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

Radiopaque drug-eluting beads for transcatheter embolotherapy: Experimental study of drug penetration and coverage in swine

Purpose: To determine local doxorubicin levels surrounding radiopaque drug-eluting beads (DEBs) in normal swine liver and kidney following transcatheter arterial chemoembolization. The influence of bead size (70150 μm or 100300 μm) was compared with regard to tissue penetration and spatial distribution of the bead, as well as eventual drug coverage (ie, amount of tissue exposed to drug). Materials and Methods: Radiopaque DEBs were synthesized by suspension polymerization followed by incorporation of iodized oil and doxorubicin. Chemoembolization of swine liver and kidney was performed under fluoroscopic guidance. Three-dimensional tissue penetration of imageable DEBs was investigated ex vivo with microcomputed tomography (microCT). Drug penetration from the bead surface and drug coverage was evaluated with epifluorescence microscopy, and cellular localization of doxorubicin was evaluated with confocal microscopy. Necrosis was evaluated with hematoxylin and eosin staining. Results: MicroCT demonstrated that 70150-μm DEBs were present in more distal arteries and located in a more frequent and homogeneous spatial distribution. Tissue penetration of doxorubicin from the bead appeared similar (∼300 μm) for both DEBs, with a maximum tissue drug concentration at 1 hour coinciding with nuclear localization of doxorubicin. The greater spatial frequency of the 70150-μm DEBs resulted in approximately twofold improved drug coverage in kidney. Cellular death is predominantly observed around the DEBs beginning at 8 hours, but increased at 24 and 168 hours. Conclusions: Smaller DEBs penetrated further into targeted tissue (ie, macroscopic) with a higher spatial density, resulting in greater and more uniform drug coverage (ie, microscopic) in swine. © 2012 SIR