Vascular Remodeling During Late-Gestation Pregnancy: An In-Vitro Assessment of the Murine Ascending Thoracic Aorta.

Maternal mortality due to cardiovascular disease is a rising concern in the U.S. Pregnancy triggers changes in the circulatory system, potentially influencing the structure of the central vasculature. Evidence suggests a link between a woman's pregnancy history and future cardiovascular health, but our understanding remains limited. To fill this gap, we examined the passive mechanics of the murine ascending thoracic aorta during late gestation. By performing biaxial mechanical testing on the ascending aorta, we were able to characterize the mechanical properties of both control and late-gestation tissues. By examining mechanical, structural, and geometric properties, we confirmed that remodeling of the aortic wall occurred. Morphological and mechanical properties of the tissue indicated an outward expansion of the tissue, as reflected in changes in wall thickness (∼12% increase) and luminal diameter (∼6% increase) at its physiologically loaded state in the pregnant group. With these geometric adaptations and despite increased hemodynamic loads, pregnancy did not induce significant changes in the tensile wall stress at the similar physiological pressure levels of the pregnant and control tissues. The alterations also included reduced intrinsic stiffness in the circumferential direction (∼18%) and reduced structural stiffness (∼26%) in the pregnant group. The observed vascular remodeling maintained the elastic stored energy of the aortic wall under systolic loads, indicating preservation of vascular function. Data from our study of pregnancy-related vascular remodeling will provide valuable insights for future investigations of maternal cardiovascular health.

Quantitative Assessment Characteristics of Small Pulmonary Vessel Remodelling in Populations at High Risk for COPD and Smokers Using Low-Dose CT.

Purpose: To explore the morphological alterations in small pulmonary vessels in populations at high risk for chronic obstructive pulmonary disease (COPD) and smokers based on multiple computed tomography (CT) quantitative parameters. Patients and Methods: A total of 1969 Three Major Chest Diseases Screening Study participants with available demographic data and smoking history who underwent low-dose chest CT from 2018 to 2020 were included. All subjects were divided into normal, high risk for COPD, and COPD groups according to their pulmonary function test (PFT) results. Furthermore, the three groups were further subdivided into never-smokers, current smokers, and former smokers subgroups according to their smoking history. Quantitative parameters, such as the number, area at 6 mm~24 mm subpleura and volume of small pulmonary vessels, were extracted by computer software. Differences in small pulmonary vessel parameters among the groups were compared using two-way ANOVA. Results: The number, area at 6 mm~24 mm subpleura and volume of small pulmonary vessels in the group at high risk for COPD were lower than those in the normal group (P<0.05). The number, area at 6 mm~24 mm subpleura and volume of small pulmonary vessels in the COPD group were higher than those in the normal group (P<0.05). The number, area of small pulmonary vessels at 6 mm~12 mm subpleura in current smokers with high risk for COPD were higher than those in former smokers with high risk for COPD (P<0.05). Conclusion: The number, area, and volume of small pulmonary vessels in populations at high risk for COPD were decreased. Smoking cessation may impede structural changes in small pulmonary vessels in populations at high risk for COPD.

Optical coherence tomography assessment of pulmonary vascular remodeling in advanced heart failure. The OCTOPUS-CHF study.

INTRODUCTION AND OBJECTIVES: Pulmonary vascular remodeling is common among patients with advanced heart failure. Right heart catheterization is the gold standard to assess pulmonary hypertension, but is limited by indirect measurement assumptions, a steady-flow view, load-dependency, and interpretation variability. We aimed to assess pulmonary vascular remodeling with intravascular optical coherence tomography (OCT) and to study its correlation with hemodynamic data. METHODS: This observational, prospective, multicenter study recruited 100 patients with advanced heart failure referred for heart transplant evaluation. All patients underwent right heart catheterization together with OCT evaluation of a subsegmentary pulmonary artery. RESULTS: OCT could be performed and properly analyzed in 90 patients. Median age was 57.50 [interquartile range, 48.75-63.25] years and 71 (78.88%) were men. The most frequent underlying heart condition was nonischemic dilated cardiomyopathy (33 patients [36.66%]). Vascular wall thickness significantly correlated with mean pulmonary artery pressure, pulmonary vascular resistance, and transpulmonary gradient (R coefficient=0.42, 0.27 and 0.32 respectively). Noninvasive estimation of pulmonary artery systolic pressure, acceleration time, and right ventricle-pulmonary artery coupling also correlated with wall thickness (R coefficient of 0.42, 0.27 and 0.49, respectively). Patients with a wall thickness over 0.25mm had significantly higher mean pulmonary pressures (37.00 vs 25.00mmHg; P=.004) and pulmonary vascular resistance (3.44 vs 2.08 WU; P=.017). CONCLUSIONS: Direct morphological assessment of pulmonary vascular remodeling with OCT is feasible and is significantly associated with classic hemodynamic parameters. This weak association suggests that structural remodeling does not fully explain pulmonary hypertension.

