Translational Oncologic Imaging

Cardiovascular Imaging Group

Radiologische Forschung (Radiology Research)

Muskuloskelettale Radiologie (Musculoskeletal Radiology)

Molekulare Bildgebung (Molecular imaging)

 

 

AG Braren

Contact Details

Assistant Prof. Rickmer F. Braren, MD

Institute of Diagnostic and Interventional Radiology
Technische Universität München
Klinikum rechts der Isar
Ismaninger Str. 22, 81675 Munich

phone: +49 89 4140-5627
email: rbraren@tum.de

Research Background

Multiparametric Imaging in Oncology

Traditionally imaging in oncology serves to determine the exact (i) tumor size, (ii) tumor location, and (iii) its relationship to adjacent structures and to identify the potential spread of tumor cells (iv) to lymph nodes and (v) other organs. Oncological staging is then based on the TNM classification system. Therapy response in oncology is evaluated based on change in tumor size (i.e. RECIST). However, a more comprehensive tumor characterization and the efficacy testing of and the monitoring of response to novel therapeutic agents, which target specific aspects of tumor biology (i.e. tumor vasculature, stromal content, etc.) would greatly benefit from quantitative measures of these tumor constituents.

Magnetic resonance imaging (MRI) is a non-invasive imaging modality that allows the quantitative assessment of multiple physiological parameters. For example, dynamic contrast enhanced (DCE) - MRI in combination with pharmacokinetic (PK) modeling and diffusion weighted (DW) - MRI can provide information on tumor vasculature and structural composition. Other MRI based techniques such as the detection of hyperpolarized 13C metabolites could aid in the physiological characterization (e.g. metabolic activity.

Similarly, computer tomography (CE-CT) provides quantitative measurements. Spectral CT based on the recently clinically introduced dual layer technology can further differentiate tissue properties based on the separation of high and low energy photons.

The careful validation of these imaging parameters in oncology is the focus of our research group. To this end we employ various endogenous tumor (e.g. hepatocellular carcinoma, pancreatic adenocarcinoma) model systems and human subject research. Imaging data is co-registered and correlated with histopathological, molecular and genetic information.

Image interpretation and deep learning

Radiological classification systems are for the most part qualitative. Determination of a specific disease stage is based on the presence/absence of certain descriptors (e.g. tumor encasement of the major visceral arteries in pancreatic cancer) with the goal to then deduct a stage specific treatment plan (e.g. surgery versus chemotherapy). With the appreciation of intra- and inter-individual tumor heterogeneity as a major reason for differences in therapy efficacy/resistance more sophisticated classification systems could aid the development of individualized treatment plans in oncology. More sophisticated image analysis algorithms are required. The complexity of such data analyses, especially considering multi-parametric multimodality imaging (multiphasic CT and MRI, multiparametric MRI, PET-MRI) requires computer aided techniques. In collaboration with the Image-Based Biological Modeling Group (Prof. Björn Menze) we develop predictive automatic frameworks based on fully convolutional and 3D convolutional neural networks.

Clinical Studies

ETAP  (Evaluation des Therapieansprechens mittels FDG PET/MRT bei Patienten mit Pankreaskarzinom) is a prospective, multicenter, exploratory, pilot study. It is planned, executed, financed and run by the Institute for Diagnostic and Interventional Radiology, the II. Medical and Nuclear Medicine Clinic and Polyclinic and the Department of Surgery of the Klinikum rechts der Isar of the Technical University of Munich, the University Hospital Essen (Prof. Jens Siveke) and the University Hospital Münster (Prof. Moritz Wildgruber).

The aim of the study is to find out whether a tumor response can be established by means of a combined PET / MRI examination before and/or early (i.e. 2 weeks) after the initiation of systemic chemotherapy in patients with advanced pancreatic carcinoma.

