Biology subjects

McElhinney, D. B.

Publications and source records attributed to McElhinney, D. B..

3 recordsLinked to original sources

bioRxiv2024

Assessing the Impact of Valve Sizing and Orientation on Bioprosthetic Pulmonary Valve Hemodynamics Using In Vitro 4D-Flow MRI

PurposePulmonary valve replacement (PVR) using bioprosthetic valves is a common procedure performed in patients with repaired Tetralogy of Fallot and other conditions, but these valves frequently become dysfunctional within 15 years of implantation. Since PVR is often performed in adolescence, valves are typically oversized to account for somatic growth. However, the contribution of oversizing to early valve failure are not clearly understood. The purpose of this study was to explore the impact of valve sizing and orientation on local hemodynamics and valve performance. MethodsDifferent valve sizes were represented by changing the cardiac output through a 25 mm bioprosthetic valve implanted in an idealized 3D-printed model of the right ventricular outflow tract (RVOT). The local hemodynamics at three valve sizes and two valve orientations were assessed using 4D-Flow MRI and high-speed camera imaging. ResultsNoticeable differences in jet asymmetry, the amount of recirculation, leaflet opening patterns, as well as the size and location of reversed flow regions were observed with varying valve sizes. Rotation of the valve resulted in drastic differences in reversed flow regions, but not forward flow. ConclusionFlow features observed in the oversized valve in this study have previously been correlated with calcification, hemolysis, and leaflet fatigue. Therefore, valve oversizing can negatively impact local hemodynamics and leaflet performance.

bioengineering↗

bioRxiv2023

Hemodynamics in Patients with Aortic Coarctation: A Comparison of in vivo 4D-Flow MRI and FSI Simulation

The analysis of quantitative hemodynamics provides information for the diagnosis and treatment planning in patients with aortic coarctation (CoA). Patient-specific computational fluid dynamics (CFD) simulations reveal detailed hemodynamic information, but their agreement with the clinical standard 4D-Flow magnetic resonance imaging (MRI) needs to be characterized. This work directly compares in vivo CFD fluid-structure interaction (FSI) simulations against 4D-Flow MRI in patients with CoA (N=5). 4D-Flow MRI-derived flow waveforms and cuff blood pressure measurements were used to tune the boundary conditions for the FSI simulations. Flow rates from 4D-Flow MRI and FSI were compared at cross-sections in the ascending aorta (AAo), CoA and descending aorta (DAo). Qualitative comparisons showed an overall agreement of flow patterns in the aorta between the two methods. The R2 values for the flow waveforms in the AAo, CoA, and DAo were 0.97, 0.84 and 0.81 respectively, representing a strong correlation between 4DFlow MRI measurements and FSI results. This work characterizes the use of patient-specific FSI simulations in quantifying and analyzing CoA hemodynamics to inform CoA treatment planning.

bioengineering↗

bioRxiv2020

Quantitative LCMS for ceramides/dihydroceramides: pregnancy baseline biomarkers and potential metabolic messengers

Ceramides and dihydroceramides are sphingolipids that present in abundance at the cellular membrane of eukaryotes. Although their metabolic dysregulation has been implicated in many diseases, our knowledge about circulating ceramide changes during the pregnancy remains limited. In this study, we present the development and validation of a high-throughput liquid chromatography-tandem mass spectrometric (LC/MS/MS) method for simultaneous quantification of 16 ceramides and 10 dihydroceramides in human serum within 5 mins by using stable isotope-labeled ceramides as internal standards (ISs). This method employs a protein precipitation method for high throughput sample preparation, reverse phase isocratic elusion for chromatographic separation, and Multiple Reaction Monitoring (MRM) for mass spectrometric detection. To qualify for clinical applications, our assay was validated against the FDA guidelines: the Lower Limit of Quantitation (LLOQ as low as 1 nM), linearity (R2>0.99), precision (Coefficient of Variation<15%), accuracy (Percent Error<15%), extraction recovery (>90%), stability (>85%), and carryover (<0.1%). With enhanced sensitivity and specificity from this method, we have, for the first time, determined the serological levels of ceramides and dihydroceramides to reveal unique temporal gestational patterns. Our approach could have value in providing insights into disorders of pregnancy.

biochemistry↗