Characterizing the normal heart using quantitative three-dimensional echocardiography.

We present normative data on cardiac volume, geometry and shape derived using three-dimensional echocardiography (3-DE). Three-dimensional reconstructions were created using the piecewise smooth surface subdivision (PSSS) reconstruction technique of the left and right ventricular (LV and RV) endocardium and the mitral and tricuspid annuli (MA and TA) of 67 normal subjects. We derived LV end-diastolic (ED) and end-systolic (ES) volume indices (VI) of 76.5 +/- 16.8 ml m(-2) and 35.3 +/- 14.1 ml m(-2), LV ejection fraction (EF) of 56.1 +/- 9.93%, RV EDVI and ESVI of 93.2 +/- 20.0 ml m(-2) and 49.9 +/- 13.5 ml m(-2) and RVEF of 47.3 +/- 7.69%, along with data on the geometry and shape of the MA, TA, LV and RV. There was no pattern of consistent understatement or overstatement of volumes or dimensions compared with other imaging modalities, and observed variance in data can largely be accounted for through examination of the physics or protocol of each modality.

Early recovery of left ventricular function after thrombolytic therapy for acute myocardial infarction: an important determinant of survival.

Thrombolytic therapy for acute myocardial infarction reduces early mortality, but full recovery of left ventricular function after reperfusion is delayed. Therefore, the relations among reperfusion, survival and the time course of left ventricular functional recovery were examined in 226 patients treated with intracoronary streptokinase; 77% (134 patients) had sustained reperfusion and 31 patients had no reperfusion or had reocclusion by day 3. Wall motion was measured from contrast ventriculograms performed in the acute period and 3 days later in the central and peripheral infarct regions and the noninfarct region by the centerline method in 165 patients. Patients with reperfusion had better survival (p less than 0.05, mean follow-up 4.5 years) and a higher ejection fraction at 3 days (52 +/- 12 versus 46 +/- 10%, p less than 0.02) attributable to a significantly different change in peripheral infarct region function between the acute and 3 day studies (0.1 +/- 1.0 versus -0.3 +/- 0.9 SD, p less than 0.05). These early functional changes were significant in patients with anterior myocardial infarction and showed similar trends in those with inferior myocardial infarction. On Cox regression analysis, function measured at 3 days was more predictive of survival than was function measured acutely (chi square for acute ejection fraction = 11.48 versus 24.59 at 3 days). Although, as previously reported, greater than 45% of total recovery of left ventricular function occurs later, the ejection fraction achieved by day 3 is already predictive of survival. Thus, the mechanism by which successful thrombolytic therapy enhances survival is improvement of regional and global left ventricular function early after acute myocardial infarction.

Influence of coronary arterial thrombus location on left ventricular function in acute myocardial infarction.

In 238 patients with acute myocardial infarction studied during intracoronary streptokinase therapy, the circumferential extent of left ventricular hypokinesis was measured by 5 methods and correlated with the location of the infarct-related coronary artery segment and with 1-year survival. Of the 5 methods, 1 focused only on the infarct region, and 4 varied in the complexity of the noise filter. Hypokinetic segment length measurements by all 5 methods correlated significantly with the location of occlusion along the left anterior descending coronary artery. No method yielded measurements that correlated with occlusion location along the right coronary artery. Measurements by all methods correlated significantly with survival, but the method that focused on the infarct region performed least well. Thus, the circumferential extent of hypokinesis in patients with acute myocardial infarction is greater for proximal than mid- or distal occlusions of the left anterior descending but not the right coronary artery. Survival is influenced by the function of periinfarct and noninfarct regions and by the function of the infarct region. Complex noise filters provide no advantage over simpler filters in measuring the extent of hypokinesis.

Percutaneous transluminal coronary angioplasty and subsequent restenosis: quantitative and qualitative methodology for their assessment.

