Lesion Volume Fraction Research Articles

Quantitative susceptibility mapping of the normal-appearing white matter as a potential new marker of disability progression in multiple sclerosis.

To investigate the normal-appearing white matter (NAWM) susceptibility in a cohort of newly diagnosed multiple sclerosis (MS) patients and to evaluate possible correlations between NAWM susceptibility and disability progression. Fifty-nine patients with a diagnosis of MS (n = 53) or clinically isolated syndrome (CIS) (n = 6) were recruited and followed up. All participants underwent neurological examination, blood sampling for serum neurofilament light chain (sNfL) level assessment, lumbar puncture for the quantification of cerebrospinal fluid (CSF) β-amyloid1-42 (Aβ) levels, and brain MRI. T2-weighted scans were used to quantify white matter (WM) lesion loads. For each scan, we derived the NAWM volume fraction and the WM lesion volume fraction. Quantitative susceptibility mapping (QSM) of the NAWM was calculated using the susceptibility tensor imaging (STI) suite. Susceptibility maps were computed with the STAR algorithm. Primary progressive patients (n = 9) showed a higher mean susceptibility value in the NAWM than relapsing-remitting (n = 44) and CIS (n = 6) (p = 0.01 and p = 0.02). Patients with a higher susceptibility in the NAWM showed increased sNfL concentration (ρ = 0.38, p = 0.004) and lower CSF Aβ levels (ρ = -0.34, p = 0.009). Mean NAWM susceptibility turned out to be a predictor of the expanded disability status scale (EDSS) worsening at follow-up (β = 0.41, t = 2.66, p = 0.01) and of the MS severity scale (MSSS) (β = 0.38, t = 2.43, p = 0.019). QSM in the NAWM seems to predict the EDSS increment over time. This finding might provide evidence on the role of QSM in identifying patients with an increased risk of early disability progression. • NAWM-QSM is higher in PPMS patients than in RRMS. • NAWM-QSM seems to be a predictor of EDSS worsening over time. • Patients with higher NAWM-QSM show increased sNfL concentration and lower CSF Aβ levels.

Multiple sclerosis lesions in motor tracts from brain to cervical cord: spatial distribution and correlation with disability.

Despite important efforts to solve the clinico-radiological paradox, correlation between lesion load and physical disability in patients with multiple sclerosis remains modest. One hypothesis could be that lesion location in corticospinal tracts plays a key role in explaining motor impairment. In this study, we describe the distribution of lesions along the corticospinal tracts from the cortex to the cervical spinal cord in patients with various disease phenotypes and disability status. We also assess the link between lesion load and location within corticospinal tracts, and disability at baseline and 2-year follow-up. We retrospectively included 290 patients (22 clinically isolated syndrome, 198 relapsing remitting, 39 secondary progressive, 31 primary progressive multiple sclerosis) from eight sites. Lesions were segmented on both brain (T2-FLAIR or T2-weighted) and cervical (axial T2- or T2*-weighted) MRI scans. Data were processed using an automated and publicly available pipeline. Brain, brainstem and spinal cord portions of the corticospinal tracts were identified using probabilistic atlases to measure the lesion volume fraction. Lesion frequency maps were produced for each phenotype and disability scores assessed with Expanded Disability Status Scale score and pyramidal functional system score. Results show that lesions were not homogeneously distributed along the corticospinal tracts, with the highest lesion frequency in the corona radiata and between C2 and C4 vertebral levels. The lesion volume fraction in the corticospinal tracts was higher in secondary and primary progressive patients (mean = 3.6 ± 2.7% and 2.9 ± 2.4%), compared to relapsing-remitting patients (1.6 ± 2.1%, both P < 0.0001). Voxel-wise analyses confirmed that lesion frequency was higher in progressive compared to relapsing-remitting patients, with significant bilateral clusters in the spinal cord corticospinal tracts (P < 0.01). The baseline Expanded Disability Status Scale score was associated with lesion volume fraction within the brain (r = 0.31, P < 0.0001), brainstem (r = 0.45, P < 0.0001) and spinal cord (r = 0.57, P < 0.0001) corticospinal tracts. The spinal cord corticospinal tracts lesion volume fraction remained the strongest factor in the multiple linear regression model, independently from cord atrophy. Baseline spinal cord corticospinal tracts lesion volume fraction was also associated with disability progression at 2-year follow-up (P = 0.003). Our results suggest a cumulative effect of lesions within the corticospinal tracts along the brain, brainstem and spinal cord portions to explain physical disability in multiple sclerosis patients, with a predominant impact of intramedullary lesions.