Photoacoustic imaging provides an in vivo assessment of the preeclamptic placenta remodeling and function in response to therapy.

INTRODUCTION: There is a lack of effective therapeutic interventions for preeclampsia. A central factor in the etiology of the disease is the development of placental hypoxia due to abnormal vascular remodeling. However, methods to assess the impact of potential therapies on placental growth and remodeling are currently lacking. Here, we develop and validate ultrasound-guided photoacoustic imaging methods to monitor the placental response to therapeutic intervention. Establishing non-invasive tools to image placental function opens up previously unachievable understandings of placental therapeutic response. METHODS: Studies were performed in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia. Preclinical research has identified tempol, a superoxide dismutase mimetic, and the phosphodiesterase inhibitor sildenafil as potential therapeutics for preeclampsia, as both improve in vivo maternal outcomes. PA images of the placental environment were acquired in RUPP rats receiving tempol (n = 8) or sildenafil (n = 8) to assess the longitudinal effects of treatment on placental oxygenation and vascular remodeling. Imaging measurements were validated with ex vivo histological analysis. RESULTS: Spectral photoacoustic imaging non-invasively measured placental hypoxia and impaired vascular growth two days after the RUPP procedure was implemented. Sildenafil significantly improved (p < 0.05) placental oxygenation and promoted vascular remodeling in RUPP animals, while RUPP animals treated with tempol had a diminished placental therapeutic response. DISCUSSION: We demonstrate that photoacoustic imaging provides in vivo measures of placental oxygenation and vascular remodeling, a previously unobtainable assessment of preeclamptic therapeutic response. These imaging tools have tremendous potential to accelerate the search for effective therapies for preeclampsia.

Assessment of heterogeneity in collective endothelial cell behavior with multicolor clonal cell tracking to predict arteriovenous remodeling.

Arteries and veins form in a stepwise process that combines vasculogenesis and sprouting angiogenesis. Despite extensive data on the mechanisms governing blood vessel assembly at the single-cell level, little is known about how collective cell migration contributes to the organization of the balanced distribution between arteries and veins. Here, we use an endothelial-specific zebrafish reporter, arteriobow, to label small cohorts of arterial cells and trace their progeny from early vasculogenesis throughout arteriovenous remodeling. We reveal that the genesis of arteries and veins relies on the coordination of 10 types of collective cell dynamics. Within these behavioral categories, we identify a heterogeneity of collective cell motion specific to either arterial or venous remodeling. Using pharmacological blockade, we further show that cell-intrinsic Notch signaling and cell-extrinsic blood flow act as regulators in maintaining the heterogeneity of collective endothelial cell behavior, which, in turn, instructs the future territory of arteriovenous remodeling.

Resilience of the Internal Mammary Artery to Atherogenesis: Shifting From Risk to Resistance to Address Unmet Needs.

