Immunohistochemical analysis of P-glycoprotein expression in diverse histological types of epithelial ovarian tumors.

P-glycoprotein is a transmembrane protein which acts as an energy-dependent drug efflux pump for a variety of anti-cancer drugs. The mdr-1 gene which encodes P-glycoprotein was successfully cloned in 1986. To investigate P-glycoprotein expression in diverse ovarian tumors, including benign, low malignant potential and malignant, immunohistochemical study was done using a monoclonal antibody (C 219). Overall, 8 out of the 59 epithelial ovarian tumors (13.6%) expressed P-glycoprotein. It was noted that 5 of the 12 mucinous tumors were found to express P-glycoprotein, while none of the 31 serous tumors were immunohistochemically positive. In 10 malignant ovarian tumors, P-glycoprotein immunostaining was examined both prior to and after chemotherapy. Nine of them did not express any P-glycoprotein before or after chemotherapy. However, one tumor expressed P-glycoprotein after six courses of multidrug resistance-related drug administration. These findings indicate that P-glycoprotein expression is not so common in ovarian tumors, regardless of their malignant potential. Nevertheless, the results suggest a strong association between P-glycoprotein expression and certain histological cell types in epithelial ovarian tumors. It is also possible that P-glycoprotein appears as a result of chemotherapy, but such a phenomenon can not occur unless chemotherapy is administered at high doses for a long period of time.</p

Cause of apical thinning on attenuation-corrected myocardial perfusion SPECT

Objectives: Decreases in apical and apex activities - namely, \u27apical thinning\u27 - are a well-known phenomenon in attenuation-corrected (AC) myocardial perfusion. The aim of this study was to compare actual myocardial thickness derived from a multidetector-row computed tomography with AC myocardial perfusion count from a hybrid single-photon emission computed tomography/computed tomography to investigate the cause of apical thinning. Methods: We enrolled 21 participants with a low likelihood of coronary artery disease (mean age 65±21 years, 13 men) from 185 consecutive patients and 11 healthy volunteers, who independently underwent Tc-sestamibi single-photon emission computed tomography/computed tomography and 64-slice multidetector-row computed tomography scans. AC and non-AC myocardial perfusion counts and thickness were measured on the basis of a 17-segment model and averaged at the apex, apical, mid, and basal walls. Results: Myocardial thickness at the apex was significantly thinner than that at the apical and mid walls (5.1±1.3, 7.3±1.3, and 9.9±2.4 mm, respectively; P<0.005). AC count at the apex was significantly lower than that at the apical and mid regions (76.0±5.5, 82.8±4.7, and 85.6±3.8, respectively; P<0.002). Moderate relationship was observed between myocardial thickness and AC count (y=-10.5+0.22x, r=0.54, P<0.0001. No relationship was found between thickness and non-AC count (r=0.16, P=0.263). Conclusion: The low apex and apical counts were caused by anatomical thinning of the myocardium in AC myocardial perfusion imaging. Attenuation correction provided an accurate relationship between myocardial count and thickness because of the partial volume effect. © 2011 Wolters Kluwer Health | Lippincott Williams and Wilkins

Clinical usefulness of novel cardiac MDCT/SPECT fusion image

金沢大学附属病院核医学診療科Background: We evaluated the relationship between computed tomography angiography (CTA) and SPECT, and assessed to determine the clinical usefulness of the fusion image using CTA and myocardial perfusion imaging (MPI). Methods: Forty-one consecutive patients [after coronary artery bypass operation (n = 13) and suspected stenosis (n = 28)] underwent MPI and CTA. SPECT/CTA fused images were generated. Results: In total, 687 segments including bypass graft in 164 coronary arteries were analyzed. Myocardial ischemia on MPI was observed in 11 patients among 28 with CTA abnormalities, one had both ischemia and infarction, and 7 had only infarction. Segment-based analysis showed that ischemia was found in 14 segments (24%) among 59 stenoses on CTA. Forty stenotic segments (69%) were not associated with perfusion abnormality. The rest 5 stenotic segments were considered equivocal (8%). A fusion image made it possible to associate perfusion defects with its corresponding coronary artery in 4 out of 5 equivocal lesions on side-by-side analysis. Patients with incremental diagnostic information on SPECT/CTA fusion (n = 4) had significant smaller coronary diameter than that of not-improved coronary vessels (2.0 ± 0.4 vs. 3.9 ± 0.4 mm, p = 0.001). Conclusion: Cardiac fusion imaging accurately diagnosed functionally relevant coronary stenosis. SPECT/CTA fusion images in coronary artery disease may provide added diagnostic information on functional relevance of coronary artery disease. © 2009 The Japanese Society of Nuclear Medicine

Standardization of metaiodobenzylguanidine heart to mediastinum ratio using a calibration phantom: effects of correction on normal databases and a multicentre study

