Radiogenomics in clear cell renal cell carcinoma: correlations between advanced CT imaging (texture analysis) and microRNAs expression

Purpose: A relevant challenge for the improvement of clear cell renal cell carcinoma management could derive from the identification of novel molecular biomarkers that could greatly improve the diagnosis, prognosis, and treatment choice of these neoplasms. In this study, we investigate whether quantitative parameters obtained from computed tomography texture analysis may correlate with the expression of selected oncogenic microRNAs. Methods: In a retrospective single-center study, multiphasic computed tomography examination (with arterial, portal, and urographic phases) was performed on 20 patients with clear cell renal cell carcinoma and computed tomography texture analysis parameters such as entropy, kurtosis, skewness, mean, and standard deviation of pixel distribution were measured using multiple filter settings. These quantitative data were correlated with the expression of selected microRNAs (miR-21-5p, miR-210-3p, miR-185-5p, miR-221-3p, miR-145-5p). Both the evaluations (microRNAs and computed tomography texture analysis) were performed on matched tumor and normal corticomedullar tissues of the same patients cohort. Results: In this pilot study, we evidenced that computed tomography texture analysis has robust parameters (eg, entropy, mean, standard deviation) to distinguish normal from pathological tissues. Moreover, a higher coefficient of determination between entropy and miR-21-5p expression was evidenced in tumor versus normal tissue. Interestingly, entropy and miR-21-5p show promising correlation in clear cell renal cell carcinoma opening to a radiogenomic strategy to improve clear cell renal cell carcinoma management. Conclusion: In this pilot study, a promising correlation between microRNAs and computed tomography texture analysis has been found in clear cell renal cell carcinoma. A clear cell renal cell carcinoma can benefit from noninvasive evaluation of texture parameters in adjunction to biopsy results. In particular, a promising correlation between entropy and miR-21-5p was found

The effect and stability of MVCT images on adaptive TomoTherapy.

Use of helical TomoTherapy-based MVCT imaging for adaptive planning is becoming increasingly popular. Treatment planning and dose calculations based on MVCT require an image value to electron density calibration to remain stable over the course of treatment time. In this work, we have studied the dosimetric impact on TomoTherapy treatment plans due to variation in image value to density table (IVDT) curve as a function of target degradation. We also have investigated the reproducibility and stability of the TomoTherapy MVCT image quality over time. Multiple scans of the TomoTherapy "Cheese" phantom were performed over a period of five months. Over this period, a difference of 4.7% in the HU values was observed in high-density regions while there was no significant variation in the image values for the low densities of the IVDT curve. Changes in the IVDT curves before and after target replacement were measured. Two clinical treatment sites, pelvis and prostate, were selected to study the dosimetric impact of this variation. Dose was recalculated on the MVCTs with the planned fluence using IVDT curves acquired before and after target change. For the cases studied, target replacement resulted in an overall difference of less than 5%, which can be significant for hypo-fractionated cases. Hence, it is recommended to measure the IVDT curves on a monthly basis and after any major repairs/replacements