ProActive (Multiparametrische MRT zur aktiven Überwachung von Patienten mit low-risk Prostatakarzinom: Eine prospektive, longitudinale multizentrische Vergleichsstudie (Coordinating principle investigators: Prof. K. Nikolaou, Prof. F. Bamberg).

Aim of the study is to compare the value of multiparametric MRI (mpMRI) and MR-guided biopsy versus systematic biopsies with regard to progression rate from low-risk to intermediate/high-risk

Funding sources

  • SFB 824 (Bildgebung zur Selektion, Überwachung und Individualisierung der Krebstherapie) „Imaging of structural and metabolic heterogeneity in pancreatic cancer“
  • NVIDIA Academic Hardware Grant:  Deep Learning for Tumor Recognition and Segmentation in MR Images
  • BMBF Projekt m4 (Personalisierte Medizin, PM8: Entwicklung und Evaluation neuer CT und MRT Techniken als Biomarker für die Beurteilung eines medikamentösen Therapieerfolgs) Development of Magnetic Virotargeting for Vesicular Stomatitis Virus based Tumortherapy
  • Fakultätsinterne Förderung von Rotationsstellen für promovierte Ärzte der TU München (KKF) Imaging biodistribution and replication of oncolytic vesicular stomatitis virus (VSV) by MRI and bioluminescence in a rat model of HCC
  • NVIDIA Academic Hardware Grant:  Convolutional neural network applications for cancer patient outcome prediction in hepatocellular carcinoma: The DEVELOP study (DEep learning using Volumetric datasEts for Liver cancer Outcome Prediction)
  • Stipendium Promotionsprogramm Translationale Medizin (Mathias Schillmaier)
  • Stipendium DAAD GERLS (Omar Kamal)
  • DKTK Strategische Initiative im Bereich Bildgebung - JIP (Prof. Schlemmer, A. Radbruch et al)

Group Members

Group leader

Rickmer Braren (MD)

Postdocs

Irina Heid (Ph.D.)
Georgios Kaissis (MD)
Fabian Lohöfer (MD)
Omar Kamal (MD)

Graduate students

Mathias Schillmaier (MD/PhD student)
Elisabeth Blimsrieder (DVM)

Medical students

Sabine Maderthaner
Moritz Meyer
Julia Danner
Daniel Havel
Sebastian Ziegelmayer
Francis Koester
Marie Hörl
Julia Danner
Lia Gebrekidan
Dominik Keim

Technicians

Iryna Skuratovska
Felix Gebser

Collaborators

Moritz Wildgruber, MD, Institut für Klinische Radiologie, Universitätsklinikum Münster, Translational Research Imaging Center (TRIC)

Donna P. Ankerst, PhD, Zentrum Mathematik, Lehrstuhl für mathematische Modellierung biologischer Systeme, Technische Universität München

www.sfb824.de

Peer Review Publications

Borderline-resectable pancreatic adenocarcinoma: Contour irregularity of the venous confluence in pre-operative computed tomography predicts histopathological infiltration. Kaissis GA, Lohöfer FK, Ziegelmayer S, Danner J, Jäger C, Schirren R, Ankerst D, Ceyhan GO, Friess H, Rummeny EJ, Weichert W, Braren RF. PLoS One. 2019 Jan 2;14(1)

Arterial Pseudoaneurysm within a Pancreatic Pseudocyst. Phillip V, Braren R, Lukas N, Schmid RM, Geisler F. Case Rep Gastroenterol. 2018 Aug 28;12(2):513-518.

Characterization of the Heart and Skeletal Muscle Reveals Widespread Arginine ADP-Ribosylation by the ARTC1 Ectoenzyme. Leutert M, Menzel S, Braren R, Rissiek B, Hopp AK, Nowak K, Bisceglie L, Gehrig P, Li H, Zolkiewska A, Koch-Nolte F, Hottiger MO. Cell Rep. 2018 Aug 14;24(7):1916-1929.e5.

