Research

Optical Coherence Tomography

About OCT

Optical Coherence Tomography (OCT) is a high resolution, noninvasive 3D-imaging technique employing light. OCT is often referred to as the ‘optical analogue’ of ultrasound imaging. Similar to ultrasound imaging, OCT creates a cross sectional (or 3D) image of tissue from the depth resolved backscattered intensity. The major difference between OCT and ultrasound imaging, is that OCT uses light, instead of sound. This has the direct consequence that the resolution is many times better in OCT (in the order of 1 to several micrometers), but the imaging depth in tissue is lower (maximally 2 mm).

OCT is based on the principle of low coherence interferometry (LCI): a low coherent (i.e. broadband) light source illuminates the sample of interest, as well as a reference path. Only if the reference path has exactly the same length as the path towards the sample, interference occurs between the backscattered light by the sample and the back reflected light from a mirror in the reference path. The backscattered intensity by the sample as a function of depth (A-scan) can be obtained by either changing the length of the reference path, or by means of Fourier domain detection. Lateral scanning in one direction results in an OCT B-scan, and lateral scanning in two directions results in a 3D OCT image of the tissue of interest.


Image: OCT B-scans of muscular tissue (left) and fatty tissue (right).

As a clinical diagnostic tool, OCT is highly successful in the field of ophthalmology. Examination of the retina by OCT facilitates the noninvasive diagnosis of numerous retinal abnormalities and diseases, that would otherwise have been impossible. Besides ophthalmology, OCT is being used as a clinical research tool in many other medical fields: dermatology, gynecology, dentistry, cardiology, pulmonology, urology, gastroenterology and more. Many of its applications focus on the noninvasive grading and staging of cancerous tissue, but also on other highly relevant clinical applications, like the intravascular investigation of atherosclerotic plaques.

OCT research at BMPI

At BMPI, we go beyond imaging with OCT. By investigating the spectroscopic content of the OCT signal at every depth inside the tissue of interest, we perform depth-resolved spectroscopy. Spectroscopy relates the wavelength dependent absorption and scattering of tissue to its chemical composition. As a result, we not only obtain structural information about the tissue of interest, but also chemical information.

This functional extension of OCT, called spectroscopic OCT (sOCT) or low-coherence spectroscopy (LCS) has two major advantages compared to conventional (diffuse) reflectance spectroscopy: 1) it is localized, since we exactly know the depth from which our spectroscopic signal originates inside the tissue, and 2) it is quantitative, since we do not have make any assumptions on the optical path length that the light has traveled when calculating the optical absorption and/or scattering inside tissue.

Noninvasive blood analysis in newborns by spectroscopic OCT

Jaundice is a common and often harmless clinical condition in newborns, related to elevated concentrations of bilirubin in blood and extravascular tissue. However, in the case of severe jaundice, there is a high risk of bilirubin extravasation into the brain, causing irreversible brain damage (kernicterus) to the patient. Newborns at risk of severe jaundice are therefore subject to frequent invasive blood sampling. If the blood bilirubin concentration exceeds the acceptable limits, immediate treatment (i.e. phototherapy or exchange transfusion) is started. Invasive blood sampling is related to pain, stress, substantial blood loss and increased risk of infections – all factors that have been proven to impair the growth and development of this extremely vulnerable patient group.

A possible alternative to invasive blood testing is optical spectroscopy: the wavelength dependent analysis of remitted light from skin. This is a fast, noninvasive technique, sensitive to the concentration dependent absorption of light by bilirubin. Transcutaneous bilirubinometers are based on this principle and are currently applied to effectively reduce the number of required invasive blood samples for bilirubin determinations in the clinic. Unfortunately, they cannot replace all invasive blood samples, as their accuracy is inherently limited by the fact that they measure the skin concentration of bilirubin. This skin concentration is not directly (one to one) related to the blood concentration that is used for medical decision making.

