Metabolic imaging using SPECT

金沢大学医学部附属病院核医学診療科Introduction: In normal condition, the heart obtains more than two-thirds of its energy from the oxidative metabolism of long chain fatty acids, although a wide variety of substrates such as glucose, lactate, ketone bodies and amino acids are also utilised. In ischaemic myocardium, on the other hand, oxidative metabolism of free fatty acid is suppressed and anaerobic glucose metabolism plays a major role in residual oxidative metabolism. Therefore, metabolic imaging can be an important technique for the assessment of various cardiac diseases and conditions. Materials and methods: In SPECT, several iodinated fatty acid traces have been introduced and studied. Of these, 123I-labelled 15-(p-iodophenyl)3-R, S-methylpentadecanoic acid (BMIPP) has been the most commonly used tracer in clinical studies, especially in some of the European countries and Japan. Results and discussion: In this review article, several fatty acid tracers for SPECT are characterised, and the mechanism of uptake and clinical utility of BMIPP are discussed in detail. © 2007 Springer-Verlag

放射性ヨード標識metaiodobenzylguanidineによる心筋交感神経イメージングに関する研究

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1000号, 学位授与年月日：平成3年3月25日,学位授与年：199

99mTc-sestamibi retention characteristics during pharmacologic hyperemia in human myocardium: Comparison with coronary flow reserve measured by Doppler flowire

金沢大学大学院医学系研究科The aim of the study was to investigate the increase in myocardial 99mTc-methoxyisobutylisonitrile (sestamibi) retention in humans during pharmacologic vasodilation. Methods: For calculation of the increase in 99mTc-sestamibi retention during hyperemia, baseline and adenosine triphosphate (ATP)-induced hyperemic stress sestamibi studies were performed using a same-day rest-stress protocol. On the injection of sestamibi, left ventricular dynamic data were obtained for 90 s. The increase in sestamibi retention from baseline to hyperemia was calculated by the formula Cmh(t) ∫01 Cbb(τ)dτ/Cmb(t) ∫01 Cbh(τ)dτ, where Cmh(t) and Cmb(t) are myocardial counts on the tomographic image, and Cbb(τ) and Cbh(τ) are the left ventricular blood-pool counts during the first transit of sestamibi at baseline and during hyperemia, respectively. Coronary flow increase during intravenous ATP stress was measured using intracoronary Doppler flow guide wire and compared with the scintigraphic results of 28 measurements in 22 patients. Results: Sestamibi retention increased as coronary flow velocity increased but plateaued at >2.5-3 times baseline flow velocity. The relationship between the increase in sestamibi retention (Y) and the increase in flow (X) is expressed as follows: Y = 0.44 + 0.60X - 0.068X2 (r = 0.82). Conclusion: In humans, the increase in 99mTc-sestamibi myocardial retention underestimates coronary flow reserve, particularly at high flow rates. Knowledge of these tracer retention characteristics will contribute to a more comprehensive understanding of the manner and interpretation of stress sestamibi imaging

Prediction of functional recovery after revascularization using quantitative gated myocardial perfusion SPECT: a multi-center cohort study in Japan

