Assessment of revascularization impact on microvascular oxygenation and perfusion using spatial frequency domain imaging.

The microvasculature (with vessels <100 µm in diameter) plays a crucial role in tissue oxygenation, perfusion and wound healing in the lower limb. While this holds clinical significance, microvasculature evaluation in the limbs is not a standard practice. Surgical interventions focus on reestablishing blood flow in larger vessels affected by the peripheral artery disease (PAD). Nevertheless, the impact of revascularization on tissue oxygenation and perfusion in severe microvascular disease (MVD) is still unknown. We present the cases of two patients who underwent surgical revascularization for peripheral blood flow with different outcomes. Patient A had PAD, while B had PAD, severe MVD and a non-healing wound. Although both showed improvements in ankle-brachial index post-op, spatial frequency domain imaging metrics (which measure microvascular oxygenation and perfusion) remained unchanged in B, indicating a potential gap in assessing the surgical efficacy in MVD using ankle brachial index and emphasizing microcirculation evaluation in optimizing wound healing outcomes.

Stratification of Microvascular Disease Severity in the Foot Using Spatial Frequency Domain Imaging.

BACKGROUND: Microvascular disease (MVD) describes systemic changes in the small vessels (~100 um diameter) that impair tissue oxygenation and perfusion. MVD is a common but poorly monitored complication of diabetes. Recent studies have demonstrated that MVD: (i) is an independent risk factor for ulceration and amputation and (ii) increases risk of adverse limb outcomes synergistically with PAD. Despite the clinical relevance of MVD, microvascular evaluation is not standard in a vascular assessment. METHODS: We evaluated 299 limbs from 153 patients seen clinically for possible lower extremity PAD. The patients were assessed by ankle brachial index (ABI), toe brachial index (TBI), and spatial frequency domain imaging (SFDI). These measurements were evaluated and compared to patient MVD status, defined by clinical diagnoses of (in ascending order of severity) no diabetes; diabetes; diabetes + neuropathy; diabetes + neuropathy + retinopathy. RESULTS: SFDI-derived parameters HbT1 and StO2 were significantly different across the MVD groups (P < .001). A logistic regression model based on HbT1 and StO2 differentiated limbs with severe MVD (diabetes+neuropathy+retinopathy) from the larger group of limbs from patients with only diabetes (P = .001, area under the curve = 0.844). Neither ABI nor TBI significantly differentiated these populations. CONCLUSIONS: Standard assessment of PAD using ABI and TBI are inadequate for detecting MVD in at-risk populations. SFDI-defined HbT1 and StO2 are promising tools for evaluating MVD. Prospective studies with wound-based outcomes would be useful to further evaluate the role MVD assessment could play in routine clinical evaluation of patients at risk for lower extremity complications.

Integration of polarized spatial frequency domain imaging (pSFDI) with a biaxial mechanical testing system for quantification of load-dependent collagen architecture in soft collagenous tissues.

