Application of the fluorescence spectroscopy for the analysis of the state of abdominal cavity organs tissues in mini-invasive surgery

At present, minimally invasive interventions become more widespread for treating hepatopancreatoduodenal area pathologies. However, new methods and approaches are necessary for obtaining more diagnostic information in real time. Several methods within the framework of "optical biopsy" concept are considered. The features and areas of application of each method are reviewed to find out which of them can be used in further studies to assess the possibility of intraoperative use in minimally invasive abdominal surgery. Preliminary measurements with fluorescence spectroscopy method have been performed at excitation wavelengths 365 nm and 450 nm. Areas of interest were common bile duct, gallbladder and liver abscess. In our opinion, the obtained results can be a basis for further research and provide a deeper understanding of pathological processes of abdominal cavity organs tissues

Fluorescence lifetime needle optical biopsy discriminates hepatocellular carcinoma

This work presents results of in vivo and in situ measurements of hepatocellular carcinoma by a developed optical biopsy system. Here, we describe the technical details of the implementation of fluorescence lifetime and diffuse reflectance measurements by the system, equipped with an original needle optical probe, compatible with the 17.5G biopsy needle standard. The fluorescence lifetime measurements observed by the setup were verified in fresh solutions of NADH and FAD++, and then applied in a murine model for the characterisation of inoculated hepatocellular carcinoma (HCC) and adjacent liver tissue. The technique, applied in vivo and in situ and supplemented by measurements of blood oxygen saturation, made it possible to reveal statistically significant transformation in the set of measured parameters linked with the cellular pools of NADH and NADPH. In the animal model, we demonstrate that the characteristic changes in registered fluorescent parameters can be used to reliably distinguish the HCC tissue, liver tissue in the control, and the metabolically changed liver tissues of animals with the developed HCC tumour. For further transition to clinical applications, the optical biopsy system was tested during the routing procedure of the PNB in humans with suspected HCC. The comparison of the data from murine and human HCC tissues suggests that the tested animal model is generally representative in the sense of the registered fluorescence lifetime parameters, while statistically significant differences between their absolute values can still be observed

Optical diagnostics of bile duct tissues state with tumor compression

The paper presents the results of in vivo experimental measurements of the endogenous fluorescence and blood perfusion in common bile duct tissues in obstructive jaundice patients during minimally invasive surgical operations. Nowadays the type of interventions become more widespread for treating hepatopancreatobiliary pathologies. An effective feedback which can be established by one or more optical diagnostic channels integrated into the standard instruments for minimally invasive manipulations would be of particular value to practical surgeons. To collect reference data, an experimental study has been conducted using a fiber optical probe with fluorescence spectroscopy and laser Doppler flowmetry channels. For every measurement, the areas of interest were different areas of common bile duct obstructed by a malignant tumor. Obtained results demonstrated significant variety registered intensities of fluorescence spectra and values of blood perfusion. Tested fiber optical endoscopic system showed sensitivity to the tissue state in the investigated area, so the two modal approach seems to be promising for further research and implementation in clinical practice

Detection of NADH and NADPH levels in vivo identifies shift of glucose metabolism in cancer to energy production

Profound changes in the metabolism of cancer cells have been known for almost 100 years, and many aspects of these changes have continued to be actively studied and discussed. Differences in the results of various studies can be explained by the diversity of tumours, which have differing processes of energy metabolism, and by limitations in the methods used. Here, using fluorescence lifetime needle optical biopsy in a hepatocellular carcinoma (HCC) mouse model and patients with HCC, we measured reduced nicotinamide adenine dinucleotide (NADH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) in control liver, and in HCC tumours and their adjacent regions. We found that NADH level (mostly responsible for energy metabolism) is increased in tumours but also in adjacent regions of the same liver. NADPH level is significantly decreased in the tumours of patients but increased in the HCC mouse model. However, in the ex vivo tumour slices of mouse HCC, reactive oxygen species production and glutathione level (both dependent on NADPH) were significantly suppressed. Thus, glucose‐dependent NADH and NADPH production in tumours changed but with a more pronounced shift to energy production (NADH), rather than NADPH synthesis for redox balance

Detection of NADH and NADPH levels in vivo identifies shift of glucose metabolism in cancer to energy production

Profound changes in the metabolism of cancer cells have been known for almost 100 years, and many aspects of these changes have continued to be actively studied and discussed. Differences in the results of various studies can be explained by the diversity of tumours, which have differing processes of energy metabolism, and by limitations in the methods used. Here, using fluorescence lifetime needle optical biopsy in a hepatocellular carcinoma (HCC) mouse model and patients with HCC, we measured reduced nicotinamide adenine dinucleotide (NADH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) in control liver, and in HCC tumours and their adjacent regions. We found that NADH level (mostly responsible for energy metabolism) is increased in tumours but also in adjacent regions of the same liver. NADPH level is significantly decreased in the tumours of patients but increased in the HCC mouse model. However, in the ex vivo tumour slices of mouse HCC, reactive oxygen species production and glutathione level (both dependent on NADPH) were significantly suppressed. Thus, glucose-dependent NADH and NADPH production in tumours changed but with a more pronounced shift to energy production (NADH), rather than NADPH synthesis for redox balance

