Metabolic imaging using F18-fluorodeoxyglucose to assess myocardial viability

Over the past 10 years, F18-fluorodeoxyglucose (FDG) imaging with positron emission tomography (PET) has emerged as an important technique in the delineation of myocardial viability. Using this technique it has become possible to predict recovery of ventricular function after revascularization in patients with chronic coronary artery disease. Data from long-term (although retrospective) follow-up studies have demonstrated that patients with viable myocardium on FDG PET who do not undergo revascularization are prone to cardiac events, including cardiac death and non-fatal infarction. The same studies have pointed out that patients with viable tissue on FDG PET, who do undergo revascularization, improve substantially in symptoms related to congestive heart failure. To allow FDG imaging in centers without PET equipment, recent studies have evaluated the use of FDG imaging with single photon emission computed tomography (SPECT) and 511 keV collimators. Preliminary data using this alternative approach are promising, but need further confirmation. In this review the experience with FDG imaging (using either PET or SPECT) in the assessment of tissue viability in patients with coronary artery disease will be discussed.     

Use of integrated FDG PET/CT imaging in pulmonary carcinoid tumours

BACKGROUND: Integrated positron emission tomography (PET)/computed tomography (CT) scanners have been recently introduced in the diagnostic work-up of suspected pulmonary malignancy and demonstrate encouraging results in the staging of nonsmall-cell lung cancer. OBJECTIVE: To evaluate the usefulness of integrated FDG PET/CT in pulmonary carcinoid tumours. SETTING: University hospital. METHODS: We studied 13 patients (mean age +/- 1 SD, 57 +/- 11 years) with pulmonary carcinoid tumours. All patients demonstrated a single pulmonary lesion. Integrated PET/CT scan and surgical resection were performed in all patients. RESULTS: The pulmonary lesion size ranged from 1.1 to 5.0 cm. Final histological diagnosis confirmed 12 typical and one atypical pulmonary carcinoid. Mean proliferation rate of the typical carcinoids was 1.7 +/- 1.4%. None of the patients had recurrent carcinoid disease or died during follow-up (864 +/- 218 days). Mean standardized uptake value (SUV) of (18)F-fluorodeoxyglucose (FDG) in typical carcinoids was 3.0 +/- 1.5 (range 1.2 - 6.6); SUV in the atypical carcinoid was remarkably high with a value of 8.5. The SUV was lower than 2.5 in 6 of 12 patients (50%). Mediastinal lymph node metastases or extrathoracic metastases were not detected in any patient. CONCLUSIONS: (18)F-fluorodeoxyglucose PET/CT imaging improves accurate localization of metabolic activity and thus the interpretation of pulmonary lesions on CT. FDG uptake in pulmonary carcinoid tumours is often lower than expected for malignant tumours. Therefore, surgical resection or biopsy of lesions suspected to be carcinoids should be mandatory, even if they show no hypermetabolism on FDG PET images.     

Discrepancy between myocardial perfusion and fatty acid metabolism following acute myocardial infarction for evaluating the dysfunctional viable myocardium

