Reduced 123I-BMIPP uptake implies decreased myocardial flow reserve in patients with chronic stable angina

Purpose Long-chain fatty acid (LCFA) is the main energy source for normal myocardium at rest, but in ischemic myocardium, the main energy substrate shifts from LCFA to glucose. 123I-BMIPP is a radiolabeled LCFA analog. In chronic stable angina without previous infarction, we suppose that reduced 123I-BMIPP uptake is related to the substrate shift in myocardium with decreased myocardial flow reserve (MFR). The purpose of this study was to relate 123I-BMIPP uptake to rest myocardial blood flow (MBF), hyperemic MBF, and MFR assessed with 15O-water positron emission tomography (PET). Methods We enrolled 21 patients with chronic stable angina without previous infarction, all of whom underwent 123I-BMIPP single-photon emission computed tomography (SPECT) and 15O-water PET. The left ventricle was divided into 13 segments. In each segment, rest MBF and hyperemic MBF were measured by PET. 123I-BMIPP uptake was evaluated as follows: score 0=normal, 1=slightly decreased uptake, 2=moderately decreased uptake, 3=severely decreased uptake, and 4=complete defect. 123I-BMIPP uptake was compared with rest MBF, hyperemic MBF, and MFR. Results The numbers of segments with 123I-BMIPP scores 0, 1, 2, 3, and 4 were 178, 40, 25, 24, and 0, respectively. The rest MBFs for scores 0, 1, 2, and 3 were 0.93±0.25, 0.86±0.21, 0.97±0.30, and 0.99±0.37 ml/min/g, respectively. The hyperemic MBFs for scores 0, 1, 2, and 3 were 2.76±1.29, 1.84±0.74, 1.37±0.39, and 1.08±0.40 ml/min/g, respectively. The MFRs for scores 0, 1, 2, and 3 were 3.01±1.38, 2.20±0.95, 1.44±0.22, and 1.10±0.26, respectively. As 123I-BMIPP uptake declined, hyperemic MBF and MFR decreased. Conclusion In chronic stable angina without previous infarction, reduced 123I-BMIPP uptake implies decreased MFR

Translocator protein imaging with 18F-FEDAC-positron emission tomography in rabbit atherosclerosis and its presence in human coronary vulnerable plaques

Background and aims: This study aimed to investigate whether N-benzyl-N-methyl-2-[7,8-dihydro-7-(2-[18F]fluoroethyl)-8-oxo-2-phenyl-9H-purin-9-yl]acetamide (18F-FEDAC), a probe for translocator protein (TSPO), can visualize atherosclerotic lesions in rabbits and whether TSPO is localized in human coronary plaques.Methods: 18F-FEDAC-PET of a rabbit model of atherosclerosis induced by a 0.5% cholesterol diet and ballooninjury of the left carotid artery (n = 7) was performed eight weeks after the injury. The autoradiography intensity of 18F-FEDAC in carotid artery tissue sections was measured, and TSPO expression was evaluated immunohistochemically.TSPO expression was examined in human coronary arteries obtained from autopsy cases (n = 16), and in human coronary plaques (n = 12) aspirated from patients with acute myocardial infarction (AMI).Results: 18F-FEDAC-PET visualized the atherosclerotic lesions in rabbits as high-uptake areas, and the standard uptake value was higher in injured arteries (0.574 ± 0.24) than in uninjured arteries (0.277 ± 0.13, p < 0.05) or myocardium (0.189 ± 0.07, p < 0.05). Immunostaining showed more macrophages and more TSPO expression in atherosclerotic lesions than in uninjured arteries. TSPO was localized in macrophages, and arterial autoradiography intensity was positively correlated with macrophage concentration (r = 0.64) and TSPO (r = 0.67). TSPO expression in human coronary arteries was higher in AMI cases than in non-cardiac death, or in the vulnerable plaques than in early or stable lesions, respectively. TSPO was localized in macrophages in all aspirated coronary plaques with thrombi.Conclusions: 18F-FEDAC-PET can visualize atherosclerotic lesions, and TSPO-expression may be a marker of highrisk coronary plaques

