Metastasis happens when cancer cells get the ability to spread and form new tumors in different places in the body. Generally, by traveling within blood or lymph vessels. Early diagnosis is essential, since metastasis is a hallmark of advanced cancer and it severely complicates treatment. This can be found by looking for circulating tumor cells (CTCs) in blood samples.
However, CTCs can be very rare, and in small blood samples they might be completely absent despite being present in a patient’s bloodstream. A technique called diffuse in-vivo flow cytometry (DIFC) has been developed by researchers to address this problem. It shines a laser directly onto an artery, involves labeling CTCs with a fluorescent agent and capturing the emitted fluorescent signals using a detector to count the number of CTCs. While promising, by the background noise from the inherent fluorescence of the surrounding tissue called autofluorescence (AF), DIFC measurements can be highly affected.
The DR method was initially considered for spectroscopy techniques and has now been accepted for DIFC. The resulting DR DIFC system employs two laser sources and two detectors arranged carefully in space. In theory, by combining the signals of the two detectors the noise can be cancelled out. The AF contributions of the surface of the measured medium, say, skin, can also be lessened by using the DR approach.
In three ways this knowledge gap was addressed by researchers. Using various noise and AF parameters, they ran Monte-Carlo stimulations as well as for different source-detector configurations. Using an artificial tissue-mimicking flow phantom with cell-mimicking fluorescent microspheres, they conducted DR DIFC experiments. Finally, the team measured the AF of the skin and the underlying muscle of mice to gain insight into the variation of noise with tissue type and depth.
The experiment in mice suggested, than in underlying muscle the AF is much higher in skin, indicating that DR DIFC may offer an advantage over standard DIFC in most cases.
Overall, the results of this study will be essential for the development of DR DIFC as an emerging technique to noninvasively detect fluorescent molecules in the bloodstream.
This system will allow doctors to quickly detect cancer cells in the blood of patients without having to draw samples, making the diagnosis of metastasis simpler and more accurate. In the future this could be broadened to cover various other cell varieties or even universal molecules of interest in the near future.
