Number Of False-positive Findings Research Articles

Pneumologie meets Onkologie

Lung cancer is common and associated with a high mortality. After major therapeutic advances in the palliative situation of non-small cell lung cancer (NSCLC), new therapeutic concepts including immunotherapy and targeted tumor therapy have now also reached the curative stages. Osimertinib and atezolizumab have recently been approved under certain conditions in adjuvant therapy after complete tumor resection. In addition, the first approval of a neoadjuvant immunochemotherapy in Germany is expected soon. In the palliative therapy setting, comprehensive molecular pathological diagnostics on oncogenic mutations are required. Many drugs addressing these targets are now available predominantly for first line therapy but also although less for second line therapy. If there are no possibilities to address driver mutations, immunotherapy and immunochemotherapy are available depending on the programmed death ligand 1 (PD-L1) status. Overall, these new therapeutic options have already significantly improved therapy tolerability and the prognosis of lung cancer. Specific side effects must be considered. For small cell lung cancer (SCLC), palliative immunochemotherapy provides a moderate improvement in the prognosis. The introduction of lung cancer screening by low-dose computed tomography (CT) in Germany is to be expected in the coming years. The advantages are a relative reduction in lung cancer mortality of approximately 20% with a number needed to screen of 250. The disadvantage is particularly the expected number of false positive findings. A screening program must be established as a structured and quality assured procedure.

Hypermetabolic Ipsilateral Supraclavicular and Axillary Lymphadenopathy: Optimal Time Point for Performing an 18F-FDG PET/CT after COVID-19 Vaccination.

We aimed to evaluate the incidence of severe acute respiratory syndrome coronavirus type-2 (SARS-CoV2) vaccine-related hypermetabolic lymphadenopathy (HLA) and evaluate which time point produces the least number of false-positive findings in an 18F-2-Fluor-2-desoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT). For this retrospective, multi-center imaging study, patients with any form of SARS-CoV2 vaccination prior to an 18F-FDG-PET/CT were included between January 2021 and December 2021. Patients were divided into six groups according to the time point of vaccination prior to their 18F-FDG-PET/CT imaging, e.g., group one (0-6 days) and group six (35-80 days). As the reference standards, the SUVmax of the mediastinal blood pool (MBP) and the SUVmax contralateral reference lymph node (RL) were determined. (A) The absolute SUVmax of HLA, (B) the ratio of SUVmaxHLA/SUVmax mediastinal blood pool (rHLA/MBP), (C) the ratio SUVmax HLA vs. SUVmax contralateral reference lymph node (rHLA/RL), (D) and the incidence of HLA defined as rHLA/MBP > 1.5 were assessed. Group one (days 0-6) showed the highest incidence of HLA 16/23 (70%) and rHLA/MBP (2.58 ± 2.1). All three parameters for HLA reduced statistically significantly in the comparison of Groups 1-3 (days 0-20) versus Groups 4-6 (days 21-80) (p-values < 0.001). If feasible, an FDG PET should be postponed by at least 3 weeks after SARS-CoV2 vaccination, especially if an accurate evaluation of axillary status is required.

Lesion-to-Liver SUVmax Ratio to Improve the Prognostic Value of the End of Treatment PET/CT in Diffuse Large B-Cell Lymphoma.

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. After first-line therapy, 30–40% of patients relapse or experiment with refractory disease. 18F-FDG PET/CT represents a validated diagnostic tool in post-treatment evaluation of FDG-avid lymphoma, and the Deauville Score (DS), a five-point visual scale, is usually used to assess response. However, the increased number of false positive findings suggested the need to search for new parameters. The aim of this study is to evaluate the prognostic value of End-of-Treatment-PET, comparing DS to the semi-quantitative Lesion-to-Liver ratio (LLR). Methods: newly diagnosed DLBCL patients who underwent 18F-FDG PET/CT were retrospectively analyzed. End-of-Treatment PET findings were assessed first using DS; secondly, assigned the LLR. Results: a total of 105 patients were finally enrolled. ROC analysis showed an LLR of 1.80 as the optimal cutoff value for predicting a disease progression (sensitivity 58%, specificity 95%). Both DS and LLR showed a statistically significant correlation with PFS and OS. LLR resulted in a better diagnostic performance than DS. Conclusions: LLR showed to be a reliable diagnostic method to assess treatment response in DLBCL. The integration of visual and semi-quantitative criteria could help in decision making, improving specificity and PPV.

