Researchers and surgeons at a UK hospital evaluate an innovative technique for detecting breast cancer in lymph nodes utilizing Raman spectroscopy. Although surgical management of breast cancer has advanced over the years since the days of Halsted's radical mastectomy, a surgeon needs to perform two or more operations for some patients to ensure the excision of all cancerous tissue.
In the first operation, the visible breast cancer is removed and the axillary lymph nodes are then sampled to assess the signs of any spread of the disease. An additional procedure must be required if the spread is confirmed by post-operative tests to get rid of all the nodes in the affected area. This approach not only causes psychological stress and anxiety to the patient, but also poses the risks of additional surgery and general anesthesia.
A Preferable Approach Using Raman Spectroscopy
A preferable approach would be some kind of intra-operative assessment that facilitates the immediate removal of all of the axillary lymph nodes when needed. Raman spectroscopy is a light-scattering analytical technique capable of detecting differences in tissue composition and its expediency has already been shown in many cancer pathologies.
Furthermore, the research employing Raman spectroscopy and principal component analysis (PCA) to explore axillary lymph nodes has now demonstrated that the method can match the specificities and sensitivities of existing techniques.
Nevertheless, the mapping techniques require several hours to produce for each lymph node being analyzed, making it inappropriate for intra-operative use.
According to Jonathan Horsnell, a researcher at the Gloucestershire Royal Hospital in the UK, it is necessary to develop a simple and cost-effective technique capable of analyzing the node rapidly and precisely to realize a ‘one-stop’ axillary surgery.
Horsnell and colleagues explored the existing data further to reproduce the utilization of a probe-based Raman spectrometer (Figure 1) by choosing equally spread points across the maps. With specificities remaining above 90%, the results supported the potential use of a Raman probe.
While the sensitivity was not up to the mark as tinier metastatic deposits were missed, it was at a level comparable to that reported for the classical histopathological techniques of frozen section analysis and touch imprint cytology.
Figure 1. B&W Tek Raman spectrometer
When compared to a microscope, a probe’s larger spot size has the potential to overcome this reduced ability to determine tiny metastatic deposits, by gathering light scattered from a larger volume of tissue per spectrum.
After an extensive assessment of compact fiber-optic Raman spectrometers, the Gloucestershire Royal Hospital team selected the MiniRam II spectrometer from B&W Tek to illustrate this effect, as it was the only instrument in its class that employ both a volume Bragg grating (VBG) stabilized laser source and a thermoelectrically cooled CCD array.
The MiniRam II spectrometer is capable of collecting scattered light from depths of up to 4mm at an acquisition time of 16 seconds per spectra. Hence, instead of acquiring several hundreds of spectra from tiny points across a tissue field, this technique enables sampling of a much larger volume of tissue per spectrum. This, in turn, allows the researchers to perform tissue assessment within a time that would be acceptable in a clinical setting.
The clinical efficacy of this volume sampling technique was reported in the journal Analyst. In the analysis, the research team used the MiniRam II spectrometer to assess 38 lymph nodes from 20 patients undergoing breast cancer surgery, and compared the results with a typical histopathological assessment of each node.
As expected, the team achieved improved results when compared to the probe models, with sensitivities of up to 92% and specificities of up to 100% in the differentiation of normal and metastatic nodes.
This was made possible using a ‘leave one node out’, cross-validated measurement of five random spectra from each node. Consequently, the time needed to acquire five spectra was below 90 seconds, a value much faster than any existing intra operative technique.
Although encouraging, these results were experimental and achieved on tissue that had been ‘snap’ frozen during surgery, utilizing an instrument within a laser laboratory.
This information has been sourced, reviewed and adapted from materials provided by B&W Tek.
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