Value of radionuclide studies in cardiac transplantation

Effective noninvasive evaluation of acute and chronic allograft rejection remains an important challenge in patients with cardiac transplantation. Radionuclide studies have demonstrated utility because of their ease of use, giving relevant information about the pathophysiology of the transplanted heart, along with valuable diagnostic and prognostic indicators. This article focuses on reviewing the pathophysiological changes of the transplanted heart and implications for radionuclide studies.     

拮抗细胞程序性坏死——机体应激损伤防护的新策略

应激是机体对内外环境变化做出的总体反应,过度应激导致机体的组织坏死和器官衰竭,从而诱发应激损伤。细胞程序性坏死是一种新鉴定的可调控的程序性细胞死亡,具有明确的调控靶点和信号转导通路,且在缺血再灌注、外源微生物感染和炎症反应等应激因素诱导的组织损伤过程中具有重要的调控作用。同时,细胞程序性坏死抑制剂在多种应激损伤动物模型中都表现出显著的预防和治疗效果,从而表明阻断细胞程序性坏死将成为应激损伤预防和治疗的新策略,而细胞程序性坏死的调控靶蛋白也为应激损伤的药物设计提供了新的靶点。     

The detection of coronary stiffness in cardiac allografts using MR imaging

Objective

To test the hypothesis that biomechanical changes are quantitatively related to morphological features of coronary arteries in heart transplant (HTx) recipients.

Materials and methods

With IRB approval, three-dimensional (3D) magnetic resonance (MR) angiography and two-dimensional (2D) black-blood stead-state free precession (SSFP) MR imaging were performed to image coronary arteries of 36 HTx patients. Contours of coronary wall were manually drawn. For each coronary segment, coronary wall thickness, wall area, lumen area (in systole and diastole) were acquired. Coronary distensibility index (CDI) and the percent of the coronary wall occupying the vessel area (PWOV) were calculated.

Results

There are totally 98 coronary segments eligible for quantitative analysis from 27 HTx patients. The CDI is 4.90 ± 2.44 mmHg⁻¹. The mean wall thickness is 1.49 ± 0.24 mm and the PWOV is 74.6% ± 7.5%. CDI has moderate correlations with wall thickness (r = −0.531, P < 0.001) and with PWOV (R = −0.435, P < 0.001).

Conclusions

Detected with coronary MR imaging, CDI is quantitatively correlated with the morphological features of the coronary artery in HTx patients. Coronary stiffness has the potential to become an alternative imaging biomarker for the quantitative assessment of the status of cardiac allografts.     

Identification of cardiac rejection in heterotopic heart transplantation using 111In-antimyosin

It is important in heart transplantation to evaluate precisely the extent and location of cardiac rejection. At present, right ventricular endomyocardial biopsy has been used as the gold standard, however, establishment of noninvasive, simple, and easy diagnostic procedure is desired. The canine donor heart, in which atrial septal defect and tricuspid regurgitation had been produced beforehand, was heterotopically transplanted into the recipient's chest cavity. In seven dogs, two to three mCi of ¹¹¹In-antimyosin was injected intravenously upon cardiac rejection before the heart was excised. ¹¹¹In-antimyosin myocardial imaging was then performed using a gamma camera. In the same slice, a histopathological rejection score was calculated and divided into mild, moderate or severe injection. the uptake of ¹¹¹In-antimyosin was significantly higher in moderate and severe rejected myocardium, since this agent produced a specific and selective localization and concentration in areas of myocardial damage. Therefore, this new technique allows the evaluation of therapeutic intervention upon cardiac rejection and may replace right ventricular endomyocardial biopsy.     

The relationship between clinical stage,prognosis and myocardial damage in patients with Duchenne-type muscular dystrophy: five-year follow-up study

