A simple classification system (the Tree flowchart) for breast MRI can reduce the number of unnecessary biopsies in MRI-only lesions.

OBJECTIVES: To assess whether using the Tree flowchart obviates unnecessary magnetic resonance imaging (MRI)-guided biopsies in breast lesions only visible on MRI. METHODS: This retrospective IRB-approved study evaluated consecutive suspicious (BI-RADS 4) breast lesions only visible on MRI that were referred to our institution for MRI-guided biopsy. All lesions were evaluated according to the Tree flowchart for breast MRI by experienced readers. The Tree flowchart is a decision rule that assigns levels of suspicion to specific combinations of diagnostic criteria. Receiver operating characteristic (ROC) curve analysis was used to evaluate diagnostic accuracy. To assess reproducibility by kappa statistics, a second reader rated a subset of 82 patients. RESULTS: There were 454 patients with 469 histopathologically verified lesions included (98 malignant, 371 benign lesions). The area under the curve (AUC) of the Tree flowchart was 0.873 (95% CI: 0.839-0.901). The inter-reader agreement was almost perfect (kappa: 0.944; 95% CI 0.889-0.998). ROC analysis revealed exclusively benign lesions if the Tree node was ≤2, potentially avoiding unnecessary biopsies in 103 cases (27.8%). CONCLUSIONS: Using the Tree flowchart in breast lesions only visible on MRI, more than 25% of biopsies could be avoided without missing any breast cancer. KEY POINTS: • The Tree flowchart may obviate >25% of unnecessary MRI-guided breast biopsies. • This decrease in MRI-guided biopsies does not cause any false-negative cases. • The Tree flowchart predicts 30.6% of malignancies with >98% specificity. • The Tree's high specificity aids in decision-making after benign biopsy results

Diffusion-weighted imaging of breast lesions: Technical validity and clinical application

