A method of characterising the complex anatomy of vascular occlusions and 3D printing biomimetic analogues.

Chronic total occlusions (CTOs) occur in approximately 40% of individuals with symptomatic peripheral arterial disease and are indicative of critical limb ischaemia. Currently, few medical devices can effectively treat CTOs long-term, with amputation often required. This is due to a lack of knowledge of CTO anatomy, making device design and testing difficult. This study is a proof-of-concept study, which aimed to develop a workflow for further characterising the complex multi-material anatomy of CTOs and creating 3D models of CTO components, which may be useful in producing a vascular CTO biomimetic for device testing. Here, we establish such a workflow using samples of atheromatous plaques. We focus on a high-resolution, non-destructive microcomputed tomography (µCT) technique which enables visualisation of occlusion anatomy at a greater resolution than computed tomography angiography (CTA), which is the typical modality used for CTO clinical visualisation. Four arteries (n = 2 superficial femoral; n = 2 popliteal) with evidence of atheromatous plaques were cut into 8 cm segments, which were then stained with iodine and scanned at low resolution, with calcified regions rescanned at high resolution. Resulting files were manually segmented to generate 3D models, which were then 3D printed in resin using a stereolithography printer to produce parts suitable for creating a biomimetic. In total, µCT files from three arterial segments (n = 2 high resolution, n = 1 low resolution) were deemed suitably calcified for segmentation, and thus were segmented to produce 3D models. 3D models of the arterial wall, intima and atheromatous calcium deposits from a high-resolution popliteal artery scan were successfully 3D printed at several scales. While this research is at an early stage, it holds great promise. The workflow for segmentation and 3D printing various components of an atheromatous plaque established here is replicable and uses software and equipment which are accessible to research laboratories in both academia and industry. The ability to print detailed models on a desktop 3D printer is unprecedented and can be improved further, which is promising for future development of biomimetics with multi-material detail of both soft tissue and calcified components of a vascular occlusion. Indeed, this workflow provides a solid foundation for future studies of CTO anatomy and the creation of true, multi-material CTO biomimetics. Such biomimetics may enable the development of improved interventional devices, as they would mimic the general in vivo CTO environment. As this method cannot be applied in vivo, we cannot yet produce patient-specific biomimetics, however, these analogues would still be important in device development, which would improve patient outcomes in critical limb ischaemia.

Ablation Modalities for Therapeutic Intervention in Arrhythmia-Related Cardiovascular Disease: Focus on Electroporation.

Targeted cellular ablation is being increasingly used in the treatment of arrhythmias and structural heart disease. Catheter-based ablation for atrial fibrillation (AF) is considered a safe and effective approach for patients who are medication refractory. Electroporation (EPo) employs electrical energy to disrupt cell membranes which has a minimally thermal effect. The nanopores that arise from EPo can be temporary or permanent. Reversible electroporation is transitory in nature and cell viability is maintained, whereas irreversible electroporation causes permanent pore formation, leading to loss of cellular homeostasis and cell death. Several studies report that EPo displays a degree of specificity in terms of the lethal threshold required to induce cell death in different tissues. However, significantly more research is required to scope the profile of EPo thresholds for specific cell types within complex tissues. Irreversible electroporation (IRE) as an ablative approach appears to overcome the significant negative effects associated with thermal based techniques, particularly collateral damage to surrounding structures. With further fine-tuning of parameters and longer and larger clinical trials, EPo may lead the way of adapting a safer and efficient ablation modality for the treatment of persistent AF.

Ganglionated Plexi Ablation for the Treatment of Atrial Fibrillation.

Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and is associated with significant morbidity and mortality. The autonomic nervous system (ANS) plays an important role in the initiation and development of AF, causing alterations in atrial structure and electrophysiological defects. The intrinsic ANS of the heart consists of multiple ganglionated plexi (GP), commonly nestled in epicardial fat pads. These GPs contain both parasympathetic and sympathetic afferent and efferent neuronal circuits that control the electrophysiological properties of the myocardium. Pulmonary vein isolation and other cardiac catheter ablation targets including GP ablation can disrupt the fibers connecting GPs or directly damage the GPs, mediating the benefits of the ablation procedure. Ablation of GPs has been evaluated over the past decade as an adjunctive procedure for the treatment of patients suffering from AF. The success rate of GP ablation is strongly associated with specific ablation sites, surgical techniques, localization techniques, method of access and the incorporation of additional interventions. In this review, we present the current data on the clinical utility of GP ablation and its significance in AF elimination and the restoration of normal sinus rhythm in humans.

Density, abundance, survival, and ranging patterns of common bottlenose dolphins (Tursiops truncatus) in Mississippi Sound following the Deepwater Horizon oil spill.

After the Deepwater Horizon (DWH) oil spill began in April 2010, studies were initiated on northern Gulf of Mexico common bottlenose dolphins (Tursiops truncatus) in Mississippi Sound (MSS) to determine density, abundance, and survival, during and after the oil spill, and to compare these results to previous research in this region. Seasonal boat-based photo-identification surveys (2010-2012) were conducted in a section of MSS to estimate dolphin density and survival, and satellite-linked telemetry (2013) was used to determine ranging patterns. Telemetry suggested two different ranging patterns in MSS: (1) inshore waters with seasonal movements into mid-MSS, and (2) around the barrier islands exclusively. Based upon these data, dolphin density was estimated in two strata (Inshore and Island) using a spatially-explicit robust-design capture-recapture model. Inshore and Island density varied between 0.77-1.61 dolphins km-2 ([Formula: see text] = 1.42, 95% CI: 1.28-1.53) and 3.32-5.74 dolphins km-2 ([Formula: see text] = 4.43, 95% CI: 2.70-5.63), respectively. The estimated annual survival rate for dolphins with distinctive fins was very low in the year following the spill, 0.73 (95% CI: 0.67-0.78), and consistent with the occurrence of a large scale cetacean unusual mortality event that was in part attributed to the DWH oil spill. Fluctuations in density were not as large or seasonally consistent as previously reported. Total abundance for MSS extrapolated from density results ranged from 4,610 in July 2011 to 3,046 in January 2012 ([Formula: see text] = 3,469, 95% CI: 3,113-3,725).