Melissa Skala and MaryseLapierre-Landry

Optical coherence tomography (OCT) is an imaging tool commonly used in the eye for screening, diagnosis and treatment of diseases of the retina and cornea. Used regularly by researchers in the eye and vision community to better understand diseases in the human eye, OCT is also used in multiple animal eye models. OCT can quickly and noninvasively image microscopic structures in the eye without dyes, thereby rendering three-dimensional images of the layers of the retina. Also without using dyes, OCT can produce three-dimensional maps of the blood microvessels in the eye. This “multi-functional” quality of OCT makes it a versatile tool for researchers and clinicians alike. For this reason, researchers in optics and biomedical engineering are developing additional OCT modalities, which if successful could be incorporated in existing instruments and could provide functional contrast. Photothermal optical coherence tomography (PT-OCT) is one of those new modalities, which is currently being developed by Maryse Lapierre-Landry, a graduate student in Dr. Melissa Skala’s lab.

Traditional OCT detects changes in refractive index, for example between a tissue layer containing mostly cell nuclei versus a tissue layer containing mostly collagen. Conversely, PT-OCT detects optical absorbers, such as the melanin naturally present in the eye. PT-OCT achieves this added contrast by repeatedly heating the absorbers in the tissue by a few degrees (1-3°C) at a known frequency. This in turn causes a cyclical change in refractive index around each absorber, which is then scanned by the OCT beam. The OCT signal is sensitive to small changes in refractive index, and thereby detects the temperature oscillations. At the post-processing stage, sections of the tissue that are oscillating at the photothermal frequency indicate the presence of absorbers, and their position can be mapped onto the OCT image. Variations in the levels of an absorber such as melanin can occur in multiple diseases of the eye, such as melanoma or age-related macular degeneration, and PT-OCT could eventually be used to study the progression of those diseases.

PT-OCT was initially demonstrated on different types of absorbers in cells, tissue samples such as breast, and in the skin and tumors of living mice. However, Ms. Lapierre-Landry, Dr. Skala, and collaborators were the first to demonstrate PT-OCT in the eye. Collaborators at the Vanderbilt Eye Institute included Dr. John Penn and his graduate student Andrew Gordon. Initial studies were conducted in the eyes of living mice, and established a strong PT-OCT signal from melanin in the retinal pigment epithelium (RPE). In a different experiment, lesions were created at the back of the mice retina using a laser, after which the mice were injected with gold nanoparticles via the tail vein. The presence of new and “leaky” vasculature in the lesion caused the gold nanoparticles to accumulate in the retina, and their presence was detected using PT-OCT.

Dr. Skala and Ms. Lapierre-Landry moved from Vanderbilt University to the University of Wisconsin last year, and have established collaborations with McPherson Eye Research Institute members to develop PT-OCT for clinical applications. Additional research is needed to make PT-OCT a faster, more user-friendly system with a wider range of contrast agents, which is the current focus of Maryse Lapierre-Landry’s graduate work in the Skala Lab. The added contrast of PT-OCT has the potential to provide three-dimensional, non-invasive molecular imaging in the eye. In the future, this technology could facilitate automatic RPE segmentation to study diseases such as age-related macular degeneration, and could also increase contrast on OCT images during macular surgery.