Radiological evaluation of biomarkers for renal cell carcinoma

Role of MRI DWI sequences in the evaluation of early response to neo- angiogenesis inhibitors in metastatic renal cell carcinoma Purpose: Angiogenesis inhibitors have a potential role in treating metastatic renal cell carcinoma, but it is still not clear why some patients don't respond. Our objective was to look for DWI parameters able to identify patients with metastatic renal cell carcinoma who would not benefit from target therapy. RECIST1.1 was considered as Reference Standard. Methods & Materials: We prospectively enrolled 43 patients candidate to start angiogenesis inhibitors with at least one target lesion and who underwent 1,5T MRI examination with multiple bvalues DWI sequences (0,40,200,300,600): one week before (t0), 2 weeks after (t2) and 8 weeks (t8) after treatment beginning. ADC value was calculated drawing ROIs on 3 different planes. 33 patients with 38 lesions had suitable data for comparative evaluation. Results: At T8 follow-up 9 patients had partial response (PR), 20 table disease (SD), 4 progression disease (PD); average progression free survival was 272 days. PD group, as compared to DC or to PR showed significantly lower ADC values at b40 at t0 (p<0.05): we can assess that more vascularised lesions are more responsive to treatment. PD group have significantly lower ADC values then both other groups, at t0, t2 and t8, for all b-values (p<0.05). PFS and OS correlates well with ADC, in particular OS with ADC b40 at t0 (r=0,69). Coclusions: Results show that PD group has significantly lower ADC values than PR or DC everytime (t0, t2, t8) At t0 there is a better correlation between PFS or OS & ADC than PFS & dimensional criteria. ADC at t0 may help selecting patients with promising good response to angiogenesis inhibitors. Moreover at t0 and at t2 ADC has the potential to select patients who wouldn't benefit from angiogenesis inhibitors Nowadays, in the era of target therapy, it is crucial to select patients potentially responders. We have to look at cost/benefit ratio and at increasing costs of treatment options. DWI has the potential role to identify patients whose's tumor wouldn't benefit from target therapy, adding a value (ADC) to other imaging (e.g. DCE-MRI, texture imaging) and clinical parameters (e.g. miRNA) in a hypothetic multiparametric analysis.CT Texture Analysis in Clear Cell Renal Cell Carcinoma: a Radiogenomics Prospective Purpose: The aim of this study was to investigate whether quantitative parameters obtained from CT Texture Analysis (CTTA) correlate with expression of miRNA in clear cell Renal Cell Carcinoma (ccRCC). Methods and Materials: In a retrospective single centre study, multiphasic CT examination (with arterial, portal, equilibrium and urographic phases) was performed on 20 patients with clear cell renal carcinomas (14 men and 6 women; mean age 65 years ± 13). Measures of heterogeneity were obtained in post-processing by placing a ROI on the entire tumour and CTTA parameters such as entropy, kurtosis, skewness, mean, mean of positive pixels, and SD of pixel distribution histogram were measured using multiple filter settings. Quantitative data were correlated with the expression of miRNAs obtained from the same cohort of patients: 8 fresh frozen samples and 12 formalin-fixed paraffin-embedded samples (miR-21-5p, miR-210-3p, miR-185-5p, miR-221-3p, miR-145-5p). Both evaluations (miRNAs and CTTA) were performed on tumour tissues as well as on normal cortico-medullar tissues. Analysis of Variance with linear multiple regression model methods were obtained with SPSS statistic software. For all comparisons, statistical significance was assumed p<0.05 Results: We evidenced that CTTA has robust parameters (e.g. entropy, mean, sd) to distinguish normal from pathological tissues. Moreover, a higher coefficient of determination between entropy and miR-21-5p expression (R2 =0,25) was evidenced in tumour tissues as compared to normal tissues (R2 =0,15). Interestingly, excluding four patients with extreme over-expression of miR-21-5p, excellent relation between entropy and miR21-5p levels was found specifically in tumour samples (R2= 0,64; p<0.05). Conclusion: Entropy and miRNA-21-5p show promising correlation in ccRCC; in addiction CTTA features, in particular mean and entropy show a statistically significant increase in ccRCC as compared with normal renal parenchyma

The SPHERE data center: a reference for high contrast imaging processing

The objective of the SPHERE Data Center is to optimize the scientific return of SPHERE at the VLT, by providing optimized reduction procedures, services to users and publicly available reduced data. This paper describes our motivation, the implementation of the service (partners, infrastructure and developments), services, description of the on-line data, and future developments. The SPHERE Data Center is operational and has already provided reduced data with a good reactivity to many observers. The first public reduced data have been made available in 2017. The SPHERE Data Center is gathering a strong expertise on SPHERE data and is in a very good position to propose new reduced data in the future, as well as improved reduction procedures.Comment: SF2A proceeding

Monte Carlo investigations of megavoltage coneâ beam CT using thick, segmented scintillating detectors for soft tissue visualization

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134940/1/mp8957.pd

State-of-the-art MR imaging in the work-up of primary hepatocellular tumors

Magnetic resonance (MR) imaging is an imaging modality that has evolved rapidly in the past two decades. The development of advanced hardware and new sophisticated pulse sequences have allowed faster imaging, with increased temporal and spatial resolution. This has resulted in the development and implementation of new acquisition techniques that facilitate improved visualisation of neoplastic processes. In addition, faster sequences enable multiphasic dynamic imaging after intravenous administration of contrast material, which results in better tumor characterisation and improved diagnostic confidence by the reading radiologist. The radiol