Prostate Cancer Detection with mpMRI According to PI-RADS v2 Compared with Systematic MRI/TRUS-Fusion Biopsy: A Prospective Study.

Background: mpMRI assesses prostate lesions through their PI-RADS score. The primary goal of this prospective study was to demonstrate the correlation of PI-RADS v2 score and the volume of a lesion with the presence and clinical significance of prostate cancer (PCa). The secondary goal was to determine the extent of additionally PCa in inconspicuous areas. Methods: All 157 patients underwent a perineal MRI/TRUS-fusion prostate biopsy. Targeted biopsies as well as a systematic biopsy were performed. The presence of PCa in the probes was specified by the ISUP grading system. Results: In total, 258 lesions were biopsied. Of the PI-RADS 3 lesions, 24% were neoplastic. This was also true for 36.9% of the PI-RADS 4 lesions and for 59.5% of the PI-RADS 5 lesions. Correlation between ISUP grades and lesion volume was significant (p < 0.01). In the non-suspicious mpMRI areas carcinoma was revealed in 19.7% of the patients. Conclusions: The study shows that the PI-RADS v2 score and the lesion volume correlate with the presence and clinical significance of PCa. However, there are two major points to consider: First, there is a high number of false positive findings. Second, inconspicuous mpMRI areas revealed PCa.

Better Understanding the Population Size and Stigmatization of Psychologists Using Questionable Research Practices

There has been low confidence in the replicability and reproducibility of published psychological findings. Previous work has demonstrated that a population of psychologists exists that have used questionable research practices (QRPs), or behaviors during data collection, analysis, and publication that can increase the number of false-positive findings in the scientific literature. Across two survey studies, we sought to estimate the current size of the QRP-using population of American psychologists and to identify if this sub-population of scientists is stigmatized. Using a self-report direct estimator, we estimate approximately 18\% of American psychologists have used at least one QRP in the past 12 months. We then demonstrate the use of two additional estimators: the unmatched count estimate (an indirect self-report estimator) and the generalized network scale up method (an indirect social network estimator). Additionally, attitudes of psychologists towards QRP users, and ego network data collected from self-reported QRP users, suggest that QRP users are a stigmatized sub-population of psychologists. Together, these findings provide insight into how many psychologists are using questionable practices and how they exist in the social environment.

Contribution of ultrasound examination in the detection of unexpected uterine and adnexal findings in reconstructive surgery for pelvic organ prolapse.

The aim of the study was to evaluate the efficacy of ultrasound (USG) in dia-gnosing unexpected uterine and adnexal pathologies in women referred for POP. Furthermore, the benefit of USG examination by a specialist in gynaecology-oncology ultrasound was assessed. All women after a hysterectomy with or without adnexectomy in the course of a POP surgery at our tertiary centre in 2013-2018 with preoperative USG were enrolled in the study. Women with recurrent uterine bleeding, abnormal cytology, using tamoxifen, or women with already dia-gnosed uterine or adnexal pathology were excluded. 289 women were enrolled in the study - 157 (54.3%) expert USG vs. 132 (45.7%) non-expert USG. Abnormal findings were observed on the cervix in one case (non-expert USG), the endometrium 30 (10.4%) cases - 13 (8.3%) expert vs. 17 (12.9%) non-expert USG, the adnexa three (2.3%) cases (all non-expert USG), and no suspicion of malignancy on myometrium was observed. USG was false negative in four (1.4%) cases - two (1.3%) expert vs. two (1.5%) non-expert USG. Conversely, the examination was false positive in 34 (11.8%) cases - 13 (8.3%) expert vs. 21 (15.9%) non-expert USG. The risk of unexpected uterine or adnexal pathologies in POP surgery was 1.4%. The agreement between USG and histopathological benign, abnormal or malign findings was 87.2%. A sonographer specialized in oncologic sonography is able to reduce the number of false positive findings; however, this does not increase the sensitivity of the ultrasound.

Present Limitations of Artificial Intelligence in the Emergency Setting - Performance Study of a Commercial, Computer-Aided Detection Algorithm for Pulmonary Embolism.

