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Cardiovascular imaging: what have we learned from animal models?

Santos A, Fernández-Friera L, Villalba M, López-Melgar B, España S, Mateo J, Mota RA, Jiménez-Borreguero J, Ruiz-Cabello J - Front Pharmacol (2015)

Bottom Line: 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.We will also describe the physiological findings and/or learning processes for imaging applications coming from models of the most common cardiovascular diseases.Finally we will discuss the limitations and future of imaging research with animal models.

View Article: PubMed Central - PubMed

Affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III Madrid, Spain ; CIBER de Enfermedades Respiratorias (CIBERES) Madrid, Spain ; Madrid-MIT M+Visión Consortium Madrid, Spain ; Department of Anesthesia, Massachusetts General Hospital, Harvard Medical School Boston, MA, USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Examples of T2 (A) and T1 parametric maps in animal models of myocardial infarction. (A) Shows the dynamic changes in T2 relaxation times in the ischemic region after permanent coronary occlusion and reperfusion in a pig. (B) Shows pre contrast (upper row) and post-gadolinium contrast on a mouse model. Adapted from Figure 5 of Fernández-Jiménez et al. (2015a) and from Figure 2 of Coolen et al. (2011) with original publisher's permission (Bio Med Central).
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Figure 2: Examples of T2 (A) and T1 parametric maps in animal models of myocardial infarction. (A) Shows the dynamic changes in T2 relaxation times in the ischemic region after permanent coronary occlusion and reperfusion in a pig. (B) Shows pre contrast (upper row) and post-gadolinium contrast on a mouse model. Adapted from Figure 5 of Fernández-Jiménez et al. (2015a) and from Figure 2 of Coolen et al. (2011) with original publisher's permission (Bio Med Central).

Mentions: The area at risk (AAR), defined as the hypoperfused myocardium during an acute coronary occlusion, is a major determinant of infarct size and clinical outcomes in MI. Additionally, accurate AAR quantification is important because it has been used as an end-point in clinical trials testing the efficacy of cardioprotective interventions (Feiring et al., 1987). Single-photon emission computed tomography (SPECT) is the traditional reference method for determining AAR by injection of technetium-based tracer before opening of the occluded vessel. However, CMR has been proposed as an alternative approach over the last years because of higher spatial resolution and the absence of tracer administration need or radiation exposure (Carlsson et al., 2009). In particular, T2-weighted (T2W) edema-sensitive sequences have enabled the identification of acutely ischemic myocardium by detecting increased signal intensity that reflects myocardial water content (Aletras et al., 2006; Friedrich et al., 2008). T2W imaging, however, is often limited by motion artifacts, incomplete blood suppression, low signal-to-noise ratio and coil sensitivity related-issues of surface coil. Newer quantitative CMR methods include: (1) T1 and T2 mapping imaging (Figure 2) that allow direct measurement of intrinsic tissue properties. These sequences are less dependent on confounders affecting signal intensity (Ugander et al., 2012) and their accuracy for AAR quantification is high compared to microsphere blood flow analysis in a dog model of ischemia/reperfusion injury (Fernandez-Jimenez et al., 2015b); (2) BOLD or modified blood oxygen level-dependent sequences which have been recently proposed to detect ischemic myocardium in a dog model of severe coronary stenosis (Tsaftaris et al., 2013); (3) Targeted microparticles of iron oxide, which shorten T2 and T2* relaxation times. By tracking up-regulated vascular cell and intercellular adhesion molecules, such as VCAM and ICAM, it is possible to detect and localize myocardial ischemia (Grieve et al., 2013); (4) Balanced steady-state free precession sequences with T2 preparation have also been proposed to detect myocardial edema in a porcine model and in patients with reperfused acute MI (Kellman et al., 2007).


Cardiovascular imaging: what have we learned from animal models?

Santos A, Fernández-Friera L, Villalba M, López-Melgar B, España S, Mateo J, Mota RA, Jiménez-Borreguero J, Ruiz-Cabello J - Front Pharmacol (2015)

Examples of T2 (A) and T1 parametric maps in animal models of myocardial infarction. (A) Shows the dynamic changes in T2 relaxation times in the ischemic region after permanent coronary occlusion and reperfusion in a pig. (B) Shows pre contrast (upper row) and post-gadolinium contrast on a mouse model. Adapted from Figure 5 of Fernández-Jiménez et al. (2015a) and from Figure 2 of Coolen et al. (2011) with original publisher's permission (Bio Med Central).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4612690&req=5

Figure 2: Examples of T2 (A) and T1 parametric maps in animal models of myocardial infarction. (A) Shows the dynamic changes in T2 relaxation times in the ischemic region after permanent coronary occlusion and reperfusion in a pig. (B) Shows pre contrast (upper row) and post-gadolinium contrast on a mouse model. Adapted from Figure 5 of Fernández-Jiménez et al. (2015a) and from Figure 2 of Coolen et al. (2011) with original publisher's permission (Bio Med Central).
Mentions: The area at risk (AAR), defined as the hypoperfused myocardium during an acute coronary occlusion, is a major determinant of infarct size and clinical outcomes in MI. Additionally, accurate AAR quantification is important because it has been used as an end-point in clinical trials testing the efficacy of cardioprotective interventions (Feiring et al., 1987). Single-photon emission computed tomography (SPECT) is the traditional reference method for determining AAR by injection of technetium-based tracer before opening of the occluded vessel. However, CMR has been proposed as an alternative approach over the last years because of higher spatial resolution and the absence of tracer administration need or radiation exposure (Carlsson et al., 2009). In particular, T2-weighted (T2W) edema-sensitive sequences have enabled the identification of acutely ischemic myocardium by detecting increased signal intensity that reflects myocardial water content (Aletras et al., 2006; Friedrich et al., 2008). T2W imaging, however, is often limited by motion artifacts, incomplete blood suppression, low signal-to-noise ratio and coil sensitivity related-issues of surface coil. Newer quantitative CMR methods include: (1) T1 and T2 mapping imaging (Figure 2) that allow direct measurement of intrinsic tissue properties. These sequences are less dependent on confounders affecting signal intensity (Ugander et al., 2012) and their accuracy for AAR quantification is high compared to microsphere blood flow analysis in a dog model of ischemia/reperfusion injury (Fernandez-Jimenez et al., 2015b); (2) BOLD or modified blood oxygen level-dependent sequences which have been recently proposed to detect ischemic myocardium in a dog model of severe coronary stenosis (Tsaftaris et al., 2013); (3) Targeted microparticles of iron oxide, which shorten T2 and T2* relaxation times. By tracking up-regulated vascular cell and intercellular adhesion molecules, such as VCAM and ICAM, it is possible to detect and localize myocardial ischemia (Grieve et al., 2013); (4) Balanced steady-state free precession sequences with T2 preparation have also been proposed to detect myocardial edema in a porcine model and in patients with reperfused acute MI (Kellman et al., 2007).

Bottom Line: 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.We will also describe the physiological findings and/or learning processes for imaging applications coming from models of the most common cardiovascular diseases.Finally we will discuss the limitations and future of imaging research with animal models.

View Article: PubMed Central - PubMed

Affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III Madrid, Spain ; CIBER de Enfermedades Respiratorias (CIBERES) Madrid, Spain ; Madrid-MIT M+Visión Consortium Madrid, Spain ; Department of Anesthesia, Massachusetts General Hospital, Harvard Medical School Boston, MA, USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus