BMIPP Imaging Research Articles

Abstract 16793: Association of Impairment of Myocardial Metabolism and Ventricular Arrhythmic Events in Patients With Hypertrophic Cardiomyopathy by Single Photon Emission Computed Tomography With A Solid-state Dedicated Cardiac Camera

Background: Ventricular arrhythmic events have adverse implications for patients with hypertrophic cardiomyopathy (HCM). However, little has been reported on the relationship between myocardial metabolic abnormalities and ventricular arrhythmia. Iodine-123-beta-methyl iodophenyl-pentadecanoic acid (BMIPP) is used to assess myocardial metabolic abnormalities. A solid-state dedicated cardiac camera (D-SPECT) provides precise assessment of abnormal uptake and reduction of radiation dose in HCM by high sensitivity and high spatial resolution. Objective: The aim of this study was to evaluate the utility of BMIPP using D-SPECT for prediction of ventricular arrhythmic events in patients with HCM. Methods: We studied 125 consecutive HCM patients who underwent dual SPECT with D-SPECT using BMIPP and technetium-99m sestamibi (MIBI) or thallium-201 (TL). Reduced uptake on the BMIPP image compared with the MIBI / TL perfusion image was defined as perfusion-metabolic mismatch. In quantitative analysis, a polar map was divided into 17 segments and the score of each segment was derived from the average percent uptake. Mismatch scores (MS) were calculated from the differences between the BMIPP and MIBI / TL scores. Ventricular arrhythmic events were defined as ventricular tachycardia, appropriate ICD therapy and sudden cardiac death. Results: Patients with the obstructive type of HCM had a significantly higher MS than those with the non-obstructive type. Significant correlation between the MS and left ventricular mass (r = 0.28, p < 0.01) and maximal wall thickness (r = 0.27, p < 0.01) were observed. MS was significantly higher in patients with ventricular arrhythmic events than in those without events (p < 0.05). In ROC analysis, patients with a higher MS had significantly more arrhythmic events than those with a lower MS (cutoff value: 74.5, AUC: 0.644, p < 0.01). In multivariate analysis, the MS was identified as an independent factor associated with ventricular arrhythmic events (p < 0.01). Conclusions: Abnormal uptake of BMIPP in patients with HCM is associated with ventricular arrhythmic events. Dual SPECT with D-SPECT using BMIPP and MIBI / TL is a useful modality for risk stratification and may reveal the existence of substrate for ventricular arrhythmia.

Myocardial SPECT Images in Incident Hemodialysis Patients Without Ischemic Heart Disease.

Cardiovascular disease is the leading cause of death in dialysis patients and is significantly associated with poor survival in incident dialysis patients. However, little is known about the pathogenesis of cardiovascular disease in these populations. (123) I-15-(p-iodophenyl)-3(R,S)- methylpentadecanoic acid (BMIPP) imaging is useful for detection of ischemic heart disease. We examined imaging characteristics to identify potential pathologies of cardiac disease, other than ischemic heart disease. The subjects were 42 incident dialysis patients without histories of ischemic heart disease such as acute coronary syndrome. All the patients underwent BMIPP imaging in addition to a screening examination. Patients with positive findings in BMIPP imaging underwent myocardial perfusion imaging within 2 weeks after BMIPP imaging to evaluate the possibility of ischemic heart disease. Twenty-two patients were BMIPP-positive and 10 of these patients had negative findings on perfusion imaging and were defined as mismatch cases. Compared with patients who were BMIPP- and perfusion-positive, the mismatch cases had higher parathyroid hormone (PTH), serum albumin, and alkaline phosphatase levels. The mismatch cases also formed the largest proportion in the highest PTH tertile. A histologic examination of a mismatch case with no stenotic lesions in the coronary artery revealed the presence of cardiac hypertrophy and fibrosis. These findings suggest that a perfusion-metabolism mismatch may be present in incident dialysis patients without a history of ischemic heart disease. This mismatch is associated with PTH, which suggests potential involvement of uremic cardiomyopathy in the pathology of cardiac disease in these patients.