金沢大学医薬保健研究域医学系Backgrounds: Prediction of left ventricular functional recovery is important after myocardial infarction. The impact of quantitative perfusion and motion analyses with gated single-photon emission computed tomography (SPECT) on predictive ability has not been clearly defined in multi-center studies. Methods: A total of 252 patients with recent myocardial infarction (n = 74) and old myocardial infarction (n = 175) were registered from 25 institutions. All patients underwent resting gated SPECT using 99mTc-hexakis-2-methoxy-isobutyl isonitrile (MIBI) and repeated the study after revascularization after an average follow-up period of 132 ± 81 days. Visual and quantitative assessment of perfusion and wall motion were performed in 5,040 segments. Results: Non-gated segmental percent uptake and end-systolic (ES) percent uptake were good predictors of wall motion recovery and significantly differed between improved and non-improved groups (66 ± 17% and 55 ± 18%, p < 0.0001 for non-gated; 64 ± 16% and 51 ± 17% for ES percent uptake, p < 0.0001). The area under the curve of receiver operating characteristics curve for non-gated percent uptake, ES percent uptake, end-diastolic percent uptake and visual perfusion defect score was 0.70, 0.71, 0.61, and 0.56, respectively. Sensitivity and specificity of percent uptake were 68% and 64% for non-gated map and 80% and 52% for ES percent uptake map. An optimal threshold for predicting segmental improvement was 63% for non-gated and 52% for ES percent uptake values. Conclusion: Segmental 99mTc-MIBI uptake provided a useful predictor of wall motion improvement. Application of quantitative approach with non-gated and ES percent uptake enhanced predictive accuracy over visual analysis particularly in a multi-center study. © 2008 Springer-Verlag

Electrocardiographic gated 99mTc-MIBI SPECT for functional assessment of patients after coronary artery bypass surgery: Comparison of wall thickening and wall motion analysis

金沢大学大学院医学系研究科Abnormal septal motion after coronary artery bypass graft surgery (CABG) is a common finding. This study was undertaken to investigate the change in various global and regional ventricular function parameters measured by gated myocardial perfusion SPECT after surgery and to determine which quantitative parameter of WT and WM is more appropriate for the evaluation of regional cardiac function, especially in the septum of patients with CABG. Methods: Before and 3 to 5 wk after CABG (all patients underwent at least 1 bypass grafting to the left anterior descending coronary artery), 35 patients (28 men, 7 women) underwent gated SPECT using 99mTc-methoxyisobutylisonitrile. Quantitative global and regional ventricular functional analysis was performed using quantitative gated SPECT software. Results: Global ejection fraction did not change (59.3% ± 16.0% to 60.5% ± 14.5%, P = 0.24). However, end-diastolic and end-systolic volumes lessened significantly after CABG (81.4 ± 37.3 mL to 68.9 ± 28.9 mL, P < 0.0001, and 38.1 ± 33.1 mL to 30.4 ± 23.0 mL, P < 0.005, respectively). As global function parameters, the changes in both total WM (r = 0.88) and WT (r = 0.86) correlated well with the change in ejection fraction after surgery. Segmental analysis showed a significant postoperative increase in relative tracer uptake in the anterior, anteroseptal, inferoseptal, and inferior walls and in the apex. Segmental wall motion (WM) deteriorated in the anteroseptal, inferoseptal, and mid anterior walls. On the other hand, anterolateral, inferolateral, and inferior WM increased. As a whole, these WM changes showed a reduction in septal motion associated with a concomitant increase in lateral motion after surgery. Segmental wall thickening, however, did not decrease in septal areas and did not increase in the lateral wall and correlated with percentage tracer uptake (r = 0.69) better than WM did (r = 0.30) after CABG. Conclusion: In patients with CABG, postoperative WM analysis by gated SPECT underestimated septal motion and overestimated lateral motion because of exaggerated systolic anteromedial cardiac translation. Therefore, wall thickening analysis would be recommended for the evaluation of postoperative cardiac functio

Detection of cardiomyocyte death in a rat model of ischemia and reperfusion using 99mTc-labeled annexin V.