Coronary arteriography is the most commonly used technique for documenting the immediate percutaneous transluminal coronary angioplasty result and for follow-up of the dilated arterial segment for restenosis within 6 months (which occurs in about 25% to 35% of cases). Acute success in dilation of the coronary lesion is likely if there is at least a resultant 1.3 mm2 minimum lumen area, equivalent to a 1.3 mm mean minimum lumen diameter, or about a 50% diameter stenosis of a typical proximal vessel. The measurement methods applied to this problem include a digital caliper, computer-assisted border recognition techniques and a video-densitometric approach to estimation of lumen area. Calipers are recommended because of their simplicity, precision and accuracy for the routine assessment of angioplasty result. Border-recognition techniques require considerable operator input to distinguish true flow channels from cul de sacs in the dissected segment. The automated scanning videodensitometry approach has theoretical appeal and has shown promise in preliminary reports; however, there is the potential for large measurement errors in the setting of dissection. Further, certain qualitative morphologic features of the dilated segment, such as longitudinal or transverse dissection or intraluminal thrombus, may effectively contribute to the prediction of acute complications and may be useful predictors of late restenosis. Because these features are best appreciated at increased arteriographic magnification, further high resolution studies will be necessary to better understand their importance.

Limitations in the interpretation of rest-exercise ejection fraction changes after early thrombolytic therapy during acute myocardial infarction.

The effect of exercise on left ventricular wall motion in the infarct and noninfarct regions, and their contribution to the global ejection fraction response to exercise was evaluated in 24 patients studied at least 2 weeks following thrombolytic therapy for acute myocardial infarction. To achieve this goal, a nonstandard protocol was used: contrast ventriculography was performed at rest and immediately following 3 minutes of supine bicycle exercise at 50 watts. Wall motion in the infarct and noninfarct regions was measured using the centerline method. The global ejection fraction response to exercise correlated poorly with the exercise response of motion in the infarct region (r = 0.38). In 15 of the 24 patients, the function of the infarct and noninfarct regions changed in opposing directions, and in only 8 (53%) of these did the global ejection fraction response follow the exercise response of motion in the infarct region. The motion of the noninfarct region was the predominant influence on the ejection fraction response in the other 7 patients. Subgroup analysis revealed that the global ejection fraction response was more dependent on the response of motion in the anterior wall (r = 0.71, p less than 0.001) than in the inferior wall (r = 0.16), regardless of infarct location. The regional wall motion response to exercise also better distinguished reperfused from nonreperfused patients than did the ejection fraction response. These results indicate that the global ejection fraction response to exercise may be an unreliable indicator of the functional status of the infarct region.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary artery dilation and hemodynamic responses after isosorbide dinitrate therapy in patients with coronary artery disease.

The response to sublingual isosorbide dinitrate (ISDN) was studied in 10 men with suspected coronary artery disease undergoing coronary arteriography. A Swan-Ganz catheter was placed in the pulmonary artery to record hemodynamic response. Diseased coronary segments were identified during routine Judkins selective coronary angiograms. Sublingual isosorbide dinitrate (ISDN) (5 or 10 mg) was then given with the catheters in place. Multiple sequential single-view coronary angiograms and pulmonary and systemic hemodynamic responses were recorded over 30 minutes after drug administration. At 30 minutes, there was a 53% reduction (p less than 0.01) in pulmonary capillary wedge pressure and a 15% decrease (p less than 0.05) in systemic and pulmonary vascular resistance, with a net 13% decrease (p less than 0.01) in cardiac output and 20% decrease (p less than 0.01) in mean arterial pressure. Quantitative arteriography demonstrated substantial dilation of luminal cross-sectional area in both normal and diseased coronary arterial segments. Normal epicardial segments were grouped according to luminal area (1 to 4, 4 to 8 and more than 8 mm2) and demonstrated maximal area dilation at 10 minutes of 55% (p less than 0.01), 29% (p less than 0.01) and 16% (p less than 0.05), respectively. Diseased epicardial segments (stenosis 50% or greater) dilated 51% (p less than 0.01) at 10 minutes. Calculated stenosis resistance decreased 40% (p less than 0.01). Diseased segments in small and middle-sized arteries (1 to 8 mm2) are 4 times more reactive than those in larger arteries (more than 8 mm2), with peak dilation of 77 vs 21% (p less than 0.01) at 30 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Early beneficial effect of streptokinase on left ventricular function in acute myocardial infarction.