The evaluation of myocardial damage by [123I] 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) imaging, which represents free fatty acid metabolism, has not been reported in patients with Duchenne-type muscular dystrophy (DMD). To date, the relationship between clinical stage, prognosis and myocardial damage has not been evaluated by radionuclear cardiac imaging. The main goal of this study was to elucidate the relationship of quantitative indices of myocardial damage obtained by radionuclear cardiac imaging ([201Tl] and [123I] BMIPP) to clinical stage and incidence of severe cardiac events in patients with Duchenne-type muscular dystrophy (DMD). METHODS: The study population consisted of 28 male patients with DMD. The average age at the beginning of observation was 19.1 +/- 7.4 yrs. Nuclear tomographic imaging was performed using [201Tl] and [123I] BMIPP. The mid-ventricular short axial slices were classified into four anatomical regions, and the normalized count data in these areas (TL, BM) were obtained. The endpoint was the occurrence of heart failure during the follow up period. RESULTS: Thirteen cases of heart failure occurred during the 5-year follow-up period, including three cases with cardiac death due to congestive heart failure. Clinical staging correlated directly with TL (p = 0.0118) and BM (p = 0.0401) in the whole left ventricle. In regional TL analysis, an association was observed only in the septum (p = 0.0151), and in the anterior (p = 0.0361) region. The only discrepancy between the tracer parameters (TL - BM) in the septum was observed with the radionuclear cardiac values, which exhibited a relationship with cardiac events (p = 0.0124). This discordance, TL < BM, was contrary to that usually observed in patients with ischemic heart disease. CONCLUSION: The septum is the critical area of significance for cardiac events and outcome in patients with DMD. The uptake of [201Tl] in this area was representative of the clinical stage, and TL-BM correlated well with the prognosis.     

Water diffusion in a rat glioma during ganciclovir-thymidine kinase gene therapy-induced programmed cell death in vivo: correlation with cell density

PURPOSE: To study the characteristics of diffusion magnetic resonance imaging (MRI) contrast in a rat brain BT4C glioma during progression of ganciclovir (GCV)-thymidine kinase gene therapy-induced programmed cell death (PCD) in vivo. MATERIALS AND METHODS: The trace of the diffusion tensor (Dav = 1/3TraceD), T2, and spin density were determined by MRI and the apparent diffusion coefficient (ADC) of water by diffusion nuclear MR (NMR) spectroscopy using largely varying b values and diffusion times (tD) at 4.7 T. Cell count and apoptotic cells were quantified by histological means. RESULTS: Decline in cell count was strongly associated with increase in both Dav and T2. Spin density ratio between tumor and contralateral parietal cortex increased with a very similar time course as Dav and T2, indicating net water gain into the eradicating tumor. Diffusion spectroscopy showed a nonmonoexponential signal decay at all tD values ranging from 14-192 msec. During PCD, the ADC of the component yielding fast diffusion coefficient (D1), as acquired with tD > or = 47 msec, increased with kinetics similar to those of Dav (tD = 4.8 msec). The fractional size of D1 increased by 10% to 15% throughout the entire tD range. Apparent water residence time of the slow diffusion component, D2, shortened from a value of 38.3 +/- 1.7 msec on day 0 to 33.4 +/- 0.5 msec by day 8. CONCLUSION: The present results show that reduced cell density and increased water content, leading to altered water microenvironment, are associated with increased water diffusion coefficient in eradicating gliomas as a result of PCD.     

Liver transplant rejection and cholestasis: comparison of technetium 99m-diisopropyl iminodiacetic acid hepatobiliary imaging with liver biopsy

To determine whether the scintigraphic evaluation of technetium-99m diisopropyl iminodiacetic acid (DISIDA) uptake and excretion can distinguish among liver transplant patients with biopsy evidence for rejection, cholestasis or neither condition, we reviewed scintigrams and biopsies in 36 patients. There were 76 scintigrams with corresponding biopsies. Uptake and excretion were graded from image data on scales reflecting normal through severely abnormal values. Biopsies were evaluated for findings of cholestasis and rejection. The majority of scintigrams demonstrated normal uptake (60/75, 80%) and delayed excretion (65/76, 85%), which was most marked immediately after transplantation. One-way analysis of variance showed that the mean excretion values significantly differed between patients with normal biopsies and those with cholestasis and/or rejection (P =0.0003). However, mean uptake scores demonstrated no statistically significant difference between these two groups of patients (P =0.1). These findings suggest that ^99mTc-DISIDA scintigraphy can differentiate between transplants with and without rejection/cholestasis but not between rejection and cholestasis. If ^99mTc-DISIDA excretion is normal, rejection and cholestasis are unlikely. Offprint requests to: C.M. Engeler     

Macrophage labeling by SPIO as an early marker of allograft chronic rejection in a rat model of kidney transplantation.

