Hyperspectral Imaging and Machine Perfusion in Solid Organ Transplantation: Clinical Potentials of Combining Two Novel Technologies

Organ transplantation survival rates have continued to improve over the last decades, mostly due to reduction of mortality early after transplantation. The advancement of the field is facilitating a liberalization of the access to organ transplantation with more patients with higher risk profile being added to the waiting list. At the same time, the persisting organ shortage fosters strategies to rescue organs of marginal donors. In this regard, hypothermic and normothermic machine perfusion are recognized as one of the most important developments in the modern era. Owing to these developments, novel non-invasive tools for the assessment of organ quality are on the horizon. Hyperspectral imaging represents a potentially suitable method capable of evaluating tissue morphology and organ perfusion prior to transplantation. Considering the changing environment, we here discuss the hypothetical combination of organ machine perfusion and hyperspectral imaging as a prospective feasibility concept in organ transplantation

Intraoperative colon perfusion assessment using multispectral imaging

In colorectal surgery an anastomosis performed using poorly-perfused, ischaemic bowel segments may result in a leak and consequent morbidity. Traditional measures of perfusion assessment rely on clinical judgement and are mainly subjective, based on tissue appearance, leading to variability between clinicians. This paper describes a multispectral imaging (MSI) laparoscope that can derive quantitative measures of tissue oxygen saturation (SO2). The system uses a xenon surgical light source and fast filter wheel camera to capture eight narrow waveband images across the visible range in approximately 0.3 s. Spectral validation measurements were performed by imaging standardised colour tiles and comparing reflectance with ground truth spectrometer data. Tissue spectra were decomposed into individual contributions from haemoglobin, adipose tissue and scattering, using a previously-developed regression approach. Initial clinical results from seven patients undergoing colorectal surgery are presented and used to characterise measurement stability and reproducibility in vivo. Strategies to improve signal-To-noise ratio and correct for motion are described. Images of healthy bowel tissue (in vivo) indicate that baseline SO2 is approximately 75 } 6%. The SO2 profile along a bowel segment following ligation of the inferior mesenteric artery (IMA) shows a decrease from the proximal to distal end. In the clinical cases shown, imaging results concurred with clinical judgements of the location of well-perfused tissue. Adipose tissue, visibly yellow in the RGB images, is shown to surround the mesentery and cover some of the serosa. SO2 in this tissue is consistently high, with mean value of 90%. These results show that MSI is a potential intraoperative guidance tool for assessment of perfusion. Mapping of SO2 in the colon could be used by surgeons to guide choice of transection points and ensure that well-perfused tissue is used to form an anastomosis. The observation of high mesenteric SO2 agrees with work in the literature and warrants further exploration. Larger studies incorporating with a wider cohort of clinicians will help to provide retrospective evidence of how this imaging technique may be able to reduce inter-operator variability

Advances in Hyperspectral and Multispectral Optical Spectroscopy and Imaging of Tissue

The purpose of this SI is to provide an overview of recent advances made in the methods used for tissue imaging and characterization, which benefit from using a large range of optical wavelengths. Guerouah et al. has contributed a profound study of the responses of the adult human brain to breath-holding challenges based on hyperspectral near-infrared spectroscopy (hNIRS). Lange et al. contributed a timely and comprehensive review of the features and biomedical and clinical applications of supercontinuum laser sources. Blaney et al. reported the development of a calibration-free hNIRS system that can measure the absolute and broadband absorption and scattering spectra of turbid media. Slooter et al. studied the utility of measuring multiple tissue parameters simultaneously using four optical techniques operating at different wavelengths of light—optical coherence tomography (1300 nm), sidestream darkfield microscopy (530 nm), laser speckle contrast imaging (785 nm), and fluorescence angiography (~800 nm)—in the gastric conduit during esophagectomy. Caredda et al. showed the feasibility of accurately quantifying the oxy- and deoxy-hemoglobin and cytochrome-c-oxidase responses to neuronal activation and obtaining spatial maps of these responses using a setup consisting of a white light source and a hyperspectral or standard RGB camera. It is interest for the developers and potential users of clinical brain and tissue optical monitors, and for researchers studying brain physiology and functional brain activity

