![neurotracker neurite quanitifcation neurotracker neurite quanitifcation](https://image2.slideserve.com/5136212/slide8-l.jpg)
However, despite active research efforts toward PET and MR imaging of neuroinflammation, there remains no routine, widespread, and easily accessible neuroimaging tool available for the study of neuroinflammation.Īdvanced MRI diffusion weighted imaging (DWI) methods represent a conceptually innovative and technically sensitive approach for measuring cellular changes associated with neuroinflammation and microglial activation. Neuroimaging techniques have been developed to characterize neuroinflammatory processes, which generally fall into two methodological categories: positron emission tomography (PET) and MRI ( Albrecht et al., 2016). Neuroinflammation plays a critical role in the neuropathogenesis of disorders of the central nervous system (CNS) from ischemic stroke and traumatic brain injury ( Iadecola and Anrather, 2011 Woodcock and Morganti-Kossmann, 2013) to Alzheimer's disease, schizophrenia, and major depression ( Lull and Block, 2010 Mondelli et al., 2017). Our results demonstrate that clinically feasible multi-compartment diffusion weighted imaging techniques such as NODDI are sensitive to microglial density and the cellular changes associated with microglial activation and highlights its potential to improve clinical diagnostic accuracy, patient risk stratification, and therapeutic monitoring of neuroinflammation in neurologic and psychiatric disease. Quantitative immunofluorescence of microglial density reveals that microglial density is positively correlated with ODI and greater hindered diffusion in the extra-neurite space (τ = 0.386, p < 0.05). Commensurate with our simulation data, ex-vivo NODDI imaging demonstrates an increase in ODI as microglia repopulate the brain following the withdrawal of CSF1R inhibition.
![neurotracker neurite quanitifcation neurotracker neurite quanitifcation](https://d2jx2rerrg6sh3.cloudfront.net/image-handler/picture/clip_image008_0004_1.jpg)
Monte Carlo simulations demonstrate the sensitivity and positive correlation of ODI to increased occupancy in the extra-neurite space. Cell populations were calculated with the ImageJ particle analyzer tool correlation between microglial density and mean ODI values were calculated with Kendall's tau. Following imaging, all brains were immunostained with Iba-1, NeuN, and GFAP for quantitative fluorescence microscopy.
![neurotracker neurite quanitifcation neurotracker neurite quanitifcation](https://www.ahajournals.org/cms/asset/d195cbe9-2d08-43d9-a01e-4ce2e731f7ea/hs1153232003.jpg)
12-week-old C57BL/6J male mice ( n = 48 24 control, 24 treated with colony stimulating factor 1 receptor (CSF1R) inhibitor, PLX5622) were sacrificed at 0, 1, 3, and 7 days following withdrawal of CSF1R inhibition and were imaged ex-vivo to obtain measures of the orientation dispersion index (ODI). Monte Carlo simulations of water diffusion using a NODDI acquisition scheme were performed to measure changes in a virtual MRI signal following modeled cellular changes within the extra-neurite space. We explored the sensitivity of quantitative multi-compartment diffusion MRI, and specifically neurite orientation dispersion and density imaging (NODDI), to detect changes in microglial density in the brain. Neuroinflammation plays a central role in the neuropathogenesis of a wide-spectrum of neurologic and psychiatric disease, but current neuroimaging methods to detect and characterize neuroinflammation are limited. 5Department of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States.
![neurotracker neurite quanitifcation neurotracker neurite quanitifcation](https://d2jx2rerrg6sh3.cloudfront.net/image-handler/picture/clip_image020_0001.jpg)
4Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States.3Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States.2Department of Biomedical Engineering, College of Engineering, University of Wisconsin–Madison, Madison, WI, United States.1Neuroscience Training Program, Wisconsin Institutes for Medical Research, University of Wisconsin–Madison, Madison, WI, United States.Rowley 3, Diego Hernando 3,4 and John-Paul J. Barnett 1, Maribel Torres-Velázquez 2, Yuxin Zhang 3,4, Samuel A.