Environmental enteric dysfunction (EED) is a subclinical disorder of intestinal function common in tropical countries and settings of poverty and economic disadvantage. EED manifests during infancy and is associated with undernutrition, poor sanitation, and gut infections. EED is characterised by inflammation, reduced absorptive capacity, and reduced barrier function (i.e., increased permeability) in the small intestine. The precise mechanisms underlying changes in gut barrier function (and other aspects of intestinal function) in EED remain elusive. Furthermore, current diagnostic methods to assess gut permeability (e.g., endoscopic biopsies or permeability assays such as the Lactulose:Mannitol test) are invasive, unreliable and/or challenging to perform in infants and patients with other coexisting urological conditions. Consequently, there is an urgent need to develop diagnostic technologies that can non-invasively and affordably monitor intestinal permeability in low-resource settings where EED is prevalent.
To address this need, we present a prototype semi-wearable, wireless sensor for non-invasive assessment of intestinal permeability via transcutaneous fluorescence spectroscopy. The approach relies on the ingestion of a fluorescent contrast agent (fluorescein) and the subsequent detection of its permeation from the gut into the bloodstream using a wearable probe. We outline the development of the semi-wearable sensor and report preliminary in vivo deployment. This showcases the potential of transcutaneous fluorescence spectroscopy as a wearable and non-invasive diagnostic tool for assessing gut function in low-resource settings.
SignificanceThe integrity of the intestinal barrier is gaining recognition as a significant contributor to various pathophysiological conditions, including inflammatory bowel disease, celiac disease, environmental enteric dysfunction (EED), and malnutrition. EED, for example, manifests as complex structural and functional changes in the small intestine leading to increased intestinal permeability, inflammation, and reduced absorption of nutrients. Despite the importance of gut function, current techniques to assess intestinal permeability (such as endoscopic biopsies or dual sugar assays) are either highly invasive, unreliable, and/or difficult to perform in certain patient populations (e.g., infants).AimWe present a portable, optical sensor based on transcutaneous fluorescence spectroscopy to assess gut function (in particular, intestinal permeability) in a fast and noninvasive manner.ApproachParticipants receive an oral dose of a fluorescent contrast agent, and a wearable fiber-optic probe detects the permeation of the contrast agent from the gut into the blood stream by measuring the fluorescence intensity noninvasively at the fingertip. We characterized the performance of our compact optical sensor by comparing it against an existing benchtop spectroscopic system. In addition, we report results from a human study in healthy volunteers investigating the impact of skin tone and contrast agent dose on transcutaneous fluorescence signals.ResultsThe first study with eight healthy participants showed good correlation between our compact sensor and the existing benchtop spectroscopic system [correlation coefficient (r)>0.919, p<0.001]. Further experiments in 14 healthy participants revealed an approximately linear relationship between the ingested contrast agent dose and the collected signal intensity. Finally, a parallel study on the impact of different skin tones showed no significant differences in signal levels between participants with different skin tones (p>0.05).ConclusionsIn this paper, we demonstrate the potential of our compact transcutaneous fluorescence sensor for noninvasive monitoring of intestinal health.
Tumour hypoxia is a critical factor in treatment failure and resistance, and its accurate measurement with diffuse reflectance spectroscopy (DRS) could be used for prognostic and response monitoring purposes. In this in vivo characterisation study, we sequentially measured oxygenation trends over the entire course of tumour growth in mice using a multi-depth, fibre-optic DRS probe. Results demonstrated a clear downtrend in oxygenation over time. This progression was not always linear, with significant heterogeneity over time and between mice. Our findings will be further validated against gold standards prior to investigating whether hypoxia can be used to predict radiotherapy responses.
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