Uhl's anomaly (parchment right ventricle): clinical, echocardiographic, radionuclear, hemodynamic and angiocardiographic features in 2 patients.
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Biomedical subjects
Publications and source records attributed to E Henze.
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Phase analysis of radionuclide ventriculograms is used for identifying ischemic wall motion abnormalities. Myocardial segments with an abnormal phase, that is, delayed onset of wall motion, can be localized on a phase distribution image, and the synchronicity of left ventricular (LV) wall motion can be assessed from a histogram of LV phase distribution. The standard deviation of the LV peak on this histogram (SDP-LV) describes the width of the peak and is used as an index of the synchronicity of wall motion. We examined in this study the sensitivity of SDP-LV for identifying coronary artery disease (CAD) and its specificity in patients with normal and various degrees of LV impairment. A total of 84 patients were studied. Forty-five patients had CAD and 39 had congestive cardiomyopathy or valvular heart disease. Patients were grouped according to their LV ejection fraction (EF). In group I (37 patients) resting LVEF was equal to or greater than 50%, in group II (24 patients) it ranged from 35% to 50%, and in group III (23 patients) it was less than 25%. SDP-LV was highly specific in groups I and II for CAD with sensitivities of 48% and 89% at rest that increased with exercise to 88% and 100%. In group III patients, SDP-LV remained highly sensitive but was no longer specific for CAD. Therefore, in severe LV impairment, phase analysis does not aid in distinguishing CAD from other causes of ventricular dysfunction. By contrast, phase analysis is highly sensitive and specific for CAD in patients with normal or moderately depressed LV function.
To improve the accuracy of scintigraphic ventricular volume determination, which is limited by photon attenuation between the heart and the gamma camera, a method was developed for directly measuring the photon attenuation of radioactivity delivered as a bolus through a Swan-Ganz catheter into the right atrium. Comparison of the count rate recovered from this bolus with the total ex vivo measured activity determined by imaging an aliquot of the administered activity allowed calculation of the attenuation factor. Left ventricular stroke volumes determined scintigraphically by the count method in gated blood pool studies and then corrected with this attenuation factor correlated well with stroke volumes determined from thermodilution cardiac output and heart rate (r = 0.92; SEE, 6.1 ml). The agreement between the two measurements was markedly less when an average attenuation factor was employed for correction of scintigraphic volumes (r = 0.52; SEE, 14.8 ml). The results indicate that correction for photon attenuation is needed for accurate measurement of left ventricular volumes. Correction of left ventricular counts based on body weight or body surface area improves the accuracy of volume estimates.
Studies at necropsy have shown that the cardiomyopathy of Duchenne muscular dystrophy selects the posterobasal and contiguous lateral left ventricular (LV) walls as initial and primary sites of myocardial dystrophy in the absence of small-vessel coronary artery disease in these areas. The present investigation was designed chiefly to determine whether a myocardial metabolic abnormality could be identified in these same areas during a patient's life. Positron emission computed tomography was used to study regional LV metabolism with 18F 2-fluorodeoxyglucose, and metabolism and/or perfusion was studied with 13NH3. In addition, all subjects had the following performed: thallium-201 scans, technetium-99m multiple-gated equilibrium blood pool imaging, electrocardiograms, vectorcardiograms, and M mode and two-dimensional echocardiograms. 18F 2-fluorodeoxyglucose activity was selectively increased in the posterobasal and posterolateral walls of the left ventricle in 11 of 12 patients with technically adequate images, indicating accelerated regional exogenous glucose utilization. 13NH3 activity was selectively decreased in the same areas in 13 of 15 patients, indicating either a regional metabolic alteration in uptake and trapping, a reduction in regional blood flow, or both. These data identify a myocardial metabolic abnormality concentrated in specific segments of the LV free wall in living patients with Duchenne dystrophy.
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Studies have shown that the extraction of glucose per unit flow is increased in moderately ischemic myocardium primarily due to anaerobic glucose metabolism manifested as lactate production, whereas myocardial infarction is characterized by the loss of metabolically active myocardium. To determine the feasibility of demonstrating these metabolic abnormalities reflecting both ischemia and infarction, we used positron computed tomography (PCT) to evaluate relative regional myocardial exogenous glucose utilization and perfusion in 15 patients with recent myocardial infarction. The positron-emitting tracers of glucose metabolism and perfusion, 18F-2-fluoro-2-deoxyglucose (FDG) and N-13 ammonia, respectively, were used. Fourteen of 19 documented infarctions were demonstrated by PCT to have concordantly decreased glucose utilization and perfusion. However, in an additional 11 regions, glucose utilization was disproportionately increased relative to perfusion, consistent with ischemic glucose consumption. These findings correlated with the presence of postinfarction angina, the site of ischemic electrocardiographic changes during chest pain, and the presence of regional left ventricular dysfunction and severe coronary artery disease. Because three ECG infarct zones not detected by PCT demonstrated ischemic glucose utilization, only two of 19 electrocardiographically defined infarctions had no detectable metabolic abnormality. We conclude that the changes in regional FDG and N-13 ammonia concentrations detected with PCT in patients who had had a recent myocardial infarction are consistent with regional exogenous glucose utilization and perfusion in moderately ischemic and irreversibly infarcted myocardium. This approach has the potential to identify and differentiate resting myocardial ischemia from infarction and to assess tissue viability after an ischemic event.
