Background:
Multiple sclerosis (MS) affects both brain and spinal cord. However, studies of the neuraxis with advanced magnetic resonance imaging (MRI) are rare because of long acquisition times. We ...investigated neurodegeneration in MS brain and cervical spinal cord using neurite orientation dispersion and density imaging (NODDI).
Objective:
The aim of this study was to investigate possible alterations, and their clinical relevance, in neurite morphology along the brain and cervical spinal cord of relapsing–remitting MS (RRMS) patients.
Methods:
In total, 28 RRMS patients and 20 healthy controls (HCs) underwent brain and spinal cord NODDI at 3T. Physical and cognitive disability was assessed. Individual maps of orientation dispersion index (ODI) and neurite density index (NDI) in brain and spinal cord were obtained. We examined differences in NODDI measures between groups and the relationships between NODDI metrics and clinical scores using linear regression models adjusted for age, sex and brain tissue volumes or cord cross-sectional area (CSA).
Results:
Patients showed lower NDI in the brain normal-appearing white matter (WM) and spinal cord WM than HCs. In patients, a lower NDI in the spinal cord WM was associated with higher disability.
Conclusion:
Reduced neurite density occurs in the neuraxis but, especially when affecting the spinal cord, it may represent a mechanism of disability in MS.
Background:
Pathology in the spinal cord of patients with primary progressive multiple sclerosis (PPMS) contributes to disability progression. We previously reported abnormal Q-space imaging ...(QSI)-derived indices in the spinal cord at baseline in patients with early PPMS, suggesting early neurodegeneration.
Objective:
The aim was to investigate whether changes in spinal cord QSI over 3 years in the same cohort are associated with disability progression and if baseline QSI metrics predict clinical outcome.
Methods:
Twenty-three PPMS patients and 23 healthy controls recruited at baseline were invited for follow-up cervical cord 3T magnetic resonance imaging (MRI) and clinical assessment after 1 year and 3 years. Cord cross-sectional area (CSA) and QSI measures were obtained, together with standard brain MRI measures. Mixed-effect models assessed MRI changes over time and their association with clinical changes. Linear regression identified baseline MRI indices associated with disability at 3 years.
Results:
Over time, patients deteriorated clinically and showed an increase in cord QSI indices of perpendicular diffusivity that was associated with disability worsening, independently of the decrease in CSA. Higher perpendicular diffusivity and lower CSA at baseline predicted worse disability at 3 years.
Conclusion:
Increasing spinal cord perpendicular diffusivity may indicate ongoing neurodegeneration, which underpins disability progression in PPMS, independently of the development of spinal cord atrophy.
In early multiple sclerosis, a clearer understanding of normal-brain tissue microstructural and metabolic abnormalities will provide valuable insights into its pathophysiology. We used ...multi-parametric quantitative MRI to detect alterations in brain tissues of patients with their first demyelinating episode. We acquired neurite orientation dispersion and density imaging to investigate morphology of neurites (dendrites and axons) and 23Na MRI (to estimate total sodium concentration, a reflection of underlying changes in metabolic function). In this cross-sectional study, we enrolled 42 patients diagnosed with clinically isolated syndrome or multiple sclerosis within 3 months of their first demyelinating event and 16 healthy controls. Physical and cognitive scales were assessed. At 3 T, we acquired brain and spinal cord structural scans, and neurite orientation dispersion and density imaging. Thirty-two patients and 13 healthy controls also underwent brain 23Na MRI. We measured neurite density and orientation dispersion indices and total sodium concentration in brain normal-appearing white matter, white matter lesions, and grey matter. We used linear regression models (adjusting for brain parenchymal fraction and lesion load) and Spearman correlation tests (significance level P ≤ 0.01). Patients showed higher orientation dispersion index in normal-appearing white matter, including the corpus callosum, where they also showed lower neurite density index and higher total sodium concentration, compared with healthy controls. In grey matter, compared with healthy controls, patients demonstrated: lower orientation dispersion index in frontal, parietal and temporal cortices; lower neurite density index in parietal, temporal and occipital cortices; and higher total sodium concentration in limbic and frontal cortices. Brain volumes did not differ between patients and controls. In patients, higher orientation dispersion index in corpus callosum was associated with worse performance on timed walk test (P = 0.009, B = 0.01, 99% confidence interval = 0.0001 to 0.02), independent of brain and lesion volumes. Higher total sodium concentration in left frontal middle gyrus was associated with higher disability on Expanded Disability Status Scale (rs = 0.5, P = 0.005). Increased axonal dispersion was found in normal-appearing white matter, particularly corpus callosum, where there was also axonal degeneration and total sodium accumulation. The association between increased axonal dispersion in the corpus callosum and worse walking performance implies that morphological and metabolic alterations in this structure could mechanistically contribute to disability in multiple sclerosis. As brain volumes were neither altered nor related to disability in patients, our findings suggest that these two advanced MRI techniques are more sensitive at detecting clinically relevant pathology in early multiple sclerosis.
