Background-deflection Brillouin microscopy reveals altered biomechanics of intracellular stress granules by ALS protein FUS

Altered cellular biomechanics have been implicated as key photogenic triggers in age-related diseases. An aberrant liquid-to-solid phase transition, observed in in vitro reconstituted droplets of FUS protein, has been recently proposed as a possible pathogenic mechanism for amyotrophic lateral sclerosis (ALS). Whether such transition occurs in cell environments is currently unknown as a consequence of the limited measuring capability of the existing techniques, which are invasive or lack of subcellular resolution. Here we developed a non-contact and label-free imaging method, named background-deflection Brillouin microscopy, to investigate the three-dimensional intracellular biomechanics at a sub-micron resolution. Our method exploits diffraction to achieve an unprecedented 10,000-fold enhancement in the spectral contrast of single-stage spectrometers, enabling, to the best of our knowledge, the first direct biomechanical analysis on intracellular stress granules containing ALS mutant FUS protein in fixed cells. Our findings provide fundamental insights on the critical aggregation step underlying the neurodegenerative ALS disease

Large Deformation Diffeomorphic Metric Mapping Registration of Reconstructed 3D Histological Section Images and in vivo MR Images

Our current understanding of neuroanatomical abnormalities in neuropsychiatric diseases is based largely on magnetic resonance imaging (MRI) and post mortem histological analyses of the brain. Further advances in elucidating altered brain structure in these human conditions might emerge from combining MRI and histological methods. We propose a multistage method for registering 3D volumes reconstructed from histological sections to corresponding in vivo MRI volumes from the same subjects: (1) manual segmentation of white matter (WM), gray matter (GM) and cerebrospinal fluid (CSF) compartments in histological sections, (2) alignment of consecutive histological sections using 2D rigid transformation to construct a 3D histological image volume from the aligned sections, (3) registration of reconstructed 3D histological volumes to the corresponding 3D MRI volumes using 3D affine transformation, (4) intensity normalization of images via histogram matching, and (5) registration of the volumes via intensity based large deformation diffeomorphic metric (LDDMM) image matching algorithm. Here we demonstrate the utility of our method in the transfer of cytoarchitectonic information from histological sections to identify regions of interest in MRI scans of nine adult macaque brains for morphometric analyses. LDDMM improved the accuracy of the registration via decreased distances between GM/CSF surfaces after LDDMM (0.39 ± 0.13 mm) compared to distances after affine registration (0.76 ± 0.41 mm). Similarly, WM/GM distances decreased to 0.28 ± 0.16 mm after LDDMM compared to 0.54 ± 0.39 mm after affine registration. The multistage registration method may find broad application for mapping histologically based information, for example, receptor distributions, gene expression, onto MRI volumes

Quantification in cardiac MRI: advances in image acquisition and processing

Cardiac magnetic resonance (CMR) imaging enables accurate and reproducible quantification of measurements of global and regional ventricular function, blood flow, perfusion at rest and stress as well as myocardial injury. Recent advances in MR hardware and software have resulted in significant improvements in image quality and a reduction in imaging time. Methods for automated and robust assessment of the parameters of cardiac function, blood flow and morphology are being developed. This article reviews the recent advances in image acquisition and quantitative image analysis in CMR

Optimization of Spiral MRI Using a Perceptual Difference Model

We systematically evaluated a variety of MR spiral imaging acquisition and reconstruction schemes using a computational perceptual difference model (PDM) that models the ability of humans to perceive a visual difference between a degraded “fast” MRI image with subsampling of k-space and a “gold standard” image mimicking full acquisition. Human subject experiments performed using a modified double-stimulus continuous-quality scale (DSCQS) correlated well with PDM, over a variety of images. In a smaller set of conditions, PDM scores agreed very well with human detectability measurements of image quality. Having validated the technique, PDM was used to systematically evaluate 2016 spiral image conditions (six interleave patterns, seven sampling densities, three density compensation schemes, four reconstruction methods, and four noise levels). Voronoi (VOR) with conventional regridding gave the best reconstructions. At a fixed sampling density, more interleaves gave better results. With noise present more interleaves and samples were desirable. With PDM, conditions were determined where equivalent image quality was obtained with 50% sampling in noise-free conditions. We conclude that PDM scoring provides an objective, useful tool for the assessment of fast MR image quality that can greatly aid the design of MR acquisition and signal processing strategies

DIFFUSE OPTICAL TOMOGRAPHY: AN ADVANCED MULTISTAGE INVERSE METHOD AND AN OPTIMIZATION METHOD OF SOURCE AND DETECTOR ARRANGEMENTS

Ph.DDOCTOR OF PHILOSOPH