Total Vessel Volume Research Articles

Pulmonary Vascular Structure and Function Are Related to Exercise Capacity in Health and COPD

Although it is generally accepted that aerobic exercise training does not change lung structure or function, some work suggests that greater pulmonary vascular structure and function is associated with higher exercise capacity (VO2peak). Is there a cross-sectional association between the pulmonary vasculature and VO2peak? We hypothesized that those with higher computed tomography (CT) blood vessel volumes, and pulmonary diffusing capacity for carbon monoxide (DLCO) would have higher VO2peak, independent of airflow limitation. Participants from the CanCOLD study were categorized as: never-smokers with normal spirometry (n=263); ever-smokers with normal spirometry (n=407); and chronic obstructive pulmonary disease (COPD): individuals with spirometric airflow obstruction (n=334). Total vessel volume (TVV), the volume for all vessels with a cross-sectional area ≤5 mm2 (BV5), and between 5-10 mm2 (BV5-10) were generated from CT scans and used as indices of pulmonary vascular structure. DLCO was used as an index of pulmonary microvascular function. VO2peak was evaluated via incremental cardiopulmonary exercise testing. General linear regression models revealed that even after controlling for FEV1, emphysema severity and body morphology, DLCO, TVV, BV5 and BV5-10, were independently associated with VO2peak. Interaction effects were observed between COPD and TVV, BV5, and BV5-10 indicating a weaker association between pulmonary vascular volumes and VO2peak in COPD. Our results suggest that pulmonary vascular structure and DLCO is independently associated with VO2peak, regardless of severity of airflow limitation and emphysema, suggesting that these associations are not limited to COPD.

Pathophysiology of carotid atherosclerosis: Calcification, intraplaque haemorrhage and pulse pressure as key players

PurposeIntraplaque haemorrhage (IPH) is a well-known risk factor for faster plaque progression (volume increase); however, its etiology is unclear. We aimed at determining what other local plaque- and systemic factors contribute to plaque progression and to the development and progression of IPH. MethodsWe examined 98 asymptomatic participants with carotid plaque using serial multi-contrast magnetic resonance imaging. We measured the percent of wall volume (%WV=100 x [wall volume] / [total vessel volume]) and measured IPH and calcification volumes. We used generalized estimating equations-based regression to analyze predictors of %WV change and new IPH while accounting for covariates (sex, age and statin use), and multiple non-independent observations per participant. ResultsTotal follow-up was 1.8 ± 0.8 years on average. The presence of IPH (β: 0.6 %/y, p = 0.033) and calcification (β: 1.2 %/y, p = 0.028) were each associated with faster plaque progression. New IPH, detected on a subsequent scan in 4 % of arteries that did not initially have IPH, was associated with larger calcification (odds ratio [OR]: 2.6 per 1-SD increase, p = 0.038) and higher pulse pressure (OR: 2.3 per 1-SD increase, p = 0.016). Larger calcification was associated with greater increases in pulse pressure (β: 1.4 mm Hg/y per 1-SD increase, p = 0.040). ConclusionsIPH and calcification are each independently associated with faster plaque progression. The association of carotid calcification to increased pulse pressure and new IPH development suggests a possible mechanism by which calcification drives IPH development and plaque progression.

Sex-related differences in pulmonary vascular volume distribution.

Pulmonary arterial hypertension affects females more frequently than males, and there are known sex-related differences in the lungs. However, normal sex-related differences in pulmonary vascular structure remain incompletely described. We aimed to contrast computed tomography-derived pulmonary vascular volume and its distribution within the lungs of healthy adult females and males. From the CanCOLD Study, we retrospectively identified healthy never-smokers. We analyzed full-inspiration computed tomography images, using vessel and airway segmentation to generate pulmonary vessel volume, vessel counts, and airway counts. Vessels were classified by cross-sectional area >10, 5-10, and <5 mm2 into bins, with volume summed within each area bin and in total. We included 46 females and 36 males (62 ± 9 years old). Females had lower total lung volume, total airway counts, total vessel counts, and total vessel volume (117 ± 31 vs. 164 ± 28 mL) versus males (all p < 0.001). Females also had lower vessel volume >10 mm2 (14 ± 8 vs. 27 ± 9 mL), vessel volume 5-10 mm2 (35 ± 11 vs. 55 ± 10 mL), and vessel volume <5 mm2 (68 ± 18 vs. 82 ± 19 mL) (all p < 0.001). Normalized to total vessel volume, vessel volume >10 mm2 (11 ± 4 vs. 16 ± 4%, p < 0.001) and 5-10 mm2 (30 ± 6 vs. 34 ± 5%, p = 0.001) remained lower in females but vessel volume <5 mm2 relative to total volume was 18% higher (59 ± 8 vs. 50 ± 7%, p < 0.001). Among healthy older adults, pulmonary vessel volume is distributed into smaller vessels in females versus males.