Fueled by the global surge in aging, atherosclerotic cardiovascular disease reached pandemic dimensions putting affected individuals at enhanced risk of myocardial infarction, stroke, and premature death. Atherosclerosis is a systemic disease driven by a wide spectrum of factors, including cholesterol, pressure, and disturbed flow. Although all arterial beds encounter a similar atherogenic milieu, the development of atheromatous lesions occurs discontinuously across the vascular system. Indeed, the internal mammary artery possesses unique biological properties that confer protection to intimal growth and atherosclerotic plaque formation, thus making it a conduit of choice for coronary artery bypass grafting. Its endothelium abundantly expresses nitric oxide synthase and shows accentuated nitric oxide release, while its vascular smooth muscle cells exhibit reduced tissue factor expression, high tPA (tissue-type plasminogen activator) production and blunted migration and proliferation, which may collectively mitigate intimal thickening and ultimately the evolution of atheromatous plaques. We aim here to provide insights into the anatomy, physiology, cellular, and molecular aspects of the internal mammary artery thereby elucidating its remarkable resistance to atherogenesis. We propose a change in perspective from risk to resilience to decipher mechanisms of atheroresistance and eventually identification of novel therapeutic targets presently not addressed by currently available remedies.

Pretransplantation and Post-Transplantation Liver Disease Assessment in Adolescents Undergoing Isolated Heart Transplantation for Fontan Failure.

OBJECTIVE: To describe the assessment of Fontan-associated liver disease and determine the clinical and imaging measures that may identify hepatic morbidity risk in isolated heart transplantation candidates and trend those measures post-isolated heart transplantation. STUDY DESIGN: Retrospective analysis of pre-isolated heart transplantation and post-isolated heart transplantation Fontan-associated liver disease (FALD) status using blood tests, magnetic resonance imaging (MRI), and liver biopsy analysis within 6 months before isolated heart transplantation and 12 months after isolated heart transplantation in 9 consecutive patients with Fontan. Pre- and post-isolated heart transplantation standard laboratory values; varices, ascites, splenomegaly, thrombocytopenia (VAST) score; Fontan liver MRI score; liver biopsy scores; Model for End-stage Liver Disease (MELD); MELD excluding the International Normalized Ratio (MELD-XI); AST to platelet ratio index, and cardiac catheterization data were compared. RESULTS: Pretransplantation maximum MELD and MELD-XI was 15 and 16, respectively. Central venous pressures and VAST scores decreased significantly post-transplantation. In 5 paired studies, Fontan liver MRI score maximum was 10 pretransplantation and decreased significantly post-transplantation. Arterially enhancing nodules on MRI persisted in 2 patients post-transplantation. Pretransplantation and post-transplantation liver biopsy scores did not differ in 4 paired biopsy specimens. CONCLUSIONS: Patients with FALD and MELD <15, MELD-XI <16, Fontan liver MRI score <10, and VAST score ≤2 can have successful short-term isolated heart transplantation outcomes. Liver MRI and VAST scores improved post-transplantation. Post-transplantation liver biopsy scores did not change significantly. Pretransplantation liver biopsy demonstrating fibrosis alone should not exclude consideration of isolated heart transplantation. The persistence of hepatic vascular remodeling and fibrosis post-isolated heart transplantation suggests that continued surveillance for hepatic complications post-transplantation for patients with Fontan is reasonable.

Contrast-enhanced ultrasound for the assessment of placental development and function.

The use of contrast agents as signal enhancers during ultrasound improves visualization and the diagnostic utility of this technology in medical imaging. Although widely used in many disciplines, contrast ultrasound is not routinely implemented in obstetrics, largely due to safety concerns of administered agents for pregnant women and the limited number of studies that address this issue. Here the microbubble characteristics that make them beneficial for enhancement of the blood pool and the quantification of real-time imaging are reviewed. Literature from pregnant animal model studies and safety assessments are detailed, and the potential for contrast-enhanced ultrasound to provide clinically relevant data and benefit our understanding of early placental development and detection of placental dysfunction is discussed.

Clinical effectiveness and radial artery remodeling assessment via very-high-frequency ultrasound/ultra biomicroscopy after applying slender 7Fr sheath for transradial approach in left main bifurcation disease.

