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1 Physikalisches Institut (EP5), Universitat Wuerzburg, Wuerzburg, Germany; Medizinische Universitatsklinik, Universitat Wuerzburg, Wuerzburg, Germany
2 Physikalisches Institut (EP5), Universitat Wuerzburg, Wuerzburg, Germany
3 Medizinische Universitatsklinik, Universitat Wuerzburg, Wuerzburg, Germany
4 Department of Cardiovascular Medicine, John Radcliffe Hospital, Oxford University, Oxford, United Kingdom
* To whom correspondence should be addressed. E-mail: Nahrendorf_M{at}Medizin.uni-wuerzburg.de.
Objective. To study morphological, functional and metabolic changes induced by chronic ischemia in myocardium supplied by the stenotic vessel and in the remote area by MR techniques. A new technique of image fusion is proposed for analysis of coronary artery stenosis involving coronary MR angiography and spectroscopic imaging. Methods. Cine-MRI was performed 2 weeks after induction of coronary stenosis. Global heart function and regional wall thickening were determined in 11 Wistar rats with stenosis and compared to 7 control. In 14 isolated hearts 2 weeks after induction of stenosis spin labeling MRI for measurement of perfusion was performed. In 8 isolated hearts with coronary stenosis, MR spectroscopy was performed followed by angiography. 31 P phosphorus metabolite maps were fused with 3D coronary angiograms. Results. Induction of stenosis led to reduced segmental wall thickening (control: 75±9%, ischemic region: 9±3%, p<0.05 vs control), but also to impaired function of the remote region and lower cardiac output. Perfusion was reduced by 74.9±4.0% within ischemic segments when compared to a septal control region. PCr/ATP ratio as a marker of ischemia was reduced in the region associated with stenosis (1.09±0.09) when compared to remote (1.27±0.08) and to control hearts (1.43±0.08; p<0.05). The histological fraction of fibrosis within the ischemic region (12.8±1.4%) correlated to ATP signal reduction from remote to the ischemic region (r=0.71, p<0.05), but not to reduced wall thickening. Conclusion. Coronary narrowing caused declining function accompanied by diminished PCr/ATP ratios, indicating impaired energy metabolism. Neither decline of function nor PCr signal decline correlated to fraction of fibrosis in histology. In contrast, reduction of ATP correlated to fibrosis and therefore to loss of viability. Impaired function within the ischemic region is associated with decreased phosphocreatine. Function of the remote region was affected as well. The fusion of PCr metabolite maps and the coronary angiogram may help to assess coronary morphology and resulting metabolic changes simultaneously.
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