Prospective study for commercial and low-cost hyperspectral imaging systems to evaluate thermal tissue effect on bovine liver samples

Thermal ablation modalities, for example radiofrequency ablation (RFA) and microwave ablation, are intended to prompt controlled tumour removal by raising tissue temperature. However, monitoring the size of the resulting tissue damage during the thermal removal procedures is a challenging task. The objective of this study was to evaluate the observation of RFA on an ex vivo liver sample with both a commercial and a low-cost system to distinguish between the normal and the ablated regions as well as the thermally affected regions. RFA trials were conducted on five different ex vivo normal bovine samples and monitored initially by a custom hyperspectral (HS) camera to measure the diffuse reflectance (Rd) utilising a polychromatic light source (tungsten halogen lamp) within the spectral range 348–950 nm. Next, the light source was replaced with monochromatic LEDs (415, 565 and 660 nm) and a commercial charge-coupled device (CCD) camera was used instead of the HS camera. The system algorithm comprises image enhancement (normalisation and moving average filter) and image segmentation with K-means clustering, combining spectral and spatial information to assess the variable responses to polychromatic light and monochromatic LEDs to highlight the differences in the Rd properties of thermally affected/normal tissue regions. The measured spectral signatures of the various regions, besides the calculation of the standard deviations (δ) between the generated six groups, guided us to select three optimal wavelengths (420, 540 and 660 nm) to discriminate between these various regions. Next, we selected six spectral images to apply the image processing to (at 450, 500, 550, 600, 650 and 700 nm). We noticed that the optimum image is the superimposed spectral images at 550, 600, 650 and 700 nm, which are capable of discriminating between the various regions. Later, we measured Rd with the CCD camera and commercially available monochromatic LED light sources at 415, 565 and 660 nm. Compared to the HS camera results, this system was more capable of identifying the ablated and the thermally affected regions of surface RFA than the side-penetration RFA of the investigated ex vivo liver samples. However, we succeeded in developing a low-cost system that provides satisfactory information to highlight the ablated and thermally affected region to improve the outcome of surgical tumour ablation with much shorter time for image capture and processing compared to the HS system

Prediction of In Vivo Laser-Induced Thermal Damage with Hyperspectral Imaging Using Deep Learning.

Thermal ablation is an acceptable alternative treatment for primary liver cancer, of which laser ablation (LA) is one of the least invasive approaches, especially for tumors in high-risk locations. Precise control of the LA effect is required to safely destroy the tumor. Although temperature imaging techniques provide an indirect measurement of the thermal damage, a degree of uncertainty remains about the treatment effect. Optical techniques are currently emerging as tools to directly assess tissue thermal damage. Among them, hyperspectral imaging (HSI) has shown promising results in image-guided surgery and in the thermal ablation field. The highly informative data provided by HSI, associated with deep learning, enable the implementation of non-invasive prediction models to be used intraoperatively. Here we show a novel paradigm "peak temperature prediction model" (PTPM), convolutional neural network (CNN)-based, trained with HSI and infrared imaging to predict LA-induced damage in the liver. The PTPM demonstrated an optimal agreement with tissue damage classification providing a consistent threshold (50.6 ± 1.5 °C) for the damage margins with high accuracy (~0.90). The high correlation with the histology score (r = 0.9085) and the comparison with the measured peak temperature confirmed that PTPM preserves temperature information accordingly with the histopathological assessment

Spectral imaging of thermal damage induced during microwave ablation in the liver

Induction of thermal damage to tissue through delivery of microwave energy is frequently applied in surgery to destroy diseased tissue such as cancer cells. Minimization of unwanted harm to healthy tissue is still achieved subjectively, and the surgeon has few tools at their disposal to monitor the spread of the induced damage. This work describes the use of optical methods to monitor the time course of changes to the tissue during delivery of microwave energy in the porcine liver. Multispectral imaging and diffuse reflectance spectroscopy are used to monitor temporal changes in optical properties in parallel with thermal imaging. The results demonstrate the ability to monitor the spatial extent of thermal damage on a whole organ, including possible secondary effects due to vascular damage. Future applications of this type of imaging may see the multispectral data used as a feedback mechanism to avoid collateral damage to critical healthy structures and to potentially verify sufficient application of energy to the diseased tissue.Comment: 4pg,6fig. Copyright 2018 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other work

Linearly chirped fiber Bragg grating response to thermal gradient: from bench tests to the real-time assessment during in vivo laser ablations of biological tissue

