Technical Brief

A Novel In Vivo Approach to Assess Radial and Axial Distensibility of Large and Intermediate Pulmonary Artery Branches

[+] Author and Article Information
A. Bellofiore

Department of Biomedical Engineering,
University of Wisconsin-Madison,
Madison, WI 53706-1609;
Department of Chemical,
Biomedical and Materials Engineering,
San José State University,
San José, CA 95192-0082

J. Henningsen, C. G. Lepak, L. Tian

Department of Biomedical Engineering,
University of Wisconsin-Madison,
Madison, WI 53706-1609

A. Roldan-Alzate, D. W. Consigny, C. J. Francois

Department of Radiology,
University of Wisconsin-Madison,
Madison, WI 53792-3252

H. B. Kellihan

Department of Veterinary Medicine,
University of Wisconsin-Madison,
Madison, WI 53706-1102

N. C. Chesler

Department of Biomedical Engineering,
University of Wisconsin-Madison,
2146 ECB, 1550 Engineering Drive,
Madison, WI 53706-1609
e-mail: chesler@engr.wisc.edu

1Corresponding author.

Manuscript received April 28, 2014; final manuscript received January 10, 2015; published online February 5, 2015. Assoc. Editor: Jonathan Vande Geest.

J Biomech Eng 137(4), 044501 (Apr 01, 2015) (6 pages) Paper No: BIO-14-1182; doi: 10.1115/1.4029578 History: Received April 28, 2014; Revised January 10, 2015; Online February 05, 2015

Pulmonary arteries (PAs) distend to accommodate increases in cardiac output. PA distensibility protects the right ventricle (RV) from excessive increases in pressure. Loss of PA distensibility plays a critical role in the fatal progression of pulmonary arterial hypertension (PAH) toward RV failure. However, it is unclear how PA distensibility is distributed across the generations of PA branches, mainly because of the lack of appropriate in vivo methods to measure distensibility of vessels other than the large, conduit PAs. In this study, we propose a novel approach to assess the distensibility of individual PA branches. The metric of PA distensibility we used is the slope of the stretch ratio–pressure relationship. To measure distensibility, we combined invasive measurements of mean PA pressure with angiographic imaging of the PA network of six healthy female dogs. Stacks of 2D images of the PAs, obtained from either contrast enhanced magnetic resonance angiography (CE-MRA) or computed tomography digital subtraction angiography (CT-DSA), were used to reconstruct 3D surface models of the PA network, from the first bifurcation down to the sixth generation of branches. For each branch of the PA, we calculated radial and longitudinal stretch between baseline and a pressurized state obtained via acute embolization of the pulmonary vasculature. Our results indicated that large and intermediate PA branches have a radial distensibility consistently close to 2%/mmHg. Our axial distensibility data, albeit affected by larger variability, suggested that the PAs distal to the first generation may not significantly elongate in vivo, presumably due to spatial constraints. Results from both angiographic techniques were comparable to data from established phase-contrast (PC) magnetic resonance imaging (MRI) and ex vivo mechanical tests, which can only be used in the first branch generation. Our novel method can be used to characterize PA distensibility in PAH patients undergoing clinical right heart catheterization (RHC) in combination with MRI.

Copyright © 2015 by ASME
Your Session has timed out. Please sign back in to continue.