Prospective deep learning-based quantitative assessment of coronary plaque by computed tomography angiography compared with intravascular ultrasound: the REVEALPLAQUE study.

Coronary computed tomography angiography provides non-invasive assessment of coronary stenosis severity and flow impairment. Automated artificial intelligence (AI) analysis may assist in precise quantification and characterization of coronary atherosclerosis, enabling patient-specific risk determination and management strategies. This multicentre international study compared an automated deep learning-based method for segmenting coronary atherosclerosis in coronary computed tomography angiography (CCTA) against the reference standard of intravascular ultrasound (IVUS). The study included clinically stable patients with known coronary artery disease from 15 centres in the USA and Japan. An AI-enabled plaque analysis was utilized to quantify and characterize total plaque (TPV), vessel, lumen, calcified plaque (CP), non-calcified plaque (NCP), and low-attenuation plaque (LAP) volumes derived from CCTA and compared with IVUS measurements in a blinded, core laboratory-adjudicated fashion. In 237 patients, 432 lesions were assessed; mean lesion length was 24.5 mm, and mean IVUS-TPV was 186.0 mm3. AI-enabled plaque analysis on CCTA showed strong correlation and high accuracy when compared with IVUS; correlation coefficient, slope, and Y intercept for TPV were 0.91, 0.99, and 1.87, respectively; for CP volume 0.91, 1.05, and 5.32, respectively; and for NCP volume 0.87, 0.98, and 15.24, respectively. Bland-Altman analysis demonstrated strong agreement with little bias for these measurements. AI-enabled CCTA quantification and characterization of atherosclerosis demonstrated strong agreement with IVUS reference standard measurements. This tool may prove effective for accurate evaluation of coronary atherosclerotic burden and cardiovascular risk assessment.

Atherosclerotic coronary plaque regression from lipid-lowering therapies: A meta-analysis and meta-regression

BackgroundStudies reporting collective and comprehensive data on plaque regression of different lipid-lowering therapies (LLTs) are limited. ObjectivesWe evaluated plaque regression of LLTs based on multiple markers and performed subgroup analyses based on LLT type and post-treatment LDL-C levels MethodsA literature search was performed to identify studies assessing plaque regression from LLTs. The following LLTs groups were included: High-intensity statin (HIS), HIS+ eicosapentaenoic acid (EPA), HIS + ezetimibe, Low-intensity statin (LIS), LIS + EPA, LIS + Ezetimibe, and PCSK9 inhibitors. Our primary outcomes were change in percent atheroma volume (PAV). Secondary outcomes included mean differences in total atheroma volume (TAV), lumen, plaque, and vessel volumes, fibrous cap thickness (FCT), and lipid arc (LA). Subgroup analyses were performed on LLT type and post-treatment LDL-C levels. Meta-regression was performed to control for covariates. ResultsWe identified 51 studies with 9,113 adults (22 % females). LLTs reduced PAV levels (-1.10 % [-1.63, -0.56], p < 0.01), with significant reduction observed with HIS, LIS + ezetimibe, LIS + EPA, and PCSK9 inhibitors. LLTs reduced TAV levels (-5.84 mm3 [-8.64 to -3.04] p < 0.01), mainly driven by HIS (-7.60 mm3 [-11.89, -3.31] p < 0.01). LLTs reduced plaque volume and LA and increased FCT. ConclusionThe plaque regression associated with LLTs is observed to be mainly driven by HIS, reducing both TAV and PAV. This suggest that HIS is the most effective LLT for plaque regression Unstructured abstractWe evaluated plaque regression of LLTs from 51 studies. We found that while reduction of PAV (-1.10 % [-1.63, -0.56], p < 0.01) were present across different LLT types, reduction of TAV (-5.84 mm3 [-8.64 to -3.04] p < 0.01) was mainly driven by HIS (-7.60 mm3 [-11.89, -3.31] p < 0.01). These results suggest that HIS is the most effective LLT for plaque regression.

Hemorrhage risk prediction after computed tomography-guided lung biopsy: Clinical parameters and quantitative pulmonary vascular analysis

