Mana Ishibashi

Detection and localization of prostate cancer with the targeted biopsy strategy based on ADC Map: A prospective large-scale cohort study

To investigate the usefulness of targeted biopsy strategy based on apparent diffusion coefficient (ADC) maps in the detection and localization of prostate cancer.

Can Complementary 68Ga-DOTATATE and 18F-FDG PET/CT Establish the Missing Link Between Histopathology and Therapeutic Approach in Gastroenteropancreatic Neuroendocrine Tumors?

Gastroenteropancreatic neuroendocrine tumors (GEPNETs) are indolent neoplasms presenting unpredictable and unusual biologic behavior that causes many clinical challenges. Tumor size, existence of metastasis, and histopathologic classification remain incapable in terms of treatment decision and prognosis estimation. This study aimed to compare 68Ga-DOTATATE and 18F-FDG PET/CT in GEPNETs and to investigate the relation between the complementary PET/CT results and histopathologic findings in the management of therapy, particularly in intermediate-grade patients. Methods: The relation between complementary 68Ga-DOTATATE and 18F-FDG PET/CT results of 27 GEPNET patients (mean age, 56 y; age range, 33–79 y) and histopathologic findings was evaluated according to grade and localization using standardized maximum uptake values and Ki67 indices. Grade 2 (G2) patients were further evaluated in 2 groups as G2a (3%–9%) and G2b (10%–20%) according to Ki67 indices. Results: The sensitivity of 68Ga-DOTATATE and 18F-FDG PET/CT was 95% and 37%, respectively, and the positive predictive values were 93.8% and 36.2%, respectively. The sensitivity in detecting liver metastasis, lymph nodes, bone metastasis, and primary lesion was 95%, 95%, 90%, and 93% for 68Ga-DOTATATE and 40%, 28%, 28%, and 75% for 18F-FDG, respectively. Statistically significant differences were found between grades 1–2, 2a–2b, and 1–2b with respect to 68Ga-DOTATATE PET/CT as well as between 1–2a and 1–2b with respect to 18F-FDG PET/CT. However, no statistical differences were found between 1 and 2a (P > 0.05) for 68Ga-DOTATATE and 2a and 2b (P = 0.484) for 18F-FDG. The impact of the combined 18F-FDG and 68Ga-DOTATATE PET/CT on the therapeutic decision was 59%. Conclusion: Combined 68Ga-DOTATATE and 18F-FDG PET/CT is helpful in the individual therapeutic approach of GEPNETs and can overcome the shortcomings of histopathologic grading especially in intermediate-grade GEPNETs.

Cell-sheet Therapy With Omentopexy Promotes Arteriogenesis and Improves Coronary Circulation Physiology in Failing Heart

Cell-sheet transplantation induces angiogenesis for chronic myocardial infarction (MI), though insufficient capillary maturation and paucity of arteriogenesis may limit its therapeutic effects. Omentum has been used clinically to promote revascularization and healing of ischemic tissues. We hypothesized that cell-sheet transplantation covered with an omentum-flap would effectively establish mature blood vessels and improve coronary microcirculation physiology, enhancing the therapeutic effects of cell-sheet therapy. Rats were divided into four groups after coronary ligation; skeletal myoblast cell-sheet plus omentum-flap (combined), cell-sheet only, omentum-flap only, and sham operation. At 4 weeks after the treatment, the combined group showed attenuated cardiac hypertrophy and fibrosis, and a greater amount of functionally (CD31(+)/lectin(+)) and structurally (CD31(+)/α-SMA(+)) mature blood vessels, along with myocardial upregulation of relevant genes. Synchrotron-based microangiography revealed that the combined procedure increased vascularization in resistance arterial vessels with better dilatory responses to endothelium-dependent agents. Serial (13)N-ammonia PET showed better global coronary flow reserve in the combined group, mainly attributed to improvement in the basal left ventricle. Consequently, the combined group had sustained improvements in cardiac function parameters and better functional capacity. Cell-sheet transplantation with an omentum-flap better promoted arteriogenesis and improved coronary microcirculation physiology in ischemic myocardium, leading to potent functional recovery in the failing heart.

Paradoxical reduction of cerebral blood flow after acetazolamide loading: a hemodynamic and metabolic study with (15)O PET.

