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

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

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