TY - JOUR A1 - Salpati, Laurent A1 - Chu, Xiaoyan A1 - Chen, Liangfu A1 - Prasad, Bhagwat A1 - Dallas, Shannon A1 - Evers, Raymond A1 - Mamaril-Fishman, Donna A1 - Geier, Ethan G. A1 - Kehler, Jonathan A1 - Kunta, Jeevan A1 - Mezler, Mario A1 - Laplanche, Loic A1 - Pang, Jodie A1 - Soars, Matthew G. A1 - Unadkat, Jashvant D. A1 - van Waterschoot, Robert A.B. A1 - Yabut, Jocelyn A1 - Schinkel, Alfred H. A1 - Scheer, Nico A1 - Rode, Anja T1 - Evaluation of organic anion transporting polypeptide 1B1 and 1B3 humanized mice as a translational model to study the pharmacokinetics of statins JF - Drug Metabolism and Disposition N2 - Organic anion transporting polypeptide (Oatp) 1a/1b knockout and OATP1B1 and -1B3 humanized mouse models are promising tools for studying the roles of these transporters in drug disposition. Detailed characterization of these models will help to better understand their utility for predicting clinical outcomes. To advance this approach, we carried out a comprehensive analysis of these mouse lines by evaluating the compensatory changes in mRNA expression, quantifying the amounts of OATP1B1 and -1B3 protein by liquid chromatography–tandem mass spectrometry, and studying the active uptake in isolated hepatocytes and the pharmacokinetics of some prototypical substrates including statins. Major outcomes from these studies were 1) mostly moderate compensatory changes in only a few genes involved in drug metabolism and disposition, 2) a robust hepatic expression of OATP1B1 and -1B3 proteins in the respective humanized mouse models, and 3) functional activities of the human transporters in hepatocytes isolated from the humanized models with several substrates tested in vitro and with pravastatin in vivo. However, the expression of OATP1B1 and -1B3 in the humanized models did not significantly alter liver or plasma concentrations of rosuvastatin and pitavastatin compared with Oatp1a/1b knockout controls under the conditions used in our studies. Hence, although the humanized OATP1B1 and -1B3 mice showed in vitro and/or in vivo functional activity with some statins, further characterization of these models is required to define their potential use and limitations in the prediction of drug disposition and drug-drug interactions in humans. Y1 - 2014 U6 - http://dx.doi.org/10.1124/dmd.114.057976 SN - 1521-009X VL - 42 IS - 8 SP - 1301 EP - 1313 PB - ASPET CY - Bethesda, Md. ER - TY - JOUR A1 - Luisier, Raphaëlle A1 - Lempiäinen, Harri A1 - Scherbichler, Nina A1 - Braeuning, Albert A1 - Geissler, Miriam A1 - Dubost, Valerie A1 - Müller, Arne A1 - Scheer, Nico A1 - Chibout, Salah-Dine A1 - Hara, Hisanori A1 - Picard, Frank A1 - Theil, Diethilde A1 - Couttet, Philippe A1 - Vitobello, Antonio A1 - Grenet, Olivier A1 - Grasl-Kraupp, Bettina A1 - Ellinger-Ziegelbauer, Heidrung A1 - Thomson, John P. A1 - Meehan, Richard R. A1 - Elcombe, Clifford R. A1 - Henderson, Colin J. A1 - Wolf, C. Roland A1 - Schwarz, Michael A1 - Moulin, Pierre A1 - Terranova, Remi A1 - Moggs, Jonathan G. T1 - Phenobarbital Induces Cell Cycle Transcriptional Responses in Mouse Liver Humanized for Constitutive Androstane and Pregnane X Receptors JF - Toxicological Sciences N2 - The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are closely related nuclear receptors involved in drug metabolism and play important roles in the mechanism of phenobarbital (PB)-induced rodent nongenotoxic hepatocarcinogenesis. Here, we have used a humanized CAR/PXR mouse model to examine potential species differences in receptor-dependent mechanisms underlying liver tissue molecular responses to PB. Early and late transcriptomic responses to sustained PB exposure were investigated in liver tissue from double knock-out CAR and PXR (CARᴷᴼ-PXRᴷᴼ), double humanized CAR and PXR (CARʰ-PXRʰ), and wild-type C57BL/6 mice. Wild-type and CARʰ-PXRʰ mouse