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Brain atrophy is increasingly evaluated in cerebral small vessel diseases. We aim at systematically reviewing the available data regarding its extent, correlates and cognitive consequences. Given that in this context, brain atrophy measures might be biased, the first part of the review focuses on technical aspects. Thereafter, data from the literature are analyzed in light of these potential limitations, to better understand the relationships between brain atrophy and other MRI markers of cerebral small vessel diseases. In the last part, we review the links between brain atrophy and cognitive alterations in patients with cerebral small vessel diseases.

The relationship between post-menopausal osteoporosis and obesity has been mainly investigated using bone mineral density (BMD) as marker of bone health. Since BMD does not reflect bone microarchitecture, another analytical tool, the Trabecular Bone Score (TBS), has been recently developed for this purpose. In this study, we intended to investigate the validity of TBS as marker of bone quality in obese post-menopausal women. Three hundred fifty-two post-menopausal women were consecutively enrolled in the study and underwent anthropometric and dual-energy X-ray absorptiometry (DXA) examination. DXA-based BMD was used to classify subjects into osteoporotic (9%), osteopenic (58%), and controls (33%) categories. As TBS is sometimes sensitive to the effects of increased image noise with higher BMI, a corrected version of the TBS (TBS*) was also used to assess bone microarchitecture quality in this cohort. As expected, BMI was positively and negatively related to total BMD (r = 0.22, p

Background and Purpose— In cerebral small vessel diseases, small subcortical ischemic lesions (SSIL) on diffusion imaging are responsible for stroke manifestations but can also be occasionally observed in the absence of overt neurological symptoms. We aimed to determine, in a large cohort of young patients with CADASIL (Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy), a severe monogenic condition leading to SSIL in young patients, the characteristics of SSIL and of surrounding cerebral tissue associated with the presence of stroke symptoms. Methods— Among a cohort of 323 genetically confirmed CADASIL patients who were systematically evaluated every 18 months clinically and with magnetic resonance imaging, we studied all visible SSIL and documented ischemic stroke events with available magnetic resonance imaging data. We used mixed-effect logistic regression models to determine whether the presence of stroke symptoms was associated with age, sex, the volume of SSIL, their location with respect to preexisting white matter hyperintensities and with the load of the different magnetic resonance imaging markers of small vessel disease. Results— We identified 73 SSIL (30 with stroke symptoms and 43 without) in 55 patients. In multivariable models, stroke symptoms were more frequent in male patients (estimate=1.94; SE=0.82; P =0.03) and less frequent when SSIL appeared in contact to preexisting white matter hyperintensities (estimate=−2.12; SE=0.83; P =0.01). Within pyramidal tracts, stroke symptoms were more frequent in patients with extensive white matter hyperintensities (estimate=3.8×10 −5 ; SE=9.3×10 −6 ; P −4 ). Conclusions— Altogether, our results suggest that when SSIL occur, the presence of stroke symptoms may depend on sex and alterations of the surrounding brain tissue rather than on the characteristics of the SSIL itself.

Background and Purpose— Cortical microinfarcts and secondary cortical degeneration have been demonstrated in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a severe monogenic cerebral small vessel disease. The aim of this study was to determine whether focal macroscopic cortical lesions can be detected using a specific in vivo magnetic resonance imaging approach. Methods— Three-dimensional T1 magnetic resonance imaging scans were obtained in 28 nondemented nondisabled CADASIL patients and 29 age- and sex-matched controls. The cortical mantle of patients and controls were extracted using Brainvisa by an experienced user and then evaluated during a dedicated reading session by a second reader after removing the white matter to stay blind to the clinical status. Thereafter, confirmed focal macroscopic cortical lesions were characterized using all available imaging data, including 7-T magnetic resonance imaging in some patients. Results— Three focal macroscopic cortical lesions were confirmed in 3 of 28 patients (11%) but none in controls. All lesions were observed in the close vicinity of severe signal changes in the underlying white matter. Conclusions— Focal macroscopic cortical lesions can be detected using specific magnetic resonance imaging approaches in CADASIL patients long before the end stage of the disorder. The underlying mechanisms and precise clinical consequences of these cortical changes still need to be determined.