Diffusionsgewichtete Magnetresonanztomographie (DWI) gibt Einblicke in die Gewebegeometrie durch Visualisierung und Quantifizierung der Wasserdiffusionsfähigkeit. Die quantitative Auswertung des Diffusionskoeffizienten (ADC), der von DWI berechnet wird, wurde als möglicher quantitativer bildgebender Biomarker vorgeschlagen. Ziel dieser PhD Arbeit war es, die technische Validität und mögliche klinische Anwendungen der DWI von Brustläsionen zu evaluieren. Der erste Teil konzentriert sich auf die technische Validierung und bewertet die Robustheit der DWI in einer prospektiven intra-individuellen klinischen Studie. Es wurden zwei gleiche Magnetresonanztomographieuntersuchungen mit DWI an Frauen, mit einem Mindestabstand von einem Tag zwischen den beiden Untersuchungen, durchgeführt. In weiterer Folge wurden die Reproduzierbarkeit, und Diagnosegenauigkeit beurteilt. Zuerst wurde festgestellt, dass die ADC Werte bei gutartigen im Vergleich zu bösartigen Brustläsionen signifikant höher waren. Dies unterstützt somit die Aussage, dass DWI es ermöglicht, verschiedene Brusttumore zu unterscheiden. Darüber hinaus zeigt die Studie, dass DWI eine robuste Technik ist und eine hohe Übereinstimmung zwischen wiederholten DWI-Untersuchungen und Messungen zeigt. Der folgende Teil der Arbeit beschreibt den Vergleich von verschiedenen region-of-interest (ROI) Platzierungsansätzen (kleiner 2D-ROI, großer 2D-ROI und 3D-ROI) von ADC Messungen. Die Ergebnisse zeigen, dass die ROI Platzierung einen signifikanten Einfluss auf ADC Werte hat. Hinsichtlich der diagnostischen Wertigkeit der ADC Werte, erreichten der minimale und der mittlere ADC die besten Ergebnisse. Die 2D-ROIs haben sich am besten bewährt und ermöglichen eine schnelle Messung. Das nächste Kapitel liefert Beweise dafür, dass die DWI die Beurteilung von verdächtigen, nur in der MRT identifizierbaren, Brustläsionen ermöglicht. Diese klinische Anwendung ist von besonderer Bedeutung, da die Brust MRT mehr Brusttumore als jede andere bildgebende Methode darstellen kann. Auch hier zeigen weitere Daten, dass die ADC Werte bei gutartigen Läsionen signifikant höher waren als bei bösartigen Läsionen. Darüber hinaus wurden Ein- und Ausschlusskriterien mit flexiblen ADC Schwellenwerten identifiziert. Dies ermöglicht es, falsch-positive Biposien zu vermeiden. Der letzte Teil zeigt das Potenzial der DWI zur Bewertung der Invasivität des Brustkarzinoms. DWI war in der Lage, invasive Brustkarzinome von nicht-invasiven duktalen Karzinom in situ (DCIS) zu unterscheiden. Die ADC Werte unterschieden sich signifikant zwischen invasiven Karzinom und nicht-invasivem DCIS. Abschließend liefert diese Dissertation weiterführende Evidenz, dass die DWI als quantitativen bildgebenden Biomarker in der Bildgebung des Brustkarzinoms unterstützt. DWI ist eine robuste Technik, die leicht in Standard Brust Magnetresonanztomographie Protokolle integriert werden kann und hilft bei der Erkennung und biologischen Charakterisierung von Brusttumoren. Schließlich hat DWI das Potenzial, das Vorliegen von Brustkrebs auszuschließen, was eine obligatorische Eigenschaft in einem diagnostischen Test darstellt.Diffusion-weighted magnetic resonance imaging (DWI) is a technique that enables insights into tissue microstructure through the visualization and quantification of water diffusivity. Quantitative measurement of the apparent diffusion coefficient (ADC), obtained from DWI, has been introduced as a potential imaging biomarker in oncology. The aims of this PhD thesis were to assess the technical validity and clinical applications of DWI of breast tumors. The first part focuses on the technical validation, and evaluates the robustness of DWI in a prospective intra-individual clinical study. In particular, DWI examinations were repeated in the same women with at least one day in between. Consequently, the retest reproducibility, repeatability, and diagnostic accuracy were assessed. ADC values were significantly higher in benign compared to malignant breast lesions, supporting its value in distinguishing different breast tumors. Furthermore, the study revealed that DWI is a robust technique and shows high agreement between repeated DWI examinations and measurements. The subsequent part describes the comparison of different region-of-interest (ROI) placement approaches (small 2D-ROI, large 2D-ROI, and 3D-ROI) to ADC measurements. The findings showed that ROI placement significantly influences ADC values. With regard to the diagnostic performance of ADC values, the minimum and mean ADC achieved the best results. The 2D ROIs performed best and allow rapid measurement. The next chapter provides data that show that DWI enables the assessment of suspicious breast lesions visible only on MRI. This clinical application is important since breast MRI has been proven to show more breast tumors than any other imaging modality. Here also, further data has revealed that ADC values were significantly higher in benign lesions than in malignant breast lesions. Furthermore, rule-in and rule-out criteria were identified using flexible ADC threshold values, based on receiver-operating characteristic analysis. Consequently, false-positive biopsies could have been avoided. The final part presents data regarding the potential of DWI to evaluate breast cancer invasiveness. DWI was able to distinguish invasive breast cancer from non-invasive ductal carcinoma in situ (DCIS). Mean ADC values differed significantly between invasive cancers and DCIS. In conclusion, this PhD thesis adds to the body of evidence that supports DWI as a potential quantitative imaging biomarker in breast cancer imaging. DWI is a robust technique that can be easily incorporated in standard breast MRI protocols and helps in the detection and biological characterization of breast tumors. Finally, breast DWI has the potential to rule-out breast cancer, a mandatory characteristic in a test applied to diagnose breast cancer.submitted by Claudio Spick, MDZusammenfassung in deutscher SpracheMedizinische Universität Wien, Dissertation, 2016OeBB(VLID)192236

18 F-FDG PET/CT and PET/MRI perform equally well in cancer: evidence from studies on more than 2, 300 patients

(18)F-FDG PET/CT has become the reference standard in oncologic imaging against which the performance of other imaging modalities is measured. The promise of PET/MRI includes multiparametric imaging to further improve diagnosis and phenotyping of cancer. Rather than focusing on these capabilities, many investigators have examined whether (18)F-FDG PET combined with mostly anatomic MRI improves cancer staging and restaging. After a description of PET/MRI scanner designs and a discussion of technical and operational issues, we review the available literature to determine whether cancer assessments are improved with PET/MRI. The available data show that PET/MRI is feasible and performs as well as PET/CT in most types of cancer. Diagnostic advantages may be achievable in prostate cancer and in bone metastases, whereas disadvantages exist in lung nodule assessments. We conclude that (18)F-FDG PET/MRI and PET/CT provide comparable diagnostic information when MRI is used simply to provide the anatomic framework. Thus, PET/MRI could be used in lieu of PET/CT if this approach becomes economically viable and if reasonable workflows can be established. Future studies should explore the multiparametric potential of MRI

European Radiology / Malignancy rates and diagnostic performance of the Bosniak classification for the diagnosis of cystic renal lesions in computed tomography : a systematic review and meta-analysis

