Augmented myocardial perfusion reserve after coronary angioplasty quantified by positron emission tomography with H2(15)O

Effects of coronary angioplasty on myocardial flow reserve have been difficult to characterize noninvasively because conventional imaging techniques cannot quantitate blood flow in absolute terms. The effects of coronary angioplasty on myocardial perfusion and perfusion reserve were delineated with positron emission tomography and oxygen-15-labeled water (H2(15)O) in 13 patients before and after single vessel angioplasty. In 11 patients, angioplasty was successful (minimal cross-sectional area increased from 0.60 +/- 0.59 to 3.45 +/- 1.09 mm2, p less than 0.001). In these patients, regional H2(15)O radioactivity (the ratio of nutritional perfusion in regions distal to the stenosis compared with regions supplied by angiographically normal arteries) at rest before angioplasty was 55 +/- 22% of peak myocardial radioactivity and did not increase significantly afterward (70 +/- 16%, p = NS). However, after administration of intravenous dipyridamole, hyperemic perfusion in regions distal to a stenosis averaged only 39 +/- 18% of peak myocardial counts before angioplasty, but increased to 66 +/- 22% after angioplasty (p less than 0.02). Perfusion reserve in the two patients in whom angioplasty was angiographically unsuccessful showed no change. Quantitative estimates of perfusion in absolute rather than relative terms were obtained with positron emission tomographic data from seven of the patients with successful angioplasty. At rest, perfusion in regions distal to a stenosis was not different from the values in regions supplied by normal coronary arteries (1.54 +/- 0.54 compared with 1.46 +/- 0.38 ml/g per min, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Delineation of impaired regional myocardial perfusion by positron emission tomography with H2(15)O

Positron emission tomography with 15O-labeled water (H2(15)O) can be used to delineate abnormal regional myocardial blood flow in experimental animals. To determine the feasibility of this method in humans, we studied 33 subjects (9 normal volunteers and 24 patients with angiographically documented coronary artery disease) at rest and after myocardial hyperemia induced with intravenous infusion of dipyridamole. At rest, the myocardial region demonstrating the lowest relative H2(15)O activity exhibited 71 +/- 8% of activity in the region with peak activity in control subjects and 62 +/- 17% in patients (p = NS). After the dipyridamole infusion, differences between the two groups were accentuated. In control subjects, activity in the region with lowest relative radioactivity averaged 77 +/- 5% of that in the region with peak activity. In patients, it averaged 55 +/- 22% of activity in the region with peak activity (p less than 0.01). Results in patients with ischemia with or without a history of remote myocardial infarction were not significantly different. In 22 of the 24 patients, the region with lowest relative perfusion corresponded anatomically to the region of myocardium distal to a stenosis. Thus, delineation of regional myocardial perfusion in patients with coronary artery disease is possible with positron emission tomography and H2(15)O. Further studies will be necessary to prospectively determine sensitivity and specificity.     

Quantitative measurement of human tissue hepatic blood volume by C15O inhalation with positron-emission tomography

Abstract: In order to estimate the tissue liver function, tissue hepatic blood volume was measured quantitatively and non-invasively using C¹⁵O inhalation in conjunction with positron-emission tomography. Fifty-eight patients with normal liver function, 14 patients with chronic hepatitis, 28 patients with hepatic cirrhosis, and 4 patients with obstructive jaundice were studied by positron-emission tomography scan after the single breath inhalation of 20 mCi of high specific activity ¹⁵O-labeled carbon monoxide. The mean tissue hepatic blood volume was significantly greater in patients with normal livers than in patients with chronic hepatitis or hepatic cirrhosis (mean: 20.5, 18.2, and 16.1 ml per 100 cm³, respectively, p=8.6×10^-8). Tissue hepatic blood volume (tHBV) correlated with the reaction of the mesenchymal system and protein synthesis, because there was a potent correlation between tHBV and hepatic fibrosis. In normal livers, we were able to demonstrate significant differences in tissue hepatic blood volume among liver segments.     

Detection of coronary artery disease with 13N-ammonia and high-resolution positron-emission computed tomography

In order to evaluate the detectability of coronary artery disease (CAD) with positron-emission computed tomography (PET), we performed 13N-ammonia myocardial PET scanning at rest and with exercise loading in 20 normal subjects and 40 patients with CAD, by means of a high-resolution, multi-slice, whole-body PET scanner. Myocardial PET scanning was performed 3 minutes after injection of 13N-ammonia at rest and during exercise. The circumferential profile analysis of resting PET images revealed regional hypoperfusion in 96% of CAD patients with previous myocardial infarction and in 29% of those without infarction. Exercise PET studies showed high sensitivity (93%) in detecting CAD without myocardial infarction, whereas no abnormal hypoperfusion was detected in normal subjects. Segmental analysis of regional myocardial perfusion with exercise stress identified 67 of 75 stenosed vessels (89%). We conclude that 13N-ammonia myocardial PET with exercise loading provides high-quality tomographic images of regional myocardial perfusion and is a valuable technique for detecting CAD.     