Background/purposeWe evaluated the utility of combining quantitative pulmonary vasculature measures with clinical factors for predicting pulmonary hemorrhage after computed tomography (CT)-guided lung biopsy. MethodsPatients who underwent CT-guided lung biopsy were retrospectively included in this study. Clinical and radiographic vasculature variables were evaluated as predictors of pulmonary hemorrhage. The radiographic pulmonary vascular analysis included vessel count, density, diameter, and area, and also blood volume in small vessels with a cross-sectional area ≤5 mm2 (BV5) and total blood vessel volume (TBV) in the lungs. Univariate and multivariate logistic regressions were used to identify the independent risk factors of higher-grade pulmonary hemorrhage and establish the prediction model presented as a nomogram. ResultsThe study included 126 patients; discovery cohort n = 103, and validation cohort n = 23. All pulmonary hemorrhage, higher-grade (grade ≥2) pulmonary hemorrhage, and hemoptysis occurred in 42.9%, 15.9%, and 3.2% of patients who underwent CT-guided lung biopsies. In the discovery cohort, patients with larger lesion depth (p = 0.013), higher vessel density (p = 0.033), and higher BV5 (p = 0.039) were more likely to experience higher-grade hemorrhage. The nomogram prediction model for higher-grade hemorrhage built by the discovery cohort showed similar performance in the validation cohort. ConclusionsHigher-grade pulmonary hemorrhage may occur after CT-guided lung biopsy. Lesion depth, vessel density, and BV5 are independent risk factors for higher-grade pulmonary hemorrhage. Nomograms integrating clinical parameters and radiographic pulmonary vasculature measures offer enhanced capability for assessing hemorrhage risk following CT-guided lung biopsy, thereby facilitating improved patient clinical care.

Abstract TP143: Longitudinal Evaluation of Vessel Wall MRI Demonstrates Bilaterally Symmetric Evolution of Carotid Atherosclerosis

Introduction: Carotid atherosclerosis is a leading cause of stroke worldwide. Previous studies demonstrated bilateral symmetry in atherosclerotic plaque burden and calcification scores. By leveraging longitudinal 3D vessel wall MRI, this study aims to investigate if there is a symmetrical trend of bilateral plaque progression. Methods: Asymptomatic patients with confirmed carotid stenosis were prospectively recruited in the study. Subjects underwent baseline and follow-up 3D vessel wall imaging for a time span up to 8 years. A deep learning-based pipeline was used to bilaterally segment the carotid lumen and vessel wall on axial image slices. Within each artery, the range of slices with wall thickness &gt; 2mm on any scan was included as potential atherosclerotic plaque. Plaque burden, positively associated with stroke risk, was defined as the percent wall volume (wall volume / total vessel volume х 100%). For each plaque, a linear model was fitted across all available time points to determine the growth rate of plaque burden. We used generalized estimating equation-based linear regression models to evaluate associations of the growth rate of each side with the contralateral side, adjusted for clinical risk factors and medications. Effect sizes were summarized using the partial correlation coefficient. Results: 20 subjects (mean age 73.5 years, 3 females, 14 on statins) who underwent at least three scans with bilateral carotid plaque were included in the analysis. Each subject underwent an average of 4.8 scans over 5.2 years. Overall, the plaque growth rate of one side was moderately correlated with the contralateral side (r=0.50, p=0.004), even after adjusting for age, sex and statins use. Then, for each subject, the larger of the two plaques at baseline (left or right side) was identified. The growth rate of the larger plaque was also predictive of the growth rate of the smaller plaque over the same time period (r=0.66, p=0.004). Conclusion: The systemic nature of atherosclerotic disease entails an association in symmetrical disease evolution for left and right carotid arteries. In bilaterally diseased patients, the longitudinal monitoring of the more advanced carotid lesion may provide prognostic information on the less advanced contralateral plaque.

CT quantification of pulmonary vessels in lung aging

To evaluate the effect of aging on pulmonary vessels based on computed tomography (CT) quantification and analyse the correlation between quantitative pulmonary vascular volume and pulmonary function during aging. A total of 330 healthy adult volunteers, including 161 men (53 aged 20-39 years, 61 aged 40-59 years, and 47 aged ≥60 years) and 169 women (53 aged 20-39 years, 63 aged 40-59 years, and 53 aged ≥60 years) were recruited in this study. AVIEW software was used to quantitatively measure pulmonary vascular volume, including pulmonary total blood vessel volume (TBV) and small blood vessel volume with a cross-sectional area of <5 mm2 (BV5). Pulmonary vascular volume parameters were standardised using the ratio of vascular volume to the body surface area (BSA; TBV/BSA and BV5/BSA). Subsequently, the effect of aging on the pulmonary vessels was analysed. The pulmonary vascular volume parameters TBV/BSA and BV5/BSA of the whole lung, right lung, and left lung decreased significantly with increasing age (p<0.05). Additionally, TBV/BSA and BV5/BSA of the whole lung were higher in men than in women. The declining trend of pulmonary vascular volume was consistent in men and women and increased with age. The pulmonary vascular volume parameters, TBV/BSA and BV5/BSA, decreased with age and were weakly positively correlated with pulmonary function.

Beyond early LDL cholesterol lowering to prevent coronary atherosclerosis in familial hypercholesterolaemia.

