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The gut microbiome profoundly influences brain structure and function. The gut microbiome is hypothesized to play a key role in the etiopathogenesis of neuropsychiatric and neurodegenerative illness; however, the contribution of an intact gut microbiome to quantitative neuroimaging parameters of brain microstructure and function remains unknown. Herein, we report the broad and significant influence of a functional gut microbiome on commonly employed neuroimaging measures of diffusion tensor imaging (DTI), neurite orientation dispersion and density (NODDI) imaging, and SV2A 18F-SynVesT-1 synaptic density PET imaging when compared to germ-free animals. In this pilot study, we demonstrate that mice, in the presence of a functional gut microbiome, possess higher neurite density and orientation dispersion and decreased synaptic density when compared to age- and sex-matched germ-free mice. Our results reveal the region-specific structural influences and synaptic changes in the brain arising from the presence of intestinal microbiota. Further, our study highlights important considerations for the development of quantitative neuroimaging biomarkers for precision imaging in neurologic and psychiatric illness.

Light chain deposition disease (LCDD) is a rare clinicopathologic entity first described in 1976 and is characterized by a monoclonal gammopathy resulting in nonamyloid immunoglobulin light chain tissue deposition. Only four cases of intracerebral LCDD have been previously reported, all in the setting of a known plasma cell dyscrasia or in the presence of local mature plasma cells. We present the first case of intracranial LCDD in the absence of a known plasma cell dyscrasia or local mature plasma cells.

Background Appropriate indications for radiologic evaluation of central venous ports are not fully understood. We aimed to quantitatively assess the utility of clinical history and imaging in the evaluation of malfunctioning central venous ports. Methods Clinical history, plain radiographs, and line injections intended to evaluate central venous port malfunction in 153 consecutive cases over a nearly 4-year period were retrospectively reviewed by 2 radiologists. Radiographs and line injections were separately categorized as normal or abnormal, and a consensus was reached on the final imaging diagnosis. The likelihood of a port-related abnormality necessitating immediate intervention was determined for all represented combinations of clinical history, radiographic findings, and line injection results. Results A radiologic diagnosis was made in 96.1% of cases; 19.7% of these diagnoses were classified as critical, requiring prompt intervention. Very low risk histories had a 0.0% incidence of critical port abnormalities in our cohort, regardless of imaging findings. Low risk histories had a 10.5% incidence of a critical abnormality and were best evaluated either by line injection, either directly or following an abnormal chest radiograph. Intermediate and high risk histories were associated with a 30.5% and 61.1% incidence of critical port abnormalities, respectively, and were best evaluated by line injection without preceding chest radiograph. Conclusions There are several scenarios in which imaging does not meaningfully affect management of malfunctioning central venous ports. Recognizing these inefficiencies may allow for more appropriate and cost-effective use of radiographs and line injections to evaluate the cause of port malfunction. © 2014, ASSOCIATION FOR VASCULAR ACCESS. Published by Elsevier Inc. All rights reserved.

Purpose: The clinical diagnosis and classification of Alexander disease (AxD) relies in part on qualitative neuroimaging biomarkers; however, these biomarkers fail to distinguish and discriminate different subtypes of AxD, especially in the presence of overlap in clinical symptoms. To address this gap in knowledge, we applied neurite orientation dispersion and density imaging (NODDI) to an innovative CRISPR‐Cas9 rat genetic model of AxD to gain quantitative insights into the neural substrates and brain microstructural changes seen in AxD and to potentially identify novel quantitative NODDI biomarkers of AxD. Methods: Multi‐shell DWI of age‐ and sex‐matched AxD and wild‐type Sprague Dawley rats (n = 6 per sex per genotype) was performed and DTI and NODDI measures calculated. A 3 × 2 × 2 analysis of variance model was used to determine the effect of genotype, biological sex, and laterality on quantitative measures of DTI and NODDI across regions of interest implicated in AxD. Results: There is a significant effect of genotype in the amygdala, hippocampus, neocortex, and thalamus in measures of both DTI and NODDI brain microstructure. A genotype by biological sex interaction was identified in DTI and NODDI measures in the corpus callosum, hippocampus, and neocortex. Conclusion: We present the first application of NODDI to the study of AxD using a rat genetic model of AxD. Our analysis identifies alterations in NODDI and DTI measures to large white matter tracts and subcortical gray nuclei. We further identified genotype by sex interactions, suggesting a possible role for biological sex in the neuropathogenesis of AxD. [ABSTRACT FROM AUTHOR]