金沢大学大学院医学系研究科There is increasing evidence that cell death after myocardial ischemia and reperfusion may begin as apoptosis rather than necrosis. To determine the time course, location, and extent of this process, we studied groups of rats after a 20-min interval of coronary occlusion and reperfusion. METHODS: After thoracotomy, the left coronary artery was occluded for 20 min. After release and before study, groups of animals were allowed to recover for various intervals: 0.5 h (n = 6), 1.5 h (n = 7), 6 h (n = 7), 1 d (n = 8), 3 d (n = 8), or 2 wk (n = 5). At the time of study, the rats were injected with 99mTc-annexin V (80-150 MBq). One hour later, to verify the area at risk, 201Tl (0.74 MBq) was injected intravenously just after the left coronary artery reocclusion and the rats were sacrificed 1 min later. Dual-tracer autoradiography was performed to assess 99mTc-annexin V uptake and the area at risk. RESULTS: Extensive 99mTc-annexin V uptake was observed in the mid myocardium after 0.5-1.5 h of reperfusion. The area of annexin uptake had expanded in the subendocardial and subepicardial layers at 6 h after reperfusion and then gradually lessened over 3 d. At 0.5 and 1.5 h of reperfusion, 99mTc-annexin V uptake ratios were 7.36 +/- 2.95 and 6.34 +/- 2.24 (mean +/- SD), respectively. The uptake ratios gradually decreased at 6 h, 1 d, 3 d, and 2 wk after reperfusion (4.65 +/- 1.93, 3.27 +/- 0.92 [P < 0.01 vs. 0.5 h], 1.84 +/- 0.55 [P < 0.001 vs. 0.5 h, P < 0.005 vs. 1.5 h], and 1.65 +/- 0.31 [P < 0.001 vs. 0.5 h, P < 0.005 vs. 1.5 h], respectively). CONCLUSION: These data indicate that annexin binding commences soon after ischemia and reperfusion in the mid myocardium within the area at risk and expands to include the subendocardial and subepicardial layers at 6 h after reperfusion, followed by gradual reduction of activity over 3 d

Effect of postconditioning on dynamic expression of tenascin-C and left ventricular remodeling after myocardial ischemia and reperfusion

金沢大学疾患モデル総合研究センターBackgroundTenascin-C (TNC), an extracellular matrix glycoprotein, is expressed transiently in distinct areas in association with active tissue remodeling. This study aimed to explore how ischemic postconditioning (PC) affects myocardial expression of TNC and ventricular remodeling using 125I-labeled anti-TNC antibody (125I-TNC-Ab) in a rat model of ischemia and reperfusion.MethodsIn control rats (n = 27), the left coronary artery (LCA) was occluded for 30 min followed by reperfusion for 1, 3, 7, and 14 days. PC (n = 27) was performed just after the reperfusion. At the time of the study, 125I-TNC-Ab (1.0 to 2.5 MBq) was injected. Six to 9 h later, to verify the area at risk, 99mTc-MIBI (100 to 200 MBq) was injected intravenously just after the LCA reocclusion, with the rats sacrificed 1 min later. Dual tracer autoradiography was performed to assess 125I-TNC-Ab uptake and area at risk. To examine the ventricular remodeling, echocardiography was performed 2 M after reperfusion in both groups.ResultsIn control rats, 125I-TNC-Ab uptake ratio at 1 day after reperfusion was 3.73 ± 0.71 and increased at 3 days (4.65 ± 0.87), followed by a significant reduction at 7 days (2.91 ± 0.55, P < 0.005 vs 3 days) and14 days (2.01 ± 0.17, P < 0.005 vs 1 and 3 days). PC attenuated the 125I-TNC-Ab uptake throughout the reperfusion time from 1 to 14 days; 2.59 ± 0.59 at 1 day, P < 0.05: 3.10 ± 0.42 at 3 days, P < 0.005: 1.93 ± 0.37 at 7 days, P < 0.05: 1.40 ± 0.07 at 14 days, P < 0.001. In echocardiography, PC reduced the ventricular end-diastolic and systolic dimensions (1.00 ± 0.06 cm to 0.83 ± 0.14 cm (P < 0.05) and 0.90 ± 0.15 cm to 0.62 ± 0.19 cm (P < 0.05), respectively) and prevented a decline of ventricular percentage fractional shortening (10.5 ± 3.7 to 28.2 ± 10.7, P < 0.005).ConclusionsThese data indicate that 125I-TNC-Ab imaging may be a way to monitor myocardial injury, the subsequent repair process, and its response to novel therapeutic interventions like PC by visualizing TNC expression