Reproducibility over a 1-month period of 1H-MR spectroscopic imaging NAA/Cr ratios in clinically stable multiple sclerosis patients

N-acetylaspartate/creatine (NAA/Cr) ratios, assessed with proton magnetic resonance spectroscopy, are increasingly used as a surrogate marker for axonal dysfunction and degeneration in multiple sclerosis (MS). The purpose of this study was to test short-time reproducibility of NAA/Cr ratios in patients with clinically stable MS. In 35 MS patients we analysed NAA/Cr ratios obtained with 1H-MR spectroscopic imaging at the centrum semiovale either with lateral ventricles partially included (group 1; n=15) or more cranially with no ventricles included (group 2; n=20). To test short-term reproducibility of the NAA/Cr measurements, patients were scanned twice 4 weeks apart. We determined mean NAA/Cr and Cho/Cr ratios of 12 grey matter and 24 white matter voxels. Mean NAA/Cr ratios of both the white and grey matter did not change after 4 weeks. Overall 4-week reproducibility of the NAA/Cr ratio, expressed as coefficient of variation, was 4.8% for grey matter and 3.5% for white matter. Reproducibility of cranial scanning of the ventricles was slightly better than with cerebrospinal fluid included. Our study shows good short-term reproducibility of NAA/Cr ratio measurements in the centrum semiovale, which supports the reliability of this technique for longitudinal studies

Characterisation of tissue-type metabolic content in secondary progressive multiple sclerosis: a magnetic resonance spectroscopic imaging study

Proton magnetic resonance spectroscopy yields metabolic information and has proved to be a useful addition to structural imaging in neurological diseases. We applied short-echo time Spectroscopic Imaging in a cohort of 42 patients with secondary progressive multiple sclerosis (SPMS). Linear modelling with respect to brain tissue type yielded metabolite levels that were significantly different in white matter lesions compared with normal-appearing white matter, suggestive of higher myelin turnover (higher choline), higher metabolic rate (higher creatine) and increased glial activity (higher myo-inositol) within the lesions. These findings suggest that the lesions have ongoing cellular activity that is not consistent with the usual assumption of ‘chronic’ lesions in SPMS, and may represent a target for repair therapies

Multicentre evaluation of MRI variability in the quantification of infarct size in experimental focal cerebral ischaemia

Ischaemic stroke is a leading cause of death and disability in the developed world. Despite that considerable advances in experimental research enabled understanding of the pathophysiology of the disease and identified hundreds of potential neuroprotective drugs for treatment, no such drug has shown efficacy in humans. The failure in the translation from bench to bedside has been partially attributed to the poor quality and rigour of animal studies. Recently, it has been suggested that multicentre animal studies imitating the design of randomised clinical trials could improve the translation of experimental research. Magnetic resonance imaging (MRI) could be pivotal in such studies due to its non-invasive nature and its high sensitivity to ischaemic lesions, but its accuracy and concordance across centres has not yet been evaluated. This thesis focussed on the use of MRI for the assessment of late infarct size, the primary outcome used in stroke models. Initially, a systematic review revealed that a plethora of imaging protocols and data analysis methods are used for this purpose. Using meta-analysis techniques, it was determined that T2-weighted imaging (T2WI) was best correlated with gold standard histology for the measurement of infarctbased treatment effects. Then, geometric accuracy in six different preclinical MRI scanners was assessed using structural phantoms and automated data analysis tools developed in-house. It was found that geometric accuracy varies between scanners, particularly when centre-specific T2WI protocols are used instead of a standardised protocol, though longitudinal stability over six months is high. Finally, a simulation study suggested that the measured geometric errors and the different protocols are sufficient to render infarct volumes and related group comparisons across centres incomparable. The variability increases when both factors are taken into account and when infarct volume is expressed as a relative estimate. Data in this study were analysed using a custom-made semi-automated tool that was faster and more reliable in repeated analyses than manual analysis. Findings of this thesis support the implementation of standardised methods for the assessment and optimisation of geometric accuracy in MRI scanners, as well as image acquisition and analysis of in vivo data for the measurement of infarct size in multicentre animal studies. Tools and techniques developed as part of the thesis show great promise in the analysis of phantom and in vivo data and could be a step towards this endeavour

Copy and recall of the Rey Complex figure before and after unilateral frontal- or temporal-lobe excision.

Copy and recall drawings of the Rey Complex Figure obtained during the standard clinical testing of patients with well-localized epileptic foci before and after left frontal-, left temporal-, right temporal-lobe resection were re-scored blind as to lesion site using standard protocol (18 elements scored 0, 1/2, 1, or 2 based on whether they are drawn and placed correctly for a total out of 36). They were also scored for which, and how many, elements were missing, distorted, displaced, and/or repeated. Contrary to previous findings, no main effects of side or lobe or side-by-lobe interactions were found on copy and recall scores obtained either before or after surgery, and all patients' recall improved equally from pre-operative to follow-up testing. Furthermore, patients' lesion site could not be predicted on the basis of any single measure or across all measures of performance. While group differences had been found on the previously assigned scores, the between-group overlap was almost complete and the original scoring was not done blindly. These results suggest that, despite previous claims, the Rey Complex Figure, a widely-used measure of non-verbal memory, is not an effective tool for localizing neural disturbance in temporal- and frontal-lobe epilepsy patients

Primary progressive multiple sclerosis: part of the MS disease spectrum or separate disease entity? Acta Neuropathol

Abstract Multiple sclerosis (MS), the most frequent demyelinating disease, is characterized by a variable disease course

Metabolic and functional imaging of brain tumors

info:eu-repo/semantics/publishe

In vivo differentiation of astrocytic brain tumors and isolated demyelinating lesions of the type seen in multiple sclerosis using 1H magnetic resonance spectroscopic imaging

We used computer pattern recognition of proton magnetic resonance spectroscopic image data to differentiate between brain tumors and large, isolated, demyelinating lesions of the type seen in multiple sclerosis. Leave-one-out linear discriminant analyses correctly classified resonance profiles from five acute demyelinating lesions, 20 low-grade astrocytomas, 22 anoplastic astrocytomas, and 24 glioblastomas. Classification of nonacute lesions will require further development, as the metabolic profiles of demyelinating lesions evolve over time

Improved Precision in the Measurement of Longitudinal Global and Regional Volumetric Changes via a Novel MRI Gradient Distortion Characterization and Correction Technique

Reducing measurement variability in MRI-based morphometric analysis of human brain structures will increase statistical power to detect changes between groups and longitudinally over time in individual subjects. One source of measurement error in anatomical MR is magnetic field gradient-induced geometric distortion. This work proposes a method to characterize and compensate for these distortions using a novel image processing technique relying on the image acquisition of a phantom with known geometrical dimensions, without the need to acquire the magnetic field mapping. The method is not specific to any particular shape of the phantom, as long as it provides enough coverage of the volume of interest and enough structure to densely sample the distortion field. The distortions are expressed in terms of spherical harmonic functions, which are then used to define the distortion correction field for the volume of interest. Accuracy of the distortion measurement was evaluated using numerical simulation and reproducibility was estimated using multiple scans of the phantom in the same scanner. Finally, scan-rescan experiments with nine healthy subjects demonstrated that 90% of the distortion (in terms of local volume change) can be corrected with this technique