Assessment of regional myocardial uptake and metabolism of omega-(p-123I-phenyl) pentadecanoic acid with serial single-photon emission tomography

The utility of myocardial imaging and assessment of regional myocardial metabolism of omega-(123I-paraphenyl-)pentadecanoic acid (I-PPA) by means of serial single-photon tomography is demonstrated in animal experiments. High quality cross sectional images of dog hearts with clear delineation of left ventricular walls are obtained. Myocardial infarcts are visualized as areas of deficient radioactivity uptake. I-PPA elimination from non-infarcted myocardial regions is significantly (p less than 0.001) prolonged when compared with unaffected controls. Hence, not only localized absence of uptake of free fatty acid by infarcted myocardium can be demonstrated with serial single-photon tomography but also general impairment of cardiac FFA-metabolism.     

Continuous imaging of regional myocardial blood flow in dogs using krypton-81m

The unique physical properties of the freely diffusible gas krypton-81 m allowed continuous imaging of regional myocardial blood flow in dogs when infused into the aortic root. Regional changes in myocardial perfusion related to transient coronary artery occlusion were demonstrated both as high resolution gamma camera images and as a quantitative strip chart record.     

Rest or redistribution thallium myocardial imaging for resting myocardial perfusion: a detailed comparison with regional wall motion

Redistribution thallium-201 (201T1) imaging is the most common method of assessing resting myocardial perfusion. However, the equivalence of a redistribution image and a separate rest injection is unclear. Although the presence of a defect on rest imaging has normally been equated with the presence of a myocardial infarction, it has recently been shown that a significant proportion of fixed defects on exercise-redistribution 201T1 actually represent areas of viable myocardium. This study was a detailed comparison of rest and redistribution imaging in 30 patients undergoing routine exercise 201T1 scanning for the assessment of coronary artery disease. A small dose (15 MBq) of 201T1 was administered at rest following the imaging in three standard planar views. Similar stress images were acquired using a further 50-55 MBq of 201T1 administered at peak effort. Redistribution images were acquired 3-4 h later and equilibrium blood pool ventriculography performed using in vivo labelling with 600 MBq 99Tcm-pertechnetate. Of 150 abnormal segments on the exercise scans, 74 (49%) were identified as being reversible on the redistribution scans and 58 (39%) on the rest images. Only 39 (53%) of these reversible defects were identified on both the redistribution and rest scans. Only 41% of the fixed defects on the redistribution images (32% of fixed defects on the rest images) had abnormal wall motion. Therefore, rest and redistribution images are not equivalent. Both rest and redistribution images significantly overestimate myocardial infarction. This may have significant effects on patient selection for revascularization procedures and therefore all patients having perfusion scintigraphy should also have additional assessment of regional wall motion to allow accurate classification of the functional status of myocardial segments.     

Noninvasive evaluation of regional myocardial perfusion in 112 patients using a mobile scintillation camera and intravenous nitrogen-13 labeled ammonia

The short half-life positron emitter 13N, as labeled ammonia (13NH4+), was evaluated as a myocardial imaging agent. Regional myocardial uptake of 13NH4 correlated with the distribution of labeled microspheres in experimental myocardial infarction. Using intravenous 13NH4+, myocardial scintigraphy was performed in 85 cardiac patients and 27 normal subjects. Ninety-five scintigrams were suitable for analysis. Eighteen of 24 normal subjects had homogeneous myocardial images; six had inhomogeneous images attributable to early technical problems. Perfusion defects were observed in the scintigrams of 82% (57/65) of patients with coronary artery disease, being most common in patients with myocardial infarction (27/28). Six sequential studies showed changes in perfusion consistent with the clinical course of each patient. Scintigraphic abnormalities were also observed in 4/6 patients with valvular heart disease. 13NH4+ myocardial scintigraphy is a valid and sensitive method of assessing regional myocardial perfusion and is especially useful for sequential imaging at short intervals.     