The effect of intravenous streptokinase therapy on the time course of functional recovery was investigated in a controlled study of 64 patients randomized within 3 hours after the onset of acute myocardial infarction (AMI). Contrast ventriculography was performed 1 to 4 days after AMI and repeated 5 weeks later. Wall motion was analyzed by the centerline method in the central infarct, peripheral infarct and noninfarct regions. In patients with ventriculographic data at the early catheterization, streptokinase-treated patients had less severe hypokinesia in the central infarct region than control patients (-2.9 +/- 0.9 [n = 29] vs -3.4 +/- 0.7 standard deviations below normal [n = 21], p less than 0.05). The benefit of streptokinase was more marked in the peripheral infarct region (-1.5 +/- 0.7 vs -2.1 +/- 0.6, p less than 0.001). As a result, the ejection fraction was slightly higher in treated versus control groups (46 +/- 10 vs 43 +/- 7%, respectively; difference not significant). At 5 weeks, function in the streptokinase and control groups had diverged further because of continued improvement in the streptokinase-treated patients. This study shows that streptokinase benefits left ventricular (LV) function by 1 to 4 days after AMI, earlier than previously reported. The benefit was not limited to the peripheral infarct region, where ischemia might have been less severe, but was also seen in the central infarct region. The implication is that thrombolytic therapy can improve LV function during the period of myocardial stunning, while myocardial function is still recovering.

Influence of echocardiographic scan plane location and number on the accuracy of three-dimensional left ventricular volume and shape determination.

Quantitative 3-dimensional (3-D) echocardiography provides accurate assessment of left ventricular (LV) volume, shape, and function, but depends on manual endocardial border tracing. This study determined the minimal number of borders that need to be traced to obtain an accurate analysis of not only the volume of the left ventricle but also its shape, using the integrated methods for quantitative 3-D echocardiography developed by our laboratory. Transthoracic 3-D echocardiographic studies were obtained in 9 normal subjects and 6 patients with heart disease by freehand scanning. The LV endocardium was manually traced in 17 +/- 5 imaging planes and reconstructed in 3 dimensions. The volume and shape of each reconstruction were compared with values measured from surfaces reconstructed from 8 subsets containing 2 to 7 borders; each subset was acquired from different combinations of spatially distributed parasternal and apical views. Accurate measurements were obtained from data sets having > or = 5 borders, regardless of whether the image planes were predominantly apical or parasternal views. In conclusion, the LV border should be traced in > or = 5 imaging planes to obtain accurate measurements of volume and shape. The piece-wise smooth reconstruction method and freehand scanning using a magnetic field tracing system allow the borders to be acquired from whatever combination of acoustic windows and views provides optimal image quality.

Usefulness of recanalization to luminal diameter of 0.6 millimeter or more with intracoronary streptokinase during acute myocardial infarction in predicting "normal" perfusion status, continued arterial patency and survival at one year.

To determine whether arteriographic dimensions of the acutely recanalized coronary lumen provide information about regional perfusion or clinical outcome, quantitative arteriography was used to measure minimum luminal diameter achieved with intracoronary streptokinase administration in 44 patients with acute myocardial infarction (AMI). Degree of coronary reperfusion was independently assessed visually using the criteria applied in the multicenter Thrombolysis in Myocardial Infarction study. Minimum diameter and qualitative reperfusion grade were both assessed from 172 coronary injections during thrombolysis. Partial perfusion (grade 1 or 2) was seen in 95 of 135 injections (70%) in which the minimum diameter was less than 0.6 mm and complete perfusion (grade 3) was seen in 35 of 37 injections (95%) in which it was 0.6 mm or more (p less than 0.001). Repeat cardiac catheterization was performed at 5.5 +/- 4.9 weeks after AMI (n = 20). When vessels were opened acutely to a minimum diameter of less than 0.6 mm, 5 of 12 vessels (42%) were reoccluded at the time of restudy and 8 of 29 patients (28%) died within 12 months. By contrast, 0 of 8 vessels (0%) were reoccluded when the artery was opened to a diameter of at least 0.6 mm (difference not significant), and only 1 of 15 patients (7%) died (p less than 0.05). Of the patients with grade 1 o r 2 perfusion at the end of the thrombolytic infusion, 7 of 19 (37%) died within 12 months and 2 of 4 vessels (50%) reoccluded; of the patients with grade 3 perfusion, 2 of 25 (8%) died (p less than 0.05) and 2 of 16 vessels (13%) reoccluded (difference not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

A new digital electronic caliper for measurement of coronary arterial stenosis: comparison with visual estimates and computer-assisted measurements.