Background and Purpose— Previous studies in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy showed that accumulation of lacunes strongly relate to clinical severity. However, the potential predictors of incident lacunes and their clinical consequences over a short time frame have not been investigated. This study aimed to determine the predictors and clinical impact of such lesions in a large cohort of patients. Methods— Two hundred and six NOTCH3 mutation carriers (mean age, 49.5±10.6 years) were followed up over 3 years. Incident lacunes were identified using difference imaging from 3-dimensional T1 images. Clinical events and change in different clinical scores such as the Mattis Dementia Rating Scale, Modified Rankin Scale, Barthel index, and time to complete part A and part B of Trail Making Test were recorded. Associations were analyzed with multivariable logistic regression analysis and ANCOVA. Results— Over a mean period of 3.4±0.7 years, incident lacunes occurred in 51 of 206 patients. Both the number of lacunes ( P P 140 mm Hg. Incident lacunes were also associated with incident stroke and with change in time to complete Trail Making Test part B, initiation/perseveration subscale of the Mattis Dementia Rating Scale and Barthel Index over the study period. Conclusions— Systolic blood pressure and the number of prevalent lacunes are independent predictors of incident lacunes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. These lesions mainly impact executive performances and functional independence over 3 years.

Susac syndrome is a very rare cerebral small vessel disease, which can leave patients with cognitive impairment. We aimed at evaluating processing speed slowing, executive dysfunction and apathy and their relationships with whole brain and callosal atrophy. Patients with Susac syndrome included in a prospective observational cohort study were evaluated, while clinically steady-state, with standardized brain MRI and a neuropsychological battery specifically designed to capture minimal cognitive alterations in non-disabled young patients. Brain volume and corpus callosum area were measured using 3D-T1 sequences, repeatedly overtime. Relationships between neuropsychological data and brain volumetric measures obtained the same day were tested with linear regression while controlling for sex, age, level of education, scores of depression and of apathy. Nineteen patients aged 37.5 ± 10.5 years were included. Mean follow-up time was 2.6 ± 1.3 years (5.8 ± 2.2 evaluations). While Montreal Cognitive Assessment scores were 25.1 ± 3.6, processing speed slowing was obvious (Trail Making Test version A: 43.1 ± 16.2 s; version B: 95.5 ± 67.9 s; reaction time: 314.6 ± 79.6 ms). Brain and corpus callosum atrophy was striking. No relationship was found between cognitive performances and brain volume or corpus callosum area. Patients with Susac syndrome show largely preserved global cognitive functions but important processing speed alterations. Although brain and corpus callosum area atrophy is prominent and evolving, we did not find any relationship with cognitive alterations, questioning the mechanisms underlying cognitive alterations in these patients. Clinical Trial Registration-URL: https://www.clinicaltrials.gov Unique Identifier: NCT01481662

Cerebral small vessel diseases of the brain are a major determinant of cognitive impairment in the elderly. In small vessel diseases, the most easily identifiable lesions, both at post-mortem evaluation and magnetic resonance imaging, lie in subcortical areas. However, recent results obtained post-mortem, particularly in severe cases, have highlighted the burden of cortex lesions such as microinfarcts and diffuse neuronal loss. The recent development of image post-processing methods allows now assessing in vivo multiple aspects of the cerebral cortex. This systematic review aimed to analyze in vivo magnetic resonance imaging studies evaluating cortex alterations at different stages of small vessel diseases. Studies assessing the relationships between small vessel disease magnetic resonance imaging markers obtained at the subcortical level and cortex estimates were reviewed both in community-dwelling elderly and in patients with symptomatic small vessel diseases. Thereafter, studies analyzing cortex estimates in small vessel disease patients compared with healthy subjects were evaluated. The results support that important cortex alterations develop along the course of small vessel diseases independently of concomitant neurodegenerative processes. Easy detection and quantification of cortex changes in small vessel diseases as well as understanding their underlying mechanisms are challenging tasks for better understanding cognitive decline in small vessel diseases.