Surgical spectral imaging

Recent technological developments have resulted in the availability of miniaturised spectral imaging sensors capable of operating in the multi- (MSI) and hyperspectral imaging (HSI) regimes. Simultaneous advances in image-processing techniques and artificial intelligence (AI), especially in machine learning and deep learning, have made these data-rich modalities highly attractive as a means of extracting biological information non-destructively. Surgery in particular is poised to benefit from this, as spectrally-resolved tissue optical properties can offer enhanced contrast as well as diagnostic and guidance information during interventions. This is particularly relevant for procedures where inherent contrast is low under standard white light visualisation. This review summarises recent work in surgical spectral imaging (SSI) techniques, taken from Pubmed, Google Scholar and arXiv searches spanning the period 2013–2019. New hardware, optimised for use in both open and minimally-invasive surgery (MIS), is described, and recent commercial activity is summarised. Computational approaches to extract spectral information from conventional colour images are reviewed, as tip-mounted cameras become more commonplace in MIS. Model-based and machine learning methods of data analysis are discussed in addition to simulation, phantom and clinical validation experiments. A wide variety of surgical pilot studies are reported but it is apparent that further work is needed to quantify the clinical value of MSI/HSI. The current trend toward data-driven analysis emphasises the importance of widely-available, standardised spectral imaging datasets, which will aid understanding of variability across organs and patients, and drive clinical translation

Uterine transplantation: the move from the animal model into the human setting – surgical, reproductive and clinical aspects

Women with absolute uterine factor infertility (AUFI) are considered as being ‘unconditionally infertile’. Uterine transplantation (UTx) may be a possible treatment option in the future for such women. This thesis describes a number of key areas of research that are important in order to move closer to a successful and crucially, safe transplant in the human setting. Nine allogeneic transplants were carried out in a rabbit model to investigate anatomical and surgical aspects necessary for a successful UTx. An attempt to characterise and quantify the immunological mechanisms involved in allogeneic UTx (rejection patterns) was made. Out of the nine recipients, one was a long-term survivor. Embryo transfer was performed in this one doe with the aim of establishing pregnancy. Performing UTx in a large-animal model is necessary as the pelvis resembles a woman’s reproductive system more closely. In addition, the anastomotic technique is similar. Five sheep autotransplants were performed to further define surgical techniques. The anastomotic model was internal to external iliac vessel. Out of the five transplants, three sheep demonstrated adequate perfusion in the immediate post-operative period. Furthermore, the suitability of two different imaging modalities, pulse oximetry and multispectral imaging, for assessing uterine perfusion and extent of ischaemia were been studied in both the rabbit and sheep models. Biophotonics was also applied in the form of Endoscopic Laser Speckle Contrast Analysis to characterize blood flow in the two models. Both Multispectral Imaging and Endoscopic Laser Speckle Contrast Analysis have never been assessed before in a gynecological context. In order to transfer the concept of UTx to the human, we carried out a retrospective study of abdominal radical trachelectomy (ART) as a potential replacement for radical hysterectomy in patients with early stage cervical cancer desiring a fertility-sparing procedure. ART forms the foundation of the original work into aspects of UTx. This original body of research revolved around the potential blood supply to a uterus. Furthermore, an attempt has been made to analyse the motivations, aims and feelings of patients diagnosed with AUFI towards UTx. Forty patients were interviewed. The final study involved the evaluation of the perceptions of health care professionals towards UTx, with 528 participants surveyed.Open Acces

Multispectral image analysis in laparoscopy – A machine learning approach to live perfusion monitoring