Comparison of definite chemoradiation therapy with carboplatin/paclitaxel or cisplatin/5-fluoruracil in patients with squamous cell carcinoma of the esophagus. Münch S, Pigorsch SU, Devečka M, Dapper H, Weichert W, Friess H, Braren R, Combs SE, Habermehl D. Radiat Oncol. 2018 Aug 2;13(1):139.

Dual layer computed tomography: Reduction of metal artefacts from posterior spinal fusion using virtual monoenergetic imaging. Dangelmaier J, Schwaiger BJ, Gersing AS, Kopp FF, Sauter A, Renz M, Riederer I, Braren R, Pfeiffer D, Fingerle A, Rummeny EJ, Noël PB. Eur J Radiol. 2018 Aug;105:195-203.

Spectral Computed Tomography Angiography With a Gadolinium-based Contrast Agent: First Clinical Imaging Results in Cardiovascular Applications. Nadjiri J, Pfeiffer D, Straeter AS, Noël PB, Fingerle A, Eckstein HH, Laugwitz KL, Rummeny EJ, Braren R, Rasper M. J Thorac Imaging. 2018 Jul;33(4):246-253.

Dual-layer spectral computed tomography: Virtual non-contrast in comparison to true non-contrast images. Sauter AP, Muenzel D, Dangelmaier J, Braren R, Pfeiffer F, Rummeny EJ, Noël PB, Fingerle AA. Eur J Radiol. 2018 Jul;104:108-114.

Improved detection rates and treatment planning of head and neck cancer using dual-layer spectral CT. Lohöfer FK, Kaissis GA, Köster FL, Ziegelmayer S, Einspieler I, Gerngross C, Rasper M, Noel PB, Koerdt S, Fichter A, Rummeny EJ, Braren RF. Eur Radiol. 2018 Dec;28(12):4925-4931.

Accuracy of iodine quantification in dual-layer spectral CT: Influence of iterative reconstruction, patient habitus and tube parameters. Sauter AP, Kopp FK, Münzel D, Dangelmaier J, Renz M, Renger B, Braren R, Fingerle AA, Rummeny EJ, Noël PB. Eur J Radiol. 2018 May;102:83-88.

Assessment of quantification accuracy and image quality of a full-body dual-layer spectral CT system. Ehn S, Sellerer T, Muenzel D, Fingerle AA, Kopp F, Duda M, Mei K, Renger B, Herzen J, Dangelmaier J, Schwaiger BJ, Sauter A, Riederer I, Renz M, Braren R, Rummeny EJ, Pfeiffer F, Noël PB. J Appl Clin Med Phys. 2018 Jan;19(1):204-217.

SurvivalNet: Predicting patient survival from diffusion weighted magnetic resonance images using cascaded fully convolutional and 3D convolutional neural networks Patrick Ferdinand Christ, Florian Ettlinger, Georgios Kaissis, Sebastian Schlecht, Freba Ahmaddy, Felix Grün, Alexander Valentinitsch, Seyed-Ahmad Ahmadi, Rickmer Braren, Bjoern Menze, accepted at IEEE, ISBI 2017, arXiv:1702.05941

Imaging and targeted therapy of pancreatic ductal adenocarcinoma using the theranostic sodium iodide symporter (NIS) gene. Schmohl KA, Gupta A, Grünwald GK, Trajkovic-Arsic M, Klutz K, Braren R, Schwaiger M, Nelson PJ, Ogris M, Wagner E, Siveke JT, Spitzweg C. Oncotarget. 2017 May 16;8(20):33393-33404.

Integrin-Targeted Hybrid Fluorescence Molecular Tomography/X-ray Computed Tomography for Imaging Tumor Progression and Early Response in Non-Small Cell Lung Cancer. Ma X, Phi Van V, Kimm MA, Prakash J, Kessler H, Kosanke K, Feuchtinger A, Aichler M, Gupta A, Rummeny EJ, Eisenblätter M, Siveke J, Walch AK, Braren R, Ntziachristos V, Wildgruber M. Neoplasia. 2017 Jan;19(1):8-16.

