Multiple sclerosis lesion formation and early evolution revisited: A weekly high-resolution magnetic resonance imaging study.

BACKGROUND: Several magnetic resonance imaging (MRI) studies investigated the evolution of multiple sclerosis (MS) lesions to understand the pathophysiological mechanisms leading to blood-brain barrier breakdown and lesion formation. Only a few assessed the early natural history of MS lesions using short-interval longitudinal MRI. OBJECTIVE: The purpose of this study was to characterize MS lesion occurrence and early evolution on high-resolution MRI acquired at weekly intervals. METHODS: Active lesions were characterized on 3D fluid attenuation inversion recovery (FLAIR) and gadolinium-enhanced 3D T1-weighted MRI performed weekly (seven weeks) on five untreated patients with relapsing-remitting MS (RRMS). RESULTS: Active lesions (n=212) were detected in all patients. All showed contrast-enhancement on at least one time-point. Most new lesions (83.5%) were visible on FLAIR and post-contrast T1-weighted images at first detection; 11.2% showed activity on FLAIR images, one or more weeks before the appearance of contrast-enhancement; 12.5% enhanced before being apparent on FLAIR. CONCLUSION: Blood brain barrier disruption is a constant step in the natural history of active MS lesions, but does not always constitute the initial event. These findings are consistent with the existence of a subpopulation of lesions with an 'inside-out' genesis, where neurodegenerative processes might precede microglial activation, and a subsequent adaptive immune response.

Incident lacunes preferentially localize to the edge of white matter hyperintensities: insights into the pathophysiology of cerebral small vessel disease.

White matter hyperintensities and lacunes are among the most frequent abnormalities on brain magnetic resonance imaging. They are commonly related to cerebral small vessel disease and associated with both stroke and dementia. We examined the spatial relationships between incident lacunes and white matter hyperintensities and related these findings to information on vascular anatomy to study possible mechanistic links between the two lesion types. Two hundred and seventy-six patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetically defined small vessel disease with mutations in the NOTCH3 gene were followed with magnetic resonance imaging over a total of 633 patient years. Using difference images and Jacobian maps from registered images we identified 104 incident lacunes. The majority (n = 95; 91.3%) of lacunes developed at the edge of a white matter hyperintensity whereas few lacunes were found to develop fully within (n = 6; 5.8%) or outside (n = 3; 2.9%) white matter hyperintensities. Adding information on vascular anatomy revealed that the majority of incident lacunes developed proximal to a white matter hyperintensity along the course of perforating vessels supplying the respective brain region. We further studied the spatial relationship between prevalent lacunes and white matter hyperintensities both in 365 patients with CADASIL and in 588 elderly subjects from the Austrian Stroke Prevention Study. The results were consistent with the results for incident lacunes. Lesion prevalence maps in different disease stages showed a spread of lesions towards subcortical regions in both cohorts. Our findings suggest that the mechanisms of lacunes and white matter hyperintensities are intimately connected and identify the edge of white matter hyperintensities as a predilection site for lacunes. Our observations further support and refine the concept of the white matter hyperintensity penumbra.

Frontotemporal connections in episodic memory and aging: a diffusion MRI tractography study.

Human episodic memory is supported by networks of white matter tracts that connect frontal, temporal, and parietal regions. Degradation of white matter microstructure is increasingly recognized as a general mechanism of cognitive deterioration with aging. However, atrophy of gray matter regions also occurs and, to date, the potential role of specific white matter connections has been largely ignored. Changes to frontotemporal tracts may be important for the decline of episodic memory; while frontotemporal cooperation is known to be critical, the precise pathways of interaction are unknown. Diffusion-weighted MRI tractography was used to reconstruct three candidate fasciculi known to link components of memory networks: the fornix, the parahippocampal cingulum, and the uncinate fasciculus. Age-related changes in the microstructure of these tracts were investigated in 40 healthy older adults between the ages of 53 and 93 years. The relationships between aging, microstructure, and episodic memory were assessed for each individual tract. Age-related reductions of mean fractional anisotropy and/or increased mean diffusivity were found in all three tracts. However, age-related decline in recall was specifically associated with degradation of fornix microstructure, consistent with the view that this tract is important for episodic memory. In contrast, a decline in uncinate fasciculus microstructure was linked to impaired error monitoring in a visual object-location association task, echoing the effects of uncinate transection in monkeys. These results suggest that degradation of microstructure in the fornix and the uncinate fasciculus make critical but differential contributions to the mechanisms underlying age-related cognitive decline and subserve distinct components of memory.

Intensity non-uniformity correction in MRI: existing methods and their validation.

Magnetic resonance imaging is a popular and powerful non-invasive imaging technique. Automated analysis has become mandatory to efficiently cope with the large amount of data generated using this modality. However, several artifacts, such as intensity non-uniformity, can degrade the quality of acquired data. Intensity non-uniformity consists in anatomically irrelevant intensity variation throughout data. It can be induced by the choice of the radio-frequency coil, the acquisition pulse sequence and by the nature and geometry of the sample itself. Numerous methods have been proposed to correct this artifact. In this paper, we propose an overview of existing methods. We first sort them according to their location in the acquisition/processing pipeline. Sorting is then refined based on the assumptions those methods rely on. Next, we present the validation protocols used to evaluate these different correction schemes both from a qualitative and a quantitative point of view. Finally, availability and usability of the presented methods is discussed.

Atlas-based liver segmentation and hepatic fat-fraction assessment for clinical trials.

Automated assessment of hepatic fat-fraction is clinically important. A robust and precise segmentation would enable accurate, objective and consistent measurement of hepatic fat-fraction for disease quantification, therapy monitoring and drug development. However, segmenting the liver in clinical trials is a challenging task due to the variability of liver anatomy as well as the diverse sources the images were acquired from. In this paper, we propose an automated and robust framework for liver segmentation and assessment. It uses single statistical atlas registration to initialize a robust deformable model to obtain fine segmentation. Fat-fraction map is computed by using chemical shift based method in the delineated region of liver. This proposed method is validated on 14 abdominal magnetic resonance (MR) volumetric scans. The qualitative and quantitative comparisons show that our proposed method can achieve better segmentation accuracy with less variance comparing with two other atlas-based methods. Experimental results demonstrate the promises of our assessment framework.