Anatomic nomenclature and 3-dimensional regional model of the human ovary: call for a new paradigm.

The ovaries are the female gonads that are crucial for reproduction, steroid production, and overall health. Historically, the ovary was broadly divided into regions defined as the cortex, medulla, and hilum. This current nomenclature lacks specificity and fails to consider the significant anatomic variations in the ovary. Recent technological advances in imaging modalities and high-resolution omic analyses have brought about the need for revision of the existing definitions, which will facilitate the integration of generated data and enable the characterization of organ subanatomy and function at the cellular level. The creation of these high-resolution multimodal maps of the ovary will enhance collaboration and communication among disciplines and between clinicians and researchers. Beginning in March 2021, the Pediatric and Adolescent Gynecology Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development invited subject-matter experts to participate in a series of workshops and meetings to standardize ovarian nomenclature and define the organ's features. The goal was to develop a spatially defined and semantically consistent terminology of the ovary to support collaborative, team science-based endeavors aimed at generating reference atlases of the human ovary. The group recommended a standardized, 3-dimensional description of the ovary and an ontological approach to the subanatomy of the ovary and definition of follicles. This new greater precision in nomenclature and mapping will better reflect the ovary's heterogeneous composition and function, support the standardization of tissue collection, facilitate functional analyses, and enable clinical and research collaborations. The conceptualization process and outcomes of the effort, which spanned the better part of 2021 and early 2022, are introduced in this article. The institute and the workshop participants encourage researchers and clinicians to adopt the new systems in their everyday work to advance the overarching goal of improving human reproductive health.

A Computational Pipeline for Patient-Specific Prediction of the Postoperative Mitral Valve Functional State.

While mitral valve (MV) repair remains the preferred clinical option for mitral regurgitation (MR) treatment, long-term outcomes remain suboptimal and difficult to predict. Furthermore, pre-operative optimization is complicated by the heterogeneity of MR presentations and the multiplicity of potential repair configurations. In the present work, we established a patient-specific MV computational pipeline based strictly on standard-of-care pre-operative imaging data to quantitatively predict the post-repair MV functional state. First, we established human mitral valve chordae tendinae (MVCT) geometric characteristics obtained from five CT-imaged excised human hearts. From these data, we developed a finite-element model of the full patient-specific MV apparatus that included MVCT papillary muscle origins obtained from both the in vitro study and the pre-operative three-dimensional echocardiography images. To functionally tune the patient-specific MV mechanical behavior, we simulated pre-operative MV closure and iteratively updated the leaflet and MVCT prestrains to minimize the mismatch between the simulated and target end-systolic geometries. Using the resultant fully calibrated MV model, we simulated undersized ring annuloplasty (URA) by defining the annular geometry directly from the ring geometry. In three human cases, the postoperative geometries were predicted to 1 mm of the target, and the MV leaflet strain fields demonstrated close agreement with noninvasive strain estimation technique targets. Interestingly, our model predicted increased posterior leaflet tethering after URA in two recurrent patients, which is the likely driver of long-term MV repair failure. In summary, the present pipeline was able to predict postoperative outcomes from pre-operative clinical data alone. This approach can thus lay the foundation for optimal tailored surgical planning for more durable repair, as well as development of mitral valve digital twins.

The Hyperattenuating Crescent Sign Is Not Necessarily a Sign of Impending Aortic Aneurysm Rupture.