Anatomical and functional information (renography, perfusion) was obtained by MRI in a life-supporting transplantation model, in which Lewis rats received kidneys from Fisher 344 donors. Renography and perfusion analyses were carried out with Gd-DOTA and small particles of iron oxide (SPIO), respectively. Starting 12 weeks posttransplantation, images from grafts of untreated recipients exhibited distinctive signal attenuation in the cortex. Animals treated with cyclosporin (Sandimmune Neoral; Novartis Pharma, Basel, Switzerland) to prevent acute rejection showed a signal attenuation in the cortex at 33 weeks posttransplantation, while kidneys from rats treated additionally with everolimus (Certican; Novartis), a rapamycin derivative, had no changes in anatomical appearance. A significant negative correlation was found between the MRI cortical signal intensity and the histologically determined iron content in macrophages located in the cortex. Renography revealed a significantly reduced functionality of the kidneys of untreated controls 33 weeks after transplantation, while no significant changes in perfusion were observed in any group of rats. These results suggest the feasibility, by labeling macrophages with SPIO, of detecting signs of graft rejection significantly earlier than when changes in function occur. Monitoring early changes associated with chronic rejection can have an impact in preclinical studies by shortening the duration of the experimental period and by facilitating the investigation of novel immunomodulatory therapies for transplantation.     

In vivo targeting of acute myocardial infarction with negative-charge,polymer-modified antimyosin antibody: Use of different cross-linkers

Background  

Cell surfaces and intercellular matrixes contain acidic residues, making them negatively charged. Antibodies are basic, positively charged glycoproteins. Therefore the potential for nonspecific ionic interaction exists, which could increase the background activity. Modification of antibodies with negatively charge-modified polymers have been shown to reduce this nonspecific background activity. This study was performed to investigate the appropriateness of different cross-linkers used covalently to link the chelating negatively charge-modified polylysine to antimyosin Fab (AM-Fab). The cross-linking was performed through peptide (AM-I) or thioether (AM-II) bonds. The in vitro evaluation of the immunointegrity and the in vivo assessment were performed to investigate the potential for reduction of nontarget background activity. Furthermore, the role of the charge of the polymers (whether completely negatively charge modified by succinylation [AM-IIs] or only partially negatively charge modified [AM-IIns]) was also assessed.     

MR imaging at rest early after myocardial infarction: detection of preserved function in regions with evidence for ischemic injury and non-transmural myocardial infarction

Patients with subacute myocardial infarction were studied to detect regions of ischemic injury but with preserved myocardial function combining different MRI techniques. On a 1.5-T imaging system 27 patients were examined 7–14 days after acute myocardial infarction. The imaging protocol included T2-weighted fast spin-echo imaging, a cine fast low-angle shot (FLASH) 2D technique to determine regional function at rest, and a first pass as well as late contrast enhancement perfusion study injecting 0.1 mmol/kg Gd-DTPA. Preserved function was compared with the transmural extent of first-pass perfusion phenomena, increased T2 signal intensity (SI), and late contrast enhancement. Semi-quantitative first-pass perfusion parameters were correlated with quantitative myocardial wall thickening (MWT) and degree of coronary artery stenosis. Indicating ischemic injury increased T2 SI and late enhancement was present in 29 and 26% of segments. Preserved function was found predominantly in segments with non-transmural late enhancement (112 of 338 segments with late enhancement) and transmural increase of T2 SI (129 of 386 segments with increased T2 SI). A high-grade perfusion deficit was detected in 4% of all segments and regularly associated with markedly decreased systolic function. Correlation of first-pass perfusion parameters was observed with MWT (r=0.50–0.90, p<0.001) but not with the degree of coronary artery stenosis. Our data suggest that preserved function was detected in non-transmural myocardial infarction demonstrated by non-transmural late enhancement and increase of T2 SI. Electronic Publication     

