Deep subcortical lesions (DSCL) of the brain, are present in ~60% of the ageing population, and are linked to cognitive decline and depression. DSCL are associated with demyelination, blood brain barrier (BBB) dysfunction, and microgliosis. Microglia are the main immune cell of the brain. Under physiological conditions microglia have a ramified morphology, and react to pathology with a change to a more rounded morphology as well as showing protein expression alterations. This study builds on previous characterisations of DSCL and radiologically ‘normal-appearing’ white matter (NAWM) by performing a detailed characterisation of a range of microglial markers in addition to markers of vascular integrity. The Cognitive Function and Ageing Study (CFAS) provided control white matter (WM), NAWM and DSCL human post mortem tissue for immunohistochemistry using microglial markers (Iba-1, CD68 and MHCII), a vascular basement membrane marker (collagen IV) and markers of BBB integrity (fibrinogen and aquaporin 4). The immunoreactive profile of CD68 increased in a stepwise manner from control WM to NAWM to DSCL. This correlated with a shift from small, ramified cells, to larger, more rounded microglia. While there was greater Iba-1 immunoreactivity in NAWM compared to controls, in DSCL, Iba-1 levels were reduced to control levels. A prominent feature of these DSCL was a population of Iba-1-/CD68+ microglia. There were increases in collagen IV, but no change in BBB integrity. Overall the study shows significant differences in the immunoreactive profile of microglial markers. Whether this is a cause or effect of lesion development remains to be elucidated. Identifying microglia subpopulations based on their morphology and molecular markers may ultimately help decipher their function and role in neurodegeneration. Furthermore, this study demonstrates that Iba-1 is not a pan-microglial marker, and that a combination of several microglial markers is required to fully characterise the microglial phenotype.
Diffuse optical tomography (DOT) uses near infrared light for in vivo imaging of spatially varying optical parameters in biological tissues. It is known that time-resolved measurements provides the richest information on soft tissues, among other measurement types in DOT such as steady state and intensity modulated measurements. Therefore, several integral transform based moments of the time-resolved DOT measurements has been considered, to estimate spatially distributed optical parameters. However, the use of such moments can result in low contrast images and cross-talks between the reconstructed optical parameters, limiting their accuracy. In this work we propose utilizing a truncated Fourier series approximation in time-resolved DOT. Using this approximation, we obtained optical parameter estimates with accuracy comparable to using whole time-resolved data, using low computational time and resources. The truncated Fourier series approximation based estimates also displayed good contrast and minimal parameter cross-talk, and the estimates further improved in accuracy when multiple Fourier frequencies were used.
Quantitative photoacoustic tomography aims at estimating optical parameters from photoacoustic images that are formed utilizing the photoacoustic effect caused by the absorption of an externally introduced light pulse. This optical parameter estimation is an ill-posed inverse problem, and thus it is sensitive to measurement and modeling errors. In this work, we propose a novel way to solve the inverse problem of quantitative photoacoustic tomography based on the perturbation Monte Carlo method. Monte Carlo method for light propagation is a stochastic approach for simulating photon trajectories in a medium with scattering particles. It is widely accepted as an accurate method to simulate light propagation in tissues. Furthermore, it is numerically robust and easy to implement. Perturbation Monte Carlo maintains this robustness and enables forming gradients for the solution of the inverse problem. We validate the method and apply it in the framework of Bayesian inverse problems. The simulations show that the perturbation Monte Carlo method can be used to estimate spatial distributions of both absorption and scattering parameters simultaneously. These estimates are qualitatively good and quantitatively accurate also in parameter scales that are realistic for biological tissues.
Diffuse optical tomography is a highly unstable problem with respect to modeling and measurement errors. During clinical measurements, the body shape is not always known, and an approximate model domain has to be employed. The use of an incorrect model domain can, however, lead to significant artifacts in the reconstructed images. Recently, the Bayesian approximation error theory has been proposed to handle model-based errors. In this work, the feasibility of the Bayesian approximation error approach to compensate for modeling errors due to unknown body shape is investigated. The approach is tested with simulations. The results show that the Bayesian approximation error method can be used to reduce artifacts in reconstructed images due to unknown domain shape.
PurposeAn emerging topic in diffusion magnetic resonance is imaging blood microcirculation alongside water diffusion using the intravoxel incoherent motion (IVIM) model. Recently, a combined IVIM diffusion tensor imaging (IVIM‐DTI) model was proposed, which accounts for both anisotropic pseudo‐diffusion due to blood microcirculation and anisotropic diffusion due to tissue microstructures. In this article, we propose a robust IVIM‐DTI approach for simultaneous diffusion and pseudo‐diffusion tensor imaging.MethodsConventional IVIM estimation methods can be broadly divided into two‐step (diffusion and pseudo‐diffusion estimated separately) and one‐step (diffusion and pseudo‐diffusion estimated simultaneously) methods. Here, both methods were applied on the IVIM‐DTI model. An improved one‐step method based on damped Gauss–Newton algorithm and a Gaussian prior for the model parameters was also introduced. The sensitivities of these methods to different parameter initializations were tested with realistic in silico simulations and experimental in vivo data.ResultsThe one‐step damped Gauss–Newton method with a Gaussian prior was less sensitive to noise and the choice of initial parameters and delivered more accurate estimates of IVIM‐DTI parameters compared to the other methods.ConclusionOne‐step estimation using damped Gauss–Newton and a Gaussian prior is a robust method for simultaneous diffusion and pseudo‐diffusion tensor imaging using IVIM‐DTI model. Magn Reson Med 79:2367–2378, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.