Optical imaging for screening and early cancer diagnosis in low-resource settings

Abstract

Low-cost optical imaging technologies have the potential to reduce inequalities in healthcare by improving the detection of pre-cancer or early cancer and enabling more effective and less invasive treatment. In this Review, we summarise technologies for in vivo widefield, multi-spectral, endoscopic, and high-resolution optical imaging that could offer affordable approaches to improve cancer screening and early detection at the point-of-care. Additionally, we discuss approaches to slide-free microscopy, including confocal imaging, lightsheet microscopy, and phase modulation techniques that can reduce the infrastructure and expertise needed for definitive cancer diagnosis. We also evaluate how machine learning-based algorithms can improve the accuracy and accessibility of optical imaging systems and provide real-time image analysis. To achieve the potential of optical technologies, developers must ensure that devices are easy to use; the optical technologies must be evaluated in multi-institutional, prospective clinical tests in the intended setting; and the barriers to commercial scale-up in under-resourced markets must be overcome. Therefore, test developers should view the production of simple and effective diagnostic tools that are accessible and affordable for all countries and settings as a central goal of their profession.

Figure 1:. Widefield and high resolution imaging systems to improve early detection of precancerous epithelial lesions.

a ∣ Epithelial cancers follow a similar progression beginning with initiation and hyperplasia, evolving through grades of dysplasia, and invasive cancer. Optical imaging tools can improve the detection of precancer and early cancer by visualizing architectural and morphological biomarkers in precancerous epithelial cells, stromal angiogenesis, and microinvasion of epithelial cells beneath the basement membrane. b ∣ A proposed clinical workflow for how widefield imaging, high-resolution imaging, biopsy, and slide-free histological diagnosis could be integrated into current screening and diagnosis workflows. (1) Widefield imaging modalities, including white light and autofluorescence imaging systems, can be used to visualize suspicious lesions; (2) high resolution imaging tools can delineate regions of precancer with high enough specificity to enable immediate treatment or (3) biopsy can be performed to confirm the diagnosis using (4) slide-free histology methods. LED, light emitting diode; UV, ultraviolet. c ∣ Standard endoscope which uses a charge-coupled device (CCD) and an objective lens to acquire optical images of the region of interest. d∣ An optical extension accessory for high-definition endoscopes in which the optical lens can be moved to achieve high magnification (up to 150×) . e∣ Ultrathin transnasal endoscope for upper gastrointestinal endoscopy in unsedated patients. f∣ Low-cost scanning endoscope based on commercial contact image sensor technology with a self-focusing lens array (SLA). g∣ The design of a low cost, line scanning confocal microendoscope for imaging cervical tissue in vivo. This device uses a digital light projector with a synchronized rolling shutter complementary metal-oxide semiconductor (CMOS) camera. Both widefield and confocal images can be acquired by changing the projected aperture. h∣ Lens-free microendoscope, that allows simultaneous miniaturization and wide field of view, achieved by replacing distal lenses (top) with a coded aperture together with computational image recovery (bottom). Part a is adapted from ref. , Springer Nature Limited. Part b (second step) is reprinted with permission from ref. . Part b (fourth step) is adapted from ref. , Springer Nature Limited. Part c is adapted with permission from ref. . Part e, image courtesy of Scott Inglis. Part f is adapted with permission from ref. . Part g is adapted with permission from ref. . Part h is adapted with permission from ref. .

Figure 2:. Microscopy approaches to enable rapid, low-cost, slide-free histology.

a ∣ Workflow for standard of care histology compared to slide-free approaches. The standard of care requires expensive instrumentation, trained staff, multiple steps, and results are not available for at least 30 minutes. Slide-free approaches can be performed with inexpensive instrumentation and obtain results in minutes. b ∣ Left, schematic diagram of microscopy with UV surface excitation (MUSE) in which the sample is illuminated by an ultraviolet (UV) light emitting diode (LED). The stage moves so the entire sample can be scanned. Right, the components of a pocket MUSE device, which uses a mobile phone camera to capture UV-excited fluorescence images. c ∣ Left, schematic diagram of an open-top light-sheet microscope in which the light sheet (purple) enters the sample and produces fluorescent emission (cyan), which is then transmitted through an emission filter (green) and detected by a high speed scientific complementary metal-oxide semiconductor (sCMOS) camera. Left inset, a solid immersion lens and oil layer are used for refractive index matching of the incoming and outgoing beams. Middle, the sample is mounted on a moveable stage to enable the reconstruction of a 2D image. Right, open-top light sheet microscopy can achieve both rapid scanning and deep depth of field (DOF) unlike conventional microscopy. d ∣ DeepDOF microscope uses a $10 phase mask to encode the light field and enhance the depth-invariance of the point-spread function. Left, schematic illustrating the simultaneous optimization of the phase mask and image reconstruction algorithm to extend the DOF. Right, DeepDOF uses a conventional fluorescence microscope equipped with a LED (blue) to excite fluorescence (green) and a phase mask to extend the DOF. Part b (left) is adapted from ref. , Springer Nature Limited. Part b (right) is reprinted from ref. . Part c is adapted from ref. , Springer Nature limited. Part d is adapted with permission from ref. .