Disease progression in the first 5 years of treatment in multiple sclerosis: Predictive value of early brain and lesion volume changes.

Background: Whether the degree of inflammation (and its resolution) and neurodegeneration after treatment initiation predicts disease progression in multiple sclerosis (MS) remains unclear.

Objectives: To assess the predictive value of magnetic resonance imaging (MRI)-derived brain and lesion volume (LV) changes in years 1 and 2 of treatment for disease progression.

Methods: Patients receiving early interferon beta-1a treatment in REFLEX/REFLEXION ( = 262) were included.

The spatio-temporal relationship between concurrent lesion and brain atrophy changes in early multiple sclerosis: A post-hoc analysis of the REFLEXION study.

Background: White matter (WM) lesions and brain atrophy are present early in multiple sclerosis (MS). However, their spatio-temporal relationship remains unclear.

Methods: Yearly magnetic resonance images were analysed in 387 patients with a first clinical demyelinating event (FCDE) from the 5-year REFLEXION study.

The spatio-temporal relationship between white matter lesion volume changes and brain atrophy in clinically isolated syndrome and early multiple sclerosis.

Background: White matter lesions and brain atrophy are both present early in multiple sclerosis. However, the spatio-temporal relationship between atrophy and lesion processes remains unclear.

Methods: Yearly magnetic resonance images were analyzed in 392 patients with clinically isolated syndrome from the 5-year REFLEX/REFLEXION studies.

Clinical applicability of quantitative atrophy measures on MRI in patients suspected of Alzheimer's disease.

Objectives: Neurodegeneration in suspected Alzheimer's disease can be determined using visual rating or quantitative volumetric assessments. We examined the feasibility of volumetric measurements of gray matter (GMV) and hippocampal volume (HCV) and compared their diagnostic performance with visual rating scales in academic and non-academic memory clinics.

Materials And Methods: We included 231 patients attending local memory clinics (LMC) in the Netherlands and 501 of the academic Amsterdam Dementia Cohort (ADC).

Evaluating Cancer Care Networks; A Case Study of a Lung Cancer Care Network.

Background: Networks are promoted as an organizational form that enables integrated care as well as enhanced patient outcomes. However, implementing networks is complex. It is therefore important to evaluate the quality and effectiveness of networks to ensure it is worth developing and maintaining them.

Spinal cord atrophy in a primary progressive multiple sclerosis trial: Improved sample size using GBSI.

Background: We aimed to evaluate the implications for clinical trial design of the generalised boundary-shift integral (GBSI) for spinal cord atrophy measurement.

Methods: We included 220 primary-progressive multiple sclerosis patients from a phase 2 clinical trial, with baseline and week-48 3DT1-weighted MRI of the brain and spinal cord (1 × 1 × 1 mm), acquired separately. We obtained segmentation-based cross-sectional spinal cord area (CSA) at C1-2 (from both brain and spinal cord MRI) and C2-5 levels (from spinal cord MRI) using DeepSeg, and, then, we computed corresponding GBSI.

Facing privacy in neuroimaging: removing facial features degrades performance of image analysis methods.

Background: Recent studies have created awareness that facial features can be reconstructed from high-resolution MRI. Therefore, data sharing in neuroimaging requires special attention to protect participants' privacy. Facial features removal (FFR) could alleviate these concerns.

Can measuring hippocampal atrophy with a fully automatic method be substantially less noisy than manual segmentation over both 1 and 3 years?

To quantify the "segmentation noise" of several widely used fully automatic methods for measuring longitudinal hippocampal atrophy in Alzheimer's disease and compare the results to the segmentation noise of manual segmentation over both 1 and 3 years. The segmentation noise of 5 longitudinal hippocampal atrophy measurement methods was quantified, including checking its Gaussianity, using 264 subjects from the ADNI1 back-to-back (BTB) data set over both 1 year and 3 year intervals. The segmentation methods were FreeSurfer 5.

Reproducibility of Deep Gray Matter Atrophy Rate Measurement in a Large Multicenter Dataset.

Background And Purpose: Precise in vivo measurement of deep GM volume change is a highly demanded prerequisite for an adequate evaluation of disease progression and new treatments. However, quantitative data on the reproducibility of deep GM structure volumetry are not yet available. In this paper we aim to investigate this reproducibility using a large multicenter dataset.

The value of subtraction MRI in detection of amyloid-related imaging abnormalities with oedema or effusion in Alzheimer's patients: An interobserver study.