Since artificial intelligence is transitioning from an experimental stage to clinical implementation, the aim of our study was to evaluate the performance of a commercial, computer-aided detection algorithm of computed tomography pulmonary angiograms regarding the presence of pulmonary embolism in the emergency room. This retrospective study includes all pulmonary computed tomography angiogram studies performed in a large emergency department over a period of 36months that were analyzed by two radiologists experienced in emergency radiology to set a reference standard. Original reports and computer-aided detection results were compared regarding the detection of lobar, segmental, and subsegmental pulmonary embolism. All computer-aided detection findings were analyzed concerning the underlying pathology. False-positive findings were correlated to the contrast-to-noise ratio. Expert reading revealed pulmonary embolism in 182 of 1229 patients (49 % men, 10-97 years) with a total of 504emboli. The computer-aided detection algorithm reported 3331 findings, including 258 (8 %) true-positive findings and 3073 (92 %) false-positive findings. Computer-aided detection analysis showed a sensitivity of 47 % (95 %CI: 33-61 %) on the lobar level and 50 % (95 %CI 43-56 %) on the subsegmental level. On average, there were 2.25 false-positive findings per study (median 2, range 0-25). There was no significant correlation between the number of false-positive findings and the contrast-to-noise ratio (Spearman's Rank Correlation Coefficient = 0.09). Soft tissue (61.0 %) and pulmonary veins (24.1 %) were the most common underlying reasons for false-positive findings. Applied to a population at a large emergency room, the tested commercial computer-aided detection algorithm faced relevant performance challenges that need to be addressed in future development projects. · Computed tomography pulmonary angiograms are frequently acquired in emergency radiology.. · Computer-aided detection algorithms (CADs) can support image analysis.. · CADs face challenges regarding false-positive and false-negative findings.. · Radiologists using CADs need to be aware of these limitations.. · Further software improvements are necessary ahead of implementation in the daily routine.. · Müller-Peltzer K, Kretzschmar L, Negrão de Figueiredo G et al. Present Limitations of Artificial Intelligence in the Emergency Setting - Performance Study of a Commercial, Computer-Aided Detection Algorithm for Pulmonary Embolism. Fortschr Röntgenstr 2021; 193: 1436 - 1444.

Discrimination of SINTOX® GSR against environmental particles and its automated investigation by SEM/EDS

A fundamental problem in gunshot residue (GSR) analysis by SEM/EDS is the distinction to environmental particles. The introduction of heavy metal free (HMF) primers such as SINTOX® enhanced this problem. According to the current ASTM E1588 Standard Practice, the identification of SINTOX® GSR by means of an automated classification scheme is based on the simultaneous presence of titanium and zinc in a particle, labelling them just as “consistent with GSR”. Since both elements often appear together in environmental particles, this leads to a certain number of false-positive findings. Therefore a large number of environmental particles originating from different sources such as waste incineration plants and volcanic ashes were analytically evaluated. In order to find possible distinctions between SINTOX® primer GSR and environmental particles, the components of SINTOX® ammunition and its generated residues resulting from the firing process were examined.A new classification scheme of high efficiency for SINTOX® GSR was developed extending the standard classification scheme based on the recommendations of the ASTM E1588 Standard Practice. The resulting new classes show a good selectivity and nearly no overlap with environmental particles. In casework, the new proposed classification process can reduce the total investigation time due to an improvement in the manual confirmation step of SINTOX® GSR.

Correction for Magnetic Field Inhomogeneities and Normalization of Voxel Values Are Needed to Better Reveal the Potential of MR Radiomic Features in Lung Cancer.