Quantification of myocardial tissue kinetics from serial tomographic images is limited because of bidirectional cross-contamination of recorded counts between myocardium and blood for metabolic tracers with relative slow blood clearance. We have developed and validated a new deconvolution technique that permits calculation of spillover fractions derived from geometric measurements of the imaged cross section (wall thickness, chamber diameter) and the intrinsic resolution of the tomograph. Serial gated positron-emission computerized imaging (PCT) and a-v blood sampling across the heart were performed in five dogs for 45 min after i.v. C-11 palmitate (CPA) and in five dogs for 3 hr after i.v. F-18 deoxyglucose (FDG). Tracer concentrations in myocardial tissue and arterial blood were also measured in vitro. Uncorrected PCT tissue and blood concentrations correlated poorly with in vitro measurements. After correction for count crossover, the correlation for FDG in tissue was r = 0.99, for FDG in blood r = 0.97, and for CPA in blood r = 0.99. Deconvolution techniques applied to serial PCT images provide accurate noninvasive measurement of myocardial tracer concentrations and direct determination of the arterial input function required for measurements of myocardial metabolism.
Glutamate dehydrogenase (GDH), immobilized on CNBr-activated Sepharose supports, was used with N-13 ammonia to aminate alpha-ketoisocaproic acid (KIC), and alpha-ketoisovaleric acid (KIV) to produce N-13-labeled branched-chain L-amino acids with radiochemical yields ranging from 29% to 35%. From kinetic and practical considerations, pH 7.5-8.0 was established to be optimal for the synthesis of N-13-labeled branched-chain-L-amino acids. Myocardial time-activity curves in dogs at control, during low-flow ischemia, reperfusion, and after transaminase inhibition following intracoronary bolus injection of the N-13-labeled amino acids were biexponential. Higher retention of N-13 activity was observed in ischemic segments both during low-flow ischemia (29.2%) and reperfusion (23.2%) when compared with controls (20.0%), (n = 4). On the other hand, transaminase inhibition decreased residue fractions from 21.0% at control to 13.9% (n = 4). The residual activity with L-[1-11C]leucine allows for the calculation of protein synthesis rates.
The possibility of detecting mild coronary stenoses with positron computed tomography and nitrogen (N-13) ammonia administered during pharmacologic coronary vasodilation was previously demonstrated in chronically instrumented dogs. The feasibility of using this technique in human beings and its sensitivity in determining the degree and extent of coronary artery disease were examined in 13 young normal healthy volunteers and 32 patients with angiographically documented coronary artery disease. N-13 ammonia was administered intravenously and its distribution in the left ventricular myocardium recorded at rest and during dipyridamole-induced coronary hyperemia. In the 13 volunteers, N-13 activity was homogeneous at rest and during hyperemia, whereas 31 of the 32 patients had regional defects on the hyperemic images not present during rest. All six patients with double, all 10 with triple and 15 of 16 patients with single vessel disease (97 percent) were correctly identified with the technique. Two vessel involvement was correctly identified in five of the six patients with double vessel disease and three vessel disease in six of 10 patients. Of all 58 coronary stenoses, 52 (90 percent) were correctly identified. In a subgroup of 11 patients, the technique was compared with exercise thallium-201 planar images, which were abnormal in 10 (91 percent) whereas N-13 images were abnormal in all 11. Of the 19 stenosed coronary arteries in this subgroup, 11 (58 percent) were correctly identified with thallium-201 and 17 (89 percent) with tomography (p less than 0.01). It is concluded that cross-sectional imaging of the myocardial distribution of N-13 ammonia administered during pharmacologic coronary vasodilation is a highly sensitive and accurate means for noninvasive detection of coronary stenoses in human beings and for estimating the extent of coronary artery disease.
