue Injury Using DTI, MT, and T2*-Weighted Imaging:Assessment of Normative Data and Reliability

Forty healthy subjects underwent T2WI, DTI, magnetization transfer, and T2*WI at 3T in BACKGROUND AND PURPOSE: DTI, magnetization transfer, T2*-weighted imaging, and cross-sectional area can quantify aspects of spinal cord microstructure. However, clinical adoption remains elusive due to complex acquisitions, cumbersome analysis, limited reliability, and wide ranges of normal values. We propose a simple multiparametric protocol with automated analysis and report normative data, analysis of confounding variables, and reliability. MATERIALS AND METHODS: Forty healthy subjects underwent T2WI, DTI, magnetization transfer, and T2*WI at 3T in RESULTS: T2*WI WM/GM showed lower intersubject coefficient of variation (3.5%) compared with magnetization transfer ratio (5.8%), fractional anisotropy (6.0%), and cross-sectional area (12.2%). Linear correction of cross-sectional area with cervical cord length, fractional anisotropy with age, and magnetization transfer ratio with age and height led to decreased coefficients of variation (4.8%, 5.4%, and 10.2%, respectively). Acceptable reliability was achieved for all metrics/levels (test-retest coefficient of variation <5%), with T2*WI WM/GM comparing favorably with fractional anisotropy and magnetization transfer ratio. DTI with and without cardiac triggering showed no significant differences for fractional anisotropy and test-retest coefficient of variation. CONCLUSIONS: Reliable multiparametric assessment of spinal cord microstructure is possible by using clinically suitable methods. These results establish normalization procedures and pave the way for clinical studies, with the potential for improving diagnostics, objectively monitoring disease progression, and predicting outcomes in spinal pathologies

Utility of Diffusion and Magnetization Transfer MRI in Cervical Spondylotic Myelopathy: A Pilot Study

Diffusion tensor imaging (DTI) and magnetization transfer (MT) magnetic resonance imaging (MRI) can help detect spinal cord pathology, and tract-specific analysis of their parameters, such as fractional anisotropy (FA), mean diffusivity, axial diffusivity (AD), radial diffusivity (RD) and MT ratio (MTR), can give microstructural information. We performed the tract-based acquisition of MR parameters of three major motor tracts: the lateral corticospinal (CS), rubrospinal (RuS) tract, and lateral reticulospinal (RS) tract as well as two major sensory tracts, i.e., the fasciculus cuneatus (FC) and spinal lemniscus, to detect pathologic change and find correlations with clinical items. MR parameters were extracted for each tract at three levels: the most compressed lesion level and above and below the lesion. We compared the MR parameters of eight cervical spondylotic myelopathy patients and 12 normal controls and analyzed the correlation between clinical evaluation items and MR parameters in patients. RuS and lateral RS showed worse DTI parameters at the lesion level in patients compared to the controls. Worse DTI parameters in those tracts were correlated with weaker power grasp at the lesion level. FC and lateral CS showed a correlation between higher RD and lower FA and MTR with a weaker lateral pinch below the lesion level.ope