Repeatability of Rest and Hyperemic Myocardial Blood Flow Measurements with 82Rb Dynamic PET

The repeatability of rest and hyperemic myocardial blood flow (MBF) measurements using 82Rb PET has not been evaluated. The aimof this study was to investigate the short-term repeatability of such measurements. Methods: Fifteen healthy volunteers underwent rest and pharmacologic stress 82Rb PET, repeated 60 min apart. Results: There was no significant difference in repeated rest MBF (0.77 6 0.25 vs. 0.82 6 0.25 mL/min/g, P 5 0.31; mean difference, 6.18% 6 12.22%) or repeated hyperemic MBF (3.35 6 1.37 vs. 3.39 6 1.37 mL/min/g, P 5 0.81; mean difference, 1.17% 6 13.64%). The repeatability coefficients were 0.19 mL/min/g for rest MBF and 0.92 mL/min/g for hyperemia. Conclusion:MBF using 82Rb is highly reproducible using a sameday short-term repeatability protocol. Serial MBF measurements with 82Rb PET should have the ability to quantify the acute effects of therapeutic interventions on MBF

An ultra-high-energy collimator for small animal imaging in dual-isotope study of 18F and 99mTc

We have developed a pinhole collimator for small animal imaging using dual-isotopes, such as gamma and positron emitters. A lead cylinder containing a pinhole was placed around the subject (a small animal). The cylinder was equipped with a non-collimator gamma camera, and dual-isotope (99mTc-MIBI and 18F-FDG) SPECT was performed on a Wistar King Aptekman/hok (WKAH) rat. System planar sensitivity and Full-Width at Half-Maximum (FWHM) were measured for each radionuclide. System planar sensitivities for 99mTc and 18F SPECT were 2 and 7 cps/MBq, respectively. FWHMs for 99mTc and 18F SPECT were 2.0±0.5 and 2.7±0.5 mm, respectively. The collimator is relatively light (23 kg), and thus SPECT projection data could be acquired by rotating the gamma camera while the object remained stationary. The pinhole collimator can be used with a conventional rotating gamma camera. The present study demonstrated that it is possible to image organs in vivo in sufficient detail using the newly developed pinhole collimator. Further refinements to the experimental procedure may provide simultaneous high-resolution imaging of small animals using positron and gamma emitters with this collimator

Elevated serum endothelin-1 is an independent predictor of coronary microvascular dysfunction in non-obstructive territories in patients with coronary artery disease

Endothelin-1 contributes to the constrictor response of the coronary arteries in patients with ischemia with normal coronary arteries. There is thus increasing evidence that endothelin-1 plays a role in coronary microvascular dysfunction (CMD). We investigated whether elevated endothelin-1 is associated with CMD in patients with coronary artery disease (CAD). We prospectively studied 49 consecutive CAD patients with 1- or 2-vessel disease (age 71 +/- 10 years, 43 males). Myocardial blood flow (MBF) was measured by O-15-water PET/CT at rest and during stress, and the coronary flow reserve (CFR) was calculated by dividing the stress MBF by the rest MBF. A CFR of less than 2.0 in non-obstructive regions was defined as a marker of CMD. Eighteen out of 49 (37%) CAD patients had CMD. Endothelin-1 in patients with CMD was significantly higher than in those without CMD (2.27 +/- 0.81 vs. 1.64 +/- 0.48 pg/mL, P = 0.001). Accordingly, univariate ROC analysis showed that the continuous endothelin-1 levels significantly discriminated between the presence and absence of CMD (area under the curve = 0.746 [95%CI 0.592-0.899]). The dichotomous treatment of elevated endothelin-1 as 1.961 pg/mL or more yielded the optimal discriminatory capacity, with a sensitivity of 72.2% and a specificity of 71.0%. High endothelin-1 was still a significant predictor of CMD after adjusting for diabetes mellitus (odds ratio = 6.64 [1.75-25.22], P = 0.005). Endothelin-1 is associated with CMD in non-obstructive territories in patients with CAD, suggesting that endothelin-1 is a potential target for treating CMD in CAD patients

