Machine Learning Aided Photonic Diagnostic System for Minimally Invasive Optically Guided Surgery in the Hepatoduodenal Area

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 < 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

Fluorescence Imaging System for Biological Tissues Diagnosis: Phantom and Animal Studies

Currently, optical biopsy is a promising area of diagnosing the state of tissues in real time during the surgical treatment of oncological diseases. The important part of this direction is the development of fluorescence imaging systems and ensuring the accuracy of the calibration of optical measurements. The article describes the development of fluorescence imaging system to define tumor surgical resection margins of abdominal organs. In this study, we proposed of low-cost optical tissue-mimicking phantom combining solid base and liquid part that suitable for quick calibration of fluorescence imaging systems depending on the target endogenous fluorophores. The results of two series of experimental measurements are described. The first measurements of the optical phantom with riboflavin mononucleotide (imitating flavin adenine dinucleotide) and protoporphyrin IX demonstrated the sensitivity of the developed device to proportionally changing concentrations of target fluorophores. The second part of the study included in vivomeasurements of liver tumors modeled in mice. The obtained results showed the ability of the developed fluorescence imaging system to register changes in fluorescence due to carcinogenesis

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

Fiber-optic system for intraoperative study of abdominal organs during minimally invasive surgical interventions

The paper presents the results of experimental measurements of endogenous fluorescence and blood perfusion in patients with pathology of the organs of hepatopancreatoduodenal area in vivo. A custom setup combining channels for fluorescence spectroscopy (excitation wavelengths of 365 nm and 450 nm) and laser Doppler flowmetry (1064 nm) with fibre optical probe for nondestructive laparoscopic measurements has been developed and applied during minimally invasive operation procedure. Preliminary measurements with two aforementioned channels have been performed at specified excitation wavelengths. The possibility of obtaining fluorescence spectra and laser Doppler flowmetry signals in vivo during minimally invasive interventions was shown. Obtained data show perspectives of further research on technical and methodological development of optical diagnostic methods for minimally invasive surgery. The obtained results can be used to provide a deeper understanding of pathological processes influence on optical properties of abdominal organs tissues, which will ultimately help surgeons to determine the state of vitality in tissues and mucous membranes directly during the process of surgical intervention

Tissue mimicking phantoms for fluorescence imaging

The article describes the development of the optical phantom mimicking flavin adenine dinucleotide (FAD) and skin collagen fluorescence. The results of experimental studies using fluorescence imaging and fluorescence spectroscopy methods are demonstrated. The method of optical phantom production for quick calibration of fluorescence imaging devices for further application in clinical practice is proposed

Optical fine-needle aspiration biopsy in a rat model

Fine needle aspiration biopsy technique and following histological examination show its effectiveness and safety but its performing takes several time. However, the problem of real-time analysis of pathological changes in tissues remains relevant. We demonstrate optical fine-needle biopsy method, combining a fine needle (17.5G) and a fiber-optic probe (1 mm diameter) for minimally invasive interrogation of tissue in vivo. During rat tumor experiment, we collected spectrally-resolved diffuse reflectance and fluorescence. Quantified differences between tumor and normal tissues were demonstrated and approved with morphological analysis. The proposed methodology seems promising for developing new diagnostic criteria for clinical practice

Optical fine-needle biopsy approach for intraoperative multimodal diagnostics in minimally invasive abdominal surgery

The paper describes the methodology and technical implementation of a multimodal approach for optical diagnostics in hepatopancreatobiliary organs focal and diffuse neoplasms. Fine needle aspiration biopsy technique and following cytological examination show its effectiveness and safety but its performing takes several days. However, the problem of real-time analysis of pathological changes in tissues remains relevant. The solution suggested is implementing of optical biopsy methods (namely fluorescence spectroscopy and diffuse reflectance spectroscopy) in the form of fiber-optic probe compatible with standard biopsy fine needles. The special device was designed for this purpose to conduct optical measurements and compare the results with ones obtained by conventional biopsy. The proposed methodology seems promising for developing new diagnostic criteria for clinical practice

Optical fine needle biopsy in hepatocellular carcinoma mouse model

The paper describes the results of experimental studies using custom developed optical biopsy system for diagnostics in vivo during the procedure of fine needle aspiration biopsy. Experimental studies were conducted in laboratory mice with inoculated hepatocellular carcinoma. The measurements were carried out using fluorescence spectroscopy and diffuse reflectance spectroscopy methods to reveal metabolic and morphological changes in tissues. The results show that the developed approach is sensitive for cancer detection. Quantified differences in the maximum of fluorescence spectra and diffuse reflectance spectra between tumor and normal tissues were demonstrated and approved with morphological analysis

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

Impairments of cerebral blood flow microcirculation in rats brought on by cardiac cessation and respiratory arrest

The impairments of cerebral blood flow microcirculation brought on by cardiac and respiratory arrest were assessed with multi-modal diagnostic facilities, utilising laser speckle contrast imaging, fluorescence spectroscopy and diffuse reflectance spectroscopy. The results of laser speckle contrast imaging show a notable reduction of cerebral blood flow in small and medium size vessels during a few minutes of respiratory arrest, while the same effect was observed in large sinuses and their branches during the circulatory cessation. Concurrently, the redox ratio assessed with fluorescence spectroscopy indicates progressing hypoxia, NADH accumulation and increase of FAD consumption. The results of diffuse reflectance spectra measurements display a more rapid grow of the perfusion of deoxygenated blood in case of circulatory impairment. In addition, consequent histopathological analysis performed by using new tissue staining procedure developed in-house. It shows notably higher reduction of size of the neurons due to their wrinkling within brain tissues influenced by circulation impair. Whereas, the brain tissues altered with the respiratory arrest demonstrate focal perivascular oedema and mild hypoxic changes of neuronal morphology. Thus, the study suggests that consequences of a cessation of cerebral blood flow become more dramatic and dangerous compare to respiratory arrest