^18F-FDG PET/CT显像与心脏磁共振成像对Beagle犬局部辐射后心脏损伤的诊断

目的探讨^18F-脱氧葡萄糖(FDG)PET/CT显像与心脏磁共振成像(CMR)对Beagle犬局部放射性心脏损伤(RIHD)的诊断价值。方法将24只1岁龄健康雄性Beagle犬按照随机数字表法分为对照组及照射后3、6和12个月组,每组各6只;其中各照射组左心室前壁行单次20 Gy调强放疗。对全部犬行^18F-FDG PET/CT心肌代谢显像和CMR检查,计算^18F-FDG摄取增高区平均标准摄取值(SUVmean)及面积。全部检查结束后1周处死实验犬,取心脏进行Masson染色及电子显微镜检查。采用单因素方差分析比较组间差异。结果对照组心肌^18F-FDG几乎不摄取,照射后3个月即可见犬心肌^18F-FDG摄取增加,照射后3、6和12个月组的心肌SUVmean分别为5.90±1.31、4.66±2.21和3.21±0.82,与对照组(1.13±0.21)的差异有统计学意义(F=11.81,P<0.05);照射组^18F-FDG摄取增高面积随着照射后时间延长逐渐下降(F=195.74,P<0.01)。CMR示照射后6和12个月组的心肌灌注降低、进行性纤维化加重;与对照组相比,照射后6和12个月组的舒张末期容积(EDV)和收缩末期容积(ESV)增加(F=15.479和16.908,均P<0.01),而左心室射血分数(LVEF)下降(F=63.715,P<0.01)。Masson染色发现照射后心肌纤维化进行性加重;电子显微镜检查示照射后心肌线粒体变性肿胀,线粒体数量进行性减少。结论照射后局部心肌^18F-FDG摄取增高对于RIHD的危险性有预测价值,^18F-FDG PET/CT显像能早于CMR发现RIHD。     

Mapping ischemic risk region and necrosis in the isolated heart using EPR imaging.

Reperfusion of ischemic tissue is a common event in the treatment of heart attack and stroke. To study disease pathogenesis, methods are required to measure tissue perfusion and area at risk, as well as localized regions of injury. While histology can provide this information, its destructive nature precludes assessment of time course. Thus, there is a critical need for a noninvasive technique to obtain this information. To map myocardial redox state as a possible index of cellular ischemia and viability, electron paramagnetic resonance (EPR) imaging experiments were performed on isolated rat hearts before and after the onset of regional ischemia using nitroxide spin labels. With coronary artery occlusion, the EPR images clearly showed the risk region as a void of lower intensity that reversed upon reperfusion. The extent of risk region in the heart was similar in EPR imaging and histological measurements. The unique information obtained regarding the time course of changes in redox metabolism of the risk region and normal myocardium can provide important insights regarding the mechanisms of myocardial injury during and following ischemia.     

Imaging procedures in the detection of cardiac tumors,with emphasis on echocardiography: A review

Although cardiac tumors are relatively rare, their diagnosis is important because successful treatment is usually feasible if the diagnosis is made preoperatively. An analysis of 219 reports of cardiac tumors described in the English literature from 1972 through 1977 demonstrated the predominance of benign tumors, in particular myxoma, which is in agreement with past reviews. The methods of diagnosis employed included plain chest films, echocardiography, cardiac catheterization, angiocardiography, and cardiac scintigraphy. Conventional x-ray examination of the chest was abnormal in 83% of cardiac tumors but non-specific and should lead to further evaluation, first by echocardiography. Echocardiography, the most efficient diagnostic procedure for screening possible cardiac tumors, was abnormal in 94% of the cases. Cardiac catheterization was abnormal in 80% of cardiac tumors while definitive detection was made by angiocardiography in 94% of the cases. Cardiac scintigraphy has had limited use in the diagnosis of cardiac tumors, but has been diagnostic in 100% of the cases in a small series of myxomas.     

Prognostic value of sympathetic innervation and cardiac asynchrony in dilated cardiomyopathy

Purpose  The purpose of the study is to examine prognostic values of cardiac I-123 metaiodobenzylguanidine (MIBG) uptake and cardiac dyssynchrony in patients with dilated cardiomyopathy (DCM). Materials and methods  Ninety-four patients with non-ischemic DCM underwent I-123 MIBG imaging for assessing cardiac sympathetic innervation and equilibrium radionuclide angiography. Mean phase angles and SD of the phase histogram were computed for both right ventricular (RV) and left ventricular (LV). Phase measures of interventricular (RV–LV) and intraventricular (SD–RV and SD–LV) asynchrony were computed. Results  Most patients were receiving beta-blockers (89%) and angiotensin-converting enzyme inhibitors (88%). One patient (1%) was lost to follow-up, six had cardiac death (6.4%), eight had heart transplantation (8.6%), and seven had unplanned hospitalization for heart failure (7.5%; mean follow-up: 37 ± 16 months). Patients with poor clinical outcome were older, had higher The New York Heart Association functional class, impaired right ventricular ejection fraction and left ventricular ejection fraction, and impaired cardiac I-123 MIBG uptake. On multivariate analysis, I-123 MIBG heart-to-mediastinum (H/M) uptake ratio <1.6 was the only predictor of both primary (cardiac death or heart transplantation, RR = 7.02, p < 0.01) and secondary (cardiac death, heart transplantation, or recurrent heart failure, RR = 8.10, p = 0.0008) end points. Conclusions  In patients receiving modern medical therapy involving beta-blockers, I-123 MIBG uptake, but not intra-LV asynchrony, was predictive of clinical outcome. The impact of beta-blockers on the prognostic value of ventricular asynchrony remains to be clarified.     

