Enhanced solute transport and steady mechanical stimulation in a novel dynamic perifusion bioreactor increase the efficiency of the in vitro culture of ovarian cortical tissue strips.

Introduction: We report the development and preliminary evaluation of a novel dynamic bioreactor to culture ovarian cortical tissue strips that leverages tissue response to enhanced oxygen transport and adequate mechanical stimulation. In vitro multistep ovarian tissue static culture followed by mature oocyte generation, fertilization, and embryo transfer promises to use the reserve of dormant follicles. Unfortunately, static in vitro culture of ovarian tissue does not promote development of primordial to secondary follicles or sustain follicle viability and thereby limits the number of obtainable mature oocytes. Enhancing oxygen transport to and exerting mechanical stimulation on ovarian tissue in a dynamic bioreactor may more closely mimic the physiological microenvironment and thus promote follicle activation, development, and viability. Materials and Methods: The most transport-effective dynamic bioreactor design was modified using 3D models of medium and oxygen transport to maximize strip perifusion and apply tissue fluid dynamic shear stresses and direct compressive strains to elicit tissue response. Prototypes of the final bioreactor design were manufactured with materials of varying cytocompatibility and assessed by testing the effect of leachables on sperm motility. Effectiveness of the bioreactor culture was characterized against static controls by culturing fresh bovine ovarian tissue strips for 7 days at 4.8 × 10-5 m/s medium filtration flux in air at -15% maximal total compressive strain and by assessing follicle development, health, and viability. Results and Conclusions: Culture in dynamic bioreactors promoted effective oxygen transport to tissues and stimulated tissues with strains and fluid dynamic shear stresses that, although non-uniform, significantly influenced tissue metabolism. Tissue strip culture in bioreactors made of cytocompatible polypropylene preserved follicle viability and promoted follicle development better than static culture, less so in bioreactors made of cytotoxic ABS-like resin.

Computational fluid dynamics of a novel perfusion strategy during hybrid thoracic aortic repair.

BACKGROUND AND AIM: To mitigate the risk of perioperative neurological complications during frozen elephant trunk procedures, we aimed to computationally evaluate the effects of direct cerebral perfusion strategy through a left carotid-subclavian bypass on hemodynamics in a patient-specific thoracic aorta model. METHODS: Between July 2016 and March 2019, 11 consecutive patients underwent frozen elephant trunk operation using the left carotid-subclavian bypass with a side graft anastomosis and right-axillary cannulation for systemic and brain perfusion. A multiscale model realized coupling three-dimensional computational fluid dynamics was developed and validated with in vivo data. Model comparison with direct antegrade cannulation of all epiaortic vessels was performed. Wall shear stress, wall shear stress spatial gradient, and localized normalized helicity were selected as hemodynamic indicators. Four cerebral perfusion flows were tested (6 to 15 mL/kg/min). RESULTS: Direct cerebral perfusion of the left subclavian bypass resulted in higher flow rates with augmented speeds in all epiaortic vessels in comparison with traditional perfusion model. At the level of the left vertebral artery (LVA), a speed of 22.5 vs 21 mL/min and mean velocity of 3.07 vs 2.93 cm/s were registered, respectively. With a cerebral perfusion flow of 15 mL/kg, lower LVA wall shear stress (1.596 vs 2.030 N/m2 ), and wall shear stress gradient (1445 vs 5882 N/m3 ) were observed. A less disturbed flow considering the localized normalized helicity was documented. No patients experienced neurological/spinal cord damages. CONCLUSIONS: Direct perfusion of a left carotid bypass proved to be cerebroprotective, resulting in a more physiological and stable anterior and posterior cerebral perfusion.

On the reliability of measurements for a stent positioning simulation system.