OBJECTIVE: To explore the clinical effect and radial remodeling of transradial slender 7 Fr sheath for left main bifurcation disease (LM bifurcation). METHODS: From January 2018 to September 2019, 236 patients with LM bifurcation undergoing transradial percutaneous coronary intervention (PCI) from two heart centers were divided into slender 7 Fr sheath group (n = 127) and 6 Fr sheath group (n = 109). Quantitative coronary angiography (QCA) and very high-frequency ultrasound/ultra biomicroscopy (VHFUBM) were used to assess the clinical effect and radial remodeling of transradial sheath. RESULTS: Slender 7 Fr sheath group had a higher preoperative distal bifurcation angle (67.271 ± 22.886) than 6 Fr group (55.831 ± 20.245) (p < .05). Post-PCI QCA results showed significant differences in minimum lumen diameter at proximal left anterior descending artery (LAD) and left circumflex artery (LCX) between two groups (p < .05). There were no significant differences in target vessel myocardial infarction, target vessel revascularization, death and major adverse cardiocerebrovascular events (MACCE) at 30-day and 1-year follow-up between two groups (p>.05). No significant differences were observed in radial artery diameter (RAD), intimal-medial thickness (IMT) and radial artery injury at 24-h and 90-day follow-up between two groups. CONCLUSION: With larger main and side branch diameter, larger angle of bifurcation and higher SYNTAX score, transradial slender 7 Fr sheath obtained similar clinical effects as 6 Fr sheath without increasing the occurrence of adverse events. Similar follow-up RAD, IMT and radial artery injury were observed. Therefore, slender 7 Fr sheath has safety and feasibility in applying to transradial LM-Bifurcation PCI.

Semi-Minimal Invasive Method to Induce Myocardial Infarction in Rats and the Assessment of Cardiac Function by an Isolated Working Heart System.

Myocardial infarction (MI) remains the main contributor to morbidity and mortality worldwide. Therefore, research on this topic is mandatory. An easily and highly reproducible MI induction procedure is required to obtain further insight and better understanding of the underlying pathological changes. This procedure can also be used to evaluate the effects or potency of new and promising treatments (as drugs or interventions) in acute MI, subsequent remodeling and heart failure (HF). After intubation and pre-operative preparation of the animal, an anesthetic protocol with isoflurane was performed, and the surgical procedure was conducted quickly. Using a minimally invasive approach, the left anterior descending artery (LAD) was located and occluded by a ligature. The occlusion can be performed acutely for subsequent reperfusion (ischemia/reperfusion injury). Alternatively, the vessel can be ligated permanently to investigate the development of chronic MI, remodeling or HF. Despite common pitfalls, the drop-out rates are minimal. Various treatments such as remote ischemic conditioning can be examined for their cardioprotective potential pre-, peri- and post-operatively. The post-operative recovery was quick as the anesthesia was precisely controlled and the duration of the operation was short. Post-operative analgesia was administered for three days. The minimally invasive procedure reduces the risk of infection and inflammation. Furthermore, it facilitates rapid recovery. The "working heart" measurements were performed ex vivo and enabled precise control of preload, afterload and flow. This procedure requires specific equipment and training for adequate performance. This manuscript provides a detailed step-by-step introduction for conducting these measurements.

Left Common Carotid Artery Biomechanical Properties in Individuals over 80 years: Women Have Stiffer Vessels.

BACKGROUND: Considering the longevity of the worldwide population, the cardiovascular diseases deserve particular attention, especially the carotid artery disease in the ≥80-year-old population. The stiffness of the common carotid artery, for example, has been showed in numerous clinical studies as a marker of increased risk of stroke, dementia, and depression. Besides, with the emergence of new surgical techniques such as the transcarotid artery revascularization that uses the common carotid artery as a workstation, the biomechanical and histological features of this vessel, more than ever, must be detailed. METHODS: Left common carotid artery fragments from 9 cadaver donors (≥80 years old) were evaluated. Biomechanical (failure stress, tension, and strain) and histological (percentage of collagen and elastic fibers) features of these samples were analyzed with special focus on gender differences. RESULTS: Statistically significant differences in biomechanical and histological features between the genders were observed. The percentage of collagen fiber in intima (P = 0.008) and media (P = 0.041) layers was significantly lower in men than in women. A higher elasticity (failure strain) of the specimens in male gender was also observed (P = 0.025). No significant difference was observed in the layers thickness between the genders regardless which part of the arterial wall was considered. CONCLUSIONS: These biomechanical and histological findings could be the responsible for the higher left common carotid artery stiffness observed among ≥80-year-old women when compared with men in numerous clinical studies in literature.

