Semi-automated algorithm for calculating heart-to-mediastinum ratio in cardiac Iodine-123 MIBG imaging.

BACKGROUND: We have developed novel software for semi-automatically measuring heart-to-mediastinum (H/M) ratio in cardiac Iodine-123 (¹²³I)-labeled meta-iodobenzylguanidine (MIBG) imaging. Our aim is to improve the reproducibility of the H/M ratio using the semi-automated method as opposed to the manual method. METHODS AND RESULTS: The software algorithm automatically determined the mediastinal region of interest (ROI) using information from ¹²³I-MIBG uptake of the heart, lung, liver, and thyroid after a cardiac circular ROI was manually set. A total of 37 patients who underwent both early and delayed ¹²³I-MIBG imaging was retrospectively selected. The heart-to-mediastinum (H/M) ratios were calculated by both semi-automated and manual methods and assessed for the intra- and inter-observer variability. All H/M ratios were classified into three groups: normal, slight abnormality, and severe abnormality. The H/M ratios with the new method were higher than those obtained manually (P < .001). In the test-retest reliability, the intra-class correlation coefficient from the semi-automated method showed excellent reproducibility for early (0.99) and delayed (0.99) imaging. The Bland-Altman plots demonstrated better agreement using the semi-automated method (a range of 95% limits -0.11 to 0.10) than that in the manual method (-0.34 to 0.27). The inter-observer agreement was also good using the semi-automated method (κ = 0.866). CONCLUSIONS: The H/M ratio using the semi-automated method showed high reproducibility in both early and delayed imaging.

Standardization of the heart-to-mediastinum ratio of 123I-labelled-metaiodobenzylguanidine uptake using the dual energy window method: feasibility of correction with different camera-collimator combinations.

BACKGROUND: Although the heart-to-mediastinum (H/M) ratio in a planar image has been used for practical quantification in (123)I-metaiodobenzylguanidine (MIBG) imaging, standardization of the parameter is not yet established. We hypothesized that the value of the H/M ratio could be standardized to the various camera-collimator combinations. METHODS AND RESULTS: Standard phantoms consisting of the heart and mediastinum were made. A low-energy high-resolution (LEHR) collimator and a medium-energy (ME) collimator were used. We examined multi-window correction methods with (123)I- dual-window (IDW) acquisition, and planar images were obtained with IDW correction and the LEHR collimator. The images were obtained using the following gamma camera systems: GCA 9300A (Toshiba, Tokyo), E.CAM Signature (Toshiba/Siemens, Tokyo) and Varicam (GE, Tokyo). Cardiac phantom studies demonstrated that contamination of the H/M count ratio was greater with the LEHR collimator and least with the ME collimator. The corrected H/M ratio with the LEHR collimator was similar to that with ME collimators. The uncorrected H/M ratio with the ME collimator was linearly related to the H/M ratio with IDW correction with the LEHR collimator. The relationship between the uncorrected H/M ratios determined with the LEHR (E.CAM) and the ME collimators was y = 0.56x + 0.49, where y = H/M ratio with the E.CAM and x = H/M ratio with the ME collimator. The average normal values for the low-energy collimator (n=18) were 2.2+/-0.2 (initial H/M ratio) and 2.42+/-0.2 (delayed H/M ratio), and for the low/medium-energy (LME) collimator (n=14) were 2.63+/-0.25 (initial H/M ratio) and 2.87+/-0.19 (delayed H/M ratio). H/M ratios in previous clinical studies using LEHR collimators are comparable to those with ME collimators. CONCLUSION: The IDW-corrected H/M ratios determined with the LEHR collimator were similar to those determined with the ME collimator. This finding could make it possible to standardize the H/M ratio in planar imaging among various collimators in the clinical setting.

Correction of iodine-123-labeled meta-iodobenzylguanidine uptake with multi-window methods for standardization of the heart-to-mediastinum ratio.

