Infarct artery perfusion and changes in left ventricular volume in the month after acute myocardial infarction.

The relation between perfusion of the infarct-related artery and changes in left ventricular volume and function during the month after a first myocardial infarction was examined in 40 patients who did not receive thrombolytic therapy. Infarct artery perfusion was documented at predischarge coronary angiography, and left ventricular volume was measured by nongeometric analysis of radionuclide angiograms performed within 48 hours of infarction and at 1 month. Left ventricular dilation (greater than or equal to 20% increase in volume) developed in 16 patients, whereas 5 patients had a decrease in left ventricular volume of greater than or equal to 20% by 1 month. Left ventricular dilation occurred in all 14 patients without perfusion of the infarct-related artery, compared with only 2 of 26 patients with perfusion of this artery due to subtotal occlusion or collateral vessels. All five patients whose left ventricular volume decreased by greater than or equal to 20% had a perfused infarct artery. Multiple linear regression analysis confirmed that the degree of perfusion of the infarct artery (partial r = 0.58, p = 0.001) was a more important predictor of volume change than was infarct size measured by peak creatine kinase (partial r = 0.30, p = 0.009) or QRS score (partial r = 0.20, p = 0.087). Left ventricular ejection fraction decreased from 0.38 +/- 0.10 to 0.30 +/- 0.16 (p = 0.05) in 11 patients with an anterior infarct and ventricular dilation; it increased from 0.45 +/- 0.10 to 0.62 +/- 0.07 (p = 0.02) in the 5 patients with a greater than or equal to 20% decrease in volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrocardiographic measurement of infarct size after thrombolytic therapy.

OBJECTIVES: We examined the utility of the 32-point QRS score from the 12-lead electrocardiogram (ECG) for measurement of the ischemic risk region and infarct size in patients receiving thrombolytic therapy. BACKGROUND: The QRS score offers a means of evaluating the therapeutic benefit of thrombolytic therapy by comparing final infarct size with the initial extent of ischemic myocardium. METHODS: The study included 38 patients (34 men, 4 women; mean [+/-SD] age 54 +/- 10 years) with a first infarction (18 anterior, 20 inferior). The maximal potential QRS score (QRS0) was assigned to all leads with >/= 100-microV ST elevation on the initial ECG. The QRS scores were calculated at 7 and 30 days after infarction. Left ventricular ejection fraction was measured by radionuclide ventriculography at 1 month. Twenty-eight patients had thallium (Tl)-201 and technetium (Tc)-99m pyrophosphate tomographic measurement of the ischemic region and infarct size. RESULTS: The QRS0 was 10.3 +/- 3.1 (mean +/- SD) for anterior and 10.4 +/- 3.5 for inferior infarcts. The QRS scores were similar at 7 and 30 days for both anterior (5.6 +/- 3.4 vs. 5.5 +/- 3.4) and inferior infarcts (3.7 +/- 2.6 vs. 2.9 +/- 2.2). The day 7 QRS score and ejection fraction at 1 month were inversely correlated (r = -0.74, p < 0.01). The Tl-201 perfusion defect was 34 +/- 11% of the left ventricle for anterior and 32 +/- 7% for inferior infarcts. Subsequent Tc-99m pyrophosphate infarct size was 15 +/- 9% of the left ventricle for anterior and 17 +/- 9% for inferior infarcts. The QRS0 was correlated with the extent of the Tl-201 perfusion defect (r = 0.79, p < 0.001), and the day 7 QRS score was correlated with Tc-99m pyrophosphate infarct size (r = 0.79, p < 0.005). CONCLUSIONS: The 32-point QRS score can provide useful immediate measurements of the ischemic risk region and subsequent infarct size.

Detection of deep venous thrombi and pulmonary embolus with technetium-99m-DD-3B6/22 anti-fibrin monoclonal antibody Fab' fragment.

