[Paper Review] A multiscale model of vascular function in chronic thromboembolic pulmonary hypertension

Mitchel J. Colebank, M. Umar Qureshi+3 more|arXiv (Cornell University)|Feb 12, 2021

Pulmonary Hypertension Research and Treatments76 references35 citations

TL;DR

This study develops a multiscale computational model integrating patient-specific CT-derived large pulmonary arteries with a fractal structured-tree model of small vessels to simulate hemodynamics in chronic thromboembolic pulmonary hypertension (CTEPH). By incorporating ring- and web-like lesions and vascular remodeling, the model predicts hemodynamic changes post-balloon pulmonary angioplasty (BPA), identifying optimal lesion targets using a combination of main pulmonary artery pressure, wave reflection index, and a novel flow heterogeneity metric—demonstrating improved hemodynamics after simulated BPA.

ABSTRACT

Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by recurrent or unresolved pulmonary thromboemboli, leading to perfusion defects and increased arterial wave reflections. CTEPH treatment aims to reduce pulmonary arterial pressure and reestablish adequate lung perfusion, yet patients with distal lesions are inoperable by standard surgical intervention. Instead, these patients undergo balloon pulmonary angioplasty (BPA), a multi-session, minimally invasive surgery that disrupts the thromboembolic material within the vessel lumen using a catheter balloon. However, there still lacks an integrative, holistic tool for identifying optimal target lesions for treatment. To address this insufficiency, we simulate CTEPH hemodynamics and BPA therapy using a multiscale fluid dynamics model. The large pulmonary arterial geometry is derived from a computed tomography (CT) image, whereas a fractal tree represents the small vessels. We model ring- and web-like lesions, common in CTEPH, and simulate normotensive conditions and four CTEPH disease scenarios; the latter includes both large artery lesions and vascular remodeling. BPA therapy is simulated by simultaneously reducing lesion severity in three locations. Our predictions mimic severe CTEPH, manifested by an increase in mean proximal pulmonary arterial pressure above 20 mmHg and prominent wave reflections. Both flow and pressure decrease in vessels distal to the lesions and increase in unobstructed vascular regions. We use the main pulmonary artery (MPA) pressure, a wave reflection index, and a measure of flow heterogeneity to select optimal target lesions for BPA. In summary, this study provides a multiscale, image-to-hemodynamics pipeline for BPA therapy planning for inoperable CTEPH patients.

Motivation & Objective

• To develop a patient-specific multiscale hemodynamic model for CTEPH that integrates large and small vessel dynamics.
• To simulate the effects of thromboembolic lesions and vascular remodeling on pulmonary hemodynamics.
• To evaluate the impact of balloon pulmonary angioplasty (BPA) on hemodynamic parameters in inoperable CTEPH patients.
• To identify optimal target lesions for BPA using a combination of pressure, wave reflection, and flow heterogeneity metrics.
• To establish a predictive pipeline for BPA therapy planning in distal CTEPH lesions.

Proposed method

• The large pulmonary arterial geometry is reconstructed from patient CT scans.
• A fractal structured-tree model represents the small pulmonary arteries, with hemodynamics governed by 1D fluid dynamics equations.
• Lesion types (ring- and web-like) are modeled at segmental and subsegmental branches to simulate CTEPH pathology.
• The model couples 1D wave propagation equations with frequency-domain analysis to compute pressure, flow, and impedance.
• Wave intensity analysis (WIA) and a new quantitative metric of flow heterogeneity are computed to assess hemodynamic impact.
• BPA therapy is simulated by reducing lesion severity at three locations simultaneously, with post-intervention hemodynamics evaluated.

Experimental results

Research questions

• RQ1 How do ring- and web-like lesions in the pulmonary arteries affect hemodynamic parameters such as mean pulmonary arterial pressure and wave reflections in CTEPH?
• RQ2 To what extent does small vessel remodeling contribute to increased pulmonary vascular resistance and flow heterogeneity in CTEPH?
• RQ3 Can a multiscale model accurately predict hemodynamic changes following simulated BPA in inoperable CTEPH patients?
• RQ4 Which hemodynamic indices—main pulmonary artery pressure, wave reflection index, and flow heterogeneity—best identify optimal BPA target lesions?
• RQ5 How does the model’s prediction of post-BPA hemodynamic improvement compare to clinical observations?

Key findings

• Simulated CTEPH with both large artery lesions and small vessel remodeling increases mean proximal pulmonary arterial pressure above 20 mmHg, matching clinical CTEPH thresholds.
• The model predicts prominent wave reflections and increased pulmonary vascular resistance, consistent with clinical CTEPH hemodynamics.
• Flow decreases in vessels distal to lesions and increases in unobstructed regions, reflecting perfusion heterogeneity.
• A novel quantitative metric of flow heterogeneity successfully captures regional perfusion deficits in the lung.
• Wave intensity analysis results align with clinical measurements of wave intensities in CTEPH patients.
• Post-simulated BPA, the model shows improved hemodynamics, including reduced pulmonary artery pressure and wave reflections, supporting lesion prioritization.