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J R Corbett

Publications and source records attributed to J R Corbett.

At least 37 records · Page 2Linked to original sources
PubMed1992

Synthesis and evaluation of technetium-99m monocationic mixed ligand complexes of phenyl substituted/condensed tetradentate Schiff's bases and trimethylphosphine.

Tc-99m monocationic mixed ligand complexes of phenyl substituted/condensed Schiff's bases, N,N'-ethylene-bis-(benzoylacetone imine) (Lb) or N,N'-ethylene-bis-(salicylaldehyde imine) (Lc) or N,N'-ethylene-bis-(2-hydroxyacetophenone imine) (Ld) and trimethylphosphine were synthesized to determine the influence of the presence of a phenyl group in these tracers on their heart uptake in rats. A new formulation procedure using aq. beta-hydroxypropylcyclodextrin (HPB) solution was developed for intravenous administration of nonpolar 99mTc complexes. Comparison of biodistribution data for the reference 99mTc complex from N,N'-ethylene-bis-(acetylacetone imine) and trimethylphosphine using HPB formulation and alternate formulation (0.9% saline) showed the same results. Biodistribution of the title 99mTc complexes, [99mTc Lb (PMe3)2]+, [99mTc Lc (PMe3)2]+ and [99mTc Ld (PMe3)2]+ showed heart-to-blood activity ratios of 1.7, 2.1 and 1.7, respectively, at 15 min post-injection in rats.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1992

Utility of various radionuclide techniques for distinguishing ischemic from nonischemic dilated cardiomyopathy.

BACKGROUND: Clinically, ischemic and nonischemic (idiopathic) dilated cardiomyopathy may be difficult to distinguish. Radionuclide ventriculography and exercise testing with thallium-201 scintigraphy are often used in an attempt to differentiate them noninvasively. With these techniques, the presence of (1) left ventricular (LV) regional asynergy, (2) depressed LV systolic function with normal right ventricular function, and/or (3) thallium-201 perfusion abnormalities traditionally has been regarded as evidence of ischemic heart disease. We assessed the incidence with which these abnormalities occur in patients with nonischemic-dilated cardiomyopathy. METHODS: Seventy-six patients (45 men, 31 women, aged 18 to 75 years) with invasively proven nonischemic-dilated cardiomyopathy underwent radionuclide ventriculography (n = 75) and provocative thallium-201 perfusion imaging (n = 17). RESULTS: Regional LV wall motion abnormalities were noted in 48% of patients, and 54% had LV systolic dysfunction without concomitant right ventricular dysfunction. Reversible and/or fixed exercise-induced thallium-201 perfusion abnormalities occurred in 94% of the patients studied. CONCLUSIONS: Radionuclide ventriculography and exercise testing with thallium perfusion imaging cannot be used reliably to differentiate ischemic from nonischemic dilated cardiomyopathy, since many patients with the latter have radionuclide evidence of LV segmental wall motion abnormalities, selective LV systolic dysfunction, and segmental perfusion abnormalities.

Adolescent↗
PubMed1991

Regional cardiac adrenergic function using I-123 meta-iodobenzylguanidine tomographic imaging after acute myocardial infarction.

The effect of acute myocardial infarction (AMI) on regional cardiac adrenergic function was studied in 27 patients mean +/- standard deviation 10 +/- 4 days after AMI. Regional adrenergic function was evaluated noninvasively with I-123 meta-iodobenzylguanidine (MIBG) using a dedicated 3-detector tomograph. Four hours after its administration, there was reduced MIBG uptake in the region of infarction, 0.38 +/- 0.31 counts/pixel/mCi x 103 compared with 0.60 +/- 0.30 counts/pixel/mCi x 103 and 0.92 +/- 0.35 counts/pixel/mCi x 103 in the zones bordering and distant from the infarct area, respectively, p less than 0.001. In all patients, the area of reduced MIBG uptake after 4 hours was more extensive that the associated thallium-201 perfusion defect with defect scores of 52 +/- 22 and 23 +/- 18%, respectively, p less than 0.001. After anterior wall AMI, the 4-hour MIBG defect score was 70 +/- 13% and the degree of mismatch between myocardial perfusion and MIBG uptake was 30 +/- 9% compared with 39 +/- 17 and 21 +/- 17% after inferior AMI, p less than 0.001 and p = 0.016, respectively. The 4-hour MIBG defect score correlated inversely with the predischarge left ventricular ejection fraction, r = -0.73, p less than 0.001. Patients with ventricular arrhythmia of greater than or equal to 1 ventricular premature complexes per hour, paired ventricular premature complexes or ventricular tachycardia detected during the late hospital phase had higher 4-hour MIBG defect scores, 62.5 +/- 15.0%, than patients with no detectable complex ventricular ectopic activity and a ventricular premature complex frequency of less than 1 per hour, 44.6 +/- 23.4%, p = 0.036.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Iodobenzylguanidine↗
PubMed1991