Item does not contain fulltext Brain imaging is essential for the diagnosis and characterization of cerebral small vessel disease. Several magnetic resonance imaging markers have therefore emerged, providing new information on the diagnosis, progression, and mechanisms of small vessel disease. Yet, the reproducibility of these small vessel disease markers has received little attention despite being widely used in cross-sectional and longitudinal studies. This review focuses on the main small vessel disease-related markers on magnetic resonance imaging including: white matter hyperintensities, lacunes, dilated perivascular spaces, microbleeds, and brain volume. The aim is to summarize, for each marker, what is currently known about: (1) its reproducibility in studies with a scan-rescan procedure either in single or multicenter settings; (2) the acquisition-related sources of variability; and, (3) the techniques used to minimize this variability. Based on the results, we discuss technical and other challenges that need to be overcome in order for these markers to be reliably used as outcome measures in future clinical trials. We also highlight the key points that need to be considered when designing multicenter magnetic resonance imaging studies of small vessel disease.

International audience; Objective: In CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), white matter hyperintensities (WMH) are considered to result from hypoperfusion. We hypothesized that in fact the burden of WMH results from the combination of several regional populations of WMH with different mechanisms and clinical consequences. Methods: To identify regional WMH populations, we used a 4-step approach. First, we used an unsupervised principal component algorithm to determine, without a priori knowledge, the main sources of variation of the global spatial pattern of WMH. Thereafter, to determine whether these sources are likely to include relevant information regarding regional populations of WMH, we tested their relationships with: (1) MRI markers of the disease; (2) the clinical severity assessed by the Mattis Dementia Rating scale (MDRS) (cognitive outcome) and the modified Rankin's score (disability outcome). Finally, through careful interpretation of all the results, we tried to identify different regional populations of WMH. Results: The unsupervised principal component algorithm identified 3 main sources of variation of the global spatial pattern of WMH, which showed significant and sometime inverse relationships with MRI markers and clinical scores. The models predicting clinical severity based on these sources outperformed those evaluating WMH by their volume (MDRS, coefficient of determination of 39.0 vs. 35.3%, p = 0.01; modified Rankin's score, 43.7 vs. 38.1%, p = 0.001). By carefully interpreting the visual aspect of these sources as well as their relationships with MRI markers and clinical severity, we found strong arguments supporting the existence of different regional populations of WMH. For instance, in multivariate analyses, larger extents of WMH in anterior temporal poles and superior frontal gyri were associated with better outcomes, while larger extents of WMH in pyramidal tracts were associated with worse outcomes, which could not be explained if WMH in these different areas shared the same mechanisms. Duchesnay et al. Heterogeneity of White Matter Hyperintensities in CADASIL Conclusion: The results of the present study support the hypothesis that the whole extent of WMH results from a combination of different regional populations of WMH, some of which are associated, for yet undetermined reasons, with milder forms of the disease.

White matter hyperintensities (WMH) are a hallmark of small vessel diseases (SVD). Yet, no automated segmentation method is readily and widely used, especially in patients with extensive WMH where lesions are close to the cerebral cortex. BIANCA (Brain Intensity AbNormality Classification Algorithm) is a new fully automated, supervised method for WMH segmentation. In this study, we optimized and compared BIANCA against a reference method with manual editing in a cohort of patients with extensive WMH. This was achieved in two datasets: a clinical protocol with 90 patients having 2-dimensional FLAIR and an advanced protocol with 66 patients having 3-dimensional FLAIR. We first determined simultaneously which input modalities (FLAIR alone or FLAIR + T1) and which training sets were better compared to the reference. Three strategies for the selection of the threshold that is applied to the probabilistic output of BIANCA were then evaluated: chosen at the group level, based on Fazekas score or determined individually. Accuracy of the segmentation was assessed through measures of spatial agreement and volumetric correspondence with respect to reference segmentation. Based on all our tests, we identified multimodal inputs (FLAIR + T1), mixed WMH load training set and individual threshold selection as the best conditions to automatically segment WMH in our cohort. A median Dice similarity index of 0.80 (0.80) and an intraclass correlation coefficient of 0.97 (0.98) were obtained for the clinical (advanced) protocol. However, Bland-Altman plots identified a difference with the reference method that was linearly related to the total burden of WMH. Our results suggest that BIANCA is a reliable and fast segmentation method to extract masks of WMH in patients with extensive lesions.

