Coronary flow reserve is a functional measure of stenosis severity re­ flecting the integrated effects of its geometry including percent stenosis, absolute lumen area, length and shape. Its clinical application has been primarily qualitative in non-invasive, perfusion imaging. Measurement of coronary flow reserve during routine coronary arte­ riography has been an elusive goal. Transit time and indicator dilution techniques for assessing coronary flow reserve at cardiac catheteriza­ tion are associated with marked variability compared to microspheres or flow meters, thereby making their use questionable in comparison to the precision of good quantitative arteriography. Coronary flow reserve measured by special Doppler catheters as an adjunct to coronary arte­ riography shows in man the value of this integrated functional measure of stenosis severity and the limitations of percent diameter narrowing as a measure of its physiologic significance. However, Doppler catheters require additional instrumentation that is not yet an integral part of coronary arteriography and provide measures of absolute coronary flow reserve only. Relative maximum flow or relative flow reserve has been demon­ strated to be an important independent, complimentary descriptor of stenosis severity independent of fluctuating hemodynamic conditions. The method developed for DSA by Nico Pijls, described in this book is the first approach for assessing relative coronary flow reserve as a part of routine coronary arteriography by DSA. The theory and basic con­ cepts are well developed, experimental validation thorough and clinical applications timely.

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1 Introduction.- 1.1 The limited value of classical coronary arteriography to predict the physiologic significance of coronary artery stenoses.- 1.2 Coronary flow reserve.- 1.3 Maximal coronary and myocardial blood flow.- 2 Methods of Measuring Myocardial Blood Flow.- 2.1 Laboratory methods.- 2.1.1 Timed venous collection.- 2.1.2 Electromagnetic flow measurement.- 2.1.3 Epicardial ultrasonic flow velocity measurement.- 2.1.4 Microspheres.- 2.2 Clinical methods.- 2.2.1 Coronary sinus thermodilution.- 2.2.2 Gas clearance methods.- 2.2.3 The Doppler catheter.- 2.2.4 Videodensitometry.- 2.2.5 Positron emission tomography.- 2.2.6 Other methods.- 3 Application of Indicator Dilution Theory in the Investigation of the Cardiovascular System.- 3.1 History.- 3.2 The two approaches in indicator dilution theory.- 3.2.1 Measurement of Flow.- 3.2.2 Measurement of Volume.- 3.2.3 Calculation of Mean Transit Time.- 3.3 Videodensitometry and digital arteriography for flow assessment in the coronary circulation.- 4 Problems and Limitations in the Application of Videodensitometry to Assess Coronary Blood Flow and Myocardial Perfusion.- 4.1 Influence of the contrast agent on flow.- 4.2 Changes in vascular volume.- 4.3 Contrast density vs contrast concentration.- 4.4 Difficulties in determination of mean transit time due to motion and insufficient image quality.- 4.5 Prerequisites for myocardial flow assessment by videodensitometry, according to the physiology of indicator dilution theory.- 5 A Model Study to Validate Calculation of Myocardial Blood Flow by Videodensitometry.- 5.1 Introduction.- 5.2 Materials and methods.- 5.2.1 Flow model.- 5.2.2 Image acquisition and processing.- 5.2.3 Absorption characteristics.- 5.2.4 Processing of time-density curves.- 5.2.5 Relation between flow and time parameters.- 5.3 Results.- 5.3.1 Applicability of Lambert-Beer's law.- 5.3.2 Fitting of the curves.- 5.3.3 Assessment of relative flow.- 5.3.4 Assessment of absolute flow.- 5.4 Discussion.- 5.5 Conclusions.- 6 Mean Transit Time for the Assessment of Myocardial Perfusion by Videodensitometry.- 6.1 Introduction.- 6.2 Methods.- 6.2.1 Animal instrumentation and experimental protocol.- 6.2.2 Achievement of constant vascular volume and different flow levels.- 6.2.3 Image acquisition and image processing.- 6.2.4 Processing of regions of interest and time-density curves.- 6.2.5 Data processing and statistical analysis.- 6.3 Results.- 6.3.1 Hemodynamic observations and verification of the animal model.- 6.3.2 Quality of image acquisition and time-density curves.- 6.3.3 Relation between inverse mean transit time and flow.- 6.3.4 Relation between 1/Tapp(1), 1/Tapp(2), 1/Tapp(3), Dmax, Dmax/Tapp(1), Dmax/Tapp(2), Dmax/Tapp(3), 1/Tmax and flow.- 6.4 Discussion.- 6.5 Clinical implications and limitations.- 7 The Concept of Maximal Flow Ratio for Immediate Evaluation of PTCA Result.- 7.1 Introduction.- 7.2 Methods.- 7.2.1 Patient population and study design.- 7.2.2 Image acquisition and processing.- 7.2.3 Processing of the regions of interest and time-density curves.- 7.2.4 Data processing and statistical analysis.- 7.3 Results.- 7.3.1 Clinical and hemodynamic data.- 7.3.2 Quality and reproducibility of image acquisition and time-density curves.- 7.3.3 Relation between MFR and exercise tests results.- 7.3.4 Comparison of T mn belonging to apparently normal arteries and to stenotic arteries before and after successful PTCA.- 7.4 Discussion.- 7.5 Limitations.- 8 Reproducibility of Mean Transit Time for Maximal Myocardial Flow Assessment.- 8.1 Introduction.- 8.2 Methods.- 8.2.1 Study protocol and image acquisition.- 8.2.2 Image processing and processing of TDCs.- 8.2.3 Data processing and statistical analysis.- 8.3 Results.- 8.4 Discussion.- 9 General Discussion.- 9.1 Discussion.- 9.2 Conclusions.- 9.3 Limitations.- 9.4 Spin-off and Present Applications.- A Is Nonionic Isotonic Iohexol the Contrast Agent of Choice for Quantitative Myocardial Videodensitometry?.- A.1 Introduction.- A.2 Methods.- A.2.1 Animal preparation and instrumentation.- A.2.2 Contrast injections.- A.2.3 Hemodynamic recordings.- A.2.4 Statistical analysis.- A.3 Results.- A.3.1 Baseline values and reactions to verapamil.- A.3.2 Effect of contrast injections on coronary blood flow.- A.3.3 Effect of contrast injections on left ventricular (dP/dt) max, left ventricular systolic pressure, and heart rate.- A.3.4 Reaction to 20 seconds coronary artery occlusion.- A.3.5 Relation between change in coronary blood flow and change in left ventricular (dP/dt)max.- A.4 Discussion.- A.5 Conclusion.- B Fitting Procedures for Time-Density Curves.- Summary.