Purpose: To design and validate a preprocessing procedure dedicated to T2-weighted MR images of lung cancers so as to improve the ability of radiomic features to distinguish between adenocarcinoma and other histological types.Materials and Methods: A discovery set of 52 patients with advanced lung cancer who underwent T2-weighted MR imaging at 3 Tesla in a single center study from August 2017 to May 2019 was used. Findings were then validated using a validation set of 19 additional patients included from May to October 2019. Tumor type was obtained from the pathology report after trans-thoracic needle biopsy, metastatic lymph node or metastasis samples, or surgical excisions. MR images were preprocessed using N4ITK bias field correction and by normalizing voxel intensities with fat as a reference region. Segmentation and extraction of radiomic features were performed with LIFEx software on the raw images, on the N4ITK-corrected images and on the fully preprocessed images. Two analyses were conducted where radiomic features were extracted: (1) from the whole tumor volume (3D analysis); (2) from all slices encompassing the tumor (2D analysis). Receiver operating characteristic (ROC) analysis was used to identify features that could distinguish between adenocarcinoma and other histological types. Sham experiments were also designed to control the number of false positive findings.Results: There were 31 (12) adenocarcinomas and 21 (7) other histological types in the discovery (validation) set. In 2D, preprocessing increased the number of discriminant radiomic features from 8 without preprocessing to 22 with preprocessing. 2D analysis yielded more features able to identify adenocarcinoma than 3D analysis (12 discriminant radiomic features after preprocessing in 3D). Preprocessing did not increase false positive findings as no discriminant features were identified in any of the sham experiments. The greatest sensitivity of the 2D analysis applied to preprocessed data was confirmed in the validation set.Conclusion: Correction for magnetic field inhomogeneities and normalization of voxel values are essential to reveal the full potential of radiomic features to identify the tumor histological type from MR T2-weighted images, with classification performance similar to those reported in PET/CT and in multiphase CT in lung cancers.

Lung Cancer screening? Who should get it and how it should bedone

In large clinical studies, lung cancer screening has been demonstrated to be effective in reducing lung cancer mortality in defined high risk populations using low-dose CT techniques. However, in different studies, results and definitions of persons of high risk have varied which needs to be taken into account when screening programmes should be implemented in clinical routine. In order those programmes to be as effective as possible, the careful definition of a risk population is crucial as much as the careful use of radiant exposure. Ideally, the number of false positive findings should be as low as possible with the best reduction in lung cancer mortality and limited financial burden.

Deep Convolutional Neural Network-based Software Improves Radiologist Detection of Malignant Lung Nodules on Chest Radiographs.

Background Multicenter studies are required to validate the added benefit of using deep convolutional neural network (DCNN) software for detecting malignant pulmonary nodules on chest radiographs. Purpose To compare the performance of radiologists in detecting malignant pulmonary nodules on chest radiographs when assisted by deep learning-based DCNN software with that of radiologists or DCNN software alone in a multicenter setting. Materials and Methods Investigators at four medical centers retrospectively identified 600 lung cancer-containing chest radiographs and 200 normal chest radiographs. Each radiograph with a lung cancer had at least one malignant nodule confirmed by CT and pathologic examination. Twelve radiologists from the four centers independently analyzed the chest radiographs and marked regions of interest. Commercially available deep learning-based computer-aided detection software separately trained, tested, and validated with 19 330 radiographs was used to find suspicious nodules. The radiologists then reviewed the images with the assistance of DCNN software. The sensitivity and number of false-positive findings per image of DCNN software, radiologists alone, and radiologists with the use of DCNN software were analyzed by using logistic regression and Poisson regression. Results The average sensitivity of radiologists improved (from 65.1% [1375 of 2112; 95% confidence interval {CI}: 62.0%, 68.1%] to 70.3% [1484 of 2112; 95% CI: 67.2%, 73.1%], P < .001) and the number of false-positive findings per radiograph declined (from 0.2 [488 of 2400; 95% CI: 0.18, 0.22] to 0.18 [422 of 2400; 95% CI: 0.16, 0.2], P < .001) when the radiologists re-reviewed radiographs with the DCNN software. For the 12 radiologists in this study, 104 of 2400 radiographs were positively changed (from false-negative to true-positive or from false-positive to true-negative) using the DCNN, while 56 of 2400 radiographs were changed negatively. Conclusion Radiologists had better performance with deep convolutional network software for the detection of malignant pulmonary nodules on chest radiographs than without. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Jacobson in this issue.

Biologically anchored knowledge expansion approach uncovers KLF4 as a novel insulin signaling regulator.