Previous studies showed that various types of cerebral lesions, as assessed on MRI, largely contribute to the clinical severity of CADASIL. However, the clinical impact of longitudinal changes of classical markers of small vessel disease on conventional MRI has been only poorly investigated. One hundred sixty NOTCH3 mutation carriers (mean age ± SD, 49.8 ± 10.9 years) were followed over three years. Validated methods were used to determine the percent brain volume change (PBVC), number of incident lacunes, change of volume of white matter hyperintensities and change of number of cerebral microbleeds. Multivariable logistic regression analyses were performed to assess the independent association between changes of these MRI markers and incident clinical events. Mixed-effect multiple linear regression analyses were used to assess their association with changes of clinical scales. Over a mean period of 3.1 ± 0.2 years, incident lacunes are found independently associated with incident stroke and change of Trail Making Test Part B. PBVC is independently associated with all incident events and clinical scale changes except the modified Rankin Scale at three years. Our results suggest that, on conventional MRI, PBVC and the number of incident lacunes are the most sensitive and independent correlates of clinical worsening over three years in CADASIL.

Background and Purpose— Recently, in a mouse model of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, a monogenic cerebral small vessel disease, intramyelinic edema was detected in the white matter (WM) early during the course of the disease. We hypothesized that if this mechanism holds true in patients, it would translate in larger WM volume. We aimed to measure WM volume in patients with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy in comparison with age- and sex-matched controls, along with the ratio of cortical surface area to the volume of brain hemispheres as an indirect measure that should be reduced in patients. Methods— Twenty patients at the early stage of the disease (Mini Mental State Examination >24 and modified Rankin scale ≤1) and 27 age- and sex-matched controls had high-quality 3-Tesla 3DT1 MRI acquisitions. Volumes of brain hemispheres and of WM were determined. The ratio of cortical surface area to the volume of brain hemispheres was evaluated as a proxy of underlying WM volume. Results— Patients had larger volumes of WM than controls (patients: 479.4±71.7; controls: 463.9±44.2; P =0.03). They presented a lower cortical surface area and cortical volume leading to a lower ratio of cortical surface area to the volume of brain hemispheres (patients: 15.7±0.7; controls: 16.1±0.5; P =0.004). Volume of WM tended to be associated with that of WM hyperintensities ( P =0.06). Conclusions— Patients with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy have larger WM volume than age- and sex-matched controls, a finding compatible with the hypothesis of intramyelinic edema as observed recently in mice.

Background and Purpose— Cerebral microbleeds are associated with an increased risk of intracerebral hemorrhage. Recent data suggest that microbleeds may also predict the risk of incident ischemic stroke. However, these results were observed in elderly individuals undertaking various medications and for whom causes of microbleeds and ischemic stroke may differ. We aimed to test the relationship between the presence of microbleeds and incident stroke in CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy)—a severe monogenic small vessel disease known to be responsible for both highly prevalent microbleeds and a high incidence of ischemic stroke in young patients. Methods— We assessed microbleeds on baseline MRI in all 378 patients from the Paris–Munich cohort study. Incident ischemic strokes were recorded during 54 months. Survival analyses were used to test the relationship between microbleeds and incident ischemic stroke. Results— Three hundred sixty-nine patients (mean age, 51.4±11.4 years) were followed-up during a median time of 39 months (interquartile range, 19 months). The risk of incident ischemic stroke was higher in patients with microbleeds than in patients without (35.8% versus 19.6%, hazard ratio, 1.87; 95% confidence interval, 1.16–3.01; P =0.009). These results persisted after adjustment for history of ischemic stroke, age, sex, vascular risk factors, and antiplatelet agents use (hazard ratio, 1.89; 95% confidence interval, 1.10–3.26; P =0.02). Conclusions— The presence of microbleeds is an independent risk marker of incident ischemic stroke in CADASIL, emphasizing the need to carefully interpret MRI data.

In Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), by contrast to sporadic cerebral small vessel disease related to age and hypertension, white matter hyperintensities (WMH) are frequently observed in the white matter of anterior temporal poles, external capsules, and superior frontal regions. Whether these WMH (specific WMH) differ from those observed in other white matter areas (nonspecific WMH) remains unknown. Twenty patients were scanned to compare specific and nonspecific WMH using high-resolution images and analyses of relaxation times (T1R: longitudinal relaxation time and T2*R: effective transversal relaxation time). Specific WMH were characterized by significantly longer T1R and T2*R (T1R: 2309 ± 120 ms versus 2145 ± 138 ms; T2*R: 40 ± 5 ms versus 35 ± 5 ms, p R and T2*R in the white matter nor by systematic imaging artifacts as shown by the study of 17 age- and sex-matched healthy controls. Our results suggest large differences in water content between specific and nonspecific WMH in CADASIL, supporting that mechanisms underlying WMH may differ according to their location.