The response of a fiber optic sensor [linearly chirped fiber Bragg grating (LCFBG)] to a linear thermal gradient applied on its sensing length (i.e., 1.5 cm) has been investigated. After these bench tests, we assessed their feasibility for temperature monitoring during thermal tumor treatment. In particular, we performed experi- ments during ex vivo laser ablation (LA) in pig liver and in vivo thermal ablation in animal models (pigs). We investigated the following: (i) the relationship between the full width at half maximum of the LCFBG spectrum and the temperature difference among the extremities of the LCFBG and (ii) the relationship between the mean spectrum wavelength and the mean temperature acting on the LCFBG sensing area. These relationships showed a linear trend during both bench tests and LA in animal models. Thermal sensitivity was significant although different values were found with regards to bench tests and animal experiments. The linear trend and significant sensitivity allow hypothesizing a future use of this kind of sensor to monitor both temperature gradient and mean temperature within a tissue undergoing thermal treatment

Clinical applications of non‐invasive multi and hyperspectral imaging of cell and tissue autofluorescence beyond oncology

Hyperspectral and multispectral imaging of cell and tissue autofluorescence employs fluorescence imaging, without exogenous fluorophores, across multiple excitation/ emission combinations (spectral channels). This produces an image stack where each pixel (matched by location) contains unique information about the sample's spectral properties. Analysis of this data enables access to a rich, molecularly specific data set from a broad range of cell-native fluorophores (autofluorophores) directly reflective of biochemical status, without use of fixation or stains. This non-invasive, non-destructive technology has great potential to spare the collection of biopsies from sensitive regions. As both staining and biopsy may be impossible, or undesirable, depending on the context, this technology great diagnostic potential for clinical decision making. The main research focus has been on the identification of neoplastic tissues. However, advances have been made in diverse applications—including ophthalmology, cardiovascular health, neurology, infection, assisted reproduction technology and organ transplantation.Jared M. Campbell, Saabah B. Mahbub, Abbas Habibalahi, Adnan Agha, Shannon Handley, Ayad G. Anwer, Ewa M. Goldy

Study of novel nanoparticle transport and drug release for cancer treatment.

Nano-scale particles sized 10—400 nm administered systemically preferentially extravasate from tumor vasculature due to the enhanced permeability and retention effect. Therapeutic success remains elusive, however, because of inhomogeneous particle distribution within tumor tissue. Insufficient tumor vascularization limits particle transport and also results in avascular hypoxic regions with non-proliferating cells, which can regenerate tissue after nanoparticle-delivered cytotoxicity or thermal ablation. In this study, gold nanoparticles were functionalized with phosphatidylcholine (two-layer) or phosphatidylcholine and HDL (three-layer) in the formation of “layered” nanoparticles. The diffusivity of both two- and three layered colloidal gold nanoparticles and silica gold nanoshells were examined in 3D cell cultures. Both two- and three layered nanoparticles showed enhanced diffusivity in comparison to previously developed PEGylated nanoparticles. As the two layer nanoparticles displayed enhanced diffusivity in comparison to three layer nanoparticles, the two layered nanoparticles were further examined in vivo using mice implanted with orthotopic pancreatic adenocarcinomas. The two layer colloidal gold nanoparticles showed enhanced diffusivity in comparison to silica gold nanoshells in vivo, suggesting that smaller nanoparticles were able to localize and diffuse from vasculature better than larger nanoparticles. Overall accumulation of solid gold nanoparticle accumulated in the tumor and filtering organs (liver and spleen) was 2X higher than silica gold nanoshells. Thus, two layer colloidal gold nanoparticles were loaded with cisplatin or paclitaxel to determine optimal drug release kinetics. Drug release from paclitaxel-loaded nanoparticles displayed a slower release while cisplatin-loaded nanoparticles experienced an initial burst of drug release followed by a slower release of remaining drug. Lastly, drug-loaded colloidal gold nanoparticles were tested in 3D cell cultures to determine their cytotoxicity. Both two and three layer nanoparticles loaded with cisplatin orpaclitaxel showed similar efficacy to drug alone, suggesting their viable use in vivo for cancer treatment. This study has demonstrated the potential use of layered nanoparticles for increasing the delivery of chemotherapeutics deeper into tumor tissue

Analytical and chemometrical approaches for bioimaging, sensing and metabolomics

258 p. Embargada de nuevo el 21-12-2018 a solicitud de la autoraTesi honetan batu dira hiru bi proiektutan egindako lanak. Alde batetik, hipertermia magnetikoari dagokionez, gibeletako tumoreen aurkako terapian hain zuzen, bi lan eraman dira aurrera. Lehengoa izan da FT-IR eta Raman bidezko bioirudiak lortzeko eta interpretatzeko lanak, histologian lagungarri izateko. Bigarrean , hipertermiak ekar lezakeen ondorioak gibelaren funtzionamenduan eta terapia ondoko errekuperazioa nolakoa den aztertzeko analisi metabolomikoa landu da 1H-EMN-aren bitartez. Ildo beretsutik baina terapiatik kanpo, SERS delako teknika landu da zelulen bioirudiak landu ahal izateko.Bestalde batetik, ingurumen kutsaduraren ikuspuntutik, kutsatzaile ez-polarren nahasteari esposatuta egon diren muskuiluak aztertu dira. Alde batetik, esposizioa jarraitua izan da laginketa pasiboko teknika uztartu eta gero, eta metatutako kontzentrazioaz gain, muskuiluen analisi metabolomikoa bideratu egin da hainbat ehunetan (muskulo, gonada) . Lehen bezala, analisi metabolomikoa 1H-EMN-aren bitartez eraman da aurrera eta kutsatzaileek eragin dituzten aldaketa metabolikoak aztertzeko bide eman du

