Diagnostic accuracy of double inversion recovery (DIR) in detection of cortical gray matter lesions in patients with MS

Background Conventional imaging techniques have a low sensitivity for detection of cortical and deep grey matter lesions in MS which hinder accurate assessment of the total lesion burden. Aim of this work was to assess the diagnostic accuracy of double inversion recovery (DIR) sequence in the detection of cortical grey matter lesions in MS patients. Results Forty MS patients were prospectively included in this study. Imaging was performed using Philips Ingenia 1.5 T device. The sensitivity, specificity, PPV, NPV and accuracy of DIR sequence in detection of cortical grey matter lesions were 60%, 100%, 100%, 55.6% and 73.3%, respectively. The sensitivity, specificity, positive and negative predictive values as well as accuracy of Flair sequence were 50%, 100%, 100%, 50% and 66.7%, respectively. The sensitivity, specificity, positive and negative predictive values as well as accuracy of T2 sequence in the detection of cortical grey matter lesions were 22.5%, 100%, 100%, 39.2% and 48.3%, respectively. Conclusions Detection rate of cortical gray matter lesions was significantly higher on DIR sequence than on T2 and Flair sequences.

Non-modifiable factors as moderators of the relationship between physical activity and brain volume: A cross-sectional UK Biobank study

Background: Grey matter atrophy occurs as a function of ageing and is accelerated in dementia. Previous research suggests physical activity attenuates grey matter loss; however, there appears to be individual variability in this effect. Understanding factors that can affect the relationship between physical activity and brain volume may enable prediction of individual response, and aid in identifying those that gain the greatest neural benefits from physical activity. The current study examined the relationship between objectively-measured physical activity and brain volume; and whether this relationship is moderated by age, sex, or a priori candidate genetic factors. Methods: Data from 10,083 men and women (50 years and over) of the UK Biobank were used to examine: 1) the relationship between objectively-measured physical activity and brain volume; and 2) whether the relationship between objectively-measured physical activity and brain volume is moderated by age, sex, brain-derived neurotrophic factor (BDNF) Val66Met, or apolipoprotein (APOE) e4 allele carriage. All participants underwent a magnetic resonance imaging scan to quantify grey matter volumes, physical activity monitoring via accelerometry, and genotyping. Results: Physical activity was associated with total grey matter volume (B = 0.14, p = 0.001, q = 0.005) and right hippocampal volume (B = 1.45, p = 0.008, q = 0.016). The physical activity*sex interaction predicted cortical grey matter (B = 0.22, p = 0.003, q = 0.004), total grey matter (B = 0.30, p < 0.001, q = 0.001), and right hippocampal volume (B = 3.60, p = 0.001, q = 0.002). Post-hoc analyses revealed males received benefit from higher physical activity levels, in terms of greater cortical grey matter volume (B = 0.13, p = 0.01), total grey matter volume (B=0.23, p < 0.001), and right hippocampal volume (B = 3.05, p = 0.008). No moderating effects of age, APOE e4 allele carriage, or BDNF Val66Met genotype were observed. Discussion: Our results indicate that in males, but not females, an association exists between objectively-measured physical activity and grey matter volume. Future research should evaluate longitudinal brain volumetrics to better understand the nature of sex-effects on the relationship between physical activity and brain volume.

Association of iron rim lesions with brain and cervical cord volume in relapsing multiple sclerosis

Objectives In multiple sclerosis (MS), iron rim lesions (IRLs) are indicators of chronic low-grade inflammation and ongoing tissue destruction. The aim of this study was to assess the relationship of IRLs with clinical measures and magnetic resonance imaging (MRI) markers, in particular brain and cervical cord volume. Methods Clinical and MRI parameters from 102 relapsing MS patients (no relapses for at least 6 months, no contrast-enhancing lesions) were included; follow-up data obtained after 12 months was available in 49 patients. IRLs were identified on susceptibility-weighted images (SWIs). In addition to standard brain and spinal cord MRI parameters, normalised cross-sectional area (nCSA) of the upper cervical cord was calculated. Results Thirty-eight patients had at least one IRL on SWI MRI. At baseline, patients with IRLs had higher EDSS scores, higher lesion loads (brain and spinal cord), and lower cortical grey matter volumes and a lower nCSA. At follow-up, brain atrophy rates were higher in patients with IRLs. IRLs correlated spatially with T1-hypointense lesions. Conclusions Relapsing MS patients with IRLs showed more aggressive MRI disease characteristics in both the cross-sectional and longitudinal analyses. Key Points • Multiple sclerosis patients with iron rim lesions had higher EDSS scores, higher brain and spinal cord lesion loads, lower cortical grey matter volumes, and a lower normalised cross-sectional area of the upper cervical spinal cord. • Iron rim lesions are a new lesion descriptor obtained from susceptibility-weighted MRI. Our data suggests that further exploration of this lesion characteristic in regard to a poorer prognosis in multiple sclerosis patients is warranted.

