In vivo assessment of absolute perfusion and intracapillary blood volume in the murine myocardium by spin labeling magnetic resonance imaging

Abstract

The absolute perfusion and the intracapillary or regional blood volume (RBV) in murine myocardium were assessed in vivo by spin labeling magnetic resonance imaging. Pixel-based perfusion and RBV maps were calculated at a pixel resolution of 469 ؋ 469 m and a slice thickness of 2 mm. The T 1 imaging module was a segmented inversion recovery snapshot fast low angle shot sequence with velocity compensation in all three gradient directions. The group average myocardial perfusion at baseline was determined to be 701 ؎ 53 mL (100 g ⅐ min) ؊1 for anesthesia with isoflurane (N ‫؍‬ 11) at a mean heart rate (HR) of 455 ؎ 10 beats per minute (bpm). This value is in good agreement with perfusion values determined by invasive microspheres examinations. For i.v. administration of the anesthetic Propofol, the baseline perfusion decreased to 383 ؎ 40 mL (100 g ⅐ min) ؊1 (N ‫؍‬ 17, P < 0.05 versus. isoflurane) at a mean heart rate of 261 ؎ 13 bpm (P < 0.05 versus isoflurane). In addition, six mice with myocardial infarction were studied under isoflurane anesthesia (HR 397 ؎ 7 bpm). The perfusion maps showed a clear decrease of the perfusion in the infarcted area. The perfusion in the remote myocardium decreased significantly to 476 ؎ 81 mL (100 g ⅐ min) ؊1 (P < 0.05 versus sham). Regarding the regional blood volume, a mean value of 11.8 ؎ 0.8 vol % was determined for healthy murine myocardium under anesthesia with Propofol (N ‫؍‬ 4, HR 233 ؎ 17 bpm). In total, the presented techniques provide noninvasive in vivo assessment of the perfusion and the regional blood volume in the murine myocardium for the first time and seem to be promising tools for the characterization of mouse models in cardiovascular research. Over the past decade, the mouse animal model has become an essential part of medical basic research. This is due to the high degree of similarity between the mouse and the human genomes of about 97% (1) and the resulting high relevance of mouse animal studies for human basic research. Regarding cardiovascular research, magnetic resonance imaging (MRI) provides noninvasive and accurate assessment of cardiac structure and function (2). Since the viability and the capability of the myocardium are strongly influenced by its microcirculation, a full characterization of the myocardium requires a quantification of parameters such as the perfusion and the intracapillary or regional blood volume (RBV). In particular, perfusion is of paramount importance as a physiologic parameter, since it strongly determines the function of organs and the severity of many diseases.Heart diseases involving ventricular dysfunction and hypertrophy show significant alterations of the myocardial perfusion and transgenic mouse models may be well suited to elucidate the underlying fundamental mechanisms.For the assessment of cardiac perfusion in mice, only a few methods have been presented to date. One possible approach is the quantification of the coronary flow in the isolated mouse heart by ultrasonic flow probes (3). The injection of labeled microsphe...

Visualizing Regional Myocardial Blood Flow in the Mouse

“…At present, dedicated small-animal magnetic resonance images can provide estimates of regional organ blood flow in mice. [4][5][6][7] But such instruments may not be readily available to many researchers, and high resolution requires long imaging times. Although our study was performed in an ex vivo heart preparation, the microsphere methods can be easily applied to living mice, other organs, and physiological conditions.…”

“…Magnetic resonance imaging provides a method with adequate spatial resolution to measure regional organ blood flow in mice [4][5][6][7] ; however, it requires sophisticated equipment and relatively long imaging times. Less high-tech methods to measure regional blood flow such as microspheres have been restricted to relatively larger organs that can be physically dissected to obtain spatial information and to accommodate the 400 microsphere per piece rule 8 required for confidence in the measurements.…”

Multimodal functional cardiac MRI in creatine kinase-deficient mice reveals subtle abnormalities in myocardial perfusion and mechanics

“…In addition, a second novel MR technique to quantify myocardial perfusion, which has also recently been modified to work in the small and rapidly beating mouse heart (12,22), was employed to assess myocardial perfusion in the CK Ϫ/Ϫ mice. A reduction in myocardial perfusion in hypertrophied hearts may be a significant risk for the development of systolic dysfunction over time (13,25), and the quantification of myocardial perfusion is thus important in the assessment of transgenic mice with LV hypertrophy, such as the CK Ϫ/Ϫ mice.…”

Myocardial Ischemia Without Obstructive Coronary Artery Disease: Perfusion MRI in Mouse Models

“…The use of this method in the heart is however limited in humans because of the relatively modest changes in signal due to spin labeling and cardiac motion artifacts. However, in mice, where MBF is higher than in humans, ASL has been used to measure myocardial perfusion at rest (77,(96)(97)(98)(99)(100)(101)(102), after vasodilation (77,98,102) and after MI (77,99,100).…”

“…The material for this aim is covered in Chapter 2 and this has been previously published However, it has been previously used to study myocardial perfusion in mice at rest, after vasodilation and after MI (77,96,(98)(99)(100)(101)(102)104,105). There is no published work comparing the two imaging techniques for myocardial perfusion imaging in mice.…”