Multicenter cross-calibration of I-123 metaiodobenzylguanidine heart-tomediastinum ratios to overcome camera-collimator variations

Background The heart-to-mediastinum ratio (HMR) of 123I-metaiodobenzylguanidine (MIBG) showed variations among institutions and needs to be standardized among various scinticamera-collimator combinations. Methods A total of 225 phantom experiments were performed in 84 institutions to calculate cross-calibration coefficients of HMR. Based on phantom studies, a conversion coefficient for each camera-collimator system was created, including low-energy (LE, n = 125) and a medium-energy (ME, n = 100) collimators. An average conversion coefficient from the most common ME group was used to calculate the standard HMR. In clinical MIBG studies (n = 52) from three institutions, HMRs were standardized from both LE- and ME-type collimators and classified into risk groups of <1.60, 1.60-2.19, and ≥2.20. Results The average conversion coefficients from the individual camera-collimator condition to the mathematically calculated reference HMR ranged from 0.55 to 0.75 for LE groups and from 0.83 to 0.95 for ME groups. The conversion coefficient of 0.88 was used to unify HMRs from all acquisition conditions. Using the standardized HMR, clinical studies (n = 52) showed good agreement between LE and ME types regarding three risk groups (κ = 0.83, P < .0001, complete agreement in 90%, 42% of the patients reclassified into the same risk group). Conclusion By using the reference HMR and conversion coefficients for the system, HMRs with various conditions can be converted to the standard HMRs in a range of normal to low HMRs

Enhanced diagnostic accuracy for quantitative bone scan using an artificial neural network system: A Japanese multi-center database project

Background Artificial neural network (ANN)-based bone scan index (BSI), a marker of the amount of bone metastasis, has been shown to enhance diagnostic accuracy and reproducibility but is potentially affected by training databases. The aims of this study were to revise the software using a large number of Japanese databases and to validate its diagnostic accuracy compared with the original Swedish training database. Methods The BSI was calculated with EXINIbone (EB; EXINI Diagnostics) using the Swedish training database (n = 789). The software using Japanese training databases from a single institution (BONENAVI version 1, BN1, n = 904) and the revised version from nine institutions (version 2, BN2, n = 1,532) were compared. The diagnostic accuracy was validated with another 503 multi-center bone scans including patients with prostate (n = 207), breast (n = 166), and other cancer types. The ANN value (probability of abnormality) and BSI were calculated. Receiver operating characteristic (ROC) and net reclassification improvement (NRI) analyses were performed. Results The ROC analysis based on the ANN value showed significant improvement from EB to BN1 and BN2. In men (n = 296), the area under the curve (AUC) was 0.877 for EB, 0.912 for BN1 (p = not significant (ns) vs. EB) and 0.934 for BN2 (p = 0.007 vs. EB). In women (n = 207), the AUC was 0.831 for EB, 0.910 for BN1 (p = 0.016 vs. EB), and 0.932 for BN2 (p < 0.0001 vs. EB). The optimum sensitivity and specificity based on BN2 was 90% and 84% for men and 93% and 85% for women. In patients with prostate cancer, the AUC was equally high with EB, BN1, and BN2 (0.939, 0.949, and 0.957, p = ns). In patients with breast cancer, the AUC was improved from EB (0.847) to BN1 (0.910, p = ns) and BN2 (0.924, p = 0.039). The NRI using ANN between EB and BN1 was 17.7% (p = 0.0042), and that between EB and BN2 was 29.6% (p < 0.0001). With respect to BSI, the NRI analysis showed downward reclassification with total NRI of 31.9% (p < 0.0001). Conclusion In the software for calculating BSI, the multi-institutional database significantly improved identification of bone metastasis compared with the original database, indicating the importance of a sufficient number of training databases including various types of cancers. © 2013 Nakajima et al

Nuclear medicine practice in Japan: a report of the seventh nationwide survey in 2012

