(FLASH) inversion recovery T, measurements with two differ- ent blood pool contrast ... tal data yields realistic values for RBV and perfusion. The values, which ...
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Quantitative Regional Blood Volume Studies in Rat Myocardium in Vivo Elke Kahler, Christiane Waller, Eberhard Rommel, Karl-Heinz Hiller, Sabine Voll, Andrea Broich, Kai Hu, Klaus D. Schnackerz, Wolfgang R. Bauer, Greoug Ertl, Axel Haase Many pathophysiological processes in the myocardium are in close relation to changes of the regional blood volume and regional myocardial blood flow or perfusion. Only few methods exist to obtain quantitative values for these parameters. Quantitative regional blood volume (RBV) studies in rat myocardium are presented using snapshot fast low angle shot (FLASH) inversion recovery T, measurements with two different blood pool contrast agents, gadolinium diethylenetriaminopentaacetic acid (Gd-DTPA) albumin and Gd-DTPA polylysine. In contrast to previous attempts, each snapshot FLASH image acquisition was ECG-triggered under breathhold conditions. To measure relaxation times shorter than a heart cycle, each T, sequence was repeated two times with different delays between inversion pulse and first image acquisition. The experiments were performed on a Bruker Biospec 70/21 using a homogeneous transmitter coil and a circularly polarized surface receiver coil, a special ECG trigger unit, and a respirator that is controlled by the pulse program. Based on a fast exchange model RBV, maps were calculated from the relaxation time maps for different concentrations of the two blood pool contrast agents. A significant dependence of the RBV, values on blood t,was found. This is in accordance with a model that has been developed recently relating the dependence of RBV, on T, of blood to perfusion. For GdDTPA albumin, the application of the model to the experimental data yields realistic values for RBV and perfusion. The values, which are in accordance with literature data, were obtained at highest contrast agent concentrations i.e., lowest relaxation times of blood (ca. 200 ms). Key words: quantitative MRI; RBV; myocardium; contrast agents; T, imaging; ECG triggering.
INTRODUCTION
Chronic cardiac dysfunction may be associated with alterations of coronary microcirculation (1,2). Therefore, quantitative and noninvasive measurements of intracap~~~~
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MRM 40:517-525 (1998) From the Physikalisches lnstitut (E.K., E.R., K.H.H., S.V., A.B.. K.U., A.H.), Universitat Wurzburg, Germany; Medizinische Universitatsklinik (C.W., W.R.B., G.E.), MannheidHeideIberg, Germany; and Physiologische Chemie (K.D.S.), Universitat Wurzburg, Germany, Address correspondence to: Prof. Axel Haase, Physikalisches Institut, Lehrstyhl fur Biophysik, Am Hubland, 97074 Wurzurg, Germany, Received October 10, 1997; revised January 30, 1998; accepted March 18, 1998. This work was supported by Grant SFB 355 and Graduiertskolleg "NMR" HA 1232/8-1 of the Deutsche Forschungsgemeinschaft and of the Forschungsfonds der Universitatsklinik Mannheim/Heidelberg (Projekt 42). 0740-3194/98 $3.00 Copyright 0 1998 by Williams & Wilkins All rights of reproduction in any form reserved.
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illary blood volume and myocardial perfusion are a prerequisite for the assessment of a potential pathophysiological role of microcirculatory disturbance for progressive cardiac dysfunction. Magnetic resonance (MR) techniques may provide detailed and localized information about regional blood volume (RBV) and myocardial perfusion under in vivo conditions. One approach is the evaluation of the signal time course after bolus administration of a blood pool contrast agent, called first pass imaging (3, 4). This dynamic method allows direct measurement of perfusion speed, but is only semiquantitative in relation to parameters of microcirculation as quantification is based on a linear proportionality of signal intensity and contrast agent concentration. Another approach uses fast T, imaging that is based on the measurement of T, relaxation before and after administration of an intravascular contrast medium (5). In contrast to the first pass imaging technique, TI-RBV imaging allows TI measurements under steady state conditions and is, therefore, suitable to visualize RBV alterations over time when a long-lived contrast agent is used. In addition, this technique yields absolute RBV data and has already been applied successfully to RBV determination in rat brain, liver, and skeletal muscle (5). The application of this technique to myocardium is hampered by several obstacles. First attempts suffered from motion artifacts due to heart beat and respiration (5). In addition, it is indispensable that the contrast agent remains sufficiently long in the intravascular space. To suit this purpose, it is important to use macromolecules of sufficient and preferentially equal size, which is not easy to produce (6, 7). Theoretical considerations demonstrate (8) that in tissue under steady state conditions the effect of perfusion on relaxation time in tissue must be taken into account when calculating RBV values. These perfusion effects were neglected in the first attempts to determine RBV ( 5 ) , and are responsible for an overestimation of the real RBV (9) for the following reason: Perfusion exchanges a considerable amount of intracapillary blood within relaxation time in the myocardium (10,11). Since the relaxation time of the blood in the arterial system is different from that in the capillary system, the influence of perfusion on TI relaxation in tissue must he considered (8). The relation > holds for most tissues in the absence of intravascular contrast agents. Therefore, perfusion prolongs re-
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laxation in tissue. Application of blood pool agents inverts this relation and perfusion accelerates relaxation. This dependence of relaxation on perfusion implies an overestimation of the regional blood volume when RBV is calculated by models that neglect perfusion. After the implementation of several hardware improvements (12-14), the experimental setup was suitable for quantitative in vivo RBV measurements of the myocardium. The first step was then to study the dependence of the measured RBV values on regional blood flow in the myocardium to demonstrate the validity of a model describing the effect of perfusion on relaxation time in tissue (8).After incorporation of this model into postprocessing perfusion, corrected KBV maps and an approximation of perfusion were obtained in the myocardium. In addition, two macromolecular contrast agents and their qualities as a marker of the intravascular space were compared. Finally, that it is possible to observe changes of regional blood volume after application of a vasoactive drug was demonstrated.
derived according to the mean relaxation approximation (15, 16)
TI =
M(t)dt.
[XI
In studies on perfused rat hearts (17) assuming the same model for tissue, a lower boundary for the intracapillaryextravascular exchange rate of about 7 Hz was found, which indicated a fast exchange situation. A similar fast exchange can be assumed for data of the present study is more than 200-300 ms. when The time evolution of the magnetization of the blood just before entering the capillary region is determined by m,(t) and depends on the particular TI experiment conducted, specifically on the spatial range of the inversion pulse. When all magnetization is inverted by the use of a nonselective inversion pulse at the onset of a T I experiment, then mJt) = exp(-t/Tl,b,oud).Inserting this expression into Eq. [Z] leads to
THEORY
P 1
Details of a theoretical model will be presented briefly that describe the magnetization of a two-compartment system as a function of the intrinsic relaxation rates, the exchange rate between the intracapillary and extravascular space, the intracapillary blood volume, and the perfusion (8). Tissue is divided into two compartments, the intracapillary blood volume and the extravascular space. The contribution of magnetization in the arterial and venous system is neglected because they represent only a small fraction in myocardial tissue (
