MRDAC - MR development and application center

DCE-MRI (Dynamic contrast-enhanced magnetic resonance imaging) is the key method to evaluate anti-angiogenic and anti-vascular agents in clinical trials.

  • It allows to determine the functional response of tumor to the anti cancer agents on a microvascular level where parameters like vascular permeability are important biomarkers.
  • It is a non-invasive technique with low restrictions to patient comfort and is the method of choice to follow-up drug action in tumor and surrogate tissues.
  • It directly reflects the impact of the therapeutic drug on tumor state by angiogenesis assessment.

DCE-MRI data analysis is performed by an in-house software analysis tool

  • written in Matlab according to GCP-requirements,
  • to determine pharmacological parameter (Ktrans, kep) by pharmacokinetic modelling which are related to physiological parameters like vessel permeability and extra-vascular volume.
  • with pharmacodynamic models to analyze clinical and pre clinical MRI data,
  • with region of interest (ROI) and pixel wise analysis,
  • with handling of 2D, 3D and multi echo data sets,
  • with an user-friendly graphical user interface and
  • with a flexible design to meet the demands in the progress of modeling and new study trials.

  • (please click for magnified image) Screenshot example of the analysis tool.

MRDAC provides a complete package for the implementation of clinical phase trials including standard and advanced DCE-MRI measurement protocols and DCE-MRI analysis tools using professional software.
MRDAC has more than 15 years experience performing DCE-MRI examinations and analysis in the context of clinical trials.

For more information be referred to the pages of our local partners.

Publications - Books

  • Strecker R, Hennig J:
    DCE-MRI. In: Joachim Drevs (Hrsg): Tumorangiogenese- Grundlagen und therapeutische Ansätze. ,
    1. Auflage. Bremen: Uni-Med Science, 2005; 37-40 (4.3.1)

  • Büchert M, Fasol U:
    Bildgebende Verfahren zur Beurteilung der Effiktivität antiangiogener Wirkprinzipien. In: Klaus Mross (Hrsg): Angiogeneseinhibition in der Onkologie. ,
    1. Auflage . Bremen: Uni-Med Science, 2007; 55-70 (6.)

Publications - Scientific articles
  • A Thomas, B Morgan, J Drevs, A Jivan, M Buechert, M Horsfield, J Hennig, K Mross, A Henry, H Ball, B Peng, S Fuxius, C Unger, K 'Byrne, D Laurent, M Dugan, W Steward,
    Pharmacodynamic Results Using Dynamic Contrast Enhanced Magnetic Resonance Imaging, of 2 Phase 1 Studies of the VEGF Inhibitor PTK787/ZK 222584 in Patients with Liver Metastases from Colorectal Cancer.
    Meeting: 2001 ASCO Annual Meeting Abstract No: 279

  • 2002
  • Drevs J, Müller-Driver R, Wittig C, Fuxius S, Esser N, Hugenschmidt J, Konerding MA, Allegrini PR, Wood J, Hennig J, Unger C, Marmé D.:
    PTK787/ZK 222584, a specific Vascular Endothelial Growth Factor-Receptor Tyrosine Kinase Inhibitor, Affects the anatomy of the Tumor Vascular Bed and the Functional Vascular Properties as detected by dynamic enhanced Magnetic Resonance Imaging.
    Cancer Res, 2002; 62: 4015-4022.

  • 2003
  • Strecker R, Scheffler K, Büchert M, Mross K, Drevs J, Hennig J.:
    DCE-MRI in clinical trials: data acquisition techniques and analysis methods.
    Int J Clin Pharm Th, 2003; 41 (12) : 603-605.

  • Morgan B, Thomas AL, Drevs J, Hennig J, Buechert M, Jivan A, Horsfield MA, Mross K, Ball HA, Lee L, Mietlowski W, Fuxius S, Unger C, O’Byrne K, Henry A, Cherryman GR, Laurent D, Dugan M, Marmé D, Steward WP.:
    Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: results from two phase I studies.
    J Clin Oncol, 2003; 21 (21) : 3955-3964.

  • 2004
  • M. Medinger, K. Mross, U. Zirrgiebel, R. Strecker, C. Wheeler, G. Clack, J. Lewis, T. A. Puchalski, C. Unger, J. Drevs;
    Phase I dose-escalation study of the highly potent VEGF receptor kinase inhibitor, AZD2171, in patients with advanced cancers with liver metastases.
    Meeting: 2004 ASCO Annual Meeting Abstract No: 3055

  • 2005
  • Mross K, Drevs J, Müller M, Medinger M, Marmé D, Hennig J, Morgan B, Lebwohl D, Masson E, Ho YY, Günther C, Laurent D, Unger C.:
    Phase I Clinical and Pharmacokinetic Study of PTK/ZK, a multiple VEGF Receptor Inhibitor, in Patients with Liver Metastases from Solid Tumours.
    Eur J Cancer, 2005; 41 (9) : 1291-1299.