Modern visceral surgery is often performed through small incisions. Compared to open surgery, these minimally invasive interventions result in smaller scars, fewer complications and a quicker recovery. While to the patients benefit, it has the drawback of limiting the physician’s perception largely to that of visual feedback through a camera mounted on a rod lens: the laparoscope. Conventional laparoscopes are limited by “imitating” the human eye. Multispectral cameras remove this arbitrary restriction of recording only red, green and blue colors. Instead, they capture many specific bands of light. Although these could help characterize important indications such as ischemia and early stage adenoma, the lack of powerful digital image processing prevents realizing the technique’s full potential. The primary objective of this thesis was to pioneer fluent functional multispectral imaging (MSI) in laparoscopy. The main technical obstacles were: (1) The lack of image analysis concepts that provide both high accuracy and speed. (2) Multispectral image recording is slow, typically ranging from seconds to minutes. (3) Obtaining a quantitative ground truth for the measurements is hard or even impossible. To overcome these hurdles and enable functional laparoscopy, for the first time in this field physical models are combined with powerful machine learning techniques. The physical model is employed to create highly accurate simulations, which in turn teach the algorithm to rapidly relate multispectral pixels to underlying functional changes. To reduce the domain shift introduced by learning from simulations, a novel transfer learning approach automatically adapts generic simulations to match almost arbitrary recordings of visceral tissue. In combination with the only available video-rate capable multispectral sensor, the method pioneers fluent perfusion monitoring with MSI. This system was carefully tested in a multistage process, involving in silico quantitative evaluations, tissue phantoms and a porcine study. Clinical applicability was ensured through in-patient recordings in the context of partial nephrectomy; in these, the novel system characterized ischemia live during the intervention. Verified against a fluorescence reference, the results indicate that fluent, non-invasive ischemia detection and monitoring is now possible. In conclusion, this thesis presents the first multispectral laparoscope capable of videorate functional analysis. The system was successfully evaluated in in-patient trials, and future work should be directed towards evaluation of the system in a larger study. Due to the broad applicability and the large potential clinical benefit of the presented functional estimation approach, I am confident the descendants of this system are an integral part of the next generation OR

Real-time tissue viability assessment using near-infrared light

Despite significant advances in medical imaging technologies, there currently exist no tools to effectively assist healthcare professionals during surgical procedures. In turn, procedures remain subjective and dependent on experience, resulting in avoidable failure and significant quality of care disparities across hospitals. Optical techniques are gaining popularity in clinical research because they are low cost, non-invasive, portable, and can retrieve both fluorescence and endogenous contrast information, providing physiological information relative to perfusion, oxygenation, metabolism, hydration, and sub-cellular content. Near-infrared (NIR) light is especially well suited for biological tissue and does not cause tissue damage from ionizing radiation or heat. My dissertation has been focused on developing rapid imaging techniques for mapping endogenous tissue constituents to aid surgical guidance. These techniques allow, for the first time, video-rate quantitative acquisition over a large field of view (> 100 cm2) in widefield and endoscopic implementations. The optical system analysis has been focused on the spatial-frequency domain for its ease of quantitative measurements over large fields of view and for its recent development in real-time acquisition, single snapshot of optical properties (SSOP) imaging. Using these methods, this dissertation provides novel improvements and implementations to SSOP, including both widefield and endoscopic instrumentations capable of video-rate acquisition of optical properties and sample surface profile maps. In turn, these measures generate profile-corrected maps of hemoglobin concentration that are highly beneficial for perfusion and overall tissue viability. Also utilizing optical property maps, a novel technique for quantitative fluorescence imaging was also demonstrated, showing large improvement over standard and ratiometric methods. To enable real-time feedback, rapid processing algorithms were designed using lookup tables that provide a 100x improvement in processing speed. Finally, these techniques were demonstrated in vivo to investigate their ability for early detection of tissue failure due to ischemia. Both pre-clinical studies show endogenous contrast imaging can provide early measures of future tissue viability. The goal of this work has been to provide the foundation for real-time imaging systems that provide tissue constituent quantification for tissue viability assessments.2018-01-09T00:00:00