One of the biggest challenges in analyzing high throughput omics data in biological studies is extracting information that is relevant to specific biological mechanisms of interest while simultaneously restricting the number of false positive findings. Due to random chances with numerous candidate targets and mechanisms, computational approaches often yield a large number of false positives that cannot easily be discerned from relevant biological findings without costly, and often infeasible, biological experiments. We here introduce and apply an integrative bioinformatics approach, Biologically Anchored Knowledge Expansion (BAKE), which uses sequential statistical analysis and literature mining to identify highly relevant network genes and effectively removes false positive findings. Applying BAKE to genomic expression data collected from mouse (Mus musculus) adipocytes during insulin resistance progression, we uncovered the transcription factor Krueppel-like Factor 4 (KLF4) as a regulator of early insulin signaling. We experimentally confirmed that KLF4 controls the expression of two key insulin signaling molecules, the Insulin Receptor Substrate 2 (IRS2) and Tuberous Sclerosis Complex 2 (TSC2).

Abstract PL04-02: Pharmacogenomics of chemotherapeutic-induced toxicities: Challenges and opportunities

Abstract PL04-02: Pharmacogenomics of chemotherapeutic-induced toxicities: Challenges and opportunities

Evaluation of the diagnostic value of preoperative sentinel lymph node (SLN) imaging in penile carcinoma patients without palpable inguinal lymph nodes via single photon emission computed tomography/computed tomography (SPECT/CT) as compared to planar scintigraphy

BackgroundSentinel lymph node (SLN) biopsy represents a well-established diagnostic tool for the assessment of lymphatic metastasis. Correct pre- and intraoperative visualization of SLN is of the utmost importance to ensure the safety and feasibility of the procedure. Aim of this study was to evaluate the diagnostic value of preoperative SLN imaging via single photon emission computed tomography/computed tomography (SPECT/CT) and planar scintigraphy in patients with penile carcinoma with nonpalpable inguinal lymph nodes. Materials and methodsAfter peritumoral intradermal tracer injection (150MBq/4.05mCi Tc-99m nanocolloid), we acquired planar scintigraphies including indirect body contouring using a twin head gamma camera. Subsequently we acquired SPECT/CT images of the abdomen via a hybrid system. Prospective evaluation of 52 groins in 26 examined patients was done for all image files obtained with both techniques by 2 trained experts in consensual assessment. ResultsA total of 71 SLNs in 37 groins were identified by means of planar scintigraphy. In these images, no radiolabeled lymph nodes were visualized in 15 out of 52 groins (28.8%). The SPECT/CT images showed a total of 82 SLNs in 42 groins. In 19.2% (10 of the 52 groins), there was no visualization of lymph nodes in SPECT/CT. 8 SLNs in 7 groins that were visualized in the planar technique were found to be false positive by SPECT/CT. In total, 19 SLNs in 16 groins that were overlooked by planar imaging could only be detected by SPECT/CT. In contrast to planar scintigraphy, SPECT/CT imaging enabled clear and precise anatomical localization of SLNs in all 42 groins where radiolabeled SLNs were visible. Even under consideration of all lymphatic drainage regions, statistical evaluation showed a significantly higher number of detected SLNs with SPECT/CT in comparison to the planar technique (P = 0.0022). ConclusionIn these patients SPECT/CT is capable of visualizing SLNs that cannot be detected with planar imaging. The SPECT/CT technique reduces the number of false positive findings from planar SLN imaging and is able to show anatomic SLN localization more precisely. If possible, preoperative SLN imaging should be performed by means of the SPECT/CT technique in patients with this tumor entity.

Possible explanations for why some countries were harder hit by the pandemic influenza virus in 2009 \u2013 a global mortality impact modeling study

BackgroundA global pandemic mortality study found prominent regional mortality variations in 2009 for Influenza A(H1N1)pdm09. Our study attempts to identify factors that explain why the pandemic mortality burden was high in some countries and low in others.MethodsAs a starting point, we identified possible risk factors worth investigating for Influenza A(H1N1)pdm09 mortality through a targeted literature search. We then used a modeling procedure (data simulations and regression models) to identify factors that could explain differences in respiratory mortality due to Influenza A(H1N1)pdm09. We ran sixteen models to produce robust results and draw conclusions. In order to assess the role of each factor in explaining differences in excess pandemic mortality, we calculated the reduction in between country variance, which can be viewed as an effect-size for each factor.ResultsThe literature search identified 124 publications and 48 possible risk factors, of which we were able to identify 27 factors with appropriate global datasets. The modelling procedure indicated that age structure (explaining 40% of the mean between country variance), latitude (8%), influenza A and B viruses circulating during the pandemic (3–8%), influenza A and B viruses circulating during the preceding influenza season (2–6%), air pollution (pm10; 4%) and the prevalence of other infections (HIV and TB) (4–6%) were factors that explained differences in mortality around the world. Healthcare expenditure, levels of obesity, the distribution of antivirals, and air travel did not explain global pandemic mortality differences.ConclusionsOur study found that countries with a large proportion of young persons had higher pandemic mortality rates in 2009. The co-circulation of influenza viruses during the pandemic and the circulation of influenza viruses during the preceding season were also associated with pandemic mortality rates. We found that real time assessments of 2009 pandemic mortality risk factors (e.g. obesity) probably led to a number of false positive findings.