Visual analysis of the severity of coronary stenosis is limited by observer variability. However, more complex techniques of proved accuracy are tedious and costly. Therefore, a new digital electronic caliper (DEC) was evaluated as a potentially more accurate, rapid and less costly alternative for measuring stenosis severity. Stenosis minimum diameter (Dmin) and percent diameter reduction (% S) were measured from the screen of the cine projector using a DEC. These measurements were compared with visual estimates (VIS) by 4 experienced angiographers and with measurements made by a computer-assisted method (QCA) of proved accuracy. In routine cineangiograms from 7 patients, 10 lesions were significant (greater than 50% S) and 8 were mild (less than 50% S). Variability, the standard deviation of multiple estimates of Dmin and % S, averaged 0.09 mm and 3.1% for QCA; 0.18 mm and 5.9% for DEC; and 0.26 mm and 7.4% for VIS. Compared with QCA, the visual determination of % S significantly underestimates (-5%; p less than 0.02) mild and overestimates (+11%; p less than 0.002) significant stenosis. VIS underestimates Dmin in significant lesions by 20% (p less than 0.04). In contrast, the mean error for DEC measurement of Dmin and % S was not significantly different from 0 in either lesion group. For the entire group of lesions, and particularly in significant lesions, the mean error for measurement of these 2 indexes of disease was significantly less with DEC than with VIS. Thus, variability and error with DEC are acceptably low for clinical use.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative analysis of regional wall thickening by transesophageal echocardiography.

To develop a method for quantitative analysis of regional left ventricular function from transesophageal two-dimensional echocardiograms, we conducted studies 10 and 20 minutes after induction of anesthesia in 16 patients with normal hearts who were undergoing minor orthopedic operations. Wall thickening was measured with the centerwall method along 100 chords drawn perpendicular to a line constructed around the center of the ventricular wall, midway between the endocardial and epicardial contours. Thickening, either normalized by the length of the end-diastolic perimeter or expressed as a percentage of the end-diastolic wall thickness at each chord, was compared with measurements of endocardial motion. Wall motion was relatively diminished in the anteroseptal region and enhanced on the contralateral wall, but wall thickening was homogeneous throughout the contour. Normalized wall thickening was significantly less variable (standard deviation/mean, 0.47 +/- 0.13) in the normal population than were either percent wall thickening (0.53 +/- 0.012) or wall motion (0.51 +/- 0.09) (p less than 0.005 for both comparisons). There was no significant change in regional or global function between 10 minutes and 20 minutes after the induction of anesthesia. In summary, normalized wall thickening as a parameter of regional left ventricular function is more homogeneous and less variable in subjects with normal hearts than is endocardial motion because wall thickening measurements are not subject to cardiac translocation artifacts. This low variability suggests that normalized wall thickening measured by the centerwall method may prove particularly useful for intraoperative and postoperative monitoring of regional left ventricular function by transesophageal echocardiography in patients undergoing both cardiac and noncardiac surgical procedures.

How positionally stable is a transesophageal echocardiographic probe? Implications for three-dimensional reconstruction.

Three-dimensional (3D) reconstruction from a single esophageal scanning position requires a stable relationship between the probe and the heart. The purpose of this study was to examine the movement of a transesophageal echocardiographic probe during 3D image acquisition. A new dual-axis multiplane probe was used that includes a miniature (6 x 6 x 9 mm) magnetic sensor in the tip. The sensor identifies the probe's 3D position and 3D orientation in space with respect to the location of a magnetic field generator placed beneath the subject. In vivo 3D scanning was performed in five anesthetized, ventilated dogs, with positional determinations acquired every 66 msec. Probe movement was estimated by computing the deviations of each x, y, and z position and orientation determination, compared with the average values during each 3D scan or cardiac cycle. Ten 3D scans were analyzed, involving 263 cardiac cycles and 2328 determinations. The range and SD of the translational movement of the transducer were 2.3 and 0.8 mm, 1.7 and 0.5 mm, and 2.4 and 0.7 mm in x, y, and z directions, respectively, during 3D scanning. Translational movement was more dominant than was rotational movement. Misregistration of three-dimensional reconstructions may be due to subtle probe movement. The ability to monitor probe movement may be helpful in optimizing 3D data sets.

Quantitative three-dimensional echocardiography by rapid imaging from multiple transthoracic windows: in vitro validation and initial in vivo studies.