Background:
Optic neuritis (ON) is a common feature of inflammatory demyelinating diseases (IDDs) such as multiple sclerosis (MS), aquaporin 4-antibody neuromyelitis optica spectrum disorder (AQP4 + ...NMOSD) and myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD). However, the involvement of the optic chiasm (OC) in IDD has not been fully investigated.
Aims:
To examine OC differences in non-acute IDD patients with (ON+) and without ON (ON−) using magnetisation transfer ratio (MTR), to compare differences between MS, AQP4 + NMOSD and MOGAD and understand their associations with other neuro-ophthalmological markers.
Methods:
Twenty-eight relapsing-remitting multiple sclerosis (RRMS), 24 AQP4 + NMOSD, 28 MOGAD patients and 32 healthy controls (HCs) underwent clinical evaluation, MRI and optical coherence tomography (OCT) scan. Multivariable linear regression models were applied.
Results:
ON + IDD patients showed lower OC MTR than HCs (28.87 ± 4.58 vs 31.65 ± 4.93; p = 0.004). When compared with HCs, lower OC MTR was found in ON + AQP4 + NMOSD (28.55 ± 4.18 vs 31.65 ± 4.93; p = 0.020) and MOGAD (28.73 ± 4.99 vs 31.65 ± 4.93; p = 0.007) and in ON− AQP4 + NMOSD (28.37 ± 7.27 vs 31.65 ± 4.93; p = 0.035). ON+ RRMS had lower MTR than ON− RRMS (28.87 ± 4.58 vs 30.99 ± 4.76; p = 0.038). Lower OC MTR was associated with higher number of ON (regression coefficient (RC) = −1.15, 95% confidence interval (CI) = −1.819 to −0.490, p = 0.001), worse visual acuity (RC = −0.026, 95% CI = −0.041 to −0.011, p = 0.001) and lower peripapillary retinal nerve fibre layer (pRNFL) thickness (RC = 1.129, 95% CI = 0.199 to 2.059, p = 0.018) when considering the whole IDD group.
Conclusion:
OC microstructural damage indicates prior ON in IDD and is linked to reduced vision and thinner pRNFL.
Background:
Conventional magnetic resonance imaging (MRI) does not account for all disability in multiple sclerosis.
Objective:
The objective was to assess the ability of graph metrics from ...diffusion-based structural connectomes to explain motor function beyond conventional MRI in early demyelinating clinically isolated syndrome (CIS).
Methods:
A total of 73 people with CIS underwent conventional MRI, diffusion-weighted imaging and clinical assessment within 3 months from onset. A total of 28 healthy controls underwent MRI. Structural connectomes were produced. Differences between patients and controls were explored; clinical associations were assessed in patients. Linear regression models were compared to establish relevance of graph metrics over conventional MRI.
Results:
Local efficiency (p = 0.045), clustering (p = 0.034) and transitivity (p = 0.036) were reduced in patients. Higher assortativity was associated with higher Expanded Disability Status Scale (EDSS) (β = 74.9, p = 0.026) scores. Faster timed 25-foot walk (T25FW) was associated with higher assortativity (β = 5.39, p = 0.026), local efficiency (β = 27.1, p = 0.041) and clustering (β = 36.1, p = 0.032) and lower small-worldness (β = −3.27, p = 0.015). Adding graph metrics to conventional MRI improved EDSS (p = 0.045, ΔR2 = 4) and T25FW (p < 0.001, ΔR2 = 13.6) prediction.
Conclusion:
Graph metrics are relevant early in demyelination. They show differences between patients and controls and have relationships with clinical outcomes. Segregation (local efficiency, clustering, transitivity) was particularly relevant. Combining graph metrics with conventional MRI better explained disability.
Background:
We assessed the ability of a brain-and-cord-matched quantitative magnetic resonance imaging (qMRI) protocol to differentiate patients with progressive multiple sclerosis (PMS) from ...controls, in terms of normal-appearing (NA) tissue abnormalities, and explain disability.
Methods:
A total of 27 patients and 16 controls were assessed on the Expanded Disability Status Scale (EDSS), 25-foot timed walk (TWT), 9-hole peg (9HPT) and symbol digit modalities (SDMT) tests. All underwent 3T brain and (C2-C3) cord structural imaging and qMRI (relaxometry, quantitative magnetisation transfer, multi-shell diffusion-weighted imaging), using a fast brain-and-cord–matched protocol with brain-and-cord–unified imaging readouts. Lesion and NA-tissue volumes and qMRI metrics reflecting demyelination and axonal loss were obtained. Random forest analyses identified the most relevant volumetric/qMRI measures to clinical outcomes. Confounder-adjusted linear regression estimated the actual MRI-clinical associations.
Results:
Several qMRI/volumetric differences between patients and controls were observed (p < 0.01). Higher NA-deep grey matter quantitative-T1 (EDSS: beta = 7.96, p = 0.006; 9HPT: beta = −0.09, p = 0.004), higher NA-white matter orientation dispersion index (TWT: beta = −3.21, p = 0.005; SDMT: beta = −847.10, p < 0.001), lower whole-cord bound pool fraction (9HPT: beta = 0.79, p = 0.001) and higher NA-cortical grey matter quantitative-T1 (SDMT = −94.31, p < 0.001) emerged as particularly relevant predictors of greater disability.