Familial hypercholesterolaemia (FH) patients are subjected to a high lifetime exposure to low density lipoprotein cholesterol (LDL-C), despite use of lipid-lowering therapy (LLT). This study aimed to quantify the extent of subclinical atherosclerosis and to evaluate the association between lifetime cumulative LDL-C exposure and coronary atherosclerosis in young FH patients. Familial hypercholesterolaemia patients, divided into a subgroup of early treated (LLT initiated <25 years) and late treated (LLT initiated ≥25 years) patients, and an age- and sex-matched unaffected control group, underwent coronary CT angiography (CCTA) with artificial intelligence-guided analysis. Ninety genetically diagnosed FH patients and 45 unaffected volunteers (mean age 41 ± 3 years, 51 (38%) female) were included. Familial hypercholesterolaemia patients had higher cumulative LDL-C exposure (181 ± 54 vs. 105 ± 33 mmol/L ∗ years) and higher prevalence of coronary plaque compared with controls (46 [51%] vs. 10 [22%], OR 3.66 [95%CI 1.62-8.27]). Every 75 mmol/L ∗ years cumulative exposure to LDL-C was associated with a doubling in per cent atheroma volume (total plaque volume divided by total vessel volume). Early treated patients had a modestly lower cumulative LDL-C exposure compared with late treated FH patients (167 ± 41 vs. 194 ± 61 mmol/L ∗ years; P = 0.045), without significant difference in coronary atherosclerosis. Familial hypercholesterolaemia patients with above-median cumulative LDL-C exposure had significantly higher plaque prevalence (OR 3.62 [95%CI 1.62-8.27]; P = 0.001), compared with patients with below-median exposure. Lifetime exposure to LDL-C determines coronary plaque burden in FH, underlining the need of early as well as potent treatment initiation. Periodic CCTA may offer a unique opportunity to monitor coronary atherosclerosis and personalize treatment in FH.

Structural Predictors of Lung Function Decline in Young Smokers with Normal Spirometry.

Rationale: Chronic obstructive pulmonary disease (COPD) due to tobacco smoking commonly presents when extensive lung damage has occurred. Objectives: We hypothesized that structural change would be detected early in the natural history of COPD and would relate to loss of lung function with time. Methods: We recruited 431 current smokers (median age, 39 yr; 16 pack-years smoked) and recorded symptoms using the COPD Assessment Test (CAT), spirometry, and quantitative thoracic computed tomography (QCT) scans at study entry. These scan results were compared with those from 67 never-smoking control subjects. Three hundred sixty-eight participants were followed every six months with measurement of postbronchodilator spirometry for a median of 32 months. The rate of FEV1 decline, adjusted for current smoking status, age, and sex, was related to the initial QCT appearances and symptoms, measured using the CAT. Measurements and Main Results: There were no material differences in demography or subjective CT appearances between the young smokers and control subjects, but 55.7% of the former had CAT scores greater than 10, and 24.2% reported chronic bronchitis. QCT assessments of disease probability-defined functional small airway disease, ground-glass opacification, bronchovascular prominence, and ratio of small blood vessel volume to total pulmonary vessel volume were increased compared with control subjects and were all associated with a faster FEV1 decline, as was a higher CAT score. Conclusions: Radiological abnormalities on CT are already established in young smokers with normal lung function and are associated with FEV1 loss independently of the impact of symptoms. Structural abnormalities are present early in the natural history of COPD and are markers of disease progression. Clinical trial registered with www.clinicaltrials.gov (NCT03480347).

COPD: pulmonary vascular volume associated with cardiac structure and function

BackgroundEarly recognition of cardiac dysfunction in patients with chronic obstructive pulmonary disease (COPD) may prevent future cardiac impairment and improve prognosis. Quantitative assessment of subsegmental and segmental vessel volume by Computed Tomographic (CT) imaging can provide a surrogate of pulmonary vascular remodeling. We aimed to examine the relationship between lung segmental- and subsegmental vessel volume, and echocardiographic measures of cardiac structure and function in patients with COPD.MethodsWe studied 205 participants with COPD, included in a large cohort study of cardiovascular disease in COPD patients. Participants had an available CT scan and echocardiogram. Artificial intelligence (AI) algorithms calculated the subsegmental vessel fraction as the vascular volume in vessels below 10 mm2 in cross-sectional area, indexed to total intrapulmonary vessel volume. Linear regressions were conducted, and standardized ß-coefficients were calculated. Scatterplots were created to visualize the continuous correlations between the vessel fractions and echocardiographic parameters.ResultsWe found that lower subsegmental vessel fraction and higher segmental vessel volume were correlated with higher left ventricular (LV) mass, LV diastolic dysfunction, and inferior vena cava (IVC) dilatation. Subsegmental vessel fraction was correlated with right ventricular (RV) remodeling, while segmental vessel fraction was correlated with higher pulmonary pressure. Measures of LV mass and right atrial pressure displayed the strongest correlations with pulmonary vasculature measures.ConclusionPulmonary vascular remodeling in patients with COPD, may negatively affect cardiac structure and function. AI-identified remodeling in pulmonary vasculature may provide a tool for early identification of COPD patients at higher risk for cardiac impairment.