UNLABELLED: Technetium-99m-labeled anti-fibrin DD-3B6/22 Fab' monoclonal antibody fragments, which specifically target human cross-linked fibrin with high affinity, were evaluated in humans for safety and their capacity to detect deep vein thrombi and pulmonary embolism. METHODS: Twenty patients with proven deep-vein thrombosis, documented by contrast venography, or venous duplex scan, were injected with a 600 MBq (0.5 mg) dose of antibody. Planar images of the lower limbs were recorded at 0, 2, 6 and 24 hr and chest scintigrams were recorded at 6 and 24 hr. RESULTS: All venography documented thrombus sites, calves, popliteal and femoral, were detected with the radioimmunoconjugate. For the venous duplex scan-proven thrombus sites, all except two calf thrombi in two patients with bilateral disease and other positive sites were detected. Five patients had bilateral deep-vein thrombosis with multiple sites being visualized with the radioimmunoconjugate in the calf, popliteal and femoral regions. One case of pulmonary embolus was also definitively demonstrated. Documented thrombus sites were detected at 2 and 6 hr postinjection. Nineteen patients were on heparin. No adverse reactions to the injected dose were observed and one low titer human anti-mouse antibody response may have occurred. CONCLUSION: The results indicate that 99mTc-DD-3B6/22 Fab' has potential for noninvasive detection of deep-vein thrombosis and pulmonary embolism.

Optimization of the scintigraphic segmental anatomy of the lungs.

UNLABELLED: Accurate and reproducible reporting of lung scintigraphy is predicated on a sound knowledge of the segmental anatomy of the lungs. A limited amount of hard data exists about the true segmental anatomy of the lungs. A virtual model of human lungs was created using a CT-based dataset and a Monte Carlo simulation technique to examine the optimal projections for the visualization of each segment in the lungs. METHODS: Segmental anatomy of the lungs was modeled using CT, cadaveric lungs and standard anatomical texts. The emission, scatter and attenuation of photons was modeled within these virtual lungs and the surrounding tissues. Single segmental lesions were created in eight projections and submitted for blinded reporting to four experienced nuclear medicine physicians to obtain the best views for each segment. RESULTS: The anterior and posterior oblique projections yielded the best views for 10 of 18 segments, with the laterals contributing four views, the anterior contributing two views and the posterior contributing one view. The majority of basal segments (six of nine) were best seen in the anterior and posterior oblique projections. CONCLUSION: This model overcomes the major problems associated with experimentation in the normal human and has the potential to provide answers to the major problems of scatter, attenuation and "shine-through" in lung scintigraphy.

Variability of perceived defect size in virtual lung scintigraphy.

UNLABELLED: The diagnosis of pulmonary embolism is based on the presence of mismatched segmental or subsegmental defects. An important axiom is the classification of defect sizes into small, moderate and large. Little information about the recognition and classification of such defects has been published. We undertook a study of the perception of defect size using a model of the virtual scintigraphic anatomy of the lungs to address this issue. METHODS: Segmental anatomy of the lungs was modeled with CT, cadaveric lungs and standard anatomical tests. The emission, scatter and attenuation of photons were modeled within these virtual lungs and the surrounding tissues. Single segmental lesions, each 100% of a segment, were created in eight projections and submitted for blinded reporting by four experienced nuclear medicine physicians to obtain their assessment of the size of each defect on two occasions. RESULTS: Of the 144 defects submitted for reporting, 15% were reported as <25% of a segment, 35% were reported as 25%-75% and 50% were reported as 75%-100%. The accuracy of each reporter and the intraobserver agreement were calculated; the weighted kappa value ranged from 0.34 to 0.60. The segmental defects that were most likely to be underestimated in size were in the right lower lobe. CONCLUSION: It is clear that segmental defect sizes were underestimated, particularly in the right lower lobe. Although the intraobserver agreement in reporting was fair, the accuracy of estimation was only 50%. The variability and inaccuracy might be reduced by the use of a guide to segmental anatomy.

Enhanced accuracy and reproducibility in reporting of lung scintigrams by a segmental reference chart.

UNLABELLED: The diagnostic probability of pulmonary embolic disease is based on the recognition of unmatched segmental perfusion defects. Although interobserver and intraobserver reproducibility have been studied, accuracy has been an elusive goal due to the lack of a gold standard. We investigated the accuracy and reproducibility of reporting in a virtual scintigraphic model of the lungs, with and without the use of a lung segmental reference chart. METHODS: A Monte Carlo package was used to model lung scintigraphy from a digital phantom of the human lungs. An ideal lung segmental reference chart was created from the phantom. Five experienced nuclear medicine physicians reported a set of all possible defects involving 100% of a segment, without and with the chart. A further set of defects involving 45%-55% of a segment in the lower lobes was investigated using the chart. RESULTS: There was a significant improvement in accuracy (from 48% to 72%) and intraobserver agreement (from 61% to 77%) with the chart. The accuracy of reporting defects in the upper and middle lobes was consistently better than that in the lower lobes. There was no significant difference between the accuracy of reporting large defects and that of reporting moderate defects in the lower lobes. CONCLUSION: The lung segmental reference chart significantly improves both the accuracy and reproducibility of reporting lung scintigrams; however, although reporting in the lung bases is improved, absolute accuracy is substantially less than that in the upper and middle lobes. This emphasizes the need for caution because the lung bases are the most common site of embolic disease.