Effects of bucindolol on neurohormonal activation in congestive heart failure.

To examine the effects of beta-adrenergic blockade on neurohormonal activation in patients with congestive heart failure, 15 men had assessments of hemodynamics and supine peripheral renin and norepinephrine levels before and after 3 months of oral therapy with bucindolol, a nonselective beta antagonist. At baseline, plasma renin activity did not correlate with any hemodynamic parameter. However, norepinephrine levels had a weak correlation with left ventricular end-diastolic pressure (r = 0.74, p less than 0.01), stroke volume index (r = 0.61, p less than 0.02) and pulmonary vascular resistance (r = 0.54, p less than 0.05). Plasma renin decreased with bucindolol therapy, from 11.6 +/- 13.4 to 4.3 +/- 4.1 ng/ml/hour (mean +/- standard deviation; p less than 0.05), whereas plasma norepinephrine was unchanged, from 403 +/- 231 to 408 +/- 217 pg/ml. A wide diversity of the norepinephrine response to bucindolol was observed with reduction of levels in some patients and elevation in others. Although plasma norepinephrine did not decrease, heart rate tended to decrease (from 82 +/- 20 vs 73 +/- 11 min-1, p = 0.059) with beta-adrenergic blockade, suggesting neurohormonal antagonism at the receptor level. No changes in I-123 metaiodobenzylguanidine uptake occurred after bucindolol therapy, suggesting unchanged adrenergic uptake of norepinephrine with beta-blocker therapy. Despite reductions in plasma renin activity and the presence of beta blockade, the response of renin or norepinephrine levels to long-term bucindolol therapy did not predict which patients had improved in hemodynamic status (chi-square = 0.37 for renin, 0.82 for norepinephrine).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Iodobenzylguanidine↗
PubMed1991

Spatial and temporal registration of cardiac SPECT and MR images: methods and evaluation.

Image registration may assist in the integration of information from multiple sources by allowing direct point-for-point comparisons of studies. To determine the usefulness of such a technique, a method for the spatial and temporal registration of four-dimensional single photon emission computed tomographic (SPECT) and magnetic resonance (MR) cardiac images was developed. Automatically detected left ventricular endocardial surfaces were used to determine the best transform between the two sets of surface points, and that transform was applied to the original SPECT image. A fused image created from the MR and the transformed SPECT images combined the information in both. The authors tested the method with seven patient studies. Registration reduced the distance between the MR and SPECT left ventricular endocardial surfaces by 30%, to an average of 2.7 mm. The authors found that, by using the fused images, perfusion abnormalities could be easily localized and correlated to high-resolution endocardial wall motion and systolic wall thickening.

Coronary Disease↗
PubMed1991

Three-dimensional motion and perfusion quantification in gated single-photon emission computed tomograms.

Methods for quantification and display of left ventricular (LV) functional parameters from gated single-photon emission computed tomographs are described. Using previously documented surface detection methods, we developed techniques for calculating global variables, such as volumes and areas, as well as local variables such as segmental motion and local perfusion from gated tomographic radionuclide ventriculograms (TRVG) and gated perfusion tomograms (sestamibi). We have developed three-dimensional displays to allow realistic visualizations of the results. The motion results have been validated using correlative magnetic resonance imaging (MRI) studies; motion calculated from user-traced MR images of the heart was compared to motion calculated from automatically detected surfaces in TRVG and sestamibi. The average motion error was calculated to be 0.67 mm in TRVG and -0.21 mm in sestamibi. Errors were largest in basal LV regions; we explain this phenomenon using simulations. Finally, we present additional examples of the analysis using studies obtained from normal volunteers and from subjects whose coronary artery anatomies were known.

