Magnetic resonance imaging measures of brain atrophy from the EXPEDITION3 trial in mild Alzheimer's disease.

Introduction: Solanezumab is a humanized monoclonal antibody that preferentially binds to soluble amyloid β and promotes its clearance from the brain in preclinical studies. The objective of this study was to assess the effect of solanezumab in slowing global and anatomically localized brain atrophy as measured by volumetric magnetic resonance imaging (MRI).

Methods: In the EXPEDITION3 phase 3 trial, participants with mild Alzheimer's disease were randomized to receive intravenous infusions of either 400 mg of solanezumab or placebo every 4 weeks for 76 weeks.

Amyloid-related imaging abnormalities from trials of solanezumab for Alzheimer's disease.

Introduction: Solanezumab, a humanized monoclonal antibody that binds soluble amyloid beta peptide, is being developed for treatment of Alzheimer's disease (AD).

Methods: Patients (n = 2042) with mild and moderate AD were randomized 1:1 to 400-mg solanezumab or placebo infusion every 4 weeks for 80 weeks and 1457 patients entered an open-label extension. Magnetic resonance imaging scans monitored for amyloid-related imaging abnormalities-edema/effusion (ARIA-E) and amyloid-related imaging abnormalities-hemorrhage/hemosiderin deposition.

Deformation-based atrophy computation by surface propagation and its application to Alzheimer's disease.

Obtaining regional volume changes from a deformation field is more precise when using simplex counting (SC) compared with Jacobian integration (JI) due to the numerics involved in the latter. Although SC has been proposed before, numerical properties underpinning the method and a thorough evaluation of the method against JI is missing in the literature. The contributions of this paper are: (a) we propose surface propagation (SP)-a simplification to SC that significantly reduces its computational complexity; (b) we will derive the orders of approximation of SP which can also be extended to SC.

Amyloid PET Screening for Enrichment of Early-Stage Alzheimer Disease Clinical Trials: Experience in a Phase 1b Clinical Trial.

Amyloid positron emission tomography (PET) imaging is being investigated as a screening tool to identify amyloid-positive patients as an enrichment strategy for Alzheimer disease (AD) clinical trial enrollment. In a multicenter, phase 1b trial, patients meeting clinical criteria for prodromal or mild AD underwent florbetapir PET scanning at screening. PET, magnetic resonance imaging, and coregistered PET/magnetic resonance imaging scans were reviewed by 2 independent readers and binary visual readings tabulated.

Magnetic resonance spectroscopy markers of disease progression in multiple sclerosis.

Importance: Predicting disease evolution is becoming essential for optimizing treatment decision making in multiple sclerosis (MS). Multiple sclerosis pathologic damage typically includes demyelination, neuro-axonal loss, and astrogliosis.

Objective: To evaluate the potential of magnetic resonance markers of central nervous system injury to predict brain-volume loss and clinical disability in multiple sclerosis.

Tramiprosate in mild-to-moderate Alzheimer's disease - a randomized, double-blind, placebo-controlled, multi-centre study (the Alphase Study).

Introduction: The aim of the study was to assess the clinical efficacy, safety, and disease-modification effects of tramiprosate (homotaurine, ALZHEMED(TM)) in mild-to-moderate Alzheimer's disease (AD).

Material And Methods: Double-blind, placebo-controlled, randomized trial in 67 clinical centres across North America. Patients aged ≥ 50 years, with mild-to-moderate AD (Mini-Mental State Examination score between 16 and 26) and on stable doses of cholinesterase inhibitors, alone or with memantine.

Prevalence of asymptomatic vasogenic edema in pretreatment Alzheimer's disease study cohorts from phase 3 trials of semagacestat and solanezumab.

Background: Cerebral vasogenic edema (VE) has been reported to occur during antiamyloid immunotherapy. VE may be associated with central nervous system pathology with blood-brain barrier disruptions; however, less is known about the prevalence of naturally occurring VE in patients with Alzheimer's disease (AD).

Methods: Fluid-attenuated inversion recovery imaging sequences were obtained from four ongoing multicenter, randomized, double-blind, placebo-controlled, phase 3 trials in patients with mild-to-moderate AD.

Multislice brain myelin water fractions at 3T in multiple sclerosis.

Purpose: To evaluate a multislice nonlinearly-spaced 12-echo imaging sequence at 3T covering the supratentorial brain for the quantification of myelin water fraction (MWF) in multiple sclerosis (MS) patients.

Methods: Eighty-nine patients with, or at risk of, MS (69 relapsing remitting MS [RRMS], 7 secondary progressive MS [SPMS], 13 clinically isolated syndrome [CIS]) and 28 controls were studied. Twelve-echo datasets were acquired using a multislice T2 prep spiral imaging sequence and were fitted using a nonnegative least squares algorithm.