Assessment of Vascular Patency and Inflammation with Intravascular Optical Coherence Tomography in Patients with Superficial Femoral Artery Disease Treated with Zilver PTX Stents.

PURPOSE: Zilver PTX nitinol self-expanding drug-eluting stent with paclitaxel coating is effective for treatment of superficial femoral artery (SFA) disease. However, as with any stent, it induces a measure of vascular inflammatory response. The current clinical trial (NCT02734836) aimed to assess vascular patency, remodeling, and inflammatory markers with intravascular optical coherence tomography (OCT) in patients with SFA disease treated with Zilver PTX stents. METHODS: Serial OCT examinations were performed in 13 patients at baseline and 12-month follow-up. Variables evaluated included neointimal area, luminal narrowing, thrombus area, stent expansion as well as measures of inflammation including, peri-strut low-intensity area (PLIA), macrophage arc, neovascularization, stent strut apposition and coverage. RESULTS: Percentage of malapposed struts decreased from 10.3 ±â€¯7.9% post-intervention to 1.1 ±â€¯2.2% at 12-month follow-up, but one patient showed late-acquired stent malapposition (LASM). The percent of uncovered struts at follow-up was 3.0 ±â€¯4.5%. Average expansion of stent cross-sectional area from baseline to follow-up was 35 ±â€¯19%. The average neointimal area was 7.8 ±â€¯3.8 mm2. Maximal luminal narrowing was 61.1 ±â€¯25.0%, and average luminal narrowing was 35.4 ±â€¯18.2%. Average peri-strut low-intensity area (PLIA) per strut was 0.017 ±â€¯0.018 mm2. Average number of neovessels per mm of stent was 0.138 ±â€¯0.181. Average macrophage angle per frame at follow-up was 7 ±â€¯11°. Average thrombus area at follow-up was 0.0093 ±â€¯0.0184 mm2. CONCLUSION: At 12-month follow-up, OCT analysis of Zilver PTX stent shows outward remodeling and minimal neointimal growth, but evidence of inflammation including PLIA, neovessels, thrombus and macrophages. SUMMARY: Thirteen patients with PAD had paclitaxel-coated stents implanted in their SFAs and were then imaged with OCT at baseline and 12-month follow-up. OCT proxy metrics of inflammation were quantified.

Homologous and heterologous assessment of a novel biomaterial for venous patch.

OBJECTIVE: This study evaluated swine and bovine pulmonary visceral pleura (PVP) as a vascular patch. Venous patches are frequently used in surgery for repair or reconstruction of veins. Autologous patches are often limited by the number and dimension of donor tissue and can result in donor complications. Bovine pericardium is the most common heterologous patch used by vascular surgeons. Researchers, however, are continually seeking to improve heterologous and synthetic patches for improved outcome. METHODS: The PVP was peeled from swine and bovine lungs and cross-linked with glutaraldehyde. After sterilization and rinsing, the PVP patches were implanted in the jugular vein (10 × 35 mm) of pigs and dogs. Patency was evaluated by ultrasound, and animals were euthanized at 2 and 4 months. Neoendothelium and neomedia were evaluated by histologic analysis. RESULTS: The jugular vein patched by PVP in pigs and dogs remained patent at 2 and 4 months with no adhesions, inflammation, or aneurysm in the patches. The biomarkers of endothelial cells-factor VIII, platelet/endothelial cell adhesion molecule 1, and endothelial nitric oxide synthase-were detected in the neoendothelial cells. The expression of vascular smooth muscle cell (VSMC) α-actin was robust in the neomedia at 2 and 4 months. Neomedia composed of VSMCs developed to nearly double the thickness of adjacent jugular vein. The circumferential orientation of VSMCs in neomedia further increased in the 4-month group. CONCLUSIONS: The cross-linked swine and bovine PVP patch has a nonthrombogenic surface that maintains patency. The PVP patch may overcome the pitfall of compliance mismatch of synthetic patches. The proliferation of vascular cells assembled in the neoendothelium and neomedia in the patches may support long-term patency.