Detection of myocardial metabolic dysfunction caused by the right ventricular apical pacing using thallium 201/iodine 123-labeled beta-methyl iodophenyl pentadecanoic acid SPECT

Purpose: Many clinical trials have reported that right ventricular apical (RVA) pacing increases the risk of heart failure and atrial fibrillation, but the mechanism remains unknown. Using thallium 201 (Tl)/iodine 123-labeled beta-methyl iodophenyl pentadecanoic acid (BMIPP) single photon emission computed tomography (SPECT), we assessed the hypothesis that RVA pacing has a direct undesirable effect on myocardial metabolism. Methods: We reviewed the Tl/BMIPP SPECT studies that were performed more than one month after implantation of permanent pacemaker or implantable cardioverter defibrillator in our hospital. The ventricular pacing lead was located in right ventricular apex. Patients with ischemic heart disease, congenital heart disease and specific cardiomyopathy were excluded. All images were analyzed qualitatively in a blind manner. A positive finding was defined as reduced uptake on the BMIPP image compared with the Tl perfusion image. In quantitative analysis, a polar map was divided into 17 segments. Each segment was graded on a 5-point scale and mismatch score was calculated from the %uptake differences between the Tl and BMIPP. Results: Seventy one patients were included (mean age 65 years). Indications for device implantation were atrioventricular block (AVB) (n=31), sinus node dysfunction (SND) (n=22), both AVB and SND (n=1), ventricular tachyarrhythmia (n=10) and brady atrial fibrillation (n=2). Mean duration of pacing was 3369 days. Myocardial fatty acid metabolic dysfunction defined as a mismatch between Tl uptake and BMIPP uptake were detected in 39 patients mainly in inferior and apical segments. On multivariate analysis, percent ventricular beats that were paced (%VP) was identified as only independent factor for Tl/BMIPP mismatch, however, duration of pacing and pacing threshold were not. Cutoff value of %VP was determined (40%) by ROC analysis. Conclusions: RVA pacing leads to regional myocardial metabolic dysfunction, which may be the main cause of unfavorable clinical outcomes associated with RVA pacing.

18F-FDG Cardiac Studies for Identifying Ischemic Memory

Myocardial ischemia is associated with profound changes in substrate utilization by the myocardium for energy production. This change occurs with the onset of ischemia, but persists much longer, perhaps for several hours or even days after an episode of myocardial ischemia, which is termed ischemic memory. Recently, radiolabeled glucose analogue (Fluorine-18 labeled deoxyglucose, 18FDG) and free acid analogue (β-methyl-p-123I-iodophenyl-pentadecanoic acid, 123I-BMIPP) have been investigated to detect myocardial ischemia in stable coronary artery disease (CAD) or suspected acute coronary syndrome (ACS). These studies demonstrate that BMIPP imaging holds promise for evaluation of patients with suspected ACS in the emergency department. Exercise 18FDG imaging offers several potential advantages over conventional stress-rest perfusion imaging for the detection of CAD. Furthermore, ischemia-induced 18FDG uptake may persist for several to 24 hours in patients with stress-induced myocardial ischemia. Therefore, 18FDG may also be a useful memory marker in detection of antecedent myocardial ischemia in suspected ACS. However, some important issues about 18FDG ischemic imaging need to be further investigated. In this article the advances of myocardial ischemic imaging with 18FDG are reviewed. Several unresolved issues and the perspective of this modality are also discussed.

