Robustness to misalignment of low-cost, compact quantitative phase imaging architectures.

Non-interferometric approaches to quantitative phase imaging could enable its application in low-cost, miniaturised settings such as capsule endoscopy. We present two possible architectures and both analyse and mitigate the effect of sensor misalignment on phase imaging performance. This is a crucial step towards determining the feasibility of implementing phase imaging in a capsule device. First, we investigate a design based on a folded 4f correlator, both in simulation and experimentally. We demonstrate a novel technique for identifying and compensating for axial misalignment and explore the limits of the approach. Next, we explore the implications of axial and transverse misalignment, and of manufacturing variations on the performance of a phase plate-based architecture, identifying a clear trade-off between phase plate resolution and algorithm convergence time. We conclude that while the phase plate architecture is more robust to misalignment, both architectures merit further development with the goal of realising a low-cost, compact system for applying phase imaging in capsule endoscopy.

Quantitative phase and polarization imaging through an optical fiber applied to detection of early esophageal tumorigenesis.

Phase and polarization of coherent light are highly perturbed by interaction with microstructural changes in premalignant tissue, holding promise for label-free detection of early tumors in endoscopically accessible tissues such as the gastrointestinal tract. Flexible optical multicore fiber (MCF) bundles used in conventional diagnostic endoscopy and endomicroscopy scramble phase and polarization, restricting clinicians instead to low-contrast amplitude-only imaging. We apply a transmission matrix characterization approach to produce full-field en-face images of amplitude, quantitative phase, and resolved polarimetric properties through an MCF. We first demonstrate imaging and quantification of biologically relevant amounts of optical scattering and birefringence in tissue-mimicking phantoms. We present an entropy metric that enables imaging of phase heterogeneity, indicative of disordered tissue microstructure associated with early tumors. Finally, we demonstrate that the spatial distribution of phase and polarization information enables label-free visualization of early tumors in esophageal mouse tissues, which are not identifiable using conventional amplitude-only information.

A roadmap for the clinical implementation of optical-imaging biomarkers.

Clinical workflows for the non-invasive detection and characterization of disease states could benefit from optical-imaging biomarkers. In this Perspective, we discuss opportunities and challenges towards the clinical implementation of optical-imaging biomarkers for the early detection of cancer by analysing two case studies: the assessment of skin lesions in primary care, and the surveillance of patients with Barrett's oesophagus in specialist care. We stress the importance of technical and biological validations and clinical-utility assessments, and the need to address implementation bottlenecks. In addition, we define a translational roadmap for the widespread clinical implementation of optical-imaging technologies.

Emerging optical methods for endoscopic surveillance of Barrett's oesophagus.

Barrett's oesophagus is an acquired metaplastic condition that predisposes patients to the development of oesophageal adenocarcinoma, prompting the use of surveillance regimes to detect early malignancy for endoscopic therapy with curative intent. The currently accepted surveillance regime uses white light endoscopy together with random biopsies, but has poor sensitivity and discards information from numerous light-tissue interactions that could be exploited to probe structural, functional, and molecular changes in the tissue. Advanced optical methods are now emerging that are highly sensitive to these changes and hold potential to improve surveillance of Barrett's oesophagus if they can be applied endoscopically. The next decade will see some of these exciting new methods applied to surveillance of Barrett's oesophagus in new device architectures for the first time, potentially leading to a long-awaited improvement in the standard of care.