From Bench to Bedside
The content in this Collection covers optical Imaging as defined by the research environment: the biochemical and biomolecular laboratory, the optics and photonics laboratory, and the clinic. These complementary, yet traditionally separate, environments strengthen each other when it comes to addressing problems in healthcare.
Two Reviews in this Collection give a broad overview of the use of light in medicine and discuss the advantages of using the near-infrared spectral window. Seok Hyun Yun and Sheldon Kwok introduce the fundamental principles underpinning optical diagnosis and laser surgery and discuss the range of therapeutic and diagnostic methods that adopt such technologies. Hong et al. focus on the use of near-infrared fluorophores to achieve tissue penetration and improved signal-to-noise ratio, providing examples of preclinical and clinical applications for dyes and fluorophores operating in the entire near-infrared spectral region. Some of the principles used to covalently label proteins for imaging applications are reviewed in Xue et al.
Four research Articles highlight the use of engineering principles for the development of near-infrared reporters: two proteins and two synthetic probes. Rodriguez et al. developed a new class of fluorescent proteins that covalently attaches a biliverdin chromophore and generates an emission peak at 670 nm. Kuchimaru et al. generated a luciferin analogue that shifts the bioluminescent signal, which is typically green, to the near-infrared region and that emits at 677 nm. The probe described in Zheng et al. is instead a poly(N-vinylpyrrolidone) (PVP)-conjugated iridium (III) complex that phosphoresces in the near-infrared window and is quenched by intracellular oxygen and can thus be used to detect hypoxic cancer cells. Antaris et al. synthesized a small molecule that is rapidly cleared by the body, emits in the second near-infrared spectral region (1,000–1,700 nm) and outperforms Indocyanine Green (ICG), the well-established and FDA-approved probe most adopted for clinical applications.
A different approach to fluorescence imaging adopts the use of quantum dots. In Zhou et al. an anti-Stokes process is induced by the single-band upconversion emission of nanocrystals. Blue, green and red emissions were achieved with excitations in the near-infrared region by layering an organic dye on lanthanide nanoparticles, and used for the multiplexed tagging of cancer biomarkers.
Probing metabolic processes has been one of the most successful strategies to diagnose cancer. The parts played by glucose, oxygen and lactate have been widely described in cancer cells. In Zhao et al. a nanoprobe, labelled with an ICG molecule, displayed tight control of pH-dependent emissions and enabled the detection of small nodules during image-guided surgery. pH-based sensing is again adopted, in combination with impedance sensing and radio frequency ablation therapy for the design of an endoscope for colon cancer treatment (Lee et al.). A Cy5 derivative is also used in colonoscopy and Burggraaf et al. conjugated it to a water-soluble 26-amino-acid cyclic peptide selected for its high affinity and specificity for the extracellular domain of the human transmembrane protein c-Met.
In clinical settings, endoscopic techniques have directly benefitted from advances in optical imaging (Joshi et al.). Three Reviews in this Collection emphasize this, in the context of coronary atherosclerosis (Dwek et al.) of image-guided prostatectomy (Fried et al.) and of diagnostic imaging of the pancreas (Dimastromatteo et al.). On the other hand, in basic research settings, the use of microendoscopic techniques and miniaturised microscopes have enabled the imaging of neuronal activity via a genetically encoded calcium indicator in the deep brain of the mouse during natural behaviour (Resendez et al.).
Diagnostic imaging does not need to be restricted to the in vivo detection of diseased cells. A newer approach to deliver molecular-grade diagnostic information uses label-free methods, as demonstrated in Tu et al., where the visualisation of microstructures in fresh tissue by using non-linear optical processes achieves histochemically specific images. Fluorescent proteins can also find diagnostic validity beyond their expression in experimental cell and animal models; for example, in the context of drug discovery Kang et al. used reporter cell lines to develop a screening platform.
Optical imaging is truly a multidisciplinary field that has helped bench researchers and clinicians understand disease and improve healthcare. In combination with improved resolution and molecular-grade specificity of target recognition, the use of optical tools in diagnostics is quickly leading to exciting opportunities for personalised medicine.