ObjectiveFollowing acute myocardial infarction (AMI) the area of myocardial perfusion and metabolism mismatch is designated as dysfunctional viable myocardium. ¹²³I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) is clinically very useful for evaluating myocardial fatty acid metabolism, and ⁹⁹mTc-Tetrofosmin (TF) is a widely used tracer for myocardial perfusion. This study was designed to evaluate the degree of discrepancy between BMIPP and TF at the subacute state of AMI.MethodsFifty-two patients (aged 59 ± 10 years; mean 46 years) with AMI were enrolled, and all of them underwent percutaneous coronary intervention (PCI). Patients were classified according to ST-T change and PCI timing. ¹²³I-beta-methyl iodophenyl pentadecanoic acid and TF cardiac scintigraphy were performed on 7 ± 3.5 days of admission using a dual headed gamma camera. Perfusion and fatty acid metabolism defect were scored on a 17 segments model.ResultsThe mean BMIPP defect score on early and delayed images were 16.67 ± 10.19 and 16.25 ± 10.40, respectively. The mean TF defect score was 10 ± 7.69. Defect score of BMIPP was significantly higher than that of the TF (P < 0.0001; 95% CI 4.32–7.02), and there was a strong correlation between perfusion and metabolism defect score (r = 0.89, P < 0.00001). Forty-seven (90%) patients showed mismatched defect (BMIPP > TF), and 5 (10%) patients showed matched defect (BMIPP = TF). Mismatched defect score (MMDS) was significantly higher in patients with ST-segment elevation myocardial infarction (STEMI) than that of non-ST-segment elevation myocardial infarction (NSTEMI) (P < 0.041; 95% CI 0.11–5.19).ConclusionAt the subacute state of AMI, most of the patients showed perfusion-metabolism mismatch, which represents the dysfunctional viable myocardium, and patients with STEMI showed higher mismatch.     

Effects of right ventricular pacing on regional myocardial glucose metabolism.

AIMS: Permanent right ventricular apical pacing (RVP) is associated with a wide range of myocardial abnormalities. The purpose of this study was to determine the changes over time of RVP on myocardial blood flow (MBF) and glucose metabolism as assessed by positron emission tomography (PET). METHODS: In eight candidates for permanent pacemaker implantation PET imaging was performed with 13N-ammonia and 18F-Fluorodeoxyglucose (FDG) to assess MBF and glucose metabolism before (PET1) and repeated after 3 months of RVP (PET2). For the analysis, the left ventricle was divided into three parts (apex, mid-ventricular and base) and subdivided into six segments (inferior, posterior, lateral, anterior, antero-septal and infero-septal). RESULTS: After RVP, defects of FDG uptake were found in the left ventricle near the stimulation site, without corresponding changes in MBF. Changes over time in the mean FDG uptake were statistically significant between PET1 and PET2 in the apical inferior, apical-posterior, apical-anterior, apical antero-septal, apical infero-septal, mid-inferior and mid-infero-septal segments. CONCLUSIONS: This study shows that RVP induces major changes in the distribution of FDG uptake in the left ventricular myocardium. FDG uptake significantly decreases in the regions surrounding the pacing site.     

Enhancement of insulin-stimulated myocardial glucose uptake in patients with Type 2 diabetes treated with rosiglitazone.

AIMS: Peroxisome proliferator-activated receptor gamma (PPARgamma) activators have recently been identified as regulators of cellular proliferation, inflammatory responses and lipid and glucose metabolism. These agents prevent coronary arteriosclerosis and improve left ventricular remodelling and function in heart failure after myocardial infarction. Improvement in myocardial metabolic state may be one of the mechanisms behind these findings. The aim of this study was to investigate the effects of rosiglitazone on myocardial glucose uptake in patients with Type 2 diabetes. Placebo and metformin were used as control treatments. METHODS: Forty-four patients were randomized to treatment with rosiglitazone (4 mg b.i.d.), metformin (1 g b.i.d.) or placebo in a 26-week double-blinded trial. Myocardial glucose uptake was measured using [(18)F]-2-fluoro-2-deoxy-D-glucose ([(18)F]FDG) and positron emission tomography (PET) during euglycaemic hyperinsulinaemia before and after the treatment. RESULTS: Rosiglitazone increased insulin-stimulated myocardial glucose uptake by 38% (from 38.7 +/- 3.4 to 53.3 +/- 3.6 micromol 100 g(-1) min(-1), P = 0.004) and whole body glucose uptake by 36% (P = 0.01), while metformin treatment had no significant effect on myocardial (40.5 +/- 3.5 vs. 36.6 +/- 5.2, NS) or whole body glucose uptake. Myocardial work as determined by the rate-pressure-product was similar between the groups. Neither treatment had any significant effect on fasting serum free fatty acids (FFA) but the FFA levels during hyperinsulinaemia were more suppressed in the rosiglitazone group (-47%, P = 0.02). Myocardial glucose uptake correlated inversely to FFA concentrations both before (r =-0.54, P = 0.002) and after (r = -0.43, P = 0.01) the treatment period in the pooled data. Furthermore, the increase in myocardial glucose uptake correlated inversely with interleukin-6 (IL-6) concentrations (r = -0.58, P = 0.03). CONCLUSIONS: In addition to the improvement in whole body insulin sensitivity, rosiglitazone treatment enhances insulin stimulated myocardial glucose uptake in patients with Type 2 diabetes, most probably due to its suppression of the serum FFAs.     