Paradoxical reduction of cerebral blood flow (CBF) after administration of the vasodilator acetazolamide is the most severe stage of cerebrovascular reactivity failure and is often associated with an increased oxygen extraction fraction (OEF). In this study, we aimed to reveal the mechanism underlying this phenomenon by focusing on the ratio of CBF to cerebral blood volume (CBV) as a marker of regional cerebral perfusion pressure (CPP). In 37 patients with unilateral internal carotid or middle cerebral arterial (MCA) steno-occlusive disease and 8 normal controls, the baseline CBF (CBFb), CBV, OEF, cerebral oxygen metabolic rate (CMRO2), and CBF after acetazolamide loading in the anterior and posterior MCA territories were measured by 15O positron emission tomography. Paradoxical CBF reduction was found in 28 of 74 regions (18 of 37 patients) in the ipsilateral hemisphere. High CBFb (>47.6 mL/100 mL/min, n = 7) was associated with normal CBFb/CBV, increased CBV, decreased OEF, and normal CMRO2. Low CBFb (<31.8 mL/100 mL/min, n = 9) was associated with decreased CBFb/CBV, increased CBV, increased OEF, and decreased CMRO2. These findings demonstrated that paradoxical CBF reduction is not always associated with reduction of CPP, but partly includes high-CBFb regions with normal CPP, which has not been described in previous studies.

CBF/CBV maps in normal volunteers studied with (15)O PET: a possible index of cerebral perfusion pressure.

Local cerebral perfusion pressure (CPP) is a primary factor controlling cerebral circulation and previous studies have indicated that the ratio of cerebral blood flow (CBF) to cerebral blood volume (CBV) can be used as an index of the local CPP. In this study, we investigated whether the CBF/CBV ratio differs among different brain structures under physiological conditions, by means of 15O positron emission tomography. Nine healthy volunteers (5 men and 4 women; mean age, 47.0 ± 1.2 years) were studied by H215O bolus injection for CBF measurement and by C15O inhalation for CBV measurement. The CBF/CBV ratio maps were created by dividing the CBF images by the CBV images after anatomical normalization. Regions of interest were placed on the CBF/CBV maps and comparing the regions. The mean CBF/CBV ratio was highest in the cerebellum (19.3 ± 5.2/min), followed by the putamen (18.2 ± 3.9), pons (16.4 ± 4.6), thalamus (14.5 ± 3.3), cerebral cortices (13.2 ± 2.4), and centrum semiovale (11.5 ± 2.1). The cerebellum and putamen showed significantly higher CBF/CBV ratios than the cerebral cortices and centrum semiovale. We created maps of the CBF/CBV ratio in normal volunteers and demonstrated higher CBF/CBV ratios in the cerebellum and putamen than in the cerebral cortices and deep cerebral white matter. The CBF/CBV may reflect the local CPP and should be studied in hemodynamically compromised patients and in patients with risk factors for small-artery diseases of the brain.

Distribution of Intravenously Administered Acetylcholinesterase Inhibitor and Acetylcholinesterase Activity in the Adrenal Gland: 11C-Donepezil PET Study in the Normal Rat

Purpose Acetylcholinesterase (AChE) inhibitors have been used for patients with Alzheimers disease. However, its pharmacokinetics in non-target organs other than the brain has not been clarified yet. The purpose of this study was to evaluate the relationship between the whole-body distribution of intravenously administered 11C-Donepezil (DNP) and the AChE activity in the normal rat, with special focus on the adrenal glands. Methods The distribution of 11C-DNP was investigated by PET/CT in 6 normal male Wistar rats (8 weeks old, body weight  = 220±8.9 g). A 30-min dynamic scan was started simultaneously with an intravenous bolus injection of 11C-DNP (45.0±10.7 MBq). The whole-body distribution of the 11C-DNP PET was evaluated based on the Vt (total distribution volume) by Logan-plot analysis. A fluorometric assay was performed to quantify the AChE activity in homogenized tissue solutions of the major organs. Results The PET analysis using Vt showed that the adrenal glands had the 2nd highest level of 11C-DNP in the body (following the liver) (13.33±1.08 and 19.43±1.29 ml/cm3, respectively), indicating that the distribution of 11C-DNP was the highest in the adrenal glands, except for that in the excretory organs. The AChE activity was the third highest in the adrenal glands (following the small intestine and the stomach) (24.9±1.6, 83.1±3.0, and 38.5±8.1 mU/mg, respectively), indicating high activity of AChE in the adrenal glands. Conclusions We demonstrated the whole-body distribution of 11C-DNP by PET and the AChE activity in the major organs by fluorometric assay in the normal rat. High accumulation of 11C-DNP was observed in the adrenal glands, which suggested the risk of enhanced cholinergic synaptic transmission by the use of AChE inhibitors.