  • K. B. Mross, D. Gmehling, A. Frost, F. Baas, R. Strecker, J. Hennig, P. Stopfer, M. Stefanic, G. Stehle, L. de Rossi
    A clinical Phase I, pharmacokinetic (PK), and pharmacodynamic study of twice daily BIBF 1120 in advanced cancer patients
    J Clin Oncol (Meetings abstracts) 23(16s): 3031 (2005)

  • J. Drevs, M. Medinger, K. Mross, U. Zirrgiebel, R. Strecker, C. Unger, T. A. Puchalski, N. Fernandes, J. Roberston, P. Siegert
    Phase I clinical evaluation of AZD2171, a highly potent VEGF receptor tyrosine kinase inhibitor, in patients with advanced tumors
    J Clin Oncol (Meetings abstracts) 23(16s): 3002 (2005)

  • 2007
  • C. Morris, J. Jurgensmeier, J. Robertson, S. Hollis, T. Puchalski, H. Young, R. Strecker, J. Kendrew, S. Wedge, J. Drevs
    AZD2171, an oral, highly potent, and reversible inhibitor of VEGFR, signaling with potential for the treatment of advanced colorectal cancer
    Meeting: 2006 ASCO Gastrointestinal Cancers Symposium &xnbsp; Abstract No: 242 &xnbsp;

  • Joachim Drevs, Patrizia Siegert, Michael Medinger, Ralph Strecker, Ute Zirrgiebel, Jan Harder, Hubert Blum, Jane Robertson, Juliane M Jürgensmeier, Thomas A Puchalski, Helen Young, Owain Saunders and Clemens Unger;
    Phase I clinical study of AZD2171, an oral, highly potent VEGF signaling inhibitor, in patients with advanced solid tumors;
    Journal of Clinical Oncology J Clin Oncol. 2007 Jul 20;25(21):3045-54.

  • Steinbild S, Arends J, Medinger M, Häring B, Frost A, Drevs J, Unger C, Strecker R, Hennig J, Mross K.
    Metronomic antiangiogenic therapy with capecitabine and celecoxib in advanced tumor patients--results of a phase II study.
    Onkologie, 2007; 30 (12) : 629-635

  • 2008
  • Strumberg D, Schultheis B, Adamietz IA, Christensen O, Buechert M, Kraetzschmar J, Rajagopalan P, Ludwig M, Frost A, Steinbild S, Scheulen ME, Mross K.
    Phase I dose escalation study of telatinib (BAY 57-9352) in patients with advanced solid tumours.
    British journal of cancer 2008;99(10):1579-1585.

  • 2009
  • Sauerbier S, Palmowski M, Vogeler M, Nagursky H, Al-Ahmad A, Fisch D, Hennig J, Schmelzeisen R, Gutwald R, Fasol U.
    Onset and Maintenance of Angiogenesis in Biomaterials: In Vivo Assessment by Dynamic Contrast-Enhanced MRI.
    Tissue Eng Part C Methods 2009.

  • Mross, K., U. Fasol, A. Frost, R. Benkelmann, J. Kuhlmann, M. Buechert, C. Unger, et al.
    DCE-MRI Assessment of the Effect of Vandetanib on Tumor Vasculature in Patients with Advanced Colorectal Cancer and Liver Metastases: A Randomized Phase I Study.
    Journal of Angiogenesis Research 1 (2009): 5.

  • Strumberg, D., M. E. Scheulen, A. Frost, M. Buechert, O. Christensen, A. Wagner, R. Heinig, U. Fasol, and K. Mross.
    Phase I Study of BAY 73-4506, an Inhibitor of Oncogenic and Angiogenic Kinases, in Patients with Advanced Refractory Colorectal Carcinoma (CRC).
    Journal of Clinical Oncology 27, no. 15 (2009): 3560.

  • 2010
  • Christensen, O., M. Buechert, U. Fasol, M. Jeffers, J. Kratzschmar, D. Strumberg, M. E. Scheulen, and K. Mross.
    Ann. Oncol. 21, no. 8 (2010): 200-201.

  • Drevs, J., M. Medinger, K. Mross, S. Fuxius, J. Hennig, M. Buechert, A. Thomas, et al.
    A Phase IA, Open-Label, Dose-Escalating Study of PTK787/ZK 222584 Administered Orally on a Continuous Dosing Schedule in Patients with Advanced Cancer.
    Anticancer Research 30, no. 6 (2010): 2335-39.

  • 2011
  • K. Mross, R. Fischer, H. Richly, D .Scharr, M. Büchert, A. Stern, D. Hoth, H. Gille, L. Audoly, and M. E. Scheulen.
    First in Human Phase I Study of PRS-050 (Angiocal), a VEGF-A Targeting Anticalin, in Patients with Advanced Solid Tumors: Results of a Dose Escalation Study.
    AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, #A212. San Francisco, 2011.