livers exhibited temporally and quantitatively similar transcriptional responses during 91 days of PB exposure including the sustained induction of the xenobiotic response gene Cyp2b10, the Wnt signaling inhibitor Wisp1, and noncoding RNA biomarkers from the Dlk1-Dio3 locus. Transient induction of DNA replication (Hells, Mcm6, and Esco2) and mitotic genes (Ccnb2, Cdc20, and Cdk1) and the proliferation-related nuclear antigen Mki67 were observed with peak expression occurring between 1 and 7 days PB exposure. All these transcriptional responses were absent in CARᴷᴼ-PXRᴷᴼ mouse livers and largely reversible in wild-type and CARʰ-PXRʰ mouse livers following 91 days of PB exposure and a subsequent 4-week recovery period. Furthermore, PB-mediated upregulation of the noncoding RNA Meg3, which has recently been associated with cellular pluripotency, exhibited a similar dose response and perivenous hepatocyte-specific localization in both wild-type and CARʰ-PXRʰ mice. Thus, mouse livers coexpressing human CAR and PXR support both the xenobiotic metabolizing and the proliferative transcriptional responses following exposure to PB. Y1 - 2014 U6 - http://dx.doi.org/https://doi.org/10.1093/toxsci/kfu038 SN - 1094-2025 VL - 139 IS - 2 SP - 501 EP - 511 PB - Oxford University Press CY - Oxford ER - TY - JOUR A1 - Henderson, Colin J. A1 - Mclaughlin, Lesley A. A1 - Scheer, Nico A1 - Stanley, Lesley A. A1 - Wolf, C. Roland T1 - Cytochrome b5 Is a Major Determinant of Human Cytochrome P450 CYP2D6 and CYP3A4 Activity In Vivo s JF - Molecular Pharmacology Y1 - 2015 U6 - http://dx.doi.org/10.1124/mol.114.097394 SN - 1521-0111 VL - 87 IS - 4 SP - 733 EP - 739 PB - ASPET CY - Bethesda ER - TY - JOUR A1 - Hough, Lindsay B. A1 - Nalwalk, Julia W. A1 - Ding, Xinxin A1 - Scheer, Nico T1 - Opioid Analgesia in P450 Gene Cluster Knockout Mice: A Search for Analgesia-Relevant Isoforms JF - Drug Metabolism and Disposition Y1 - 2015 U6 - http://dx.doi.org/10.1124/dmd.115.065490 SN - 1521-009x VL - 43 IS - 9 SP - 1326 EP - 1330 ER - TY - JOUR A1 - Scheer, Nico A1 - Kapelyukh, Yury A1 - Rode, Anja A1 - Oswald, Stefan A1 - Busch, Diana A1 - Mclaughlin, Lesley A. A1 - Lin, De A1 - Henderson, Colin J. A1 - Wolf, C. Roland T1 - Defining Human Pathways of Drug Metabolism In Vivo through the Development of a Multiple Humanized Mouse Model JF - Drug Metabolism and Disposition Y1 - 2015 U6 - http://dx.doi.org/10.1124/dmd.115.065656 SN - 1521-009x VL - 43 IS - 11 SP - 1679 EP - 1690 PB - ASPET CY - Bethesda ER - TY - JOUR A1 - Dallas, Shannon A1 - Salphati, Laurent A1 - Gomez-Zepeda, David A1 - Wanek, Thomas A1 - Chen, Liangfu A1 - Chu, Xiaoyan A1 - Kunta, Jeevan A1 - Mezler, Mario A1 - Menet, Marie-Claude A1 - Chasseigneaux, Stephanie A1 - Declèves, Xavier A1 - Langer, Oliver A1 - Pierre, Esaie A1 - DiLoreto, Karen A1 - Hoft, Carolin A1 - Laplanche, Loic A1 - Pang, Jodie A1 - Pereira, Tony A1 - Andonian, Clara A1 - Simic, Damir A1 - Rode, Anja A1 - Yabut, Jocelyn A1 - Zhang, Xiaolin A1 - Scheer, Nico T1 - Generation and Characterization of a Breast Cancer Resistance Protein Humanized Mouse Model JF - Molecular Pharmacology N2 - Breast cancer resistance protein (BCRP) is expressed in various tissues, such as the gut, liver, kidney and blood brain barrier (BBB), where it mediates the unidirectional transport of substrates to the apical/luminal side of polarized cells. Thereby BCRP acts as an efflux pump, mediating the elimination or restricting the entry of endogenous compounds or xenobiotics into tissues and it plays important roles in drug disposition, efficacy and safety. Bcrp knockout mice (Bcrp−/−) have been used widely to study the role of this transporter in limiting intestinal absorption and brain penetration of substrate compounds. Here we describe the first generation and characterization of a mouse line humanized for BCRP (hBCRP), in