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Am J Physiol Heart Circ Physiol (April 29, 2004). doi:10.1152/ajpheart.00119.2004
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Submitted on February 5, 2004
Accepted on April 23, 2004

High-Resolution Imaging Reveals a Limit in the Spatial Resolution of Blood Flow Measurements by Microspheres

Ulrich K.M. Decking1*, Vinay M. Pai2, Eric Bennett2, Joni L. Taylor2, Christian D. Fingas3, Klaus Zanger4, Han Wen2, and Robert S. Balaban2

1 Department of Cardiovascular Physiology, Heinrich-Heine-University, Duesseldorf, Germany; NHLBI, Laboratory of Cardiac Energetics, National Institutes of Health, Bethesda, MD, USA
2 NHLBI, Laboratory of Cardiac Energetics, National Institutes of Health, Bethesda, MD, USA
3 Department of Cardiovascular Physiology, Heinrich-Heine-University, Duesseldorf, Germany
4 Institute for Anatomy II, Heinrich-Heine-University, Duesseldorf, Germany

* To whom correspondence should be addressed. E-mail: decking{at}uni-duesseldorf.de.

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 imaged by epifluorescence microscopy in vitro, and the patterns observed compared to MR images of iron oxide microspheres (IMS) obtained in vivo and in vitro. FMS deposition in myocardial slices revealed 1) a non-random 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 3D-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 intra-coronary adenosine (>2 µM) enhanced local MS density, but did not alter the deposition pattern (n=3). The non-random, temporally stable pattern was quantitatively confirmed by a 3D inter-microsphere 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.




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