Avidity of technetium 99m glucarate for the necrotic myocardium: In vivo and in vitro assessment

Background  Similar to other^99mTc-based infarct-avid agents,^99mTc-glucarate localizes in myocardial infarcts. Whether severely ischemic viable myocytes sequester^99mTc-glucarate is uncertain. To assess the infarct specificity, in vitro and in vivo studies were performed. Methods and Results  H9C2 embryonic rat cardiocytes cultured under normoxia (N) or hypoxia (H) for 24 hours in 7.5 μCi^99mTc-glucarate were compared with necrotic cardiocytes. Mean H/N ratio (3.0±0.004, mean±SD) was significantly less than that of the necrotic/N ratio (39.9±6.5,p<0.01). Reperfused myocardial infarction (MI) in 4 dogs confirmed by²⁰¹Tl, (0.5 to 1.0 mCi) scintigraphy were imaged serially, with simultaneously injected mixture of^99mTc-glucarate and¹¹¹In-antimyosin Fab. Infarcts were detected scintigraphically within 4 to 10 minutes with^99mTc-glucarate.¹¹¹In-antimyosin required more than 1 hour. Myocardial distribution at 5 hours showed a direct correlation between^99mTc-glucarate and¹¹¹In-antimyosin uptake (r=0.99,p<0.0001). Both^99mTc-glucarate (r=−0.777,p<0.0001) and¹¹¹In-antimyosin (r=−0.775,p<0.0001) were inversely related to²⁰¹Tl distribution. Conclusions  The near perfect correlation between^99mTc-glucarate and¹¹¹In-antimyosin uptake (r=0.99) in reperfused canine MI and the insignificant glucarate uptake by viable cardiocytes in vitro attest to the avidity of^99mTc-glucarate for the necrotic myocardium and favor its use as a specific early marker of myocyte necrosis in acute MI. Supported in part by SBIR grant 1R43-HL54410-01 and Molecular Targeting Technology, Inc.     

Macrophage uptake of ultra-small iron oxide particles for magnetic resonance imaging in experimental acute cardiac transplant rejection

Purpose: To discriminate between acutely rejecting and non-rejecting transplanted hearts using a blood pool contrast agent and T2* magnetic resonance imaging (MRI) in a clinical 1.5T scanner.

Material and Methods: Allogeneic and syngeneic heterotopic heart transplantations were performed in rats. One allogeneic and one syngeneic group each received either the ultra-small iron oxide particle (USPIO), at two different doses, or no contrast agent at all. MRI was performed on postoperative day 6. Immediately after the MR scanning, contrast agent was injected and a further MRI was done 24 h later. Change in T2* was calculated.

Results: No significant difference in change in T2* could be seen between rejecting and non-rejecting grafts in either of the doses, or in the control groups. There was a difference between the allogeneic group that received the higher contrast agent dose and the allogeneic group that did not receive any contrast agent at all.

Conclusion: In our rat model, measurements of T2* after myocardial macrophage uptake of AMI-227 in a clinical 1.5T scanner were not useful for the diagnosis of acute rejection.     