Conclusion:
Fast brain-and-cord–matched qMRI protocols are feasible and identify demyelination – combined with other mechanisms – as key for disability accumulation in PMS.
The purposes of this study were to determine whether the pretreatment apparent diffusion coefficients (ADCs) of hepatic metastatic lesions from colorectal cancer are predictive of response to ...chemotherapy and to compare the ADCs of metastatic lesions before and after chemotherapy.
Twenty patients with potentially operable hepatic lesions larger than 1 cm in diameter metastatic from colorectal carcinoma were prospectively evaluated with diffusion-weighted imaging at three b values before and after chemotherapy. Quantitative ADC maps were calculated with images with b values of 0, 150, and 500 s/mm2 (ADC0-500) and with images with b values of 150 and 500 s/mm2 (ADC150-500). Regions of interest were drawn around metastatic lesions and randomly over liver. The mean ADC0-500 and mean ADC150-500 of metastatic lesions before and after chemotherapy were compared according to response defined by Response Evaluation Criteria in Solid Tumors criteria.
Twenty-five responding and 15 nonresponding metastatic lesions were evaluated. Nonresponding lesions had a significantly higher pretreatment mean ADC0-500 and mean ADC150-500 than did responding lesions (Mann-Whitney U test, p < 0.002). There was a linear regression relation (r2 = 0.34, p = 0.02) between percentage size reduction of metastatic lesions and pretreatment mean ADC150-500. After chemotherapy, responding lesions had a significant increase in mean ADC0-500 and ADC150-500 (Wilcoxon's signed rank, p = 0.025). No significant change was observed in nonresponding metastatic lesions (Wilcoxon's signed rank, p > 0.5) or in normal liver parenchyma (Wilcoxon's signed rank, p > 0.4).
High pretreatment mean ADC0-500 and mean ADC150-500 of colorectal hepatic metastatic lesions were predictive of poor response to chemotherapy. A significant increase in mean ADC0-500 and ADC150-500 was observed in metastatic lesions that responded to chemotherapy. These findings may have implications for development of individualized therapy.
Objective
To compare the location of suspect lesions detected by computational analysis of multimodal magnetic resonance imaging data with areas of seizure onset, early propagation, and interictal ...epileptiform discharges (IEDs) identified with stereoelectroencephalography (SEEG) in a cohort of patients with medically refractory focal epilepsy and radiologically normal magnetic resonance imaging (MRI) scans.
Methods
We developed a method of lesion detection using computational analysis of multimodal MRI data in a cohort of 62 control subjects, and 42 patients with focal epilepsy and MRI‐visible lesions. We then applied it to detect covert lesions in 27 focal epilepsy patients with radiologically normal MRI scans, comparing our findings with the areas of seizure onset, early propagation, and IEDs identified at SEEG.
Results
Seizure‐onset zones (SoZs) were identified at SEEG in 18 of the 27 patients (67%) with radiologically normal MRI scans. In 11 of these 18 cases (61%), concordant abnormalities were detected by our method. In the remaining seven cases, either early seizure propagation or IEDs were observed within the abnormalities detected, or there were additional areas of imaging abnormalities found by our method that were not sampled at SEEG. In one of the nine patients (11%) in whom SEEG was inconclusive, an abnormality, which may have been involved in seizures, was identified by our method and was not sampled at SEEG.
Significance
Computational analysis of multimodal MRI data revealed covert abnormalities in the majority of patients with refractory focal epilepsy and radiologically normal MRI that co‐located with SEEG defined zones of seizure onset. The method could help identify areas that should be targeted with SEEG when considering epilepsy surgery.
Background:
Structural cortical networks (SCNs) reflect the covariance between the cortical thickness of different brain regions, which may share common functions and a common developmental ...evolution. SCNs appear abnormal in neurodegenerative conditions such as Alzheimer’s and Parkinson’s diseases, but have never been assessed in primary progressive multiple sclerosis (PPMS).
Objective:
The aim of this study was to test whether SCNs are abnormal in early PPMS and change over 5 years, and correlate with disability worsening.
Methods:
A total of 29 PPMS patients and 13 healthy controls underwent clinical and brain magnetic resonance imaging (MRI) assessments for 5 years. Baseline and 5-year follow-up cortical thickness values were obtained and used to build correlation matrices, considered as weighted graphs to obtain network metrics. Bootstrap-based statistics assessed SCN differences between patients and controls and between patients with fast and slow progression.
Results:
At baseline, patients showed features of lower connectivity (p = 0.02) and efficiency (p < 0.001) than controls. Over 5 years, patients, especially those with fastest clinical progression, showed significant changes suggesting an increase in network connectivity (p < 0.001) and efficiency (p < 0.02), not observed in controls.
Conclusion:
SCNs are abnormal in early PPMS. Longitudinal SCN changes demonstrated a switch from low- to high-efficiency networks especially among fast progressors, indicating their clinical relevance.
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