Position paper: The potential role of optical biopsy in the study and diagnosis of environmental enteric dysfunction

Environmental enteric dysfunction (EED) is a disease of the small intestine affecting children and adults in low and middle income countries. Arising as a consequence of repeated infections, gut inflammation results in impaired intestinal absorptive and barrier function, leading to poor nutrient uptake and ultimately to stunting and other developmental limitations. Progress towards new biomarkers and interventions for EED is hampered by the practical and ethical difficulties of cross-validation with the gold standard of biopsy and histology. Optical biopsy techniques — which can provide minimally invasive or noninvasive alternatives to biopsy — could offer other routes to validation and could potentially be used as point-of-care tests among the general population. This Consensus Statement identifies and reviews the most promising candidate optical biopsy technologies for applications in EED, critically assesses them against criteria identified for successful deployment in developing world settings, and proposes further lines of enquiry. Importantly, many of the techniques discussed could also be adapted to monitor the impaired intestinal barrier in other settings such as IBD, autoimmune enteropathies, coeliac disease, graft-versus-host disease, small intestinal transplantation or critical care

Optoacoustic monitoring of cutting efficiency and thermal damage during laser ablation.

Successful laser surgery is characterized by a precise cut and effective hemostasis with minimal collateral thermal damage to the adjacent tissues. Consequently, the surgeon needs to control several parameters, such as power, pulse repetition rate, and velocity of movements. In this study we propose utilizing optoacoustics for providing the necessary real-time feedback of cutting efficiency and collateral thermal damage. Laser ablation was performed on a bovine meat slab using a Q-switched Nd-YAG laser (532 nm, 4 kHz, 18 W). Due to the short pulse duration of 7.6 ns, the same laser has also been used for generation of optoacoustic signals. Both the shockwaves, generated due to tissue removal, as well as the normal optoacoustic responses from the surrounding tissue were detected using a single broadband piezoelectric transducer. It has been observed that the rapid reduction in the shockwave amplitude occurs as more material is being removed, indicating decrease in cutting efficiency, whereas gradual decrease in the optoacoustic signal likely corresponds to coagulation around the ablation crater. Further heating of the surrounding tissue leads to carbonization accompanied by a significant shift in the optoacoustic spectra. Our results hold promise for real-time monitoring of cutting efficiency and collateral thermal damage during laser surgery. In practice, this could eventually facilitate development of automatic cut-off mechanisms that will guarantee an optimal tradeoff between cutting and heating while avoiding severe thermal damage to the surrounding tissues

Optoacoustic monitoring of cutting and heating processes during laser ablation.

Laser-tissue interaction during laser surgery can be classified into two biophysical processes: tissue removal in the focal zone of the laser beam and heating in the surrounding tissue. In order to ensure a precise cut and minimal collateral thermal damage, the surgeon has to control several parameters, such as power, repetition rate and fiber movement velocity. In this study we propose utilizing optoacoustics for providing the necessary real-time feedback of cutting and heating processes. A single Q-switched Nd-YAG laser (532nm, 4 KHz, 18 W, pulse duration 7.6ns) was used for ablation and generation of optoacoustic signals in fresh bovine tissue samples. Both shockwaves, generated due to tissue removal, as well as normal optoacoustic responses from the surrounding tissue were detected using a single 10MHz piezoelectric transducer. It has been observed that rapid reduction in the shockwave amplitude occurs as more material is being removed from the focal zone, indicating decrease in cutting efficiency of the laser beam, whereas gradual decrease in the optoacoustic signal likely corresponds to coagulation around the ablation crater. Further heating of surrounding tissue leads to carbonization accompanied by a significant shift of spectral components of the optoacoustic signal. Our results hold promise for real-time monitoring of cutting efficiency and collateral thermal damage during laser surgery

Real-time monitoring of lesion profile during laser surgery using shock wave detection.

Ablation was performed in fresh bovine tissue samples using a Q-switched Nd-YAG laser (1064nm, 150mJ, 5Hz, 8ns). The beam was focused by a 50mm lens, which resulted in a deep cut of up to 9mm depth. The generated shockwaves were detected using a spherical matrix ultrasonic array. The exact cutting profile was subsequently rendered by reconstructing the origin of shockwaves detected during the entire procedure. It has been observed that the lesion profile could be characterized with high spatial accuracy in all three dimensions (std >0.1 mm). The proposed method holds promise for delivering accurate real-time feedback during laser surgeries

Real-time monitoring of incision profile during laser surgery using shock wave detection.

Lack of sensory feedback during laser surgery prevents surgeons from discerning the exact location of the incision, which increases duration and complexity of the treatment. In this study we demonstrate a new method for monitoring of laser ablation procedures. Real-time tracking of the exact three dimensional (3D) lesion profile is accomplished by detection of shock waves emanating from the ablation spot and subsequent reconstruction of the incision location using time-of-flight data obtained from multiple acoustic detectors. Here, incisions of up to 9 mm in depth, created by pulsed laser ablation of fresh bovine tissue samples, were successfully monitored in real time. It was further observed that, by utilizing as little as 12 detection elements, the incision profile can be characterized with accuracy below 0.5 mm in all three dimensions and in good agreement with histological examinations. The proposed method holds therefore promise for delivering high precision real-time feedback during laser surgeries

Integrated catheter for simultaneous radio frequency ablation and optoacoustic monitoring of lesion progression.

Radio frequency (RF) catheter ablation is commonly used to eliminate dysfunctional cardiac tissue by heating via an alternating current. Clinical outcomes are highly dependent on careful anatomical guidance, electrophysiological mapping, and careful RF power titration during the procedure. Yet, current treatments rely mainly on the expertise of the surgeon to assess lesion formation, causing large variabilities in the success rate. We present an integrated catheter design suitable for simultaneous RF ablation and real-time optoacoustic monitoring of the forming lesion. The catheter design utilizes copper-coated multimode light guides capable of delivering both ablation current and near-infrared pulsed-laser illumination to the target tissue. The generated optoacoustic responses were used to visualize the ablation lesion formation in an ex-vivo bovine heart specimen in 3D. The presented catheter design enables the monitoring of ablation lesions with high spatiotemporal resolution while the overall therapy-monitoring approach remains compatible with commercially available catheter designs