Optimized cardiac magnetic resonance imaging inversion recovery sequence for metal artifact reduction and accurate myocardial scar assessment in patients with cardiac implantable electronic devices

Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) is the gold standard for imaging myocardial viability. An important application of LGE CMR is the assessment of the location and extent of the myocardial scar in patients with ventricular tachycardia (VT), which allows for more accurate identification of the ablation targets. However, a large percentage of patients with VT have cardiac implantable electronic devices (CIEDs), which is a relative contraindication for cardiac magnetic resonance imaging due to safety and image artifact concerns. Previous studies showed that these patients can be safely scanned on 1.5 T scanners provided that an adequate imaging protocol is adopted. Nevertheless, imaging patients with a CIED result in metal artifacts due to the strong frequency off-resonance effects near the device; therefore, the spins in the surrounding myocardium are not completely inverted, and thus give rise to hyperintensity artifacts. These artifacts obscure the myocardial scar tissue and limit the ability to study the correlation between the myocardial scar structure and the electro-anatomical map during catheter ablation. In this study, we developed a modified inversion recovery technique to alleviate the CIED-induced metal artifacts and improve the diagnostic image quality of LGE images in patients with CIEDs without increasing scan time or requiring additional hardware. The developed technique was tested in phantom experiments and in vivo scans, which showed its capability for suppressing the hyperintensity artifacts without compromising myocardium nulling in the resulting LGE images.     

Indium-111 myosin-specific antibodies and technetium-99m pyrophosphate in the detection of acute cardiac rejection of transplanted hearts: studies in a heterotopic rat heart model

¹¹¹In-labelled myosin-specific antibodies were evaluated as an indicator of early changes in acute rejection in a rat heart heterotopic transplant model. Uptake of antibodies was measured in allograft and isograft hearts of animals undergoing different regimens of cyclosporine treatment and compared with the uptake of technetium-99m pyrophosphate. The data were correlated with histological estimation of the severity of myocyte necrosis and signs of early rejection (venous cuffing and endocardial inflammation, indicators of perivascular infiltrate and intermyocyte extension, respectively). Myocyte necrosis in transplanted hearts was reflected by increases in technetium-99m pyrophosphate accumulation (r=0.88) but was poorly correlated with labelled antibody uptake (r=0.58). There was no positive correlation between the degree of early cardiac rejection and uptake of either of the radiopharmaceuticals: accumulation of the labelled antibodies paradoxically declined with increased histological severity scores, whereas that of technetium-99m pyrophosphate remained unchanged. Cyclosporine treatment augmented the uptake of labelled antibodies in transplanted hearts. This may be due to alterations in plasma membrane permeability brought about by the drug, resulting in a rise in antibody binding to intracellular myosin. Offprint requests to: U. Scheffel, Sc.D.     

Comparison of radionuclide ventriculography using SPECT and planar techniques in different cardiac conditions

PURPOSE: Accurate assessment of ventricular function is required to optimize therapeutic management of cardiac diseases. The aim of this study was to correlate planar equilibrium multigated acquisition (MUGA) with tomographic ventriculography (SPECT) in patients with diverse volumes and wall motion abnormalities. METHODS: Eighty-three studies in 80 patients (56+/-14 years; 56% women) were classified according to ventricular dilation, wall motion abnormalities and systolic dysfunction. Left and right ventricular ejection fraction (LVEF and RVEF) and end-diastolic and end-systolic left ventricular volumes (EDV and ESV) were obtained using a commercial QBS program for SPECT. On planar acquisition, LVEF and RVEF were obtained using standard techniques and volumes were determined using the count-based method, without blood sampling. RESULTS: A. Total group: With the planar method, LVEF was 44+/-17%, RVEF 42+/-13%, left EDV 147+/-97 ml (range 31-487 ml) and left ESV 93+/-85 ml (range 15-423 ml); with SPECT the corresponding values were 40+/-20%, 49+/-16%,131+/-95 ml and 91+/-89 ml, respectively (p=NS for all but RVEF). Linear correlation was 0.845 for LVEF, 0.688 for RVEF, 0.927 for left EDV and 0.94 for left ESV, with good intra-class correlation. B. Subgroups: Global and intra-class correlations between planar imaging and SPECT were high for volumes, RVEF and LVEF in all subgroups, except in patients with normal wall motion and function, who showed smaller volumes with SPECT. The group with diffuse wall motion abnormalities had a lower EDV on SPECT. In the abnormal left ventricle, RVEF was higher with SPECT. CONCLUSION: Good correlation and agreement exist between SPECT and planar MUGA with respect to LVEF and left ventricular volumes. SPECT is useful in patients with functional abnormalities, but less reliable in those with normal small cavities. A combined technique is still necessary, and RVEF should be interpreted cautiously.