Relationship Between Impaired Microvascular Function in the Non-Infarct-Related Area and Left Ventricular Remodeling in Patients With Myocardial Infarction

Background. Myocardial flow reserve (MFR) in the non-infarct-related area (NIRA) has been reported to be impaired after the onset of myocardial infarction (MI). The aim of this study was to determine whether microvascular dysfunction in the NIRA is related to left-ventricular remodeling after MI. Methods. We prospectively studied 17 patients who suffered their first single-vessel MI, and who underwent successful revascularization. The MFR in the NIRA was assessed quantitatively using ^13N-ammonia positron emission tomography within 2 weeks after the onset. Peak creatinine kinase and the defect score on ^<99m>Tc-tetrofosmin myocardial perfusion imaging were used as an index of the severity of MI. The left-ventricular end-diastolic volume index (LVEDVI) was calculated using left ventriculography at 1 month and 6 months after the onset. Results. Patients with severely impaired MFR (< 2.09) had higher peak creatinine kinase values (6,000 ± 5,485 IU/L vs. 2,250 ± 1,950 IU/L, p = 0.0081), defect scores (16.3 ± 5.9 vs. 7.9 ± 6.5, p = 0.0404), and LVEDVI at 1 month (125.6 ± 34.4 mL/m^2 vs. 82.8 ± 17.7 mL/m^2, p = 0.0036) than those with mildly impaired MFR (≥ 2.09). Moreover, the differences of LVEDVI between the 2 groups persisted over 6 months (133.3 ± 43.6 mL/m^2 vs. 89.5 ± 17.3 mL/m^2, p = 0.0078). The MFR in the NIRA correlated inversely with the LVEDVI at 1 month and 6 months (r = -0.590, p = 0.0127 and r = -0.729, p = 0.0031, respectively). Conclusions. These data indicate that microvascular impairment in the NIRA might have contributed to left-ventricular remodeling after MI

Age-dependent plasticity in the superior temporal sulcus in deaf humans: a functional MRI study

BACKGROUND: Sign-language comprehension activates the auditory cortex in deaf subjects. It is not known whether this functional plasticity in the temporal cortex is age dependent. We conducted functional magnetic-resonance imaging in six deaf signers who lost their hearing before the age of 2 years, five deaf signers who were >5 years of age at the time of hearing loss and six signers with normal hearing. The task was sentence comprehension in Japanese sign language. RESULTS: The sign-comprehension tasks activated the planum temporale of both early- and late-deaf subjects, but not that of hearing signers. In early-deaf subjects, the middle superior temporal sulcus was more prominently activated than in late-deaf subjects. CONCLUSIONS: As the middle superior temporal sulcus is known to respond selectively to human voices, our findings suggest that this subregion of the auditory-association cortex, when deprived of its proper input, might make a functional shift from human voice processing to visual processing in an age-dependent manner

Prognostic value of an increased in flourine-18 deoxyglucose uptake in patients with myocardial infarction: Comparision with stress thallium imaging

AbstractObjectives. This study was undertaken to evaluate the prognostic value of an increase in fluorine (F)-18 deoxyglucose uptake compared wilh clinical, angiographic and stress thallium findings in patients with myocardial infarction.Background. Positron emission tomography (PET) imaging using F-18 deoxyglucose has been applied to assess tissue viability in patients with coronary artery disease. We hypothesized that patients with a myocardial segment with augmented F-18 deoxyglucose uptake are at high risk for a future cardiac event.Methods. One hundred fifty-eight consecutive patients with myocardial infarction referred for F-18 deoxyglucose PET and stress thallium scans were studied. Follow-up was obtained in 84 patients at a mean interval of 23 months to investigate prognostic implications of radionuclide studies.Results. Seventeen patients had a cardiac event during the follow-up interval. Univariate analysis showed that an increase in F-18 deosyglucose uptake was the best predictor of a future cardiac event (p = 0.0006), followed by the number of stenosed vessels (p = 0.008). In the multivariate analysis, when an increase in F-18 deoxyglucose uptake was entered into the model, only angiographic variables had an independent value, whereas no other radionuclide variables showed value. Among patients who did not show redistribution, a future cardiac event was observed more often in patients with than in those without an increase in F-18 deoxyglucose uptake (p < 0.05).Conclusions. Thus, an increase in F-18 deoxyglucose uptake seemed to be the best predictor of a future cardiac event among all clinical, angiographic and redionuclide variables in this study of stable patients with myocardial infarction. Even when a stress thallium-201 scan does not show redistribution, those patients who have an increase in F-18 deoxyglucose uptake in a PET study may be at risk for a future cardiac event, and these patients may need aggressive treatment to prevent a future cardiac event