Fatty Acid Imaging of the Heart

Imaging metabolic processes in the human heart yields valuable insights into the mechanisms contributing to myocardial pathology and allows assessment of the efficacy of therapies designed to treat cardiac disease. Recent advances in fatty acid (FA) imaging using positron emission tomography (PET) include the development of a method to assess endogenous triglyceride metabolism and the design of new fluorine-18 labeled tracers. Studies of patients with diabetes have shown that the heart is resistant to insulin-mediated glucose uptake and that metabolism of nonesterified FA is upregulated. Cardiac PET imaging has also recently shown the increase in myocardial FA uptake seen in obese patients can be reversed with weight loss. And a pilot study of patients with chronic kidney disease demonstrated that PET imaging can reveal myocardial metabolic alterations that parallel the decline in estimated glomerular filtration rate. Recent advances in FA imaging using single photon emission computed tomography (SPECT) have been accomplished with the tracer β-methyl-p-[(123)I]-iodophenyl-pentadecanoic acid (BMIPP). Two meta-analyses showed this imaging technique has a diagnostic accuracy for the detection of obstructive coronary artery disease that compares favorably with SPECT myocardial perfusion imaging and that BMIPP imaging yields excellent prognostic data in patients across the spectrum of coronary artery disease. A recent multicenter study of patients presenting with acute coronary syndromes found BMIPP SPECT imaging has greater diagnostic sensitivity than, and enhances the negative predictive value of, clinical assessment alone. Because of their exquisite sensitivity, nuclear imaging techniques facilitate the study of physiologic processes that are the key to our understanding of cardiac metabolism in health and disease.

Severe vasospastic angina with ventricular fibrillation suggested by iodine-123 beta-methyl-p-iodophenyl-pentadecanoic acid in a young woman

Iodine-123 beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) imaging is useful to diagnose recent myocardial ischemia. A 27-year-old woman was admitted to our hospital because of aborted cardiac arrest due to ventricular fibrillation. She underwent BMIPP imaging in order to rule out ischemic heart disease. Reduced BMIPP uptake was observed in the inferoseptal segments. Coronary angiography revealed insignificant lesions, and a severe coronary spasm was provoked in the right coronary artery by an intracoronary injection of acetylcholine. The etiology of ventricular fibrillation in this case was considered to be vasospastic angina. The application of BMIPP imaging helped diagnose fatal vasospastic angina in this case.

Prognostic value of myocardial metabolic imaging with BMIPP in the spectrum of coronary artery disease: A systematic review

BackgroundWe conducted a systematic review to summarize the current literature on the prognostic value of BMIPP imaging, fatty-acid metabolic imaging, for the prediction of cardiovascular events in coronary artery disease. Methods and ResultsElectronic databases (including Japanese medical literature search engines) were searched by a Japanese investigator using a predefined search strategy. Eleven studies, all conducted in Japan, were included in the meta-analysis. In three studies involving 541 patients with suspected acute coronary syndrome who were excluded for acute myocardial infarction (AMI), an abnormal finding on BMIPP imaging was significantly associated with future hard events (cardiac death or non-fatal myocardial infarction). The negative predictive value of BMIPP imaging for future hard events was 98.9% (96.8-99.7%) over 3.5 years. In six studies involving 542 patients with AMI, a larger defect on BMIPP imaging was significantly associated with future hard events. The prognostic value of perfusion-metabolism mismatch compared with myocardial perfusion imaging was dependent upon the relative timing of BMIPP imaging, revascularization, and myocardial perfusion damage. ConclusionsBMIPP imaging is useful for the risk stratification of patients with coronary artery disease, particularly patients with acute chest pain.

Prediction of Functional Outcome in Stunned Myocardium after Myocardial Infarction using BMIPP and Tetrofosmin Imaging

The predictive value of combined (123)iodine-labelled 15-(p-iodophenyl)-3R,S-methyl pentadecanoic acid imaging ((123)I-BMIPP) and early technetium-99m ((99m)Tc)-tetrofosmin imaging was compared with combined (123)I-BMIPP and delayed (99m)Tc-tetrofosmin or (123)I-BMIPP and thallium-201 ((201)Tl) imaging for functional outcome of stunned myocardium after acute myocardial infarction (AMI) in 37 patients with AMI. All patients underwent successful percutaneous coronary intervention with/without stenting within 24 h of symptoms. Resting (201)Tl, (99m)Tc-tetrofosmin and (123)I-BMIPP imaging were performed within 10 days of hospital admission; (99m)Tc-tetrofosmin imaging was also performed 6 months later. Segments were mismatched when the (123)I-BMIPP score was greater than the (99m)Tc-tetrofosmin or (201)Tl scores, and were matched when all scores were the same. Left ventricular function was estimated using wall motion score. Sensitivity and regional wall motion were significantly better in mismatching (99m)Tc-tetrofosmin-early/(123)I-BMIPP segments than mismatching (201)Tl/(123)I-BMIPP or (99m)Tc-tetrofosmin-delayed/(123)I-BMIPP segments. It is concluded that mismatching of (123)I-BMIPP and early (99m)Tc-tetrofosmin uptake can predict improvement in wall motion of stunned myocardium better than the other two imaging combinations.