Assessment of disease activity in Takayasu arteritis: A quantitative study with computed tomography angiography.

BACKGROUND: Identifying disease activity in Takayasu arteritis (TAK) is challenging. This study aimed to investigate the value of quantitative characterization with computed tomography angiography in the assessment of disease activity in patients with TAK. METHODS: We retrospectively analysed the data on 162 aortic CT angiography from 140 TAK patients. Patients were categorized based on disease activity according to the National Institutes of Health criteria into two groups: active disease group (n = 65) and inactive disease group (n = 97). RESULTS: Patients with active TAK had a thicker wall compared with patients with inactive TAK (5.2 ±â€¯2.4 mm vs. 2.5 ±â€¯0.8 mm, p < 0.001). The relative post-contrast enhancement ratio of the thickened wall was higher in active TAK than in inactive TAK (1.5 ±â€¯0.3 vs. 1.1 ±â€¯0.2, p < 0.001). Given a thickness cutoff of 3.3 mm, sensitivity for active-phase TAK was 83.1%, specificity 89.7%, positive predictive value 84.4%, and negative predictive value 88.8%. With a relative post-contrast enhancement ratio cutoff of 1.2, sensitivity for active-phase TAK was 89.2%, specificity 76.3%, positive predictive value 71.6%, and negative predictive value 91.3%. In receiver-operating characteristic curves comparison, maximal wall thickness and relative post-contrast enhancement ratio were superior to C-reactive protein and erythrocyte sedimentation rate for determining active phase disease (p < 0.05). CONCLUSIONS: Quantitative characterization with CT angiography was a useful tool to assess disease activity in TAK patients. Maximal wall thickness and relative post-contrast enhancement ratio have a high sensitivity and specificity for detecting TAK activity.

Assessment of anthropometric indices other than BMI to evaluate arterial stiffness.

Based on the obesity paradox, people with a normal body mass index (BMI) may have a higher risk of mortality than those with a BMI that falls within the obese range. Despite the availability of other anthropometric measures, obesity is commonly evaluated based on BMI. A body shape index (ABSI) and body roundness index (BRI) have recently been proposed as new anthropometric measures that are calculated with height, weight, and waist circumference. This study investigated the associations between the traditional and new body composition indices and arterial stiffness using the brachial-ankle pulse wave velocity (baPWV). Overall, 3512 individuals (1228 men and 2284 women) were enrolled and were divided into two groups according to BMI. Multiple regression analysis was performed to assess the relationship between baPWV and body composition. baPWV was significantly associated with ABSI (ß = 0.087, p = 0.002), visceral adipose tissue (VAT; ß = 0.081, p = 0.002), and the visceral/subcutaneous adipose tissue (VAT/SAT) ratio (ß = 0.108, p < 0.001) in non-obese men. In non-obese women, baPWV was significantly associated with several variables but not the VAT/SAT ratio. Similarly, baPWV was significantly associated with BMI (ß = 0.103, p = 0.038), BRI (ß = 0.104, p = 0.036), VAT (ß = 0.167, p = 0.001), and the VAT/SAT ratio (ß = 0.106, p = 0.028) in obese women. ABSI can be used with high accuracy to evaluate fat distribution in non-obese men to predict arterial stiffness. However, the BRI should be used in addition to BMI to assess the body composition of women more accurately. ABSI and the BRI can be used to identify predictors of vascular remodeling or organic vascular dysfunction.

Quantitative CT assessment of bronchial and vascular alterations in severe precapillary pulmonary hypertension.