Introduction\ud \ud Many consequences of cerebrovascular disease are identifiable by magnetic resonance imaging (MRI), but variation in methods limits multicenter studies and pooling of data. The European Union Joint Program on Neurodegenerative Diseases (EU JPND) funded the HARmoNizing Brain Imaging MEthodS for VaScular Contributions to Neurodegeneration (HARNESS) initiative, with a focus on cerebral small vessel disease.\ud \ud \ud \ud Methods\ud \ud Surveys, teleconferences, and an in-person workshop were used to identify gaps in knowledge and to develop tools for harmonizing imaging and analysis.\ud \ud \ud \ud Results\ud \ud A framework for neuroimaging biomarker development was developed based on validating repeatability and reproducibility, biological principles, and feasibility of implementation. The status of current MRI biomarkers was reviewed. A website was created at www.harness-neuroimaging.org with acquisition protocols, a software database, rating scales and case report forms, and a deidentified MRI repository.\ud \ud \ud \ud Conclusions\ud \ud The HARNESS initiative provides resources to reduce variability in measurement in MRI studies of cerebral small vessel disease.

Prenatal alcohol exposure is responsible for a broad range of brain structural malformations, which can be studied using magnetic resonance imaging (MRI). Advanced MRI methods have emerged to characterize brain abnormalities, but the teratogenic effects of alcohol on cortical morphol- ogy have received little attention to date. Twenty-four 9-year-old children with fetal alcohol spectrum disorders (9 with fetal alcohol syndrome, 15 heavy exposed nonsyndromal children) and 16 age- matched controls were studied to assess the effect of alcohol consumption during pregnancy on corti- cal morphology. An automated method was applied to 3D T1-weighted images to assess cortical gyrifi- cation using global and regional sulcal indices and two region-based morphological measurements, mean sulcal depth and fold opening. Increasing levels of alcohol exposure were related to reduced cortical folding complexity, even among children with normal brain size, indicating a reduction of bur- ied cortical surface. Fold opening was the strongest anatomical correlate of prenatal alcohol intake, indicating a widening of sulci in all regions that were examined. These data identify cortical morphol

Background/aim Currently, the equipment and techniques available to assess brain function during dynamic exercise are limited, which has restricted our knowledge of how the brain regulates exercise. This study assessed the brain areas activated during cycling by making use of a novel cycle ergometer, constructed to measure functional MRI (fMRI) brain images during dynamic exercise. Furthermore, we compared brain activation at different levels of ratings of perceived exertion (RPE) generated during the exercise. Methods Seven healthy adults performed cycling exercise in a novel MRI compatible cycle ergometer while undergoing brain fMRI. Participants completed a cycling block protocol comprising six trials of 2 min cycling with 16-s intervals between trials. Participants reported their RPE every minute through an audio link. The MRI cycling ergometer transferred the torque generated on the ergometer through a cardan system to a cycling ergometer positioned outside the MRI room. For data analysis, the effects of cycling as opposed to rest periods were examined after motion correction. Results The multiparticipant analysis revealed in particular the activation of the cerebellar vermis and precentral and postcentral gyrus when periods of cycling versus rest were compared. Single participant analysis in four participants revealed that activation of the posterior cingulate gyrus and precuneus occurred in cycling blocks perceived as ‘hard’ compared with exercise blocks that were less demanding. Conclusions The present study offers a new approach to assess brain activation during dynamic cycling exercise, and suggests that specific brain areas could be involved in the sensations generating the rating of perceived exertion.