Superparamagnetic Iron Oxide (SPIO)-enhanced Liver MR Imaging with Ferucarbotran

Die Superparamagnetic Iron Oxides (SPIO)-verstärkte MRT der Leber wird als sinnvolle präoperative diagnostische Methode mit einer hohen Sensitivität und Spezifität für die Detektion von fokalen Leberläsionen angewendet. Mit der SPIO-verstärkten MRT ist aber prinzipiell auch eine Differenzierung zwischen benignen und malignen fokalen Leberläsionen möglich auf der Basis ihrer zellulären Zusammensetzung und Funktion (RES-Zellen in normalem Lebergewebe und in benignen Tumoren, keine RES-Zellen in malignen Tumoren). In früheren Studien wurden die Effekte von SPIO-Kontrastmitteln fast ausschließlich auf die Detektion von Läsionen sowie die Effekte in T2-gewichteten (w) Fast-Spin Echo (FSE) und T2*-w Gradienten Echo (GRE) Sequenzen beschränkt, da SPIO hauptsächlich die T2 / T2* - Zeiten verkürzen. Ferucarbotran ist ein relativ neu zugelassenes SPIO-Kontrastmittel, welches als intravenöser Bolus appliziert werden kann und sich durch eine geringe Nebenwirkungsrate vor allem im kardiovaskulären Bereich auszeichnet. Eine dynamische T1-w Perfusionsmessung nach der Bolusapplikation von Ferucarbotran könnte Informationen über die Vaskularisation solider Tumore in der Leber liefern. Die Möglichkeit der Charakterisierung von fokalen Leberläsionen mit Hilfe der dynamischen Ferucarbotran-verstärkten MRT wurde bereits in der Literatur angedeutet und typische Befunde konnten an einer begrenzten Anzahl von Fällen für einzelne fokale Leberläsionen gezeigt werden. Das erste Ziel dieser Arbeit war die Evaluierung der diagnostischen Effizienz des SPIO Kontrastmittel Ferucarbotran in T2-w FSE and T2*-w GRE Sequenzen zur Charakterisierung von fokalen Leberläsionen. Das zweite Ziel war es typische Anreicherungsmuster fokaler Leberläsionen in der dynamischen T1-w MRT mit 2D-GRE and 3D-GRE VIBE Sequenzen zu beschreiben. An einem 1.5 Tesla MRT-System wurden native und kontrastverstärkte T2-w FSE and T2*-w GRE Sequenzen 10 Minuten nach Bolusinjektion von 1.4 ml Ferucarbotran bei 68 Patienten durchgeführt. An einem 1.5 Tesla MRT-System wurden T1-w dynamische Bilder bei 23 Patienten mit einer 2D-GRE Sequenz und bei 37 Patienten mit einer 3D-GRE-VIBE Sequenz akquiriert. Die endgültige Diagnose der 68 Patienten, bei denen T2-w FSE/ T2*-w GRE Sequenzen durchgeführt wurden war Hepatozelluläres Karzinom (HCC, n=29), Lebermetastasen (n=15), Cholangiozelluläres Karzinom (CCC, n=2), Hämangiom (n=6), Leberzelladenom (n=5), Fokal Noduläre Hyperplasie (FNH, n=3) und Zysten (n=8). Die endgültige Diagnose der 60 Patienten, bei denen eine T1-w dynamische Ferucarbotran-verstärkte MRT durchgeführt wurde war HCC (n=25), Lebermetastasen (n=14), CCC (n=2), Hämangiom (n=6), Leberzelladenom (n=3), FNH (n=3) and Zysten (n=7). In den T2-w FSE und T2*-w GRE Bildern wurde das Signal-zu-Rausch-Verhältnis (SNR) und das Kontrast-zu-Rausch-Verhältnis basierend auf Signalintensitätsmessungen in den fokalen Läsionen und dem Leberparenchym durchgeführt. Der prozentuale Signalverlust (PSIL) der verschiedenen fokalen Läsionen von der nativen zur kontrastverstärkten T2-w FSE –Sequenz wurde errechnet. Eine qualitative Auswertung der Bildqualität sowie der Abgrenzbarkeit der Läsionen im Vergleich zwischen kontrastverstärkten T2-w FSE und kontrastverstärkten T2*-w GRE Bildern erfolgte. In den T1-w dynamischen Bildern wurden Signalintensitätsmessungen im Leberparenchym, den Lebergefäßen und in fokalen Leberläsionen vorgenommen um SNR und CNR zu errechnen. Das mittlere SNR von soliden benignen Läsionen zeigte einen Abfall in der T2-w FSE Sequenz von 34.1 vor auf 21.0 (p<0,05) nach Kontrastmittelgabe; maligne Leberläsionen zeigten nur einen geringen Signalverlust von 33.3 auf 32.5 (nicht signifikant). Das mittlere CNR der malignen Läsionen war am höchsten in der kontrastverstärkten T2*-w Sequenz vergleichen mit der nativen- und kontrastverstärkten T2-w FSE Sequenz (29.9 vs. 22.7 (p<0.01) vs. 12.8 SI (p<0.01)). Bei einem Grenzwert von 25 % Signalverlust (PSIL) in der T2-w FSE Sequenz konnte eine Sensitivität und Spezifität von 97.8% beziehungsweise 92.9% mit der Ferucarbotran-verstärkten T2-w MRT erreicht werden. Der Signalverlust (PSIL) von Adenomen und FNH zeigte keine Überschneidungen. Kontrastverstärkte T2*-w GRE Bilder zeichneten sich durch eine überlegene Bildqualität und Abgrenzbarkeit von Läsionen (p < .05) im Vergleich zur kontrastverstärkten T2-w FSE Sequenz aus. In der dynamischen Ferucarbotran-verstärkten T1-w MRT konnte eine Hypervaskularisation in den typischerweise hypervaskularisierten Läsionen wie HCC, Adenom oder FNH nicht gezeigt werden. In Hämangiomen hingegen war ein frühes Enhancement in allen Fällen abzugrenzen. In der T1-w 3D-GRE Sequenz lag das mittlere CNR der soliden benignen Läsionen bei etwa null (FNH) oder war sogar positiv (Adenom), während das mittlere CNR der malignen Läsionen im negativen Bereich zu allen Zeitpunkten lag. Zusammenfassend konnte gezeigt werden, dass solide benigne Läsionen eine SPIO-Speicherung zeigen, welche einen signifikanten Signalabfall in den Läsionen in T2-w Bildern hervorruft. Mit einem Grenzwert von 25% Signalverlust (PSIL) kann eine sichere Unterscheidung von benignen und malignen Läsionen erfolgen. Für die Detektion von Läsionen ist eine zusätzliche T2*-w Sequenz hilfreich wegen des stärkeren Läsion-zu-Leber-Kontrastes (CNR), einer verbesserten subjektiven Abgrenzbarkeit der Läsionen und der besseren Bildqualität. Mit der dynamischen T1-w MRT mit einer 3D-GRE Sequenz nach Bolusinjektion von Ferucarbotran können möglicherweise Aspekte zur Charakterisierung von malignen versus benignen Leberläsionen gewonnen werden. Allerdings liefert die T1-w dynamische MRT offensichtlich weder mit 2D- noch mit 3D-GRE Sequenzen die gleiche Information über die Vaskularisation von Leberläsionen wie die Gadolinium-verstärkte MRT, da die von den extrazellulären Kontrastmitteln bekannten Anreicherungsphänomene in hypervaskularisierten Leberläsionen mit der dynamischen Ferucarbotran-verstärkten MRT nicht nachvollzogen werden konnten. Für die Praxis bedeutet dies, dass der Schwerpunkt der Ferucarbotran-verstärkten MRT Untersuchung weiterhin bei den T2-w und T2*-w Sequenzen liegt, um die in der Literatur berichteten hohen Detektionsraten und die von uns untersuchten Möglichkeiten zur Charakterisierung auszunutzen. Die während der Bolusapplikation durchgeführte T1-w dynamische Bildgebung kann in limitierten Fällen wie z.B. Häma-ngiomen differentialdiagnostische Hilfestellungen liefern, kann aber die Information einer dynamischen Untersuchung mit extrazellulären Kontrastmitteln nicht ersetzten

