Biomedical Physics
Group leader Prof. dr. Johannes F. de Boer

Optical Coherence Tomography

Optical coherence tomography (OCT) is an interferometric imaging technique which is sometimes referred to as the photon-based equivalent of ultrasound tomography. It records the scattering of photons in a sample in all three dimensions with a micrometer scale resolution. Each measurement contains information about intensity and phase of the photons' electrical field. The intensity can be used to gain information about the morphology of the sample while the phase is used in the analysis for more advanced techniques, like Doppler OCT or polarization sensitive OCT. Doppler-OCT is helpful to visualize motion and is therefore suitable to detect blood flow. Polarization sensitive OCT can measure the birefringence of tissue composed of fiber-like structures, such as collagen. Our systems are all home-built and based on optical fibers to provide maximal versatility for imaging different organs with multiple OCT modalities.

Polarization-sensitive OCT for retinal imaging

Max Grafe and Aleid van de Kreeke

We are working on an ophthalmic OCT which combines the functionality of Doppler and polarization sensitivity. Devices for those individual functions have been built by our group in the past (Braaf et al. 20 (18), 2012; Braaf et al., Biomed Opt Expr 5 (8), 2014) and the combination makes it particularly challenging because the requirements of both need to be met but it also makes it particularly unique as a diagnostic tool. On the one hand, the polarization sensitivity can reveal properties of layers with many fiber bundles like nerve fiber layers. On the other hand, we are also working on a quantification method of the blood flow with Doppler-OCT for the retinal vasculature. This technique still needs verification and therefore part of this work focuses on construction and measurements of model eyes and phantoms.  
This system can then used to investigate various retinal diseases. In age-related macular degeneration (AMD) the scar tissue (fibrosis) that forms in the retina late in the disease progress is birefringent and therefore easy to recognize with PS-OCT. Glaucoma affects mainly the birefringent retinal nerve fiber layer (RNFL). We know that about 40-50 % of the never fibers is already lost by the time patients show functional loss meaning that the visualization of the structural loss could lead to an earlier diagnosis of this disease.  AMD and diabetes-patients often suffer from neovascularization (development of abnormal blood vessels) such as wet AMD and diabetic macular edema which can be addressed with the Doppler-functionality.


Diagnostic imaging of retinoblastoma with OCT

Oleg Nadyarnykh

This is a translation research project where we have packaged the OCT technology in a clinically approved system specifically designed for diagnostic imaging of retinoblastoma in little children under inhalation anesthesia. The precise determination of tissue vitality and tumor locations is the main challenge for both initial diagnosis and optimal treatment of this retinal malignancy. The established imaging methods often lack sufficient resolution, and specificity, and the doctors rely on monitoring the patients at risk every month to confirm the absence of further morphological changes, where critical time is lost on possible tumor (re)growth. Three-dimensional visualization of tissue morphology at the 2-25 mm resolution of OCT improves retinoblastoma diagnostic capabilities in-vivo and in real time.  The clinical study with our homebuilt OCT imaging system is ongoing at the VU-MC.


Burn wound imaging with OCT

Fabio Feroldi

Burn wounds are a common injury that often leaves permanent scars on the skin of people and sometimes lifelong disability in terms of impaired movements. One problem that concerns burns is that the injured area is extremely sensitive to infections and it is very painful for several days after the accident. Because of this, most of the assessment is done by simply looking at the color and extent of the burn or by gently touching it. Therefore, a non-invasive technique that reliable predicts the behavior of the injury is desirable.

Polarization sensitive OCT is a technique that allows to highlight the presence and density of collagen bundles in tissue. Moreover it can register the degradation of collagen due, for example to exposure to temperatures higher than 56 °C. This technique might be a tool to assess a burn or a potential predictor of the evolution of a burn scar.
For this purpose, we have built a custom handheld probe that is able to perform PS-OCT on the skin, with minimal discomfort for the patients
In collaboration with the Rode Kruis Hospital in Beverwijk (NL) we have conducted imaging sessions on people with fresh burn wounds and also on people with scars caused by burns.


Miniaturized OCT and NIR-Fluorescence endoscopy

Fabio Feroldi and Helene Knaus

Our research focuses on simultaneous optical coherence tomography and near-infrared fluorescence imaging for clinical applications using miniaturized scanning devices. The combination of optical coherence tomography (OCT) and fluorescence imaging provides morphological and biochemical information of the specimen. Real time images can be obtained noninvasively by implementing these two techniques in a handheld device or an endoscope. In combination with specific labeling of cancer tumors using fluorescent dyes, this opens the door for new early stage cancer diagnostics, for example colorectal cancer or lung cancer.

We are working on a versatile imaging platform based on double-clad fibers that can be used with a motorized and flexible endoscope for inner organs inspection or a handheld device for intrasurgical imaging.


Image: Simultaneously acquired fluorescence image and en face OCT images using the handheld device, showing a gelatin embedded melanoma-cancer-cell-spheroid (mimicking a melanoma tumor).


Extending the axial focus of OCT

Judith van Santen

In the quest of diagnosing cancer in an early stage, we are working on increasing the resolution in OCT, to be able to diagnose smaller tumors. Ultimately we want to employ this for OCT endoscopy. To improve the resolution we use mathematical refocusing. This refocusing is possible due to a phase plate which is added to the sample arm of the OCT system, which creates three optical paths for the light. Because we now have three images of the same tissue, which all three inhibit different phases imposed by the phase plate, we can extract the defocus phase and correct for it, yielding refocused images. This refocusing method leads to four-fold increase of high-resolution imaging range.