MP18-10 COMPARISON OF PLANAR SCINTIGRAPHY AND SINGLE-PHOTON EMISSION COMPUTED TOMOGRAPHY /COMPUTED TOMOGRAPHY (SPECT/CT) IN PREOPERATIVE IMAGING OF SENTINEL LYMPH NODES IN PENILE CANCER PATIENTS

You have accessJournal of UrologyImaging/Radiology: Uroradiology III1 Apr 2017MP18-10 COMPARISON OF PLANAR SCINTIGRAPHY AND SINGLE-PHOTON EMISSION COMPUTED TOMOGRAPHY /COMPUTED TOMOGRAPHY (SPECT/CT) IN PREOPERATIVE IMAGING OF SENTINEL LYMPH NODES IN PENILE CANCER PATIENTS Carsten Maik Naumann, Moritz Franz Hamann, Christian Colberg, Klaus-Peter Jünemann, Daniar Osmonov, and Ulf Lützen Carsten Maik NaumannCarsten Maik Naumann More articles by this author , Moritz Franz HamannMoritz Franz Hamann More articles by this author , Christian ColbergChristian Colberg More articles by this author , Klaus-Peter JünemannKlaus-Peter Jünemann More articles by this author , Daniar OsmonovDaniar Osmonov More articles by this author , and Ulf LützenUlf Lützen More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.620AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The aim of this study was to evaluate the diagnostic value of SPECT/CT and planar lymphoscintigraphy in preoperative imaging of sentinel lymph nodes in penile cancer patients with non-palpable inguinal lymph nodes. METHODS Radio-labelling of sentinel nodes was performed by intradermal and peritumoral injection of 150MBq Tc-99 m-labelled nanocolloids according to the two day protocol. Image acquisition of planar scintigraphies was carried out by a twin head gamma camera (Siemens, ECAM and Symbia S) and indirect body contouring. Additionally, we subsequently performed SPECT/CT of the abdomen und inguinal regions using a twin-head hybrid camera system (Siemens Symbia T and Symbia Intevo). Imaging data of both modalities were prospectively evaluated by two experienced physicians in consensus reading in 52 groins of 26 patients with this tumor entity. RESULTS A total of 71 SLNs in 37 groins were identified by planar scintigraphy. Non-visualization was observed in 15 (28.8%) inguinal basins using planar scans. 82 SLNs in 42 groins were detected by SPECT/CT (non-visualization in 10 (19.2%) groins). SPECT/CT revealed 8 inguinal hotspots as shown by planar imaging in 7 groins as false positive. 19 inguinal SLNs in 16 groins were missed on planar imaging and could be detected by SPECT/CT only. In contrast to 2D planar scintigraphy, SPECT/CT allowed to determine the precise anatomical localization of the SLNs in all 42 groins. CONCLUSIONS SPECT/CT is capable of detecting SLNs missed by planar imaging, it reduces the number of false positive findings and shows the morphological location of SLNs more accurately. If available, SPECT/CT should be used for preoperative SLN imaging in penile cancer patients with non-palpable inguinal lymph node status. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e223-e224 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Carsten Maik Naumann More articles by this author Moritz Franz Hamann More articles by this author Christian Colberg More articles by this author Klaus-Peter Jünemann More articles by this author Daniar Osmonov More articles by this author Ulf Lützen More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Mammography image restoration based on a radiographic scattering model from a single projection: Experimental study