BACKGROUND: The "crescent sign" is a hyperattenuating crescent-shaped region on CT within the mural thrombus or wall of an aortic aneurysm. Although it has previously been associated with aneurysm instability or impending rupture, the literature is largely based on retrospective analyses of urgently repaired aneurysms. We strove to more rigorously assess the association between an isolated "crescent sign" and risk of impending aortic rupture. METHODS: Patients were identified by querying a single health system PACS database for radiology reports noting a crescent sign. Adult patients with a CT demonstrating a descending thoracic, thoracoabdominal, or abdominal aortic aneurysm and "crescent sign" between 2004 and 2019 were included, with exclusion of those showing definitive signs of aortic rupture on imaging. RESULTS: A total of 82 patients were identified. Aneurysm size was 7.1 ± 2.0 cm. Thirty patients had emergent or urgent repairs during their index admission (37%), 19 had elective repairs at a later date (23%), and 33 patients had no intervention due to either patient choice or prohibitive medical comorbidities (40%). Patients without intervention had a median follow up of 275 days before death or loss to follow up. In patients undergoing elective intervention, 6,968 patient-days elapsed between presentation and repair, with zero episodes of acute rupture (median 105 days). Patients undergoing elective repair had smaller aneurysms compared to those who underwent emergent/urgent repair (6.2 ± 1.3 vs. 7.7 ± 2.1 cm, P = 0.008). No surgical candidate with an aneurysm smaller than 8 cm ruptured. There were 31 patients with previous axial imaging within 2 years prior to presentation with a "crescent sign," with mean aneurysm growth rate of 0.85 ± 0.62 cm per 6 months [median 0.65, range 0-2.6]. Those with aneurysms sized below 5.5 cm displayed decreased aneurysm growth compared to patients with aneurysm's sized 5.5-6.5 cm or patients with aneurysms greater than 6.5 cm (0.12 vs. 0.64 vs. 1.16 cm per 6 months, P= 0.002). CONCLUSIONS: The finding of an isolated radiographic "crescent sign" without other signs of definitive aortic rupture (i.e., hemothorax, aortic wall disruption, retroperitoneal bleeding) is not necessarily an indicator of impending aortic rupture, but may be found in the setting of rapid aneurysm growth. Many factors, including other associated radiographic findings, aneurysm size and growth rate, and patient symptomatology, should guide aneurysm management in these patients. We found that patients with minimal symptoms, aneurysm sizes below 6.5 cm, and no further imaging findings of aneurysm instability, such as periaortic fat stranding, can be successfully managed with elective intervention after optimization of comorbid factors with no evidence of adverse outcomes.

Quantitative three-dimensional echocardiographic analysis of the bicuspid aortic valve and aortic root: A single modality approach.

BACKGROUND: Patients with bicuspid aortic valves (BAV) are heterogeneous with regard to patterns of root remodeling and valvular dysfunction. Two-dimensional echocardiography is the standard surveillance modality for patients with aortic valve dysfunction. However, ancillary computed tomography or magnetic resonance imaging is often necessary to characterize associated patterns of aortic root pathology. Conversely, the pairing of three-dimensional (3D) echocardiography with novel quantitative modeling techniques allows for a single modality description of the entire root complex. We sought to determine 3D aortic valve and root geometry with this quantitative approach. METHODS: Transesophageal real-time 3D echocardiography was performed in five patients with tricuspid aortic valves (TAV) and in five patients with BAV. No patient had evidence of valvular dysfunction or aortic root pathology. A customized image analysis protocol was used to assess 3D aortic annular, valvular, and root geometry. RESULTS: Annular, sinus and sinotubular junction diameters and areas were similar in both groups. Coaptation length and area were higher in the TAV group (7.25 ± 0.98 mm and 298 ± 118 mm2 , respectively) compared to the BAV group (5.67 ± 1.33 mm and 177 ± 43 mm2 ; P = .07 and P = .01). Cusp surface area to annular area, coaptation height, and the sub- and supravalvular tenting indices did not differ significantly between groups. CONCLUSIONS: Single modality 3D echocardiography-based modeling allows for a quantitative description of the aortic valve and root geometry. This technique together with novel indices will improve our understanding of normal and pathologic geometry in the BAV population and may help to identify geometric predictors of adverse remodeling and guide tailored surgical therapy.

Validation of semiautomated and locally resolved aortic wall thickness measurements from computed tomography.

