Interstitial lung disease (ILD) is an umbrella term for various lung disorders that are associated with dramatic changes in lung stiffness due to fibrosis of the lung parenchyma. ILD can lead to other complications, including pulmonary hypertension and respiratory failure. The ILD mortality rate has markedly increased in recent years, and this upward trend is expected to continue. High-resolution computed tomography (HRCT) is the clinical standard for assessing lung fibrosis, but it is expensive and associated with high doses of radiation that limit its use during follow-up. We have developed a noninvasive and nonionizing technique, lung surface wave elastometry (LSWE), that measures the viscoelasticity of superficial lung tissue with speed and accuracy. Our long-term goal is to establish a role for LSWE in routine clinical care because its quantitative measurement of lung viscoelastic properties can be used for sensitive evaluation of lung disease. The specific goals of this application are to evaluate LSWE in longitudinal clinical studies by measuring lung viscoelasticity and to demonstrate the clinical utility of LSWE for quantitative assessment of lung fibrosis. The rationale is that a safer and cheaper alternative to HRCT is needed because patients with ILD (especially early stage disease) need frequent follow-up to assess disease progression and response to treatment; LSWE has the potential to meet this need by reliably and sensitively assessing lung fibrosis without using invasive or ionizing techniques. The proposed work is significant because LSWE will improve clinical assessment of ILD. It also is innovative in its use of a novel surface wave ultrasonography technique to measure lung viscoelasticity and in the evaluation of its clinical utility in longitudinal studies of ILD. To acieve our goals, we propose 2 specific aims.
In Aim 1, we will improve repeatability and reproducibility of LSWE measurements and assess the clinical utility of LSWE for evaluating lung fibrosis. We will determine whether the LSWE measurements are more sensitive than current clinical methods of assessing lung fibrosis.
Aim 2 incorporates the LSWE technique into longitudinal clinical studies evaluating patients with ILD. We will study 1) whether LSWE provides sensitive data about lung stiffness changes for patients with lung fibrosis; 2) whether LSWE can assess response to therapies more accurately than current clinical methods; and 3) whether detection of subtle changes in lung viscoelasticity is more sensitive than current clinical methods of assessing the severity and course of lung fibrosis. We are confident that this project will be successful because of our feasible techniques and extensive clinical research experience. Upon successful completion of this project, we will have a novel, noninvasive, nonionizing, fast, and portable clinical technique for quantitatively assessing lung fibrosis.

Public Health Relevance

Stiffening (sclerotic) lung tissue, a hallmark of many lung diseases, usually is assessed by high-resolution computed tomography. To avoid relying on this expensive method that requires delivery of high doses of radiation, our laboratory developed an ultrasound-based noninvasive method that quantifies lung stiffness. Here, we propose to evaluate the feasibility of this rapid and safe technique in long-term studies of patients with lun fibrosis. We anticipate confirming that this new approach is superior to current clinical methods of assessing disease progression and severity.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Biomedical Imaging Technology Study Section (BMIT)
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Harabin, Andrea L
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Mayo Clinic, Rochester
United States
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Zhang, Xiaoming; Zhou, Boran; Kalra, Sanjay et al. (2018) An Ultrasound Surface Wave Technique for Assessing Skin and Lung Diseases. Ultrasound Med Biol 44:321-331
Zhang, Xiaoming; Zhou, Boran; Bartholmai, Brian et al. (2018) A quantitative method for measuring the changes of lung surface wave speed for assessing disease progression of interstitial lung disease. Ultrasound Med Biol :
Zhou, Jinling; Zhang, Xiaoming (2018) A Lung Phantom Model to Study Pulmonary Edema Using Lung Ultrasound Surface Wave Elastography. Ultrasound Med Biol 44:2400-2405
Zhou, Boran; Zhang, Xiaoming (2018) Lung mass density analysis using deep neural network and lung ultrasound surface wave elastography. Ultrasonics 89:173-177
Zhou, Jinling; Zhang, Xiaoming (2018) Effect of a Thin Fluid Layer on Surface Wave Speed Measurements: A Lung Phantom Study. J Ultrasound Med :
Zhou, Boran; Zhang, Xiaoming (2018) Comparison of five viscoelastic models for estimating viscoelastic parameters using ultrasound shear wave elastography. J Mech Behav Biomed Mater 85:109-116
Clay, Ryan; Bartholmai, Brian J; Zhou, Boran et al. (2018) Assessment of Interstitial Lung Disease Using Lung Ultrasound Surface Wave Elastography: A Novel Technique With Clinicoradiologic Correlates. J Thorac Imaging :
Zhang, Xiaoming; Osborn, Thomas; Zhou, Boran et al. (2017) Lung Ultrasound Surface Wave Elastography: A Pilot Clinical Study. IEEE Trans Ultrason Ferroelectr Freq Control 64:1298-1304
Zhang, Xiaoming (2017) A surface wave elastography technique for measuring tissue viscoelastic properties. Med Eng Phys 42:111-115
Zhang, Xiaoming; Osborn, Thomas; Kalra, Sanjay (2016) A noninvasive ultrasound elastography technique for measuring surface waves on the lung. Ultrasonics 71:183-188

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