Hereditary diffuse leukoencephalopathy with spheroids – a volumetric and radiological comparison with multiple sclerosis patients and healthy controls

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal dominant disorder caused by colony-stimulating factor 1 receptor (CSF1R) gene mutations, resulting in demyelination and axonal degeneration with spheroids. The clinical expression is variable, including behavioral changes, cognitive impairment, motor symptoms and parkinsonism. Magnetic resonance imaging (MRI) reveals white matter (WM) changes and atrophy. The indistinct phenotype has led to misdiagnoses. This study's aim was to compare brain volumetry and radiological ratings in HDLS with multiple sclerosis (MS) patients and controls. Five HDLS patients with c.2562T>A p.Asn854Lys CSF1R mutation, five age- and gender-matched MS patients and five healthy controls were cross-sectionally studied. All patients were examined neurologically. HDLS patients underwent Mini-Mental State Examination (MMSE). Brain MRI scans were analyzed volumetrically with FreeSurfer and Lesion Segmentation Toolbox and neuroradiologically with the brain MRI scoring system for HDLS. Patients with HDLS had lower brain, grey matter and WM fractions (66.3%; 37.9%; 27.6%) compared with controls (78.5%, P = 0.008; 44.4%, P = 0.008; 32.0%, P = 0.008), but not compared with MS patients (65.7%, P = 0.7; 36.8%, P = 0.4; 27.3%, P = 0.7). Cerebellar WM changes and atrophy were not seen in the HDLS group. The HDLS lesion volume fraction correlated with MMSE scores (r = -0.90, P = 0.04). Brain volume fractions in HDLS were lower than in controls and similar to those seen in MS. The cerebellum was relatively spared in HDLS, which may help in differentiating HDLS WM changes from MS. The strong relationship of HDLS lesions with MMSE scores indicates that accumulating WM pathology in HDLS is associated with cognitive decline.

Treadmill running protects spinal cord contusion from secondary degeneration

It is known that physical activity triggers changes in the central nervous system. Adult rats, trained on treadmills for 4 weeks, and a group of sedentary rats was submitted to contuse moderate spinal cord injury. A group of sedentary rats was submitted to a sham operation. The trained group continued running on treadmill after lesion for 4 weeks. Motor behavior evaluated by BBB score was smaller in the sedentary group compared to the trained rats by 7 days after lesion. Computerized activity monitor showed clear-cut differences in spontaneous motor parameters in trained rats only before lesion. After surgery, sedentary rats showed changes in motor parameters but not in later periods of analysis. Animals were euthanized by 28 days after surgery, and their spinal cords were processed for Nissl staining and immunohistochemistry. The number of the remaining neurons and the lesion areal and lesion volume fractions were obtained by stereological method. The number of the remaining neurons did not change after training. Lesion volume and lesion areal fraction per section were smaller in the trained group. Lesion index was more pronounced in the sedentary group. Microdensitometric image analysis demonstrated a microglial reaction, astroglial activation, and glial FGF-2 production more pronounced in the spinal cord of sedentary animals. GAP-43 was higher in caudal levels of contusion in the sedentary group. In conclusion, treadmill running may favor a better functional recovery in the acute period after spinal cord lesion and wound repair processes leading to neuroprotection.

Magnetic resonance imaging follow-up of liver growth of neuroendocrine tumors in an experimental mouse model

Liver metastases in patients with gastroenteropancreatic (GEP) endocrine tumors represent the main factor of adverse prognosis in this tumor type and thus have a strong effect on the therapeutic strategies. Currently, magnetic resonance imaging (MRI) is considered the modality of choice for the noninvasive, in vivo detection of liver metastases. Dedicated MRI protocols suitable for following liver lesion evolution on an experimental model of endocrine tumors could be valuable. An experimental animal model mimicking the clinical situation of intrahepatic dissemination has been designed. The goal of this study was to characterize liver lesions in this athymic nude mouse model and assess the detection sensitivity of MRI using a physiological gating strategy optimized for high magnetic fields. The experiments were performed at 7 T using a dual cardiac-respiratory-triggered multiple spin-echo sequence. This protocol was used to carry out a longitudinal follow-up of hepatic lesions in a group of eight nude mice at different stages: Day 7 (D7), Day 12 (D12), Day 17 (D17) and Day 24 (D24). The hepatic lesion volume fraction (HLVF) was quantified using an adaptive segmentation procedure based on a dual-reference limit. Mean transverse relaxation time T(2) values were quantified from multiple spin-echo images. The first lesions were detected at stage D12 on images with 20-ms TE. From D12, the HLVF increased significantly with stage. The mean T(2) values also increased significantly at D17 and D24. In conclusion, the level of detection and characterization of liver lesions were performed using a devoted protocol with a dedicated high-field MRI synchronization strategy. In future studies, MRI could be used to monitor the effects of targeted therapies on liver endocrine metastases in preclinical animal models.