Mechanism and significance of precordial ST-segment depression during inferior wall acute myocardial infarction associated with severe narrowing of the dominant right coronary artery.

The mechanism and significance of precordial ST depression during inferior wall acute myocardial infarction (AMI) is debated. This study assessed the location and extent of arterial perfusion distribution responsible for this electrocardiographic finding. Intracoronary thallium-201 was injected in 11 patients with 1-vessel right coronary disease to delineate perfusion distribution that was quantitated by a new angiographic distribution score. The angiographic score correlated with posterior (r = 0.84), posterolateral (r = 0.88) and total (r = 0.73) extent of intracoronary thallium distribution. The angiographic distribution score was related to electrocardiographic changes in 16 patients showing an inferior ST-segment elevation during angioplasty (7 with and 9 without precordial ST depression), of which 6 received intracoronary thallium injection. None had thallium distribution in the anterior or septal segment, but there was a trend toward a greater angiographic distribution score and posterior segment thallium score in patients with precordial ST depression. In another 77 patients with inferior wall AMI due to right coronary occlusion (24 with concomitant left anterior descending narrowing), precordial ST depression was present in 16 with and 31 without left anterior descending narrowing (p = NS). The angiographic distribution score was higher in those with than without precordial ST depression (0.59 +/- 0.10 vs 0.44 +/- 0.11, p < 0.001) in both patients with and without left anterior descending disease. The magnitude of both inferior ST elevation and precordial ST depression correlated with the angiographic distribution score, but only precordial ST depression was independently related in multivariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Verapamil in stable effort angina: effects on left ventricular function evaluated with exercise radionuclide ventriculography.

A double blind placebo-controlled study was performed in 12 patients with stable angina pectoris to evaluate the effects of oral verapamil (320 mg/day) on left ventricular function, as measured at rest and during exercise with gated equilibrium radionuclide ventriculography. On verapamil, patients had a lower heart rate-blood pressure product at each work load than with placebo. Anginal threshold increased by 28 +/- 19 watts (p less than 0.005), and maximal exercise capacity increased by 20 +/- 14 watts (p less than 0.001) with verapamil, but the rate-pressure product at the onset of angina and at maximal exercise was unchanged. Left ventricular ejection fraction at rest during verapamil therapy was the same as with placebo therapy. On exercise during placebo therapy, the ejection fraction decreased from 40 +/- 9 to 35 +/- 11 percent (p less than 0.025) because end-systolic volume increased disproportionately compared with end-diastolic volume. On exercise during verapamil therapy, the ejection fraction did not decrease (44 +/- 8 versus 45 +/- 12 percent) and was significantly higher at identical work loads than on placebo because of a smaller increase in end-systolic volume. Oral verapamil is effective treatment for effort angina and may prevent the decrease in left ventricular ejection fraction due to exercise-induced ischemia.

Antianginal effects of nitroglycerin during exercise-induced angina: hemodynamic and left ventricular function changes related to indexes of myocardial oxygen consumption.

In 14 patients during exercise, intravenous nitroglycerin improved anginal threshold and increased workload compared with control subjects. At similar workloads, the decreased left ventricular volumes suggested decreased myocardial oxygen consumption due to peripheral unloading. At maximal exercise with nitroglycerin (50 +/- 17 to 79 +/- 15 watts), rate-pressure product and end-diastolic volumes were higher with less ischemia, suggesting myocardial supply was improved by nitroglycerin.

Comparison of doxazosin and atenolol in mild hypertension, and effects on exercise capacity, hemodynamics and left ventricular function.

