One of the streams in advanced diagnostic technologies is non-invasive spectroscopic investigation or “spectral histopathology” as a novel alternative for rapid cancer diagnostics and label-free cancer specification. Fiber optics enable faster and more convenient way to study different biological tissues than standard techniques which require destructive sample preparation (e.g. histopathology, chemical analysis). Moving on this direction, we developed and applied various fiber optic probes for key spectroscopy methods such as Raman scattering, Mid IR-absorption, Diffuse NIR-reflection, and auto-fluorescence – to compare them and select the best combination for a real-time detection of malignant tissue in pre-clinical and clinical environment. All four spectroscopic methods have been tested for cancer diagnostics on biopsies of normal and cancer tissues (abdominal, oral and brain), ex-vivo samples and bioliquids. Obtained spectral data were evaluated by multivariate discrimination analysis to enable clear separation of malignant and normal tissues. Benefits of combination of several spectroscopic modalities and data fusion is presented for the better sensitivity, specificity and accuracy. The best synergetic effect was observed of combining Mid IR-absorption and fluorescence spectroscopy, (98% Sensitivity vs 63% or 88% for fluorescence or Mid IR-absorption correspondingly). Based on obtained results, several fiber optic probes combining several spectroscopic modalities implemented within the same single probe were designed, assembled and evaluated.
Combination of FTIR spectroscopy with fiber optics provides a powerful diagnostic tool for diagnosing of human diseases, including osteoarthritis. To detect cartilage degradation, an arthroscopic probe based on polycrystalline fibers was developed and evaluated on equine cartilage specimen. The hook shape allows reaching a significant portion of the articular surface; the flat tip ensures avoidance of tissue destruction. Efficient QCL-coupling and stable transmission of PIR fibers under bending allows the assembling of effective thin arthroscopy probes and customized multispectral systems for medical diagnostic applications. The presented work was performed within the MIRACLE project (Grant Agreement No 780598, Horizon 2020).
Single and combined fiber optic probes for key spectroscopy methods (Raman scattering, Mid IR-absorption, Diffuse NIR-reflection, and auto-fluorescence) were compares to detect malignant tissue in clinical environment. All four methods were tested on cancer diagnostics on biopsies (stomach, colon and kidney) and bioliquids (serum, plasma and urine) of patients.
Optical spectroscopy offers unique opportunities for a label-free investigation of tissues at the molecular level to identify the variety of diseases. To transfer spectroscopic analysis from the scientific laboratories to clinical environment, fiber optic probes are required as optical bridges between the equipment and tissue.
We developed single and combined fiber optic probes for the following set of spectroscopy methods: Mid IR-absorption, Raman scattering, Diffuse NIR-reflection, and auto-fluorescence. We benchmarked these methods and selected the optimal one (or their combination), that differentiate between healthy and malignant tissue, based on optical spectra. We tested cancer-normal tissue pairs of human body such as colon, kidney, brain as well as cartilages with and without injuries. Equines cartilage samples with and without osteoarthritis were tested as well. Obtained spectral data were evaluated by multivariate discrimination analysis to enable clear separation of malignant and normal tissues. Data fusion was revealed a synergic effect resulted in increasing of sensitivity, specificity and accuracy (up to 98% for kidney cancer).
Medical fiber optics as a part of laboratory and clinical diagnostic tools, surgical instrumentation and endoscopy should satisfy modern biomedical requirements. The flexibility, small size, bio-compatibility and feasibility to use sterilisable or disposable parts allow to apply fiber optic probes in clinical environment both ex-vivo and in-vivo.
To enable spectroscopic differentiation cancer and normal tissue, we developed and applied various single and combined fiber optic probes using key spectroscopy methods such as Raman scattering, Mid IR-absorption, Diffuse NIR-reflection, and fluorescence in order to compare them and select the best combination for malignant detection of tissue in clinical environment.
All four spectroscopic methods have been tested on biopsies of health and malignant tissues (colon and kidney) and bioliquids (serum, plasma and urine) of patients before and after surgery. The tiny Raman probe with 1.5 mm diameter has been developed for experimental ex-vivo tests. Further multivariate data analysis of spectroscopic data, both individual techniques and their combinations has provided a reliable cancer recognition for colon and kidney biopsies. The best synergic gain was observed of combining Mid IR-absorption and fluorescence spectroscopy (98% Sensitivity vs 63% or 88% for fluorescence or Mid IR-absorption correspondingly). Based on obtained results, both techniques were implemented within the same fiber probe to provide a simultaneous measurement of exactly the same spot at the sample surface. An innovative combi Fluo-ATR probe was designed, fabricated and tested.
Diffuse NIR-reflection and fluorescence spectroscopy as the fastest measurement techniques were used for investigation of surgically removed colorectal tissue samples in a few minutes after resection. Taking into account the necessity of rapid measurement process, we developed multispectral NIR-UV probe that enables efficient excitation and collection of NIR diffuse reflectance and fluorescence spectra of the same point. Needle probe design with diameter 0.7 mm allows to penetrate in some depth of tissue and obtain most reliable spectra avoiding artefacts related to surface drying. Multivariate data analysis proved the increased sensitivity of methods combination in one dataset (94% Sensitivity vs 85% or 85% for fluorescence or NIR reflection correspondingly).
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