OBJECTIVE: Aortic wall thickness (AWT) is important for anatomic description and biomechanical modeling of aneurysmal disease. However, no validated, noninvasive method for measuring AWT exists. We hypothesized that semiautomated image segmentation algorithms applied to computed tomography angiography (CTA) can accurately measure AWT. METHODS: Aortic samples from 10 patients undergoing open thoracoabdominal aneurysm repair were taken from sites of the proximal or distal anastomosis, or both, yielding 13 samples. Aortic specimens were fixed in formalin, embedded in paraffin, and sectioned. After staining with hematoxylin and eosin and Masson's trichrome, sections were digitally scanned and measured. Patients' preoperative CTA Digital Imaging and Communications in Medicine (DICOM; National Electrical Manufacturers Association, Rosslyn, Va) images were segmented into luminal, inner arterial, and outer arterial surfaces with custom algorithms using active contours, isoline contour detection, and texture analysis. AWT values derived from image data were compared with measurements of corresponding pathologic specimens. RESULTS: AWT determined by CTA averaged 2.33 ± 0.66 mm (range, 1.52-3.55 mm), and the AWT of pathologic specimens averaged 2.36 ± 0.75 mm (range, 1.51-4.16 mm). The percentage difference between pathologic specimens and CTA-determined AWT was 9.5% ± 4.1% (range, 1.8%-16.7%). The correlation between image-based measurements and pathologic measurements was high (R = 0.935). The 95% limits of agreement computed by Bland-Altman analysis fell within the range of -0.42 and 0.42 mm. CONCLUSIONS: Semiautomated analysis of CTA images can be used to accurately measure regional and patient-specific AWT, as validated using pathologic ex vivo human aortic specimens. Descriptions and reconstructions of aortic aneurysms that incorporate locally resolved wall thickness are feasible and may improve future attempts at biomechanical analyses.

Open-source graphical user interface for the creation of synthetic skeletons for medical image analysis.

Purpose: Deformable medial modeling is an inverse skeletonization approach to representing anatomy in medical images, which can be used for statistical shape analysis and assessment of patient-specific anatomical features such as locally varying thickness. It involves deforming a pre-defined synthetic skeleton, or template, to anatomical structures of the same class. The lack of software for creating such skeletons has been a limitation to more widespread use of deformable medial modeling. Therefore, the objective of this work is to present an open-source user interface (UI) for the creation of synthetic skeletons for a range of medial modeling applications in medical imaging. Approach: A UI for interactive design of synthetic skeletons was implemented in 3D Slicer, an open-source medical image analysis application. The steps in synthetic skeleton design include importation and skeletonization of a 3D segmentation, followed by interactive 3D point placement and triangulation of the medial surface such that the desired branching configuration of the anatomical structure's medial axis is achieved. Synthetic skeleton design was evaluated in five clinical applications. Compatibility of the synthetic skeletons with open-source software for deformable medial modeling was tested, and representational accuracy of the deformed medial models was evaluated. Results: Three users designed synthetic skeletons of anatomies with various topologies: the placenta, aortic root wall, mitral valve, cardiac ventricles, and the uterus. The skeletons were compatible with skeleton-first and boundary-first software for deformable medial modeling. The fitted medial models achieved good representational accuracy with respect to the 3D segmentations from which the synthetic skeletons were generated. Conclusions: Synthetic skeleton design has been a practical challenge in leveraging deformable medial modeling for new clinical applications. This work demonstrates an open-source UI for user-friendly design of synthetic skeletons for anatomies with a wide range of topologies.

Patient-Specific Quantitative In-Vivo Assessment of Human Mitral Valve Leaflet Strain Before and After MitraClip Repair.

PURPOSE: Mitral regurgitation (MR) is a highly prevalent and deadly cardiac disease characterized by improper mitral valve (MV) leaflet coaptation. Among the plethora of available treatment strategies, the MitraClip is an especially safe option, but optimizing its long-term efficacy remains an urgent challenge. METHODS: We applied our noninvasive image-based strain computation pipeline [1] to intraoperative transesophageal echocardiography datasets taken from ten patients undergoing MitraClip repair, spanning a range of MR etiologies and MitraClip configurations. We then analyzed MV leaflet strains before and after MitraClip implementation to develop a better understanding of (1) the pre-operative state of human regurgitant MV, and (2) the MitraClip's impact on the MV leaflet deformations. RESULTS: The MV pre-operative strain fields were highly variable, underscoring both the heterogeneity of the MR in the patient population and the need for patient-specific treatment approaches. Similarly, there were no consistent overall post-operative strain patterns, although the average A2 segment radial strain difference between pre- and post-operative states was consistently positive. In contrast, the post-operative strain fields were better correlated to their respective pre-operative strain fields than to the inter-patient post-operative strain fields. This quantitative result implies that the patient specific pre-operative state of the MV guides its post-operative deformation, which suggests that the post-operative state can be predicted using pre-operative data-derived modelling alone. CONCLUSIONS: The pre-operative MV leaflet strain patterns varied considerably across the range of MR disease states and after MitraClip repair. Despite large inter-patient heterogeneity, the post-operative deformation appears principally dictated by the pre-operative deformation state. This novel finding suggests that though the variation in MR functional state and MitraClip-induced deformation were substantial, the post-operative state can be predicted from the pre-operative data alone. This study suggests that, with use of larger patient cohort and corresponding long-term outcomes, quantitative predictive factors of MitraClip durability can be identified.