Intra- and inter-observer agreement in the visual interpretation of interim 18F-FDG PET/CT in malignant lymphoma: influence of clinical information

Background Interim PET/CT is widely performed in lymphoma patients in clinical practice and clinical trials. Visual assessment using a 5-point scale is proposed for PET/CT interpretation, but intra- and inter-observer variation is not fully investigated. Purpose To investigate intra- and inter-observer variations in the reporting of interim positron emission tomography/computed tomography (PET/CT) in lymphoma patients, and the influence of clinical information on the interpretation. Material and Methods Three expert readers from different institutions interpreted interim PET/CT images of 42 consecutive patients with malignant lymphoma twice, with and without clinical information. The intra- and inter-observer agreements were calculated using the kappa statistic on a patient and a region basis. Results On a patient basis, intra-observer agreement, inter-observer agreement without information, and inter-observer agreement with information were within the ranges 0.48–0.62, 0.51–0.62, and 0.42–0.76, respectively. In the evaluation of lymph nodes, intra-observer agreement, inter-observer agreement without information, and inter-observer agreement with information were within the ranges 0.78–0.92, 0.80–0.82, and 0.77–0.83, respectively. Observer agreements were in almost perfect to substantial agreement categories for most lymphatic organs, but were generally low for the other organs. Conclusion The intra- and inter-observer agreements in evaluating interim PET/CT were relatively low for extranodal lesions, but they were substantial to almost perfect when interpreting nodal regions in malignant lymphoma, irrespective of the provision of clinical information, although memory at the first interpretation might have affected the intra-observer results.

Assessment of mediastinal tumors using SUVmax and volumetric parameters on FDG PET/CT

Objective(s): This study aimed to evaluate the role of pretreatment SUVmax and volumetric FDG positron emission tomography (PET) parameters in the differentiation between benign and malignant mediastinal tumors. In addition, we investigated whether pretreatment SUVmax and volumetric FDG-PET parameters could distinguish thymomas from thymic carcinomas, and low-risk from high-risk thymomas. Methods: This study was conducted on 52 patients with mediastinal tumors undergoing FDG-PET/CT. Histological examination indicated that 29 mediastinal tumors were benign, and 23 cases were malignant. To obtain quantitative PET/CT parameters, we determined the maximum standardized uptake value (SUVmax), volumetric parameters, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for primary tumors using SUVmax cut-off value of 2.5. SUVmax, MTV and TLG of benign and malignant tumors were compared using the Mann-Whitney U test. Moreover, receiver-operating curve (ROC) analysis was applied to identify the cut-off values of SUVmax, MTV and TLG for the accurate differentiation of benign and malignant tumors. SUVmax, MTV and TLG were compared between thymomas and thymic carcinomas, as well as low-risk and high-risk thymomas. Results: Mean SUVmax, MTV and TLG of malignant mediastinal tumors were significantly higher compared to benign tumors (P<0.001). Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of SUVmax were 78.2%, 86.2%, 82.6%, 81.8%, and 83.3%, respectively. These values were estimated at 82.6%, 96.6%, 90.4%, 95%, and 87.5% for MTV and TLG, respectively. Additionally, optimal cut-off values for the differentiation of benign and malignant mediastinal tumors were determined at 4.2 and 22.3 mL and 79.7 g for SUVmax, MTV and TLG, respectively. Mean SUVmax, MTV and TLG of thymic carcinomas were significantly higher compared to thymomas (P<0.01), while no significant differences were observed in the mean quantitative parameters between low-risk and high-risk thymomas. Conclusion: Although SUVmax, MTV and TLG could not distinguish between low-risk and high-risk thymomas, these parameters might be able to differentiate benign tumors from malignant mediastinal tumors noninvasively. These parameters could be used to distinguish between thymomas and thymic carcinomas as well. Therefore, FDG-PET/CT parameters seem to be accurate indices for the detection of malignant mediastinal tumors.