Coronary Disease↗
PubMed1991

Radionuclide assessment of ventricular function and risk stratification after myocardial infarction.

Prognosis after acute myocardial infarction is determined primarily by left ventricular function and by the extent to which additional coronary obstructions jeopardize viable myocardium. Radionuclide ventriculography is well suited for noninvasive assessments of resting and exercise ventricular function after acute myocardial infarction. The prognostic importance of resting left ventricular function after acute myocardial infarction is well established. Several studies have reported the prognostic utility of submaximal exercise radionuclide ventriculography at the time of hospital discharge. Patients with globally depressed left ventricular function after acute myocardial infarction are at increased risk for cardiac death, while patients with normal resting ventricular function but abnormal function during exercise appear to be at risk for nonfatal ischemic events. The development of gated tomographic techniques and new radiopharmaceuticals will make available more accurate and detailed assessments of ventricular function and combined assessments of function and perfusion. These new developments require further investigation but appear to be promising new techniques with the potential for providing improved assessments of prognosis after acute myocardial infarction.

Cardiac Volume↗
PubMed1990

Development and prospective application of quantitative 2-day stress-rest Tc-99m methoxy isobutyl isonitrile SPECT for the diagnosis of coronary artery disease.

The clinical diagnostic accuracy of 2-day stress/rest quantitative Technetium-99m (Tc-99m) methoxy-isobutyl-isonitrile (Tc-sestamibi) single photon emission computerized tomography (SPECT) was assessed in a validation population of 61 patients from two different sites using two different camera/computer systems. The study population was made up of 53 catheterized patients, 29 from Cedars-Sinai Medical Center (CSMC) and 24 from the University of Texas Southwestern Medical Center (UTSMC), and eight UTSMC patients with a less than 5% pre-test likelihood of coronary artery disease. Interpretation employed gender-specific normal limits developed in an additional 15 men and 8 women at CSMC with less than a 5% likelihood of significant coronary artery disease. The results from CSMC compared with those from UTSMC were not different from each other. The overall sensitivity for detection of patients with coronary artery disease (greater than or equal to 50% stenosis) was 94% (CSMC: 92%, UTSMC: 95%). Overall specificity in the five patients with normal coronary arteriograms was 80% (CSMC: 67%, UTSMC: 100%). The normalcy rate in patients with a low likelihood of coronary artery disease was 88%. Vessel sensitivity was 85% (CSMC: 84%, UTSMC: 85%), while vessel specificity was 71% (CSMC: 72%, UTSMC: 69%). There was also no significant difference in the sensitivities and specificities between male and female populations. In addition, the agreement with coronary angiography for assessment of disease extent (normal coronary arteriogram, single or multivessel disease) was 75% (kappa = 0.6 +/- 0.1). This study demonstrated that Tc-sestamibi SPECT by quantitative analysis is accurate for the detection and localization of coronary artery disease. Furthermore, the CSMC quantitative method was shown to provide similar diagnostic accuracy when applied to data acquired at a different site using a different camera/computer system.

Adult↗
PubMed1990

Radioiodinated tracers for myocardial imaging.