Use of fractional myocardial flow reserve to assess the functional significance of intermediate coronary stenoses

The goal of the present study was to compare the use of pressure-derived myocardial fractional flow reserve for detecting ischemia with nuclear stress imaging in patients undergoing stent placement for intermediate coronary lesions. We demonstrated that myocardial fractional flow reserve detects ischemia in intermediate coronary lesions accurately when compared with nuclear stress imaging.     

Quantitative coronary angiography in predicting functional significance of stenoses in an unselected patient cohort

Objectives. This study investigated the value of quantitative coronary angiography for predicting coronary flow reserve, as calculated from the transstenotic pressure gradient in a large, unselected patient cohort.Background. In patients with extensive coronary artery disease, quantitative coronary angiographic findings fail to correlate with functional variables of coronary stenoses. New developments in pressure-monitoring wire technology permitted validation in humans of the concept of myocardial fractional flow reserve as assessed from coronary pressure measurements.Methods. One hundred ten patients with normal left ventricular function were studied in the setting of coronary angioplasty. Quantitative coronary angiography was performed on-line using the ACA system. Myocardial and coronary fractional flow reserve were calculated from aortic and distal coronary pressures during maximal coronary hyperemia.Results. When data before and after angioplasty were pooled, a curvilinear relation was found between myocardial fractional flow reserve and both diameter stenosis (r = 0.79) and minimal lumen diameter (r = 0.82), and a linear relation was found between myocardial fractional flow reserve and angiographic stenosis flow reserve (r = 0.78). Correlations between quantitative angiographic and pressure-derived indexes, although significant, were characterized by a large dispersion of the values of myocardial fractional flow reserve for a similar angiographic degree of stenosis. Nevertheless, the sensitivity and specificity of a minimal lumen diameter <1.5 mm to predict myocardial fractional flow reserve <0.72 were 96% and 89%, respectively. The corresponding values for a diameter stenosis >50% were 93% and 85%, respectively.Conclusions. 1) In an unselected patient cohort, geometric indexes of stenosis severity derived from quantitative coronary angiography correlate significantly with physiologic variables, although these relations are imprecise in individual patients. 2) Nevertheless, the diagnostic accuracy of quantitative coronary angiography in predicting myocardial fractional flow reserve <0.72 is high and allows its use for clinical decision making in the individual patient during diagnostic or interventional procedures.     

Standard versus user-interactive assessment of significant coronary stenoses with multislice computed tomography coronary angiography

Forty-four patients in sinus rhythm with suspected coronary artery disease underwent 16-row multislice computed tomography coronary angiography and conventional coronary angiography. Two protocols for image analysis were applied to the multislice computed tomographic images: standard projections versus interactive postprocessing. The diagnostic accuracy of both methods for the detection of significant lesions (>50% lumen reduction) was compared with quantitative coronary angiography. Sensitivity and specificity were 58% and 96% and 96% and 97%, for standard projections and interactive postprocessing protocol, respectively.     

Intravascular ultrasound criteria for the assessment of the functional significance of intermediate coronary artery stenoses and comparison with fractional flow reserve

The functional significance of coronary artery stenoses of intermediate severity is important in determining strategy in patient care. Intravascular ultrasound (IVUS) is often used to evaluate coronary stenosis severity. However, at present, few data are available about the role IVUS in the assessment of functional significance of intermediate lesions. Myocardial fractional flow reserve (FFR) <0.75 is a reliable index of a functionally severe coronary stenosis. In 53 lesions we assessed (1) by pressure wire: FFR (index of functional significance), and (2) by IVUS: minimal lumen cross-sectional area (MLA, square millimeters), minimal lumen diameter (MLD, millimeters), lesion length (millimeters), and percent area stenosis at the lesion site. By regression analysis, percent area stenosis and lesion length had a significant inverse correlation with FFR (r = -0.58, p <0.001, r = -0.41, p <0.004, respectively). MLD and MLA showed a significant positive relation with FFR (r = 0.51, p <0.001, r = 0.41, p <0.004, respectively). By using a receiver operating characteristic (ROC) curve, we identified a percent area stenosis > 70% (sensitivity 100%, specificity 68%), a MLD < or = 1.8 mm (sensitivity 100%, specificity 66%), a MLA < or =4.0 mm2 (sensitivity 92%, specificity 56%), and a lesion length of >10 mm (sensitivity 41%, specificity 80%) to be the best cut-off values to fit with a FFR <0.75. The combined evaluation of both percent area stenosis and MLD made the IVUS examination more specific (sensitivity 100%, specificity 76%). In 53 intermediate coronary lesions found by angiography, IVUS area stenosis >70%, MLD < or =1.8 mm, MLA < or =4.0 mm2, and lesion length > 10 mm reliably identified functionally critical intermediate coronary stenoses.     

