Introduction
Small vessel disease (SVD) causes most spontaneous intracerebral haemorrhage (ICH) and is associated with widespread microstructural brain tissue disruption, which can be quantified via ...diffusion tensor imaging (DTI) metrics: mean diffusivity (MD) and fractional anisotropy (FA). Little is known about the impact of whole-brain microstructural alterations after SVD-related ICH. We aimed to investigate: (1) association between whole-brain DTI metrics and functional outcome after ICH; and (2) predictive ability of these metrics compared to the pre-existing ICH score.
Methods
Sixty-eight patients (38.2% lobar) were retrospectively included. We assessed whole-brain DTI metrics (obtained within 5 days after ICH) in cortical and deep grey matter and white matter. We used univariable logistic regression to assess the associations between DTI and clinical-radiological variables and poor outcome (modified Rankin Scale > 2). We determined the optimal predictive variables (via LASSO estimation) in: model 1 (DTI variables only), model 2 (DTI plus non-DTI variables), model 3 (DTI plus ICH score). Optimism-adjusted C-statistics were calculated for each model and compared (likelihood ratio test) against the ICH score.
Results
Deep grey matter MD (OR 1.04 95% CI 1.01–1.07,
p
= 0.010) and white matter MD (OR 1.11 95% CI 1.01–1.23,
p
= 0.044) were associated (univariate analysis) with poor outcome. Discrimination values for model 1 (0.67 95% CI 0.52–0.83), model 2 (0.71 95% CI 0.57–0.85) and model 3 (0.66 95% CI 0.52–0.82) were all significantly higher than the ICH score (0.62 95% CI 0.49–0.75).
Conclusion
Our exploratory study suggests that whole-brain microstructural disruption measured by DTI is associated with poor 6-month functional outcome after SVD-related ICH. Whole-brain DTI metrics performed better at predicting recovery than the existing ICH score.
A first-ever spinal cord imaging meeting was sponsored by the International Spinal Research Trust and the Wings for Life Foundation with the aim of identifying the current state-of-the-art of spinal ...cord imaging, the current greatest challenges, and greatest needs for future development. This meeting was attended by a small group of invited experts spanning all aspects of spinal cord imaging from basic research to clinical practice. The greatest current challenges for spinal cord imaging were identified as arising from the imaging environment itself; difficult imaging environment created by the bone surrounding the spinal canal, physiological motion of the cord and adjacent tissues, and small crosssectional dimensions of the spinal cord, exacerbated by metallic implants often present in injured patients. Challenges were also identified as a result of a lack of “critical mass” of researchers taking on the development of spinal cord imaging, affecting both the rate of progress in the field, and the demand for equipment and software to manufacturers to produce the necessary tools. Here we define the current state-of-the-art of spinal cord imaging, discuss the underlying theory and challenges, and present the evidence for the current and potential power of these methods. In two review papers (part I and part II), we propose that the challenges can be overcome with advances in methods, improving availability and effectiveness of methods, and linking existing researchers to create the necessary scientific and clinical network to advance the rate of progress and impact of the research.
•Clinical challenges encountered in imaging of the spinal cord are presented.•Description of functional MRI of the spinal cord applications•Description of diffusion tensor imaging of the spinal cord applications•Specific findings in spinal cord pathologies
There is a need to assess spinal cord involvement in multiple sclerosis with new imaging techniques in order to understand better the underlying pathology. We aimed to evaluate whether quantitative ...MRI measures, obtained using single-voxel 1H-MR spectroscopy of the cervical cord and diffusion-based tractography of the major spinal cord pathways, in patients with a cervical cord relapse, differed from controls and correlated with acute disability. Fourteen patients at the onset of a cervical cord relapse with at least one lesion between C1 and C3 were imaged on a 1.5 T scanner and clinically assessed on the Expanded Disability Status Scale (EDSS), 9-hole peg test (HPT) and timed 25-foot walk test. Thirteen age- and gender-matched control subjects were also scanned. Metabolite concentrations, including total N-acetyl-aspartate (tNAA), choline-containing compounds (Cho), creatine plus phosphocreatine (Cr) and myo-Inositol (m-Ins), were quantified at C1–C3. Probabilistic tractography was performed at C1–C3 to track the lateral cortico-spinal tracts in the lateral columns, the anterior cortico-spinal tracts and the anterior spino-thalamic fasciculi in the anterior columns, and the bilateral fasciculus gracilis and cuneatus in the posterior columns. Diffusion- and tractography-derived measures of these tracts, including fractional anisotropy and voxel-based connectivity, which reflect fibre integrity, were obtained. These MRI measures were compared between patients and controls using the Mann–Whitney test. Univariate correlations between MRI measures and disability were assessed using the