Olmesartan, but not amlodipine, improves endothelium-dependent coronary dilation in hypertensive patients

Objectives: We aimed to compare the effects of angiotensin II receptor blocker (ARB) olmesartan versus calcium channel blocker (CCB) amlodipine on coronary endothelial dysfunction in patients with hypertension. Background: ARB is thought to have greater beneficial effects on coronary vasomotion via directly blocking action of angiotensin II than CCB. Methods: Twenty-sex patients with untreated essential hypertension were prospectively assigned to the treatment with either olmesartan (27.7±12.4 mg per day, n=13) or amlodipine (5.6±1.5 mg per day, n=13) for 12 weeks. Changes of corrected myocardial blood flow (ΔMBF) and coronary vascular resistance (ΔCVR) from rest to cold pressor were measured by using 15O-water and positron emission tomography before and after treatment. Blood biomarkers including lipids, glucose, insulin, hs-CRP, interleukin-6, tumor necrosis factor-α, and superoxide dismutase (SOD) were also measured. Results: Olmesartan and amlodipine reduced blood pressure (BP) to the same extent (−28.7±16.2 vs. −26.7±10.8 mmHg). In olmesartan group, ΔMBF tended to be greater (−0.15±0.19 vs. 0.03±0.17 ml/g/min, P=0.09 by 2-way ANOVA) and ΔCVR was significantly decreased (7.9±23.5 vs. −16.6±18.0 mmHg/[ml/g/min], P<0.05) after treatment whereas they did not change in amlodipine group (ΔMBF: −0.15±0.12 vs. −0.12±0.20 ml/g/min; ΔCVR: 6.5±18.2 vs. 4.8±23.4 mmHg/[ml/g/min]). Serum SOD activity tended to increase (4.74±4.77 vs. 5.57±4.74 U/ml, P=0.07 by 2-way ANOVA) only in olmesartan group. Conclusions: Olmesartan, but not amlodipine, improved endothelium-dependent coronary dilation in hypertensive patients independently of BP lowering. These beneficial effects on coronary vasomotion might be via an antioxidant property of ARBs

A new dynamic myocardial phantom for the assessment of left ventricular function by gated single-photon emission tomography.

Gated myocardial perfusion single-photon emission tomography (SPET) has been used for the measurement of left ventricular (LV) function and validated by means of comparison with other imaging modalities. We have designed a new dynamic myocardial phantom in order to validate the LV function as assessed by the use of gated myocardial perfusion SPET. The phantom consists of two half-ellipsoids (an endocardial surface and an epicardial surface) and a thorax. The myocardial space is filled with a radioactive solution. The endocardial surface moves continuously towards and away from the epicardial surface in the longitudinal axis to vary the LV volume [143 ml at end-diastole (ED), 107 ml at end-systole (ES)] and thickness (apex 8 mm at ED and 26 mm at ES, midplane 8 mm). The mean values of wall motion (WM) for the apical midplane region and the basal midplane region were 5 mm and 2 mm, respectively. Gated myocardial SPET was performed during 8 and 16 intervals. These projection data sets were processed using a Butterworth filter with an order of 5 and a critical frequency of 0.34 cycles/cm. LV function was calculated using the quantitative gated SPET (QGS) algorithm. The LV function values estimated by gated SPET during 16 intervals [22% for ejection fraction (EF), 3.7 mm for WM of the apical midplane, 1.7 mm for WM of the basal midplane] closely resembled actual LV functions [25% for EF, 5 mm for WM of the apical midplane, 2 mm for WM of the basal midplane]. However, the estimated values during 8 intervals were smaller than those during 16 intervals (19% for EF, 3.3 mm for WM of the apical-midplane, 1.1 mm for WM of the basal-midplane). The estimated LV volumes closely correlated with the actual volumes (r=0.99 for 16 intervals, r=0.95 for 8 intervals). Utilizing this phantom, LV function estimated using gated myocardial SPET can be compared with actual values