Technology Development

Clinical examination crucially relies on the ability to quickly examine large tissue areas  and rapidly zoom in to regions of interest. Skin lesions often show irregularity in color and appearance, especially when they start to progress towards malignancy. Examination of the entire lesion is essential to avoid false negative diagnostic assessments. Therefore, imaging of large field of views (FOVs) and automatic translation of the inspected area are practical requirements for reliable clinical imaging.

We have recently designed and developed an MPM-based imaging platform for rapidly generating images with large FOVs without compromising resolution. This system is designed specifically for clinical imaging of human skin, and features a large FOV of 800×800 μm2 acquired at speeds of less than 2 seconds per 1 MPx frame for high signal-to-noise ratio, with lateral and axial resolutions of 0.5 μm and 3.3 μm,. A field of view of 1.2×1.2 mm2 can be obtained at the expense of increased field curvature.

Ex vivo MPM mesoscale imaging of human skin. MPM image of the DEJ in human skin showing keratin in skin folds (green) and fibrilar structure of dermal papilla (collagen fibers-blue; elastin fibers-green). The wide area image (3.1 x 2.5 mm2) includes a mosaic of 20 frames and was acquired in 2 minutes. The image shown as inset was acquired as single frame in 2.4 s. Scale bar is 0.25 mm.

Related publications:

Balu M, Mikami H, Hou J, Potma EO, and Tromberg BJ, “Rapid mesoscale multiphoton microscopy of human skin,” Biomed. Opt. Express 2016; 7, 4375-4387 PMC5119580

Balu M, Potma E, Tromberg B, Mikami H. Imaging platform based on nonlinear optical microscopy for rapid scanning large areas of tissue US20180106729A1.

In recent stages of the development we have combined optical and mechanical scanning mechanisms with deep learning image restoration approaches to allow millimeter-to-centimeter scale imaging within minutes while maintaining sub-micron resolution. This advanced bench-top prototype imaging platform also features time-resolved single photon counting detection for enhanced molecular contrast. This system is currently being converted into a portable, compact instrument, appropriate for clinical skin imaging.

The opto-mechanical design of an MPM imaging platform that allows macroscopic imaging with microscopic resolution within minutes in order to enhance the effectiveness of the clinical skin imaging.

Fast ALal ADurkin AFZachary CBGanesan AKBalu M, “FLAME: Macroscopic imaging with microscopic resolution. Optical biopsy of human skin”, bioRxiv