Hunter, K. S., Lee, P.-F., Lanning, C. J., Ivy, D. D., Kirby, K. S., Claussen, L. R., Chan, K. C., and Shandas, R., 2008, “Pulmonary Vascular Input Impedance is a Combined Measure of Pulmonary Vascular Resistance and Stiffness and Predicts Clinical Outcomes Better Than Pulmonary Vascular Resistance Alone in Pediatric Patients With Pulmonary Hypertension,” Am. Heart J., 155(1), pp. 166–174. [CrossRef] [PubMed]
Mahapatra, S., Nishimura, R. A., Sorajja, P., Cha, S., and McGoon, M. D., 2006, “Relationship of Pulmonary Arterial Capacitance and Mortality in Idiopathic Pulmonary Arterial Hypertension,” J. Am. Coll. Cardiol., 47(4), pp. 799–803. [CrossRef] [PubMed]
Ooi, C. Y., Wang, Z., Tabima, D. M., Eickhoff, J. C., and Chesler, N. C., 2010, “The Role of Collagen in Extralobar Pulmonary Artery Stiffening in Response to Hypoxia-Induced Pulmonary Hypertension,” Am. J. Physiol. Heart Circ. Physiol., 299(6), pp. H1823–H1831. [CrossRef] [PubMed]
Gan, C. T.-J., Lankhaar, J.-W., Westerhof, N., Marcus, J. T., Becker, A., Twisk, J. W. R., Boonstra, A., Postmus, P. E., and Vonk-Noordegraaf, A., 2007, “Noninvasively Assessed Pulmonary Artery Stiffness Predicts Mortality in Pulmonary Arterial Hypertension,” Chest, 132(6), pp. 1906–1912. [CrossRef] [PubMed]
Sanz, J., Kariisa, M., Dellegrottaglie, S., Prat-González, S., Garcia, M. J., Fuster, V., and Rajagopalan, S., 2009, “Evaluation of Pulmonary Artery Stiffness in Pulmonary Hypertension With Cardiac Magnetic Resonance,” JACC Cardiovasc. Imaging, 2(3), pp. 286–295. [CrossRef] [PubMed]
D'Alonzo, G. E., Barst, R. J., Ayres, S. M., Bergofsky, E. H., Brundage, B. H., Detre, K. M., Fishman, A. P., Goldring, R. M., Groves, B. M., and Kernis, J. T., 1991, “Survival in Patients With Primary Pulmonary Hypertension. Results From a National Prospective Registry,” Ann. Intern. Med., 115(5), pp. 343–349. [CrossRef] [PubMed]
Dodson, R. B., Morgan, M., Galambos, C., Hunter, K. S., and Abman, S. H., 2014, “Chronic Intrauterine Pulmonary Hypertension Increases Main Pulmonary Artery Stiffness and Adventitial Remodeling in Fetal Sheep,” Am. J. Physiol. Lung Cell. Mol. Physiol., 307(11), pp. L822–L828. [CrossRef] [PubMed]
Swift, A. J., Rajaram, S., Condliffe, R., Capener, D., Hurdman, J., Elliot, C., Kiely, D. G., and Wild, J. M., 2012, “Pulmonary Artery Relative Area Change Detects Mild Elevations in Pulmonary Vascular Resistance and Predicts Adverse Outcome in Pulmonary Hypertension,” Invest. Radiol., 47(10), pp. 571–577. [CrossRef] [PubMed]
Su, Z., Tan, W., Shandas, R., and Hunter, K. S., 2013, “Influence of Distal Resistance and Proximal Stiffness on Hemodynamics and RV Afterload in Progression and Treatments of Pulmonary Hypertension: A Computational Study With Validation Using Animal Models,” Comput. Math. Methods Med., 2013, p. 618326. [CrossRef] [PubMed]
Su, Z., Hunter, K. S., and Shandas, R., 2012, “Impact of Pulmonary Vascular Stiffness and Vasodilator Treatment in Pediatric Pulmonary Hypertension: 21 Patient-Specific Fluid–Structure Interaction Studies,” Comput. Methods Programs Biomed., 108(2), pp. 617–628. [CrossRef] [PubMed]
Saouti, N., Westerhof, N., Helderman, F., Marcus, J. T., Stergiopulos, N., Westerhof, B. E., Boonstra, A., Postmus, P. E., and Vonk-Noordegraaf, A., 2009, “RC Time Constant of Single Lung Equals That of Both Lungs Together: A Study in Chronic Thromboembolic Pulmonary Hypertension,” Am. J. Physiol. Heart Circ. Physiol., 297(6), pp. H2154–H2160. [CrossRef] [PubMed]
