Correlated Heterospectral Lipidomics for Biomolecular Profiling of Remyelination in Multiple Sclerosis

Analyzing lipid composition and distribution within the brain is important to study white matter pathologies that present focal demyelination lesions, such as multiple sclerosis. Some lesions can endogenously re-form myelin sheaths. Therapies aim to enhance this repair process in order to reduce neurodegeneration and disability progression in patients. In this context, a lipidomic analysis providing both precise molecular classification and well-defined localization is crucial to detect changes in myelin lipid content. Here we develop a correlated heterospectral lipidomic (HSL) approach based on coregistered Raman spectroscopy, desorption electrospray ionization mass spectrometry (DESI-MS), and immunofluorescence imaging. We employ HSL to study the structural and compositional lipid profile of demyelination and remyelination in an induced focal demyelination mouse model and in multiple sclerosis lesions from patients ex vivo. Pixelwise coregistration of Raman spectroscopy and DESI-MS imaging generated a heterospectral map used to interrelate biomolecular structure and composition of myelin. Multivariate regression analysis enabled Raman-based assessment of highly specific lipid subtypes in complex tissue for the first time. This method revealed the temporal dynamics of remyelination and provided the first indication that newly formed myelin has a different lipid composition compared to normal myelin. HSL enables detailed molecular myelin characterization that can substantially improve upon the current understanding of remyelination in multiple sclerosis and provides a strategy to assess remyelination treatments in animal models

Assessment of intracochlear ossification by three-dimensional reconstruction of computerised scans

This is a publisher’s version of an article published in Annals of Otology, Rhinology & Laryngology published by Annals Publishing Company. This version is reproduced with permission from Annals Publishing Company. http://www.annals.com/The aim of the study was to investigate whether the three-dimensional (3-D) images from computed tomography (CT) scans of the ears could adequately define the site and extent of new bone in the cochlea, and how these images compared with those created by magnetic resonance imaging (MRI). The patients whose investigations were used in the study were being assessed for a cochlear implant and were selected on the basis of their history and the appearance of their two-dimensional (2-D) CT scans. Four patients had progressive mixed deafness, a family history of deafness, and stapedectomies. They were considered to be deaf from otosclerosis and needed further assessment because their scans showed either obstructed cochleas from new bone, or demineralized otic capsules to the point that we could not determine whether new bone was present or not. The fifth patient was being assessed within 3 months of suffering deafness from meningitis. In one ear he had extensive ossification, and in the other the degree of opacification shown in axial and coronal cuts of the basal turn was inconsistent. Essentially the problem is that at the magnification used in examination of the inner ear, the resolution of 2-D CT scans gives indistinct borders between bone and water. Magnetic resonance imaging has commonly been used in these cases. The study showed that it is now possible to confirm whether or not there is new bone and to demonstrate the site and extent of new bone with both 3-D and MRI images. It is not possible to give a degree of sensitivity and specificity for this observation because of the small group of subjects in the study. It should be worth applying the reconstruction software to scans from helical scanners with a view to assessing whether the resolution of the 3-D images can be improved further