Clinical Application of PET/CT Fusion Imaging for Three-Dimensional Myocardial Scar and Left Ventricular Anatomy during Ventricular Tachycardia Ablation

Background: Image integration has the potential to display three-dimensional (3D) scar anatomy and facilitate substrate characterization for ventricular tachycardia (VT) ablation. However, the current generation of clinical mapping systems cannot display 3D left ventricle (LV) anatomy with embedded 3D scar reconstructions or allow display of border zone and high-resolution anatomic scar features.
Objective: This study reports the first clinical experience with a mapping system allowing an integrated display of 3D LV anatomy with detailed 2D/3D scar and border zone reconstruction.
Methods: Ten patients scheduled for VT ablation underwent contrast-enhanced computed tomography (CT) and Rubidium-82 perfusion/F-18 Fluorodeoxyglucose metabolic Positron Emission Tomography (PET) imaging to reconstruct 3D LV and scar anatomy. LV and scar models were co-registered using a 3D mapping system and analyzed with a 17-segment model. Metabolic thresholding was used to reconstruct the 3D border zone. Real-time display of CT images was performed during ablation.
Results: Co-registration (error 4.3 ± 0.7 mm) allowed simultaneous visualization of 3D LV anatomy and embedded scar and guided additional voltage mapping. Segments containing homogenous or partial scar correlated in 94.4% and 85.7% between voltage maps and 3D PET scar reconstructions, respectively. Voltage-defined scar and normal myocardium had relative FDG uptakes of 40 ± 13% and 89 ± 30% (P < 0.05). The 3D border zone correlated best with a 46% metabolic threshold. Real-time display of registered high-resolution CT images allowed the simultaneous characterization of scar-related anatomic changes.
Conclusion: Integration of PET/CT reconstruction allows simultaneous 3D display of myocardial scar and border zone embedded into the LV anatomy as well as the display of detailed scar anatomy. Multimodality imaging may enable a new image-guided approach to substrate-guided VT ablation.     

18F-FDG PET/CT纳入肝细胞癌肝移植标准的趋势与价值

肝移植是治疗肝细胞癌(HCC)的有效方法,为降低HCC肝移植术后可能出现较高肿瘤复发率,有学者率先提出著名的Milan标准。但该标准过于严格,部分患者因其肿瘤病变较大或多个结节,虽其生物行为相对“温良”,也被排除在等待肝移植名单之外,随之世界各地出现了众多的“扩大Milan版标准”。HCC组织病理学的微血管侵犯(MVI)、肿瘤组织低分化与HCC肝移植术后较高复发率有显著相关性。复习总结了近年来国内外18氟-脱氧葡萄糖(18F-FDG)PET/CT在HCC肝移植方面的应用文献,发现18F-FDG在HCC病变部位不同的摄取程度,反映了肿瘤组织生物学行为特征即侵袭性的差异;18F-FDG高摄取与HCC病变的MVI、低分化呈正相关;18F-FDG还能敏感、准确地发现HCC肝外转移灶。认为术前18F-FDG PET/CT结果对HCC肝移植预后评估有巨大价值,将其结果纳入HCC肝移植标准是趋势所归,也有望统一“扩大Milan版标准”。建议新的肝移植标准可定义为,原则上遵循Milan标准;对超出Milan标准者,满足HCC病变18F-FDG PET/CT阴性,且排除大血管侵犯和肝外转移。     

