Optical biopsy using very short laser pulses

Ultrafast optical spectroscopy for depth resolved optical biopsy: ULTRADOC

Optical spectroscopy is a non-invasive and safe diagnostic technique, using light sources and fibre-optics, in combination with spectrographs. The obtained spectra contain information about the scattering and absorption properties of the sampled tissue. Analysis of these optical properties could allow us to assess resection margins in breast cancer surgery. Researchers of Amsterdam UMC join forces with their colleagues from Single Quantum to develop an innovative, ultra-fast spectroscopy system using the fastest light detector available in combination with picosecond laser pulses to obtain this information from shallow depths at resolutions in the order of 1-2 mm.  

The presence of tumours in the outer 2 mm of tissue resected from a patient during surgery can currently only determined off-line. In case of positive margins, re-operations have to be scheduled with massive burden to the patient and increased health care costs. Both aspects can be reduced when these positive margins are detected directly during the surgical procedure, allowing to surgically remove the additional tumorous tissue.

The aim of this project is to develop and validate hardware and theoretical models that enable to perform spectroscopic measurements with a depth resolution of 1-2 mm in a small sensing volume. In these models both the optical properties of the tissue as well as the geometrical design must be incorporated.

In the project we first develop and validate a novel theory for ultrafast time-resolved sub-diffuse spectroscopy, which allows us to see changes in tissue properties in the top 2 mm of the tissue. We design and validate the proof-of-concept of the instrumentation to measure these changes in tissue properties. Finally, we test and validate the system on tissue mimicking materials.

 

Researchers of Amsterdam UMC worked together with colleagues from Single Quantum B.V. to evaluate their ultrafast detector in order to perform ultrafast spectroscopic measurements. We therefore developed and tested a detection system with a temporal resolution of 12 picoseconds which allowed us to distinguish between light that had propagated through superficial tissue and light that had traveled into deeper layers. 

Up to now, no physics-based model was available to describe the light trajectories in tissue for these small distances. We therefore developed and validated a novel theoretical model that enabled us to describe the photon counts as a function of time. We demonstrated that the model described the measured photon distributions with an unprecedented temporal resolution of 1 picosecond for various scattering tissues, for various distances between the launching and detection fibre (ranging from 0 to 5 mm). Next, we tested different fibre configurations to demonstrate the depth sensitivity of the measured signals and determined the optimal configuration to detect signals that are related to changes in optical properties of the top 2 mm of tissue.

Thus, in this project the equipment was developed and validated on highly controlled tissue-mimicking materials. Relations between source-detector configuration and monitored depth were established. Furthermore, algorithms for extracting the optical properties of the tissue layer were developed and tested.

Summary
We developed an innovative, ultra-fast spectroscopy system to determine the changes in the optical properties of tissue in the first 2 mm. These superficial changes can reflect the presence changes in the constituent of tissue (e.g. by tumours) and therefore our ultrafast-spectroscopy may facilitate improved medical diagnostics during surgical interventions.
Technology Readiness Level (TRL)
4 - 5
Time period
48 months
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