Diagnostic and Therapeutic Ultrasound

Ultrasound is one of the most frequently used imaging modalities in clinical routine. It is real-time, safe, transportable and offers excellent spatial resolution and tissue contrast. However, for a long period of time its clinical applications did not exploit its full potential. With the introduction of microbubbles as contrast agents, ultrasound enables a detailed and quantitative characterization of tissue microvascularisation, and recently, the first molecularly targeted microbubbles have entered clinical application. In addition, there is clear evidence that contrast-enhanced ultrasound has significant potential to improve drug delivery by using mechanical forces from oscillating microbubbles to open biological barriers. Furthermore, microbubbles can also be loaded with drugs and act as drug carriers releasing their content only at the target site after local ultrasound exposure.
Ultrasound imaging has been one of the main research topics of Professor Fabian Kiessling for over 10 years. With the new “Diagnostic and Therapeutic Ultrasound” group in ExMI, it is our intention to intensify our efforts in ultrasound research and to focus our translational research on

  • multifunctional microbubble design
  • quantitative, functional and molecular vascular characterization
  • combination of ultrasound and photoacoustic imaging
  • sonopermeabilisation and sonoporation

Univ.-Prof. Dr. med.
Fabian Kiessling

Selected publications

Research Papers

  1. Lammers T, Koczera P, Fokong S, Gremse F, Ehling J, Vogt M, Pich A, Storm G, van Zandvoort M, and Kiessling F. Theranostic USPIO-Loaded Microbubbles for Mediating and Monitoring Blood-Brain Barrier Permeation. Advanced Functional Materials. 2014;25(1):36‑43.
  2. Liu Z, Lammers T, Ehling J, Fokong S, Bornemann J, Kiessling F, and Gätjens J. Iron oxide nanoparticle-containing microbubble composites as contrast agents for MR and ultrasound dual-modality imaging. Biomaterials. 2011;32(26):6155‑63.
  3. Palmowski M, Lederle W, Gaetjens J, Socher M, Hauff P, Bzyl J, Semmler W, Günther RW, and Kiessling F. Comparison of conventional time–intensity curves vs. maximum intensity over time for post-processing of dynamic contrast-enhanced ultrasound. European Journal of Radiology. 2010;75(1):149.
  4. Kiessling F, Krix M, Heilmann M, Vosseler S, Lichy M, Fink C, Farhan N, Kleinschmidt K, Schad L, Fusenig NE, and Delorme S. Comparing Dynamic Parameters of Tumor Vascularization in Nude Mice Revealed by Magnetic Resonance Imaging and Contrast-Enhanced Intermittent Power Doppler Sonography. Investigative Radiology. 2003;38(8):516‑24.
  5. Grouls C, Hatting M, Rix A, Pochon S, Lederle W, Tardy I, Kuhl CK, Trautwein C, Kiessling F, and Palmowski M. Liver Dysplasia: US Molecular Imaging with Targeted Contrast Agent Enables Early Assessment. Radiology. 2013;267(2):487‑95.
  6. Baetke SC, Rix A, Tranquart F, Schneider R, Lammers T, Kiessling F, and Lederle W. Squamous Cell Carcinoma Xenografts: Use of VEGFR2-targeted Microbubbles for Combined Functional and Molecular US to Monitor Antiangiogenic Therapy Effects. Radiology. 2016;278(2):430‑40.
  7. Palmowski M, Huppert J, Hauff P, Reinhardt M, Schreiner K, Socher MA, Hallscheidt P, Kauffmann GW, Semmler W, and Kiessling F. Vessel Fractions in Tumor Xenografts Depicted by Flow- or Contrast-Sensitive Three-Dimensional High-Frequency Doppler Ultrasound Respond Differently to Antiangiogenic Treatment. Cancer Research. 2008;68(17):7042‑9.
  8. Palmowski M, Huppert J, Ladewig G, Hauff P, Reinhardt M, Mueller MM, Woenne EC, Jenne JW, Maurer M, Kauffmann GW, Semmler W, and Kiessling F. Molecular profiling of angiogenesis with targeted ultrasound imaging: early assessment of antiangiogenic therapy effects. Molecular Cancer Therapeutics. 2008;7(1):101‑9.
  9. Curaj A, Wu Z, Fokong S, Liehn EA, Weber C, Burlacu A, Lammers T, van Zandvoort M, and Kiessling F. Noninvasive Molecular Ultrasound Monitoring of Vessel Healing After Intravascular Surgical Procedures in a Preclinical Setup. Arteriosclerosis, Thrombosis, and Vascular Biology. 2015;35(6):1366‑73.
  10. Kiessling F. Application of Molecular Ultrasound for Imaging Integrin Expression. Theranostics. 2011. doi: 10.7150/thno/v01p0127 [Epub ahead of print]