BACKGROUND: Little is known about in vivo alterations at bronchial and vascular levels in severe pulmonary hypertension (PH) of different etiologies. We aimed to compare quantitative computed tomography (CT) data from the following three groups of severe precapillary PH patients: COPD, idiopathic pulmonary arterial hypertension (iPAH), and chronic thromboembolic PH (CTEPH). PATIENTS AND METHODS: This study was approved by the institutional review board. Severe PH patients (mean pulmonary arterial pressure [mPAP] ≥35 mmHg) with COPD, iPAH, or CTEPH (n=24, 16, or 16, respectively) were included retrospectively between January 2008 and January 2017. Univariate analysis of mPAP was performed in each severe PH group. Bronchial wall thickness (WT) and percentage of cross sectional area of pulmonary vessels less than 5 mm2 normalized by lung area (%CSA<5) were measured and compared using CT, and then combined to arterial partial pressure of oxygen (PaO2) to generate a "paw score" compared within the three groups using Kruskal-Wallis and its sensitivity using Fisher's exact test. RESULTS: WT was higher and %CSA<5 was lower in the COPD group compared to iPAH and CTEPH groups. Mosaic pattern was higher in CTEPH group than in others. In severe PH patients secondary to COPD, mPAP was positively correlated to %CSA<5. By contrast, in severe iPAH, this correlation was negative, or not correlated in severe CTEPH groups. In the COPD group, "paw score" showed higher sensitivity than in the other two groups. CONCLUSION: Unlike in severe iPAH and CTEPH, severe PH with COPD can be predicted by "paw score" reflecting bronchial and vascular morphological differential alterations.

Assessment of geometrical remodelling of the aortic arch after hybrid treatment.

OBJECTIVES: The aim of this study was to measure the morphological remodelling of the ascending aorta, aortic arch and thoracic aorta after aortic arch hybrid treatment including debranching and stent graft implantation. METHODS: Preoperative, 1-month and 1-year follow-up of computed tomography angiography scans of 22 patients were analysed to compute the lumen centreline from the aortic root to the coeliac trunk, and the following measurements were derived: the total centreline length, distance from the aortic root to the left subclavian artery, distance from the left subclavian artery to the distal landing zone. For both pre- and postoperative centrelines, the pointwise curvature was measured at the proximal and the distal landing zones. The mean curvature values of the whole aortic segment and the endografting region of the ascending and the descending aorta were measured. Surface outerline was computed as well, and curvature values at the endograft landing points were extracted. RESULTS: At the 1-month follow-up, centreline length were already significantly increased (382.66 ± 48.69 to 388.1 ± 50.75 mm; P = 0.01). Centreline pointwise curvature increased in the proximal (+29%, P = 0.011) and the distal zones (+63%, P = 0.004). Similarly, pointwise curvature of the outerline significantly increased in the proximal (+77%, P = 0.01) and the distal landing zones (+100%, P = 0.04). The centreline mean curvature increased in the ascending aorta (+7%, P = 0.02) and decreased in the endografting region (-3.3%, P = 0.004). No evidence of a relationship of such a remodelling with the type of endograft and the type of pathology was observed. This remodelling trend was confirmed by the analysis of 1-year computed tomography angiographies. CONCLUSIONS: Hybrid arch repair was associated with a significant elongation of the vessel and a significant increase in the curvature on the ascending aorta and the descending aorta and on the endograft proximal and the distal landing zones.

PECAM/eGFP transgenic mice for monitoring of angiogenesis in health and disease.

For the monitoring of vascular growth as well as adaptive or therapeutic (re)vascularization endothelial-specific reporter mouse models are valuable tools. However, currently available mouse models have limitations, because not all endothelial cells express the reporter in all developmental stages. We have generated PECAM/eGFP embryonic stem (ES) cell and mouse lines where the reporter gene labels PECAM+ endothelial cells and vessels with high specificity. Native eGFP expression and PECAM staining were highly co-localized in vessels of various organs at embryonic stages E9.5, E15.5 and in adult mice. Expression was found in large and small arteries, capillaries and in veins but not in lymphatic vessels. Also in the bone marrow arteries and sinusoidal vessel were labeled, moreover, we could detect eGFP in some CD45+ hematopoietic cells. We also demonstrate that this labeling is very useful to monitor sprouting in an aortic ring assay as well as vascular remodeling in a murine injury model of myocardial infarction. Thus, PECAM/eGFP transgenic ES cells and mice greatly facilitate the monitoring and quantification of endothelial cells ex vivo and in vivo during development and injury.

Quantitative assessment of pulmonary vascular alterations in chronic obstructive lung disease: Associations with pulmonary function test and survival in the KOLD cohort.