Myocardial tactile stiffness: a variable of regional myocardial function

OBJECTIVES: We developed a new sensor system for in situ measurement of myocardial tactile stiffness-stiffness in a direction perpendicular to the wall-and validated its use for providing a reasonable estimation of regional myocardial function. BACKGROUND: Numerous attempts have been made to directly assess regional myocardial function. The complexity and highly invasive nature of the measuring devices have hampered their in situ application. METHODS: In open chest mongrel dogs, myocardial tactile stiffness, ventricular pressure and ventricular volume were monitored. Under the preload reduction, these variables were measured to determine the relation between the end-systolic pressure-volume relation (ESPVR) and the end-systolic tactile stiffness-volume relation (ESSVR). The changes in myocardial tactile stiffness were monitored in the regional ischemic myocardial model and infarcted model to evaluate their usefulness as indexes of regional myocardial function. RESULTS: Myocardial tactile stiffness changed cyclically and followed a time course similar to left ventricular pressure. When preload was altered, the ESSVR was as linear as the ESPVR. The slope of the ESSVR and that of the ESPVR showed a strong correlation over a wide range of contractility. These results suggest that myocardial tactile stiffness can be a good index of regional wall stress or fiber stress. End-systolic myocardial tactile stiffness of ischemic and infarcted regions decreased significantly, with a concomitant increase in end-diastolic stiffness compared with that of intact myocardium. CONCLUSIONS: Using our tactile sensor system, regional myocardial tactile stiffness of a beating heart was measured with reasonable temporal resolution. We consider myocardial tactile stiffness to be a useful index of regional myocardial function.     

Comparison of regional myocardial velocities assessed by quantitative 2-dimensional and M-mode color Doppler tissue imaging: influence of the signal-to-noise ratio of color Doppler myocardial images on velocity estimators of the Doppler tissue imaging system

M-mode color Doppler imaging of the myocardium affords a greater sampling rate and signal-to-noise (S/N) ratio than 2-dimensional (2D) imaging. In this study, we compared myocardial velocities assessed by 2D and M-mode Doppler tissue imaging (DTI) at the same site and evaluated the influence of the S/N ratio on velocity estimates of the currently used DTI systems. In patients with and without impaired regional left ventricular function, myocardial velocities assessed by 2D DTI were lower than those obtained with M-mode DTI. The difference between regional velocities derived from both imaging techniques was positively correlated with the extent of the "black zone," which could be considered as indirectly reflecting the S/N ratio for each frame. Thus in the clinical setting and on currently used echocardiographs, 2D DTI may provide underestimated regional myocardial velocities when compared with M-mode, mainly because of the influence of the lower sampling rate and S/N ratio on velocity estimators of the imaging system.     

Fasting and nonfasting iodine-123-idophenylpentadecanoic acid myocardial SPECT imaging in coronary artery disease

Iodine-123-labeled idophenylpentadecanoic acid (IPPA) metabolic imaging has been shown to be clinically useful for the identification of myocardial viability in patients with coronary artery disease and left ventricular dysfunction. Imaging is usually performed under fasting conditions since nonfasting conditions may affect myocardial uptake of 123I-IPPA. The purpose of this study was to examine the impact of dietary condition on 123I-IPPA metabolic imaging. METHODS: Forty patients with stable coronary artery disease underwent, in randomized order and on separate days, 123I-IPPA SPECT myocardial imaging under fasting and nonfasting conditions. Patients were injected with 123I-IPPA (4-5 mCi) at rest with imaging performed at 4 (initial) and 30 (delay) min. For each image (initial and delay images), 10 segments were analyzed by three experienced observers without knowledge of patient identity or dietary condition using a 5-point grading system (O = no uptake to 4 = normal uptake). A summed global score was obtained for each image by adding the scores for all 10 segments. Image quality was assessed using a 3-point grading system. RESULTS: Visual agreement for normal and abnormal segments between fasting and nonfasting conditions was 82% (kappa = 0.63). There were no significant differences in the summed global scores for both conditions. Image quality was equivalent for both conditions in 65% of cases and superior under the nonfasting condition in 25% of cases. CONCLUSION: Image quality as well as the presence, location and severity of defects are similar under fasting and nonfasting conditions with 123I-IPPA. Therefore, fasting is not necessary before 123I-IPPA SPECT imaging for the assessment of myocardial viability.     