Recent advances in the efficient production of high purity radioiodine (123I) and new efficient radiolabeling techniques have allowed the development of new classes of cardiovascular radiopharmaceuticals. These include 123I-labeled fatty acids to assess myocardial metabolism, 123I-metaiodobenzylguanidine (MIBG) for myocardial neuronal activity, labeled monoclonal antibodies for myocardial necrosis, and labeled lipoproteins for receptor concentration. 123I-labeled fatty acids and MIBG are under clinical investigation with encouraging results. 123I- and 111In-labeled fragments of monoclonal antibodies to myosin have been used for imaging myocardial necrosis in humans. The development of radiotracers for imaging of cholinergic and adrenergic receptors is still in the experimental stage. Recent advances in imaging instrumentation and radiopharmaceuticals have resulted in cardiac imaging applications beyond blood pool ventriculography, perfusion, and infarct-avid imaging. Developments of radioiodine (123I)-labeled agents promise to play an important role in the assessment of myocardial metabolism, neuronal activity, and receptor concentration. The chemistry of iodine is well defined compared with that of 99mTc; therefore, iodine isotopes are well suited for labeling biologically important molecules. Among the iodine isotopes, 123I has nearly ideal nuclear properties for nuclear medical applications with a 13.3-hour half-life (T1/2) and 159 keV gamma emission (83%). Despite the nearly ideal chemical and nuclear properties of 123I, the widespread application of 123I-based radiopharmaceuticals in clinical practice has been limited by high production costs (123I is produced in a cyclotron), relatively limited availability, and the presence of undesirable radionuclidic impurities (124I, T1/2 = 4.2 days; 125I, T1/2 = 60 days; 126I, T1/2 = 13.1 days). The relatively long T1/2 and beta particle emission can substantially increase the higher radiation burden to the patient. High energy gamma rays (greater than 600 KeV) from these impurities can degrade images obtained using low energy collimators. Recent developments in production techniques have greatly reduced the levels of the undesirable radionuclides in 123I. Ready availability of pure 123I at modest cost, in concentrations suitable for the radio-labeling of a variety of useful biomolecules, should enhance the clinical applications of 123I-labeled compounds. Molecules labeled with 123I that are useful in cardiac imaging studies are fatty acid analogs, monoclonal antibodies, receptor binding agents, and norepinephrine analogs. This article will discuss developments in radioiodine (123I)-labeled radiotracers for myocardial imaging.

Heart↗
PubMed1990

Iodine-123 phenylpentadecanoic acid myocardial scintigraphy in patients with left ventricular hypertrophy: alterations in left ventricular distribution and utilization.

Regional alterations in myocardial substrate uptake and/or utilization have been demonstrated in rats with hypertension. To determine whether alterations in left ventricular fatty acid uptake and/or utilization are present in patients with left ventricular hypertrophy (LVH), we compared the results of rest and exercise iodine-123 phenylpentadecanoic acid (IPPA) myocardial scintigraphy in 10 patients with hypertension who had concentric LVH without evidence of coronary artery disease and in 15 normal subjects. Patients with LVH had more heterogeneous left ventricular activity of IPPA compared to normal subjects after exercise but not at rest (23 +/- 8% versus 13 +/- 5% difference in maximum segmental activity at 4 minutes after exercise; p = 0.005). Although IPPA clearance was similar in both patients with LVH and normal subjects, postexercise washout in segments showing decreased initial IPPA uptake was reduced compared to washout at rest in patients with LVH (11.7 +/- 7.5% versus 21.5 +/- 8.4% at 20 minutes after injection, n = 15; p = 0.005). Exercise thallium-201 (TI-201) scintigraphy was normal in all seven patients with LVH tested. Patients with LVH showed significantly greater heterogeneity in IPPA uptake compared to TI-201 uptake immediately after exercise (25 +/- 5% versus 16 +/- 6%; p = 0.013). We conclude that (1) compared to normal subjects, patients with LVH show heterogeneous myocardial IPPA activity after exercise but not at rest; (2) postexercise washout of IPPA was decreased in segments with reduced uptake after exercise in patients with LVH; and (3) the distribution of IPPA is more heterogeneous than that of TI-201 immediately after exercise in patients with concentric LVH. The postexercise heterogeneity in IPPA uptake and delayed washout in segments with reduced initial uptake is consistent with exercise-induced myocardial ischemia in patients with LVH.

Adult↗
PubMed1989

Estimation of jeopardized left ventricular myocardium in symptomatic and silent ischemia as determined by iodine-123 phenylpentadecanoic acid rotational tomography.