In conventional mammography, contrast sensitivity remains limited due to the superimposition of breast tissue and scattered X-rays, which induces low visibility of lesions in the breast and, thus, an excessive number of false-positive findings. Several methods, including digital breast tomosynthesis as a multiplanar imaging modality, air-gap and slot techniques for the reduction of scatters, phase-contrast imaging as another image-contrast modality, etc., have been investigated in attempt to overcome these difficulties. However, those techniques typically require a higher imaging dose or special equipment. In this work, as an alternative, we propose a new image restoration method based on a radiographic scattering model in which the intensity of scattered X-rays and the direct transmission function of a given medium are estimated from a single projection by using the dark-channel prior. We implemented the proposed algorithm and performed an experiment to demonstrate its viability. Our results indicate that most of the structures in the examined breast were very discernable even with no adjustment in the display-window level, thus preserving superior image features and edge sharpening.

Increased accuracy of single photon emission computed tomography (SPECT) myocardial perfusion scintigraphy using iterative reconstruction of images.

Filtered back projection (FBP) is a common way of processing myocardial perfusion imaging (MPI)studies. There are artifacts in FBP which can cause false-positive results. Iterative reconstruction (IR) is developed to reduce false positive findings in MPI studies. The aim of this study was to evaluate the difference in the number of false-positive findings in MPI studies, between FBP and IR processing. We examined 107 patients with angina pectoris with MPI and coronary angiography (CAG), 77 man and 30 woman, aged 32-82. MPI studies were processed with FBP and with IR. Positive finding at MPI was visualization of the perfusion defect. Positive finding at CAG was stenosis of coronary artery. Perfusion defect at MPI without coronary artery stenosis at CAG was considered like false positive. The results were statistically analyzed with bivariate correlation, and with one sample t-test. There were 20.6% normal, and 79.4% pathologic findings at FBP, 30.8% normal and 69.2% pathologic with IR and 37.4% normal and 62.6% pathologic at CAG. FBP produced 19 false positive findings, at IR 11 false positive findings. The correlation between FBP and CAG was 0.658 (P < 0.01) and between IR and CAG 0.784 (P < 0.01). The number of false positive findings at MPI with IR was significantly lower than at FBP (p < 0.01). Our study shows that IR processing MPI scintigraphy has less number of false positive findings, therefore it is our choice for processing MPI studies.

Abstract 2763: Maternal folate intake at periconception and genome-wide DNA methylation modifications at birth in children

Abstract Introduction Folate supplementation during pregnancy was previously associated with a lower risk of acute lymphoblastic childhood leukemia (ALL). Folate is involved in the “one-carbon” metabolic cycle necessary for shuttling methyl groups for DNA methylation. Given the observation that aberrant DNA methylation patterns are a characteristic of leukemic cells during ALL oncogenesis, we hypothesized that (1) low folate exposure during fetal development might modify the neonate's DNA genome-wide methylation pattern, and that (2) such a modified pattern can lead to ALL development. Here we investigate the first part of this hypothesis. Methods We analyzed healthy control participants of the California Childhood Leukemia case-control study. Participants’ peri-conception folate exposure was estimated from self-reported maternal folate intake and supplements, which was derived from a food frequency questionnaire on the diet in the year prior to pregnancy, as a surrogate for nutrient “environment” during the peri-conception period. DNA obtained from archived neonatal blood spots was purified, treated with bisulfite and assayed on the Illumina Infinium 450K genome-wide DNA methylation array. After removing cross-reacting probes, SNP-related and polymorphic CpGs, we analyzed the association of folate with methylation intensity of 319,265 CpGs in two independent datasets (n set 1 = 167 and n set 2 = 176). Models were adjusted for cell mixture, sex, gestational age, and race. We used a false discovery rate with random resampling to reduce the number of false-positive findings and we cross-validated the results between sets. Results Maternal folate intake was broadly associated with less child's DNA methylation: with a q-value &amp;lt;0.05, we found more than 122,000 CpG sites associated with folate intake in common in both sets. Because a fraction of these CpGs were sign discordant between sets, we constrained our analysis to the most significant CpGs, in order to avoid false positive associations. The three most significant CpGs found in common in both sets were negatively associated with folate. First, cg21039708 (chr.14) in the gene OTX2OS1 (q &amp;lt;10-14 in both sets) is implicated in facial and eye defects. Second, cg13499966 (chr.2) in the gene CYS1 (q &amp;lt;10-14 in both sets) is implicated in cystic kidney disease and biliary liver fibrosis. Third, cg22664307 (chr.6) in the gene STX11 (q &amp;lt;10-14 in both sets) is associated with lymphohistiocytosis. Conclusions This study was the first to investigate the association between maternal folate intake during the peri-conception period and DNA methylation at birth with a genome-wide approach and it found numerous associations throughout the genome. The relationships between folate-sensitive CpG sites and DNA methylation events critical to childhood leukemogenesis will be considered in our subsequent research. Citation Format: Semira Gonseth, Ritu Roy, E. Andres Houseman, Adam de Smith, Mi Zhou, Seung-Tae Lee, Sébastien Nusslé, Amanda W. Singer, Margaret R. Wrensch, Catherine Metayer, Joseph L. Wiemels. Maternal folate intake at periconception and genome-wide DNA methylation modifications at birth in children. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2763. doi:10.1158/1538-7445.AM2015-2763

