Prof. H.J.C.M. Sterenborg MEng PhD

foto

Prof. MEng PhD H.J.C.M. Sterenborg

Position
Research Associate
Main activities
Research
Specialisation
Optical techniques for diagnosis of disease and monitorring of treatment
Focus of research

Over the years my research activities have been centered around development and clinical implementation of optical methods for minimally invasive diagnosis and treatment of disease. The work comprises the entire track from basic research and development of methodology to clinical validation and implementation.

The optical diagnostic techniques I have been using have changed over the years. Initially work was focussed around imaging and spectroscopy of autofluorescence and fluorescent contrast agents. In later years the emphasis moved to diffuse reflection spectroscopy and nonlinear optical spectroscopy and imaging. My current research focus lies entirely on elastic scattering spectroscopy and imaging.

Elastic Scattering Spectroscopy uses broadband white light and guides it to the tissue through optical fibers. Light entering the tissue will be scattered around before it is being absorbed, or leaves the tissue at the surface. This backscattered light is detected with an optical fiber and then analysed by a spectrograph. Current research activities have been focussed at development of quantitative approaches, i.e. methods to measure the scattering and absorption spectra quantitatively. So far I developed methods to measure absorption quantitatively, translate these into biologically related parameters and evaluated these extensively in clinical studies. Current focus is on developing methods for quantitative scattering information. Here both the absolute amount of scattering is of interest, but also the relation between forward and backward scattering is of particular interest because it is thought to be sensitive to intracellular biology. Light scattering occurs due to spatial variations in refractive index. Based on analysis of the wavelength dependence of scattering observed in measurements of tissue it can be concluded that the size of these scattering entities lies well below the resolution of an optical microscope (i.e. 100nm). Other types of microscopes can visualize much smaller structures, but do not do so on the basis of the refractive index. Hence the nature of these scattering entities is not known, but it is speculated that they relate to aspects of the cellular microarchitecture, such as folds in mitochondrial membranes, the presence and distribution of endosomes etc. At present I am focussing on measurement forward-to-backward ratio of scattering in vivo. This uses different fiber diameters and will shortly be tested clinically for screening of Barrett’s esophagus, prostate cancer and for diagnosing mediastinal lymph nodes. In addition, a setup is being developed to measure the angular dependence of back scattering on ex vivo samples.

Key publications
  • Thomas Giju, Nadiarnykh Oleg, van Voskuilen Johan, Hoy Christopher L., Gerritsen Hans C., Sterenborg Henricus J. C. M. Estimating the risk of squamous cell cancer induction in skin following nonlinear optical imaging Journal of biophotonics 2014;7 (7):492-505 [PubMed]
  • Nachabé Rami, van der Hoorn José W. A., van de Molengraaf Roland, Lamerichs Rolf, Pikkemaat Jeroen, Sio Charles F., Hendriks Benno H. W., Sterenborg Henricus J. C. M. Validation of Interventional Fiber Optic Spectroscopy With MR Spectroscopy, MAS-NMR Spectroscopy, High-Performance Thin-Layer Chromatography, and Histopathology for Accurate Hepatic Fat Quantification Investigative radiology 2012;47 (4):209-216 [PubMed]
  • Ungureanu Constantin, Amelink Arjen, Rayavarapu Raja G., Sterenborg Henricus J. C. M., Manohar Srirang, van Leeuwen Ton G. Differential Pathlength Spectroscopy for the Quantitation of Optical Properties of Gold Nanoparticles ACS nano 2010;4 (7):4081-4089 [PubMed]
  • Doornbos R. M., Lang R., Aalders M. C., Cross F. W., Sterenborg H. J. The determination of in vivo human tissue optical properties and absolute chromophore concentrations using spatially resolved steady-state diffuse reflectance spectroscopy Physics in medicine and biology 1999;44 (4):967-981 [PubMed]
  • Zhang Xu U., Faber Dirk J., Post Anouk L., van Leeuwen Ton G., Sterenborg Henricus J. C. M. Refractive index measurement using single fiber reflectance spectroscopy Journal of biophotonics 2019:e201900019 [PubMed]
All Publications
Curriculum Vitae

Dick Sterenborg (Researcher ID, H-9401-2013) graduated from the Physics Department at the Technical University of Eindhoven in 1982. After a postdoctoral internship at the St. Joseph Ziekenhuis in Veldhoven he accepted a position as a PhD student at the Department of Dermatology of the University Hospital of Utrecht. In 1987 he successfully defended his PhD thesis "The actionspectrum for tumorigenesis with ultraviolet radiation" (Promotor Prof J.C. van der Leun). He was a postdoc for the Laser Application and Information Center Amsterdam until 1989. Then he accepted a tenure track position at the Laser Center of the Academic Medical Center in Amsterdam and worked there with Prof M.J.C. van Gemert until 1998. During this period he worked on Laserlithortipsy and on optical imaging and spectroscopy. In 1992 he spent a sabbatical at MD Anderson Cancer Center in Houston TX where he focussed on skin cancer diagnosis using autofluorescence imaging and spectroscopy.

