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Dr. ir. M. Siebes PhD

Position
Associate professor (UHD)
Main activities
Research
Specialisation
Cardiovascular Hemodynamics and Perfusion
Focus of research
  • Mechanics of coronary perfusion
  • Cardiac-coronary interaction
  • Coronary microvascular dysfunction
  • Structural and functional adaptation of vascular networks
  • 3D imaging of vascular networks and fluorescent biomarkers
Key publications
  • Lockie TPE, Rolandi MC, Guilcher A, Perera D, de Silva K, Williams R, Asrress KN, Patel K, Plein S, Chowienczyk P, Siebes M, Redwood SR, Marber MS, Synergistic Adaptations to Exercise in the Systemic and Coronary Circulations That Underlie the Warm-Up Angina Phenomenon. CIRCULATION 2012;126 (22):2565-2574 [PubMed]
  • Rolandi MC, de Silva K, Lumley M, Lockie TPE, Clapp B, Spaan JAE, Perera D, Siebes M, Wave speed in human coronary arteries is not influenced by microvascular vasodilation: implications for wave intensity analysis. BASIC RES CARDIOL 2014;109 (2):405 [PubMed]
  • Jeremias A, Maehara A, Généreux P, Asrress KN, Berry C, de Bruyne B, Davies JE, Escaned J, Fearon WF, Gould KL, Johnson NP, Kirtane AJ, Koo BK, Marques KM, Nijjer S, Oldroyd KG, Petraco R, Piek JJ, Pijls NH, Redwood S, Siebes M, Spaan JAE, van 't Veer M, Mintz GS, Stone GW, Multicenter core laboratory comparison of the instantaneous wave-free ratio and resting Pd/Pa with fractional flow reserve: the RESOLVE study. J AM COLL CARDIOL 2014;63 (13):1253-1261 [PubMed]
  • van de Hoef TP , Siebes M, Spaan JAE, Piek JJ, Fundamentals in clinical coronary physiology: why coronary flow is more important than coronary pressure. EUR HEART J 2015;36 (47):3312-339a [PubMed]
  • Rolandi MC, Wiegerinck EMA, Casadonte L, Yong ZY, Koch KT, Vis M, Piek JJ, Baan J Jr, Spaan JAE, Siebes M, Transcatheter Replacement of Stenotic Aortic Valve Normalizes Cardiac-Coronary Interaction by Restoration of Systolic Coronary Flow Dynamics as Assessed by Wave Intensity Analysis. CIRC-CARDIOVASC INTE 2016;9 (4):e002356 [PubMed]
All Publications
Curriculum Vitae

Education:
1981  Diplom-Ing. Technical Health Sciences, Univ. of Applied Sciences, Giessen, Germany
          Thesis (with honors): Quantitative Angiography: In vitro experiments for the evaluation of a computer program for the geometric and hemodynamic assessment of stenoses from angiograms. 
1984  MSc Biomedical Engineering, Univ. of Southern California, Los Angeles, CA
1989  PhD Biomedical Engineering, Univ. of Southern California, Los Angeles, CA
           Thesis: Modeling and simulation of a compliant coronary stenosis during the cardiac cycle.

Professional Experience:
2011- date  Assoc. Professor, Biomedical Engineering and Physics, AMC, Amsterdam
2007- date  Principal Investigator, AMC, Amsterdam
2002-2011  Univ. Docent (tenured), Dept. of Biomed. Engineering & Physics, AMC, Amsterdam
1997-2002  Senior Res. Scientist, Dept. of Cardiology, AMC, Amsterdam
1996           Visiting Scientist, Cardiovasc. Research Inst., Academic Medical Center, Amsterdam
1989-1997  Asst. Professor, Dept. of Biomedical Engineering, University of Iowa, Iowa City, IA
1983-1989  Scientist III, Biomed. Image Proc. Group, JPL/CalTech, Pasadena, CA
1981-1983  Research Engineer, Dept. of Cardiology, Kerckhoff Clinic, Bad Nauheim, Germany

Honors & Awards:
1983 Fulbright Scholarship
1984 Fellowship, American Assoc. of Univ. Women (AAUW)
1985 & 1986 Amelia Earhart Fellowship, ZONTA International
1986 Scholarship, Germanistic Society of America
1987 Scholarship, Phi Beta Kappa (USC)
1992 Outstanding Teacher Award, Univ. of Iowa
1992 Iowa Career Development Award for Translational Research, Univ. of Iowa
1994 Alumni Member, Tau Beta Pi (Eng. Honors Soc.)
2010 Fellow, American Inst. for Medical and Biol. Engineering (AIMBE)
2012 Fellow, European Alliance for Medical and Biol. Engineering and Science (EAMBES)