Linehan, J. H., Haworth, S. T., Nelin, L. D., Krenz, G. S., and Dawson, C. A., 1992, “A Simple Distensible Vessel Model for Interpreting Pulmonary Vascular Pressure-Flow Curves,” J. Appl. Physiol., 73(3), pp. 987–994. [PubMed]
Blyth, K. G., Syyed, R., Chalmers, J., Foster, J. E., Saba, T., Naeije, R., Melot, C., and Peacock, A. J., 2007, “Pulmonary Arterial Pulse Pressure and Mortality in Pulmonary Arterial Hypertension,” Respir. Med., 101(12), pp. 2495–2501. [CrossRef] [PubMed]
Argiento, P., Chesler, N., Mulè, M., D'Alto, M., Bossone, E., Unger, P., and Naeije, R., 2010, “Exercise Stress Echocardiography for the Study of the Pulmonary Circulation,” Eur. Respir. J., 35(6), pp. 1273–1278. [CrossRef] [PubMed]
Vanderpool, R. R., Kim, A. R., Molthen, R., and Chesler, N. C., 2011, “Effects of Acute Rho Kinase Inhibition on Chronic Hypoxia-Induced Changes in Proximal and Distal Pulmonary Arterial Structure and Function,” J. Appl. Physiol., 110(1), pp. 188–198. [CrossRef] [PubMed]
Reeves, J. T., Linehan, J. H., and Stenmark, K. R., 2005, “Distensibility of the Normal Human Lung Circulation During Exercise,” Am. J. Physiol. Lung Cell. Mol. Physiol., 288(3), pp. L419–L425. [CrossRef] [PubMed]
Krenz, G. S., and Dawson, C. A., 2003, “Flow and Pressure Distributions in Vascular Networks Consisting of Distensible Vessels,” Am. J. Physiol. Heart Circ. Physiol., 284(6), pp. H2192–H2203. [CrossRef] [PubMed]
Scott-Drechsel, D., Su, Z., Hunter, K., Li, M., Shandas, R., and Tan, W., 2012, “A New Flow Co-Culture System for Studying Mechanobiology Effects of Pulse Flow Waves,” Cytotechnology, 64(6), pp. 649–666. [CrossRef] [PubMed]
Morrell, N. W., 2006, “Pulmonary Hypertension Due to BMPR2 Mutation: A New Paradigm for Tissue Remodeling?,” Proc. Am. Thorac. Soc., 3(8), pp. 680–686. [CrossRef] [PubMed]
Pavelescu, A., Vanderpool, R., Vachiéry, J.-L., Grunig, E., and Naeije, R., 2012, “Echocardiography of Pulmonary Vascular Function in Asymptomatic Carriers of BMPR2 Mutations,” Eur. Respir. J., 40(5), pp. 1287–1289. [CrossRef] [PubMed]
Naeije, R., 2013, “Physiology of the Pulmonary Circulation and the Right Heart,” Curr. Hypertens. Rep., 15(6), pp. 623–631. [CrossRef] [PubMed]
Bellofiore, A., Roldán-Alzate, A., Besse, M., Kellihan, H. B., Consigny, D. W., Francois, C. J., and Chesler, N. C., 2013, “Impact of Acute Pulmonary Embolization on Arterial Stiffening and Right Ventricular Function in Dogs,” Ann. Biomed. Eng., 41(1), pp. 195–204. [CrossRef] [PubMed]
Kalender, W. A., and Kyriakou, Y., 2007, “Flat-Detector Computed Tomography (FD-CT),” Eur. Radiol., 17(11), pp. 2767–2779. [CrossRef] [PubMed]
Kamran, M., Nagaraja, S., and Byrne, J. V., 2010, “C-Arm Flat Detector Computed Tomography: The Technique and Its Applications in Interventional Neuro-Radiology,” Neuroradiology, 52(4), pp. 319–327. [CrossRef] [PubMed]
Raman, S. V., Tran, T., Simonetti, O. P., and Sun, B., 2009, “Dynamic Computed Tomography to Determine Cardiac Output in Patients With Left Ventricular Assist Devices,” J. Thorac. Cardiovasc. Surg., 137(5), pp. 1213–1217. [CrossRef] [PubMed]
Rogers, T., Ratnayaka, K., and Lederman, R. J., 2014, “MRI Catheterization in Cardiopulmonary Disease,” Chest, 145(1), pp. 30–36. [CrossRef] [PubMed]