Targeting PI3K/mTOR signaling exerts potent antitumor activity in pheochromocytoma in vivo. Lee M, Minaskan N, Wiedemann T, Irmler M, Beckers J, Yousefi BH, Kaissis G, Braren R, Laitinen I, Pellegata NS. Endocr Relat Cancer. 2017 Jan;24(1):1-15.

Co-clinical Assessment of Tumor Cellularity in Pancreatic Cancer. Heid I, Steiger K, Trajkovic-Arsic M, Settles M, Eßwein MR, Erkan M, Kleeff J, Jäger C, Friess H, Haller B, Steingötter A, Schmid RM, Schwaiger M, Rummeny EJ, Esposito I, Siveke JT, Braren RF. Clin Cancer Res. 2017 Mar 15;23(6):1461-1470.

Tumor Uptake of Anti-CD20 Fabs Depends on Tumor Perfusion. Mendler CT, Feuchtinger A, Heid I, Aichler M, D'Alessandria C, Pirsig S, Blechert B, Wester HJ, Braren R, Walch A, Skerra A, Schwaiger M. J Nucl Med. 2016 Dec;57(12):1971-1977.

Membranous CD24 drives the epithelial phenotype of pancreatic cancer. Lubeseder-Martellato C, Hidalgo-Sastre A, Hartmann C, Alexandrow K, Kamyabi-Moghaddam Z, Sipos B, Wirth M, Neff F, Reichert M, Heid I, Schneider G, Braren R, Schmid RM, Siveke JT. Oncotarget. 2016 Aug 2;7(31):49156-49168.

Multiparametric human hepatocellular carcinoma characterization and therapy response evaluation by hyperpolarized (13) C MRSI. Düwel S, Durst M, Gringeri CV, Kosanke Y, Gross C, Janich MA, Haase A, Glaser SJ, Schwaiger M, Schulte RF, Braren R, Menzel MI. NMR Biomed. 2016 Jul;29(7):952-60.

Transarterial Administration of Oncolytic Viruses for Locoregional Therapy of Orthotopic HCC in Rats. Altomonte J, Muñoz-Álvarez KA, Shinozaki K, Baumgartner C, Kaissis G, Braren R, Ebert O. J Vis Exp. 2016 Apr 15;(110).

Multiplexed pancreatic genome engineering and cancer induction by transfection-based CRISPR/Cas9 delivery in mice. Maresch R, Mueller S, Veltkamp C, Öllinger R, Friedrich M, Heid I, Steiger K, Weber J, Engleitner T, Barenboim M, Klein S, Louzada S, Banerjee R, Strong A, Stauber T, Gross N, Geumann U, Lange S, Ringelhan M, Varela I, Unger K, Yang F, Schmid RM, Vassiliou GS, Braren R, Schneider G, Heikenwalder M, Bradley A, Saur D, Rad R. Nat Commun. 2016 Feb 26;7:10770.

Modeling Therapy Response and Spatial Tissue Distribution of Erlotinib in Pancreatic Cancer. Grüner BM, Winkelmann I, Feuchtinger A, Sun N, Balluff B, Teichmann N, Herner A, Kalideris E, Steiger K, Braren R, Aichler M, Esposito I, Schmid RM, Walch A, Siveke JT. Mol Cancer Ther. 2016 May;15(5):1145-52.

CRISPR/Cas9 somatic multiplex-mutagenesis for high-throughput functional cancer genomics in mice. Weber J, Öllinger R, Friedrich M, Ehmer U, Barenboim M, Steiger K, Heid I, Mueller S, Maresch R, Engleitner T, Gross N, Geumann U, Fu B, Segler A, Yuan D, Lange S, Strong A, de la Rosa J, Esposito I, Liu P, Cadiñanos J, Vassiliou GS, Schmid RM, Schneider G, Unger K, Yang F, Braren R, Heikenwälder M, Varela I, Saur D, Bradley A, Rad R. Proc Natl Acad Sci U S A. 2015 Nov 10;112(45):13982-7.