Spearman's rho correlation coefficient. Multiple regression analyses were performed to investigate which MRI measures independently correlated with the clinical scores, adjusting also for cross-sectional cord area, age and gender. Patients showed lower tNAA of the cervical cord, lower connectivity and lower fractional anisotropy of the lateral cortico-spinal tracts and posterior tracts, than controls. In patients, there were significant correlations between: (i) EDSS and m-Ins, Cho, Cr and radial diffusivity of the lateral cortico-spinal tracts; (ii) HPT and Cr, radial diffusivity of the lateral cortico-spinal tracts, connectivity and fractional anisotropy of the posterior tracts, and connectivity of the anterior tracts. M-Ins was independently associated with the EDSS, while Cr, tNAA and connectivity of the posterior tracts were independently associated with the HPT. MR spectroscopy and diffusion-based tractography of the cervical cord provide measures that are sensitive to the tissue damage occurring in this area in patients with a cervical cord relapse. These measures were found to correlate with acute disability. Our findings suggest that it would be worthwhile performing longitudinal studies and extending these novel techniques to other neurological diseases affecting the spinal cord.
A first-ever spinal cord imaging meeting was sponsored by the International Spinal Research Trust and the Wings for Life Foundation with the aim of identifying the current state-of-the-art of spinal ...cord imaging, the current greatest challenges, and greatest needs for future development. This meeting was attended by a small group of invited experts spanning all aspects of spinal cord imaging from basic research to clinical practice. The greatest current challenges for spinal cord imaging were identified as arising from the imaging environment itself; difficult imaging environment created by the bone surrounding the spinal canal, physiological motion of the cord and adjacent tissues, and small cross-sectional dimensions of the spinal cord, exacerbated by metallic implants often present in injured patients. Challenges were also identified as a result of a lack of “critical mass” of researchers taking on the development of spinal cord imaging, affecting both the rate of progress in the field, and the demand for equipment and software to manufacturers to produce the necessary tools. Here we define the current state-of-the-art of spinal cord imaging, discuss the underlying theory and challenges, and present the evidence for the current and potential power of these methods. In two review papers (part I and part II), we propose that the challenges can be overcome with advances in methods, improving availability and effectiveness of methods, and linking existing researchers to create the necessary scientific and clinical network to advance the rate of progress and impact of the research.
•Methodological challenges encountered in imaging of the spinal cord are presented.•Techniques to overcome these challenges for fMRI and DTI are presented.•Methods for spinal cord MRI (fMRI, DTI, MWF, MTR), MRS, and PET are presented.•Post-processing methods to improve spinal cord MRI are discussed.•We discuss the future directions, and current needs, for spinal cord imaging.
Spinal cord pathology can be functionally very important in neurological disease. Pathological studies have demonstrated the involvement of spinal cord grey matter (GM) and white matter (WM) in ...several diseases, although the clinical relevance of abnormalities detected histopathologically is difficult to assess without a reliable way to assess cord GM and WM in vivo. In this study, the feasibility of GM and WM segmentation was investigated in the upper cervical spinal cord of 10 healthy subjects, using high-resolution images acquired with a commercially available 3D gradient-echo pulse sequence at 3T. For each healthy subject, tissue-specific (i.e. WM and GM) cross-sectional areas were segmented and total volumes calculated from a 15mm section acquired at the level of C2–3 intervertebral disc and magnetisation transfer ratio (MTR) values within the extracted volumes were also determined, as an example of GM and WM quantitative measurements in the cervical cord. Mean (±SD) total cord cross-sectional area (TCA) and total cord volume (TCV) of the section studied across 10 healthy subjects were 86.9 (±7.7) mm2 and 1302.8 (±115) mm3, respectively; mean (±SD) total GM cross-sectional area (TGMA) and total GM volume (TGMV) were 14.6 (±1.1) mm2 and 218.3 (±16.8) mm3, respectively; mean (±SD) GM volume fraction (GMVF) was 0.17 (±0.01); mean (±SD) MTR of the total WM volume (WM-MTR) was 51.4 (±1.5) and mean (±SD) MTR of the total GM volume (GM-MTR) was 49.7 (±1.6). The mean scan-rescan, intra- and inter-observer % coefficient of variation for measuring the TCA were 0.7%, 0.5% and 0.5% and for measuring the TGMA were 6.5%, 5.4% and 12.7%. The difference between WM-MTR and GM-MTR was found to be statistically significant (p=0.00006). This study has shown that GM and WM segmentation in the cervical cord is possible and the MR imaging protocol and analysis method presented here in healthy controls can be potentially extended to study the cervical cord in disease states, with the option to explore further quantitative measurements alongside MTR.