Diagnostic accuracy of β-methyl- p-[123I]-iodophenyl-pentadecanoic acid (BMIPP) imaging: A meta-analysis

beta-Methyl-p-[(123)I]-iodophenyl-pentadecanoic acid (BMIPP) imaging has been used extensively to detect coronary artery disease (CAD), primarily in Japan. However, the reported sensitivity and specificity vary considerably from study to study. This meta-analysis was conducted to summarize the evidence for the diagnostic accuracy of resting BMIPP imaging in the detection of CAD. A MEDLINE search of the literature published through the end of 2006 was performed. Seven studies (528 patients) met the inclusion criteria. Using random-effects models, the overall sensitivity and specificity to detect CAD were 78% (95% confidence interval, 73% to 81%) and 84% (95% confidence interval, 77% to 89%), respectively. A significant threshold effect was identified among studies, which was expected given the between-study variability in study methodology. A summary receiver-operating characteristic curve yielded an asymmetric curve with an area under the curve of 0.91 (SE, 0.020), indicating excellent diagnostic performance. Imaging with BMIPP at rest exhibits a moderate sensitivity and high specificity to detect CAD in patients with a high prevalence of CAD. Thus, this tracer may be of great value for patients with acute chest pain and those with relative contraindications to exercise or pharmacologic stress myocardial perfusion imaging (MPI).

Prediction of cardiac events in patients with dilated cardiomyopathy using 123I-BMIPP and 201Tl myocardial scintigraphy

Various clinical trials for dilated cardiomyopathy (DCM) have demonstrated that the prognosis as well as cardiac function is improved by the administration of beta-blocker therapy. On the other hand, 123I-betamethyl-p-iodophenyl-pentadecanoic acid (BMIPP) reflects myocardial fatty acid metabolism and is considered to be a more sensitive tracer than perfusion tracers. In this study, the efficacy of DCM for the evaluation of myocardial damage and the prediction of cardiac events was studied using 123I-BMIPP and 201TI (Tl) myocardial scintigraphy. Study subjects comprised 33 DCM patients, divided into a cardiac event group (event, n = 9) and an event-free group (event free, n = 24). An extent score (ES) and severity score (SS) were calculated for each BMIPP image. BMIPP and Tl images were divided into 17 segments, and total defect scores (TDS) were calculated for each. The TDS of the BMIPP and Tl images were compared with score differences greater than or equal to 4 and less than 4 defined as mismatch and non-mismatch, respectively. The TDS of BMIPP was significantly higher in the event group than in the event-free group (P < 0.05). The ES and SS were significantly higher in the event group than in the event-free group (P < 0.01). The comparison in the 2 x 2 contingency tables showed that the occurrence of non-mismatch was significantly higher in the event-free group (chi2 test; P < 0.01). The ES of BMIPP was a significant predictor of cardiac events in the multivariate analysis (P < 0.01). These results suggest that the ES for BMIPP is useful as a predictor of cardiac events in DCM.

The Japanese experience with metabolic imaging in the clinical setting

Reduced utilization of fatty acids at rest often is observed in severely ischemic myocardium and possibly postischemic myocardium despite normal perfusion at rest. The role of metabolic imaging in identifying postischemic insult as ischemic memory imaging has been the focus of recent investigations. A number of reports from Japan show quite acceptable diagnostic accuracy of BMIPP imaging for detecting coronary patients without prior MI. In addition, recent data indicate that BMIPP imaging has prognostic value when applied in patients with documented or suspected coronary disease. The major advantage of BMIPP imaging is to demonstrate ischemic myocardium as an area of altered metabolism at rest. Thus this study is of clinical importance for elderly patients or for patients not suitable for a stress study. Furthermore, this radiopharmaceutical tracer may hold promise in demonstrating early alteration of energy metabolism in a variety of myocardial disorders.