Objective The Subcommittee on the Survey of Nuclear Medical Practice in Japan has performed a nationwide survey of nuclear medicine practice every 5 years since 1982 to survey contemporary nuclear medicine practice and its changes over the years. Methods The subcommittee sent questionnaires, including the number and category of examinations as well as the kind and dose of the radiopharmaceuticals during the 30 days of June 2012, to all the nuclear medicine institutes. The total numbers for the year 2012 were then estimated. Results A total of 1,167 institutes responded to the survey, including the 14 in vitro assay institutes and 266 PET centers. The recovery rate was 92 %. The number of gamma cameras installed was 1,425 in total, with 9 % decrease in 5 years. Dual-head cameras and hybrid SPECT/CT scanners accounted for 84 and 10.5 %, respectively. The number of single-photon tracer studies in 2012 was 1.15 million which means decrease in 19 % in 5 years and 29 % in 10 years. All but cerebral perfusion study and sentinel lymphoscintigraphy have decreased. Bone scintigraphy was a leading examination (38.7 %), followed by cardiac studies (29.4 %) and cerebral perfusion study (18.5 %) in order. SPECT studies showed an increase from 42.3 to 47.2 %. PET centers have also increased from 212 to 295, as compared to the last survey. The 135 PET centers have installed one or two in-house cyclotrons. PET studies showed 25.5 % increase in 5 years, with oncology accounting for 96.3 %. 18F-FDG accounted for 98.2 % (505,990 examinations). PET examinations using 11C-methionine have been increasing, with 3,352 examinations in 2012. The number of new PET studies using 11C-PIB PET was 695. 131I-radioiodine targeted therapies showed an increase, including 3,644 patients (53.6 %) for thyroid cancer and 4,889 patients (17.9 %) for hyperthyroidism. Out-patient thyroid bed ablation therapy with 30 mCi of 131I accounted for 21.0 % of cancer patients. The number of admission rooms decreased from 158 to 135 in 5 years. In vitro radioassays have been declining continuously since 1992, with the number of studies of 9.0 million in 2012. Conclusions Single-photon examinations showed a continuous tendency toward a decline in the survey. In contrast, the number of hybrid SPECT/CT scanner examinations has increased. PET/CT study in the oncology field and radionuclide targeted therapy have steadily increased. © 2014 The Japanese Society of Nuclear Medicine