Three-dimensional echocardiography has demonstrated superiority over two-dimensional techniques in the determination of left ventricular mass and volumes. We describe a technique based on a magnetic tracking system which provides rapid three-dimensional image acquisition from multiple acoustic windows. Interactive three-dimensional border tracking and reconstruction with a piecewise smooth subdivision model accurately reproduced phantom volume (calculated volume = 1.00 true volume - 0.6 ml, r = 1.000, standard error of the estimate = 1.3 ml), in vitro heart volume (calculated volume = 1.02 true volume - 1.3 ml, r = 1.000, standard error of the estimate = 0.4 ml), in vitro heart mass (calculated mass = 0.98 true mass + 1.4 gm, r = 0.998, standard error of the estimate = 2.5 gm), and in vivo stroke volume (calculated stroke volume = 1.18 Doppler stroke volume - 17.9 ml, r = 0.990, standard error of the estimate = 2.8 ml). The three-dimensional in vivo data sets, which include views from three acoustic windows, were acquired in less than 90 seconds. We conclude that this method of three-dimensional echocardiographic data acquisition and analysis overcomes limitations inherent in currently available systems.

Left ventricular shape analysis from three-dimensional echocardiograms.

The objective of this study was to develop and validate a three-dimensional technique of left ventricular shape analysis. Geometric phantoms and left ventricles of excised calf hearts, normal human subjects, and one subject each with aortic stenosis and dilated cardiomyopathy were reconstructed from three-dimensional echocardiograms. The fit between the reconstructions and true surfaces of the geometric phantoms and excised ventricles was determined. To evaluate in vivo left ventricular shape, a center axis was constructed from the centroid of the mitral annulus to the furthest endocardial point. Regional shape was evaluated as the relative distances of 16 separate myocardial segments from the center axis compared with a population-derived mean value. Global shape was evaluated as the average standard deviation from the normal value over the 16 segments. The system precisely reproduced the shapes of the phantoms and excised left ventricles (root-mean-square error between true and reconstructed surface 1.0 0.2 mm and 1.2 0.8 mm, respectively). The in vivo shape analysis differentiated the pathological from normal left ventricles.

Estimation of the human liver volume and configuration using three-dimensional ultrasonography: effect of a high-caloric liquid meal.

The aim of this study was to investigate whether or not a magnetic position sensing system for free-hand acquisition of 3-D ultrasound images could be used to estimate liver volumes, and to study the effect of a high-caloric meal on these volumes in healthy subjects. In vitro accuracy was evaluated by scanning porcine and rabbit livers. Ten healthy subjects were examined fasting and 30 min after ingesting a high-caloric liquid meal. Portal and hepatic vein blood flow were measured by 2-D duplex sonography. The 3-D system yielded a strong correlation (r = 0.99) between true and estimated volumes in vitro. No significant increase in liver volume in response to the meal was seen. However, portal and hepatic vein flow volume increased significantly. Experience in human subjects suggests that a complete 3-D study of liver volumes can be obtained from multiple acoustic windows. In healthy subjects, no significant increase in liver volume was seen in response to ingestion of a high-caloric liquid meal.

System for quantitative three-dimensional echocardiography of the left ventricle based on a magnetic-field position and orientation sensing system.

Accurate measurement of left-ventricular (LV) volume and function are important to monitor disease progression and assess prognosis in patients with heart disease. Existing methods of three-dimensional (3-D) imaging of the heart using ultrasound have shown the potential of this modality, but each suffers from inherent restrictions which limit its applicability to the full range of clinical situations. We have developed a technique for image acquisition using a magnetic-field system to track the 3-D echocardiographic imaging planes and 3-D image analysis software including the piecewise smooth subdivision method for surface reconstruction. The technique offers several advantages over existing methods of 3-D echocardiography. The results of validation using in vitro LV's show that the technique allows accurate measurement of LV volume and anatomically accurate 3-D reconstruction of LV shape and is, therefore, suitable for analysis of regional as well as global function.

Three dimensional ultrasound analysis of fascicle orientation in human tibialis anterior muscle enables analysis of macroscopic torque at the cellular level.

