Liver-specific 3D sectioning molds for correlating in vivo CT and MRI with tumor histopathology in woodchucks (Marmota monax).

PurposeTo evaluate the spatial registration and correlation of liver and tumor histopathology sections with corresponding in vivo CT and MRI using 3D, liver-specific cutting molds in a woodchuck (Marmota monax) hepatic tumor model.MethodsFive woodchucks chronically infected with woodchuck hepatitis virus following inoculation at birth and with confirmed hepatic tumors were imaged by contrast enhanced CT or MRI. Virtual 3D liver or tumor models were generated by segmentation of in vivo CT or MR imaging. A specimen-specific cavity was created inside a block containing cutting slots aligned with an imaging plane using computer-aided design software, and the final cutting molds were fabricated using a 3D printer. Livers were resected two days after initial imaging, fixed with formalin or left unfixed, inserted into the 3D molds, and cut into parallel pieces by passing a sharp blade through the parallel slots in the mold. Histopathology sections were acquired and their spatial overlap with in vivo image slices was quantified using the Dice similarity coefficient (DSC).ResultsImaging of the woodchucks revealed heterogeneous hepatic tumors of varying size, number, and location. Specimen-specific 3D molds provided accurate co-localization of histopathology of whole livers, liver lobes, and pedunculated tumors with in vivo CT and MR imaging, with or without tissue fixation. Visual inspection of histopathology sections and corresponding in vivo image slices revealed spatial registration of analogous pathologic features. The mean DSC for all specimens was 0.83+/-0.05.ConclusionUse of specimen-specific 3D molds for en bloc liver dissection provided strong spatial overlap and feature correspondence between in vivo image slices and histopathology sections

Prelesional arterial endothelial phenotypes in hypercholesterolemia: universal ABCA1 upregulation contrasts with region-specific gene expression in vivo

Atherosclerosis originates as focal arterial lesions having a predictable distribution to regions of bifurcations, branches, and inner curvatures where blood flow characteristics are complex. Distinct endothelial phenotypes correlate with regional hemodynamics. We propose that systemic risk factors modify regional endothelial phenotype to influence focal susceptibility to atherosclerosis. Transcript profiles of freshly isolated endothelial cells from three atherosusceptible and three atheroprotected arterial regions in adult swine were analyzed to determine the initial prelesional effects of hypercholesterolemia on endothelial phenotypes in vivo. Cholesterol efflux transporter ATP-binding cassette transporter A1 (ABCA1) was upregulated at all sites in response to short-term high-fat diet. Proinflammatory and antioxidative endothelial gene expression profiles were induced in atherosusceptible and atheroprotected regions, respectively. However, markers for endoplasmic reticulum stress, a signature of susceptible endothelial phenotype, were not further enhanced by brief hypercholesterolemia. Both region-specific and ubiquitous (ABCA1) phenotype changes were identified as early prelesional responses of the endothelium to hypercholesterolemia

Development of Imageable Beads for Transcatheter Embolotherapy

Purpose: To develop and characterize radiopaque embolization microspheres capable of in vivo detection with intraprocedural fluoroscopy and computed tomography (CT) imaging and to evaluate their spatial distribution inside target tissues during and after transcatheter embolization. Materials and Methods: Polyvinyl alcohol hydrogel microspheres were loaded with Lipiodol and examined for iodine content, stability of loading, and conspicuity with fluoroscopy and CT in vitro. Transcatheter embolization of swine liver and kidney was performed with the radiopaque microspheres and spatial distribution was evaluated with intraprocedural fluoroscopy and CT. Ex vivo evaluation was performed with light microscopy and micro-CT. Results: In vitro analyses demonstrated that radiopaque microspheres could be loaded with sufficient iodine content to be detected with routine fluoroscopy and CT imaging and that such loading was relatively stable. Radiopaque microspheres were visible in vivo with fluoroscopy and CT during transcatheter embolization. CT imaging during embolization procedures demonstrated a dose-dependent relationship in the number and size of visualized embolized arteries. Imaging features of radiopaque microsphere distribution inside target tissues correlated well with ex vivo light microscopic and micro-CT evaluation of microsphere distribution. Conclusions: Radiopaque embolization microspheres are visualized during transcatheter embolization with routine intraprocedural fluoroscopy and CT. These radiopaque microspheres provided the three-dimensional spatial distribution of embolic material inside target organs during the procedure, and therefore can provide real-time intraprocedural feedback for the interventional radiologist. These microspheres may be useful for demonstrating the influence of material and technical variability in transcatheter embolization in addition to providing intraprocedural identification of tissue at risk of undertreatment. © 2010 SIR