  • Kanefendt, Friederike, Andreas Lindauer, Martina Kinzig, Dirk Strumberg, Max Scheulen, Richard Fischer, Martin Büchert, et al.
    Modeling Biomarker Response in Patients with Metastatic Colorectal Cancer Receiving Sunitinib. CESAR Jahrestagung 2011, P22. Greifswald, 2011.

  • Mross, K., A. Frost, M. E. Scheulen, J. Krauss, D. Strumberg, B. Schultheiss, U. Fasol, et al.
    Phase I Study of Telatinib (BAY 57-9352): Analysis of Safety, Pharmacokinetics, Tumor Efficacy, and Biomarkers in Patients with Colorectal Cancer.
    Vascular Cell 3, no. 1 (2011): 16.

  • Mross, K., M. Buchert, U. Fasol, U. Jaehde, F. Kanefendt, D. Strumberg, J. Arends, et al.
    A Preliminary Report of a Phase II Study of Folinic Acid, 5-Fluorouracil, Irinotecan (FOLFIRI) plus Sunitinib with Toxicity, Efficacy, Pharmacokinetics, Biomarker, Imaging Data in Patients with Colorectal Cancer with Liver Metastases as 1st Line Treatment.
    International Journal of Clinical Pharmacology and Therapeutics 49, no. 1 (2011): 96-98.

  • Pilutti D, Weidensteiner C, Buechert M, Fasol U, and Hadjidemetriou S.
    An Overview of Registration Methods Used for the Automatic Analysis of Abdominal DCE-MRI.
    19th Scientific Meeting International Society for Magnetic Resonance in Medicine, #4687. Montreal, 2011.

  • Strumberg D, Scheulen M, Schultheis B, Kramer A, Frost A, Buchert M, Christensen O, et al.
    Preliminary Activity of Regorafenib (BAY 73-4506) in Patients with Advanced Colorectal Carcinoma.
    CESAR Jahrestagung 2011, V04. Greifswald, 2011.

  • 2012
  • Buechert, M., and K. Mross.
    IR-TrueFISP: A New DCE-MRI Approach in Comparison with 3D-Flash Multi Flip Angle Method.
    Magnetic Resonance Insights, no. 5 (2012): 7-16. download.

  • Buechert, M, and K Mross.
    Sampling Duration in DCE-MRI: In Vivo Comparison Using Data Acquired within a Clinical Phase I Study.
    20th Annual Meeting & Exhibition of ISMRM, Melbourne, Australia (07.05-11.05.2012), Vol. 3506, 2012.

  • Fasol, U, A Frost, M Büchert, J Arends, U Fiedler, D Scharr, J Scheuenpflug, and K Mross.
    Vascular and Pharmacokinetic Effects of EndoTAG-1 in Patients with Advanced Cancer and Liver Metastasis.
    Annals of Oncology: Official Journal of the European Society for Medical Oncology / ESMO 23, no. 4 (April 2012): 1030-36.

  • Mross, K., A. Frost, S. Steinbild, S. Hedbom, M. Buchert, U. Fasol, C. Unger, et al.
    A Phase I Dose-Escalation Study Of Regorafenib (BAY 73-4506), An Inhibitor Of Oncogenic, Angiogenic And Stromal Kinases, In Patients With Advanced Solid Tumors.
    Clin Cancer Res 18 (9) (2012): 2658-67.

  • Strumberg, D, M E Scheulen, B Schultheis, H Richly, A Frost, M Büchert, O Christensen, et al.
    Regorafenib (BAY 73-4506) in Advanced Colorectal Cancer: A Phase I Study.
    British Journal of Cancer 106, no. 11 (May 22, 2012): 1722-27.

  • 2013
  • Pilutti, David, Martin Buchert, and Stathis Hadjidemetriou.
    Registration of Abdominal Tumor DCE-MRI Data Based on Deconvolution of Joint Statistics.
    Annual International Conference of the IEEE Engineering in Medicine and Biology Society. 2013: 2611-14.

  • 2014
  • Mross, K., M. Büchert, A. Frost, M. Medinger, P. Stopfer, M. Studeny, and R. Kaiser.
    Vascular Effects, Efficacy and Safety of Nintedanib in Patients with Advanced, Refractory Colorectal Cancer: A Prospective Phase I Subanalysis.
    BMC Cancer 14 (2014): 510.

  • Mross, K., M. Scheulen, D. Strumberg, J. Kuhlmann, F. Kanefendt, F. Sörgel, U. Jaehde, I. Burkholder, B. Moritz, and M. Büchert.
    FOLFIRI and Sunitinib as First-Line Treatment in Metastatic Colorectal Cancer Patients with Liver Metastases
    International Journal of Clinical Pharmacology and Therapeutics 52, no. 8 (2014): 642-52.

  • 2016
  • Pilutti, David, Maddalena Strumia, Martin Buchert, and Stathis Hadjidemetriou.
    Non-Parametric Bayesian Registration (NParBR) of Body Tumors in DCE-MRI Data.
    IEEE Transactions on Medical Imaging 35, no. 4 (2016): 1025-35.

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