Whether patients with silent myocardial ischemia have a lesser mass of ischemic myocardium than patients with symptomatic ischemia is controversial. Forty-five patients with angiographic coronary artery disease (greater than or equal to 70% luminal diameter narrowing) were studied. All patients had ischemic patterns of myocardial uptake and clearance of the long-chain fatty acid perfusion/metabolic imaging agent iodine-123 phenylpentadecanoic acid after maximal exercise. Single-photon emission computed tomography was performed and 25 myocardial segments were analyzed using circumferential activity profile curves. The 21 patients with silent treadmill ischemia exercised longer than the 24 patients with painful treadmill ischemia (430 +/- 137 vs 337 +/- 96 seconds, p less than 0.01) and to a higher heart rate (138 +/- 21 vs 125 +/- 18 beats/min, p less than 0.05). Patients with treadmill silent ischemia had the same number of abnormally perfused myocardial segments as patients with painful treadmill ischemia (8.6 +/- 4.5 vs 6.5 +/- 4.1 segments, difference not significant) and the same number of reversibly ischemic myocardial segments (4.0 +/- 1.4 vs 4.2 +/- 3.0 segments, difference not significant). The angiographic severity and extent of coronary artery disease were similar in the 2 groups. Thus, in this selected group of patients, those with silent treadmill ischemia appear to have at least as great an extent of ischemic myocardium as patients with painful exertional ischemia.

Angina Pectoris↗
PubMed1989

Quantitative rotational tomography with 201Tl and 99mTc 2-methoxy-isobutyl-isonitrile. A direct comparison in normal individuals and patients with coronary artery disease.

We tested the hypothesis that 99mTc 2-methoxy-isobutyl-isonitrile (99mTc MIBI), a new radiopharmaceutical for myocardial perfusion imaging, provides accurate noninvasive detection of coronary artery disease (CAD). Imaging in patients after exercise and at rest with 99mTc MIBI was compared with imaging after exercise and redistribution with 201Tl in 12 normal subjects and 38 patients with angiographic documentation of CAD (greater than or equal to 50% diameter stenosis). We used single-photon emission computed tomography (SPECT) and computer quantitation of regional tracer distribution. The quality of reconstructed images with 99mTc MIBI judged visually was superior to that of 201Tl in 88% of all studies performed and was comparable in the others. With the limits of normal as 2.5 SD below the mean of gender-matched normal volunteers, 201Tl SPECT identified 32 and 99mTc MIBI identified 36 patients with CAD (p = 0.2). 201Tl SPECT identified 45 of 75 (60%) and 99mTc MIBI identified 59 of 75 (79%) stenosed coronary arteries (p less than 0.05). The quantitative severity of perfusion defects was similar for the two tracers. 201Tl SPECT identified 104 reversibly ischemic myocardial segments compared with 134 with 99mTc MIBI (p less than 0.05). Thus, SPECT myocardial perfusion imaging with 99mTc MIBI and computer quantitation provides an accurate method for the noninvasive detection of significant coronary artery disease. Furthermore, image quality is generally superior to 201Tl, and reversibly ischemic myocardial segments may be better identified with 99mTc MIBI.

Adult↗
PubMed1989

New radionuclide agents for cardiac imaging: description and application.

The introduction of three new radiopharmaceuticals into clinical research and practice has broadened the potential applications and scope of nuclear cardiology examinations. Technetium-99m labeled isonitrile perfusion agents have excellent imaging characteristics allowing the accurate identification of coronary artery disease. Simultaneous assessments of ventricular function are possible with these agents. Iodine-123 phenylpentadecanoic acid myocardial scintigraphy permits assessments of myocardial perfusion and fatty acid metabolism, and permits investigations of myocardial metabolism with conventional imaging equipment. Iodine-123 meta-iodobenzyl-guanidine serves as an indicator of the functional integrity of the sympathetic nervous system and permits evaluations of the effects of various disease states on catecholamine handling by the heart.

3-Iodobenzylguanidine↗
PubMed1989

Quantification of three-dimensional left ventricular segmental wall motion and volumes from gated tomographic radionuclide ventriculograms.