Tissue damage detected by quantitative gradient echo MRI correlates with clinical progression in non-relapsing progressive MS

Background: Imaging biomarkers of progressive MS are needed. Quantitative gradient recalled echo (qGRE) MRI technique allows evaluation of tissue damage associated with microstructural damage in multiple sclerosis (MS). Objective: To evaluate qGRE-derived R2t* as an imaging biomarker of MS disease progression as compared to atrophy and lesion burden. Methods: Twenty-three non-relapsing progressive MS (PMS), twenty-two relapsing-remitting MS (RRMS) and eighteen healthy control participants were imaged with qGRE at 3T. PMS subjects were imaged and neurologically assessed every nine months over five sessions. In each imaging session, lesion burden, atrophy and R2t* in cortical grey matter (GM), deep GM, normal-appearing white matter (NAWM) were measured. Results: R2t* reductions correlated with neurological impairment cross-sectionally and longitudinally. PMS patients with clinically defined disease progression showed significantly faster decrease of R2t* in NAWM and deep GM compared with the clinically stable PMS group. Importantly, tissue damage measured by R2t* outperformed lesion burden and atrophy as a biomarker of progression during the study period. Conclusion: Clinical impairment and progression correlated with accumulating R2t*-defined microstructural tissue damage in deep GM and NAWM. qGRE-derived R2t* is a potential imaging biomarker of MS progression.

Perfusion imaging with arterial spin labeling (ASL)–MRI predicts malignant progression in low‑grade (WHO grade II) gliomas

Purpose Predicting malignant progression of grade II gliomas would allow for earlier initiation of treatment. The hypothesis for this single-centre, case–control study was that the perfusion signal on ASL-MRI predicts such malignant progression in the following 12 months. Methods Consecutive patients with the following criteria were included: ≥ 18 years, grade II glioma (biopsied or resected) and an ASL-MRI 6–12 months prior to malignant progression (cases) or stable disease (controls). Malignant progression was defined either radiologically (new T1w-contrast enhancement) or histologically (neurosurgical tissue sampling). Three controls were matched with each case. Some patients served as their own control by using earlier imaging. The ASL-MRIs were reviewed by two neuroradiologists and classified as positive (hyper-intense or iso-intense compared to cortical grey matter) or negative (hypo-intense). In patients with epilepsy, a neurologist reviewed clinicoradiological data to exclude peri-ictal pseudoprogression. The statistical analysis included diagnostic test properties, a Cohen’s Kappa interrater reliability coefficient and stratification for previous radiotherapy. Results Eleven cases (median age = 48, IQR = 43–50 years) and 33 controls (43, 27–50 years) were included. Malignant progression appeared at 37 months (median, IQR = 17–44) after first surgery. Thirty ASL-MRIs were assessed as negative and 14 as positive. None of the MRIs showed signs of peri-ictal pseudoprogression. ASL significantly predicted subsequent malignant progression (sensitivity = 73%; specificity = 82%; OR = 12; 95%-CI = 2.4–59.1; p = 0.002). The interrater reliability coefficient was 0.65. In stratified analysis, ASL-MRI predicted malignant progression both in patients with previous radiotherapy and in those without (Mantel–Haenszel test, p = 0.003). Conclusion Perfusion imaging with ASL-MRI can predict malignant progression within 12 months in patients with grade II glioma.

Increase of blood-brain barrier leakage is related to cognitive decline in vascular mild cognitive impairment

Background Blood-brain barrier (BBB) breakdown, as an early biomarker for vascular mild cognitive impairment (vMCI), has only been validated by a few studies. The aim of this study was to investigate whether compromised BBB integrity is involved in vMCI patients, and detect the relationship between BBB breakdown and cognitive function. BBB leakage in vMCI was explored, and the relationship between BBB leakage and cognitive function was discussed in this study. Methods This is a cross-sectional study involving 26 vMCI patients and 21 sex- and age-matched healthy controls. Dynamic contrast-enhanced-magnetic resonance imaging was performed for all participants, to determine BBB leakage. Leakage volume, leakage rate, and fractional blood plasma volume (Vp) in the grey and white matter were evaluated. Neuropsychological tests were used to determine cognitive function. Leakage rate, leakage volume, and Vp in different brain locations, including deep grey matter, cortical grey matter, white matter hyperintensity, and normal-appearing white matter were compared between the two groups. Results Multivariable linear regression analyses revealed that in all regions of interest, the leakage rate was significantly higher in vMCI patients relative to controls. Leakage volume in normal-appearing white matter and white matter hyperintensity were significantly higher, while Vp in normal-appearing white matter, deep grey matter, and cortical grey matter were significantly lower in vMCI patients. Moreover, Montreal Cognitive Assessment scores decreased with the increase of leakage rate in white matter hyperintensity. Conclusion Increased BBB permeability was detected in vMCI patients and was related to cognitive decline, which suggested that BBB breakdown might be involved in cognitive dysfunction pathogenesis.

Grey matter abnormality in progressive multifocal leucoencephalopathy

Progressive multifocal leucoencephalopathy (PML) is a demyelinating white matter disease that most often affects immunocompromised people infected by JC virus. The diagnostic gold standard is demonstrable viral DNA or protein from histopathological tissue. However, there are few detailed descriptions of cortical grey matter involvement on neuroimaging. Here we describe the histopathological correlate of cerebral grey matter involvement and radiological accompaniment in a patient with biopsy proven PML.