Strain estimation in aortic roots from 4D echocardiographic images using medial modeling and deformable registration.

Even though the central role of mechanics in the cardiovascular system is widely recognized, estimating mechanical deformation and strains in-vivo remains an ongoing practical challenge. Herein, we present a semi-automated framework to estimate strains from four-dimensional (4D) echocardiographic images and apply it to the aortic roots of patients with normal trileaflet aortic valves (TAV) and congenital bicuspid aortic valves (BAV). The method is based on fully nonlinear shell-based kinematics, which divides the strains into in-plane (shear and dilatational) and out-of-plane components. The results indicate that, even for size-matched non-aneurysmal aortic roots, BAV patients experience larger regional shear strains in their aortic roots. This elevated strains might be a contributing factor to the higher risk of aneurysm development in BAV patients. The proposed framework is openly available and applicable to any tubular structures.

Development of a semi-automated method for mitral valve modeling with medial axis representation using 3D ultrasound.

PURPOSE: Precise 3D modeling of the mitral valve has the potential to improve our understanding of valve morphology, particularly in the setting of mitral regurgitation (MR). Toward this goal, the authors have developed a user-initialized algorithm for reconstructing valve geometry from transesophageal 3D ultrasound (3D US) image data. METHODS: Semi-automated image analysis was performed on transesophageal 3D US images obtained from 14 subjects with MR ranging from trace to severe. Image analysis of the mitral valve at midsystole had two stages: user-initialized segmentation and 3D deformable modeling with continuous medial representation (cm-rep). Semi-automated segmentation began with user-identification of valve location in 2D projection images generated from 3D US data. The mitral leaflets were then automatically segmented in 3D using the level set method. Second, a bileaflet deformable medial model was fitted to the binary valve segmentation by Bayesian optimization. The resulting cm-rep provided a visual reconstruction of the mitral valve, from which localized measurements of valve morphology were automatically derived. The features extracted from the fitted cm-rep included annular area, annular circumference, annular height, intercommissural width, septolateral length, total tenting volume, and percent anterior tenting volume. These measurements were compared to those obtained by expert manual tracing. Regurgitant orifice area (ROA) measurements were compared to qualitative assessments of MR severity. The accuracy of valve shape representation with cm-rep was evaluated in terms of the Dice overlap between the fitted cm-rep and its target segmentation. RESULTS: The morphological features and anatomic ROA derived from semi-automated image analysis were consistent with manual tracing of 3D US image data and with qualitative assessments of MR severity made on clinical radiology. The fitted cm-reps accurately captured valve shape and demonstrated patient-specific differences in valve morphology among subjects with varying degrees of MR severity. Minimal variation in the Dice overlap and morphological measurements was observed when different cm-rep templates were used to initialize model fitting. CONCLUSIONS: This study demonstrates the use of deformable medial modeling for semi-automated 3D reconstruction of mitral valve geometry using transesophageal 3D US. The proposed algorithm provides a parametric geometrical representation of the mitral leaflets, which can be used to evaluate valve morphology in clinical ultrasound images.

Local aortic aneurysm wall expansion measured with automated image analysis.

