173 research outputs found
Multimodality imaging of chronic thromboembolic pulmonary hypertension : new insights into old challenges
No full textBACKGROUND:Most forms of pulmonary hypertension carry unsatisfactory prognosis with the notable exception of chronic thromboembolic pulmonary hypertension (CTEPH), a complication of acute pulmonary embolism (APE) where complete cure is possible with pulmonary endarterectomy (PEA). CTEPH is often underdiagnosed leading to delayed referral or missed diagnosis. Computed Tomography Pulmonary Angiography (CTPA) is commonly performed in patients with suspected CTEPH or dyspnoea of unknown cause; however, the frequency of misdiagnosis of CTEPH findings on CTPA is currently unknown. There is abundant CT literature describing arterial abnormalities of CTEPH but none regarding venous flow disturbances. Hypodense filling defects within the pulmonary veins (pulmonary vein sign: PVS) has been noted in APE but its presence and relevance in CTEPH is unascertained. CTPA used for CTEPH diagnosis contains information on cardiac chamber size that has potential for adverse outcome prediction but this is unproven. As normative values for atrial volumes on non-ECG gated CTPA is lacking, it is necessary to establish normal ranges prior to appreciating morphological differences in CTEPH. OBJECTIVES: Comprehend extent of CTEPH misdiagnosis on CT by radiologists, evaluate venous flow abnormalities in CTEPH with proximal and distal distribution with hemodynamic correlation, derive normal ranges for biatrial volumes on non-ECG gated CT and assess if cardiac chamber size on CTPA is useful for CTEPH risk estimation and outcome prediction. MATERIALS & METHODS: Study 1: Original CT reports 35 patients awaiting PEA scored for pulmonary vascular, cardiovascular and lung parenchymal abnormalities and compared to reading by two investigators with cardiothoracic subspeciality experience. Control group for expert reads included 35 CTPAs negative for thromboembolism. Study 2: Blinded CTPA analysis of 50 proximal CTEPH cases and 50 controls each in 3 groups— APE, nonthromboembolic cohort, and pulmonary arterial hypertension (PAH). Pulmonary venous flow reduction was assessed by the presence of filling defect of at least 2 cm in a pulmonary vein draining into left atrium. Study 3: Retrospective multi-institutional study of 93 CTEPH cases with CTPA and right heart catheterisation performed with in 3- month period. After excluding 17 suboptimal CTPAs, there were 52 proximal and 24 distal cases. Blood flow in the major pulmonary veins was graded. Subgroup analysis of PVS was performed in 38 proximal cases before and after PEA. Study 4: Of 3334 cases who had CTPA over a 12-month period, 304 also had transthoracic echocardiography (TTE) within a 6-month period. Of these 74 had normal diastology on TTE. After applying CT exclusion criteria (thromboembolic disease, LA attenuation Study 5: Out of 53 patients who had PEA between 2014-2019, 44 had paired CTPA and right heart catheterisation before and after surgery. After excluding 11 cases with suboptimal CTPA, semiautomated and manual CT biatrial and biventricular size quantifications were performed in 33 patients and correlated with hemodynamic parameters. RESULTS: Study 1: Expert readers correctly identified all 35 CTEPH cases. Amongst original reporters, the terminology “CTEPH” was used in 2 patients. Another 7 descriptive reports picked up combination of PH and few vascular signs of CTEPH without stating a definitive diagnosis. Taking these 9 reports as being consistent with radiologists diagnosing CTEPH, overall sensitivity for original reporters was 26%. Pulmonary arterial abnormalities were described in isolation in 63% with no mention of PH or CTEPH. Signs of PH and mosaic attenuation were documented in 53% and 6% respectively. Study 2: PVS was most prevalent in CTEPH. Compared with all controls, sensitivity and specificity of PVS for CTEPH was 78.0% and 85.3% (95% CI, 64.0–88.5 & 78.6–90.6) versus 