Tomographic radionuclide ventriculograms may be used for three-dimensional wall motion analysis. We propose that automatic quantification of these images is possible, and here we describe the implementation and validation of a method to perform this task. Automatic computer methods were developed to locate the left ventricular (LV) endocardial surfaces in all time frames of the cardiac cycle. Global, regional, and local motion and volume were computed. Results were displayed using three-dimensional graphics. The methods were validated using phantom, canine, and human studies. Actual phantom values correlated well with experimentally determined volumes, y = 1.01x + 1.29ml, r = 0.99. In the canine model, the LV endocardial surfaces were located to within an average of 1.9 mm and 3.7 mm at end-diastole and end-systole, respectively. Areas of obvious wall motion abnormalities in automatically processed patient studies corresponded well with angiographically documented coronary artery disease. End-diastolic and end-systolic volumes computed automatically from single photon emission computed tomography averaged errors of 9% and 38%, respectively, when compared with contrast ventriculographic volumes. These results indicate that it is possible to automatically identify the left ventricular endocardial surface in gated tomographic radionuclide ventriculograms. The location of these surfaces corresponds well with the location of implanted endocardial markers, and global volume computed from these surfaces corresponds well with known volumes.

Adult↗
PubMed1989

Quantitation of postexercise lung thallium-201 uptake during single photon emission computed tomography.

To test the hypothesis that analysis of lung thallium uptake measured during single photon emission computed tomography (SPECT) yields supplementary clinical information as reported for planar imaging, quantitative analysis of lung thallium uptake following maximal exercise was performed in 40 clinically normal subjects (Group 1) and 15 angiographically normal subjects (Group 2). Lung thallium uptake was measured from anterior projection images using a ratio of heart-to-lung activities. Seventy subjects with coronary artery disease (CAD) (Group 3) determined by angiography (greater than or equal to 70% luminal stenosis) underwent thallium perfusion SPECT. Thirty-nine percent of these subjects had multivessel and 61% had single vessel CAD. Lung thallium uptake was elevated in 47 of 70 (67%) Group 3 subjects. Group 3 subjects with elevated lung thallium uptake did not differ from Group 3 subjects with normal lung thallium uptake with respect to extent or distribution of coronary artery disease, left ventricular function, or severity of myocardial ischemia as determined by exercise and redistribution thallium SPECT. Thus, the measurement of thallium lung uptake from anterior projection images obtained during SPECT frequently identifies patients with CAD, but it may not provide supplementary information regarding the extent of myocardial ischemia or ventricular dysfunction.

Adult↗
PubMed1988

Abnormal myocardial fatty acid metabolism in dilated cardiomyopathy detected by iodine-123 phenylpentadecanoic acid and tomographic imaging.

The radioidinated synthetic fatty acid iodine-123 phenylpentadecanoic acid (IPPA) has proven useful in the identification of regional abnormalities of cardiac metabolism in patients with myocardial ischemia. The present study was performed to test the hypothesis that the myocardial distribution and turnover of fatty acids, assessed noninvasively with IPPA, are altered in patients with cardiomyopathy. Nine normal volunteers and 19 patients with dilated cardiomyopathy of various etiologies underwent cardiac imaging with single-photon emission computed tomography (SPECT) after intravenous injection of IPPA. Apical short-axis and basal short-axis sections were reconstructed and quantitatively analyzed for relative IPPA activity distribution and washout. Patients with congestive cardiomyopathy demonstrated significantly greater heterogeneity of IPPA uptake than normal subjects (maximal percent variation of activity 27 +/- 11 vs 18 +/- 4, p less than 0.01). They also demonstrated a more rapid percent washout rate than control subjects (24 +/- 8 vs 17 +/- 6 for the apical short-axis section, p less than 0.05; 26 +/- 7 vs 18 +/- 5 for the basal short-axis section, p less than 0.01). These abnormalities of fatty acid distribution and turnover were independent of the etiology of the cardiomyopathy. The degree of heterogeneity of IPPA uptake was significantly related to the patients' New York Heart Association functional class (r = 0.64, p less than 0.01). Thus, compared with normal myocardium, the myocardium of patients with congestive cardiomyopathy demonstrates a more heterogeneous distribution of fatty acid uptake, which parallels the clinical severity of the disease. Furthermore, patients with congestive cardiomyopathy demonstrate a more rapid myocardial clearance of the labeled fatty acid, as assessed with SPECT imaging.

Adult↗