Calculation of accurate stroke count ratios for the assessment of valvular regurgitation from equilibrium blood pool images has been difficult and did not permit computation of regurgitant fractions (RF) because of contamination of right ventricular (RV) stroke counts by right atrial activity. We describe a new approach to correct for this contamination by subtracting one half of the right atrial counts from the RV counts, assuming that in the standard or "modified" left anterior oblique projection commonly used about one half of the right atrial activity is superimposed to the RV. This new method was tested in 20 patients without valvular disease or shunts. Left ventricular (LV) to RV stroke count ratio approached unity (1.01 +/- 0.14). RV ejection fractions (EF) derived by this technique agreed well with those obtained by gated first-pass studies recorded in the right anterior oblique projection. In 9 normals and 17 patients with moderate severe or severe aortic (12 patients or mitral (7 patients) regurgitation, LVEF, RVEF, and RF were determined at rest and maximum exercise. In patients at rest, LVEF (56.0 +/- 6.4%) and RVEF (49.0 +/- 7.3%) did not differ significantly from LVEF (59.6 +/- 4.2%) and RVEF (52.5 +/- 6.4%) in normals. The calculated RF was negligible in normals (1.9 +/- 8.6%), but averaged 51.8 +/- 9.8% in patients with valvular disease. During exercise, LVEF fell significantly (p less than 0.001) to 44.1 +/- 7.2% in patients but increased to 70.5 +/- 3.8% in normals. RVEF increased in aortic regurgitation to 64.5 +/- 9.8% (NS to normals) but fell in mitral regurgitation to 36.6 +/- 5.9% (p greater than 0.001). In both patient subsets RF decreased with exercise to 25.4 +/- 15.0% in aortic and 39.1 +/- 12.7% in mitral regurgitation. The results indicate that this new approach permits assessment of RVEF and RF from gated equilibrium blood pool studies and is suitable to evaluate the hemodynamic response to physiologic and therapeutic interventions in patients with valvular regurgitation.
Positron-emission computed tomography (PCT) is a new means of studying regional myocardial metabolism. This new device permits quantitative, cross-sectional imaging of the tissue concentrations of positron-emitting tracers of blood flow and metabolism in the myocardium. To examine the potential value of PCT for evaluating regional alterations in myocardial metabolism, acute myocardial ischemia was induced by rapid atrial pacing in open-chest dogs with partial coronary stenoses. Regional myocardial glucose uptake and utilization of free fatty acids were examined with the glucose analog F-18 2-fluoro-2-deoxyglucose (FDG) and C-11-labeled palmitic acid. Myocardial blood flow was evaluated with N-13 ammonia. In the ischemic segment, uptake of C-11 palmitic acid was reduced in proportion to blood flow and its rate of clearance as an index of beta oxidation was delayed. There was a relative or absolute increase in FDG uptake (depending on the uptake of FDG in the normal myocardium). Similar observations were made in patients with ischemic heart disease and anginal symptoms at the time study. The observed alterations in the regional distribution of positron-emitting tracers of metabolic substrates in ischemic myocardium are in agreement with previously reported animal experimental studies in which a fall in free fatty acid utilization associated with an increase in glycolytic flux was observed. These studies indicate that metabolic alterations associated with acute myocardial ischemia observed previously in destructive animal experiments do indeed occur in humans and can now be demonstrated noninvasively in humans by PCT.
The value of phase analysis of multiple gated acquisition blood pool images for identifying wall motion abnormalities due to stress-induced ischemia was examined. Myocardial segments with an abnormal phase, i.e., delayed onset of wall motion, were localized on a phase distribution image of the LV and the synchrony of LV systolic wall motion was assessed from histograms of the LV phase distribution, i.e., the standard deviation (SD) from the mean of this peak, which was defined as SDP, its upper limits of normal at rest and exercise were established in seven normals as the mean +2 SD and were 12 degrees at rest and 10 degrees at maximum exercise. Of the 56 patients, 37 had coronary artery disease (CAD), 11 had valvular disease but normal coronary arteries, and eight had normal coronary arteries, no valvular disease, but had either cardiomyopathy or typical angina. In the CAD patients, SDP was abnormal in 95% during exercise while only 86% had an abnormal ejection fraction (EF) response and/Or exercise-induced wall motion abnormalities by visual interpretation. By contrast, in the 11 valvular heart disease patients, SDP was abnormal in only two despite exercise-induced wall motion abnormalities in five and an abnormal EF response in all 11. Thus, although an abnormal EF response to exercise is a sensitive indicator of cardiac disease, it is, however, like exercise-induced wall motion abnormalities, not specific for CAD. By contrast, phase analysis not only permitted separation of wall motion abnormalities induced by ischemia from those associated with valvular disease, but was also an objective, highly sensitive, and specific indicator of regional myocardial ischemia.
Sterile, pyrogen-free L-[4-11C]aspartic acid was prepared from 11CO2 using phosphoenolpyruvate carboxylase and glutamic/oxaloacetic acid transaminase immobilized on Sepharose supports to determine if it is a useful indicator for in vivo, noninvasive determination of myocardial metabolism. An intracoronary bolus injection of L-[4-11C]aspartic acid into dog myocardium showed a triexponential clearance curve with maximal production of 11CO2 100 s after injection. Inactivation of myocardial transaminase activity modified the tracer clearance and inhibited the production of 11CO2. Positron-computed tomography imaging showed that the 11C activities retained in rhesus monkey myocardium are higher than those observed in dog heart after intravenous injection of L-[4-11C]aspartic acid. These findings demonstrated the rapid incorporation of the carbon skeleton of L-aspartic acid into the tricarboxylic acid cycle after enzymatic transamination in myocardium and suggested that L-[4-11C]aspartic acid could be of value for in vivo, noninvasive assessment of local myocardial metabolism.