The natural history and prediction of 10-year plaque progression on serial coronary CT angiography

Abstract Background Several studies have shown that plaque subcomponents such as low-attenuation or non-calcified plaque volume from coronary CT angiography (CCTA) are associated with the occurrence of major adverse cardiovascular events. However, it remains unknown how plaque morphology progresses over the long-term. Furthermore, it is unknown which plaque characteristics put patients at increased risk of plaque progression which would require more intensive image-guided follow-up. This study investigated the natural history and predictors of long-term coronary plaque progression in a serial CCTA cohort of patients with suspected coronary artery disease (CAD). Methods In this follow-up study, 539 patients from an earlier published CCTA cohort (Diemen, 2021) were invited for repeat CCTA imaging per-protocol, regardless of symptoms. A total of 299 patients underwent follow-up CCTA imaging with a median scan interval of 10.2 [8.7-11.2] years. Patients who underwent coronary artery bypass grafting (CABG) between baseline and follow-up imaging were excluded. All scans were analyzed using artificial intelligence-guided quantitative CCTA (AI-QCT). Revascularized vessels were excluded. Quantitative plaque volumes (total, low-density, non-calcified and calcified plaque) depicted by AI-QCT were divided by the total vessel volume to represent percent atheroma volume (PAV). PAV progression was calculated subtracting baseline PAV from follow-up PAV. The association of the plaque components with PAV progression was evaluated in a multivariate linear regression model adjusted for clinical risk characteristics (age, sex, hypertension, hypercholesterolemia, diabetes, BMI, smoking, family history of CAD and statin use). Results In total, 274 patients without CABG were used for the serial analysis, mean age was 57 years, 42% were women. At baseline, median PAV was 2.5% [IQR 0.7-8.1], which increased to 6.1% [IQR 1.2-12.9] at follow-up (Figure). The mean PAV progression was 0.4±0.5% per year. Adjusted for clinical risk characteristics and other plaque volumes, baseline percent non-calcified plaque volume (NCP) was the only plaque volume associated with PAV progression (0.5% PAV progression increase per % increase in baseline non-calcified plaque volume). Conclusion Using an unique long-term serial CCTA cohort undergoing per-protocol repeat imaging with a 10-year scan interval, we found that coronary plaque burden more than doubled. Interestingly, the amount of non-calcified plaque volume at baseline was the only predictor for disease progression.Figure

Comparison of CT-derived Plaque Characteristic Index With CMR Perfusion for Ischemia Diagnosis in Stable CAD.

Coronary computed tomography angiography (CCTA) and cardiac magnetic resonance (CMR) have been used to diagnose lesion-specific ischemia in patients with coronary artery disease. The aim of this study was to investigate the diagnostic performance of CCTA-derived plaque characteristic index compared with myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) derived from CMR perfusion in the assessment of lesion-specific ischemia. Between October 2020 and March 2022, consecutive patients with suspected or known coronary artery disease, who were clinically referred for invasive coronary angiography were prospectively enrolled. All participants sequentially underwent CCTA and CMR and invasive fractional flow reserve within 2 weeks. The diagnostic performance of CCTA-derived plaque characteristics, CMR perfusion-derived stress MBF, and MPR were compared. Lesions with fractional flow reserve ≤0.80 were considered to be hemodynamically significant stenosis. Nighty-two patients with 141 vessels were included in this study. Plaque length, minimum luminal area, plaque area, percent area stenosis, total atheroma volume, vessel volume, lipid-rich volume, spotty calcium, napkin-ring signs, stress MBF, and MPR in flow-limiting stenosis group were significantly different from nonflow-limiting group. The overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of lesion-specific ischemia diagnosis were 61.0%, 55.3%, 63.1%, 35.6%, and 79.3% for stress MBF, and 89.4%, 89.5%, 89.3%, 75.6%, 95.8% for MPR; meanwhile, 82.3%, 79.0%, 84.5%, 65.2%, and 91.6% for CCTA-derived plaque characteristic index. In our prospective study, CCTA-derived plaque characteristics and MPR derived from CMR performed well in diagnosing lesion-specific myocardial ischemia and were significantly better than stress MBF in stable coronary artery disease.

Neurovascular Development in Pten and Tsc2 Mouse Mutants.