Relationship Between the Mismatch of 123I-BMIPP and 201Tl Myocardial Single-Photon Emission Computed Tomography and Autonomic Nervous System Activity in Patients With Acute Myocardial Infarction

The purpose of this study was to elucidate the relationship between the mismatch of thallium-201(Tl) and iodine-123-beta-methyl-iodophenyl-pentadecanoic acid (BMIPP) myocardial single-photon emission computed tomography (SPECT) and autonomic nervous system activity in myocardial infarction (MI) patients. The subjects were 40 patients (34 males, 6 females) who underwent examinations by 123I-BMIPP and 201Tl myocardial SPECT imaging and 24-hour Holter monitoring within a 3-day period 3 weeks after the onset of their first MI. R-R intervals were analyzed every hour over a period of 24 hours by fast Fourier transformation (FFT). High frequency (HF) and low frequency (LF) were defined as markers of cardiac vagal activity in the former and the LF/HF ratio as sympathetic activity. Greater or more extensive decreases in the BMIPP image than that in the Tl image were defined as a positive mismatch. Patients were divided into positive and negative mismatch groups of 20 patients each. There were no significant differences between the 2 groups in age, sex, site of infarction, max CK (creatine kinase), max CK-MB, or left ventricular ejection fraction. The incidences of clinical signs suggesting residual myocardial ischemia were significantly greater in the positive than in the negative mismatch group (P < 0.05). The mean values for HF over the entire 24-hour period and over the 5-hour nocturnal period (0-5 AM) in the positive mismatch group were both significantly lower than those in the negative mismatch group (P < 0.001 in both groups). The 24-hour mean HF and mean nighttime HF in patients with signs of residual ischemia were both significantly lower than in those without signs of residual ischemia in the positive mismatch group (P < 0.05 in both groups). The mean LF/HF ratio for both the entire 24-hour and the nocturnal period in the positive mismatch group were significantly higher than those in the negative mismatch group (P < 0.001, P < 0.05, respectively). The daily profile of hourly HF measurements was significantly lower in the positive mismatch group than in the negative mismatch group (P < 0.02). The mean values of HF for 24-hour and 5-hour periods were significantly lower in patients with signs of residual ischemia in the positive mismatch group than in those with signs of residual ischemia in the negative mismatch group (P < 0.01, P < 0.02, respectively). There were no significant differences between the patients with signs of residual ischemia in the negative mismatch group and those without signs of residual ischemia in the positive and negative mismatch group with regard to the mean values of HF and the LF/HF ratio measured every hour for 24 hours and 5 hours. It is concluded from the present study that the findings of a mismatch on 123I-BMIPP and 201Tl myocardial SPECT 3 weeks after a first acute myocardial infarction with uncomplicated moderate or severe heart failure and decreased heart rate variability are related to residual myocardial ischemia. A combined assessment of heart rate variability in 24-hour Holter ECG monitoring and perfusion-metabolism mismatch in 123I-BMIPP and 201Tl myocardial SPECT is useful for determining residual myocardial ischemia in the follow-up of those with acute myocardial infarction.

Diagnostic Significance of Positive I-123 BMIPP Despite Negative Stress Tl-201 Myocardial Imaging in Patients With Suspected Coronary Artery Disease

There is frequently discordance in the interpretation of myocardial single-photon emission computed tomography images using both rest iodine-123 15-(p-iodophenyl)-3-(R,S) methylpentadecanoic acid (BMIPP) and stress thallium-201 ((201)Tl); that is, negative BMIPP vs positive (201)Tl studies. However, little attention has been paid to reverse discordance (ie, positive BMIPP despite negative stress (201)Tl). In the present study 105 consecutive patients with suspected coronary artery disease (CAD) who underwent both rest BMIPP and stress (201)Tl imaging were evaluated. No patient with previous myocardial infarction was included. Scintigraphic studies revealed that BMIPP was in concordance with (201)Tl in 71 patients: both were positive in 38 and negative in 33, whereas both were discordant in 20 and reverse discordant in 14. In patients with reverse discordance, the pattern of BMIPP abnormality was segmental in 8 and spotty in 6; the former was related to coronary territory. Based on the BMIPP findings and clinical symptoms, 7 patients with positive BMIPP despite negative (201)Tl underwent coronary angiography: 3-vessel CAD was found in 3 patients, 2-vessel CAD in 1, coronary spasm in 2, and insignificant lesions in 1. In the remaining 7 patients, no cardiac event was observed during 2-year follow-up. In patients showing positive BMIPP despite negative (201)Tl, a segmental BMIPP perfusion abnormality indicates a high likelihood for CAD, despite normal stress (201)Tl imaging. Thus, adding BMIPP to (201)Tl imaging may help to better identify patients with significant CAD, including multivessel disease.

