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Gastrointestinal diagnosis using non-white light imaging capsule endoscopy


Capsule endoscopy (CE) has proved to be a powerful tool in the diagnosis and management of small bowel disorders since its introduction in 2001. However, white light imaging (WLI) is the principal technology used in clinical CE at present, and therefore, CE is limited to mucosal inspection, with diagnosis remaining reliant on visible manifestations of disease. The introduction of WLI CE has motivated a wide range of research to improve its diagnostic capabilities through integration with other sensing modalities. These developments have the potential to overcome the limitations of WLI through enhanced detection of subtle mucosal microlesions and submucosal and/or transmural pathology, providing novel diagnostic avenues. Other research aims to utilize a range of sensors to measure physiological parameters or to discover new biomarkers to improve the sensitivity, specificity and thus the clinical utility of CE. This multidisciplinary Review summarizes research into non-WLI CE devices by organizing them into a taxonomic structure on the basis of their sensing modality. The potential of these capsules to realize clinically useful virtual biopsy and computer-aided diagnosis (CADx) is also reported.

Key points

  • White light imaging (WLI) remains the dominant diagnostic modality in capsule endoscopy after nearly two decades of clinical use.

  • WLI technology limits diagnosis to the mucosal surface of the gut owing to the limited penetration depth of optical wavelengths beyond the tissue surface.

  • In the past few years, there has been an increase in the application of non-WLI diagnostic imaging and sensing technologies to capsule endoscopy, some of which are at a more advanced stage of testing than others.

  • Integrating specific diagnostic imaging technologies into capsule endoscopy devices enables submucosal imaging, improved differentiation between malignant and benign tissue and new avenues for investigating the aetiology of disease.

  • Many of these capsules require further testing to determine their clinical efficacy fully owing to the small sample sizes of the reported studies.

  • New diagnostic capsule designs will provide new opportunities for improved computer-aided diagnosis, virtual biopsy and capsule localization that could benefit clinical practice in the future.

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Fig. 1: Examples of images obtained using alternative imaging technologies.
Fig. 2: Modalities for virtual biopsy.


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This work was supported by the UK Engineering and Physical Sciences Research Council under the grant EP/K034537/1, entitled Sonopill, and by the European Commission within the framework of the “Endoscopic versatile robotic guidance, diagnosis and therapy of magnetic-driven soft-tethered endoluminal robots” Project-H2020-ICT-24-2015 (EU Project-G.A. number: 688592). The authors acknowledge the support of V. Mitrakos in reviewing this manuscript.

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G.Cu., B.F.C., G.Ci., T.A. and M.P.Y.D. wrote the article. All authors researched data and discussed content for the article and reviewed and edited the manuscript before submission.

Corresponding author

Correspondence to Gerard Cummins.

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Competing interests

A.K. has received material support for research from SynMedUK and travel support from Aquilant/Jinshan Technology. He was awarded a European Society of Gastrointestinal Endoscopy (ESGE)-Given Imaging grant in 2011 and is a co-founder of AJM Medicaps. J.N.P. sits on the advisory board of Dr Falk and has previously received research support from Fujifilm. S.C., M.P.Y.D., B.F.C. and G.Cu. were all members of the Sonopill project, which was funded by the Engineering and Physical Sciences Research Council. G.Ci. and A.K. are funded by the European Commission under the “Endoscopic versatile robotic guidance, diagnosis and therapy of magnetic-driven soft-tethered endoluminal robots” Project-H2020-ICT-24-2015 (EU Project-G.A. number: 688592).

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Supplementary information


Single-element transducers

Devices generally consisting of a piezoelectric material housed in a casing that can both transmit and receive ultrasound signals.


The permanent loss of fluorescence in a fluorophore owing to photon-induced chemical damage.

Quantum yield

The number of times a specific event occurs per photon absorbed by the system in a radiation-induced process.

Volumetric imaging

A sequence of 2D images that are grouped together to form a 3D image of a volume of space.

Compton scattering

The scattering of a photon by a charge particle that results in a decrease in energy of the photon.

Potentiostatic circuits

Electronic circuits that enable the control of the voltage difference between electrodes in an electrochemical cell.

Cyclic voltammetry

A type of voltammetric experiment in which the potential is varied as a linear function of time. It is one of the most commonly used electrochemical techniques.

Pulsed voltammetry

A type of voltammetric experiment in which the varying potential consists of a series of increasing amplitude, with the potential returning to the initial value after each pulse.


Plots of cell current versus the potential arising from a voltammetry experiment.

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Cummins, G., Cox, B.F., Ciuti, G. et al. Gastrointestinal diagnosis using non-white light imaging capsule endoscopy. Nat Rev Gastroenterol Hepatol 16, 429–447 (2019).

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