Hyperactivation of the mechanistic target of rapamycin (mTOR) signaling pathway is linked to more than a dozen neurologic diseases, causing a range of pathologies, including excess neuronal growth, disrupted neuronal migration, cortical dysplasia, epilepsy and autism. The mTOR pathway also regulates angiogenesis. For the present study, therefore, we queried whether loss of Pten or Tsc2, both mTOR negative regulators, alters brain vasculature in three mouse models: one with Pten loss restricted to hippocampal dentate granule cells [DGC-Pten knock-outs (KOs)], a second with widespread Pten loss from excitatory forebrain neurons (FB-Pten KOs) and a third with focal loss of Tsc2 from cortical excitatory neurons (f-Tsc2 KOs). Total hippocampal vessel length and volume per dentate gyrus were dramatically increased in DGC-Pten knock-outs. DGC-Pten knock-outs had larger dentate gyri overall, however, and when normalized to these larger structures, vessel density was preserved. In addition, tests of blood-brain barrier integrity did not reveal increased permeability. FB-Pten KOs recapitulated the findings in the more restricted DGC-Pten KOs, with increased vessel area, but preserved vessel density. FB-Pten KOs did, however, exhibit elevated levels of the angiogenic factor VegfA. In contrast to findings with Pten, focal loss of Tsc2 from cortical excitatory neurons produced a localized increase in vessel density. Together, these studies demonstrate that hypervascularization is not a consistent feature of mTOR hyperactivation models and suggest that loss of different mTOR pathway regulatory genes exert distinct effects on angiogenesis.

Treatment Response Evaluation by Computed Tomography Pulmonary Vasculature Analysis in Patients With Chronic Thromboembolic Pulmonary Hypertension.

To quantitatively assess the pulmonary vasculature using non-contrast computed tomography (CT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) pre- and post-treatment and correlate CT-based parameters with right heart catheterization (RHC) hemodynamic and clinical parameters. A total of 30 patients with CTEPH (mean age, 57.9 years; 53% female) who received multimodal treatment, including riociguat for ≥ 16 weeks with or without balloon pulmonary angioplasty and underwent both non-contrast CT for pulmonary vasculature analysis and RHC pre- and post-treatment were included. The radiographic analysis included subpleural perfusion parameters, including blood volume in small vessels with a cross-sectional area ≤ 5 mm² (BV5) and total blood vessel volume (TBV) in the lungs. The RHC parameters included mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and cardiac index (CI). Clinical parameters included the World Health Organization (WHO) functional class and 6-minute walking distance (6MWD). The number, area, and density of the subpleural small vessels increased after treatment by 35.7% (P < 0.001), 13.3% (P = 0.028), and 39.3% (P < 0.001), respectively. The blood volume shifted from larger to smaller vessels, as indicated by an 11.3% increase in the BV5/TBV ratio (P = 0.042). The BV5/TBV ratio was negatively correlated with PVR (r = -0.26; P = 0.035) and positively correlated with CI (r = 0.33; P = 0.009). The percent change across treatment in the BV5/TBV ratio correlated with the percent change in mPAP (r = -0.56; P = 0.001), PVR (r = -0.64; P < 0.001), and CI (r = 0.28; P = 0.049). Furthermore, the BV5/TBV ratio was inversely associated with the WHO functional classes I-IV (P = 0.004) and positively associated with 6MWD (P = 0.013). Non-contrast CT measures could quantitatively assess changes in the pulmonary vasculature in response to treatment and were correlated with hemodynamic and clinical parameters.

Abstract 11126: Longitudinal MRI-Based Superficial Femoral Artery Velocity Measurements in Peripheral Artery Disease: An Analysis of the Effect of Lipid Modification on Peripheral Artery Disease After Endovascular Intervention Trial (ELIMIT)

Introduction: Peripheral artery disease (PAD) causes lower extremity dysfunction and is associated with an increased risk of cardiovascular mortality and morbidity. We analyzed longitudinal associations of non-invasive 2-dimensional-phase-contrast magnetic resonance imaging (2D-PC-MRI) velocity markers of the distal superficial femoral artery (SFA) with characteristics of PAD. Hypothesis: Longitudinal changes in MRI-based measures of SFA velocity are associated with changes in SFA lumen volumes in PAD. Methods: A total of 33 (11 diabetic, 22 non-diabetic) PAD patients, who completed baseline and 2-year follow-up MRI were included in this secondary analysis of ELIMIT. Electrocardiographically-gated 2D-PC-MRI was performed at a proximal and a distal imaging location of the distal SFA territory. SFA lumen, wall, and total vessel volumes were averaged over all distal SFA MRI slices. Results: Baseline characteristics did not differ between diabetic and non-diabetic PAD patients (Table). Proximal and distal SFA velocity measures did not differ between baseline and 2-years (41.98: IQR (23.58, 72.6) cm/s; vs. 40.31: IQR (26.69, 61.29) cm/s; p=0.30, for maximum SFA velocity). The velocity amplitude (defined as the difference between the SFA minimum and maximum velocity) was significantly lower in the distal compared to the proximal SFA location at both baseline and at the 2-year visit (p=0.003, p&lt;0.001). In a pooled analysis of all 33 PAD patients, the 2-year change of the average SFA velocity was significantly associated with the 2-year change in the averaged SFA lumen volume (beta: 0.00011, r 2 : 0.175, p=0.017). In a subgroup analysis, a similar pattern was observed in diabetic patients (beta: 0.00006, r 2 : 0.714, p=0.001), but not in non-diabetics (beta: -0.000019, r 2 : 0.0095, p=0.68). Conclusion: Longitudinal 2D-PC-MRI SFA velocity changes are associated with 2-year SFA lumen changes. 2D-PC-MRI velocity measures may be of interest in assessing PAD.