In 1989 he accepted a position as associate professor at the Daniel den Hoed Cancer Center of the Erasmus Medical Center in Rotterdam where he worked with Dr Willem Star. Two years later he became head of the Photodynamic Therapy and Optical Spectroscopy research programme at the erasmus Medical Centre. In 2004 he founded the Center for Optical Diagnostics and Therapy, an ErasmusMC-wide research programme for Biomedical Optics, in the Postgraduate School Molecular Medicine. In 2008 he was appointed professor of Photodynamic Therapy at the Erasmus University. During his period at Erasmus he co-founded several startup companies.

Currently he is back in Amsterdam; he has a joint appointment at the Department of Biomedical Engineering and Physics (Prof. A.G.J.M. van Leeuwen) of the Academic Medical Center and the department fo Surgery of the Netherlands Cancer Insitute (Prof. Th. Ruers). His current research activities are focussed on Elastic Scattering Spectroscopy and Imaging.

Academic education and other degrees

  • 2006 Biopartner Master Class Biobusiness, Wageningen University, Erasmus School of management.
  • 2000 Registration according to article 9 of the Dutch law on animal experiments. 
  • 1987 PhD (April 7th, 1987) Utrecht University, Faculty of Medicine, Dept. of Dermatology. Title thesis: The action spectrum of tumourigenesis by ultraviolet radiation.
  • 1982 Ingenieurs diploma, (February 3rd 1982) Eindhoven University of Technology, dept. of Applied Physics

Appointments (previous and current)

  • 2014-now Senior Researcher, Department of oncologic Surgery, Netherlands Cancer Institute
  • 2013-now PI Biomedical Engineering and Physics, Academic Medical Center, Amsterdam.
  • 2014-now CTO and founder of QuaSpec b.v. a startup company developping applications of Elastic Scattering Spectroscopy.
  • 2011-2018 CTO and founder of Nano4Therapy b.v. an ErasmusMC spin-off company aiming to commercialize nanotechnology based drugs for photodynamic therapy and optical diagnostics.
  • 2008-now Professor of Photodynamic therapy, Erasmus University Rotterdam
  • 2006-2015 CEO and founder of Luminostix b.v., an ErasmusMC spin-off company aiming to commercialize fiberoptic optic technology for medical applications.
  • 2001-2015 Universitair Hoofddocent, Erasmus University Rotterdam.
  • 1998-2015 Head of the Laboratory for Photodynamic Therapy and Optical Spectroscopy, Dept of Radiotherapy, Erasmus MC Rotterdam.
  • 1996-1998 Assistant department head, Laser Center, Academic Medical Center, Amsterdam.
  • 1992-1993 Visiting Assistant Professor, University of Texas Medical Branch at Galveston and UT-MD Anderson Cancer Centre, Houston TX.
  • 1988-1998 Staff member and junior researcher, Laser Center, Academic Medical Center. Amsterdam.
  • 1986-1988 Post Doc, Laser Application and Information Center, Department of Atomic Spectroscopy, Faculty of Physics, Free University, Amsterdam

(Co)-Promotorships
The following PhD theses were written under my direct supervision:

  1. 2020-Esther Kho Hyperspectral imaging for  margin assessment in breast cancer surgery Sept 2020
  2. 2020-Xu Zhang Pressure induced variations in Single Fiber Spectroscopy. Sept 2020
  3. 2020-Anouk Post Quantifying tissue optical properties with Single Fiber Reflectance spectroscopy. University of Amsterdam, June 3rd 2020
  4. 2020-Lisanne Balthussen The clinical implementation of optical spectroscopy in colorectal cancer surgery. Twente University, March 4th 2020
  5. 2018-Niels Langhout Optical Tissue identification Oct 19th 2018
  6. 2015-Giju Thomas Nonlinear optical imaging as a diagnostic tool for cutaneous squamous cell carcinoma. University of Amsterdam, Jan 14th 2015
  7. 2014-Floor van Zaanen Fiber optic spectroscopy for the optimization of photodynamic therapy Erasmus University april 9th 2014
  8. 2014-Sebastiaan de Visscher mTHPC mediated PDT of Head and Neck Cancer Jan 8th 2014 University of Groningen
  9. 2014-Baris Karacullukcu New insights into photodynamic therapy of the head and neck University of Amsterdam Feb 27th 2014
  10. 2013-Ute Gamm. Quantification of tissue scattering properties by use of fiber optic spectroscopy Erasmus University Rotterdam, oktober 4th 2013
  11. 2013-Hanke de Vijlder. New insights into photodynamic therapy using porphyrin precursors. Erasmus University Rotterdam, April 26th 2013
  12. 2012-Ramí Nachabé. Diagnosis with near infrared spectroscopy during minimally invasive procedures. Erasmus University Rotterdam, May 29th 2012
  13. 2010-Cor van der Leest. Optical and Functional Imaging of lung cancer. Erasmus University Rotterdam may 28th 2010
  14. 2010-Bastiaan Kruijt. In vivo monitoring of PDT: from lab to clinic. Erasmus University Rotterdam January 15th 2010
  15. 2008-Henriëtte de Bruijn. The mechanism behind the increase in response of tissues to 5ALA based photodynamic therapy using a twofold illumination scheme. Erasmus University Rotterdam, June 12th 2008
  16. 2007-Ellen de Haas. Fractionated ALA PDT of basal cell carcinoma. Erasmus University Rotterdam, October10th 2007
  17. 2007-Jonathan Palero. Non linear spectral imaging in vivo. Utrecht University, July 11th 2007 (joint supervision with prof Gerritsen HC, Utrecht University)
  18. 2006-A Bogaards. In Vivo Optical Imaging of Fluorescent Probes for Cancer Detection and Optically Guided Surgery, Erasmus University Rotterdam, September 7th 2006. (joint supervision with prof B.C. Wilson, Ontario Cancer Center)
  19. 2006-Robert van Veen. Measurement of In-vivo optical properties; Consequences for photodynamic therapy and optical diagnostics. Erasmus University Rotterdam, June 7th 2006.
  20. 2005-Martin Bard. Detection of lung cancer using optical spectroscopy. Erasmus University Rotterdam, September 28th 2005.
  21. 2005-Diana de Veld. Auto fluorescence spectroscopy for classification of oral lesions. University of Groningen, May 11th 2005 (joint supervision with Prof J.Roodenburg, UMCG)
  22. 2003-Johanna Van den Akker. In vivo and in vitro studies on the localization and kinetics of new porphyrin related drugs for photo detection and photodynamic therapy. Erasmus University Rotterdam, November 13th 2003.
  23. 2001-Maurice Aalders. Aspects of photo-detection in cervical and ovarian neoplasia. University of Amsterdam, September 18th 2001.
  24. 2001 -Jeroen Rovers. Photodynamic therapy for colorectal liver metastases; a preclinical study. University of Leiden, May 16th 2001. (joint supervision with Dr M.F. Grahn, Univ of London and Prof O T terpstra)
  25. 1999-Anne Saarnak. Evaluation of fluorescence measurement techniques for tumour detection in vivo. University of Amsterdam, january 12th 1999.
  26. 1995-Konnie Hebeda. Photodynamic therapy of malignant glioma. Free University of Amsterdam November 13th 1995. (joint supervision with Dr. Wolbers JG)
  27. 1993-Johan Beek. Pneumothorax monitoring by remittance measurement. University of Amsterdam June 25th 1993

