Serial MRI characterization of the functional and morphological changes in mouse lung in response to cardiac remodeling following myocardial infarction

Alsaid, Hasan; Bao, Weike; Rambo, Mary V.; Logan, Gregory A.; Figueroa, David J.; Lenhard, Stephen C.; Kotzer, Charles J.; Burgert, Mark; Willette, Robert N.; Ferrari, Victor A.; Jucker, Beat M.

doi:10.1002/mrm.22973

Cited by 7 publications

(6 citation statements)

References 22 publications

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“…Magnetic resonance imaging (MRI) was used to assess pulmonary edema after MI (27), demonstrating an increased lung water signal intensity and lung volume associated with pulmonary edema ( Table 2). This was observed in both the left and the right lungs and was associated with an increased lung weight.…”

Section: Impact Of Trpv4 Blockade On Osmoregulationmentioning

confidence: 99%

“…Next, we used a myocardial infarction (MI) HF model to assess the effects of TRPV4 blockade during chronically elevated left ventricular diastolic pressure in mice. Magnetic resonance imaging (MRI) was used to assess pulmonary edema after MI (27), demonstrating an increased lung water signal intensity and lung volume associated with pulmonary edema (Table 2). This was observed in both the left and the right lungs and was associated with an increased lung weight.…”

Section: Trpv4 Blockade and The Activity Of Diureticsmentioning

confidence: 99%

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An Orally Active TRPV4 Channel Blocker Prevents and Resolves Pulmonary Edema Induced by Heart Failure

et al. 2012

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Pulmonary edema resulting from high pulmonary venous pressure (PVP) is a major cause of morbidity and mortality in heart failure (HF) patients, but current treatment options demonstrate substantial limitations. Recent evidence from rodent lungs suggests that PVP-induced edema is driven by activation of pulmonary capillary endothelial transient receptor potential vanilloid 4 (TRPV4) channels. To examine the therapeutic potential of this mechanism, we evaluated TRPV4 expression in human congestive HF lungs and developed small-molecule TRPV4 channel blockers for testing in animal models of HF. TRPV4 immunolabeling of human lung sections demonstrated expression of TRPV4 in the pulmonary vasculature that was enhanced in sections from HF patients compared to controls. GSK2193874 was identified as a selective, orally active TRPV4 blocker that inhibits Ca(2+) influx through recombinant TRPV4 channels and native endothelial TRPV4 currents. In isolated rodent and canine lungs, TRPV4 blockade prevented the increased vascular permeability and resultant pulmonary edema associated with elevated PVP. Furthermore, in both acute and chronic HF models, GSK2193874 pretreatment inhibited the formation of pulmonary edema and enhanced arterial oxygenation. Finally, GSK2193874 treatment resolved pulmonary edema already established by myocardial infarction in mice. These findings identify a crucial role for TRPV4 in the formation of HF-induced pulmonary edema and suggest that TRPV4 blockade is a potential therapeutic strategy for HF patients.

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Section: Impact Of Trpv4 Blockade On Osmoregulationmentioning

confidence: 99%

Section: Trpv4 Blockade and The Activity Of Diureticsmentioning

confidence: 99%

An Orally Active TRPV4 Channel Blocker Prevents and Resolves Pulmonary Edema Induced by Heart Failure

et al. 2012

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“…In this study, the ZTE protocols developed provide full lung coverage with an isotropic resolution of 313 µm and an SNR between 8.0 and 18.5, within scan times between 1 min 21 s and 4 min 44 s. Furthermore, consistently good image quality is observed for all of the six mice. Thus, with respect to all previously reported similar studies , an improvement is achieved for one or multiple key criteria.…”

Section: Discussionmentioning

confidence: 73%

“…The latter is caused by the many tissue–air interfaces, with large differences in magnetic susceptibility and thus strong microscopic magnetic field inhomogeneities, leading to rapid intra‐voxel signal decay, which is further aggravated by diffusion . Therefore, in images obtained with conventional gradient echo techniques, the lung has a very low signal‐to‐noise ratio (SNR) and appears dark . The application of spin echoes only partly enables refocusing of the T 2 * decay, which is caused by diffusion, and is furthermore hampered by cardiac and respiratory motion .…”

Section: Introductionmentioning

confidence: 99%

Rapid and robust pulmonary proton ZTE imaging in the mouse

Weiger

Wurnig

et al. 2014

NMR Biomed.