Molecular imaging: a novel tool for translational research

分子イメージングの概要とその背景について概説し，腫瘍の治療に向けた新しい機能画像診断のさまざまな取り組みについて紹介した。-1st Hokkaido International Crosscutting Symposium: Molecular Bio-imaging and 4D Image-guided Radiotherap

Molecular Therapy of Human Neuroblastoma Cells Using Auger Electrons of 111In-Labeled N-myc Antisense Oligonucleotides

Auger electrons can create breaks in nucleic acids, giving them possible therapeutic utility. We investigated the therapeutic effect of Auger electrons emitted by 111In-labeled phosphorothioate antisense oligonucleotides on human neuroblastoma cells in which N-myc was overexpressed. METHODS: Human SK-N-DZ neuroblastoma cells (5 x 10(6) cells) were treated with cationic reverse-phase evaporation vesicles (REVs) encapsulating 111In-labeled antisense (40 MBq/2 nmol of oligonucleotides/mumol of total phospholipids) that had an average diameter of 250 nm. Hybridization of the radiolabeled oligonucleotides with N-myc messenger RNA (mRNA), N-myc expression, and cell proliferation were investigated. The tumorigenicity of treated cells was analyzed in nude mice. Nonradiolabeled antisense, 111In-labeled sense, or empty cationic REVs were used as controls. RESULTS: 111In-Labeled antisense, which hybridized with N-myc mRNA, was detected in cells at 12 and 24 h after the initiation of treatment. Reduced N-myc expression and inhibited cell proliferation were shown in the same cells at 48 h after the completion of treatment. N-myc expression-suppressed cells produced intraperitoneal tumors in nude mice, but the average weight of the tumors was lower than that of tumors in control mice. CONCLUSION: Auger electrons emitted from 111In in close proximity to their target N-myc mRNA may prolong the time to cell proliferation in human neuroblastoma cells due to inhibition of the translation of N-myc. Auger electron therapy therefore has potential as an internally delivered molecular radiotherapy targeting the mRNA of a tumor cell

Double-tracer autoradiography with Cu-ATSM/FDG and immunohistochemical interpretation in four different mouse implanted tumor models

Background: We studied the regional characteristics within tumor masses using PET tracers and immunohistochemical methods.Methods: The intratumoral distribution of 64Cu-diacetyl-bis(N4-methylthiosemicarbazone) ([64Cu]Cu-ATSM) and [18F] 2-fluoro-2-deoxyglucose (18F]FDG) in mice with tumors of four different origins (LLC1, Meth-A, B16 and colon26) was compared with theimmunohistochemical staining of proliferating cells (Ki67), blood vessels (CD34 or von Willebrand factor), and apoptotic cells (terminaldeoxynucleotidyltransferase-mediated dUTP nick end labeling method).Results: With all cell lines, [64Cu]Cu-ATSM and [18F]FDG were distributed with different gradation in the tumor mass. Theimmunohistochemical study demonstrated that the high [64Cu]Cu-ATSM uptake regions were hypovascular and consisted of tumor cellsarrested in the cell cycle, whereas the high [18F]FDG uptake regions were hypervascular and consisted of proliferating cells.Conclusion: In our study, it was revealed that one tumor mass contained two regions with different characteristics, which could bedistinguished by [64Cu]Cu-ATSM and [18F]FDG. Because hypoxia and cell cycle arrest are critical factors to reduce tumor sensitivity toradiation and conventional chemotherapy, regions with such characteristics should be treated intensively as one of the primary targets.[64Cu]Cu-ATSM, which can delineate hypoxic and cell cycle-arrested regions in tumors, may provide valuable information for cancertreatment as well as possibly for treating such regions directly as an internal radiotherapy reagent.D 2006 Elsevier Inc. All rights reserved.Keywords: Cu-ATSM; FDG; Hypoxia; Immunohistochemistry; Cancer imagin