Teaching experience

  • 2014-now Elastic Scattering spectroscopy. Contribution to Masters Curriculum Faculty of Physics University of Amsterdam and Free University of Amsterdam
  • 2010-2014, Clinical Photodynamic Therapy. In: Basic and Advanced Translational Oncology, (Postgraduate School Molecular Medicine, Erasmus University, annual course)
  • 2009-2014, Photodynamic Therapy. Contribution to base curriculum medicine 2nd year (Erasmus University. annual course)
  • 2008-2014, Writing successful grant proposals (Postgraduate School Molecular Medicine and Taalcentrum Vrije Universiteit Amsterdam annual course)
  • 2008, 2010, 2012 In vivo optical spectroscopy for diagnosis of disease. Fifteenth International School on Quantum Electronics: Laser Physics and Applications Bourgas, Bulgaria.
  • 2008, 2010 Laser Course for Dermatologists Rotterdam Sept 25th (Postgraduate School Molecular Medicine)
  • 2007-now Contribution to third year minor: Biomedical Engineering ( 3ME Technical university of Delft annual course).
  • 2007 Photonics in Medical Diagnosis and Therapy. Opportunities for Integration. ePIXnet Winter school, March 11-17, Pontresina Switzerland.
  • 2006-2012  Annual Basic Laser Course (Postgraduate School Molecular Medicine)
  • 2000-2010 Introduction to photodynamic therapy. Bi-annual contribution to education of Radiotherapy Technicians.
  • 2001, Laser-tissue interaction One day course in Laser surgery. Erasmus Universiteit Rotterdam.
  • 2002-2005 Photodynamic Therapy and Optical Spectroscopy. Contribution to Physics Curriculum, Physics department, Hogeschool Rotterdam.
  • 1992-now 2 to 6 undergraduate Physics/Photonics/healthcare technology students per year from University of Delft, Twente and Haagse Hogeschool and Hogeschool Rotterdam.
  • 1994 Laser Tissue Interactions and Laser Safety. Contributions to SWEN workshop ‘Prostate treatment with Nd:YAG laser light’, Academic Medical Centre Amsterdam, April 29th 1994 en Academic Hospital Utrecht, October 7th 1994 Academic Hospital Nijmegen st Radboud, June 4th 1994.
  • 1992 Pulsed lasers: selective thermolysis and calcified tissue fragmentation, Laser safety and standards of safety and Using lasers to screen for melanomas. Contributions to ‘Laser didactic course’, The University of Texas MD Anderson Cancer Center, September 26th 1992.
  • 1991 Laser Safety. Annual training Netherlands Society for Radiation Hygiene, KEMA, Arnhem, September 27th 1991.
  • 1991 Medical lasers. Contribution to ‘Setmana Laser’, organized by the Academy of Sciences of Cataluña, Tarragona, Spain, December 9th 1991.
  • 1991 Medical safety standards and precautions. Contribution to ‘VI Curso international teoretico-practico lasers en medicina y cirurgia’, Cambrils, Spain December 14th-15th 1991. 1990-1993
  • 1990-1993 A three day course in laser medicine. Amsterdam January 24th 1990, January 24th 1991, June 5th 1992, November 25th 1993.
  • 1987-1988 Backgrounds of medical laser use. A 4 hr class for O.R. assistants, Free University Hospital Amsterdam, November 25th 1987, November 2nd 1988. Anna Reijnvaan school, Academic Medical Center Amsterdam: January 8th, 15th, 29th and February 5th, 19th, and 26th 1988.

Spin-off companies

  • QuaSpec b.v. is an independent startup company. It focusses on developing applications of Elastic Scattering Spectroscopy.
  • Luminostix b.v. commercializes Differential Pathlength Spectroscopy (DPS), a patented optical technology for quantitative measurements in optically diffuse media. 
  • Nano4therapy b.v. is an ErasmusMC spin off company that develops a novel technology platform that yields nanoparticle-conjugates for use in targeted photodynamic therapy. 

 

 

Research programmes

Prof. MEng PhD H.J.C.M. Sterenborg (Optical Spectroscopy and Hyperspectral Imaging for non-invasive diagnosis of disease)

 Over the years my research activities have been centered around development and clinical implementation of optical methods for minimally invasive diagnosis and treatment of disease. The work comprises the entire track from basic research and development of methodology to clinical validation and implementation.

The optical diagnostic techniques I have been using have changed over the years. Initially work was focussed around imaging and spectroscopy of autofluorescence and fluorescent contrast agents. In later years the emphasis moved to diffuse reflection spectroscopy and nonlinear optical spectroscopy and imaging. My current research focus lies entirely on elastic scattering spectroscopy and imaging.

Elastic Scattering Spectroscopy uses broadband white light and guides it to the tissue through optical fibers. Light entering the tissue will be scattered around before it is being absorbed, or leaves the tissue at the surface. This backscattered light is detected with an optical fiber and then analysed by a spectrograph. Current research activities have been focussed at development of quantitative approaches, i.e. methods to measure the scattering and absorption spectra quantitatively. So far I developed methods to measure absorption quantitatively, translate these into biologically related parameters and evaluated these extensively in clinical studies. Current focus is on developing methods for quantitative scattering information. Here both the absolute amount of scattering is of interest, but also the relation between forward and backward scattering is of particular interest because it is thought to be sensitive to intracellular biology. Light scattering occurs due to spatial variations in refractive index. Based on analysis of the wavelength dependence of scattering observed in measurements of tissue it can be concluded that the size of these scattering entities lies well below the resolution of an optical microscope (i.e. 100nm). Other types of microscopes can visualize much smaller structures, but do not do so on the basis of the refractive index. Hence the nature of these scattering entities is not known, but it is speculated that they relate to aspects of the cellular microarchitecture, such as folds in mitochondrial membranes, the presence and distribution of endosomes etc. At present I am focussing on measurement forward-to-backward ratio of scattering in vivo. This uses different fiber diameters and will shortly be tested clinically for screening of Barrett’s esophagus, prostate cancer and for diagnosing mediastinal lymph nodes. In addition, a setup is being developed to measure the angular dependence of back scattering on ex vivo samples.

PhD Students
L. Balthussen
S. Brouwer-de Koning
E. Kho
N. Langhout

Prof. MSc PhD A.G.J.M. van Leeuwen (Biomedical photonics for functional and molecular imaging)