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

Analysis of changes in blood flow oscillations under different probe pressure using laser Doppler spectrum decomposition

Presently, in the modern laser Doppler flowmetry (LDF) the distribution of blood perfusion and its changes along the Doppler shift frequencies are simply ignored and/or not properly addressed. Utilizing the registered power spectrum of photocurrent, we introduce an LDF signal processing approach suitable for expanding of diagnostic capabilities of the technique. In particular, we demonstrate that it is possible to determine how the oscillations of blood flow (cardiac, breathe, myogenic, etc.) are distributed along the Doppler shift frequency. Wavelet analysis is utilized to extract the oscillations corresponded to the particular frequency sub-bands of blood perfusion. The main purpose of this study is to identify influence of local pressure by fiber optic probe on cardiac oscillations and their distribution along frequency of Doppler shift

Brain metabolism changes in cases of impaired breathing or blood circulation in rodents evaluated by real time optical spectroscopy methods

The aim of the study was to compare the metabolic activity of brain cortex after the acute hypoxia caused by the impairment of breathing or blood circulation. Male Wistar rats were randomized in two groups: impaired breathing and blood circulation failure groups. Fluorescence under 365 and 450 nm excitation and diffuse reflectance intensity at 550-820 nm range were estimated. We found that after long-term hypoxic conditions, notable metabolic changes occur. We suppose that oxygen deficiency causes an activation of the GABA shunt mechanism. In cases of blood circulation failure, fluorescence intensity changes faster than in cases of breathing impairment

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

Digital diaphanoscopy of maxillary sinus pathologies supported by machine learning

Maxillary sinus pathologies remain among the most common ENT diseases requiring timely diagnosis for successful treatment. Standard ENT inspection approaches indicate low sensitivity in detecting maxillary sinus pathologies. In this paper, we report on capabilities of digital diaphanoscopy combined with machine learning tools in the detection of such pathologies. We provide a comparative analysis of two machine learning approaches applied to digital diapahnoscopy data, namely, convolutional neural networks and linear discriminant analysis. The sensitivity and specificity values obtained for both employed approaches exceed the reported accuracy indicators for traditional screening diagnosis methods (such as nasal endoscopy or ultrasound), suggesting the prospects of their usage for screening maxillary sinuses alterations. The analysis of the obtained values showed that the linear discriminant analysis, being a simpler approach as compared to neural networks, allows one to detect the maxillary sinus pathologies with the sensitivity and specificity of 0.88 and 0.98, respectively

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

Analysis of changes in blood flow oscillations under different probe pressure using laser Doppler spectrum decomposition

Abstract Presently, in the modern laser Doppler flowmetry (LDF) the distribution of blood perfusion and its changes along the Doppler shift frequencies are simply ignored and/or not properly addressed. Utilizing the registered power spectrum of photocurrent, we introduce an LDF signal processing approach suitable for expanding of diagnostic capabilities of the technique. In particular, we demonstrate that it is possible to determine how the oscillations of blood ow (cardiac, breathe, myogenic, etc.) are distributed along the Doppler shift frequency. Wavelet analysis is utilized to extract the oscillations corresponded to the particular frequency sub-bands of blood perfusion. The main purpose of this study is to identify influence of local pressure by fiber optic probe on cardiac oscillations and their distribution along frequency of Doppler shift