In this project, we use visible sOCT to confine the spectroscopic measurement volume to blood only, for instance a single blood vessel. In that way, we exclude the background disturbance of extravasated bilirubin in the skin and measure the bilirubin concentration in blood directly. With that, we hope to achieve the highest possible measurement accuracy for noninvasive bilirubinometry, and reduce as many invasive blood samples as possible.

Contact

Dr. ir. Nienke Bosschaart
Assistant Professor
+31(0)53 489 3877
 n.bosschaart@utwente.nl
MSc. Colin Veenstra
PhD Candidate
+31(0)53 489 5493
 c.veenstra@utwente.nl

Funding

This research is funded by

  • a personal VENI grant in the Innovational Research Incentives Scheme from the Netherlands Organization for Scientific Research (NWO), division of Applied and Engineering Sciences (TTW)
  • a Pioneers in Healthcare Voucher from the joint innovation fund by Medisch Spectrum Twente (MST), Ziekenhuisgroep Twente (ZGT) and the University of Twente (UT)

Scientific awards

  • Simon Stevin Gezel Award, 2013
    from the Organization for Scientific Research (NWO), division Applied and Engineering Sciences (TTW)
  • PhD thesis award, 2013
    from the Dutch association for Biophysics and Biomedical Engineering (BIOPM)
  • Tweelingprijs for best publication in the research field of Pediatrics, 2013
    from the Maarten Kapelle foundation and the Dutch Association for Pediatrics (NVK)
  • Best poster award, 2011
    from Photonics Cluster Netherlands at the Dutch Photonics Event
  • Simon Stevin Student Award, 2010
    from the Organization for Scientific Research (NWO), division Applied and Engineering Sciences (TTW)

 Students who received awards on this project:

  • Rosaline Mentink: Abbott Prize for best scientific internship in pediatrics, 2011
    from VU Medical Center
  • Rosaline Mentink: Student Research Prize for best student research project, 2010
    from VU Medical Center

Selected publications

  1. N. Bosschaart, J.H. Kok, A.M. Newsum, D.M. Ouweneel, R. Mentink, T.G. van Leeuwen, M.C.G. Aalders, Limitations and opportunities of transcutaneous bilirubin measurements, Pediatrics 129, 689-694 (2012)
  2. N. Bosschaart, M.C.G. Aalders, D.J. Faber, J.J.A. Weda, M.J.C. van Gemert, T.G. van Leeuwen, Quantitative measurements of absorption spectra in scattering media by low-coherence spectroscopy, Optics Letters 34, 3746-3748 (2009)
  3. N. Bosschaart, D.J. Faber, T.G. van Leeuwen, M.C.G. Aalders, In vivo low-coherence spectroscopic measurements of local hemoglobin absorption spectra in human skin, Journal of Biomedical Optics 16, 100504 (2011)
  4. N. Bosschaart, D.J. Faber, T.G. van Leeuwen, M.C.G. Aalders, Measurements of wavelength dependent scattering and backscattering coefficients by low-coherence spectroscopy, Journal of Biomedical Optics 16, 030503 (2011)
  5. N. Bosschaart, M.C.G. Aalders, T.G. van Leeuwen, D.J. Faber, Spectral domain detection in low-coherence spectroscopy, Biomedical Optics Express 3, 2263-2272 (2012)
  6. N. Bosschaart, T.G. van Leeuwen, M.C.G. Aalders, D.J. Faber, Quantitative comparison of analysis methods for spectroscopic optical coherence tomography, Biomedical Optics Express 4, 2570-2584 (2013)
  7. N. Bosschaart, R. Mentink, J.H. Kok, T.G. van Leeuwen, M.C.G. Aalders, Optical properties of neonatal skin measured in vivo as a function of age and skin pigmentation, Journal of Biomedical Optics 16, 097003 (2011)
  8. N. Bosschaart, G.J. Edelman, M.C.G. Aalders, T.G. van Leeuwen, D.J. Faber, A literature review and novel theoretical approach on the optical properties of whole blood, Lasers in Medical Science 29, 453-479 (2014)