► A method for cervical cord grey matter and white matter segmentation is proposed. ► This method enables tissue-specific volume measurements in the cervical cord. ► This method facilitates tissue-specific quantitative MR investigations in the cord. ► The proposed segmentation method can be readily implemented in the clinical setting.
Background:
Spinal cord pathology is an important substrate for long-term disability in multiple sclerosis (MS).
Objective:
To investigate longitudinal changes in spinal cord lesions and atrophy in ...patients with a non-spinal clinically isolated syndrome (CIS), and how they relate to the development of disability.
Methods:
In all, 131 patients with a non-spinal CIS had brain and spinal cord imaging at the time of CIS and approximately 5 years later (median: 5.2 years, range: 3.0–7.9 years). Brain magnetic resonance imaging (MRI) measures consisted of T2-hyperintense and T1-hypointense lesion loads plus brain atrophy. Spinal cord MRI measures consisted of lesion number and the upper cervical cord cross-sectional area (UCCA). Disability was measured using the Expanded Disability Status Scale (EDSS). Multiple linear regression was used to identify independent predictors of disability after 5 years.
Results:
During follow-up, 93 (71%) patients were diagnosed with MS. Baseline spinal cord lesion number, change in cord lesion number and change in UCCA were independently associated with EDSS (R2 = 0.53) at follow-up. Including brain T2 lesion load and brain atrophy only modestly increased the predictive power of the model (R2 = 0.64).
Conclusion:
Asymptomatic spinal cord lesions and spinal cord atrophy contribute to the development of MS-related disability over the first 5 years after a non-spinal CIS.
Introduction
Diffusion tensor imaging (DTI) can assess the structural integrity of the corticospinal tract (CST) in vivo. We aimed to investigate whether CST DTI metrics after intracerebral ...haemorrhage (ICH) are associated with 6-month functional outcome and can improve the predictive performance of the existing ICH score.
Methods
We retrospectively included 42 patients with DTI performed within 5 days after deep supratentorial spontaneous ICH. Ipsilesional-to-contralesional ratios were calculated for fractional anisotropy (rFA) and mean diffusivity (rMD) in the pontine segment (PS) of the CST. We determined the most predictive variables for poor 6-month functional outcome modified Rankin Scale (mRS) > 2 using the least absolute shrinkage and selection operator (LASSO) method. We calculated discrimination using optimism-adjusted estimation of the area under the curve (AUC).
Results
Patients with 6-month mRS > 2 had lower rFA (0.945 ± 0.139 vs 1.045 ± 0.130; OR 0.004 95% CI 0.00–0.77;
p
= 0.04) and higher rMD (1.233 ± 0.418 vs 0.963 ± 0.211; OR 22.5 95% CI 1.46–519.68;
p
= 0.02). Discrimination (AUC) values were: 0.76 (95% CI 0.61–0.91) for the ICH score, 0.71 (95% CI 0.54–0.89) for rFA, and 0.72 (95% CI 0.61–0.91) for rMD. Combined models with DTI and non-DTI variables offer an improvement in discrimination: for the best model, the AUC was 0.82 (95% CI 0.68–0.95;
p
= 0.15).
Conclusion
In our exploratory study, PS-CST rFA and rMD had comparable predictive ability to the ICH score for 6-month functional outcome. Adding DTI metrics to clinical-radiological scores might improve discrimination, but this needs to be investigated in larger studies.
In multiple sclerosis (MS), pathological studies have identified substantial demyelination and neuronal loss in the spinal cord grey matter (GM). However, there has been limited in vivo investigation ...of cord GM abnormalities and their possible functional effects using MRI combined with clinical evaluation.
We recruited healthy controls (HC) and people with a clinically isolated syndrome (CIS), relapsing remitting (RR) and secondary progressive (SP) MS. All subjects had 3 T spinal cord MRI with measurement of cord cross-sectional area and diffusion tensor imaging metrics in the GM and posterior and lateral column white matter tracts using region of interest analysis. Physical disability was assessed using the expanded disability status scale (EDSS) and motor components of the MS functional composite scale. We calculated differences between MS and HC using a ANOVA and associations with disability using linear regression.