Reviews / Perspectives

  1. Kiessling F, Fokong S, Bzyl J, Lederle W, Palmowski M, and Lammers T. Recent advances in molecular, multimodal and theranostic ultrasound imaging. Advanced Drug Delivery Reviews. 2014;72:15‑27.
  2. Kiessling F, Fokong S, Koczera P, Lederle W, and Lammers T. Ultrasound Microbubbles for Molecular Diagnosis, Therapy, and Theranostics. Journal of Nuclear Medicine. 2012;53(3):345‑8.
  3. Paefgen V, Doleschel D, and Kiessling F. Evolution of contrast agents for ultrasound imaging and ultrasound-mediated drug delivery. Frontiers in Pharmacology. 2015;6.

Group members

Adelina Curaj

Adelina (MD, University of Medicine and Pharmacy “Carol Davila”, Bucharest, 2010) uses in vivo and ex vivo US imaging to monitor the MB binding of MB to atherosclerotic plaques. Ex vivo experiments include studies in which TNF-stimulated carotids are excised and mounted onto flow chambers, and in which the binding of antibody-targeted MB is being visualized and quantified. In vivo experiments are performed under similar conditions, as well as in wire-injury and ApoE-knockout mice. In cooperation with the Institute for Molecular Cardiovascular Research at RWTH Aachen, she furthermore works on myocardial infarction.

A. Curaj

Eva Fiegle

Eva (MD Student, RWTH Aachen University) is working on “Multimodal assessment of drug side effects and tumor response to chemo- and radiotherapy”.

Portrait of Eva Fiegle
E. Fiegle

Tatjana Opacic

Tatjana (MD University of Medicine, Belgrade, Serbia, 2012), is involved in establishing materials and methods to design microbubbles co-loaded with chemotherapeutic drugs and targeting ligands to maximize amount of MB delivered to tumor. Therefor result of her work is enhancing drug delivery to tumor in order to individualize and improve antitumor treatment.

T. Opacic

Vera Päfgen

Vera (M.Sc. in Biology, RWTH Aachen University, 2013) works in collaboration with the groups of Prof. Bernhard Blümich (ITMC, RWTH Aachen University) and Prof. Louis Bouchard (University of California, Los Angeles) on hyperpolarized contrast agents for MRI to target tumor angiogenesis in vivo and increase signal intensity. She received a DAAD-funded scholarship (ACalNet), enabling her to work for some time at the UCLA. Additionally she develops and establishes an experimental in vitro setup for imaging the specific binding of targeted USPIO-microbubbles to endothelial cells under flow conditions in both MRI and MPI.

V. Päfgen

Anne Rix

Anne (B.Sc. in Molecular Biology, JGU Mainz) works as a lab technician and her main focus is functional and molecular ultrasound methods for assessing tumor angiogenesis and anti-angiogenic therapy effects. In addition, she is working on immunohistochemistry, microscopy and on different diagnostic and therapeutic in vivo and ex vivo experiments.

A. Rix

Benjamin Theek

Benjamin (M.Sc. in Biomedical Engineering, RWTH Aachen University, 2011) focuses on the design and evaluation of polymeric and liposomal nanomedicines for vascular normalization, in order to improve the efficacy of combined modality anticancer therapy. In addition, he develops methods for using ultrasound-based perfusion monitoring to reduce the interindividual variability in image-guided drug delivery and tumor targeting studies. Furthermore, he is involved in several different studies focusing on (theranostic) microbubbles, angiogenesis and liver fibrosis.

B. Theek

Yoanna Tsvetkova

Yoanna (Dipl.-Chem., RWTH Aachen, 2011) develops adsorptive and fluorescent coatings for USPIO-based nanoparticles for MR, NIRF and PET/SPECT imaging. In this regard she particularly focuses on riboflavin and its analogues, FMN and FAD.

Y. Tsvetkova