Measurement of in vivo multi-component T2 relaxation times for brain tissue using multi-slice T2 prep at 1.5 and 3 T.

The objective of this study was to implement a clinically relevant multi-slice multi-echo imaging sequence in order to quantify multi-component T2 relaxation times for normal volunteers at both 1.5 and 3 T. Multi-echo data were fitted using a nonnegative least square algorithm.

Quantitative apparent diffusion coefficients and T2 relaxation times in characterizing contrast enhancing brain tumors and regions of peritumoral edema.

Purpose: To investigate the potential value and relationship of in vivo quantification of apparent diffusion coefficients (ADCs) and T2 relaxation times for characterizing brain tumor cellularity and tumor-related edema.

Materials And Methods: A total of 26 patients with newly diagnosed gliomas, meningiomas, or metastases underwent diffusion-weighted and six-echo multisection T2-preparation imaging. Regions of interest (ROIs) were drawn on conventional MR images to include tumor (as defined by contrast agent enhancement) and immediate and peripheral edema.

Corpus callosum axonal injury in multiple sclerosis measured by proton magnetic resonance spectroscopic imaging.

Background: Axonal damage has been observed in normal-appearing white matter (NAWM) for patients with multiple sclerosis (MS).

Objectives: To investigate changes in brain metabolite ratios in a region of normal-appearing corpus callosum (CC) for patients with MS and to test its relationship to changes in other regions of NAWM.

Design And Methods: Data were collected from 24 patients with MS and 15 control subjects.

Survival analysis in patients with glioblastoma multiforme: predictive value of choline-to-N-acetylaspartate index, apparent diffusion coefficient, and relative cerebral blood volume.

Purpose: To investigate the potential value of pre-external-beam radiation therapy (XRT) choline-to-NAA (N-acetylaspartate) index (CNI), apparent diffusion coefficient (ADC), and relative cerebral blood volume (rCBV) for predicting survival in newly diagnosed patients with glioblastoma multiforme (GBM).

Materials And Methods: Twenty-eight patients with GBM were studied using in vivo proton magnetic resonance spectroscopic imaging (1H MRSI) and diffusion- and perfusion-weighted imaging after surgery but prior to XRT. Patients were categorized on the basis of their volumes of morphologic and metabolic abnormalities (volume of CNI > or = 2 and CNI values), normalized ADC (nADC), or rCBV values within the T1 contrast-enhancing and T2 regions.

3D MRSI for resected high-grade gliomas before RT: tumor extent according to metabolic activity in relation to MRI.

Purpose: To evaluate the presence of residual disease after surgery but before radiotherapy (RT) in patients with high-grade glioma by MRI and magnetic resonance spectroscopy imaging (MRSI) and to estimate the impact of MRSI on the definition of postoperative target volumes for RT treatment planning.

Methods And Materials: Thirty patients (27 glioblastoma multiforme, 3 Grade III astrocytoma) underwent MRI and MRSI within 4 weeks after surgery but before the initiation of RT. The MRI data were manually contoured; the regions of interest included T(2)-weighted hyperintensity (T(2)), T(1)-weighted contrast enhancement (T(1)), and the resection cavity (RC).

Identification of MRI and 1H MRSI parameters that may predict survival for patients with malignant gliomas.

Although MR imaging (MRI) and MR spectroscopic imaging (MRSI) have been applied in the diagnosis and treatment planning for brain tumors, their prognostic significance has not yet been determined. The goal of this study was to identify pre-treatment MRI and MRSI parameters for patients with malignant glioma that may be useful in predicting survival. Two populations of patients with newly-diagnosed malignant glioma were examined with MRI and three-dimensional proton ((1)H) MRSI.

Directional diffusion in relapsing-remitting multiple sclerosis: a possible in vivo signature of Wallerian degeneration.

Purpose: To examine the role of directional dependence of the apparent diffusion coefficients in the evaluation of normal-appearing brain regions of patients with relapsing-remitting multiple sclerosis.

Materials And Methods: The role of diffusion tensor eigenvalues was investigated in the normal-appearing brain regions for 18 patients with relapsing-remitting multiple sclerosis and 15 age-matched normal controls.

Results: The isotropic apparent diffusion was increased in all regions.

Dissociating perceptual and conceptual implicit memory in multiple sclerosis patients.

Previous studies indicate that Multiple Sclerosis (MS) patients exhibit deficits in tests of explicit memory such as free recall, but show normal priming on implicit tests of memory such as word stem completion. However, the memory performance of patients with different MS disease subtypes has not been fully examined. In the current study, memory was assessed in Primary Progressive (PPMS), Relapsing Remitting (RRMS), and Secondary Progressive (SPMS) MS subgroups.