Serial Alterations and Prognostic Implications of Myocardial Perfusion and Fatty Acid Metabolism in Patients With Acute Myocardial Infarction

Impaired fatty acid metabolism the myocardial infarction (MI)-related area has prognostic value, but can alter over time. The aim of this study was to correlate alterations in myocardial fatty acid uptake and perfusion assessed by serial imaging with future outcomes in post-MI patients. Following 2 imaging procedures using 15-4-iodophenyl-3-(R,S)-methylpentadecanoic acid (BMIPP) and perfusion tracers at an 11-month interval, 97 patients with acute MI were followed up for 33 months with respect to the primary endpoints of death, non-fatal MI and heart failure. Regional tracer uptake was semi-quantified for both the MI-related and remote coronary territories. A large BMIPP defect relative to a perfusion defect appeared on MI-related coronary territories. Thirteen patients with cardiac events had a greater prevalence of large BMIPP and perfusion defect scores for the MI-related areas on the first scan, previous MI, diabetes mellitus, and worsening of perfusion tracer uptake in the MI-related area than those without cardiac events. Multivariate analysis identified worsening perfusion in the MI-related area on the second scan, a large BMIPP defect in the same area on the first scan and previous MI as significant predictors with chi-square values of 3.48, 6.41 and 6.84, respectively. A combination of 3 predictors significantly (p<0.05) increased the global chi-square value to 15.45 compared with each chi-square value. The size of the infarct-related risk area assessed by early cardiac BMIPP imaging and deterioration of perfusion tracer uptake in the compromised area for the first 12 months following acute MI are related to future cardiac events, indicating a rationale for identifying metabolically damaged but viable myocardium for further risk stratification of post-MI patients.

In vivo imaging of hepatic fatty acid metabolism in patients with nonalcoholic steatohepatitis using semiquantative I-BMIPP liver scan

Recent progress of studies in NASH displays multi-disciplinary characters of the pathogeneses. Despite these advances, the strategic use of imaging modalities such as CT, US, and MRI, remains a relatively low priority in clinical situations, because these can only visualize the presence of fatty infiltration to the hepatic parenchyma, impossible to figure out the dynamic function of NASH liver. Morphological alteration such as CT value, MR signal intensity and echo-grade do not distinguish NASH from simple fatty liver. In this presentation, from a radiologic viewpoint, we show the feasibility of in vivo fatty acid imaging with (123)I-beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP). BMIPP is an (123)I labeled fatty acid analog for imaging damaged myocardium, using conventional nuclear imaging equipment. Under normal conditions, the energy source for myocardial utilization is dependent on the beta-oxidation of fatty acids. For energy production in ischemic myocardium, the drastic switch from reduced beta-oxidation of fatty acids to glucose metabolism is well known. BMIPP can detect the area of reduced fatty acids metabolism on myocardial imaging and the data can be converted into semiquantitative analysis. Therefore, we speculate that the use of BMIPP to in vivo hepatic imaging in NASH could highlight a lot of matters of NASH. Details of this presentation include: (1) Hepatic imaging with BMIPP; (2) Clearance of BMIPP from NASH liver; (3) semiquantitative analysis of hepatic BMIPP clearance and clinical features of NASH; (4) Profiles of NASH categorized by BMIPP imaging and (5) Preliminary data of BMIPP clearance in patients with Tamoxifen-induced NASH. The core of our stance in this presentation is searching for valuable advice on clinical use of BMIPP in patients with NASH from specialists in the field of HEPATOLOGY.