PURPOSE: Despite the high prevalence of pulmonary vascular alterations and their substantial impact on chronic obstructive pulmonary disease (COPD), tools for the direct in vivo assessment of pulmonary vascular alterations remain limited. Thus, the purpose of this study was to automatically extract pulmonary vessels from volumetric chest CT and evaluate the associations between the derived quantitative pulmonary vessel features and clinical parameters, including survival, in COPD patients. METHODS: This study included 344 adult COPD patients. Pulmonary vessels were automatically extracted from volumetric chest CT data. Quantitative pulmonary vessel features were obtained from various lung surface areas (LSAs), which are theoretical surface areas drawn at different depths from the pleural borders. The total number of vessels (Ntotal) and number of vessels with vessel area (VA) less than 5 mm2 (N<5mm) were counted as both robust values and as values per 10 cm2 of LSA (Ntotal/LSA; N<5mm/LSA). The average VA (VAmean) and percentage of measured VA in the corresponding LSA (%VA) were measured. Associations between quantitative pulmonary vessel features and clinical parameters, including survival and the pulmonary function test (PFT), were evaluated. RESULTS: The pulmonary vessels were automatically extracted with 100% technical success. Cox regression analysis showed Ntotal/LSA, N<5mm/LSA, VAmean, and %VA to be significant predictors of survival (hazard ratio (HR), 0.80, 0.75, 0.70, 0.49, respectively). Patients classified into high-risk groups by %VA18mm (cut-off = 3.258), chosen because it demonstrated the strongest statistical influence on survival in a univariate Cox analysis, were associated with worse overall survival before (HR, 4.83; p < 0.001) and after adjustment for patient age and BMI (HR, 2.18; p = 0.014). Of the quantitative pulmonary vessel features, Ntotal/LSA, N<5mm/LSA, and %VA were correlated with FEV1, FEV1/FVC, and DLCO in all LSAs. The strongest correlation with PFTs was noted at LSA9mm for both Ntotal (FEV1, r = 0.33; FEV1/FVC, r = 0.51) and N<5mm (FEV1, r = 0.35; FEV1/FVC, r = 0.52). For %VA, the association was most evident at LSA18mm (FEV1, r = 0.27; FEV1/FVC, r = 0.47). Significant moderate to strong correlations were consistently observed between the extent of emphysema and quantitative pulmonary vessel features (r = 0.44-0.66; all p < 0.001). CONCLUSIONS: The automated extraction of pulmonary vessels and their quantitative assessment are technically feasible. Various quantitative pulmonary vessel features demonstrated significant relationships with survival and PFT in COPD patients. Of the various quantitative features, the percentage of total VA measured at 18 mm depth from the pleural surface (%VA18mm) and the number of small vessels counted per 10 cm2 of LSA at 9 mm depth from the pleural surface (N<5mm/LSA9mm) had the strongest predictability for the clinical parameters.

Uncertainty Quantification of a Multiscale Model for In-Stent Restenosis.

PURPOSE: Coronary artery stenosis, or abnormal narrowing, is a widespread and potentially fatal cardiac disease. After treatment by balloon angioplasty and stenting, restenosis may occur inside the stent due to excessive neointima formation. Simulations of in-stent restenosis can provide new insight into this process. However, uncertainties due to variability in patient-specific parameters must be taken into account. METHODS: We performed an uncertainty quantification (UQ) study on a complex two-dimensional in-stent restenosis model. We used a quasi-Monte Carlo method for UQ of the neointimal area, and the Sobol sensitivity analysis (SA) to estimate the proportions of aleatory and epistemic uncertainties and to determine the most important input parameters. RESULTS: We observe approximately 30% uncertainty in the mean neointimal area as simulated by the model. Depending on whether a fast initial endothelium recovery occurs, the proportion of the model variance due to natural variability ranges from 15 to 35%. The endothelium regeneration time is identified as the most influential model parameter. CONCLUSION: The model output contains a moderate quantity of uncertainty, and the model precision can be increased by obtaining a more certain value on the endothelium regeneration time. We conclude that the quasi-Monte Carlo UQ and the Sobol SA are reliable methods for estimating uncertainties in the response of complicated multiscale cardiovascular models.