Measurement of regional aortic compliance by MR imaging: a study of reproducibility

The reproducibility of MR imaging for the measurement of aortic compliance was studied in 47 healthy volunteers. Long and short term reproducibility and intraobserver variability were tested. The method was modified to improve image quality and short term reproducibility and intraobserver variability retested. For comparison, spin echo imaging was compared with cine gradient echo imaging. Initial long term reproducibility showed a mean difference (+/-SE) of 3% (+/- 7%) with 95% confidence interval (CI) for limits of agreement of +/- 69%. Short term reproducibility (7% +/- 6%, 95% CI +/- 46%) and intraobserver variability (1% +/- 2%, 95% CI +/- 31%) were better. After modification of the technique and optimization of image quality, both short term reproducibility and intraobserver variability improved (0% +/- 3%, 95% CI +/- 17% and 5% +/- 2%, 95% CI +/- 16% respectively). Aortic compliance can be measured using spin echo MR imaging with good reproducibility provided care is taken to obtain good quality images with high spatial resolution.     

Comparison of supine versus prone tomographic myocardial imaging. Effect on false-positive rate

As in most other nuclear medicine facilities, tomographic myocardial imaging was started here with the patients in the supine position. However, previous planar imaging experience indicated a high number of false-positive results using the supine position for left lateral views of the myocardium. Evaluating the accuracy of supine position SPECT imaging was considered necessary. In 1991, 228 myocardial imaging procedures were performed during a period of 3 months. Coronary arteriography followed within 3 months in 67 of these patients, permitting evaluation of the accuracy of the imaging procedure interpretations. These correlations revealed the accuracy of myocardial imaging to be only 73%. This was caused mainly by a rather large number of false-positive results (24%) occurring mostly in the inferior-posterior wall. A similar comparison was performed in 1992 after a change to prone position for routine tomographic myocardial imaging with 63 of 295 patients undergoing coronary arteriography. These data revealed an increase in the overall accuracy to 81% and a decrease in the false-positive results to 16%. The improvements were almost entirely in the inferior-posterior regions with no significant change in the false-positive results in the anterior wall. These findings provide convincing evidence that the prone position should be selected for tomographic myocardial imaging.     

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The noninvasive assessment of myocardial viability in patients with coronary artery disease and depressed left ventricular function has proven clinically useful for identifying those patients with ischemic cardiomyopathy who benefit most from coronary revascularization. Thallium-201 (201Tl) imaging at rest has been the radionuclide imaging technique most often utilized for distinguishing viable myocardium from scar. However, new technetium-99m (99mTc) perfusion agents such as 99mTc-sestamibi and 99mTc-tetrofosmin have emerged as alternatives to 201Tl for imaging of regional myocardial perfusion. Whether these new agents, which have better physical properties for imaging with a gamma camera than 201Tl, are valid for use in assessing myocardial viability is still uncertain. Recent clinical studies have demonstrated that these agents, when imaged using quantitative SPECT, can identify patients with myocardial hibernation who exhibit improved regional systolic function following revascularization. Experimental laboratory studies have shown that the uptake of 99mTc-sestamibi and 99mTc-tetrofosmin in ischemic myocardium is only slightly lower than the uptake of 201Tl. These 99mTc-labeled agents remain bound intracellularly in mitochondria of viable myocytes under conditions of myocardial stunning and short-term hibernation, producing severe myocardial asynergy. With respect to determination of viability, the inferior wall region is at times problematic since attenuation of 99mTc-sestamibi and 99mTc-tetrofosmin is greatest in this area. Demonstration of preserved systolic thickening on ECG-gated SPECT images is indicative of viability in the instance of decreased regional 99mTc counts due to attenuation and not scar. Administration of nitrates prior to tracer injection improves the sensitivity for identifying viable myocardial segments using rest imaging with 99mTc-sestamibi or 99mTc-tetrofosmin. Thus, it appears that the new 99mTc perfusion imaging agents can be successfully employed for the determination of myocardial viability in the setting of severe regional dysfunction and chronic coronary artery disease. The greater the myocardial uptake of these agents in the resting state, the greater the probability of improved systolic function after coronary revascularization.     