BACKGROUND: Assessment of regional aortic wall deformation (RAWD) might better predict for abdominal aortic aneurysm (AAA) rupture than the maximal aortic diameter or growth rate. Using sequential computed tomography angiograms (CTAs), we developed a streamlined, semiautomated method of computing RAWD using deformable image registration (dirRAWD). METHODS: Paired sequential CTAs performed 1 to 2 years apart of 15 patients with AAAs of various shapes and sizes were selected. Using each patient's initial CTA, the luminal and aortic wall surfaces were segmented both manually and semiautomatically. Next, the same patient's follow-up CTA was aligned with the first using automated rigid image registration. Deformable image registration was then used to calculate the local aneurysm wall expansion between the sequential scans (dirRAWD). To measure technique accuracy, the deformable registration results were compared with the local displacement of anatomic landmarks (fiducial markers), such as the origin of the inferior mesenteric artery and/or aortic wall calcifications. Additionally, for each patient, the maximal RAWD was manually measured for each aneurysm and was compared with the dirRAWD at the same location. RESULTS: The technique was successful in all patients. The mean landmark displacement error was 0.59 ± 0.93 mm with no difference between true landmark displacement and deformable registration landmark displacement by Wilcoxon rank sum test (P = .39). The absolute difference between the manually measured maximal RAWD and dirRAWD was 0.27 ± 0.23 mm, with a relative difference of 7.9% and no difference using the Wilcoxon rank sum test (P = .69). No differences were found in the maximal dirRAWD when derived using a purely manual AAA segmentation compared with using semiautomated AAA segmentation (P = .55). CONCLUSIONS: We found accurate and automated RAWD measurements were feasible with clinically insignificant errors. Using semiautomated AAA segmentations for deformable image registration methods did not alter maximal dirRAWD accuracy compared with using manual AAA segmentations. Future work will compare dirRAWD with finite element analysis-derived regional wall stress and determine whether dirRAWD might serve as an independent predictor of rupture risk.

Patient-Specific Quantification of Normal and Bicuspid Aortic Valve Leaflet Deformations from Clinically Derived Images.

The clinical benefit of patient-specific modeling of heart valve disease remains an unrealized goal, often a result of our limited understanding of the in vivo milieu. This is particularly true in assessing bicuspid aortic valve (BAV) disease, the most common cardiac congenital defect in humans, which leads to premature and severe aortic stenosis or insufficiency (AS/AI). However, assessment of BAV risk for AS/AI on a patient-specific basis is hampered by the substantial degree of anatomic and functional variations that remain largely unknown. The present study was undertaken to utilize a noninvasive computational pipeline ( https://doi.org/10.1002/cnm.3142 ) that directly yields local heart valve leaflet deformation information using patient-specific real-time three-dimensional echocardiographic imaging (rt-3DE) data. Imaging data was collected for patients with normal tricuspid aortic valve (TAV, [Formula: see text]) and those with BAV ([Formula: see text] with fused left and right coronary leaflets and [Formula: see text] with fused right and non-coronary leaflets), from which the medial surface of each leaflet was extracted. The resulting deformation analysis resulted in, for the first time, quantified differences between the in vivo functional deformations of the TAV and BAV leaflets. Our approach was able to capture the complex, heterogeneous surface deformation fields in both TAV and BAV leaflets. We were able to identify and quantify differences in stretch patterns between leaflet types, and found in particular that stretches experienced by BAV leaflets during closure differ from those of TAV leaflets in terms of both heterogeneity as well as overall magnitude. Deformation is a key parameter in the clinical assessment of valvular function, and serves as a direct means to determine regional variations in structure and function. This study is an essential step toward patient-specific assessment of BAV based on correlating leaflet deformation and AS/AI progression, as it provides a means for assessing patient-specific stretch patterns.

Quantitative in vivo assessment of human mitral valve coaptation area after undersized ring annuloplasty repair for ischemic mitral regurgitation.

Objectives: Long-term outcomes of mitral valve repair procedures to correct ischemic mitral regurgitation remain unpredictable, due to an incomplete understanding of the disease process and the inability to reliably quantify the coaptation zone using echocardiography. Our objective was to quantify patient-specific mitral valve coaptation behavior from clinical echocardiographic images obtained before and after repair to assess coaptation restoration and its relationship with long-term repair durability. Methods: To circumvent the limitations of clinical imaging, we applied a simulation-based shape-matching technique that allowed high-fidelity reconstructions of the complete mitral valve in the systolic configuration. We then applied this method to an extant database of human regurgitant mitral valves before and after undersized ring annuloplasty to quantify the effect of the repair on mitral valve coaptation geometry. Results: Our method was able to successfully resolve the coaptation zone into distinct contacting and redundant regions. Results indicated that in patients whose regurgitation recurred 6 months postrepair, both the contacting and redundant regions were larger immediately postrepair compared with patients with no recurrence (P < .05), even when normalized to account for generally larger recurrent valves. Conclusions: Although increasing leaflet coaptation area is an intuitively obvious way to improve long-term repair durability, this study has implied that this may not be a reliable target for mitral valve repair. This study underscores the importance of a rigorous understanding of the consequences of repair techniques on mitral valve behavior, as well as a patient-specific approach to ischemic mitral regurgitation treatment within the context of mitral valve and left ventricle function.