The effects of once-daily therapy with doxazosin (1 to 8 mg/day) on exercise capacity, left ventricular performance and hemodynamics (radionuclide ventriculography) were compared with those of atenolol (50 to 100 mg/day) and placebo in a randomized, double-blind crossover trial in 16 patients (9 men) with mild hypertension. Both medications controlled blood pressure (BP) to a similar degree (mean BP was 150 +/- 12, 137 +/- 17 and 141 +/- 14 mm Hg for placebo, atenolol and doxazosin, respectively) but by different mechanisms. Changes during maximal semierect bicycle exercise were similar to those seen at rest. Doxazosin decreased total peripheral resistance and maintained cardiac output, whereas atenolol decreased cardiac output. Exercise capacity (136 +/- 56 watts with placebo) was maintained by doxazosin (135 +/- 56 watts) but decreased with atenolol (122 +/- 55 watts). Compared with atenolol, doxazosin slightly increased the left ventricular ejection fraction at rest and during exercise. The significance of this study is in the choice of a first-line antihypertensive agent. Both are once-a-day medications that control BP. However, doxazosin does so by improving the abnormal physiology of essential hypertension and, consequently, does not adversely affect exercise performance.

Preclinical evaluation of 99m technetium-labeled DD-3B6/22 Fab' for thrombus detection.

Injection of 99mTc-labeled Fab' fragments of the anti-fibrin antibody DD-3B6/22, in the baboon, resulted in clear visualisation of both fresh and aged autologous thrombi by gamma scintigraphy. Whole body scintigraphy, pharmacokinetics and urine analysis showed rapid renal excretion of the conjugate with little accumulation of label in other organs. 99mTc-DD-3B6/22 Fab' appears a suitable candidate for further investigation as a radioimaging agent for thrombi in humans.

Anti-fibrin monoclonal antibodies for radioimmunodetection: preliminary assessment in a rat model system.

The D Dimer (DD) site formed by linkage of D domains from adjacent fibrin (FN) molecules is unique to cross-linked FN and its degradation products and is not found in FN monomer or fibrinogen (FB). Thus monoclonal antibodies (MAb) reactive to DD should have a very suitable specificity for in vivo thrombus detection. Two anti-DD MAbs have been labelled with 131-I and assessed as scintigraphic agents in a normal rat model system. Each rat received 3 sc implants of antigen covalently coupled to Sepharose beads: 1) Human DD 2) Human FB 3) Glycine (GL) (control). Scintigraphic images taken 7 days after injection of 131-I anti DD MAb showed clear localisation of both anti-DD MAbs to the DD implant rather than to the FB or GL implants with no localisation in normal tissues. This was confirmed in biodistribution studies. Injection of anti-DD MAbs DD-3B6/22 and DD-IC3/108 resulted in DD: blood ratios of 10.4 +/- 0.6 and 4.9 +/- 0.3 respectively. These results suggest that anti-DD MAbs will have potential for thrombus radioimmunodetection.

Optimized acquisition time and image sampling for dynamic SPECT of Tl-201.

With the recent development in scatter and attenuation correction algorithms, dynamic single photon emission computerized tomography (SPECT) can potentially yield physiological parameters, with tracers exhibiting suitable kinetics such as thallium-201 (Tl-201). A systematic way is proposed to investigate the minimum data acquisition times and sampling requirements for estimating physiological parameters with quantitative dynamic SPECT. Two different sampling schemes were investigated with Monte Carlo simulations: 1) Continuous data collection for total study duration ranging from 30-240 min. 2) Continuous data collection for first 10-45 min followed by a delayed study at approximately 3 h. Tissue time activity curves with realistic noise were generated from a mean plasma time activity curve and rate constants (K1 - k4) derived from Tl-201 kinetic studies in 16 dogs. Full dynamic sampling schedules (DynSS) were compared to optimum sampling schedules (OSS). We found that OSS can reliably estimate the blood flow related K1 and Vd comparable to DynSS. A 30-min continuous collection was sufficient if only K1 was of interest. A split session schedule of a 30-min dynamic followed by a static study at 3 h allowed reliable estimation of both K1 and Vd avoiding the need for a prolonged (>60-min) continuous dynamic acquisition. The methodology developed should also be applicable to optimizing sampling schedules for other SPECT tracers.

Monte Carlo and experimental evaluation of accuracy and noise properties of two scatter correction methods for SPECT.