Abstract Background Dual degree program MD/PhD candidates typically train extensively in basic science research and in clinical medicine, but often receive little formal experience or mentorship in clinical and translational research. Methods To address this educational and curricular gap, the University of Wisconsin Medical Scientist Training Program partnered with the University of Wisconsin Institute for Clinical and Translational Research to create a new physician-scientist preceptorship in clinical and translational research. This six-week apprentice-style learning experience—guided by a physician-scientist faculty mentor—integrates both clinical work and a translational research project, providing early exposure and hands-on experience with clinically oriented research and the integrated career of a physician-scientist. Five years following implementation, we retrospectively surveyed students and faculty members to determine the outcomes of this preceptorship. Results Over five years, 38 students and 36 faculty members participated in the physician-scientist preceptorship. Based on student self-assessments (n = 29, response rate 76%), the course enhanced competency in conducting translational research and understanding regulation of clinical research among other skills. Mentor assessments (n = 17, response rate 47%) supported the value of the preceptorship in these same areas. Based on work during the preceptorship, half of the students produced a peer-reviewed publication or a meeting abstract. At least eleven peer-reviewed manuscripts were generated. The preceptorship also provided a structure for physician-scientist mentorship in the students’ clinical specialty of choice. Conclusion The physician-scientist preceptorship provides a new curricular model to address the gap of clinical research training and provides for mentorship of physician-scientists during medical school. Future work will assess the long-term impact of this course on physician-scientist career trajectories.

The continuous accumulation of artisanal and small-scale gold mining (ASGM) tailings in the Philippines without adequate storage and disposal facility could lead to human health and environmental disasters in the long run. In this study, ASGM tailings was simultaneously stabilized and repurposed as construction material via geopolymerization using coal fly ash, palm oil fuel ash and a powder-based alkali activator. Scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDS) identified iron sulfides in the tailings containing arsenic (As), cadmium (Cd), copper (Cu), lead (Pb) and zinc (Zn), which could be released via weathering. The average unconfined compressive strengths (UCS) of tailings-based geopolymers at 14 days curing were 7.58 MPa and 7.7 MPa with fly ash and palm oil fuel ash, respectively. The tailings-based geopolymers with palm oil fuel ash had higher UCS most likely due to CASH reaction product formation that improved strength formation. The toxicity characteristic leaching procedure (TCLP) results showed very low leachabilities of As, Pb and Fe in the geopolymer materials suggesting ASGM tailings was effectively encapsulated within the geopolymer matrix. Overall, the geopolymerization of ASGM tailings is a viable and promising solution to simultaneously stabilize mining and industrial wastes and repurpose them into construction materials.

Rationale and objectivesRadiation exposure from medical imaging has received increasing attention in recent years. Ongoing calls to report radiation doses received during radiology studies as a means of recording cumulative exposure and identifying rare over-exposures have culminated in the State of California passing a mandatory reporting requirement effective July 1, 2012. Herein we describe a radiology housestaff-led quality improvement project to track radiation dose reporting a full year prior to state reporting mandates using a template-driven reporting system and our results over the first 12 months of its implementation.Materials and methodsEffective July 2011, all radiology trainees were instructed to use a standard computed tomography (CT) report template that included a CT dose measurement derived from dose information routinely displayed on our picture archiving and communication system. Consecutive reports from July 1, 2011, to June 30, 2012, of patients who underwent CT examinations at our institution were then retrospectively reviewed. Compliance of each study with the reporting requirement was assessed based on the presence or absence of a radiation dose statement within the finalized report.ResultsA total of 36,217 eligible consecutive CT reports were identified within the review period. Of these, 91.9% reported the radiation dose for the examination, greatly exceeding the initial goal of 80% compliance with the dose reporting requirement.ConclusionSuccessful reporting of CT radiation doses resulted from template-driven reporting, readily accessible calculation tools to facilitate dose calculation, and minimization of reporting burden on the radiologist a full year prior to state regulatory mandates.

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. 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. 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. 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). Following imaging, all brains were immunostained with Iba-1, NeuN, and GFAP for quantitative fluorescence microscopy. Cell populations were calculated with the ImageJ particle analyzer tool; correlation between microglial density and mean ODI values were calculated with Kendall's tau. Monte Carlo simulations demonstrate the sensitivity and positive correlation of ODI to increased occupancy in the extra-neurite space. 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. 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). 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.