Next-generation metabolic imaging in pancreatic cancer. Braren RF, Siveke JT. Gut. 2016 Mar;65(3):367-9.

Combined inhibition of BET family proteins and histone deacetylases as a potential epigenetics-based therapy for pancreatic ductal adenocarcinoma. Mazur PK, Herner A, Mello SS, Wirth M, Hausmann S, Sánchez-Rivera FJ, Lofgren SM, Kuschma T, Hahn SA, Vangala D, Trajkovic-Arsic M, Gupta A, Heid I, Noël PB, Braren R, Erkan M, Kleeff J, Sipos B, Sayles LC, Heikenwalder M, Heßmann E, Ellenrieder V, Esposito I, Jacks T, Bradner JE, Khatri P, Sweet-Cordero EA, Attardi LD, Schmid RM, Schneider G, Sage J, Siveke JT. Nat Med. 2015 Oct;21(10):1163-71.

Resectability After First-Line FOLFIRINOX in Initially Unresectable Locally Advanced Pancreatic Cancer: A Single-Center Experience. Nitsche U, Wenzel P, Siveke JT, Braren R, Holzapfel K, Schlitter AM, Stöß C, Kong B, Esposito I, Erkan M, Michalski CW, Friess H, Kleeff J. Ann Surg Oncol. 2015 Dec;22 Suppl 3:S1212-20.

Outcomes of resections for pancreatic adenocarcinoma with suspected venous involvement: a single center experience. Michalski CW, Kong B, Jäger C, Kloe S, Beier B, Braren R, Esposito I, Erkan M, Friess H, Kleeff J. BMC Surg. 2015 Aug 22;15:100.

Model Matters: Differences in Orthotopic Rat Hepatocellular Carcinoma Physiology Determine Therapy Response to Sorafenib. Groß C, Steiger K, Sayyed S, Heid I, Feuchtinger A, Walch A, Heß J, Unger K, Zitzelsberger H, Settles M, Schlitter AM, Dworniczak J, Altomonte J, Ebert O, Schwaiger M, Rummeny E, Steingötter A, Esposito I, Braren R. Clin Cancer Res. 2015 Oct 1;21(19):4440-50.

Characterization of magnetic viral complexes for targeted delivery in oncology. Almstätter I, Mykhaylyk O, Settles M, Altomonte J, Aichler M, Walch A, Rummeny EJ, Ebert O, Plank C, Braren R. Theranostics. 2015 Mar 18;5(7):667-85.

Targeting PI3K/mTOR Signaling Displays Potent Antitumor Efficacy against Nonfunctioning Pituitary Adenomas. Lee M, Wiedemann T, Gross C, Leinhäuser I, Roncaroli F, Braren R, Pellegata NS. Clin Cancer Res. 2015 Jul 15;21(14):3204-15.

Multimodality multiparametric imaging of early tumor response to a novel antiangiogenic therapy based on anticalins. Meier R, Braren R, Kosanke Y, Bussemer J, Neff F, Wildgruber M, Schwarzenböck S, Frank A, Haller B, Hohlbaum AM, Schwaiger M, Gille H, Rummeny EJ, Beer AJ. PLoS One. 2014 May 6;9(5):e94972.

Multimodal molecular imaging of integrin αvβ3 for in vivo detection of pancreatic cancer. Trajkovic-Arsic M, Mohajerani P, Sarantopoulos A, Kalideris E, Steiger K, Esposito I, Ma X, Themelis G, Burton N, Michalski CW, Kleeff J, Stangl S, Beer AJ, Pohle K, Wester HJ, Schmid RM, Braren R, Ntziachristos V, Siveke JT. J Nucl Med. 2014 Mar;55(3):446-51.