Measurement of absolute myocardial blood flow with H215O and dynamic positron-emission tomography. Strategy for quantification in relation to the partial-volume effect

An in vivo technique was developed for measuring the absolute myocardial blood flow with H215O and dynamic positron-emission tomography. This technique was based on a new model involving the concept of the tissue fraction, which was defined as the fraction of the tissue mass in the volume of the region of interest. The myocardium was imaged dynamically by positron-emission tomography, starting at the time of intravenous bolus injection of H215O. The arterial input function was measured continuously with a beta-ray detector. A separate image after C15O inhalation was also obtained for correction of the H215O radioactivity in the blood. The absolute myocardial blood flow and the tissue fraction were calculated for 15 subjects with a kinetic technique under region-of-interest analysis. These results seem consistent with their coronary angiographic findings. The mean value of the measured absolute myocardial blood flows in normal subjects was 0.95 +/- 0.09 ml/min/g. This technique detected a diffuse decrease of myocardial blood flow in patients with triple-vessel disease.     

Accuracy of thin-slice computed tomography in the detection of coronary stenoses.

AIM: Our aim was to investigate the accuracy of multislice spiral computed tomography (MSCT) in the detection of significant (>50%) coronary stenosis using a scanner equipped for 16 x 0.625 mm collimation. METHODS: In 64 patients (59 male, mean age 58 +/- 5 years) with suspected coronary artery disease, MSCT (GE Light Speed-16, collimation: 16 x 0.625 mm) was performed 20 +/- 5 days before coronary angiography (CAG). Only angiographic segments >1.5 mm were considered for analysis. RESULTS: In all patients, MSCT was carried out without complications. Three patients were excluded from the analysis. Of 729 angiographic segments, 613 (84%) were judged evaluable by MSCT. Considering only the segments judged evaluable, the sensitivity was 89%, specificity 98%, positive predictive value 90%, and negative predictive value 98%. Including all segments in the analysis (evaluable and nonevaluable), sensitivity was 78%. CONCLUSIONS: Using a scanner with a collimation of 16 x 0.625 mm, our study confirms the potential role of MSCT in the detection of significant coronary stenosis with a sensitivity of 89% and a very high specificity (98%). Exclusion criteria and less than full evaluability of the coronary arteries must still be considered limitations of the method.     

Quantification of liver perfusion with [(15)O]H(2)O-PET and its relationship with glucose metabolism and substrate levels

BACKGROUND/AIMS: Hepatic perfusion plays an important role in liver physiology and disease. This study was undertaken to (a) validate the use of Positron Emission Tomography (PET) and oxygen-15-labeled water ([(15)O]H(2)O) to quantify hepatic and portal perfusion, and (b) examine relationships between portal perfusion and liver glucose and lipid metabolism. METHODS: Liver [(15)O]H(2)O-PET images were obtained in 14 pigs during fasting or hyperinsulinemia. Carotid arterial and portal venous blood were sampled for [(15)O]H(2)O activity; Doppler ultrasonography was used invasively as the reference method. A single arterial input compartment model was developed to estimate portal tracer kinetics and liver perfusion. Endogenous glucose production (EGP) and insulin-mediated whole body glucose uptake (wbGU) were determined by standard methods. RESULTS: Hepatic arterial and portal venous perfusions were 0.15+/-0.07 and 1.11+/-0.34 ml/min/ml of tissue, respectively. The agreement between ultrasonography and [(15)O]H(2)O-PET was good for total and portal liver perfusion, and poor for arterial perfusion. Portal perfusion was correlated with EGP (r=or+0.62, p=0.03), triglyceride (r=or+0.66, p=0.01), free fatty acid levels (r=or+0.76, p=0.003), and plasma lactate levels (r=or-0.81, p=0.0009). CONCLUSIONS: Estimates of liver perfusion by [(15)O]H(2)O-PET compared well with those by ultrasonography. The method allowed to predict portal tracer concentrations which is essential in human studies. Portal perfusion may affect liver nutrient handling.     

Comparison of the degree of coronary stenoses by multidetector computed tomography versus by quantitative coronary angiography

Sixteen-slice multidetector computed tomography (MDCT) and quantitative coronary angiography (QCA) were performed in 29 patients. Quantification of the degree of luminal narrowing and lesion length measurements were performed independently on MDCT and QCA at 42 sites with sufficient computed tomographic image quality. The correlation between MDCT and QCA for quantifying the degree of stenosis was excellent (r2 = 0.93), although a systematic overestimation was observed by MDCT (bias 4% +/- 8%). The correlation between MDCT and QCA was moderate with respect to lesion length (r2 = 0.54). In the absence of severe calcifications or motion artifacts, MDCT permits noninvasive quantification of coronary stenosis.