Background: Immunotherapeutic treatments targeting amyloid-β plaques in Alzheimer's disease (AD) are associated with the presence of amyloid-related imaging abnormalities with oedema or effusion (ARIA-E), whose detection and classification is crucial to evaluate subjects enrolled in clinical trials.

Purpose: To investigate the applicability of subtraction MRI in the ARIA-E detection using an established ARIA-E-rating scale.

Methods: We included 75 AD patients receiving bapineuzumab treatment, including 29 ARIA-E cases.

Performance of five research-domain automated WM lesion segmentation methods in a multi-center MS study.

Background And Purpose: In vivoidentification of white matter lesions plays a key-role in evaluation of patients with multiple sclerosis (MS). Automated lesion segmentation methods have been developed to substitute manual outlining, but evidence of their performance in multi-center investigations is lacking. In this work, five research-domain automated segmentation methods were evaluated using a multi-center MS dataset.

Reproducibility of hippocampal atrophy rates measured with manual, FreeSurfer, AdaBoost, FSL/FIRST and the MAPS-HBSI methods in Alzheimer's disease.

The purpose of this study is to assess the reproducibility of hippocampal atrophy rate measurements of commonly used fully-automated algorithms in Alzheimer disease (AD). The reproducibility of hippocampal atrophy rate for FSL/FIRST, AdaBoost, FreeSurfer, MAPS independently and MAPS combined with the boundary shift integral (MAPS-HBSI) were calculated. Back-to-back (BTB) 3D T1-weighted MPRAGE MRI from the Alzheimer's Disease Neuroimaging Initiative (ADNI1) study at baseline and year one were used.

The SIENA/FSL whole brain atrophy algorithm is no more reproducible at 3T than 1.5 T for Alzheimer's disease.

The back-to-back (BTB) acquisition of MP-RAGE MRI scans of the Alzheimer׳s Disease Neuroimaging Initiative (ADNI1) provides an excellent data set with which to check the reproducibility of brain atrophy measures. As part of ADNI1, 131 subjects received BTB MP-RAGEs at multiple time points and two field strengths of 3T and 1.5 T.

Mean upper cervical cord area (MUCCA) measurement in long-standing multiple sclerosis: relation to brain findings and clinical disability.

Background: The majority of patients with multiple sclerosis (MS) present with spinal cord pathology. Spinal cord atrophy is thought to be a marker of disease severity, but in long-disease duration its relation to brain pathology and clinical disability is largely unknown.

Objective: Our aim was to investigate mean upper cervical cord area (MUCCA) in patients with long-standing MS and assess its relation to brain magnetic resonance imaging (MRI) measures and clinical disability.

Long-term effects of amyloid, hypometabolism, and atrophy on neuropsychological functions.

Objective: To assess how amyloid deposition, glucose hypometabolism, and cerebral atrophy affect neuropsychological performance in patients with Alzheimer disease (AD) dementia, patients with mild cognitive impairment (MCI), and controls over time.

Methods: A total of 41 patients with AD dementia, 28 patients with MCI, and 19 controls underwent [(11)C]-Pittsburgh compound B ((11)C-PiB) and [(18)F]-2-fluoro-2-deoxy-d-glucose ((18)F-FDG)-PET and MRI scans at baseline. We extracted global binding potential for (11)C-PiB, the number of abnormal voxels for (18)F-FDG, and gray matter volumes using SIENAX for MRI as measures of amyloid, hypometabolism, and atrophy.

Hippocampal volume change measurement: quantitative assessment of the reproducibility of expert manual outlining and the automated methods FreeSurfer and FIRST.

Background: To measure hippocampal volume change in Alzheimer's disease (AD) or mild cognitive impairment (MCI), expert manual delineation is often used because of its supposed accuracy. It has been suggested that expert outlining yields poorer reproducibility as compared to automated methods, but this has not been investigated.

Aim: To determine the reproducibilities of expert manual outlining and two common automated methods for measuring hippocampal atrophy rates in healthy aging, MCI and AD.

Measurements of medial temporal lobe atrophy for prediction of Alzheimer's disease in subjects with mild cognitive impairment.

Our aim was to compare the predictive accuracy of 4 different medial temporal lobe measurements for Alzheimer's disease (AD) in subjects with mild cognitive impairment (MCI). Manual hippocampal measurement, automated atlas-based hippocampal measurement, a visual rating scale (MTA-score), and lateral ventricle measurement were compared. Predictive accuracy for AD 2 years after baseline was assessed by receiver operating characteristics analyses with area under the curve as outcome.

Recommendations to improve imaging and analysis of brain lesion load and atrophy in longitudinal studies of multiple sclerosis.

