A porcine model of thoracic aortic aneurysms created with a retrievable drug infusion stent graft mirrors human aneurysm pathophysiology.

Objective: Aneurysm pathophysiology remains poorly understood, in part from the disparity of murine models with human physiology and the requirement for invasive aortic exposure to apply agents used to create aneurysm models. A retrievable drug infusion stent graft (RDIS) was developed to isolate the aortic wall intraluminally for drug exposure. We hypothesized that an RDIS could deliver aneurysm-promoting enzymes to create a porcine model of thoracic aneurysms without major surgical exposure. Methods: Retrievable nitinol stent graft frames were designed with an isolated drug delivery chamber, covered with polytetrafluoroethylene, and connected to a delivery wire with a drug infusion catheter installed to the outer chamber. Institutional Animal Care and Use Committee-approved Yorkshire pigs (n = 5) underwent percutaneous access of the femoral artery, baseline aortogram and stent placement in the thoracic aorta followed by 30-minute exposure to a cocktail of elastase, collagenase, and trypsin. After aspiration of excess drug, stent retrieval, and femoral artery repair, animals were recovered, with angiograms at 1 and 4 weeks followed by explant. Histological analysis, in situ zymography, and multiplex cytokine assays were performed. Results: The RDIS isolated a segment of anterior aorta angiographically, while the center lumen preserved distal perfusion during drug treatment (baseline femoral mean arterial pressure, 70 ± 14 mm Hg; after RDIS, 75 ± 12; P = .55). Endovascular induction of thoracic aneurysms did not require prior mechanical injury and animals revealed no evidence of toxicity. Within 1 week, significant aneurysmal growth was observed in all five animals (1.4 ± 0.1 cm baseline to 2.9 ± 0.7 cm; P = .002) and only within the treated region of the aorta. Aneurysms persisted out to 4 weeks. Aneurysm histology demonstrated loss of elastin and collagen that was otherwise preserved in untreated aorta. Proinflammatory cytokines and increased matrix metalloproteinase activity were increased significantly within the aneurysm. Conclusions: An RDIS achieves isolated drug delivery while preserving distal perfusion to achieve an endovascular porcine model of thoracic aneurysms without major surgery. This model may have value for surgical training, device testing, and to better understand aneurysm pathogenesis. Most important, although the RDIS was used to simulate aortic pathology, this tool offers intriguing horizons for focused therapeutic drug delivery directly to aneurysms and, more broadly, focused locoregional drug delivery to vessels and vascular beds.

Topology of the lateral visual system: The fundus of the superior temporal sulcus and parietal area H connect nonvisual cerebrum to the lateral occipital lobe.

BACKGROUND AND PURPOSE: Mapping the topology of the visual system is critical for understanding how complex cognitive processes like reading can occur. We aim to describe the connectivity of the visual system to understand how the cerebrum accesses visual information in the lateral occipital lobe. METHODS: Using meta-analytic software focused on task-based functional MRI studies, an activation likelihood estimation (ALE) of the visual network was created. Regions of interest corresponding to the cortical parcellation scheme previously published under the Human Connectome Project were co-registered onto the ALE to identify the hub-like regions of the visual network. Diffusion Spectrum Imaging-based fiber tractography was performed to determine the structural connectivity of these regions with extraoccipital cortices. RESULTS: The fundus of the superior temporal sulcus (FST) and parietal area H (PH) were identified as hub-like regions for the visual network. FST and PH demonstrated several areas of coactivation beyond the occipital lobe and visual network. Furthermore, these parcellations were highly interconnected with other cortical regions throughout extraoccipital cortices related to their nonvisual functional roles. A cortical model demonstrating connections to these hub-like areas was created. CONCLUSIONS: FST and PH are two hub-like areas that demonstrate extensive functional coactivation and structural connections to nonvisual cerebrum. Their structural interconnectedness with language cortices along with the abnormal activation of areas commonly located in the temporo-occipital region in dyslexic individuals suggests possible important roles of FST and PH in the integration of information related to language and reading. Future studies should refine our model by examining the functional roles of these hub areas and their clinical significance.

Parcellation-based tractographic modeling of the salience network through meta-analysis.

BACKGROUND: The salience network (SN) is a transitory mediator between active and passive states of mind. Multiple cortical areas, including the opercular, insular, and cingulate cortices have been linked in this processing, though knowledge of network connectivity has been devoid of structural specificity. OBJECTIVE: The current study sought to create an anatomically specific connectivity model of the neural substrates involved in the salience network. METHODS: A literature search of PubMed and BrainMap Sleuth was conducted for resting-state and task-based fMRI studies relevant to the salience network according to PRISMA guidelines. Publicly available meta-analytic software was utilized to extract relevant fMRI data for the creation of an activation likelihood estimation (ALE) map and relevant parcellations from the human connectome project overlapping with the ALE data were identified for inclusion in our SN model. DSI-based fiber tractography was then performed on publicaly available data from healthy subjects to determine the structural connections between cortical parcellations comprising the network. RESULTS: Nine cortical regions were found to comprise the salience network: areas AVI (anterior ventral insula), MI (middle insula), FOP4 (frontal operculum 4), FOP5 (frontal operculum 5), a24pr (anterior 24 prime), a32pr (anterior 32 prime), p32pr (posterior 32 prime), and SCEF (supplementary and cingulate eye field), and 46. The frontal aslant tract was found to connect the opercular-insular cluster to the middle cingulate clusters of the network, while mostly short U-fibers connected adjacent nodes of the network. CONCLUSION: Here we provide an anatomically specific connectivity model of the neural substrates involved in the salience network. These results may serve as an empiric basis for clinical translation in this region and for future study which seeks to expand our understanding of how specific neural substrates are involved in salience processing and guide subsequent human behavior.