which the mouse coding sequence from the start to stop codon was replaced with the corresponding human genomic region, such that the human transporter is expressed under control of the murine Bcrp promoter. We demonstrate robust human and loss of mouse BCRP/Bcrp mRNA and protein expression in the hBCRP mice and the absence of major compensatory changes in the expression of other genes involved in drug metabolism and disposition. Pharmacokinetic and brain distribution studies with several BCRP probe substrates confirmed the functional activity of the human transporter in these mice. Furthermore, we provide practical examples for the use of hBCRP mice to study drug-drug interactions (DDIs). The hBCRP mouse is a promising model to study the in vivo role of human BCRP in limiting absorption and BBB penetration of substrate compounds and to investigate clinically relevant DDIs involving BCRP. Y1 - 2016 U6 - http://dx.doi.org/10.1124/mol.115.102079 SN - 1521-0111 VL - 89 IS - 5 SP - 492 EP - 504 PB - ASPET CY - Bethesda, Md. ER - TY - JOUR A1 - Zhang, Jin A1 - Heimbach, Tycho A1 - Scheer, Nico A1 - Barve, Avantika A1 - Li, Wenkui A1 - Lin, Wen A1 - He, Handan T1 - Clinical Exposure Boost Predictions by Integrating Cytochrome P450 3A4–Humanized Mouse Studies With PBPK Modeling JF - Journal of Pharmaceutical Sciences N2 - NVS123 is a poorly water-soluble protease 56 inhibitor in clinical development. Data from in vitro hepatocyte studies suggested that NVS123 is mainly metabolized by CYP3A4. As a consequence of limited solubility, NVS123 therapeutic plasma exposures could not be achieved even with high doses and optimized formulations. One approach to overcome NVS123 developability issues was to increase plasma exposure by coadministrating it with an inhibitor of CYP3A4 such as ritonavir. A clinical boost effect was predicted by using physiologically based pharmacokinetic (PBPK) modeling. However, initial boost predictions lacked sufficient confidence because a key parameter, fraction of drug metabolized by CYP3A4 (ƒₘCYP3A4), could not be estimated with accuracy on account of disconnects between in vitro and in vivo preclinical data. To accurately estimate ƒₘCYP3A4 in human, an in vivo boost effect study was conducted using CYP3A4-humanized mouse model which showed a 33- to 56-fold exposure boost effect. Using a top-down approach, human ƒₘCYP3A4 for NVS123 was estimated to be very high and included in the human PBPK modeling to support subsequent clinical study design. The combined use of the in vivo boost study in CYP3A4-humanized mouse model mice along with PBPK modeling accurately predicted the clinical outcome and identified a significant NVS123 exposure boost (∼42-fold increase) with ritonavir. Y1 - 2016 U6 - http://dx.doi.org/doi.org/10.1016/j.xphs.2016.01.021 SN - 0022-3549 VL - Volume 105 IS - Issue 4 SP - 1398 EP - 1404 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Wilson, Ian D. A1 - Wilson, Claire E. A1 - Scheer, Nico A1 - Dickie, A.P. A1 - Schreiter, K. A1 - Wilson, E. M. A1 - Riley, R. J. A1 - Wehr, R. A1 - Bial, J. T1 - The Pharmacokinetics and Metabolism of Lumiracoxib in Chimeric Humanized and Murinized FRG Mice JF - Biochemical pharmacology Y1 - 2017 U6 - http://dx.doi.org/10.1016/j.bcp.2017.03.015 SN - 1873-2968 VL - Volume 135 SP - 139 EP - 150 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Leschinger, Tim A1 - Birgel, Stefan A1 - Hackl, Michael A1 - Staat, Manfred A1 - Müller, Lars Peter A1 - Wegmann, Kilian T1 - A musculoskeletal shoulder simulation of moment arms and joint reaction forces after medialization of the supraspinatus footprint in rotator cuff repair JF - Computer Methods in Biomechanics and Biomedical Engineering Y1 - 2019 U6 - http://dx.doi.org/10.1080/10255842.2019.1572749 IS - Early view PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Wilson, C. E. A1 - Dickie, A. P. A1 - Schreiter, K. A1 - Wehr, R. A1 - Wilson, E. M. A1 - Bial, J. A1 - Scheer, Nico A1 - Wilson, I. D. A1 - Riley, R. J. T1 - The pharmacokinetics and metabolism of diclofenac in chimeric humanized and murinized FRG mice JF - Archives of Toxicology N2 - The pharmacokinetics of diclofenac were investigated following single oral doses of 10 mg/kg to chimeric liver humanized and murinized FRG and C57BL/6 mice. In addition, the metabolism and excretion were investigated in chimeric liver humanized and murinized FRG mice. Diclofenac reached maximum blood concentrations of 2.43 ± 0.9 µg/mL (n = 3) at 0.25 h post-dose with an AUCinf of 3.67 µg h/mL and an effective half-life of 0.86 h (n = 2). In the murinized animals, maximum blood concentrations were determined as 3.86 ± 2.31 µg/mL at 0.25 h post-dose with an AUCinf of 4.94 ± 2.93 µg h/mL and a half-life of 0.52 ± 0.03 h (n = 3). In C57BL/6J mice, mean peak blood concentrations of 2.31 ± 0.53 µg/mL were seen 0.25 h post-dose with a mean AUCinf of 2.10 ± 0.49 µg h/mL and a half-life of 0.51 ± 0.49 h (n = 3). Analysis of blood indicated only trace quantities of drug-related material in chimeric humanized and murinized FRG mice. Metabolic profiling of urine, bile and faecal extracts revealed a complex pattern of metabolites for both humanized and murinized animals with, in addition to unchanged parent drug, a variety of hydroxylated and conjugated metabolites detected. The profiles in humanized mice were different to those of both murinized and wild-type animals, e.g., a higher proportion of the dose was detected in the form of acyl glucuronide metabolites and much reduced amounts as taurine conjugates. Comparison of the metabolic profiles obtained from the present study with previously published data from C57BL/6J mice and humans revealed a greater, though not complete, match between chimeric humanized mice and humans, such that the liver humanized FRG model may represent a model for assessing the biotransformation of such compounds in humans. Y1 - 2018 U6 - http://dx.doi.org/10.1007/s00204-018-2212-1 SN - 1432-0738 VL - 92 IS - 6 SP - 1953 EP - 1967 PB - Springer ER - TY - JOUR A1 - Hüning, Felix A1 - Hillgärtner, Michael A1 - Reke, Michael T1 - Rolling Labs – Teaching Vehicle Electronics from the Beginning JF - International Journal of Engineering Pedagogy (iJEP) Y1 - 2019 U6 - http://dx.doi.org/10.3991/ijep.v9i1.9241 SN - 2192-4880 VL - 9 IS - 1 SP - 34 EP - 49 ER - TY - JOUR A1 - Raupp, Sebastian M. A1 - Schmitt, Marcel A1 - Walz, Anna-Lena A1 - Diehm, Ralf A1 - Hummel, Helga A1 - Scharfer, Philip A1 - Schabel, Wilhelm T1 - Slot die stripe coating of low viscous fluids JF - Journal of Coatings Technology and Research N2 - Slot die coating is applied to deposit thin and homogenous films in roll-to-roll and sheet-to-sheet applications. The critical step in operation is to choose suitable process parameters within the process window. In this work, we investigate an upper limit for stripe coatings. This maximum film thickness is characterized by stripe merging which needs to be avoided in a stable process. It is shown that the upper limit reduces the process window for stripe coatings to a major extent. As a result, stripe coatings at large coating gaps and low viscosities are only possible for relatively thick films. Explaining the upper limit, a theory of balancing the side pressure in the gap region in the cross-web direction has been developed. Y1 - 2018 U6 - http://dx.doi.org/10.1007/s11998-017-0039-y SN - 1935-3804 VL - 15 IS - 5 SP - 899 EP - 911 PB - Springer ER - TY - JOUR A1 - Ziebura, Dawid A1 - Bremen, Sebastian A1 - Schleifenbaum, Johannes Henrich A1 - Gebhardt, Andreas T1 - Machbarkeitsstudie zur Verarbeitung von nicht rostendem Stahl 1.4404 unter Verwendung einer Diodenlaser-basierten LPBF-Maschine mit kartesischem Achssystem JF - RTejournal - Forum für Rapid Technologie Y1 - 2018 SN - 1614-0923 VL - 15 ER - TY - JOUR A1 - Dotzauer, Martin A1 - Pfeiffer, Diana A1 - Lauer, Markus A1 - Pohl, Marcel A1 - Mauky, Eric A1 - Bär, Katharina A1 - Sonnleitner, Matthias A1 - Zörner, Wilfried A1 - Hudde, Jessica A1 - Schwarz, Björn A1 - Faßauer, Burkhardt A1 - Dahmen, Markus A1 - Rieke, Christian A1 - Herbert, Johannes A1 - Thrän, Daniela T1 - How to measure flexibility – Performance indicators for demand driven power generation from biogas plants JF - Renewable Energy Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.renene.2018.10.021 SN - 0960-1481 SP - 135 EP - 146 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Kotliar, Konstantin A1 - Lanzl, Ines T1 - Vaskuläre Biomarker der retinalen Gefäβanalyse T1 - Vascular Biomarkers in Retinal Vessel Analysis JF - Klinische Monatsblätter fur Augenheilkunde N2 - Mit modernen nicht invasiven bildgebenden Verfahren lassen sich anhand der Fundusfotografie bzw. der optischen Verfilmung Aspekte der funktionellen und strukturellen retinalen Gefäßveränderungen objektiv untersuchen. Der Zustand und das Verhalten retinaler Gefäße beeinflussen im prä-, post- und kapillaren Bereich den Blutfluss und strömungsbedingte Stoffwechselverhältnisse passiv und aktiv über den Gefäßdurchmesser. Retinale Gefäße gleichen von Aufbau und Funktion den zerebralen Gefäßen und spiegeln den Zustand der Mikrozirkulation wider. Mithilfe von aus den Gefäßweiten berechneten Biomarkern soll eine Aussage über die Prognose von systemischen vaskulär bedingten Erkrankungen getroffen werden. Die statische retinale Gefäßanalyse befasst sich mit der Untersuchung des Zustandes der prä- und postkapillaren Gefäßdurchmesser der retinalen Mikrozirkulation anhand einer optischen Fundusaufnahme. Bei der dynamischen retinalen Gefäßanalyse wird der Längsschnitt eines retinalen Gefäßes nicht invasiv funktionell und strukturell über einen Zeitraum vor, während und nach einer spezifischen vaskulären Stimulation untersucht. Die genaue Methodologie der Auswertung und die Bezeichnung der Parameter variieren bei unterschiedlichen Ansätzen. Mittels retinaler Gefäßanalyse wurden bislang mehrere klinische Querschnitts- und Interventionsstudien in der Augenheilkunde und anderen Fachgebieten, inkl. Kardiologie, Neurologie, Neurochirurgie, Nephrologie, Gynäkologie, Sportmedizin, Diabetologie, Hypertensiologie usw. durchgeführt. Mit der statischen retinalen Gefäßanalyse steht eine kostengünstige, reproduzierbare, nicht invasive Screeningtechnik zur Verfügung, um eine prognostische Aussage über die Gefäßgesundheit eines individuellen Patienten zu treffen. Die dynamische retinale Gefäßanalyse besitzt ein weiteres diagnostisches Anwendungsspektrum als die statische, da sie das Verhalten retinaler Gefäße zeitkontinuierlich untersucht. Die Evaluation vaskulärer Erkrankungen sowie zerebro- bzw. kardiovaskulärer Morbidität und Mortalität mittels mehrerer methodologischer Modalitäten retinaler Gefäßanalyse mit ihren jeweiligen quantitativen Biomarkern bietet eine zukunftsträchtige diagnostische Perspektive. Die interdisziplinäre klinische Anwendung dieser vaskulären Biomarker gewinnt zunehmend an Bedeutung, sowohl in der Augenheilkunde als auch in anderen Fachgebieten. Y1 - 2018 U6 - http://dx.doi.org/10.1055/a-0774-7987 SN - 0023-2165 VL - 235 IS - 12 SP - 1352 EP - 1359 PB - Thieme CY - Stuttgart ER - TY - JOUR A1 - Bleilevens, Christian A1 - Hill, Aileen A1 - Grzanna, Tim A1 - Fechter, Tamara A1 - Bohnen, Melanie A1 - Weber, Hans-Joachim A1 - Beckers, Christian A1 - Borosch, Sebastian A1 - Zayat, Rashad A1 - Benstoem, Carin A1 - Rossaint, Rolf A1 - Goetzenich, Andreas T1 - In vitro head-to-head comparison of anticoagulation properties of two heparin brands in a human blood miniature mock loop JF - Interactive cardiovascular and thoracic surgery Y1 - 2019 