核素心肌显像测定MBF和CFR在冠心病的诊断价值及展望

心血管疾病是世界范围内最主要的死亡原因,其治疗和诊断的经济成本很高,在过去的20年里,对冠心病患者诊断、评估及治疗越来越准确和有效。正电子发射断层显像技术是一种强大而多功能的无创性影像学检查,特别是通过量化心肌血流量(MBF)及冠状动脉血流储备(CFR)可以更好地描述冠状动脉疾病的特征,在冠状动脉微血管病变及缺血性心肌病的早期诊断、分级及治疗中发挥着重大作用。     

The persistence of hibernating myocardium after acute myocardial infarction

Objective To establish the persistence of hibernating myocardium initiallydetected after myocardial infarction treated with thrombolysis. Methods and results Fourteen patients underwent gated positron emission tomographywith 18-fluoro-deoxyglucose and N13-ammonia at a median of 8days after first myocardial infarction. Repeat scans were performedat a median of 13 weeks post-infarction. A total of 148 (30·9%)myocardial segments showed reduced N13-ammonia uptake at thetime of the first scan compared with 154·5 (32·2%)segments at the time of repeat imaging. The median change inthe number of segments with reduced perfusion was –1·0.Initially 13 subjects had hibernating myocardium, seven patientshad large areas and six had smaller regions. Six (46·2%)subjects had repeat scans showing unchanged areas of hibernatingtissue and seven had second scans demonstrating changes in thesize of the region of hibernating myocardium. One patient hadno hibernating myocardium on either scan. Conclusions Positron emission tomography performed several months aftermyocardial infarction demonstrates significant changes in myocardialperfusion. However, a reduction in the number of segments withreduced perfusion does not always result in an improvement inmyocardial metabolism and contraction. Whilst most regions ofhibernating myocardium were still present several months afterinfarction, in only approximately half was the size of the mismatchedregion unchanged. Therefore it is not possible to predict thefate of hibernating myocardium which is present after infarction.     

Hibernation and myocardial ischemia: Clinical detection by positron emission tomography

Summary Regions of myocardium supplied by severely diseased epicardial arteries may develop chronic ischemia at rest and exhibit reduced contractility, contributing to a reduction in global left ventricular function. However, after revascularization, contractility in these regions may return to normal. These regions of asynergy are described as hibernating myocardium. Such myocardium in which normal contractility may be restored often coexists with areas of infarcted, or scar, tissue, leading to the definition of hypoperfused hibernating myocardium as viable myocardium. It is important to identify viable myocardium, as revascularization of these areas should lead to the greatest improvement in left ventricular function and, thus, improvement in survival. Positron emission tomography is the best noninvasive method for quantifying regional myocardial blood flow and metabolism. Using ¹⁸F-fluorodeoxyglucose, which measures myocardial glucose utilization, it is possible to identify myocardial tissue that is hypoperfused at rest with preserved or increased glucose uptake. This mismatch of blood flow to metabolism has a high predictive accuracy in the recovery of contractile function. In order to reduce the need for metabolic imaging in documenting myocardial viability, a regional index of perfusable tissue derived from imaging with ¹⁵O water has been recently developed that also allows the quantification of tissue viability.     

Glucose metabolism in human gliomas: Correspondence ofin situ andin vitro metabolic rates and altered energy metabolism

