Diffusely Abnormal White Matter, T Burden of Disease, and Brain Volume in Relapsing-Remitting Multiple Sclerosis.

Background And Purpose: Multiple sclerosis (MS) diffusely abnormal white matter (DAWM) is a mildly hyperintense magnetic resonance imaging abnormality distinct from typical lesions. Our goal was to investigate the prevalence and natural history of DAWM in a large cohort (n = 348) of relapsing-remitting MS (RRMS) patients.

Methods: The presence of DAWM and relationship to changes in T burden of disease (BOD), brain volume (brain fractional ratio, BFR), and disability (Expanded Disability Status Scale, EDSS) were investigated at baseline and year 7-8 (long-term follow-up, LTF).

Trial of Minocycline in a Clinically Isolated Syndrome of Multiple Sclerosis.

Background: On the basis of encouraging preliminary results, we conducted a randomized, controlled trial to determine whether minocycline reduces the risk of conversion from a first demyelinating event (also known as a clinically isolated syndrome) to multiple sclerosis.

Methods: During the period from January 2009 through July 2013, we randomly assigned participants who had had their first demyelinating symptoms within the previous 180 days to receive either 100 mg of minocycline, administered orally twice daily, or placebo. Administration of minocycline or placebo was continued until a diagnosis of multiple sclerosis was established or until 24 months after randomization, whichever came first.

Low-fat, plant-based diet in multiple sclerosis: A randomized controlled trial.

Background: The role that dietary interventions can play in multiple sclerosis (MS) management is of huge interest amongst patients and researchers but data evaluating this is limited. Possible effects of a very-low-fat, plant-based dietary intervention on MS related progression and disease activity as measured by brain imaging and MS related symptoms have not been evaluated in a randomized-controlled trial. Despite use of disease modifying therapies (DMT), poor quality of life (QOL) in MS patients can be a significant problem with fatigue being one of the common disabling symptoms.

Personalized activity index, a new safety monitoring tool for multiple sclerosis clinical trials.

Background: An abnormal increase of contrast-enhancing lesion (CEL) counts on frequent MRIs is interpreted as a signal of potential worsening in multiple sclerosis (MS) clinical trials. We demonstrate the utility of the MR personalized activity index (MR-pax) to identify such increases.

Methods: We analyzed a previous Phase II study in relapsing patients ( = 167) with MRIs at screening, baseline and months 1-6.

Further investigation of safety monitoring guidelines based on magnetic resonance imaging lesion activity in multiple sclerosis clinical trials.

We assess two modified guidelines for monitoring patient safety in multiple sclerosis (MS) trials. These guidelines flag patients with an increase in contrast enhancing lesion (CEL) count above a threshold over the CEL level 1-2 months earlier. We compare the new guidelines to the original guideline where the threshold is set according to the baseline by applying the guidelines to two previous studies.

Improving the clinical correlation of multiple sclerosis black hole volume change by paired-scan analysis.

The change in T 1-hypointense lesion ("black hole") volume is an important marker of pathological progression in multiple sclerosis (MS). Black hole boundaries often have low contrast and are difficult to determine accurately and most (semi-)automated segmentation methods first compute the T 2-hyperintense lesions, which are a superset of the black holes and are typically more distinct, to form a search space for the T 1w lesions. Two main potential sources of measurement noise in longitudinal black hole volume computation are partial volume and variability in the T 2w lesion segmentation.

Optimizing the use of radiologist seed points for improved multiple sclerosis lesion segmentation.

Many current methods for multiple sclerosis (MS) lesion segmentation require radiologist seed points as input, but do not necessarily allow the expert to work in an intuitive or efficient way. Ironically, most methods also assume that the points are placed optimally. This paper examines how seed points can be processed with intuitive heuristics, which provide improved segmentation accuracy while facilitating quick and natural point placement.

Detection and measurement of coverage loss in interleaved multi-acquisition brain MRIs due to motion-induced inter-slice misalignment.

In MRI scans that are acquired in a slice-by-slice manner, patient motion during scanning can cause adjacent slices to overlap, resulting in duplicate coverage in some areas and missing coverage in others. Scans in which multiple slices are acquired simultaneously and interleaved with other sets of slices are particularly vulnerable because a single movement can result in the misalignment and overlap of many slices. Despite the fact that considerable data losses can occur even with few visible artifacts, this problem has received very little attention from MRI researchers.

Cognitive impairment no dementia - neuropsychological and neuroimaging characterization of an amnestic subgroup.

Background/aims: Cognitive impairment no dementia (CIND) describes individuals whose cognitive functioning falls below normal but who do not meet dementia criteria. An important goal within CIND is to identify subgroups that will predictably progress to Alzheimer disease. CIND with amnestic deficits has been associated with high risk of Alzheimer disease but has until now been investigated on a retrospective basis.

The use of MRI as an outcome measure in clinical trials.

Because the changes on MRI likely reflect various aspects of the underlying pathology of multiple sclerosis, MRI outcome measures have become an important component of most MS clinical trials, providing objective, supportive evidence for the clinical endpoints. Although there is currently insufficient evidence to support any single or combination of MRI measures as a fully validated surrogate, it is now generally accepted that if the aim of a new therapy is to prevent relapses, new Gd-enhancing and T2 lesions can be considered an appropriate surrogate outcome measure of relapses, and MRI activity outcomes can be recommended as the primary measure of treatment efficacy.