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Pulmonary MRI is challenging because of the low proton density and rapid transverse relaxation in the lung associated with microscopic magnetic field inhomogeneities caused by tissue-air interfaces. Therefore, low signal is obtained in gradient and spin echo proton images. Alternatively, non-proton MRI using hyperpolarized gases or radial techniques with ultrashort or zero TE have been proposed to image the lung. Also with the latter approach, the general challenge remains to provide full coverage of the lung at sufficient spatial resolution, signal-to-noise ratio (SNR) and image quality within a reasonable scan time. This task is further aggravated by physiological motion and is particularly demanding in small animals, such as mice. In this work, three-dimensional (3D) zero echo time (ZTE) imaging is employed for efficient pulmonary MRI. Four protocols with different averaging and respiratory triggering schemes are developed and compared with respect to image quality and SNR. To address the critical issue of background signal in ZTE images, a subtraction approach is proposed, providing images virtually free of disturbing signal from nearby hardware parts. The protocols are tested for pulmonary MRI in six mice at 4.7 T, consistently providing images of high quality with a 3D isotropic resolution of 313 µm and SNR values in the lung between 8.0 and 18.5 within scan times between 1 min 21 s and 4 min 44 s. A generally high robustness of the ZTE approach against motion is observed, whilst respiratory triggering further improves the SNR and visibility of image details. The developed techniques are expected to enable efficient preclinical animal studies in the lung and will also be of importance for human applications. Further improvements are expected from radiofrequency (RF) coils with increased SNR and reduced background signal.

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“…Finally, CMR can be simultaneously used to assess the progression of ventricular dysfunction with lung congestion. This non-invasive technology is especially applicable to serial studies and in drug discovery programs exploring the use of novel pharmacological or molecular agents for treatment of heart failure and/or pulmonary congestion (Alsaid et al, 2012 ).…”

Section: Heart Failurementioning

confidence: 99%

Cardiovascular imaging: what have we learned from animal models?

et al. 2015

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Cardiovascular imaging has become an indispensable tool for patient diagnosis and follow up. Probably the wide clinical applications of imaging are due to the possibility of a detailed and high quality description and quantification of cardiovascular system structure and function. Also phenomena that involve complex physiological mechanisms and biochemical pathways, such as inflammation and ischemia, can be visualized in a non-destructive way. The widespread use and evolution of imaging would not have been possible without animal studies. Animal models have allowed for instance, (i) the technical development of different imaging tools, (ii) to test hypothesis generated from human studies and finally, (iii) to evaluate the translational relevance assessment of in vitro and ex-vivo results. In this review, we will critically describe the contribution of animal models to the use of biomedical imaging in cardiovascular medicine. We will discuss the characteristics of the most frequent models used in/for imaging studies. We will cover the major findings of animal studies focused in the cardiovascular use of the repeatedly used imaging techniques in clinical practice and experimental studies. We will also describe the physiological findings and/or learning processes for imaging applications coming from models of the most common cardiovascular diseases. In these diseases, imaging research using animals has allowed the study of aspects such as: ventricular size, shape, global function, and wall thickening, local myocardial function, myocardial perfusion, metabolism and energetic assessment, infarct quantification, vascular lesion characterization, myocardial fiber structure, and myocardial calcium uptake. Finally we will discuss the limitations and future of imaging research with animal models.

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Serial MRI characterization of the functional and morphological changes in mouse lung in response to cardiac remodeling following myocardial infarction

Cited by 7 publications

References 22 publications

An Orally Active TRPV4 Channel Blocker Prevents and Resolves Pulmonary Edema Induced by Heart Failure

An Orally Active TRPV4 Channel Blocker Prevents and Resolves Pulmonary Edema Induced by Heart Failure

Rapid and robust pulmonary proton ZTE imaging in the mouse

Cardiovascular imaging: what have we learned from animal models?

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