Multi-wavelength probe for tumor margin detection during breast conserving surgery

Abstract

Breast cancer is the most prevalent form of cancer among women, leading to 2.3 million new diagnosis and almost 685,000 deaths in 2020. Currently, one of the preferred treatments is breast conserving surgery (BCS), but its success depends on the correct identification of tumor margins during surgery. A promising optical intraoperative margin assessment technique is diffuse reflectance spectroscopy (DRS). However, the DRS instrumentation is complex, since it uses dedicated broadrange lights and sensors. In addition, the system is expensive and voluminous. Thus, a simpler alternative is desired. A possible approach is to probe the tissue’s optical response at only a few relevant wavelengths.

This thesis, developed within an ongoing collaboration between TU Delft and Philips, represents a first proof-of-concept study towards the development of a multi-wavelength hand-held probe for real-time tumor detection during BCS.

A multi-wavelength sensor was developed for testing based on an existing prototype, able to measure with an infrared photodetector the optical response from two independent light emitting diodes.

The working principle of the detection system was based on the known differences in fat/water-ratio between healthy and tumor tissue. It was investigated whether the optical response of tissue-mimicking phantoms with different fat and water content, measured with infrared LEDs in a transmittance-based configuration, could provide a means to quantify the composition of the phantoms. A measurement method was proposed based on the linear relationship observed between the percentage of fat in the phantoms and the ratio of transmitted light intensity measured at 970 nm or 1300 nm, and 1200 nm. The test was repeated with new phantoms, and it was found that the parameters of the fat-intensity relationship varied between the experiments. The scattering parameter was identified as the main cause of this variation.

To demonstrate the feasibility of integrating the system in a hand-held device, the sensor was tested with optical fibers in a reflectance-based configuration. Infrared lasers were found to be suitable light sources to detect differences in reflected light intensity depending on the probing wavelength and phantom composition. However, the wavelengths of the available lasers were not significant for tissue discrimination, so the working principle of the measurement system was not tested in this configuration.

Overall, the results demonstrated that it is possible to use multi-wavelength optical measurements to detect differences between healthy and tumor tissue based on the fat and water concentrations. Further investigation is required to determine a robust method which allows to exactly quantify the tissue content based on the measured reflected intensity. Furthermore, following miniaturization and optimization, the sensor is suitable for integration in a hand-held surgical instrument. Despite the limitations, this study reveals the potential of multi-wavelength optical devices for tumor detection in breast, and encourages further research for their integration in the surgical practice.