Magnetic Resonance Elastography and Computational Modeling Identify Heterogeneous Lung Biomechanical Properties during Cystic Fibrosis.

The lung is a dynamic mechanical organ and several pulmonary disorders are characterized by heterogeneous changes in the lung's local mechanical properties (i.e. stiffness). These alterations lead to abnormal lung tissue deformation (i.e. strain) which have been shown to promote disease progression. Although heterogenous mechanical properties may be important biomarkers of disease, there is currently no non-invasive way to measure these properties for clinical diagnostic purposes. In this study, we use a magnetic resonance elastography technique to measure heterogenous distributions of the lung's shear stiffness in healthy adults and in people with Cystic Fibrosis. Additionally, computational finite element models which directly incorporate the measured heterogenous mechanical properties were developed to assess the effects on lung tissue deformation. Results indicate that consolidated lung regions in people with Cystic Fibrosis exhibited increased shear stiffness and reduced spatial heterogeneity compared to surrounding non-consolidated regions. Accounting for heterogenous lung stiffness in healthy adults did not change the globally averaged strain magnitude obtained in computational models. However, computational models that used heterogenous stiffness measurements predicted significantly more variability in local strain and higher spatial strain gradients. Finally, computational models predicted lower strain variability and spatial strain gradients in consolidated lung regions compared to non-consolidated regions. These results indicate that spatial variability in shear stiffness alters local strain and strain gradient magnitudes in people with Cystic Fibrosis. This imaged-based modeling technique therefore represents a clinically viable way to non-invasively assess lung mechanics during both health and disease.

Magnetic Resonance Elastography (MRE) of Bleomycin-Induced Pulmonary Fibrosis in an Animal Model.

BACKGROUND: Idiopathic pulmonary fibrosis is responsible for 40,000 deaths annually in the United States. A hallmark of idiopathic pulmonary fibrosis is elevated collagen deposition, which alters lung stiffness. Clinically relevant ways to measure changes in lung stiffness during pulmonary fibrosis are not available, and new noninvasive imaging methods are needed to measure changes in lung mechanical properties. OBJECTIVES: Magnetic resonance elastography (MRE) is an in vivo magnetic resonance imaging technique proven to detect changes in shear stiffness in different organs. This study used MRE, histology, and bronchoalveolar lavage (BAL) to study changes in the mechanical and structural properties of the lungs after bleomycin-induced pulmonary fibrosis in pigs. MATERIALS AND METHODS: Pulmonary fibrosis was induced in 9 Yorkshire pigs by intratracheal instillation of 2 doses of bleomycin into the right lung only. Magnetic resonance elastography scans were performed at baseline and week 4 and week 8 postsurgery in a 1.5 T magnetic resonance imaging scanner using a spin-echo echo planar imaging sequence to measure changes in lung shear stiffness. At the time of each scan, a BAL was performed. After the final scan, whole lung tissue was removed and analyzed for histological changes. RESULTS: Mean MRE-derived stiffness measurements at baseline, week 4, and week 8 for the control (left) lungs were 1.02 ± 0.27 kPa, 0.86 ± 0.29 kPa, and 0.68 ± 0.20 kPa, respectively. The ratio of the shear stiffness in the injured (right) lung to the uninjured control (left) lung at baseline, week 4, and week 8 was 0.98 ± 0.23, 1.52 ± 0.41, and 1.64 ± 0.40, respectively. High-dose animals showed increased protein in BAL fluid, elevated inflammation observed by the presence of patchy filtrates, and enhanced collagen and α-smooth muscle actin staining on histological sections. Low-dose animals and the control (left) lungs of high-dose animals did not show significant histopathological changes. CONCLUSION: This study demonstrated that MRE can be used to detect changes in lung stiffness in pigs after bleomycin challenge.

Free-breathing MR elastography of the lungs: An in vivo study.

PURPOSE: Lung stiffness alters with many diseases; therefore, several MR elastography (MRE) studies were performed earlier to investigate the stiffness of the right lung during breathhold at residual volume and total lung capacity. The aims of this study were 1) to estimate shear stiffness of the lungs using MRE under free breathing and demonstrate the measurements' repeatability and reproducibility, and 2) to compare lung stiffness under free breathing to breathhold and as a function of age and gender. METHODS: Twenty-five healthy volunteers were scanned on a 1.5 Tesla MRI scanner. Spin-echo dual-density spiral and a spin-echo EPI MRE sequences were used to measure shear stiffness of the lungs during free breathing and breathhold at midpoint of tidal volume, respectively. Concordance correlation coefficient and Bland-Altman analyses were performed to determine the repeatability and reproducibility of the spin-echo dual-density spiral-derived shear stiffness. Repeated measures analyses of variances were used to investigate differences in shear stiffness between spin-echo dual-density spiral and spin-echo EPI, right and left lungs, males and females, and different age groups. RESULTS: Free-breathing MRE sequence was highly repeatable and reproducible (concordance correlation coefficient > 0.86 for both lungs). Lung stiffness was significantly lower in breathhold than in free breathing (P < .001), which can be attributed to potential stress relaxation of lung parenchyma or breathhold inconsistencies. However, there was no significant difference between different age groups (P = .08). The left lung showed slightly higher stiffness values than the right lung (P = .14). There is no significant difference in lung stiffness between genders. CONCLUSION: This study demonstrated the feasibility of free-breathing lung MRE with excellent repeatability and reproducibility. Stiffness changes with age and during the respiratory cycle. However, gender does not influence lungs stiffness.

