Optical sensing of specific molecular targets and pathways deep inside living mice has become possible as a result of a number of advances. These include design of biocompatible near-infrared fluorochromes, development of targeted and activatable 'smart' imaging probes, engineered photoproteins and advances in photon migration theory and reconstruction. Together, these advances will provide new tools making it possible to understand more fully the functioning of protein networks, diagnose disease earlier and speed along drug discovery.

Shedding light onto live molecular targets

Imaging sciences have grown exponentially during the past three decades, and many techniques, such as magnetic resonance imaging, nuclear tomographic imaging and X-ray computed tomography, have become indispensable in clinical use. Advances in imaging technologies and imaging probes for humans and for small animals are now extending the applications of imaging further into drug discovery and development, and have the potential to considerably accelerate the process. This review summarizes some of the recent developments in conventional and molecular imaging, and highlights their impact on drug discovery.

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Molecular imaging in drug discovery and development

The extension of in vivo optical imaging for disease screening and image-guided surgical interventions requires brightly emitting, tissue-specific materials that optically transmit through living tissue and can be imaged with portable systems that display data in real-time. Recent work suggests that a new window across the short-wavelength infrared region can improve in vivo imaging sensitivity over near infrared light. Here we report on the first evidence of multispectral, real-time short-wavelength infrared imaging offering anatomical resolution using brightly emitting rare-earth nanomaterials and demonstrate their applicability toward disease-targeted imaging. Inorganic-protein nanocomposites of rare-earth nanomaterials with human serum albumin facilitated systemic biodistribution of the rare-earth nanomaterials resulting in the increased accumulation and retention in tumour tissue that was visualized by the localized enhancement of infrared signal intensity. Our findings lay the groundwork for a new generation of versatile, biomedical nanomaterials that can advance disease monitoring based on a pioneering infrared imaging technique.

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Rare-earth-doped biological composites as in vivo shortwave infrared reporters

A survey of the literature is presented that provides an analysis of the optical properties of human skin, with particular regard to their applications in medicine. Included is a description of the primary interactions of light with skin and how these are commonly estimated using radiative transfer theory (RTT). This is followed by analysis of measured RTT coefficients available in the literature. Orders of magnitude differences are found within published absorption and reduced-scattering coefficients. Causes for these discrepancies are discussed in detail, including contrasts between data acquired in vitro and in vivo. An analysis of the phase functions applied in skin optics, along with the remaining optical coefficients (anisotropy factors and refractive indices) is also included. The survey concludes that further work in the field is necessary to establish a definitive range of realistic coefficients for clinically normal skin.

https://www.spiedigitallibrary.org/journals/journal-of-biomedical-optics/volume-17/issue-9/090901/Optical-properties-of-human-skin/10.1117/1.JBO.17.9.090901.pdf

Optical properties of human skin.

We investigate the hypothesis that colour vision in primates was selected for discriminating the spectral modulations on the skin of conspecifics, presumably for the purpose of discriminating emotional states, socio-sexual signals and threat displays. Here we show that, consistent with this hypothesis, there are two dimensions of skin spectral modulations, and trichromats but not dichromats are sensitive to each. Furthermore, the M and L cone maximum sensitivities for routine trichromats are optimized for discriminating variations in blood oxygen saturation, one of the two blood-related dimensions determining skin reflectance. We also show that, consistent with the hypothesis, trichromat primates tend to be bare faced.

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Julie Bykowski

Papers

Skin melanin, hemoglobin, and light scattering properties can be quantitatively assessed in vivo using diffuse reflectance spectroscopy