Metabolic Imaging With β-Methyl- p -[ 123 I]-Iodophenyl-Pentadecanoic Acid Identifies Ischemic Memory After Demand Ischemia

After myocardial ischemia, prolonged suppression of fatty acid metabolism may persist despite restoration of blood flow, which is called metabolic stunning. We hypothesized that a branched-chain fatty acid, beta-methyl-p-[(123)I]-iodophenyl-pentadecanoic acid (BMIPP), might identify the presence of myocardial ischemia late after demand ischemia at rest up to 30 hours later. In 32 patients with exercise-induced ischemia on thallium SPECT, BMIPP was injected at rest within 30 hours of ischemia. SPECT images were acquired beginning 10 minutes after injection (early) and again 30 minutes after injection (delayed). Thallium and BMIPP SPECT data were read separately by 3 observers blinded to other imaging and clinical data. Agreement between BMIPP and thallium data for the presence of an abnormality on the patient level was 91% (95% CI, 75 to 98) for the early BMIPP data and 94% (95% CI, 79 to 99) for the delayed BMIPP data. Agreement between delayed BMIPP and thallium was 95% among 21 patients studied on the same day, a mean of 6.2+/-1.4 hours after exercise-induced ischemia, and 91% among the 11 patients studied on the next calendar day, a mean of 24.9+/-2.6 hours after ischemia (P=NS). The magnitude of resting BMIPP metabolic defect by semiquantitative visual analysis was correlated to the magnitude of exercise-induced thallium perfusion defect (r=0.6, P<0.001 for early BMIPP; r=0.5, P=0.005 for delayed BMIPP). Metabolic imaging with BMIPP identifies patients with recent exercise-induced myocardial ischemia. These findings support the concept that BMIPP imaging can successfully demonstrate the metabolic imprint of a stress-induced ischemic episode, also known as ischemic memory.

Myocardial I-123 BMIPP imaging and serum fatty acid binding protein levels in patients with congestive heart failure

Myocardial I-123 BMIPP imaging and serum fatty acid binding protein levels in patients with congestive heart failure

Prognostic value of fatty acid imaging in patients with angina pectoris without prior myocardial infarction: comparison with stress thallium imaging

A fatty acid analogue, 123I-labelled beta-methyl iodophenyl pentadecanoic acid (BMIPP), has been used to identify ischaemic and metabolically impaired myocardium. However, the prognostic value of BMIPP imaging, particularly in relation to stress myocardial perfusion imaging, remains unclear. Data from 167 consecutive patients with angina pectoris but without prior myocardial infarction (MI) who had undergone both BMIPP and stress 201Tl (sTL) imaging were analysed. Tracer uptake was graded using a 13-segment, 4-point scoring model. Patients were followed up for 48 months with primary end points (cardiac death, non-fatal MI) as hard cardiac events and with secondary end points (late revascularisation, recurrent angina and heart failure) as soft events. For overall cardiac events (5 hard and 29 soft events), Kaplan-Meier analysis revealed significantly lower event rates in subgroups with normal BMIPP uptake, a summed difference score of sTL (SDS) of <3 or absence of diabetes mellitus when compared to each counterpart. Multivariate Cox's analysis revealed reduced BMIPP uptake, SDS > or =3, diabetes and reduced ejection fraction to be significant predictors. Negative predictive values of normal BMIPP and SDS <3 for all events were 91% and 84%, respectively. No hard event occurred in 66 patients with normal BMIPP uptake, whereas two patients with SDS <3 but impaired BMIPP uptake had hard events. In conclusion, normal BMIPP imaging is an excellent prognostic sign, independently of stress myocardial perfusion imaging, in patients with angina pectoris without prior MI.