Objective To systematically review the literature on the Bosniak classification system in CT to determine its diagnostic performance to diagnose malignant cystic lesions and the prevalence of malignancy in Bosniak categories. Methods A predefined database search was performed from 1 January 1986 to 18 January 2016. Two independent reviewers extracted data on malignancy rates in Bosniak categories and several covariates using predefined criteria. Study quality was assessed using QUADAS-2. Meta-analysis included data pooling, subgroup analyses, meta-regression and investigation of publication bias. Results A total of 35 studies, which included 2,578 lesions, were investigated. Data on observer experience, inter-observer variation and technical CT standards were insufficiently reported. The pooled rate of malignancy increased from Bosniak I (3.2 %, 95 % CI 06.8, I2 = 5 %) to Bosniak II (6 %, 95 % CI 2.79.3, I2 = 32 %), IIF (6.7 %, 95 % CI 58.4, I2 =(VLID)353393

Human Biodistribution and Radiation Dosimetry of 18F-Clofarabine, a PET Probe Targeting the Deoxyribonucleoside Salvage Pathway.

18F-clofarabine, a nucleotide purine analog, is a substrate for deoxycytidine kinase (dCK), a key enzyme in the deoxyribonucleoside salvage pathway. 18F-clofarabine might be used to measure dCK expression and thus serve as a predictive biomarker for tumor responses to dCK-dependent prodrugs or small-molecule dCK inhibitors, respectively. As a prerequisite for clinical translation, we determined the human whole-body and organ dosimetry of 18F-clofarabine. Methods: Five healthy volunteers were injected intravenously with 232.4 ± 1.5 MBq of 18F-clofarabine. Immediately after tracer injection, a dynamic scan of the entire chest was acquired for 30 min. This was followed by 3 static whole-body scans at 45, 90, and 135 min after tracer injection. Regions of interest were drawn around multiple organs on the CT scan and copied to the PET scans. Organ activity was determined and absorbed dose was estimated with OLINDA/EXM software. Results: The urinary bladder (critical organ), liver, kidney, and spleen exhibited the highest uptake. For an activity of 250 MBq, the absorbed doses in the bladder, liver, kidney, and spleen were 58.5, 6.6, 6.3, and 4.3 mGy, respectively. The average effective dose coefficient was 5.1 mSv. Conclusion: Our results hint that 18F-clofarabine can be used safely in humans to measure tissue dCK expression. Future studies will determine whether 18F-clofarabine may serve as a predictive biomarker for responses to dCK-dependent prodrugs or small-molecule dCK inhibitors

Quantitative apparent diffusion coefficient measurements obtained by 3-Tesla MRI are correlated with biomarkers of bladder cancer proliferative activity.

PURPOSE:To investigate the association between Apparent Diffusion Coefficient (ADC) values and cell cycle and proliferative biomarkers (p53, p21, Ki67,) in order to establish its potential role as a noninvasive biomarker for prediction of cell cycle, proliferative activity and biological aggressiveness in bladder cancer. MATERIALS AND METHODS:Patients with bladder cancer who underwent 3,0 Tesla DW-MRI of the bladder before TUR-B or radical cystectomy were eligible for this prospective IRB-approved study. Histological specimen were immunohistochemically stained for the following markers: p53, p21 and ki67. Two board-certified uropathologists reviewed the specimens blinded to DW-MRI results. Histological grade and T-stage were classified according to the WHO 2004 and the 2009 TNM classification, respectively. Nonparametric univariate and multivariate statistics including correlation, logistic regression and ROC analysis were applied. RESULTS:Muscle invasive bladder cancer was histologically confirmed in 10 out of 41 patients. All examined tissue biomarkers were significantly correlated with ADC values (p<0.05, respectively). Based on multivariate analysis, p53 and ADC are both independent prognostic factors for muscle invasiveness of bladder cancer (>/ = T2). (p = 0.013 and p = 0.018). CONCLUSION:ADC values are associated with cell cycle and proliferative biomarkers and do thereby reflect invasive and proliferative potential in bladder cancer. ADC and p53 are both independent prognostic factors for muscle invasiveness in bladder cancer

Loss of a pyoverdine secondary receptor in Pseudomonas aeruginosa results in a fitter strain suitable for population invasion