BACKGROUND: To overcome differences in the choice of collimator for an iodine-123 ((123)I)-labeled meta-iodobenzylguanidine (MIBG) heart-to-mediastinum (H/M) ratio, we examined multi-window correction methods with (123)I dual-window (IDW) and triple-energy window (TEW) acquisition. METHODS AND RESULTS: Standard phantoms, which consisted of the heart, mediastinum, lung, and liver, were generated. Three correction methods were compared: TEW and two IDW methods (IDW(0) and IDW(1)). Low-energy high-resolution (LEHR), medium-energy (ME), and (123)I-specific low-medium-energy high-resolution (LMEHR) collimators were used. Clinical studies were performed in 10 patients. In the phantom study, the H/M ratio was significantly underestimated without correction, with both the LEHR and ME collimators (70% and 88% of the true value). When H/M with the LEHR collimator was divided by uncorrected H/M with the ME collimator, the ratio (mean +/- SD) was 80% +/- 5%, 98% +/- 5%, 104% +/- 7%, and 98% +/- 5% for the no-correction, TEW, IDW(0), and IDW(1) methods, respectively. Clinical studies with the LEHR collimator after TEW and IDW correction (uncorrected average H/M ratio, 1.86 +/- 0.23; TEW, 2.47 +/- 0.46, P = .0015; IDW, 2.46 +/- 0.46, P = .0017) provided comparable values to the uncorrected ME collimator (2.56 +/- 0.46, P = NS vs TEW and IDW). CONCLUSIONS: The H/M ratio with the ME collimator, after application of the TEW or IDW methods, was close to the theoretical value in the phantom study. However, the corrected H/M ratios with the LEHR collimator provided comparable H/M ratios to the uncorrected ME data in phantom and clinical studies.

Relationship between stereochemistry and the beta3-adrenoceptor agonistic activity of 4'-hydroxynorephedrine derivative as an agent for treatment of frequent urination and urinary incontinence.

This report proposes a beta(3)-adrenoceptor (AR) selective agonist, 2-[2-chloro-4-(2-([(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino)ethyl)phenoxy]acetic acid (1a), as a novel agent for treating urinary bladder dysfunction. This compound and its relatives have a unique feature among beta(3)-AR agonists: two chiral carbons are adjacently structured on the left side of the molecule. To study the relationship between the stereoconfiguration of the vicinal chiral carbons in 1a and beta-AR agonistic activity, the four stereoisomers were synthesized via oxazolidinone prepared by intracyclization involving inversion of the beta-hydroxy group. The in vitro assays using rat atria for beta(1)-AR, rat uteri for beta(2)-AR, and ferret detrusor for beta(3)-AR showed that 1a possessed potent beta(3)-AR agonistic activity (EC(50) = 3.85 nM) and 3700- and 1700-fold selectivity for beta(3)-AR relative to beta(1)- and beta(2)-AR, respectively. Comparison of the four isomers revealed that the (alphaS,betaR)-compound (1a) was not only the most potent agonist but was also the most selective for beta(3)-AR. In the anesthetized rat, intravenous administration of 1a brought about a sufficient decrement of the intrabladder pressure (ED(50) = 12 microg/kg), and intraduodenal administration of 2a, which is the ethyl ester of 1a, led to same result (ED(50) = 0.65 mg/kg). Moreover, no effects on the cardiovascular system were observed in either test.

Effects of intravenous atrial natriuretic peptide on cardiac sympathetic nerve activity in patients with decompensated congestive heart failure.