Fully Automated 3D Segmentation and Diffeomorphic Medial Modeling of the Left Ventricle Mitral Valve Complex in Ischemic Mitral Regurgitation.

There is an urgent unmet need to develop a fully-automated image-based left ventricle mitral valve analysis tool to support surgical decision making for ischemic mitral regurgitation patients. This requires an automated tool for segmentation and modeling of the left ventricle and mitral valve from immediate pre-operative 3D transesophageal echocardiography. Previous works have presented methods for semi-automatically segmenting and modeling the mitral valve, but do not include the left ventricle and do not avoid self-intersection of the mitral valve leaflets during shape modeling. In this study, we develop and validate a fully automated algorithm for segmentation and shape modeling of the left ventricular mitral valve complex from pre-operative 3D transesophageal echocardiography. We performed a 3-fold nested cross validation study on two datasets from separate institutions to evaluate automated segmentations generated by nnU-net with the expert manual segmentation which yielded average overall Dice scores of 0.82±0.03 (set A), 0.87±0.08 (set B) respectively. A deformable medial template was subsequently fitted to the segmentation to generate shape models. Comparison of shape models to the manual and automatically generated segmentations resulted in an average Dice score of 0.93-0.94 and 0.75-0.81 for the left ventricle and mitral valve, respectively. This is a substantial step towards automatically analyzing the left ventricle mitral valve complex in the operating room.

Dynamic Annular Modeling of the Unrepaired Complete Atrioventricular Canal Annulus.

BACKGROUND: Repair of complete atrioventricular canal (CAVC) is often complicated by atrioventricular valve regurgitation, particularly of the left-sided valve. Understanding the 3-dimensional (3D) structure of the atrioventricular canal annulus before repair may help to inform optimized repair. However, the 3D shape and movement of the CAVC annulus has been neither quantified nor rigorously compared with a normal mitral valve annulus. METHODS: The complete annuli of 43 patients with CAVC were modeled in 4 cardiac phases using transthoracic 3D echocardiograms and custom code. The annular structure was compared with the annuli of 20 normal pediatric mitral valves using 3D metrics and statistical shape analysis (Procrustes analysis). RESULTS: The unrepaired CAVC annulus varied in shape significantly throughout the cardiac cycle. Procrustes analysis visually demonstrated that the average normalized CAVC annular shape is more planar than the normal mitral annulus. Quantitatively, the annular height-to-valve width ratio of the native left CAVC atrioventricular valve was significantly lower than that of a normal mitral valve in all systolic phases (P < .001). CONCLUSIONS: The left half of the CAVC annulus is more planar than that of a normal mitral valve with an annular height-to-valve width ratio similar to dysfunctional mitral valves. Given the known importance of annular shape to mitral valve function, further exploration of the association of 3D structure to valve function in CAVC is warranted.

Increased wall stress of saccular versus fusiform aneurysms of the descending thoracic aorta.

BACKGROUND: Repair of fusiform descending thoracic aortic aneurysms (DTAs) is indicated when aneurysmal diameter exceeds a certain threshold; however, diameter-related indications for repair of saccular DTA are less well established. METHODS: Human subjects with fusiform (n = 17) and saccular (n = 17) DTAs who underwent computed tomographic angiography were identified. Patients with aneurysms related to connective tissue disease were excluded. The thoracic aorta was segmented, reconstructed, and triangulated to create a mesh. Finite element analysis was performed using a pressure load of 120 mm Hg and a uniform aortic wall thickness of 3.2 mm to compare the pressure-induced wall stress of fusiform and saccular DTAs. RESULTS: The mean maximum diameter of the fusiform DTAs (6.0 ± 1.5 cm) was significantly greater (p = 0.006) than that of the saccular DTAs (4.4 ± 1.8 cm). However, mean peak wall stress of the fusiform DTAs (0.33 ± 0.15 MPa) was equivalent to that of the saccular DTAs (0.30 ± 0.14 MPa), as found by using an equivalence threshold of 0.15 MPa. The mean normalized wall stress (peak wall stress divided by maximum aneurysm radius) of the saccular DTAs was greater than that of the fusiform DTAs (0.16 ± 0.09 MPa/cm vs. 0.11 ± 0.03 MPa/cm, p = 0.035). CONCLUSIONS: The normalized wall stress for saccular DTA is greater than that for fusiform DTA, indicating that geometric factors such as aneurysm shape influence wall stress. These results suggest that saccular aneurysms may be more prone to rupture than fusiform aneurysms of similar diameter, provide a theoretical rationale for the repair of saccular DTAs at a smaller diameter, and suggest investigation of the role of biomechanical modeling in surgical decision making is warranted.