Abstract 831: In utero polycyclic aromatic hydrocarbons exposure and genome-wide DNA methylation modifications at birth in children who develop acute lymphoblastic leukemia

Abstract Introduction Previously, residential dust content of polycyclic aromatic hydrocarbons (PAHs) was associated with an increased risk of acute lymphoblastic childhood leukemia (ALL), and PAHs exposure levels have been associated with differentially methylated regions (DMRs) in candidate genes studies. Thus, we hypothesized that in utero exposure to residential PAHs may be associated with genome-wide DMRs in genes that may influence ALL development. Methods PAHs were measured in dust samples collected using a high-volume surface sampler or household vacuum cleaners from homes of California Childhood Leukemia Study participants who have lived in the same home since diagnosis. The different PAHs were summed according to their toxic equivalency. DNA was extracted from archived neonatal blood spots of participants, then treated with bisulfite and assayed on Illumina Infinium 450K genome-wide DNA methylation arrays. Following removal of cross-reacting probes, SNP-related and polymorphic CpGs, we analyzed the association of residential PAH levels with methylation intensity of 319,265 CpGs in two independent case-only datasets (model #1: set 1 cases n = 84, set 2 cases n = 51). We used a false discovery rate with random resampling to reduce the number of false-positive findings and cross-validated the results between sets. This first step of the analysis gave 11 significant and sign concordant CpGs. Then we assessed interactions between case/control status and PAHs levels with methylation intensities at those 11 CpGs in set 1 (model #2: total cases and controls n = 306). Models were adjusted for cell mixture, sex, gestational age, race and the first 2 principal components of the models’ residuals. Results In model #1, methylation levels at 11 CpGs were significantly associated with residential PAH levels and sign concordant in both sets with a corresponding q-value &amp;lt; 10−08. In model #2, the interaction terms between PAH and case/control status were significant (p&amp;lt;0.05) in 7 of these 11 CpGs, and the 3 most significant were: cg13484813 (p &amp;lt;0.001) in LGR5 (chr12q21.1) which is differentially expressed in pre-B cell vs. leukemia cells; cg23196133 (p &amp;lt;0.01) in ZBTB4 (chr17p13.1) which is a transcription factor linked to p53; and cg07617339 (p &amp;lt;0.01) in ATF6B (chr6p21.3) which encodes a transcription factor. Conclusions For the first time, our genome-wide methylation investigation found that residential PAH levels were associated with 11 CpGs at birth among children who later developed ALL. Moreover, the future cases had significantly different DNA methylation responses to PAH exposures than the unaffected controls for 7 CpGs. This may suggest a case/control difference present at birth in the sensitivity to PAHs in particular cell-cycle and tumor-suppressor genes. These CpGs may be good candidates to further investigate with respect to leukemogenesis. Citation Format: Semira Gonseth, Todd P. Whitehead, Ritu Roy, E. Andres Houseman, Adam J. de Smith, Mi Zhou, Seung-Tae Lee, Margaret R. Wrensch, Stephen M. Rappaport, Catherine Metayer, Joseph L. Wiemels. In utero polycyclic aromatic hydrocarbons exposure and genome-wide DNA methylation modifications at birth in children who develop acute lymphoblastic leukemia. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 831. doi:10.1158/1538-7445.AM2015-831