Quantitative two-dimensional echocardiographic assessment of regional wall motion during transient ischemia and reperfusion in the rat

Nonlethal myocardial ischemia produces profound and long-lasting effects on regional ventricular function and metabolism (myocardial stunning) and protects against myocardial infarction from subsequent prolonged ischemia (ischemic preconditioning). Two-dimensional echocardiography (2DE) is an essential tool for quantitative analysis of regional and global left ventricular (LV) function during myocardial ischemia and reperfusion and the study of these phenomena. However, the inability to perform 2DE in the open-chest rat heart has seriously limited the use of this model. To investigate the effect of transient coronary occlusion on segmental wall motion and LV geometry, we employed a 20 MHz intravascular ultrasound catheter placed on the epicardial surface of the rat heart (n = 15) to yield 2DE images suitable for quantitative analysis. Three 2-minute left coronary occlusions were made, separated by 5 minutes of reperfusion, with imaging during occlusion and at 5 and 60 minutes of reperfusion. Ischemic and nonischemic wall thicknesses, LV cross-sectional area, estimated LV volume, and the fractional changes of these parameters were measured. In eight animals these values were also compared with necropsy measurements of wall thickness, LV cross-sectional area, and volume. LV and right ventricular structures were well visualized in short-axis cross-sectional images in all animals, and images suitable for quantitative analysis were obtained in 92% of the periods. Coronary occlusion caused immediate, marked LV cavitary expansion, which rapidly returned to normal by 5 minutes of reperfusion. Active systolic thickening of the anterior wall at baseline (47% +/- 3%) became passive thinning during occlusion (-6% +/- 2%) and recovered partially, to 30% +/- 3% at 5 minutes of reperfusion and 42% +/- 4% at 60 minutes (p < 0.0005 at 5 minutes of reperfusion vs baseline; p not significant at 60 minutes). Recovery of thickening after 5 minutes of reperfusion was not different after the first versus third occlusion (23% +/- 4% vs 30% +/- 3%; p = 0.19). Measurements made by 2DE correlated well with those made by necropsy, although wall thickness was slightly thicker by 2DE. We conclude that epicardial echocardiography with an intravascular ultrasound catheter provides quantifiable 2DE images in this model and yields accurate information on segmental wall thickening and ventricular geometry not available by other techniques. Left coronary occlusion in the rat is associated with marked global and segmental LV expansion, which rapidly reverses with reperfusion. Postischemic regional wall motion abnormalities are present after coronary occlusion as brief as 2 minutes and can be measured accurately. The effect of multiple brief occlusions is not cumulative.(ABSTRACT TRUNCATED AT 400 WORDS)     

Three-dimensional 31P magnetic resonance spectroscopic imaging of regional high-energy phosphate metabolism in injured rat heart

The purpose of this study was to measure the spatially varying 31P MR signals in global and regional ischemic injury in the isolated, perfused rat heart. Chronic myocardial infarcts were induced by occluding the left anterior descending coronary artery eight weeks before the MR examination. The effects of acute global low-flow ischemia were observed by reducing the perfusate flow. Chemical shift imaging (CSI) with three spatial dimensions was used to obtain 31P spectra in 54-microl voxels. Multislice 1H imaging with magnetization transfer contrast enhancement provided anatomical information. In normal hearts (n = 8), a homogeneous distribution of high-energy phosphate metabolites (HEP) was found. In chronic myocardial infarction (n = 6), scar tissue contained negligible amounts of HEP, but their distribution in residual myocardium was uniform. The size of the infarcted area could be measured from the metabolic images; the correlation of infarct sizes determined by histology and 31P MR CSI was excellent (P < 0.006). In global low-flow ischemia (n = 8), changes of HEP showed substantial regional heterogeneity. Three-dimensional 31P MR CSI should yield new insights into the regionally distinct metabolic consequences of various forms of myocardial injury.     

Clinical applications of transpulmonary contrast echocardiography

BACKGROUND: The recent development of new fluorocarbon-based echocardiographic contrast agents that are capable of opacification of the left-sided cardiac chambers after intravenous injection is a major new advance in diagnostic cardiac imaging. METHODS AND RESULTS: This is a review article focusing on these novel contrast agents, new echocardiographic imaging techniques to optimize their efficacy, and their clinical applications. Specific clinical applications of these agents are (1) enhancement of endocardial border definition to improve assessment of regional and global left ventricular function, (2) myocardial perfusion imaging by intravenous contrast echocardiography, (3) augmentation of spectral and color flow Doppler images, and (4) tissue-specific targeting of microbubbles for delivery of therapeutic agents. CONCLUSIONS: New intravenous contrast agents offer the possibility to assess myocardial perfusion echocardiographically. It is also possible to use these agents for delivery of therapeutic agents, including gene therapy.     