Multimodal image analysis and subvalvular dynamics in ischemic mitral regurgitation.

Background: The exact geometric pathogenesis of leaflet tethering in ischemic mitral regurgitation (IMR) and the relative contribution of each component of the mitral valve complex (MVC) remain largely unknown. In this study, we sought to further elucidate mitral valve (MV) leaflet remodeling and papillary muscle dynamics in an ovine model of IMR with magnetic resonance imaging (MRI) and 3-dimensional echocardiography (3DE). Methods: Multimodal imaging combining 3DE and MRI was used to analyze the MVC at baseline, 30 minutes post-myocardial infarction (MI), and 12 weeks post-MI in ovine IMR models. Advanced 3D imaging software was used to trace the MVC from each modality, and the tracings were verified against resected specimens. Results: 3DE MV remodeling was regionally heterogenous and observed primarily in the anterior leaflet, with significant increases in surface area, especially in A2 and A3. The posterior leaflet was significantly shortened in P2 and P3. Mean posteromedial papillary muscle (PMPM) volume was decreased from 1.9 ± 0.2 cm3 at baseline to 0.9 ± 0.3 cm3 at 12 weeks post-MI (P < .05). At 12 weeks post-MI, the PMPM was predominately displaced horizontally and outward along the intercommissural axis with minor apical displacement. The subvalvular contribution to tethering is a combination of unilateral movement, outward displacement, and degeneration of the PMPM. These findings have led to a proposed new framework for characterizing PMPM dynamics in IMR. Conclusions: This study provides new insights into the complex interrelated and regionally heterogenous valvular and subvalvular mechanisms involved in the geometric pathogenesis of IMR tethering.

Pre-surgical Prediction of Ischemic Mitral Regurgitation Recurrence Using In Vivo Mitral Valve Leaflet Strains.

Ischemic mitral regurgitation (IMR) is a prevalent cardiac disease associated with substantial morbidity and mortality. Contemporary surgical treatments continue to have limited long-term success, in part due to the complex and multi-factorial nature of IMR. There is thus a need to better understand IMR etiology to guide optimal patient specific treatments. Herein, we applied our finite element-based shape-matching technique to non-invasively estimate peak systolic leaflet strains in human mitral valves (MVs) from in-vivo 3D echocardiographic images taken immediately prior to and post-annuloplasty repair. From a total of 21 MVs, we found statistically significant differences in pre-surgical MV size, shape, and deformation patterns between the with and without IMR recurrence patient groups at 6 months post-surgery. Recurrent MVs had significantly less compressive circumferential strains in the anterior commissure region compared to the recurrent MVs (p = 0.0223) and were significantly larger. A logistic regression analysis revealed that average pre-surgical circumferential leaflet strain in the Carpentier A1 region independently predicted 6-month recurrence of IMR (optimal cutoff value - 18%, p = 0.0362). Collectively, these results suggest greater disease progression in the recurrent group and underscore the highly patient-specific nature of IMR. Importantly, the ability to identify such factors pre-surgically could be used to guide optimal treatment methods to reduce post-surgical IMR recurrence.

Dynamic Volumetric Assessment of the Aortic Root: The Influence of Bicuspid Aortic Valve Competence.