UNLABELLED: The activation of the renin-angiotensin-aldosterone system (RAAS) prevents the uptake of norepinephrine in the myocardium. Atrial natriuretic peptide (ANP), a circulating hormone of cardiac origin, has vasodilatory and diuretic properties and can inhibit the RAAS. However, its effect on cardiac sympathetic nerve activity has not been determined. METHODS: We studied 58 patients with decompensated nonischemic acute heart failure who were treated with intravenous low-dose dopamine and diuretics. Twenty-nine patients (group A) were assigned to also receive intravenous ANP, whereas the remaining 29 patients (group B) continued their established drug regimen. The dopamine or ANP was continuously infused for >96 h. The left ventricular end-diastolic volume and ejection fraction were determined by echocardiography before and 4 wk after treatment. The delayed heart-to-mediastinum (H/M) count ratio, delayed total defect score, and washout rate were determined from (123)I-metaiodobenzylguanidine (MIBG) images 3 wk after treatment. RESULTS: Fifty-six patients enrolled in the trial completed the entire protocol. After treatment of group A (n = 28), the left ventricular end-diastolic volume decreased from 186 +/- 42 to 174 +/- 48 mL (P < 0.05), and left ventricular ejection fraction increased from 32% +/- 9% to 36% +/- 7% (P < 0.05). In group B (n = 28), these parameters did not change significantly. In addition, 3 wk after treatment of group A, the total defect score was significantly lower (30 +/- 9 vs. 38 +/- 9, P < 0.01), the H/M count ratio was significantly higher (1.86 +/- 0.21 vs. 1.62 +/- 0.23, P = 0.0001), and washout rate was significantly lower (42% +/- 12% vs. 49% +/- 12%, P < 0.05) than in group B. CONCLUSION: The present study demonstrates an improvement in echocardiographic parameters with ANP infusion. In addition, cardiac (123)I-MIBG scintigraphic parameters were better in patients who received ANP infusion along with dopamine and diuretics than in patients who received standard conventional therapy. These findings indicate that intravenous administration of ANP can benefit cardiac sympathetic nerve activity and improve left ventricular remodeling in patients with acute heart failure.

Quantification of myocardial perfusion SPECT using freeware package (cardioBull).

OBJECTIVE: We have developed freeware package for automatically quantifying myocardial perfusion and (123)I-labeled radiopharmaceutical single-photon emission computed tomography (SPECT), which is called "cardioBull". We aim to evaluate diagnostic performance of the detection of coronary artery disease (CAD) on the developed software in comparison with commercially available software package [Quantitative Perfusion SPECT (QPS)]. METHODS: Stress-rest (99m)Tc-sestamibi myocardial perfusion SPECT was performed in 36 patients with CAD and 35 control patients. A ≥ 75% stenosis in the coronary artery was identified by coronary angiography in the CAD group. Segmental perfusion defect score was automatically calculated by both cardioBull and QPS software. Summed stress score (SSS) was obtained to detect CAD by the receiver operator characteristic (ROC) analysis. Areas under the ROC curves (AUC) were calculated in patient-based and coronary-based analyses. RESULTS: Mean SSSs showed no significant difference between cardioBull and QPS (6.0 ± 7.1 vs. 5.6 ± 7.0). The AUC for cardioBull was equivalent to that for QPS (0.91 ± 0.04 vs. 0.87 ± 0.04, p = n.s.). Sensitivity, specificity, and accuracy for cardioBull were 89, 74, and 82%, respectively. For the regional detection of CAD, the AUC showed largest value in left anterior descending coronary artery (LAD) territory (0.86 ± 0.06 for cardioBull, 0.87 ± 0.06 for QPS, p = n.s.). Sensitivity, specificity and accuracy of cardioBull were 70, 88, and 83% for the LAD; 91, 62, and 66% for the left circumflex coronary artery (LCx); and 78, 69, and 70% for the right coronary artery (RCA), respectively. CONCLUSIONS: The AUC, sensitivity, specificity and accuracy for the detection of CAD showed high diagnostic performance on the developed software. In addition, the developed software provided comparable diagnostic performance to the commercially available software package.

Asymmetric borane reduction of prochiral ketone using chiral bis(alpha, alpha-diphenyl-2-pyrrolidinemethanol) carbonate.

Chiral bis(alpha, alpha-diphenyl-2-pyrrolidinemethanol) carbonate (DPP(2).H(2)CO(3)) is a useful asymmetric auxiliary for the asymmetric borane reduction of prochiral ketones. Chiral DPP(2).H(2)CO(3) is recoverable from the reaction and directly reusable for the reaction. The intermediate of KUR-1246, which we are developing as a new uterine relaxant, was synthesized using the methodology.