Estimates of regional work in the canine left ventricle

Assessment of the magnitude of regional myocardial work requires knowledge of regional fiber stress and fiber shortening. The theoretical development and experimental validation of a method is presented which used values of estimated active and passive fiber stress according to a fluid-fiber model, and measured fiber strain values. This enables the construction of regional stress-strain diagrams, a regional analog of the pressure-volume area model by Suga and co-investigators, which can be linked to regional oxygen consumption. In the left ventricle, either normally or asynchronously activated, the method yields reliable data on strain and active and passive fiber stress. The relation between estimated regional work and myocardial oxygen demand is in quantitative agreement with previously reported relations between global oxygen demand and measured pressure-volume area. During coronary artery occlusion, however, these values were less reliable, which might be due to inaqdequate knowledge of the (passive) material properties of the myocardium.     

Noninvasive myocardial imaging with potassium-43 and rubidium-81 in patients with left bundle branch block

Noninvasive myocardial imaging with potassium-43 and rubidium-81 has been used successfully to identify areas of infarction and exercise-induced ischemia as regions of decreased radioactivity. The image defects observed are believed to be due to a decreased radionuclide uptake in regions of myocardial scar or to heterogeneous myocardial accumulation of tracer as a result of regional ischemia. Of 27 patients with left bundle branch block studied with noninvasive imaging at rest and during exercise, 25 manifested at rest reduced radioactivity in the region of the interventricular septum. This pattern is similar to that seen in patients with anteroseptal myocardial infarction. Sixteen of the 27 patients underwent diagnostic coronary arteriography and left ventriculography. Only five of these patients had evidence of either previous infarction or significant obstructive coronary artery disease as assessed with clinical or angiographic criteria, or both. Although the image defect was routinely demonstrated at rest in patients with left bundle branch block, this defect was generally normalized or less distinct with exercise in patients with no anatomic heart disease. In contrast, a larger, more distinct or new image defect with exercise correctly identified the presence of significant obstructive coronary artery disease in patients with left bundle branch block. In the clinical application of noninvasive myocardial imaging, these image defects observed at rest can lead to the false pasitive radionuclide interpretation of anteroseptal myocardial infarction.     

MR first pass imaging: quantitative assessment of transmural perfusion and collateral flow

Recent advances with fast switching gradient coils, and the optimization of magnetic resonance techniques for multislice imaging have made it possible to apply models of contrast agent transit for the quantification of myocardial perfusion, and determination of the transmural distribution of blood flow. This article summarizes some of these recent developments and presents examples of quantitative, multi-slice myocardial perfusion imaging studies in patients and animal models. Multi-slice, true first pass imaging, with high temporal resolution, and T1-weighted, arrhythmia insensitive contrast enhancement is used for the quantification of perfusion changes accompanying mild to severe ischemia. The first pass imaging technique and the modeling approach are sufficiently robust for fitting of tissue residue curves corresponding to a wide, physiologically realistic range of myocardial blood flows. In animals this was validated by comparison to blood flow measurements with radiolabeled microspheres as gold standard. It is demonstrated that with the proposed modeling approach one can determine the myocardial perfusion reserve from two consecutive MR first pass measurements under resting and hyperemic conditions. In patients with microvascular dysfunction the MR studies show for the first time that the myocardial perfusion reserve correlates with Doppler flow measurements (linear regression with slope of 1.02 +/- 0.09; r = 0.80). Since perfusion limitations usually begin in the subendocardium as coronary flow is gradually reduced, first pass imaging with the prerequisitie spatial and temporal resolution allows early detection of a mild coronary stenosis.     