113 people were included in this study: 30 controls, 21 CIS, 33 RR and 29 SPMS. Spinal cord radial diffusivity (RD), fractional anisotropy and mean diffusivity in the GM and posterior columns were significantly more abnormal in SPMS than in RRMS. Spinal cord GM RD (β=0.33, p<0.01) and cord area (β=-0.45, p<0.01) were independently associated with EDSS (R(2)=0.77); spinal cord GM RD was also independently associated with a 9-hole peg test (β=-0.33, p<0.01) and timed walk (β=-0.20, p=0.04).
The study findings suggest that pathological involvement of the spinal cord GM contributes significantly to physical disability in relapse-onset MS and SPMS in particular.
Brain structural covariance networks (SCNs) based on pairwise statistical associations of cortical thickness data across brain areas reflect underlying physical and functional connections between ...them. SCNs capture the complexity of human brain cortex structure and are disrupted in neurodegenerative conditions. However, the longitudinal assessment of SCN dynamics has not yet been explored, despite its potential to unveil mechanisms underlying neurodegeneration. Here, we evaluated the changes of SCNs over 12 months in patients with a first inflammatory-demyelinating attack of the Central Nervous System and assessed their clinical relevance by comparing SCN dynamics of patients with and without conversion to multiple sclerosis (MS) over one year. All subjects underwent clinical and brain MRI assessments over one year. Brain cortical thicknesses for each subject and time point were used to obtain group-level between-area correlation matrices from which nodal connectivity metrics were obtained. Robust bootstrap-based statistical approaches (allowing sampling with replacement) assessed the significance of longitudinal changes. Patients who converted to MS exhibited significantly greater network connectivity at baseline than non-converters (p = 0.02) and a subsequent connectivity loss over time (p = 0.001-0.02), not observed in non-converters' network. These findings suggest SCN analysis is sensitive to brain tissue changes in early MS, reflecting clinically relevant aspects of the condition. However, this is preliminary work, indicated by the low sample sizes, and its results and conclusions should be treated with caution and confirmed with larger cohorts.
The secondary progressive phase of multiple sclerosis is characterised by disability progression due to processes that lead to neurodegeneration. Surrogate markers such as those derived from MRI are ...beneficial in understanding the pathophysiology that drives disease progression and its relationship to clinical disability. We undertook a 1H-MRS imaging study in a large secondary progressive MS (SPMS) cohort, to examine whether metabolic markers of brain injury are associated with measures of disability, both physical and cognitive.
A cross-sectional analysis of individuals with secondary-progressive MS was performed in 119 participants. They underwent
H-MR spectroscopy to obtain estimated concentrations and ratios to total Cr for total NAA, mIns, Glx, and total Cho in normal-appearing WM and GM. Clinical outcome measures chosen were the following: Paced Auditory Serial Addition Test, Symbol Digit Modalities Test, Nine-Hole Peg Test, Timed 25-foot Walk Test, and the Expanded Disability Status Scale. The relationship between these neurometabolites and clinical disability measures was initially examined using Spearman rank correlations. Significant associations were then further analyzed in multiple regression models adjusting for age, sex, disease duration, T2 lesion load, normalized brain volume, and occurrence of relapses in 2 years preceding study entry.
Significant associations, which were then confirmed by multiple linear regression, were found in normal-appearing WM for total NAA (tNAA)/total Cr (tCr) and the Nine-Hole Peg Test (ρ = 0.23; 95% CI, 0.06-0.40); tNAA and tNAA/tCr and the Paced Auditory Serial Addition Test (ρ = 0.21; 95% CI, 0.03-0.38) (ρ = 0.19; 95% CI, 0.01-0.36); mIns/tCr and the Paced Auditory Serial Addition Test, (ρ = -0.23; 95% CI, -0.39 to -0.05); and in GM for tCho and the Paced Auditory Serial Addition Test (ρ = -0.24; 95% CI, -0.40 to -0.06). No other GM or normal-appearing WM relationships were found with any metabolite, with associations found during initial correlation testing losing significance after multiple linear regression analysis.
This study suggests that metabolic markers of neuroaxonal integrity and astrogliosis in normal-appearing WM and membrane turnover in GM may act as markers of disability in secondary-progressive MS.
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