Ratnayaka, K., Faranesh, A. Z., Hansen, M. S., Stine, A. M., Halabi, M., Barbash, I. M., Schenke, W. H., Wright, V. J., Grant, L. P., Kellman, P., Kocaturk, O., and Lederman, R. J., 2013, “Real-Time MRI-Guided Right Heart Catheterization in Adults Using Passive Catheters,” Eur. Heart J., 34(5), pp. 380–389. [CrossRef] [PubMed]
Muthurangu, V., Atkinson, D., Sermesant, M., Miquel, M. E., Hegde, S., Johnson, R., Andriantsimiavona, R., Taylor, A. M., Baker, E., Tulloh, R., Hill, D., and Razavi, R. S., 2005, “Measurement of Total Pulmonary Arterial Compliance Using Invasive Pressure Monitoring and MR Flow Quantification During MR-Guided Cardiac Catheterization,” Am. J. Physiol. Heart Circ. Physiol., 289(3), pp. H1301–H1306. [CrossRef] [PubMed]
Kuehne, T., Yilmaz, S., Steendijk, P., Moore, P., Groenink, M., Saaed, M., Weber, O., Higgins, C. B., Ewert, P., Fleck, E., Nagel, E., Schulze-Neick, I., and Lange, P., 2004, “Magnetic Resonance Imaging Analysis of Right Ventricular Pressure–Volume Loops,” Circulation, 110(14), pp. 2010–2016. [CrossRef] [PubMed]
Naeije, R., and Chesler, N., 2012, “Pulmonary Circulation at Exercise,” Compr. Physiol., 2(1), pp. 711–741. [CrossRef] [PubMed]
Graham, R., Skoog, C., Macedo, W., Carter, J., Oppenheimer, L., Rabson, J., and Goldberg, H. S., 1983, “Dopamine, Dobutamine, and Phentolamine Effects on Pulmonary Vascular Mechanics,” J. Appl. Physiol., 54(5), pp. 1277–1283.
Borlaug, B. A., Melenovsky, V., Marhin, T., Fitzgerald, P., and Kass, D. A., 2005, “Sildenafil Inhibits Beta-Adrenergic-Stimulated Cardiac Contractility in Humans,” Circulation, 112(17), pp. 2642–2649. [CrossRef] [PubMed]
Argiento, P., Vanderpool, R. R., Mule, M., Russo, M. G., D'Alto, M., Bossone, E., Chesler, N. C., and Naeije, R., 2012, “Exercise Stress Echocardiography of the Pulmonary Circulation: Limits of Normal and Gender Differences,” Chest, 142(5), pp. 1158–1165. [CrossRef] [PubMed]
Tian, L., and Chesler, N. C., 2012, “In Vivo and In Vitro Measurements of Pulmonary Arterial Stiffness: A Brief Review,” Pulm. Circ., 2(4), pp. 505–517. [CrossRef] [PubMed]


Grahic Jump Location
Fig. 1

Flow chart of the process used to assess radial and axial distensibility from angiographic images. Stacks of 2D images, obtained with either CT-DSA or CE-MRA, were segmented to reconstruct 3D surface models of the PA network. Radial and axial distensibility were calculated for the first six branch generations. Note that in the text the branches R1 and L1 indicate the extralobar RPA and LPA, respectively.

Grahic Jump Location
Fig. 2

Change in average diameter of the six branch generations of RPA (solid line) and LPA (dashed line) from PRE to POST. Error bars show the SE. The straight dotted line represents the spatial resolution limit of CE-MRA (1.5 mm).

Grahic Jump Location
Fig. 3

Change in length of the six branch generations of RPA (solid line) and LPA (dashed line) from PRE to POST. Error bars show the SE. The straight dotted line represents the spatial resolution limit of CE-MRA (1.5 mm).



Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging and repositioning the boxes below.

Related Journal Articles
Related eBook Content
Topic Collections

Sorry! You do not have access to this content. For assistance or to subscribe, please contact us:

  • TELEPHONE: 1-800-843-2763 (Toll-free in the USA)
  • EMAIL: asmedigitalcollection@asme.org
Sign In