The rates of disappearance of glucose from the medium of 13 human glioma-derived cell lines and one cultured of normal human cortical astrocytes were determined by ftuorometric techniques. High-grade glioma-derived cultures showed a range of glucose consumption between 1 and 5 nmol/min/mg protein. Normal astrocyte cultures and cultures derived from grades I–III gliomas had a glucose consumption rate of 2–3 nmol/min/mg protein. Seven high-grade glioma lines were derived from surgical samples taken from patients who had been scanned by¹⁸F-2-deoxy-d-glucose positron computed tomography. The rate of glucose consumption in these high-grade glioma-derived lines was close to the maximum local cerebral metabolic rate for glucose (LCMRglc) measuredin situ in the tumors from which the cultures were derived. In cultured glioma-derived lines, approximately one-half of the glucose consumed was recovered as lactate and pyruvate, suggesting a reliance of glioma cells on aerobic glycolysis. ATP and phosphocreatine (PCr) levels were variable in the gliomaderived lines, and ATP was lower in the glioma-derived lines than in the normal astrocytes. Levels and regulation of glycogen differed significantly among the various glioma-derived cell lines. Glycogen content did not diminish as glucose was consumed, suggesting that glycogen utilization is not tightly regulated by the glucose metabolic rate. These results suggest that human glioma-derived cell cultures (1) adequately reflect the metabolic capacity of gliomasin situ and (2) are significantly altered in several aspects of their glycolytic metabolism.     

Hyperdynamic performance of remote myocardium in acute infarction: Correlation between regional contractile function and myocardial perfusion

During and after myocardial infarction (MI), compensatory contractileand structural changes taking place in the remote uninvolvedmyocardial regions have been well described, in both experimentaland clinical settings. However, quantitative information onthe changes in perfusion in these regions in relation to theiraltered contractile function have not been available. This studywas designed to assess the in vivo relationship between contractilefunction and perfusion in remote uninvolved hypercontractilemyocardial regions, subtended by angiographically normal coronaryarteries in patients with MI and single-vessel coronary arterydisease. We utilized two-dimensional echocardiography and ¹⁵O-water positronemission tomography imaging to assess regional contractile functionand myocardial blood flow, respectively. Measurements were performedin nine patients with single-vessel coronary artery diseaseand angiographically confirmed recanalization of the infarct-relatedartery, 1–2 days after MI (group A). Only patients demonstratingseverely impaired wall motion of the infarcted area and reactivehypercontractility of the remote uninvolved regions were enrolledSeven patients with previous non-reperf used MI (6–8 monthspost-MI) served as a control (group B). Systolic wall thickeningand regional myocardial blood flow data sets were created forthe remote myocardial segments perfused by angiographicallydetected patent coronary arteries by assigning regions on thetomo grams to equivalent echocardio graphic segments. In the remote regions, wall thickening and regional myocardialblood flow were higher in group A patients by 26% (43 ±6% vs 34 ± 4%; P=0·005) and 20% (1·06 ±0·15 vs 0·89 ± 0·06 ml. g^–1per minute; P=0·019), respectively. For both groups ofpatients, a significant correlation (r=0·67, P=0·004)between systolic wall thickening and regional myocardial bloodflow was obtained. Infarcted regions in both groups showed nosystolic wall thickening. In this selected group of patients these data demonstrate: (1)a proportionate increase in contractility and regional myocardialblood flow in uninvolved territories in patients with recentand old MI; (2) the in vivo relationship between contractilefunction and myocardial perfusion in man in these regions. Wheninfarcted zones in both groups are equally affected, enhancedlevels of catecholamines and sympathetic drive as well as differentloading conditions may account for the hyperkinetic performanceand consequently for the increased perfusion level in uninvolvedsegments in patients with recent MI.     

Hyperdynamic performance of remote myocardium in acute infarction: Correlation between regional contractile function and myocardial perfusion