Society Memberships: Sigma Xi, IEEE-EMBS (Senior Member), American Heart Assoc., American Physiol. Society, Dutch Soc. for Biophysics & Biomed. Technology, Dutch Soc. for Microcirc. and Vasc. Biology

Research Grants: Sigma Xi, NIH, NSF, Whitaker Foundation, Carver Scientific Research (UI), GE Foundation Faculty Fellowship, Dutch Heart Foundation, European Community (FP7-ICT euHeart), Center for Translational Molecular Medicine (CTMM Eminence), Neth. Org. for Health Research & Development (ZonMw), Dutch Science Foundation (NWO) Investment Grant

Research programmes

Cardiovascular Hemodynamics and Perfusion

The research of our group encompasses multidisciplinary investigations in areas of coronary disease and microvascular pathologies ranging from bench to bedside. Physiological measurements, imaging and biofluid mechanics are integrated with model-based analysis in translational studies. Experimental studies on vascular network analysis and regional perfusion complement and support the mechanistic interpretation of functional clinical data obtained in humans. Our projects are carried out in close collaboration with (inter-)national basic science and clinical collaborators, as well as with industrial partners.

Much of our research is conceptually embedded in the Virtual Physiological Human initiative (www.vph-institute.org). We participated in the FP7-ICT euHeart project (www.euheart.eu) to develop individualized, computer-based human heart models using patient-specific data and multi-scale modeling techniques.
 

Functional assessment of coronary epicardial and microvascular pathophysiology:
Novel approaches were developed for analysis of intracoronary hemodynamic signals obtained with sensor-equipped guide wires in patients, to advance diagnostic capabilities with respect to epicardial disease and/or microvascular dysfunction. Wave intensity analysis is used to unravel cardiac-coronary interaction associated with exercise, chronic ischemia or aortic valve replacement.

We established a Physiology Core Laboratory for the analysis of combined intracoronary pressure and flow velocity measurements to guide treatment of coronary stenoses based on functional parameters of coronary epicardial and microvascular disease (DEFINE-FLOW trial, NCT02328820).   

3D Vascular network quantification and regional perfusion assessment:

A unique Imaging Cryomicrotome has been developed (Prof. dr. ir. J.A. Spaan) to visualize and quantify detailed vascular networks and regional perfusion by 3D episcopic imaging of fluorescently labeled markers (vascular casting, microspheres, cells). Focus is on understanding the role of microvascular structure in perfusion distribution and its adaptation in pathophysiological conditions, including acute and chronic local oxygen deficiency due to a stenosis, or cardiomyopathies induced by pressure overload.

Pre-clinical investigations on validation of multi-modal probes for molecular imaging of neovascularization in cardiovascular disease were carried out within the CTMM-Eminence consortium. This project aimed at developing sensitive novel targets to detect and quantify early neovascularization using non-invasive diagnostic imaging technologies.

Supported by an NWO Investment grant, we recently built a novel 3D Fluorescence Imaging Cryomicrotome System (3D-FICS) for high-resolution, co-registered structural and molecular imaging. Multispectral investigations are facilitated by a broad-band tunable laser light source and tunable emission filter. Successful realization of this unique 3D imaging device has been made possible through the professional precision instrument design by the AMC Medical Innovation & Development unit and the mechatronics and optics expertise in our department.
The 3D-FICS is used in pre-clinical research for visualization of disease progression & early response to therapy, and receptor-targeted application development, with applications in cardiovascular & neurovascular disease, oncology, pathology, and urology.

 

Faculty
Dr. ir. M. Siebes PhD

PhD Students
M.G.J.T.B. van Lier MSc
J.C.V. Schwarz MSc

Other research related activities
  • Membership of editorial board / Editorship, AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
  • Membership of editorial board / Editorship, INTERNATIONAL JOURNAL OF CARDIOLOGY
  • Membership of editorial board / Editorship, INTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN BIOMEDICAL ENGINEERING
  • Membership of medical or scientific committee, Other, Admin. Council, Int'l Federation for Medical & Biological Engineering