Optical needle biopsy for multimodal detection of the malignant liver tumours

Abstract At the moment, percutaneous needle biopsy (PNB) remains the gold standard for diagnosing liver cancer. However, the relatively high probability of false-negative results can still be an issue with the method. The introduction of real-time feedback for the precise navigation of the biopsy tool is an up-and-coming technology to immensely reduce the mistakes in taking relevant tissue samples. This work presents the technical details of the developed optical biopsy system, which implements fluorescence lifetime and diffuse reflectance measurements. Also, we demonstrate the most recent results of measurements by the system equipped with a novel needle optical probe, compatible with the 17.5G biopsy needle standard. At the first stage, measurements were verified in the murine model with inoculated hepatocellular carcinoma (HCC). With that model, we demonstrate that the registered set of independent diagnostic parameters allows us to reliably distinguish the HCC tissue, liver tissue in the control and the metabolically changed liver tissues of animals with the developed HCC tumour. At the second stage, the optical biopsy system was tested during the routing procedure of the transcutaneous biopsy in humans with suspected cancerous processes in the liver. Our results demonstrate that the developed technique can reliably discriminate malignant tumours of different nature (primary HCC and adenocarcinoma metastasis) from liver tissues. We conclude that, being supported by machine learning approaches, the presented technique can significantly decrease the rate of false-negative results for transcutaneous biopsy

Fluorescence lifetime needle optical biopsy discriminates hepatocellular carcinoma

Abstract This work presents results of in vivo and in situ measurements of hepatocellular carcinoma by a developed optical biopsy system. Here, we describe the technical details of the implementation of fluorescence lifetime and diffuse reflectance measurements by the system, equipped with an original needle optical probe, compatible with the 17.5G biopsy needle standard. The fluorescence lifetime measurements observed by the setup were verified in fresh solutions of NADH and FAD++, and then applied in a murine model for the characterisation of inoculated hepatocellular carcinoma (HCC) and adjacent liver tissue. The technique, applied in vivo and in situ and supplemented by measurements of blood oxygen saturation, made it possible to reveal statistically significant transformation in the set of measured parameters linked with the cellular pools of NADH and NADPH. In the animal model, we demonstrate that the characteristic changes in registered fluorescent parameters can be used to reliably distinguish the HCC tissue, liver tissue in the control, and the metabolically changed liver tissues of animals with the developed HCC tumour. For further transition to clinical applications, the optical biopsy system was tested during the routing procedure of the PNB in humans with suspected HCC. The comparison of the data from murine and human HCC tissues suggests that the tested animal model is generally representative in the sense of the registered fluorescence lifetime parameters, while statistically significant differences between their absolute values can still be observed

Machine learning aided photonic diagnostic system for minimally invasive optically guided surgery in the hepatoduodenal area

Abstract Abdominal cancer is a widely prevalent group of tumours with a high level of mortality if diagnosed at a late stage. Although the cancer death rates have in general declined over the past few decades, the mortality from tumours in the hepatoduodenal area has significantly increased in recent years. The broader use of minimal access surgery (MAS) for diagnostics and treatment can significantly improve the survival rate and quality of life of patients after surgery. This work aims to develop and characterise an appropriate technical implementation for tissue endogenous fluorescence (TEF) and assess the efficiency of machine learning methods for the real-time diagnosis of tumours in the hepatoduodenal area. In this paper, we present the results of the machine learning approach applied to the optically guided MAS. We have elaborated tissue fluorescence approach with a fibre-optic probe to record the TEF and blood perfusion parameters during MAS in patients with cancers in the hepatoduodenal area. The measurements from the laser Doppler flowmetry (LDF) channel were used as a sensor of the tissue vitality to reduce variability in TEF data. Also, we evaluated how the blood perfusion oscillations are changed in the tumour tissue. The evaluated amplitudes of the cardiac (0.6–1.6 Hz) and respiratory (0.2–0.6 Hz) oscillations was significantly higher in intact tissues (p %lt; 0.001) compared to the cancerous ones, while the myogenic (0.2–0.06 Hz) oscillation did not demonstrate any statistically significant difference. Our results demonstrate that a fibre-optic TEF probe accompanied with ML algorithms such as k-Nearest Neighbours or AdaBoost is highly promising for the real-time in situ differentiation between cancerous and healthy tissues by detecting the information about the tissue type that is encoded in the fluorescence spectrum. Also, we show that the detection can be supplemented and enhanced by parallel collection and classification of blood perfusion oscillations

Optical diagnostics of bile duct tissues state with tumor compression

Abstract The paper presents the results of in vivo experimental measurements of the endogenous fluorescence and blood perfusion in common bile duct tissues in obstructive jaundice patients during minimally invasive surgical operations. Nowadays the type of interventions become more widespread for treating hepatopancreatobiliary pathologies. An effective feedback which can be established by one or more optical diagnostic channels integrated into the standard instruments for minimally invasive manipulations would be of particular value to practical surgeons. To collect reference data, an experimental study has been conducted using a fiber optical probe with fluorescence spectroscopy and laser Doppler flowmetry channels. For every measurement, the areas of interest were different areas of common bile duct obstructed by a malignant tumor. Obtained results demonstrated significant variety registered intensities of fluorescence spectra and values of blood perfusion. Tested fiber optical endoscopic system showed sensitivity to the tissue state in the investigated area, so the two modal approach seems to be promising for further research and implementation in clinical practice