The rapid emergence of antibiotic resistant bacterial pathogens constitutes a critical problem in healthcare and requires the development of novel treatments. Potential strategies include the exploitation of microbial social interactions based on public goods, which are produced at a fitness cost by cooperative microorganisms, but can be exploited by cheaters that do not produce these goods. Cheater invasion has been proposed as a ‘Trojan horse’ approach to infiltrate pathogen populations with strains deploying built-in weaknesses (e.g., sensitiveness to antibiotics). However, previous attempts have been often unsuccessful because population invasion by cheaters was prevented by various mechanisms including the presence of spatial structure (e.g., growth in biofilms), which limits the diffusion and exploitation of public goods. Here we followed an alternative approach and examined whether the manipulation of public good uptake and not its production could result in potential ‘Trojan horses’ suitable for population invasion. We focused on the siderophore pyoverdine produced by the human pathogen Pseudomonas aeruginosa MPAO1 and manipulated its uptake by deleting and/or overexpressing the pyoverdine primary (FpvA) and secondary (FpvB) receptors. We found that receptor synthesis feeds back on pyoverdine production and uptake rates, which led to strains with altered pyoverdine-associated costs and benefits. Moreover, we found that the receptor FpvB was advantageous under iron-limited conditions but revealed hidden costs in the presence of an antibiotic stressor (gentamicin). As a consequence, FpvB mutants became the fittest strain under gentamicin exposure, displacing the wildtype in liquid cultures, and in biofilms and during infections of the wax moth larvae Galleria mellonella, which both represent structured environments. Our findings reveal that an evolutionary trade-off associated with the costs and benefits of a versatile pyoverdine uptake strategy can be harnessed for devising a Trojan-horse candidate for medical interventions

European Radiology / 3D T2-weighted imaging to shorten multiparametric prostate MRI protocols

Objectives To determine whether 3D acquisitions provide equivalent image quality, lesion delineation quality and PI-RADS v2 performance compared to 2D acquisitions in T2-weighted imaging of the prostate at 3 T. Methods This IRB-approved, prospective study included 150 consecutive patients (mean age 63.7 years, 3584 years; mean PSA 7.2 ng/ml, 0.431.1 ng/ml). Two uroradiologists (R1, R2) independently rated image quality and lesion delineation quality using a five-point ordinal scale and assigned a PI-RADS score for 2D and 3D T2-weighted image data sets. Data were compared using visual grading characteristics (VGC) and receiver operating characteristics (ROC)/area under the curve (AUC) analysis. Results Image quality was similarly good to excellent for 2D T2w (mean score R1, 4.3 0.81; R2, 4.7 0.83) and 3D T2w (mean score R1, 4.3 0.82; R2, 4.7 0.69), p = 0.269. Lesion delineation was rated good to excellent for 2D (mean score R1, 4.16 0.81; R2, 4.19 0.92) and 3D T2w (R1, 4.19 0.94; R2, 4.27 0.94) without significant differences (p = 0.785). ROC analysis showed an equivalent performance for 2D (AUC 0.5800.623) and 3D (AUC 0.5760.629) T2w (p > 0.05, respectively). Conclusions Three-dimensional acquisitions demonstrated equivalent image and lesion delineation quality, and PI-RADS v2 performance, compared to 2D in T2-weighted imaging of the prostate. Three-dimensional T2-weighted imaging could be used to considerably shorten prostate MRI protocols in clinical practice. Key points 3D shows equivalent image quality and lesion delineation compared to 2D T2w. 3D T2w and 2D T2w image acquisition demonstrated comparable diagnostic performance. Using a single 3D T2w acquisition may shorten the protocol by 40%. Combined with short DCE, multiparametric protocols of 10 min are feasible.(VLID)357502

European Radiology / A simple classification system (the Tree flowchart) for breast MRI can reduce the number of unnecessary biopsies in MRI-only lesions

Objectives To assess whether using the Tree flowchart obviates unnecessary magnetic resonance imaging (MRI)-guided biopsies in breast lesions only visible on MRI. Methods This retrospective IRB-approved study evaluated consecutive suspicious (BI-RADS 4) breast lesions only visible on MRI that were referred to our institution for MRI-guided biopsy. All lesions were evaluated according to the Tree flowchart for breast MRI by experienced readers. The Tree flowchart is a decision rule that assigns levels of suspicion to specific combinations of diagnostic criteria. Receiver operating characteristic (ROC) curve analysis was used to evaluate diagnostic accuracy. To assess reproducibility by kappa statistics, a second reader rated a subset of 82 patients. Results There were 454 patients with 469 histopathologically verified lesions included (98 malignant, 371 benign lesions). The area under the curve (AUC) of the Tree flowchart was 0.873 (95% CI: 0.8390.901). The inter-reader agreement was almost perfect (kappa: 0.944; 95% CI 0.8890.998). ROC analysis revealed exclusively benign lesions if the Tree node was 2, potentially avoiding unnecessary biopsies in 103 cases (27.8%). Conclusions Using the Tree flowchart in breast lesions only visible on MRI, more than 25% of biopsies could be avoided without missing any breast cancer. Key Points The Tree flowchart may obviate >25% of unnecessary MRI-guided breast biopsies. This decrease in MRI-guided biopsies does not cause any false-negative cases. The Tree flowchart predicts 30.6% of malignancies with >98% specificity. The Trees high specificity aids in decision-making after benign biopsy results.(VLID)355057