We have explored the possibility of imaging the cardiac blood pool with dextran (Dx) labeled with Tc-99m (Tc) after Sn2+ reduction. Stannous dextran (SnDx) kits were prepared in advance and labeling was performed by adding Tc-99m. The labeling efficiency was greater than 95%. Technetium-99m dextran (TcDx) was highly stable both in vivo and in vitro. In seven dogs we compared the quality of blood-pool images obtained with TcDx of different molecular weights (4 X 10(4) = Dx-40; 5 X 10(5) = Dx-500; 2 X 10(6) = Dx-2000) and with Tc-99m red blood cells (TcRBC) labeled in vitro, and determined the organ distribution of this new agent by whole-body scanning and blood sampling. TcDx provided high-quality cardiac blood-pool images up to 60 min after injection. The heart-to-lung ratios averaged 3.7 for TcDx-40, 3.9 for TcDx-500, and 5.4 for TcRBC at 60 min. Whereas TcDx-40 showed a relatively rapid initial urinary excretion and TcDx-2000 was degraded rapidly, TcDx-500 demonstrated the best kinetics for blood-pool imaging. Thus, TcDx is a new radiopharmaceutical with high labeling efficiency and stability. It overcomes a number of the limitations of currently used blood-labeling agents and may become useful for blood-pool imaging in man.
Current agents for lymphoscintigraphy have limitations because of slow migration of the colloidal tracers from the injection site and the unknown effect of phagocytosis on the removal of the labeled particles. The usefulness of Tc-99m dextran (TcDx) with a molecular weight of 110,000 has been tested for lymphoscintigraphy. Computer-assisted dynamic imaging and serial blood sampling in 13 dog experiments demonstrated that the tracer cleared only by lymph drainage from an interstitial injection site. Following interdigital injection of 1.0 ml (0.5-5.0 mCi), TcDx reached the knee or elbow lymph nodes in 12.4 +/- 6.5 (1 s.d.) sec, and the inguinal or axillary lymph nodes in 98.0 +/- 42.3 sec. It cleared from the injection site with a half-time of 31.5 min. In a dog with surgically induced lymphedema, tracer migration was markedly delayed in the edematous leg and the radionuclide lymphoscintigram resembled the contrast lymphangiogram. Initial studies in man yielded high-quality radionuclide lymphograms of the leg, and the pelvic and paraaortic lymph nodes. We conclude that TcDx is very promising for lymphoscintigraphy.
To determine the usefulness of the rotating slant-hole (RSH) collimator, a new imaging device for tomographic myocardial imaging, we evaluated its performance in phantom studies. Perfusion defects of variable size, location, and tracer concentration were simulated and imaging was performed with a conventional parallel-hole collimator and the RSH collimator. Planar and depth resolutions assessed with a line source compared favorably with those reported previously for the seven-pinhole collimator. The results also showed RSH tomography to be more sensitive than planar imaging in detecting simulated myocardial defects but indicated some limitations, especially the occurrence of artifactual defects that may reduce the specificity of the imaging device for the detection of perfusion abnormalities.
The deoxyglucose method originally developed for measurements of the local cerebral metabolic rate for glucose has been investigated in terms of its application to cardiac studies with positron computed tomography (PCT) and fluorodeoxyglucose (FDG). Studies were performed in dogs to measure the tissue kinetics of FDG with PCT and by arterial and venous sampling. The operational equation developed in our laboratory as an extension of the Sokoloff model was used to analyze the data. Error propagation, primarily from corrections applied to remove spillover of activity from the myocardial blood pool to tissue and from partial-volume effects in the PCT images, limited accuracy in the estimation of the individual rate constants for transport, phosphorylation, and dephosphorylation. However, a constant representing the combination of transport and phosphorylation was accurately determined and yielded measured values of the myocardial metabolic rate for glucose (MMRGlc) that were in good agreement with direct determinations using the Fick method over a wide range of glucose metabolic rates (from 1.7 to 21.1 mg/min-100 g). The lumped constant (0.67 +/- 0.10) was also found accurate and stable over this range of metabolism. The FDG method accurately predicted the true MMRGlc even when the glucose metabolic rate was normal but myocardial blood flow (MBF) was five times the control value, or when metabolism was reduced to 10% of normal and MBF increased to five times normal. Improvements of PCT resolution are required to improve the accuracy of the estimates of the rate constant and the MMRGlc.