34.0% and 70.7% in APE, 8.0% and 62% in nonthromboembolic and 2.0% and 60% in PAH. Occlusive arterial disease was most commonly associated with corresponding absent venous flow. Study 3: There was no significant difference in hemodynamic parameters (mPAP 46±11 and 41±12 mm Hg and PVR 9.4±4.5 and 8.4 ±4.8 WU) between the 2 groups but PVS was more frequent in proximal (79%) than distal (29%) CTEPH. PVS was present in 29/38 patients (76%) before surgery. Postoperatively, 33/38 cases (87%, PStudy 4: Normal ranges for indexed LA and RA volumes were 27 + 5 and 20 + 6 mL/m2, and 30 + 8 and 29 + 9 mL/m2 for TTE and CT respectively. Bland–Altman analysis revealed underestimation of biatrial volumes by TTE. CT intraclass correlation coefficients (ICC 95% CI) for LA and RA volumes were 0.99 (0.96– 1.00) and 0.96 (0.76–0.99), respectively with excellent correlation between semiautomated and manual measurements for left (r 0.99, 95% CI 0.98–0.99) and right atrium (r 0.99, 95% CI 0.99–1.00). Study 5: Indexed right atrioventricular volumes were twice that of left atrioventricular volumes pre-PEA with significant (p CONCLUSION: Radiologists frequently miss CTEPH findings giving falsely low sensitivity for CT. PVS is easy to detect with higher sensitivity and specificity in CTEPH compared with APE and is not a PAH characteristic. Asymmetric pulmonary venous enhancement is an additional parameter in CT assessment of CTEPH and can differentiate CTEPH from PAH. PVS is a common feature in proximal but infrequent in distal CTEPH. PVS does not correlate with hemodynamic severity. PVS resolution following PEA can be a measure of successful clearance. Cardiac chamber assessment on CTPA is easy and reproducible. A RV:LV ratio of ≥1.01 is a simple metric that can be used for CTEPH outcome prediction.LIST OF SCIENTIFIC PAPERSI. Rogberg AN, Gopalan D, Westerlund E, Lindholm P. Do radiologists detect chronic thromboembolic disease on computed tomography? Acta Radiol. 2019 Nov;60(11):1576-1583. PMID: 30897932.https://doi.org/10.1177/0284185119836232II. Gopalan D, Nordgren-Rogberg A, Le EPV, Pavey H, Tarkin J, Nyrén S, Auger W, Lindholm P. Abnormal Pulmonary Venous Filling: An Adjunct Feature in the Computed Tomography Pulmonary Angiogram Assessment of Chronic Thromboembolic Pulmonary Hypertension. J Am Heart Assoc. 2020 Nov 3;9(21):e018075. PMID: 33115320; PMCID: PMC7763423.https://doi.org/10.1161/JAHA.120.018075III. Gopalan D, Riley JYJ, Leong K, Guo HH, Zamanian RT, Hsi A, Auger W, Lindholm P. Pulmonary Vein Sign on Computed Tomography Pulmonary Angiography in Proximal and Distal Chronic Thromboembolic Pulmonary Hypertension With Hemodynamic Correlation. J Thorac Imaging. 2023 May 1;38(3):159-164. PMID: 36919975; PMCID: PMC10128904.https://doi.org/10.1097/RTI.0000000000000706IV. Gopalan D, Riley J, Leong K, Alsanjari S, Ariff B, Auger W, Lindholm P. Biatrial Volumetric Assessment by Non-ECG-Gated CT Pulmonary Angiography Correlated with Transthoracic Echocardiography in Patients with Normal Diastology. Tomography. 2022 Nov 17;8(6):2761-2771. PMID: 36412689; PMCID: PMC9680340.https://doi.org/10.3390/tomography8060230V. Gopalan D, Riley JYJ, Leong K, Alsanjari S, Auger W, Lindholm P. Computed Tomography Pulmonary Angiography Prediction of Adverse Long-Term Outcomes in Chronic Thromboembolic Pulmonary Hypertension: Correlation with Hemodynamic Measurements Pre- and Post-Pulmonary Endarterectomy. Tomography. 2023 Sep 26;9(5):1787-1798. PMID: 37888734; PMCID: PMC10611069.https://doi.org/10.3390/tomography9050142</p
Exploring disease-related changes in pulmonary arterial geometries and endothelial dysfunction in CTEPH
No full textChronic thromboembolic pulmonary hypertension (CTEPH) is a severe lung condition resulting from non-resolving pulmonary emboli, which cause vascular remodelling and elevated pulmonary arterial pressure. However, the exact role of alterations in arterial geometries and the resulting endothelial dysfunction in the development of CTEPH remains unclear.