U6 - http://dx.doi.org/10.1093/icvts/ivy206 SN - 1569-9285 VL - 28 IS - 1 SP - 120 EP - 127 ER - TY - JOUR A1 - Heinke, Lars N. A1 - Knicker, Axel J. A1 - Albracht, Kirsten T1 - Evaluation of passively induced shoulder stretch reflex using an isokinetic dynamometer in male overhead athletes JF - Isokinetics and Exercise Science N2 - BACKGROUND: Muscle stretch reflexes are widely considered to beneficially influence joint stability and power generation in the lower limbs. While in the upper limbs and especially in the muscles surrounding the shoulder joint such evidence is lacking. OBJECTIVE: To quantify the electromyographical response in the muscles crossing the shoulder of specifically trained overhead athletes to an anterior perturbation force. METHODS: Twenty healthy male participants performed six sets of different external shoulder rotation stretches on an isokinetic dynamometer over a range of amplitudes and muscle pre-activation moment levels. All stretches were applied with a dynamometer acceleration of 10,000∘/s2 and a velocity of 150∘/s. Electromyographical response was measured via sEMG. RESULTS: Consistent reflexes were not observed in all experimental conditions. The reflex latencies revealed a significant muscle main effect (F (2,228) = 99.31, p< 0.001; η2= 0.466; f= 0.934) and a pre-activation main effect (F (1,228) = 142.21, p< 0.001; η2= 0.384; f= 1.418). The stretch reflex amplitude yielded a significant pre-activation main effect (F (1,222) = 470.373, p< 0.001; η2= 0.679; f= 1.454). CONCLUSION: Short latency muscle reflexes showed a tendency to an anterior to posterior muscle recruitment whereby the main internal rotator muscles of the shoulder revealed the most consistent results. Y1 - 2018 U6 - http://dx.doi.org/10.3233/IES-184111 SN - 1878-5913 VL - 26 IS - 4 SP - 265 EP - 274 PB - IOS Press CY - Amsterdam ER - TY - JOUR A1 - Viti, Nicolo A1 - Valero, Daniel A1 - Gualtieri, Carlo T1 - Numerical Simulation of Hydraulic Jumps. Part 2: Recent Results and Future Outlook JF - Water Y1 - 2019 U6 - http://dx.doi.org/10.3390/w11010028 SN - 2073-4441 VL - 11 IS - 1 SP - Art. Nr. 28 ER - TY - JOUR A1 - Valero, Daniel A1 - Viti, Nicolo A1 - Gualtieri, Carlo T1 - Numerical Simulation of Hydraulic Jumps. Part 1: Experimental Data for Modelling Performance Assessment JF - Water Y1 - 2019 U6 - http://dx.doi.org/10.3390/w11010036 SN - 2073-4441 VL - 11 IS - 1 SP - Art. Nr. 36 PB - MDPI CY - Basel ER - TY - JOUR A1 - Laura, C.O. A1 - Drechsler, Klaus A1 - Erdt, M. A1 - Wesarg, S. A1 - Bale, R. T1 - Intervention assessment tool for primary tumors in the liver JF - Current Directions in Biomedical Engineering N2 - After a liver tumor intervention the medical doctor has to compare both pre and postoperative CT acquisitions to ensure that all carcinogenic cells are destroyed. A correct assessment of the intervention is of vital importance, since it will reduce the probability of tumor recurrence. Some methods have been proposed to support the medical doctors during the assessment process, however, all of them focus on secondary tumors. In this paper a tool is presented that enables the outcome validation for both primary and secondary tumors. Therefore, a multiphase registration (preoperative arterial and portal phases) followed by a registration between the pre and postoperative CT images is carried out. The first registration is in charge of the primary tumors that are only visible in the arterial phase. The secondary tumors will be incorporated in the second registration step. Finally, the part of the tumor that was not covered by the necrosis is quantified and visualized. The method has been tested in 9 patients, with an average registration error of 1.41 mm. Y1 - 2018 U6 - http://dx.doi.org/10.1515/cdbme-2018-0081 SN - 2364-5504 VL - 4 IS - 1 SP - 337 EP - 340 PB - De Gruyter CY - Berlin ER -