Scatter correction is a prerequisite for quantitative SPECT, but potentially increases noise. Monte Carlo simulations (EGS4) and physical phantom measurements were used to compare accuracy and noise properties of two scatter correction techniques: the triple-energy window (TEW), and the transmission dependent convolution subtraction (TDCS) techniques. Two scatter functions were investigated for TDCS: (i) the originally proposed mono-exponential function (TDCSmono) and (ii) an exponential plus Gaussian scatter function (TDCSGauss) demonstrated to be superior from our Monte Carlo simulations. Signal to noise ratio (S/N) and accuracy were investigated in cylindrical phantoms and a chest phantom. Results from each method were compared to the true primary counts (simulations), or known activity concentrations (phantom studies). 99mTc was used in all cases. The optimized TDCS(Gauss) method overall performed best, with an accuracy of better than 4% for all simulations and physical phantom studies. Maximum errors for TEW and TDCS(mono) of -30 and -22%, respectively, were observed in the heart chamber of the simulated chest phantom. TEW had the worst S/N ratio of the three techniques. The S/N ratios of the two TDCS methods were similar and only slightly lower than those of simulated true primary data. Thus, accurate quantitation can be obtained with TDCS(Gauss), with a relatively small reduction in S/N ratio.

Correlation between post-ejection shortening and improvement in regional wall motion after revascularization in patients with coronary artery disease.

This study investigates the relationship between regional post-ejection shortening and improvement in wall motion after revascularization in patients with severe regional left ventricular contractile dysfunction. Canine studies have documented the phenomenon of post-systolic shortening during acute ischemia, and this predicted recovery of contractile function when ischemia was relieved. This delayed shortening from the ischemic segment would cause regional emptying while the other normal portion of the left ventricle starts to have diastolic relaxation. This was detectable by standard phase analysis of the radionuclide ventriculogram, the abnormal region with delayed emptying being distinguished from the normal portion of left ventricle as an area with a homogeneous phase delay. Twelve patients with successful revascularization and a pre-operative study demonstrating a single homogeneous area of phase delay were identified. The area was demarcated and the regional volume-time curve constructed. The volume-time curve of the abnormal region is analogous to the myocardial segment length versus time relationship in the canine model. We quantitated the amount of delayed (post-systolic) emptying in the demarcated region as the difference between end-systole counts and post-systolic nadir counts, and this was normalised to left ventricular stroke count. After revascularization, regional ejection fraction improved from 44 +/- 10% to 62 +/- 14% (P < 0.001), representing a 47 +/- 50% improvement over baseline. The percentage improvement in regional ejection fraction correlated with post-systolic emptying (r = 0.74, P < 0.05) but not with initial regional ejection fraction. In conclusion, post-ejection shortening causes regional post-systolic emptying and this correlates with post-revascularization improvement in regional wall motion.

The diagnosis of renal osteodystrophy: a comparison of Technetium-99m-pyrophosphate bone scintigraphy with other techniques.

In order to determine the place of Technetium-99m-pyrophosphate bone scintigraphy in the assessment of renal osteodystrophy, 17 patients with chronic renal failure requiring hemodialysis underwent bone scans and these were compared to results of biochemical, radiological and histologic studies. Bone histology was abnormal in all patients with most having evidence of osteomalacia and hyperparathyroid bone disease. Using semi-quantitative scan scores and regional bone-standard ratios, isotope uptake was increased in 16 patients, while 15 had elevated alkaline phosphatase levels and 7 had X-ray changes. An osteoid-osteoclast index combining histological osteomalacia and hyperparathyroid disease was derived and was found to correlate more closely with alkaline phosphatase and parathyroid hormone levels than with scan parameters. It was concluded that bone scans did not provide therapeutically useful information that could not be obtained from biochemical and radiological studies. It appeared that only bone histology could differentiate osteomalacia and hyperparathyroid bone disease.

Tc-99m white cell scintigraphy in suspected acute infection.

The usefulness of In-111 labeled white cells in acute infection is well documented but the role of Tc-99m labeled white cell scintigraphy (WCS) has not been as clearly established. Using stannous fluoride colloid and a simple labelling procedure with 20 ml of autologous whole blood, three cases are presented in which Tc-99m WCS established unexpected diagnoses in patients who had remained undiagnosed despite extensive investigation.

Detection of malignant tumors using Tc-99m labeled Fab' fragments from a monoclonal antibody with specificity for D-dimer of cross-linked fibrin.

The authors present the case studies of two patients whose malignant tumors were detected with a Tc-99m labeled antifibrin monoclonal antibody (DD-3B6/22), which is specific for cross-linked fibrin. The first case was a malignant fibrous histiocytoma involving the proximal aspect of the left thigh, whereas in the second case, the patient was receiving treatment for a squamous cell carcinoma of the right mainstem bronchus. The results highlight the potential of this anti-D-dimer radiopharmaceutical for noninvasive detection of malignant tumors.