International audience; Objective: To obtain simple models predicting disease evolution at 3 years for a given patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Methods: Based on data obtained in a prospective study of 236 patients, we built and validated models predicting, at the individual level, 3-year changes in Mini-Mental State Examination (MMSE), Mattis Dementia Rating Scale (MDRS), Trail Making Test version B (TMTB), and modified Rankin Scale (mRS). These models were based on different sets of predictors obtained at base-line, including either clinical data (epidemiologic data and cardiovascular risk factors) or clinical data and quantitative MRI markers (volume of lacunes [LL$_V$ ], volume of white matter hyperinten-sities, normalized brain volume [BPF], number of microbleeds). The Bayesian information criterion (BIC) and the coefficient of determination (R$^2$) were used to determine models with the highest predictive ability and the lowest numbers of predictors. Results: We obtained validated models with a demonstrated ability to predict, for a given patient, 3-year changes in MMSE, MDRS, TMTB, and mRS (R$^2$ on independent samples: 0.22, 0.12, 0.09, and 0.17, respectively). In all cases, the best models according to R$^2$ and BIC values included only the baseline values of the outcome, of BPF, and of LL V. Inclusion of other potential predictors always led to a loss of generalizability. Conclusions: The prediction of 3-year changes in MMSE, MDRS, TMTB, and mRS for a given patient with CADASIL can be obtained using simple models relying only on the initial values of the considered score, BPF, and LL$_V$. GLOSSARY BIC Bayesian Information Criterion; BPF 5 brain parenchymal fraction; CADASIL 5 cerebral autosomal dominant arterio-pathy with subcortical infarcts and leukoencephalopathy; CI 5 confidence interval; LLV 5 volume of lacunes; MBN 5 number of microbleeds; MDRS 5 Mattis Dementia Rating Scale; MMSE 5 Mini-Mental State Examination; mRS 5 modified Rankin Scale; MSPE 5 mean squared prediction error; SVD 5 small vessel disease; TMTB 5 Trail Making Test part B; WMHV 5 white matter hyperintensities of presumed vascular origin. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most frequent hereditary cerebral small vessel disease (SVD), caused by mutations of the NOTCH3 gene. In CADASIL, the clinical course appears highly variable. Some patients develop dementia and become heavily disabled around their 50s while others live independently during their 80s. Age, male sex, active smoking, brain atrophy, and volume of lacunes are associated with clinical severity and with further clinical worsening, while associations between other factors, such as blood pressure, number of microbleeds, or volume of white matter hyperintensities, and clinical severity have been inconsistently observed. Among all these factors, those that actually predict disease evolution for a given patient remain undetermined. Identifying such factors would be useful for patient care and for selection of homogeneous samples in clinical trials.

Various magnetic resonance imaging (MRI) markers have emerged to describe the in vivo teratogenic effects of prenatal alcohol exposure on the structure of the brain. As for other brain structures, disturbance of the cortex has been implicated in fetal alcohol spectrum disorders (FASD). This chapter focuses on MRI-based cortical morphology in FASD and aims to (1) explain the principles of cortical morphology, (2) describe the various cortical parameters that can be measured from high-resolution anatomical MRI, (3) review the results obtained so far in subjects with FASD, and (4) discuss the possible applications to the development of biomarkers for the diagnosis and study of the pathophysiology of FASD.

Background and Purpose— Both brain and cognitive reserves modulate the clinical impact of chronic brain diseases. Whether a motor reserve also modulates the relationships between stroke and disability is unknown. We aimed to determine whether the shape of the central sulcus, a marker of the development of underlying motor connections, is independently associated with disability in patients with a positive history of small subcortical ischemic stroke. Methods— Shapes of central sulci were reconstructed from high-resolution magnetic resonance imaging and ordered without supervision according to a validated algorithm in 166 patients with a positive history of small subcortical ischemic stroke caused by CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy), a severe monogenic cerebral small vessel disease affecting young patients. Ordinal logistic regression modeling was used to test the relationships between modified Rankin scale, a disability scale strongly weighted toward motor disability, and sulcal shape. Results— Modified Rankin scale was strongly associated with sulcal shape, independent of age, sex, and level of education (proportional odds ratio =1.19, 95% confidence interval =1.06–1.35; P =0.002). Results remained significant after further adjustment for brain atrophy, volume of lacunes, and volume of white matter hyperintensities of presumed vascular origin. Conclusions— The severity of disability in patients with a positive history of small subcortical ischemic stroke caused by a severe cerebral small vessel disease is related to the shape of the central sulcus, independently of the main determinants of disability. These results support the concept of a motor reserve that could modulate the clinical severity in patients with a positive history of small subcortical ischemic stroke.