Focal lesions and brain atrophy are the most extensively studied aspects of multiple sclerosis (MS), but the image acquisition and analysis techniques used can be further improved, especially those for studying within-patient changes of lesion load and atrophy longitudinally. Improved accuracy and sensitivity will reduce the numbers of patients required to detect a given treatment effect in a trial, and ultimately, will allow reliable characterization of individual patients for personalized treatment. Based on open issues in the field of MS research, and the current state of the art in magnetic resonance image analysis methods for assessing brain lesion load and atrophy, this paper makes recommendations to improve these measures for longitudinal studies of MS.

Location of brain lesions predicts conversion of clinically isolated syndromes to multiple sclerosis.

Objectives: To assess in a large population of patients with clinically isolated syndrome (CIS) the relevance of brain lesion location and frequency in predicting 1-year conversion to multiple sclerosis (MS).

Methods: In this multicenter, retrospective study, clinical and MRI data at onset and clinical follow-up at 1 year were collected for 1,165 patients with CIS. On T2-weighted MRI, we generated lesion probability maps of white matter (WM) lesion location and frequency.

Static and dynamic loading of mandibular condyles and their positional changes after bilateral sagittal split advancement osteotomies.

This study analysed the effects of change of direction of masseter (MAS) and medial pterygoid muscles (MPM) and changes of moment arms of MAS, MPM and bite force on static and dynamic loading of the condyles after surgical mandibular advancement. Rotations of the condyles were assessed on axial MRIs. 16 adult patients with mandibular hypoplasia were studied.

Optimizing parameter choice for FSL-Brain Extraction Tool (BET) on 3D T1 images in multiple sclerosis.

Background: Brain atrophy studies often use FSL-BET (Brain Extraction Tool) as the first step of image processing. Default BET does not always give satisfactory results on 3DT1 MR images, which negatively impacts atrophy measurements. Finding the right alternative BET settings can be a difficult and time-consuming task, which can introduce unwanted variability.

Positional changes of the masseter and medial pterygoid muscles after surgical mandibular advancement procedures: an MRI study.

This study evaluated whether surgical mandibular advancement procedures induced a change in the direction and the moment arms of the masseter (MAS) and medial pterygoid (MPM) muscles. Sixteen adults participated in this study. The sample was divided in two groups: Group I (n=8) with a mandibular plane angle (mpa) <39° and Group II (n=8) with an mpa >39°.

Assessing the reproducibility of the SienaX and Siena brain atrophy measures using the ADNI back-to-back MP-RAGE MRI scans.

SienaX and Siena are widely used and fully automated algorithms for measuring whole brain volume and volume change in cross-sectional and longitudinal MRI studies and are particularly useful in studies of brain atrophy. The reproducibility of the algorithms was assessed using the 3D T1 weighted MP-RAGE scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. The back-to-back (BTB) MP-RAGE scans in the ADNI data set makes it a valuable benchmark against which to assess the performance of algorithms of measuring atrophy in the human brain with MRI scans.

Risk factors and outcome of changes in adrenal response to ACTH in the course of critical illness.

Background: To evaluate the concept of critical illness-related corticosteroid insufficiency (CIRCI) by studying the clinical significance, in terms of risk factors and outcome, of changes in the cortisol response to repeated adrenocorticotropic hormone (ACTH) testing in the course of critical illness.

Patients And Methods: In a retrospective study in a medical-surgical intensive care unit (ICU) of a university hospital, we retrospectively included 54 consecutive patients during a 3-year period, who underwent 2 conventional 250 μg ACTH tests at an interval >24 hours, because of ≥6 hours hypotension requiring repeated fluid challenges or vasopressor/inotropic treatment, while corticosteroid treatment was not (yet) initiated. Serum cortisol was measured immediately before and 30 and 60 minutes after intravenous injection of 250 μg of ACTH.

Long-interval T2-weighted subtraction magnetic resonance imaging: a powerful new outcome measure in multiple sclerosis trials.

Objective: To compare long-interval T2-weighted subtraction (T2w-Sub) imaging with monthly gadolinium-enhanced T1-weighted (Gd-T1w) imaging for (1) detection of active lesions, (2) assessment of treatment efficacy, and (3) statistical power, in a multiple sclerosis (MS), phase 2, clinical trial setting.

Methods: Magnetic resonance imaging (MRI) data over 9 months from 120 patients (61 treatment, 59 placebo) from the oral temsirolimus trial were used. T2w-Sub images were scored for active lesions, independent of the original reading of the monthly Gd-T1w images.