Using 3D-printed in vitro models of pulmonary arterial stenoses found in CTEPH, the effects of arterial geometries and resulting changes in flow patterns on pulmonary endothelial function were characterised. Severe degrees of stenosis (60-80%) induced non-laminar, disturbed flow patterns in the post-stenotic dilatation region of the in vitro channels, which correlated with a loss of human pulmonary arterial endothelial cells (HPAECs) alignment and endothelial junctional integrity. Differential gene expression was observed in HPAECs cultured in various regions of the stenotic channels, with the levels of pro-inflammatory, pro-thrombotic and pro-angiogenic responses depending on the degree of stenosis. Additionally, increased platelet adhesion was observed in regions of disturbed flow.
The vascular stenosis models presented in this thesis highlight the importance of acute changes in vascular geometry on blood flow patterns, and the resulting impact on endothelial function and platelet aggregation. These CT scans-derived in vitro models have the potential to improve our understanding of pulmonary endothelial cells’ responses to vascular occlusion, not only in the context of CTEPH but also other diseases caused by stenosis, and demonstrate the potential of microfluidic platforms to bridge the gap between basic and clinical research.Open Acces
Direct numerical simulation of two-phase stratified flows in the primary coolant of a nuclear reactor
No full textMultiphase flows are very common in many Nuclear engineering applications. During high pressurized conditions there are possibilities of high thermal loads on the pressure vessel, leading to pipe ruptures. As part of breakdown measures, the emergency core cooling system is activated and the coolant is mixed with the fluid in the cold leg, giving rise to multiphase turbulent flow. These regimes can comprise of large scale interfaces, leading to stratified flows. These postulated accidents or events need to be identified and understood to improve nuclear reactor safety. Computational fluid dynamics can serve as an excellent tool to model these scenarios, contributes towards reactor safety. Coarse models which are widely used in industries such as RANS are known to over-predict turbulent producing unphysical gradients. Thus the turbulent mass and momentum are not yet fully understood. Using high resolution tools such as Direct Numerical Simulations (DNS), can potentially avoid these over-prediction and could model these large scale interfaces accurately. As a long term goal, the data sets generated from these simulations can be used to train such coarse models or simply support for validation. Placing the focus on a configuration where two fluids are in a stratified scenario, this graduation thesis will show a systematic approach towards the development and modelling of air and water moving in both co-current and counter-current direction, wherein simulations are performed in RK-Basilisk. Primarily, the work starts with studying a single phase turbulent channel flow to forma basis of understanding of concepts and code. The model of (Liu et al. 2009), who use realistic properties of air-water is chosen to be implemented in RK-Basilisk. It is realized that, implementing this is in RK-Basilisk is not straightforward and thus the constraints are identified and a general mathematical framework is developed to resolve this. One of the main objectives in this thesis is to model and understand the turbulent behavior near the interface of both air and water. To do so, the physical mechanisms which govern the generation and decay of turbulence called the TKE Budgets is studied by modelling the individual terms that complete it. The budgets are modelled and validated against (Liu et al. 2009). Interesting conclusions are drawn which depict the trends of budget terms and the kinetic energy, giving a good picture of the underlying interfacial turbulent mechanisms. The same mathematical framework, along with some additional modelling lead to an extension of this study to counter-current flows, wherein another set ofconclusions are drawn.Applied Mathematics | COSSE (Computer Simulations for Science and Engineering
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