BACKGROUND: Aortic root evaluation is conventionally based on 2-dimensional measurements at a single phase of the cardiac cycle. This work presents an image analysis method for assessing dynamic 3-dimensional changes in the aortic root of minimally calcified bicuspid aortic valves (BAVs) with and without moderate to severe aortic regurgitation. METHODS: The aortic root was segmented over the full cardiac cycle in 3-dimensional transesophageal echocardiographic images acquired from 19 patients with minimally calcified BAVs and from 16 patients with physiologically normal tricuspid aortic valves (TAVs). The size and dynamics of the aortic root were assessed using the following image-derived measurements: absolute mean root volume and mean area at the level of the ventriculoaortic junction, sinuses of Valsalva, and sinotubular junction, as well as normalized root volume change and normalized area change of the ventriculoaortic junction, sinuses of Valsalva, and sinotubular junction over the cardiac cycle. RESULTS: Normalized volume change over the cardiac cycle was significantly greater in BAV roots with moderate to severe regurgitation than in normal TAV roots and in BAV roots with no or mild regurgitation. Aortic root dynamics were most significantly different at the mid-level of the sinuses of Valsalva in BAVs with moderate to severe regurgitation than in competent TAVs and BAVs. CONCLUSIONS: Echocardiographic reconstruction of the aortic root demonstrates significant differences in dynamics of BAV roots with moderate to severe regurgitation relative to physiologically normal TAVs and competent BAVs. This finding may have implications for risk of future dilatation, dissection, or rupture, which warrant further investigation.

In vivo noninvasive temperature measurement by B-mode ultrasound imaging.

OBJECTIVE: This study investigated the use of ultrasound image analysis in quantifying temperature changes in tissue, both ex vivo and in vivo, undergoing local hyperthermia. METHODS: Temperature estimation is based on the thermal dependence of the acoustic speed in a heated medium. Because standard beam-forming algorithms on clinical ultrasound scanners assume a constant acoustic speed, temperature-induced changes in acoustic speed produce apparent scatterer displacements in B-mode images. A cross-correlation algorithm computes axial speckle pattern displacement in B-mode images of heated tissue, and a theoretically derived temperature-displacement relationship is used to generate maps of temperature changes within the tissue. Validation experiments were performed on excised tissue and in murine subjects, wherein low-intensity ultrasound was used to thermally treat tissue for several minutes. Diagnostic temperature estimation was performed using a linear array ultrasound transducer, while a fine-wire thermocouple invasively measured the temperature change. RESULTS: Pearson correlations ± SDs between the image-derived and thermocouple-measured temperature changes were R² = 0.923 ± 0.066 for 4 thermal treatments of excised bovine muscle tissue and R² = 0.917 ± 0.036 for 4 treatments of in vivo murine tumor tissue. The average differences between the two temperature measurements were 0.87°C ± 0.72°C for ex vivo studies and 0.97°C ± 0.55°C for in vivo studies. Maps of the temperature change distribution in tissue were generated for each experiment. CONCLUSIONS: This study demonstrates that velocimetric measurement on B-mode images has potential to assess temperature changes noninvasively in clinical applications.

Intraoperative post-annuloplasty three-dimensional valve analysis does not predict recurrent ischemic mitral regurgitation.

BACKGROUND: High ischemic mitral regurgitation (IMR) recurrence rates continue to plague IMR repair with undersized ring annuloplasty. We have previously shown that pre-repair three-dimensional echocardiography (3DE) analysis is highly predictive of IMR recurrence. The objective of this study was to determine the quantitative change in 3DE annular and leaflet tethering parameters immediately after repair and to determine if intraoperative post-repair 3DE parameters would be able to predict IMR recurrence 6 months after repair. METHODS: Intraoperative pre- and post-repair transesophageal real-time 3DE was performed in 35 patients undergoing undersized ring annuloplasty for IMR. An advanced modeling algorhythm was used to assess 3D annular geometry and regional leaflet tethering. IMR recurrence (≥ grade 2) was assessed with transthoracic echocardiography 6 months after repair. RESULTS: Annuloplasty significantly reduced septolateral diameter, commissural width, annular area, and tethering volume and significantly increased all segmental tethering angles (except A2). Intraoperative post-repair annular geometry and leaflet tethering did not differ significantly between patients with recurrent IMR (n = 9) and patients with non-recurrent IMR (n = 26). No intraoperative post-repair predictors of IMR recurrence could be identified. CONCLUSIONS: Undersized ring annuloplasty changes mitral geometry acutely, exacerbates leaflet tethering, and generally fixes IMR acutely, but it does not always fix the delicate underlying chronic problem of continued left ventricular dilatation and remodeling. This may explain why pre-repair 3D valve geometry (which reflects chronic left ventricular remodeling) is highly predictive of recurrent IMR, whereas immediate post-repair 3D valve geometry (which does not completely reflect chronic left ventricular remodeling anymore) is not.