Collagen fiber networks provide the structural strength of tissues, such as tendons, skin and arteries. Quantifying the fiber architecture in response to mechanical loads is essential towards a better understanding of the tissue-level mechanical behaviors, especially in assessing disease-driven functional changes. To enable novel investigations into these load-dependent fiber structures, a polarized spatial frequency domain imaging (pSFDI) device was developed and, for the first time, integrated with a biaxial mechanical testing system. The integrated instrument is capable of a wide-field quantification of the fiber orientation and the degree of optical anisotropy (DOA), representing the local degree of fiber alignment. The opto-mechanical instrument''s performance was assessed through uniaxial loading on tendon tissues with known collagen fiber microstructures. Our results revealed that the bulk fiber orientation angle of the tendon tissue changed minimally with loading (median ± 0.5*IQR of 52.7° ± 3.3° and 51.9° ± 3.3° under 0 and 3% longitudinal strains, respectively), whereas on a micro-scale, the fibers became better aligned with the direction of loading: the DOA (mean ± SD) increased from 0.149 ± 0.032 to 0.198 ± 0.056 under 0 and 3% longitudinal strains, respectively, p < 0.001. The integrated instrument was further applied to study two representative mitral valve anterior leaflet (MVAL) tissues subjected to various biaxial loads. The fiber orientations within these representative MVAL tissue specimens demonstrated noticeable heterogeneity, with the local fiber orientations dependent upon the sample, the spatial and transmural locations, and the applied loading. Our results also showed that fibers were generally better aligned under equibiaxial (DOA = 0.089 ± 0.036) and circumferentially-dominant loading (DOA = 0.086 ± 0.037) than under the radially-dominant loading (DOA = 0.077 ± 0.034), indicating circumferential predisposition. These novel findings exemplify a deeper understanding of the load-dependent collagen fiber microstructures obtained through the use of the integrated opto-mechanical instrument. STATEMENT OF SIGNIFICANCE: In this study, a novel quantitative opto-mechanical system was developed by combining a polarized Spatial Frequency Domain Imaging (pSFDI) device with a biaxial mechanical tester. The integrated system was used to quantify the load-dependent collagen fiber microstructures in representative tendon and mitral valve anterior leaflet (MVAL) tissues. Our results revealed that MVAL's fiber architectures exhibited load-dependent spatial and transmural heterogeneities, suggesting further microstructural complexity than previously reported in heart valve tissues. These novel findings were possible through the system's ability to, for the first time, capture the load-dependent collagen architecture in the mitral valve anterior leaflet tissue over a wide field of view (e.g., 10 × 10 mm for the MVAL tissue specimens). Such capabilities afford unique future opportunities to improve patient outcomes through concurrent mechanical and microstructural assessments of healthy and diseased tissues in conditions such as heart valve regurgitation and calcification.

Load-dependent collagen fiber architecture data of representative bovine tendon and mitral valve anterior leaflet tissues as quantified by an integrated opto-mechanical system.

The data presented in this article provide load-dependent collagen fiber architecture (CFA) of one representative bovine tendon tissue sample and two representative porcine mitral valve anterior leaflet tissues, and they are stored in a MATLAB MAT-file format. Each dataset contains: (i) the number of pixel points, (ii) the array of pixel's x- and y-coordinates, (iii) the three acquired pixel intensity arrays, and (iv) the Delaunay triangulation for visualization purpose. This dataset is associated with a companion journal article, which can be consulted for further information about the methodology, results, and discussion of the opto-mechanical characterization of the tissue's CFA's (Jett et al. [1]).

A Pilot Study on Linking Tissue Mechanics with Load-Dependent Collagen Microstructures in Porcine Tricuspid Valve Leaflets.

The tricuspid valve (TV) is composed of three leaflets that coapt during systole to prevent deoxygenated blood from re-entering the right atrium. The connection between the TV leaflets' microstructure and the tissue-level mechanical responses has yet to be fully understood in the TV biomechanics society. This pilot study sought to examine the load-dependent collagen fiber architecture of the three TV leaflets, by employing a multiscale, combined experimental approach that utilizes tissue-level biaxial mechanical characterizations, micro-level collagen fiber quantification, and histological analysis. Our results showed that the three TV leaflets displayed greater extensibility in the tissues' radial direction than in the circumferential direction, consistently under different applied biaxial tensions. Additionally, collagen fibers reoriented towards the direction of the larger applied load, with the largest changes in the alignment of the collagen fibers under radially-dominant loading. Moreover, collagen fibers in the belly region of the TV leaflets were found to experience greater reorientations compared to the tissue region closer to the TV annulus. Furthermore, histological examinations of the TV leaflets displayed significant regional variation in constituent mass fraction, highlighting the heterogeneous collagen microstructure. The combined experimental approach presented in this work enables the connection of tissue mechanics, collagen fiber microstructure, and morphology for the TV leaflets. This experimental methodology also provides a new research platform for future developments, such as multiscale models for the TVs, and the design of bioprosthetic heart valves that could better mimic the mechanical, microstructural, and morphological characteristics of the native tricuspid valve leaflets.

Regional biaxial mechanical data of the mitral and tricuspid valve anterior leaflets.

