Emerging roles for multimodal optical imaging in early cancer detection: a global challenge

Abstract

Medical imaging technologies have become increasingly important in the clinical management of cancer, and now play key roles in cancer screening, diagnosis, staging, and monitoring response to treatment. Standard imaging modalities such as MRI, PET, and CT require significant financial resources and infrastructure, which limits access to these modalities to those patients in high-resource settings. In contrast, optical imaging strategies, with the potential for reduced cost and enhanced portability, are emerging as additional tools to facilitate the early detection and diagnosis of cancer. This article presents a vision for an expanding role for optical imaging in global cancer management, including screening, early detection at the point-of-care, biopsy guidance, and real-time histology. Multi-modal optical imaging - the combination of widefield and high resolution imaging - has the potential to aid in the detection and management of precancer and early cancer for traditionally underserved populations. Several recent widefield and high-resolution optical imaging technologies are described, along with requirements for implementing such devices into lower-resource - settings.

Figure 1

These images illustrate the application of light induced fluorescence endoscopy to improve screening for lung cancer with a widefield optical imaging system; white light and autofluorescence images acquired with light-induced fluorescence endoscopy (top, Xillix LIFE; bottom, Pentax 3000) show typical image features associated with atypical cells, with suspicious areas indicated by white arrows (12, 13). The white light images (A, C) represent the clinician's conventional viewing mode, allowing anatomical inspection at low magnification. Autofluorescence images (B, D) are sensitive to the natural fluorescence of tissue, which originates predominantly from stromal collagen. The development of neoplasia is associated with loss of stromal autofluorescence and this loss of fluorescence intensity can be used to assist clinicians in identifying pre-cancerous and suspicious cancerous lesions (as shown by decreased fluorescence intensity within areas in B, D).

Figure 2

High-resolution confocal microendoscope images of excised ovarian tissue after the application of acridine orange (16). Fluorescence imaging enabled visualization of individual nuclei and the underlying stroma (A-C). Images from a healthy ovary were characterized by a homogeneous distribution of nuclei, whereas images from carcinoma revealed a disordered tissue structure and variable nuclear size (A, D). Other more subtle pathologic changes such as sclerosis and endometriosis were also detectable (E, F).

Figure 3

Combined portable widefield and high-resolution imaging systems. (A) The portable screening system weighs only 3 lb. (B) High-resolution microendoscope contained in a briefcase. (C) Widefield and high-resolution images of normal human oral mucosa acquired with the multimodal imaging system. In the widefield image (left frame), the green autofluorescence of normal tissue is apparent, as well as the microvascular network. The high-resolution fiber-optic probe can be seen in contact with the mucosal surface, approaching from the base of the widefield frame. The high-resolution image, acquired simultaneously, is displayed in the lower right frame, with the 800 μm diameter field-of-view corresponding to the tissue located beneath the tip of the fiber-optic probe. Following topical application of 0.05% proflavine solution to the probe tip, nuclei appear as discrete bright regions within each epithelial cell.