Background and Purpose— Previous pathological studies in humans or in animal models have shown alterations of small arteries and veins within white matter lesions in cerebral small vessel disease. We aimed to evaluate in vivo, the integrity of the cerebral venous network using high-resolution MRI both within and outside white matter hyperintensities in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Methods— High-resolution T 2 *-weighted images were obtained at 7-T in 13 CADASIL patients with no or only mild symptoms and 13 age- and sex-matched controls. Macroscopic veins were automatically counted in the centrum semiovale and compared between patients and controls. In addition, T 2 * was compared between groups in the normal-appearing white matter. Results— Vein density was found lower in CADASIL patients compared with that in controls (−14.6% in patients, P 2 *, that is presumably inversely related to the venous density, was also found increased in normal-appearing white matter of patients (+7.2%, P =0.006). All results were independent from the extent of white matter hyperintensities. Conclusions— A significant reduction in the number of visible veins was observed in the centrum semiovale of CADASIL patients both within and outside white matter hyperintensities, together with an increase of T 2 * in the normal-appearing white matter. Additional studies are needed to decipher the exact implication of such vasculature changes in the appearance of white matter lesions.

Microstructure determines the mechanical and transport properties of fruit tissues. One important characteristic of the microstructure is the relative volume fraction of gas-filled intercellular spaces, i.e., the tissue microporosity. Quantification of this microporosity is fundamental for investigating the relationship between gas transfer and various disorders in fruit. We present a new method for quantifying the apparent microporosity using magnetic resonance imaging (MRI). The method is based on the differences in magnetic susceptibility between gas-filled intercellular spaces and their environment inside fruit tissues. It was tested at two different magnetic fields (1.5 and 0.2 T) on apple and tomato fruit. The method was validated by comparing the MRI results with estimation of local tissue porosity using X-ray microtomography experiments. MRI was shown to be effective in determining the distribution of apparent microporosity in fruit.

Characterization of magnetic susceptibility artefacts with assessment of the gradient-echo signal decay function of echo time, pixel size, and object geometry in the case of air-filled cylinders embedded in water. Experiments were performed with a 0.2 T magnet on a network of small interacting air-filled cylinders along with Magnetic resonance imaging (MRI) simulations integrating intravoxel dephasing. Signal decay over echo time was assessed at different pixel sizes on real and simulated images. The effects of radius, distance between cylinders and main magnetic field were studied using simulation. Signal loss was greater as echo time or pixel size increased. Voxel signal decay was not exponential but was weighted by sinus cardinalis functions integrating echo time, pixel size and field inhomogeneities which depended on main magnetic field strength and geometric configuration of the object. Simulation was able to model signal decay, even for a complex object constituted of several cylinders. The specific experimental signal modulation we observed was thus reproduced and explained by simulation. The quantitative signal decay approach at 0.2 T can be used in characterization studies in the case of locally regular air/water interfaces as the signal depends on object size relative to pixel size and is relevant to the geometric configuration. Moreover, the good concordance between simulation and experiments should lead to further studies of magnetic susceptibility effects with other objects such as networks of spheres. MRI simulation is thus a potential tool for molecular and porous media imaging.

In a recent postmortem study, R-2* relaxometry in gray matter (GM) of the brain has been validated as a noninvasive measure for iron content in brain tissue. Iron accumulation in the normal aging brain is a common finding and relates to brain maturation and degeneration. The goal of this study was to assess the determinants of iron accumulation during brain aging. The study cohort consisted of 314 healthy community-dwelling participants of the Austrian Stroke Prevention Study. Their age ranged from 38-82 years. Quantitative magnetic resonance imaging was performed on 3T and included R-2* mapping, based on a 3D multi-echo gradient echo sequence. The median of R-2* values was measured in all GM regions, which were segmented automatically using FreeSurfer. We investigated 25 possible determinants for cerebral iron deposition. These included demographics, brain volume, lifestyle factors, cerebrovascular risk factors, serum levels of iron, and single nucleotide polymorphisms related to iron regulating genes (rs1800562, rs3811647, rs1799945, and rs1049296). The body mass index (BMI) was significantly related to R-2* in 15/32 analyzed brain regions with the strongest correlations found in the amygdala (p = 0.0091), medial temporal lobe (p = 0.0002), and hippocampus (p

