Introduction Dimethyl sulfoxide (DMSO) is a widely used solvent to dissolve hydrophobic substances for clinical uses and experimental in vivo purposes. While usually regarded safe, our prior studies suggest changes to behavior following DMSO exposure. We therefore evaluated the effects of a five‐day, short‐term exposure to DMSO on postnatal infant rats (P6‐10). Methods DMSO was intraperitoneally injected for five days at 0.2, 2.0, and 4.0 ml/kg body mass. One cohort of animals was sacrificed 24 hr after DMSO exposure to analyze the neurometabolic changes in four brain regions (cortex, hippocampus, basal ganglia, and cerebellum) by hydrophilic interaction liquid chromatography. A second cohort of animals was used to analyze chronic alterations to behavior and pathological changes to glia and neuronal cells later in life (P21‐P40). Results 164 metabolites, including key regulatory molecules (retinoic acid, orotic acid, adrenic acid, and hypotaurine), were found significantly altered by DMSO exposure in at least one of the brain regions at P11 (p < .05). Behavioral tests showed significant hypoactive behavior and decreased social habits to the 2.0 and 4.0 ml DMSO/kg groups (p < .01). Significant increases in number of microglia and astrocytes at P40 were observed in the 4.0 ml DMSO/kg group (at p < .015.) Conclusions Despite short‐term exposure at low, putatively nontoxic concentrations, DMSO led to changes in behavior and social preferences, chronic alterations in glial cells, and changes in essential regulatory brain metabolites. The chronic neurological effects of DMSO exposure reported here raise concerns about its neurotoxicity and consequent safety in human medical applications and clinical trials.

Introduction: Digital pathology whole slide images (WSI) have been recently approved by the FDA for primary diagnosis in clinical surgical pathology practices. These WSI are generated by digitally scanning standard formalin-fixed and paraffin-embedded (FFPE) H&E-stained tissue sections mounted on glass microscope slides. Novel imaging methods are being developed that can capture the surface of tissue without requiring prior fixation, paraffin embedding, or tissue sectioning. One of these methods, FIBI (Fluorescence Imitating Brightfield Imaging), an optically simple and low-cost technique, was developed by our team and used in this study. Methods: 100 de-identified surgical pathology samples were obtained from the UC Davis Health Pathology Laboratory. Samples were first digitally imaged by FIBI, and then embedded in paraffin, sectioned at 4 microns, mounted on glass slides, H&E stained, and scanned using the Aperio/Leica AT2 scanner. The resulting digital images from both FIBI and H&E scan sets were uploaded to PathPresenter and viewed in random order and modality (FIBI or H&E) by each of 4 reading pathologists. After a 30-day washout, the same 100 cases, in random order, were presented in the alternate modality to what was first shown, to the same 4 reading pathologists. The data set consisted, therefore, of 100 reference diagnoses and 800 study pathologist reads (400 FIBI and 400 H&E). Each study read was compared to the reference diagnosis for that case, and also compared to that reader's diagnosis across both modalities for each case. Categories of concordance, minor and major discordance were adjudicated by the study team based on established criteria. Results: The combined category, concordance or minor discordance, was scored as no major discordance. The overall agreement rate (compared to the reference diagnosis), across 800 reads, was 97.9%. This consisted of 400 FIBI reads at 97.0% vs. reference and 400 H&E reads vs. reference at 98.8%. Minor discordances (defined as alternative diagnoses without clinical treatment or outcome implications) were 6.1% overall, 7.2% for FIBI and 5.0% for HE. Conclusions: Pathologists without specific experience or training in FIBI imaging interpretation can provide accurate diagnosis from FIBI slide-free images. Concordance/discordance rates are similar to published rates for comparisons of WSI to standard light microscopy of glass slides for primary diagnosis that led to FDA approval. The present study was more limited in scope but suggests that a follow-on formal clinical trial is feasible. It may be possible, therefore, to develop a slide-free, non-destructive approach for primary pathology diagnosis. Such a method promises improved speed, reduced cost, and better conservation of tissue for advanced ancillary studies.

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Fluorescence imitating brightfield imaging (FIBI) is a novel microscopy method that allows for real-time, nondestructive, slide-free tissue imaging of fresh, formalin-fixed, or paraffin-embedded tissue. The nondestructive nature of the technology permits tissue preservation for downstream analyses. The objective of this observational study was to assess the utility of FIBI compared with conventional hematoxylin and eosin (H&E)-stained histology slides in feline gastrointestinal histopathology. Formalin-fixed paraffin-embedded full-thickness small intestinal tissue specimens from 50 cases of feline chronic enteropathy were evaluated. The ability of FIBI to evaluate predetermined morphological features (epithelium, villi, crypts, lacteals, fibrosis, submucosa, and muscularis propria) and inflammatory cells was assessed on a 3-point scale (0 = FIBI cannot identify the feature; 1 = FIBI can identify the feature; 2 = FIBI can identify the feature with more certainty than H&E). H&E and FIBI images were also scored according to World Small Animal Veterinary Association (WSAVA) Gastrointestinal Standardization Group guidelines. FIBI identified morphological features with similar or, in some cases, higher confidence compared with H&E images. The identification of inflammatory cells was less consistent. FIBI and H&E images showed an overall poor agreement with regard to the assigned WSAVA scores. While FIBI showed an equal or better ability to identify morphological features in intestinal biopsies, its ability to identify inflammatory cells is currently inferior compared with H&E-based imaging. Future studies on the utility of FIBI as a diagnostic tool for noninflammatory histopathologic lesions are warranted.

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