The role of tissue fluorescence in in vivo optical bioimaging

The following article appeared in Journal of Applied Physics 128.17 (2020): 171101 and may be found at https://doi.org/10.1063/5.0021854The technological advancements made in optics and semiconductors (e.g., cameras and laser diodes) working with infrared have brought interest in optical bioimaging back to the forefront of research investigating in vivo medical imaging techniques. The definition of the near-infrared transparency windows has turned optical imaging into more than just a method for topical imaging applications. Moreover, this has focused attention back to tissue fluorescence, emissions by tissues and organs that occur when excited by external illumination sources. Most endogenous fluorophores emit in the blue to green range of the electromagnetic spectrum and the resulting tissue fluorescence can be employed in studies from cells to tissue metabolism or avoided by shifting to the red if seen as unwanted autofluorescence. With the more recent move to infrared, it was discovered that autofluorescence is not limited to the visible but also strongly affects in vivo imaging in the infrared. In this Tutorial, we give an overview on tissue fluorescence and tissue interactions with excitation light as well as their effect on in vivo imaging. Furthermore, potential sources of tissue fluorescence in the near-infrared are identified and we describe approaches for successful biomedical imaging in the biological windows, taking into consideration infrared autofluorescence and summarizing techniques for avoiding it in in vivo imaging experimentsThis work was supported by the Spanish Ministry of Economy and Competitiveness under Project No. MAT2016-75362-C3-1-R, the Spanish Ministry of Sciences, Innovation and Universities under Project No. PID2019-106211RB-I00 (NANONERV), by the Instituto de Salud Carlos III (Nos. PI16/00812 and PI19/00565), and through the Comunidad Autónoma de Madrid (No. B2017/ BMD-3867RENIMCM), and co-financed by the European Structural and investment fund. Additional funding was provided by the European Union’s Horizon 2020 FET Open project NanoTBTech (Grant Agreement No. 801305), the Fundación para la Investigación Biomédica del Hospital Universitario Ramón y Cajal under Project No. IMP18_38(2018/0265), and also COST action CA17140. Y.S. acknowledges a scholarship from the China Scholarship Council (No.201806870023), E.X. is grateful for a Juan de la Cierva Formación scholarship (No. FJC2018-036734-I), and D.H.O. is thankful to the Instituto de Salud Carlos III for a Sara Borrell Fellowship (No. CD17/00210). The authors thank Dr. Blanca del Rosal for the helpful discussion and input on the manuscrip

Interactions of composite gold nanoparticles with cells and tissue : implications in clinical translation for cancer imaging and therapy

textCurrent methods to diagnose and treat cancer often involve expensive, time-consuming equipment and materials that may lead to unwanted side effects and may not even increase a patient’s chance of survival. Thus, for a while now, a large part of the research community has focused on developing improved methods to detect, diagnose, and treat cancer on the molecular scale. One of the most recently discovered methods of cancer therapy is targeted therapy. These targeted therapies have potential to provide a patient with a form of personalized medicine because these therapies are biological molecules that specifically target other molecules involved with a cancer’s growth. Past trials using these therapeutic molecules, however, have led to controversial results, where certain patients responded better than others to the therapy for unknown reasons. Elucidating the reason behind these mixed results can be accomplished using metal nanoparticle technologies which could provide a bright signal to monitor the path that these therapeutic molecules take in vivo as well as enhance the molecule’s efficacy. Literature has shown that presenting targeting molecules in a dense manner to their target will increase these molecules’ binding affinity. This concept has been explored here to increase binding affinity of therapeutic molecules by attaching these molecules in a dense manner on the surface of gold nanoparticles, and correlating this increased affinity with therapeutic efficacy. Additionally, gold nanoparticles provide an easy surface for molecules to be functionalized on and have shown to be effective imaging, x-ray, and photothermal therapy agents. A major roadblock to using these gold nanoparticles clinically is their non-degradability and thus potential to cause long-term negative side effects in vivo. A platform for developing biodegradable gold nanoparticles is also explored here to take advantage of the gold nanoparticles’ excellent imaging and drug delivery capabilities while still allowing them to be used safely in the long term.Biomedical Engineerin