International audience; Magnetic resonance imaging has proved to be suitable and efficient for in vivo investigation of the early process of brain gyrification in fetuses and preterm newborns but the question remains as to whether cortical-related measurements derived from both cases are comparable or not. Indeed, the developmental folding trajectories drawn up from both populations have not been compared so far, neither from cross-sectional nor from longitudinal datasets. The present study aimed to compare features of cortical folding between healthy fetuses and early imaged preterm newborns on a cross-sectional basis, over a developmental period critical for the folding process (21-36 weeks of gestational age [GA]). A particular attention was carried out to reduce the methodological biases between the 2 populations. To provide an accurate group comparison, several global parameters characterizing the cortical morphometry were derived. In both groups, those metrics provided good proxies for the dramatic brain growth and cortical folding over this developmental period. Except for the cortical volume and the rate of sulci appearance, they depicted different trajectories in both groups suggesting that the transition from into ex utero has a visible impact on cortical morphology that is at least dependent on the GA at birth in preterm newborns.

Background and Purpose: Recent data suggest that early symptoms may be related to cortex alterations in CADASIL (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), a monogenic model of cerebral small vessel disease (SVD). The aim of this study was to investigate cortical alterations using both high-resolution T2* acquisitions obtained with 7 Tesla MRI and structural T1 images with 3 Tesla MRI in CADASIL patients with no or only mild symptomatology (modified Rankin’s scale #1 and Mini Mental State Examination (MMSE) $24). Methods: Complete reconstructions of the cortex using 7 Tesla T2* acquisitions with 0.7 mm isotropic resolution were obtained in 11 patients (52.1613.2 years, 36% male) and 24 controls (54.8611.0 years, 42% male). Seven Tesla T2* within the cortex and cortical thickness and morphology obtained from 3 Tesla images were compared between CADASIL and control subjects using general linear models. Results: MMSE, brain volume, cortical thickness and global sulcal morphology did not differ between groups. By contrast, T2* measured by 7 Tesla MRI was significantly increased in frontal, parietal, occipital and cingulate cortices in patients after correction for multiple testing. These changes were not related to white matter lesions, lacunes or microhemorrhages in patients having no brain atrophy compared to controls. Conclusions: Seven Tesla MRI, by contrast to state of the art post-processing of 3 Tesla acquisitions, shows diffuse T2* alterations within the cortical mantle in CADASIL whose origin remains to be determined.

This study compared brain activation during unpaced rhythmic finger tapping in 12-year-old children with that of adults. Subjects pressed a button at a pace initially indicated by a metronome (12 consecutive tones), and then continued for 16 seconds of unpaced tapping to provide an assessment of their ability to maintain a steady rhythm. These analyses focused on the superior vermis of the cerebellum, which is known to play a key role in timing. Twelve adults and 12 children performed this rhythmic finger tapping task in a 3 T scanner. Whole-brain analyses were performed in Brain Voyager, with a random-effects analysis of variance using a general linear model. A dedicated cerebellar atlas was used to localize cerebellar activations. As in adults, unpaced rhythmic finger tapping in children demonstrated activations in the primary motor cortex, premotor cortex, and cerebellum. However, overall activation was different, in that adults demonstrated much more deactivation in response to the task, particularly in the occipital and frontal cortices. The other main differences involved the additional recruitment of motor and premotor areas in children compared with adults, and increased activity in the vermal region of the cerebellum. These findings suggest that the timing component of the unpaced rhythmic finger tapping task is less efficient and automatic in children, who need to recruit the superior vermis more intensively to maintain the rhythm, although they performed somewhat more poorly than adults.

[Departement_IRSTEA]Ecotechnologies [TR1_IRSTEA]SPEE; Magnetic resonance imaging has proven its potential application in bread dough and gas cell monitoring studies, and dynamic processes such as dough proving and baking can be monitored. However, undesirable magnetic susceptibility effects often affect quantification studies, especially at high fields. A new low-field method is presented based on local assessment of porosity in spin-echo imaging, local characterization of signal loss in gradient-echo imaging and prediction of relaxation times by simulation to estimate bubble radii in bread dough during proving. Maps of radii showed different regions of dough constituting networks which evolved during proving. Mean radius and bubble distribution were assessed during proving.