The collective data associated with this article presents the biaxial mechanical behavior for six smaller, delimited regions of the mitral valve and tricuspid valve anterior leaflets. Each data set consists of five columns of data, specifically: (i) biaxial testing protocol ID, (ii) circumferential stretch, (iii) radial stretch, (iv) circumferential membrane tension, and (v) radial membrane tension. For further elaboration regarding methodologies or results of the biaxial mechanical characterization please refer to the companion article Laurence, 2019.

An investigation of regional variations in the biaxial mechanical properties and stress relaxation behaviors of porcine atrioventricular heart valve leaflets.

The facilitation of proper blood flow through the heart depends on proper function of heart valve components, and alterations to any component can lead to heart disease or failure. Comprehension of these valvular diseases is reliant on thorough characterization of healthy heart valve structures for use in computational models. Previously, computational models have treated these leaflet structures as a structurally and mechanically homogenous material, which may not be an accurate description of leaflet mechanical response. In this study, we aimed to characterize the mechanics of the heart valve leaflet as a structurally heterogenous material. Specifically, porcine mitral valve and tricuspid valve anterior leaflets were sectioned into six regions and biaxial mechanical tests with various loading ratios and stress-relaxation test were performed on each regional tissue sample. Three main findings from this study were summarized as follows: (i) the central regions of the leaflet had a more anisotropic nature than edge regions, (ii) the mitral valve anterior leaflet was more extensible in regions closer to the annulus, and (iii) there was variance in the stress-relaxation behavior among all six regions, with mitral valve leaflet tissue regions exhibiting a greater decay than the tricuspid valve regions. This study presents a novel investigation of the regional variations in the heart valve biomechanics that has not been comprehensively examined. Our results thus allow for a refinement of computational models for more accurately predicting diseased or surgically-intervened condition, where tissue heterogeneity plays an essential role in the heart valve function.

Biaxial mechanical data of porcine atrioventricular valve leaflets.

This dataset contains the anisotropic tissue responses of porcine atrioventricular valve leaflets to force-controlled biaxial mechanical testing. The set includes the first Piola-Kirchhoff Stress and the specimen stretches (λ) in both circumferential and radial tissue directions (C and R, respectively) for the mitral valve anterior and posterior leaflets (MVAL and MVPL), and the tricuspid valve anterior, posterior, and septal leaflets (TVAL, TVPL, and TVSL) from six porcine hearts at five separate force-controlled biaxial loading protocols. This dataset is associated with a companion journal article, which can be consulted for further information about the methodology, results, and discussion of this biaxial mechanical testing (Jett et al., in press) [1].

An investigation of the anisotropic mechanical properties and anatomical structure of porcine atrioventricular heart valves.

Valvular heart diseases are complex disorders, varying in pathophysiological mechanism and affected valve components. Understanding the effects of these diseases on valve functionality requires a thorough characterization of the mechanics and structure of the healthy heart valves. In this study, we performed biaxial mechanical experiments with extensive testing protocols to examine the mechanical behaviors of the mitral valve and tricuspid valve leaflets. We also investigated the effect of loading rate, testing temperatures, species (porcine versus ovine hearts), and age (juvenile vs adult ovine hearts) on the mechanical responses of the leaflet tissues. In addition, we evaluated the structure of chordae tendineae within each valve and performed histological analysis on each atrioventricular leaflet. We found all tissues displayed a characteristic nonlinear anisotropic mechanical response, with radial stretches on average 30.7% higher than circumferential stretches under equibiaxial physiological loading. Tissue mechanical responses showed consistent mechanical stiffening in response to increased loading rate and minor temperature dependence in all five atrioventricular heart valve leaflets. Moreover, our anatomical study revealed similar chordae quantities in the porcine mitral (30.5 ±â€¯1.43 chords) and tricuspid valves (35.3 ±â€¯2.45 chords) but significantly more chordae in the porcine than the ovine valves (p < 0.010). Our histological analyses quantified the relative thicknesses of the four distinct morphological layers in each leaflet. This study provides a comprehensive database of the mechanics and structure of the atrioventricular valves, which will be beneficial to development of subject-specific atrioventricular valve constitutive models and toward multi-scale biomechanical investigations of heart valve function to improve valvular disease treatments.