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Am J Physiol Heart Circ Physiol 287: H1132-H1140, 2004. First published April 29, 2004; doi:10.1152/ajpheart.00119.2004
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High-resolution imaging reveals a limit in spatial resolution of blood flow measurements by microspheres

Ulrich K. M. Decking,1,3 Vinay M. Pai,3 Eric Bennett,3 Joni L. Taylor,3 Christian D. Fingas,1 Klaus Zanger,2 Han Wen,3 and Robert S. Balaban3

1Department of Cardiovascular Physiology, 2Institute for Anatomy II, Heinrich-Heine-University, 40225 Düsseldorf, Germany; and 3Laboratory of Cardiac Energetics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892

Submitted 5 February 2004 ; accepted in final form 23 April 2004

Density of 15-µm microspheres after left atrial application is the standard measure of regional perfusion. In the heart, substantial differences in microsphere density are seen at spatial resolutions <5 ml, implying perfusion heterogeneity. Microsphere deposition imaging permits a superior evaluation of the distribution pattern. Therefore, fluorescent microspheres (FMS) were applied, FMS deposition in the canine heart was imaged by epifluorescence microscopy in vitro, and the patterns were observed compared with MR images of iron oxide microspheres (IMS) obtained in vivo and in vitro. FMS deposition in myocardial slices revealed the following: 1) a nonrandom distribution, with sequentially applied FMS of different color stacked within the same vessel, 2) general FMS clustering, and 3) rather large areas devoid of FMS (n = 3). This pattern was also seen in reconstructed three-dimensional images (<1 nl resolution) of FMS distribution (n = 4). Surprisingly, the deposition pattern of sequentially applied FMS remained virtually identical over 3 days. Augmenting flow by intracoronary adenosine (>2 µM) enhanced local microsphere density, but did not alter the deposition pattern (n = 3). The nonrandom, temporally stable pattern was quantitatively confirmed by a three-dimensional intermicrosphere distance analysis of sequentially applied FMS. T2-weighted short-axis MR images (2-µl resolution) of IMS revealed similar patterns in vivo and in vitro (n = 6), as seen with FMS. The observed temporally stable microsphere patterns are not consistent with the notion that microsphere deposition is solely governed by blood flow. We propose that at high spatial resolution (<2 µl) structural aspects of the vascular network dominate microsphere distribution, resulting in the organized patterns observed.

myocardial perfusion; microscopy; fluorescence; magnetic resonance; iron oxide particle



Address for reprint requests and other correspondence: U. K. M. Decking, Dept. of Cardiovascular Physiology, Heinrich-Heine-Univ., Universitätsstrasse, Bldg. 22.03, 40225 Düsseldorf, Germany (E-mail: decking{at}uni-duesseldorf.de).




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