Effects of compressive lesions on intraoperative human spinal cord elasticity.

OBJECTIVE: Although evaluating tissue elasticity has various clinical applications, spinal cord elasticity (SCE) in humans has never been well documented. In this study, the authors aimed to evaluate the impact of compression on human SCE in vivo. METHODS: The authors prospectively assessed SCE using intraoperative shear wave elastography (SWE). All consecutive patients undergoing spinal cord (SC) decompression (laminectomy or corpectomy) between June 2018 and June 2019 were included. After intraoperative exposure of the patient's dura mater, at least three SWE measurements of the SC and its coverings were performed. Intraoperative neurological monitoring in the form of motor and somatosensory evoked potentials was utilized. Cases were divided into two groups based on the state of SC compression following bone removal (laminectomy or corpectomy): patients with adequate decompression (the decompressed SC group [DCG]) following bone removal and patients with remining compression, e.g., compressing tumor or instability (the compressed SC group [COG]). RESULTS: A total of 25 patients were included (8 females and 17 males) with a mean age of 48.28 ± 21.47 years. Most cases were degenerative diseases (10 cases) followed by tumors (6 cases), and the compression was observed at cervical (n = 14), thoracic (n = 9), and conus medullaris (n = 2) levels. The COG (6 cases) expressed significantly higher elasticity values, i.e., greater stiffness (median 93.84, IQR 75.27-121.75 kPa) than the decompressed SC in DCG (median 9.35, IQR 6.95-11.22 kPa, p < 0.001). Similarly, the compressed dura mater in the COG was significantly stiffer (mean ± SD 121.83 ± 70.63 kPa) than that in the DCG (29.78 ± 18.31 kPa, p = 0.042). Following SC decompression in COG, SCE values were significantly reduced (p = 0.006; adjusted for multiple comparisons). Intraoperative monitoring demonstrated no worsening from the baseline. CONCLUSIONS: The current study is to the authors' knowledge the first to quantitatively demonstrate increased stiffness (i.e., elasticity value) of the human SC and dura mater in response to external compression in vivo. It appears that SCE is a dynamic phenomenon and is reduced following decompression. Moreover, the evaluation of human SCE using the SWE technique is feasible and safe. Information from future studies aiming to further define SCE could be valuable in the early and accurate diagnosis of the compressed SC.

Magnetic resonance elastography of the lungs: A repeatability and reproducibility study.

Lung diseases are one of the leading causes of death worldwide, from which four million people die annually. Lung diseases are associated with changes in the mechanical properties of the lungs. Several studies have shown the feasibility of using magnetic resonance elastography (MRE) to quantify the lungs' shear stiffness. The aim of this study is to investigate the reproducibility and repeatability of lung MRE, and its shear stiffness measurements, obtained using a modified spin echo-echo planar imaging (SE-EPI) MRE sequence. In this study, 21 healthy volunteers were scanned twice by repositioning the volunteers to image right lung both at residual volume (RV) and total lung capacity (TLC) to assess the reproducibility of lung shear stiffness measurements. Additionally, 19 out of the 21 volunteers were scanned immediately without moving the volunteers to test the repeatability of the modified SE-EPI MRE sequence. A paired t-test was performed to determine the significant difference between stiffness measurements obtained at RV and TLC. Concordance correlation and Bland-Altman's analysis were performed to determine the reproducibility and repeatability of the SE-EPI MRE-derived shear stiffness measurements. The SE-EPI MRE sequence is highly repeatable with a concordance correlation coefficient (CCC) of 0.95 at RV and 0.96 at TLC. Similarly, the stiffness measurements obtained across all volunteers were highly reproducible with a CCC of 0.95 at RV and 0.92 at TLC. The mean shear stiffness of the lung at RV was 0.93 ± 0.22 kPa and at TLC was 1.41 ± 0.41 kPa. TLC showed a significantly higher mean shear stiffness (P = 0.0004) compared with RV. Lung MRE stiffness measurements obtained using the SE-EPI sequence were reproducible and repeatable, both at RV and TLC. Lung shear stiffness changes across respiratory cycle with significantly higher stiffness at TLC than RV.

Cardiovascular magnetic resonance elastography: A review.

Cardiovascular diseases are the leading cause of death worldwide. These cardiovascular diseases are associated with mechanical changes in the myocardium and aorta. It is known that stiffness is altered in many diseases, including the spectrum of ischemia, diastolic dysfunction, hypertension and hypertrophic cardiomyopathy. In addition, the stiffness of the aortic wall is altered in multiple diseases, including hypertension, coronary artery disease and aortic aneurysm formation. For example, in diastolic dysfunction in which the ejection fraction is preserved, stiffness can potentially be an important biomarker. Similarly, in aortic aneurysms, stiffness can provide valuable information with regard to rupture potential. A number of studies have addressed invasive and non-invasive approaches to test and measure the mechanical properties of the myocardium and aorta. One of the non-invasive approaches is magnetic resonance elastography (MRE). MRE is a phase-contrast magnetic resonance imaging technique that measures tissue stiffness non-invasively. This review article highlights the technical details and application of MRE in the quantification of myocardial and aortic stiffness in different disease states.