Purpose: This study was performed to demonstrate that the results obtained with a calibration phantom could be used as a tool for standardizing measurement of heart to mediastinum (H/M) ratio in cardiac metaiodobenzylguanidine (MIBG) imaging. Methods: Images of the phantom containing 123I-MIBG were acquired on the cameras in 10 hospitals (11 camera types) to determine the relationship between H/M ratios using different collimators: low-energy (LE) and medium-energy (ME)/low-medium-energy (LME) collimators. The effect of standardization on the ME-comparable H/M ratio was examined in two settings: a Japanese standard MIBG database (n = 62) and multicentre studies (n = 49). In a multicentre study, probable Alzheimer\u27s disease (AD, n = 18) and probable dementia with Lewy bodies (DLB, n = 31) were studied and standardized by the calibration phantom method. Results: Linear regression equations between LE and ME collimators were obtained for the phantom study in all institutions. When the H/M ratio with an LE collimator was corrected based upon the calibration phantom, the corrected values were comparable to those obtained using ME collimators. The standard database also exhibited a normal distribution after standardization as determined by skewness and goodness-of-fit test. A mixture of the populations by LE and ME collimators showed significant separation of AD and DLB groups (F ratio = 24.9 for the late H/M), but the corrected values resulted in higher F ratios for both early and late H/M (F ratio = 34.9 for the late H/M). Conclusion: Standardization of H/M ratios by the heart-chest calibration phantom method is feasible among different collimator types. This method could be practically used for multicentre comparison of H/M ratios. © 2011 Springer-Verlag

Regional wall thickening in gated myocardial perfusion SPECT in a Japanese population: Effect of sex, radiotracer, rotation angles and frame rates

金沢大学医薬保健研究域医学系Purpose: Gated single-photon emission computed tomography (SPECT) imaging of myocardium by 99mTc and 201Tl is used extensively to measure quantitative cardiac functional parameters. However, factors affecting normal values for myocardial functional parameters and population-specific standards have not yet been established. The aim of the study was to determine the effect of sex, radiotracer, rotation angles and frame rates on resting myocardial wall thickening (WT) and to develop a Japanese standard of normal values for WT. Methods: Data from a total of 202 patients with low possibility of having cardiac problems were collected from nine hospitals throughout Japan. Patients were divided into five groups according to study protocol, and WT was evaluated according to the 17-segment and four-region (basal, mid and apical regions and the apex) polar map distribution. Result: WT was generally higher in women than in men irrespective of the use of radiotracers, rotation angles or frame rates, and the difference was highly significant in the mid and apical regions. In any protocol used, resting myocardial thickening in the apex was higher than in the mid and apical regions, and thickening was lowest in the basal region, suggesting heterogeneous regional myocardial thickening (%) in normal subjects. Different rotation angles showed no significant change on WT, but different frame rates and tracers showed significant WT change in both sexes. Percent thickening of the myocardium was significantly higher in imaging by 99mTc-labelled tracers than in 201Tl. Conclusion: Sex, radiotracers and frame rates had a significant effect on myocardial thickening, and the importance of population-specific standards should be emphasized. A normal database can serve as a standard for gated SPECT evaluation of myocardial thickening in a Japanese population and might be applicable to Asian populations having a similar physique. © 2008 Springer-Verlag.This article has not been published yet

Quantification of myocardial perfusion SPECT using freeware package (cardioBull)

Objective: We have developed freeware package for automatically quantifying myocardial perfusion and 123I-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 99mTc-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. © 2011 The Japanese Society of Nuclear Medicine

The validity of multi-center common normal database for identifying myocardial ischemia: Japanese Society of Nuclear Medicine Working Group Database

金沢大学医薬保健研究域医学系Purpose The Japanese Society of Nuclear Medicine (JSNM) working group has created a myocardial perfusion imaging database applicable to standard acquisition protocol. The aim of this study is to validate the diagnostic accuracy of the common normal database compared with the expert interpretation of each institute. Methods Five institutions participated in this study and used different acquisition settings which included 360°/ 180° rotation, camera configuration and camera orbits. The software and its version used in each institution also varied. The working group database was applied to detect the culprit coronary territory from a total of 166 patients with coronary artery disease (CAD) and 145 patients with lowlikelihood of CAD. Results When summed stress score C4 was defined as significant abnormality, overall sensitivity, specificity and accuracy of patient-based analysis were 77, 72 and 75%, respectively, based on quantitative analysis using the common database, whereas those by institutional visual expert reading were 72, 79 and 75%, respectively. Conclusion The common database, which was created by a multi-center working group and separated between male/ female with 180/360° acquisitions, demonstrated comparable diagnostic accuracy to expert interpretation by each institute, and it may be applicable to multi-center studies

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

金沢大学附属病院核医学診療科Background: Although the heart-to-mediastinum (H/M) ratio in a planar image has been used for practical quantification in 123I- 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 123I- 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. © 2008 Springer-Verlag