Abstract 12773: Computed Tomography Angiography Evaluation of Coronary Plaque Burden in South Asians and Non-Hispanic Whites Over 65 Years of Age

Introduction: South Asians (SA) have greater atherosclerotic cardiovascular disease (ASCVD) rates than non-Hispanic whites (NHW). SA ethnicity is a risk factor for cardiovascular disease, according to ACC/AHA guidelines. However, data on pattern of atherosclerosis in SA is limited. This study examines plaque burden in SA using quantitative plaque analysis from coronary CT angiography (CCTA). Methods: This is a cross-sectional study comparing the prevalence of atherosclerosis in SA to that of NHW. We identified 104 South Asians who underwent CCTA and quantitative plaque analysis. We then matched 1:1 with 104 non-Hispanic whites. Age, gender, diabetes, hypertension and smoking were utilized to perform a 1: 1 covariate match. Quantification of coronary plaque was conducted using automated plaque analysis software (Cleerly, NY, NY). Percentage atheroma volume (PAV), which is a measure of total plaque divided by total vessel volume, was calculated for each plaque subtypes. Results: A total of 208 subjects formed the study population. The mean age was 71.2±4.9, 66% being male, 38% had DM, 72% reported hypertension, and 10% were past smokers in each group. The SA cohort had significantly higher calcified plaque PAV compared to NHW cohort, median (IQR), 7.6(1.9, 15.5) versus 3.9(1.3, 9.6), (p=0.027). Noncalcified plaque PAV was higher in SA 5.2 (3.0, 7.9) versus 4.5 (2.6,7.2), but not statistically significant (p=0.35). The number of subjects with obstructive disease (&amp;gt50% stenosis) trended higher in the SA cohort (71% of SA versus 60% of NHW) (p=0.08). Conclusions: South Asians had significantly higher calcified plaque PAV and a higher prevalence of obstructive disease compared to the NHW cohort. These results are suggestive of a unique plaque burden and distinctive characteristics in the SA population, which may explain the greater incidence of cardiovascular events and supports the current guidelines.

Abstract 13967: Association Between Artificial Intelligence Identified Radiographic Pulmonary Vascular Injury and Cardiac Structure and Function in Patients With Chronic Obstructive Pulmonary Disease

Background Early recognition of cardiac dysfunction in patients with chronic obstructive pulmonary disease (COPD) may prevent future cardiac impairment and improve prognosis. Artificial intelligence (AI) using neural networks on Computed Tomographic (CT) imaging provides a measurement of loss of small vessel volume, as a surrogate of pulmonary vascular injury, and a compensatory increase in large vessel volume. This study investigated pulmonary vascular alteration in patients with COPD and its association with cardiac structure and function assessed by echocardiography. Methods: We studied 205 prospectively enrolled patients with COPD with an available CT scan and echocardiogram. AI algorithms calculated the small - and large vessel fraction as respectively the vascular volume in small vessels (5-10 mm 2 ) and large vessels (20-90 mm 2 ), indexed to total intrapulmonary vessel volume. Univariable and multivariable linear regressions were conducted, and standardized ß-coefficients were calculated. The multivariable model was adjusted by CT reconstruction kernel (spatial resolution). Results: In the unadjusted model, we found that loss in small vessel fraction and increase in large vessel volume were associated with higher left ventricular (LV) mass, LV diastolic dysfunction, and inferior vena cava dilatation. Small vessel fraction was also associated with right ventricular remodeling, while large vessel fraction was associated with higher pulmonary pressure. After adjustment, all measures remained significantly associated, except for tricuspid annular plane systolic excursion which did not. Measures of LV mass and right atrial pressure displayed the greatest associations with pulmonary vascular damage. Conclusion: We found that pulmonary vascular damage assessed by loss in small vessel fraction and increase in large vessel fraction, as assessed by AI on CT imaging, may negatively affect cardiac structure and function in patients with COPD.