Opposing role of Notch1 and Notch2 in a Kras(G12D)-driven murine non-small cell lung cancer model. Baumgart A, Mazur PK, Anton M, Rudelius M, Schwamborn K, Feuchtinger A, Behnke K, Walch A, Braren R, Peschel C, Duyster J, Siveke JT, Dechow T. Oncogene. 2015 Jan 29;34(5):578-88.

Microvascular dysfunction in the course of metabolic syndrome induced by high-fat diet. Aoqui C, Chmielewski S, Scherer E, Eissler R, Sollinger D, Heid I, Braren R, Schmaderer C, Megens RT, Weber C, Heemann U, Tschöp M, Baumann M. Cardiovasc Diabetol. 2014 Feb 3;13:31.

Cardioprotective C-kit⁺ bone marrow cells attenuate apoptosis after acute myocardial infarction in mice - in-vivo assessment with fluorescence molecular imaging. Ale A, Siebenhaar F, Kosanke K, Aichler M, Radrich K, Heydrich S, Schiemann M, Bielicki I, Noel PB, Braren R, Maurer M, Walch AK, Rummeny EJ, Ntziachristos V, Wildgruber M. Theranostics. 2013 Nov 2;3(11):903-13.

X-ray phase-contrast CT of a pancreatic ductal adenocarcinoma mouse model. Tapfer A, Braren R, Bech M, Willner M, Zanette I, Weitkamp T, Trajkovic-Arsic M, Siveke JT, Settles M, Aichler M, Walch A, Pfeiffer F. PLoS One. 2013;8(3):e58439.

Silica-iron oxide magnetic nanoparticles modified for gene delivery: a search for optimum and quantitative criteria. Mykhaylyk O, Sobisch T, Almstätter I, Sanchez-Antequera Y, Brandt S, Anton M, Döblinger M, Eberbeck D, Settles M, Braren R, Lerche D, Plank C. Pharm Res. 2012 May;29(5):1344-65.

Assessing antiangiogenic therapy response by DCE-MRI: development of a physiology driven multi-compartment model using population pharmacometrics. Steingoetter A, Menne D, Braren RF. PLoS One. 2011;6(10):e26366.

Different capacity of monocyte subsets to phagocytose iron-oxide nanoparticles. Settles M, Etzrodt M, Kosanke K, Schiemann M, Zimmermann A, Meier R, Braren R, Huber A, Rummeny EJ, Weissleder R, Swirski FK, Wildgruber M. PLoS One. 2011;6(10):e25197.

Free-breathing quantitative dynamic contrast-enhanced magnetic resonance imaging in a rat liver tumor model using dynamic radial T(1) mapping. Braren R, Curcic J, Remmele S, Altomonte J, Ebert O, Rummeny EJ, Steingoetter A. Invest Radiol. 2011 Oct;46(10):624-31.

Validation of preclinical multiparametric imaging for prediction of necrosis in hepatocellular carcinoma after embolization. Braren R, Altomonte J, Settles M, Neff F, Esposito I, Ebert O, Schwaiger M, Rummeny E, Steingoetter A. J Hepatol. 2011 Nov;55(5):1034-40.

Reference region-based pharmacokinetic modeling in quantitative dynamic contract-enhanced MRI allows robust treatment monitoring in a rat liver tumor model despite cardiovascular changes. Steingoetter A, Svensson J, Kosanke Y, Botnar RM, Schwaiger M, Rummeny E, Braren R. Magn Reson Med. 2011 Jan;65(1):229-38.

Synergistic antitumor effects of transarterial viroembolization for multifocal hepatocellular carcinoma in rats. Altomonte J, Braren R, Schulz S, Marozin S, Rummeny EJ, Schmid RM, Ebert O. Hepatology. 2008 Dec;48(6):1864-73.