Non-invasive diagnostic tests for Helicobacter pylori infection

BACKGROUND: Helicobacter pylori (H pylori) infection has been implicated in a number of malignancies and non-malignant conditions including peptic ulcers, non-ulcer dyspepsia, recurrent peptic ulcer bleeding, unexplained iron deficiency anaemia, idiopathic thrombocytopaenia purpura, and colorectal adenomas. The confirmatory diagnosis of H pylori is by endoscopic biopsy, followed by histopathological examination using haemotoxylin and eosin (H & E) stain or special stains such as Giemsa stain and Warthin-Starry stain. Special stains are more accurate than H & E stain. There is significant uncertainty about the diagnostic accuracy of non-invasive tests for diagnosis of H pylori. OBJECTIVES: To compare the diagnostic accuracy of urea breath test, serology, and stool antigen test, used alone or in combination, for diagnosis of H pylori infection in symptomatic and asymptomatic people, so that eradication therapy for H pylori can be started. SEARCH METHODS: We searched MEDLINE, Embase, the Science Citation Index and the National Institute for Health Research Health Technology Assessment Database on 4 March 2016. We screened references in the included studies to identify additional studies. We also conducted citation searches of relevant studies, most recently on 4 December 2016. We did not restrict studies by language or publication status, or whether data were collected prospectively or retrospectively. SELECTION CRITERIA: We included diagnostic accuracy studies that evaluated at least one of the index tests (urea breath test using isotopes such as13C or14C, serology and stool antigen test) against the reference standard (histopathological examination using H & E stain, special stains or immunohistochemical stain) in people suspected of having H pylori infection. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the references to identify relevant studies and independently extracted data. We assessed the methodological quality of studies using the QUADAS-2 tool. We performed meta-analysis by using the hierarchical summary receiver operating characteristic (HSROC) model to estimate and compare SROC curves. Where appropriate, we used bivariate or univariate logistic regression models to estimate summary sensitivities and specificities. MAIN RESULTS: We included 101 studies involving 11,003 participants, of which 5839 participants (53.1%) had H pylori infection. The prevalence of H pylori infection in the studies ranged from 15.2% to 94.7%, with a median prevalence of 53.7% (interquartile range 42.0% to 66.5%). Most of the studies (57%) included participants with dyspepsia and 53 studies excluded participants who recently had proton pump inhibitors or antibiotics.There was at least an unclear risk of bias or unclear applicability concern for each study.Of the 101 studies, 15 compared the accuracy of two index tests and two studies compared the accuracy of three index tests. Thirty-four studies (4242 participants) evaluated serology; 29 studies (2988 participants) evaluated stool antigen test; 34 studies (3139 participants) evaluated urea breath test-13C; 21 studies (1810 participants) evaluated urea breath test-14C; and two studies (127 participants) evaluated urea breath test but did not report the isotope used. The thresholds used to define test positivity and the staining techniques used for histopathological examination (reference standard) varied between studies. Due to sparse data for each threshold reported, it was not possible to identify the best threshold for each test.Using data from 99 studies in an indirect test comparison, there was statistical evidence of a difference in diagnostic accuracy between urea breath test-13C, urea breath test-14C, serology and stool antigen test (P = 0.024). The diagnostic odds ratios for urea breath test-13C, urea breath test-14C, serology, and stool antigen test were 153 (95% confidence interval (CI) 73.7 to 316), 105 (95% CI 74.0 to 150), 47.4 (95% CI 25.5 to 88.1) and 45.1 (95% CI 24.2 to 84.1). The sensitivity (95% CI) estimated at a fixed specificity of 0.90 (median from studies across the four tests), was 0.94 (95% CI 0.89 to 0.97) for urea breath test-13C, 0.92 (95% CI 0.89 to 0.94) for urea breath test-14C, 0.84 (95% CI 0.74 to 0.91) for serology, and 0.83 (95% CI 0.73 to 0.90) for stool antigen test. This implies that on average, given a specificity of 0.90 and prevalence of 53.7% (median specificity and prevalence in the studies), out of 1000 people tested for H pylori infection, there will be 46 false positives (people without H pylori infection who will be diagnosed as having H pylori infection). In this hypothetical cohort, urea breath test-13C, urea breath test-14C, serology, and stool antigen test will give 30 (95% CI 15 to 58), 42 (95% CI 30 to 58), 86 (95% CI 50 to 140), and 89 (95% CI 52 to 146) false negatives respectively (people with H pylori infection for whom the diagnosis of H pylori will be missed).Direct comparisons were based on few head-to-head studies. The ratios of diagnostic odds ratios (DORs) were 0.68 (95% CI 0.12 to 3.70; P = 0.56) for urea breath test-13C versus serology (seven studies), and 0.88 (95% CI 0.14 to 5.56; P = 0.84) for urea breath test-13C versus stool antigen test (seven studies). The 95% CIs of these estimates overlap with those of the ratios of DORs from the indirect comparison. Data were limited or unavailable for meta-analysis of other direct comparisons. AUTHORS' CONCLUSIONS: In people without a history of gastrectomy and those who have not recently had antibiotics or proton ,pump inhibitors, urea breath tests had high diagnostic accuracy while serology and stool antigen tests were less accurate for diagnosis of Helicobacter pylori infection.This is based on an indirect test comparison (with potential for bias due to confounding), as evidence from direct comparisons was limited or unavailable. The thresholds used for these tests were highly variable and we were unable to identify specific thresholds that might be useful in clinical practice.We need further comparative studies of high methodological quality to obtain more reliable evidence of relative accuracy between the tests. Such studies should be conducted prospectively in a representative spectrum of participants and clearly reported to ensure low risk of bias. Most importantly, studies should prespecify and clearly report thresholds used, and should avoid inappropriate exclusions

Genetic analysis of body weight in wild populations of medaka fish from different latitudes.

The genetic bases of growth and body weight are of economic and scientific interest, and teleost fish models have proven useful in such investigations. The Oryzias latipes species complex (medaka) is an abundant freshwater fish in Japan and suitable for genetic studies. We compared two wild medaka stocks originating from different latitudes. The Maizuru population from higher latitudes weighed more than the Ginoza population. We investigated the genetic basis of body weight, using quantitative trait locus (QTL) analysis of the F2 offspring of these populations. We detected one statistically significant QTL for body weight on medaka chromosome 4 and identified 12 candidate genes that might be associated with body weight or growth. Nine of these 12 genes had at least one single nucleotide polymorphism that caused amino acid substitutions in protein-coding regions, and we estimated the effects of these substitutions. The present findings might contribute to the marker-assisted selection of economically important aquaculture species