Integration of micro-CT and histology data for vasculature morpho-functional analysis in tissue regeneration

The demand for artificial or bioartificial engineered tissues is increasing today in regenerative medicine techniques to replace and restore the physiological function of damaged tissues. Such engineered constructs hold different properties depending on the tissue to be replicated. As for vascularized tissues, complex biocompatible structures, namely scaffolds, play a key role in supporting oxygen and nutrient supply, thus sustaining tissue neoformation and integration with the host. Scaffold architecture significantly impacts its regenerative potential, while preclinical trials are essential to define scaffold-host interactions. In compliance with the 3 R principle, there is a clear need to optimize both the procedures to evaluate scaffold performance and the analysis methodology decreasing the number of animals required to gain consistent data. In parallel, current technologies used in preclinical research generate huge amounts of data that need to be elaborated and interpreted correctly. Therefore, we designed this study to evaluate the results of scaffold integration with the host tissue after implantation in a mouse subcutaneous pocket model. We evaluated the angiogenic response developed by the host and the degree of scaffold integration by using a combined morphometric approach based on both histological and micro-CT analyses. Six-layer scaffolds, made of polycaprolactone (PCL) microspheres, with an ordered structure were produced by thermal sintering. Scaffolds were then implanted in BALB/c mice and retrieved 21 days post-implantation when the animals were deeply anesthetized and perfused with Microfil, a contrast agent for micro-CT. Here, we describe a method to extract quantitative data from micro-CT reconstructions such as (i) total vessel volume; (ii)% of vessel penetration; (iii) distribution of vessel diameters. The general principle of this approach is the refinement of the region of interest (ROI), thus producing a volume of interest (VOI) that matches scaffold volume. This VOI serves as a dataset from which to extract volumetric information. Then VOIs are divided into three identical parts, proximal, median, and distal, to follow the vessel progression into the scaffold, thus obtaining their depth of penetration (DoP). By this methodology, we observed in mean, among the analyzed samples, a vessel invasion for 1,38 mm3 corresponding to the 1,53% of the scaffold volume. We then looked at the diameter distribution being this value a key indicator of vessel maturity, highlighting that 55% of vessels fall into the range from 5,99–53.99 µm while the remaining 45% are distributed into intervals from 54 to 136 µm. In parallel, to evaluate tissue integration in detail, histological and immunofluorescent analyses were performed to look at vessel distribution and collagen synthesis. Histological results strongly correlate with the micro-CT data providing, however, an overview of the ingrowth tissues. In addition, by immunofluorescent analysis we demonstrate that newly formed vessels are mature at the considered time point and tissue collagen deposition is widespread within the scaffolds. Collectively, we propose a new method to track vessel formation by using a multi-modal approach posing the basis for: i) the fabrication of novel scaffolds for Tissue Engineering; ii) the integration of detailed information for a wide range of morphological and functional analyses.

Additional clinical impact of plaque analysis for on-site CT-derived FFR in coronary CT angiography on midterm prognosis

Abstract Background We previously reported that per-patient on-site computed tomography-fractional flow reserve (CT-FFR), which can be acquired on-site workstation using fluid structure interaction during the multiple optimal diastolic phases measured 1 to 2 cm distal to a target lesion may be feasible for risk stratification based on future cardiac events for patients who did not undergo planned revascularization. However, per-vessel CT-FFR and the additional impact of plaque analysis on CT-FFR have not been evaluated. Purpose The aim of this study is to assess the clinical and additional impact of novel plaque analysis using labeling method for per-vessel CT-FFR on midterm prognosis. Methods A total of 254 consecutive patients with 354 vessels showing 50–90% stenosis but not revascularized within 90 days from coronary CT angiography (CCTA) on 320-row CT were retrospectively analyzed and followed during a median follow up 3.6 years. Plaque characteristics by labeling method (necrotic core/total plaque volume (% necrotic core), non-calcified plaque (NCP)/vessel volume (%NCP), and total plaque/vessel volume (%total plaque) for both total vessel volume (mm3) and at minimum lumen area (MLA, mm2)), positive remodeling (PR) and CT-FFR were analyzed on per-target vessels. The endpoint was vessel oriented-composite outcome (VOCO), including cardiac death, non-fatal MI, and unplanned revascularization. Results The incidence of VOCO occurred in 6.8% (24/354). In the cox proportional hazard model, a multivariate analysis identified CT-FFR≤0.80 was the most associated factor with VOCO (all values &amp;lt;0.01 for other plaque morphologies), but %necrotic core, %NCP, %total plaque at MLA and PR were significantly independent of CT-FFR≤0.80. (%necrotic core HR; 3.43 (p&amp;lt;0.01 [95% confidence interval (CI) 1.42–8.29]), %NCP HR; 4.05 (p=0.03 [95% CI 1.19–13.71]), %total plaque at MLA HR; 2.82 (p=0.02 [95% CI 1.18–6.76]), and PR HR; 2.90 (p&amp;lt;0.01 [95% CI 1.30–6.51]), respectively.) Conclusion From a view point of clinical outcomes for vessels with moderate to severe stenosis but not revascularized at initial CCTA, CT-FFR demonstrated the significant impact on per-vessel analysis. Moreover, %necrotic core, %NCP and %total plaque at MLA analyzed by labeling method provided better prognostic value in addition to CT-FFR. Funding Acknowledgement Type of funding sources: None.