On the development of a novel detector for simultaneous imaging and dosimetry in radiotherapy

Radiotherapy uses x-ray beams to deliver prescribed radiation doses that conform to target anatomy and minimise exposure of healthy tissue. Accuracy of dose delivery is essential, thus verification of dose distributions in vivo is desirable to monitor treatments and prevent errors from compromising patient outcomes. Electronic portal imaging devices (EPIDs) are commonly used x-ray imagers, however their non water-equivalent response complicates use for dosimetry. In this thesis, a Monte Carlo (MC) model of a standard EPID was developed and extended to novel water-equivalent configurations based on prototypes in which the high atomic number components were replaced with an array of plastic scintillator fibres. The model verified that full simulation of optical transport is not necessary to predict the standard EPID dose response, which can be accurately quantified from energy deposited in the phosphor screen. By incorporating computed tomography images into the model, its capacity to predict portal dose images of humanoid anatomy was also demonstrated. The prototype EPID’s water-equivalent dose response was characterised experimentally and with the MC model. Despite exhibiting lower spatial resolution and contrast-to-noise ratio relative to the standard EPID, its image quality was sufficient to discern gross anatomical structures of an anthropomorphic phantom. Opportunities to improve imaging performance while maintaining a water-equivalent dose response were identified using the model. Longer fibres increased efficiency and use of an extra-mural absorber maximised spatial resolution. Optical coupling between the scintillator fibres and the imaging panel may further improve performance. This thesis demonstrates the feasibility of developing a next-generation EPID for simultaneous imaging and dosimetry in radiotherapy. Such a detector could monitor treatment deliveries in vivo and thereby facilitate adaptations to treatment plans in order to improve patient outcomes