A quantitative analysis of I-123 BMIPP uptake in the heart and surrounding tissues

Background: After an exercise-induced ischemia, recent studies have shown prolonged disturbances in myocardial fatty acid metabolism, termed “ischemic memory”, which can be successfully imaged by [ 123I] BMIPP at rest. A potential advantage of BMIPP is that it permits uncoupling of the treadmill stress from tracer injection. In this study, we determined the cardiac image quality of BMIPP by quantifying regional tracer uptake in the heart and surrounding tissues in coronal slices. The results were compared with thallium images obtained in the same patients. Methods: 13 pts with documented reversible thallium defects during exercise underwent subsequent rest BMIPP SPECT imaging within 30 hours of the thallium study. The mean thallium dose injected was 5.2 ± 0.4 mCi while the mean BMIPP dose injected was 3.6 ± 0.4 mCi. After BMIPP injection, two sets of SPECT images were acquired; a 10-minute acquisition obtained 10 minutes after BMIPP injection and a 20-minute acquisition obtained 35–60 minutes after injection. A circular region of interest (ROI) was drawn around the heart, which was then duplicated and repositioned over the lung, liver, and left upper quadrant bowel in coronal slices. Mean counts in each ROI were expressed as lung/heart, liver/heart, and bowel/heart region ratios for thallium, 10-minute BMIPP and 35–60 minute BMIPP images (table). Results: BMIPP images showed excellent cardiac tracer uptake by quantitative SPECT analysis without lung or abdominal visceral interference. The lung/heart and bowel/heart ratios were similar for thallium and BMIPP images. However, the liver/heart ratio was higher for BMIPP images than thallium. Conclusion: The cardiac imaging characteristics of BMIPP are excellent with greater tracer uptake in the heart than the surrounding tissues of lung, liver and bowel. Compared to thallium, BMIPP shows higher liver/heart but similar lung/heart and bowel/heart ratios. However, when the more favorable physical properties of I-123 are taken into consideration, [ 123I] BMIPP becomes an excellent “ischemic memory” cardiac agent. * lung/heart liver/heart bowel/heart BMIPP 10 minute .30 ± .03 .65 ± .18 .25 ± .09 BMIPP 35–60 minute .33 ± .06 .61 ± .15 .30 ± .10 thallium .23 ± .14 .22 ± .07 * .21 ± .06 * different from BMIPP (10 and 35–60 minute) p < 0.03.

The spillover fraction of thallium photons in the I-123 energy window: Implications for post-exercise dual isotope simultaneous [ 123i] BMIPP and thallium imaging

Background: β-Methyl-ω-[p- 123I-phenyl]pentadecanoic acid (BMIPP) is a radiolabeled branched-chain fatty acid analog under clinical investigation in the United States for the detection of myocardial “ischemic memory”. In a recent Phase II clinical trial, BMIPP images acquired within 30 hours of an exercise-induced ischemia by Tl-201 SPECT, showed fatty acid disturbances at rest that were similar in extent and severity to the thallium perfusion defects on stress. The clinical relevance of these data is in the potential for uncoupling the treadmill portion of cardiac SPECT from BMIPP injection and imaging. This sets the stage for post-treadmill dual isotope simultaneous imaging of the ischemic metabolic signal (BMIPP) with rest perfusion signal (Tl-201). The current study, therefore, was undertaken to determine the spillover fraction of Tl-201 photons in the I-123 energy window of BMIPP. Methods: Spillover was calculated by acquiring SPECT data in both Tl-201 and I-123 energy windows for a phantom filled only with Tl-201. The phantom arrangement consisted of a water filled thorax phantom (300 × 230 mm) with a central cylindrical compartment (50 mm diameter) to simulate the heart. The background and heart regions had activity concentrations of 5.3 kBq/ml and 104.9 kBq/ml respectively. All image data were acquired on a dual-head DST gamma camera (SMV, Twinsburg, OH) with low-energy high-resolution collimators. Two separate SPECT acquisitions were performed immediately after one another using the Tl-201 (73 keV 30% + 167 keV 20%) and the I-123 (159 keV 20%) energy windows. The resulting pair of images were analyzed by placing regions-of-interest (ROIs) over corresponding parts of the heart compartment. The spillover fraction was defined as the ROI counts in the I-123 window divided by the ROI counts in the Tl-201 window. Results: The spillover fraction was 0.14 +- 0.01. Conclusion: The spillover fraction of Tl-201 photons in the I-123 energy window is only 14%. If confirmed in the clinical setting, post-treadmill dual isotope simultaneous imaging of BMIPP and thallium may become an attractive alternative to exercise myocardial perfusion SPECT.