BACKGROUND AND OBJECTIVE: Computer aided simulations are useful to support the physician in many steps of the surgical activity, but also in pre-surgical patient classification and in post-surgical diagnosis and treatment decisions. At a broader level, computerized technologies and infrastructures permeate every aspect of the medical activity, from patient management to surgery and patients' follow up with outcomes analyses. Radiography assisted surgery is often used in hemodynamic surgery to study and support cardio-circulatory stents positioning with the use of radioscopy coupled with contrast liquid injected into the vessels. Computer based surgery instruments (both software and hardware) are used to support clinicians during interventions, e.g., to reduce radioscopy time exposure, to minimize errors and to estimate tissues and organs dimension. In this paper we present the use of a newly developed system which supports physicians during transcatheter percutaneous coronary interventions. METHODS: This paper presents a Java-based tool which acquires images from angiographic equipment during surgery procedures. An high performance image acquisition module has been used and a stent simulation environment module is available to simulate stent positioning and to measure vessels. Operators may acquire images, perform measurements and simulations on DICOM images. We performed tests off-line on images to validate the reliability of the tool. Real cases and on line tests have been performed by operators showing the robustness of the system to be used in surgery room. The system has been integrated in the surgery room control panel and allows (i) vascular images acquisition, (ii) vessels and coronary measurement and (iii) stent positioning simulations. The tool is an aid for the physician for both measuring tissues or lesions and for defining the stent's geometry and position before its deployment in the patient's vessels. RESULTS: Experiments have been performed on lesions and vessels by different operators using the system and an available commercial system, on both real patient cases and synthetic images designed with a CAD. It has been tested on 76 images extracted from real angiography cases and on 11 synthetic images created by using CAD. Five different operators performed 2128 measurements for the real cases images (for both Cartesio and CAAS tools) and 112 for the synthetic dataset. Results show the efficacy of the system compared with the commercial one by means of several statistical tests. CONCLUSIONS: The proposed system is a reliable tool for hemodynamic surgery and can be used both for decision support in stent positioning procedures and for didactic training of new physicians.

An Innovative Framework for Bioimage Annotation and Studies.

The collection and analysis of clinical data are needed to investigate diseases and to define medical protocols and treatments. Bioimages, medical annotations and patient history are clinical data acquired and studied to perform a correct diagnosis and to propose an appropriate therapy. Currently, hospital departments manage these data using legacy systems which do not often allow data integration among different departments or health structures. Thus, in many cases clinical information sharing and exchange are difficult to implement. This is also the case for biomedical images for which data integration or data overlapping is usually not available. Image annotations and comparison can be crucial for physicians in many case studies. In this paper, a general purpose framework for bioimage management and annotations is proposed. Moreover, a simple-to-use information system has been developed to integrate clinical and diagnosis codes. The framework allows physicians (1) to integrate DICOM images from different platforms and (2) to report notes and highlights directly on images, thus offering, among the others, to query and compare similar clinical cases. This contribution is the result of a framework aimed to support oncologists in managing DICOM images and clinical data from different departments. Data integration is performed using a here-proposed XML-based module also utilized to trace temporal changes in image annotations.

Apicoaortic conduit and cerebral perfusion in mixed aortic valve disease: a computational analysis.

OBJECTIVES: The revival of the apicoaortic conduit has attracted new interest in this alternative treatment for severe aortic stenosis unsuitable for conventional valve replacement. However, doubts still exist about the perfusion of the epiaortic vessels after apicoaortic conduit implantation, especially when severe aortic stenosis is associated with aortic valve insufficiency. The aim of the study was to evaluate the perfusion of the epiaortic vessels (innominate artery, left carotid artery and left subclavian artery) in cases of mixed aortic valve disease before and after apicoaortic conduit implantation. METHODS: Starting from the data of a real patient with severe aortic stenosis and mild aortic insufficiency who underwent apicoaortic conduit implantation, we created a computational model where severe aortic valve stenosis was associated with different grades of aortic insufficiency (mild, medium and moderate). RESULTS: A total of six combinations were analysed. In all simulations, the more severe the concomitant aortic insufficiency, the more the flow through the epiaortic vessels was diminished. After apicoaortic conduit implantation, there was an absolute augmentation of the median output in each epiaortic vessel compared with the same combination of mixed aortic valve disease before implantation. Interestingly, retrograde flow from the conduit in the descending aorta was minimal and did not contribute to the improved output of the epiaortic vessels. CONCLUSIONS: The computational analysis suggested a protective effect, rather than steal phenomenon, of the apicoaortic conduit towards the cerebral perfusion, even in cases of mixed aortic valve disease.