Advanced MR imaging techniques for evaluation of the heart and great vessels

A "one-stop shop" for evaluating cardiac disease with magnetic resonance (MR) imaging is progressing toward clinical reality and promises to have a major effect on the care of patients with cardiac disease. T1-weighted conventional spin-echo imaging gated to the cardiac cycle yields good anatomic detail but requires long imaging times and provides only static images of a single cardiac phase. Fast MR imaging with electrocardiographically (ECG) gated, low-flip-angle, segmented k-space gradient-recalled-echo (GRE) sequences provides excellent image quality with sufficiently high temporal resolution to "freeze" cardiac motion. Segmented k-space sequences improve on standard ECG-gated GRE sequences by allowing many cardiac phases, or frames of a cine sequence, to be imaged in a single breath hold with prospective cardiac gating. As commercial implementations of segmented k-space imaging become more widely available, the applications of this technique are expanding from research protocols to include many clinical applications in the heart and great vessels. Such applications include evaluation of vascular anatomy (coronary angiography, aortic disease, aberrant vessels, vascular access), cardiac anatomy (congenital anomalies, right ventricular dysplasia, constrictive pericarditis, valvular function), myocardial perfusion, and myocardial wall motion.     

Computerised infrared imaging system for studying thermal activation on the skull following somatic stimulation in small animals

Stress radionuclide myocardial perfusion imaging and stress echocardiography are noninvasive imaging techniques with high diagnostic and prognostic utility. Previously, patient cohorts for studies using these methods have comprised predominantly men, but recent investigations have focused on women. Stress myocardial perfusion imaging is highly accurate for diagnosing coronary disease in women, particularly with newer techniques such as gated single-photon emission computed tomography, and has been shown to be a powerful prognostic predictor in both women and men. Comparable data for stress echocardiography are emerging. Older studies reported that for similar image findings fewer women than men were referred for invasive procedures, however, newer studies suggest an absence of such a gender bias. Further developments in attenuation correction for perfusion imaging and phase-contrast magnetic resonance imaging promise to enhance the utility of noninvasive imaging for both men and women.     

Extent of myocardial damage in regions with reverse redistribution at 3 h and at 24 h on 201Tl SPET: evaluation based on regional myocardial oxidative metabolism

Reverse redistribution (RRD) of 201Tl is often observed in patients with recent myocardial infarction. However, the difference in the extent of myocardial damage between regions with 3-h RRD and those with 24-h RRD remains unknown. Accordingly, we investigated RRD from the standpoint of myocardial oxidative metabolism. Carbon-11 (11C) acetate dynamic myocardial PET scanning was performed at rest in 14 patients with recent myocardial infarction, and the clearance rate constant (Kmono) of 11C-acetate was calculated in 6-7 ROIs on the transaxial image in each patient using a monoexponential fit as an index of myocardial oxidative metabolism. Exercise 201Tl myocardial SPET was also performed. Ninety-two regions corresponding to the PET study were then classified based on the findings of transaxial 201Tl SPET imaging; that is, regions with reverse redistribution, regions with severely decreased 201Tl activity or no 201Tl activity on the 24-h delayed images, and regions with normal 201Tl activity throughout the study. Kmono in regions with reverse redistribution (0.051 +/- 0.009 min-1) was significantly lower than that in regions with normal 201Tl activity throughout the study (0.066 +/- 0.011 min-1) (P < 0.001) but significantly higher than that in regions with severely decreased or no 201Tl activity on the 24-h delayed images (0.037 +/- 0.003 min-1) (P < 0.001). Percent Kmono (i.e. Kmono in region with RRD/the mean of Kmono in all regions with a normal 201Tl SPET result) was significantly lower in the 3-h RRD regions (81.3 +/- 6.3%) than in the 24-h RRD regions (87.6 +/- 6.1%) (P < 0.05). Impairment of myocardial oxidative metabolism is observed in regions with RRD, suggesting that RRD corresponds to mild myocardial damage. Reverse redistribution on 24-h delayed images may indicate much milder myocardial damage compared with RRD on 3-h delayed images.     

Stress echocardiography versus scintigraphy in evaluating coronary heart disease: stress echocardiography is superior

Stress echocardiography has evolved as a routinely employed non-invasive method for the evaluation of patients with coronary artery disease. The diagnostic accuracy of stress echocardiography for the detection of myocardial ischemia is comparable to scintigraphic myocardial perfusion imaging, and may even have a higher specificity for the evaluation of myocardial viability. User-friendliness including patient and investigator safety, availability and mobility of the method, and environmental compatibility, is superior to that of scintigraphy. The potential for future developments, especially in the field of digital imaging and telecommunication, is great. Last but not least, echocardiography is the method most familiar to cardiologists. The sum of these arguments renders stress echocardiography the superior method to scintigraphy in the evaluation of patients with coronary artery disease.