During and after myocardial infarction (MI), compensatory contractileand structural changes taking place in the remote uninvolvedmyocardial regions have been well described, in both experimentaland clinical settings. However, quantitative information onthe changes in perfusion in these regions in relation to theiraltered contractile function have not been available. This studywas designed to assess the in vivo relationship between contractilefunction and perfusion in remote uninvolved hypercontractilemyocardial regions, subtended by angiographically normal coronaryarteries in patients with MI and single-vessel coronary arterydisease. We utilized two-dimensional echocardiography and ¹⁵O-water positronemission tomography imaging to assess regional contractile functionand myocardial blood flow, respectively. Measurements were performedin nine patients with single-vessel coronary artery diseaseand angiographically confirmed recanalization of the infarct-relatedartery, 1–2 days after MI (group A). Only patients demonstratingseverely impaired wall motion of the infarcted area and reactivehypercontractility of the remote uninvolved regions were enrolledSeven patients with previous non-reperf used MI (6–8 monthspost-MI) served as a control (group B). Systolic wall thickeningand regional myocardial blood flow data sets were created forthe remote myocardial segments perfused by angiographicallydetected patent coronary arteries by assigning regions on thetomo grams to equivalent echocardio graphic segments. In the remote regions, wall thickening and regional myocardialblood flow were higher in group A patients by 26% (43 ±6% vs 34 ± 4%; P=0.005) and 20% (1.06 ± 0.15 vs0.89 ± 0.06 ml. g^–1 per minute; P=0.019), respectively.For both groups of patients, a significant correlation (r=0.67,P=0.004) between systolic wall thickening and regional myocardialblood flow was obtained. Infarcted regions in both groups showedno systolic wall thickening. In this selected group of patients these data demonstrate: (1)a proportionate increase in contractility and regional myocardialblood flow in uninvolved territories in patients with recentand old MI; (2) the in vivo relationship between contractilefunction and myocardial perfusion in man in these regions. Wheninfarcted zones in both groups are equally affected, enhancedlevels of catecholamines and sympathetic drive as well as differentloading conditions may account for the hyperkinetic performanceand consequently for the increased perfusion level in uninvolvedsegments in patients with recent MI.     

Abnormalities in myocardial metabolism in patients with unstable angina as assessed by positron emission tomography

Summary Regional myocardial perfusion and glucose metabolism were assessed in six normal volunteers and 29 patients with coronary heart disease and stable or unstable angina using rubidium-82 (Rb-82) and F-18 fluoro 2-deoxy-D-glucose (FDG) with positron emission tomography.All normals and patients were studied following overnight fasting, at rest, with no angina or electrocardiographic signs of acute myocardial ischemia or necrosis. Rb-82 myocardial cross-sectional images were obtained employing the continuous infusion technique, while dynamic FDG imaging was employed after intravenous tracer bolus injection. Regional Rb-82 and FDG myocardial concentrations were then calculated by drawing regions of interest over the interventricular septum, anterior and lateral wall of the left ventricle.The mean Rb-82 uptake for each left ventricular region analyzed was found to be similar between both groups of patients and normal volunteers. The mean myocardial glucose utilization was found to be similar in normal volunteers and patients with stable angina (0.023±0.032 vs. 0.012±0.008 m ml/min p<0.42). However, myocardial glucose utilization was found to be significantly higher in patients with unstable angina compared with both normals and patients with stable angina (0.048±0.047 M/ml/min p<0.001 for both comparisons). Thus, in patients with severe coronary artery disease and unstable angina, myocardial glucose utilization was enhanced in spite of the absence of clinical, electrocardiographic, or detectable perfusion evidence of acute ischemia.     

The Evolving Roles of Nuclear Cardiology

The use of cardiac imaging modalities has grown steadily, and cardiac nuclear studies constitute a large part of this number. Nuclear Cardiology is often mistakenly considered a synonym of myocardial perfusion imaging (MPI), but has broader applications, including metabolic imaging, innervation imaging, among other technologies. MPI has been a powerful diagnostic and prognostic tool in the assessment of patients for known or suspected CAD for decades, and is now increasingly used for the evaluation of the anti-ischemic effects of various therapies, according to changes in left ventricular perfusion defect size defined by sequential MPI. Neuronal dysfunction identified with iodine-123-metaiodobenzylguanidine may give information on prognosis in different disease conditions, such as after myocardial infarction, in diabetes and dilated cardiomyopathy. Molecular imaging may identify the predominant cellular population in the atherosclerotic plaque and help predict the likelihood of clinical events. Therefore, although its usefulness is well established, Nuclear Cardiology remains a moving science, whose roles keep in pace with evolving clinical needs and expectations.