The purpose of this study was to test the hypothesis that the internal structure of the bipennate human tibialis anterior muscle is sufficiently homogenous throughout the muscle that the cellular stresses could be interpreted correctly from measurable anatomic properties and torque in the limb. This result is needed for facile comparison of extrinsic mechanical data and intrinsic energetic fluxes. Three-dimensional imaging of the fascicles of the human tibialis anterior muscle was made by capturing a series of ultrasound images while registering their location in space. Subsequent tracing of hundreds of structures in the ultrasound images with the use of custom software identified muscle boundaries, tendon surfaces, and fascicles as anatomic elements in 3-D space. The tendon was reconstructed as a mesh through the tracings identified as a component of the tendon. The angle of insertion of each identified fascicle at the tendon was calculated against the nearest normal in the mesh of the tendon. In three subjects the average angle of insertion of the fascicles onto the internal tendon was 11 degrees (coefficient of variation 40%). The angle decreased along the length of the muscle from approximately 15 degrees near the belly of the muscle to 6 degrees near the ankle in fascicles superior and inferior to the central tendon. The angle increased by several degrees during a voluntary contraction. Despite the differences in angles of insertion that can be measured, these distinctions have little significance for the distribution of forces along cellular axes within the muscle: the angles, their distribution within the muscle and change with contraction are small. For this bipennate muscle the cosine of the angle of insertion of the cellular bundles is always close to unity. Thus measurements of whole muscle mechanical data are simply related to mechanical stress of its cells.

Applications of three dimensional echocardiography beyond the left ventricle: other chambers and structural detail.

The authors' system for quantitative three-dimensional echocardiography (3D echo) now enables analysis of all four heart chambers, valves and associated structures. After image acquisition using freehand scanning and a magnetic field tracking device, the borders of cardiac structures are manually traced. Chambers are reconstructed with a piecewise smooth subdivision surface. The mitral and tricuspid annuli are fitted using a 4 term Fourier series. Other valves and orifices are reconstructed as ellipses. Anatomic labeling enables identification of the chordae, coronary sinus, intervalvular fibrosa, septum, and right and left ventricular apex. The dimensions, shape, and function of cardiac components and the spatial relationships between them such as distance and angle can be determined. These methods provide capability and flexibility for clinical applications such as modeling heart motion, investigating the mechanism of functional mitral regurgitation, and tracking left ventricular remodeling.

Dynamic mechanisms in human coronary stenosis.

At the clinical level, coronary stenoses frequently behave as though the obstruction to flow were variable and not as rigidly fixed as previously imagined. Pressure (energy) lost in flow through a stenosis is the primary determinant of its hemodynamic impact. Ischemic episodes occur when pressure distal to the stenosis falls below that needed to perfuse the subendocardium. Three important properties of the stenosis contribute to variation in its pressure loss. First, loss is proportional to the square of stenosis flow. Thus proper distribution of perfusion is doubly vulnerable to conditions such as exercise, anemia, or pharmacologic vasodilation, which ordinarily increase myocardial blood flow. Second, pressure loss is proportional to the inverse fourth power of minimum lumen diameter. As a result, seemingly small changes in diameter are amplified to large changes in stenosis resistance. Third, a compliant arc of normal arterial wall borders part of the lumen in the majority of coronary lesions. This extremely important morphologic feature of stenoses permits transient variation in stenosis lumen diameter in response to drugs or to variation in endogenous vasomotor activity or intraluminal pressure. Although our understanding is incomplete, many of the clinical features of coronary disease and its pharmacologic responses are explained in terms of these stenosis properties and their interaction.

Arteriographic assessment of coronary atherosclerosis. Review of current methods, their limitations, and clinical applications.

Coronary arteriography is presently the definitive procedure for characterizing the location and severity of coronary atherosclerosis; and despite certain reported limitations, we believe that the properly performed coronary arteriogram provides a true picture of the arterial lumen in life. Yet this widely-used clinical tool is currently limited by imprecise and, to a certain extent, inappropriate subjective methods of interpretation. More objective methods for analysis of the arteriographic information content have been described. These include caliper- and vernier- based systems for measuring relative arterial narrowing, computer-assisted methods for making accurate measurements of absolute stenosis dimensions, and photodensitometric methods for extracting three-dimensional information from a planar image of the stenosis. The availability of these objective techniques has resulted in a considerable increase in our understanding of pathogenic mechanisms in coronary disease. Advances include an expanded understanding of the mechanisms of action of nitroglycerin and verapamil and of the coronary artery constriction induced by drugs of isometric stress. Stenosis measurements have served as the basis for evaluation of certain noninvasive techniques used to detect coronary disease. An analytical approach has been developed to characterize the progression (and regression) of coronary disease from serial arteriograms. We believe clinical investigations based on these techniques hold considerable promise for further advances in the understanding of human coronary pathophysiology.