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Ultrasound Imaging and Therapeutics Research Laboratory

Design of Stimuli-responsive OCT Contrast Agents to Visualize a Disease Region of Interest Without Background Noise

Researchers: Myeongsoo Kim, Samuel Morais

Fig 1Optical coherence tomography (OCT) is an imaging modality that provides millimeter-scale depth penetration and submicrometer spatial resolution, enabling the generation of microscale cross-sectional images of biological tissues. OCT is conceptually similar to ultrasound B-mode imaging or radar but uses a near-infrared (NIR) light source for image reconstruction. As an optical imaging technique, OCT thus achieves spatial resolution an order of magnitude higher than conventional ultrasound imaging. Specifically, OCT captures depth-resolved backscattered light resulting from interactions between incident light and tissue molecules. Because biological tissues exhibit heterogeneity in optical refractive indices, OCT enables imaging of fine tissue microstructures without requiring tissue excision. Therefore, since its invention, OCT has been widely adopted for various bio-medical applications, such as cancer diagnosis, ophthalmology, surgical guidance, cardiology, and pulmonology.

While endogenous molecules, such as cell nuclei, mitochondria, and hemoglobin, are typically used to characterize tissue morphology with OCT, exogenous contrast agents with large scattering cross-sections at NIR wavelengths, such as gold nanoparticles, copper sulfide quantum dots, and microbubbles, can enhance imaging by providing better visualization of specific molecular and cellular events with enhanced contrast. Despite robust scattering responses from designed contrast agents, they often encounter challenges in clearly identifying specific biomolecular processes in tissue due to poor efficiency or difficulty in coupling the agents to the targeted biological processes, leading to unnoticeable signals compared to background noise.

To address these challenges, we are developing OCT contrast agents that respond to endogenous or external stimuli, as a trigger to modulate their scattering responses, thereby enhancing the localization of such agents by comparing OCT signals and contrast between pre- and post-stimulus treatment via image-pixel subtraction. When the signal change from the stimulus-responsive contrast agents pre- and post-stimulus treatment is significantly greater than that of background tissue, this approach can provide enhanced imaging contrast with high specificity in the region of interest where the agents are localized. We recently demonstrated “magnetically controlled reversible photomagnetic actuators for dynamic contrast enhancement in OCT” that allow clear visualization of particles in vivo without background noise [1].

Further reading

[1] M. Kim, S. M. A. Morais, A. Jhunjhunwala, S. Subramanian, P. S. Pelkowski, S. Y. Emelianov, “Magnetically Controlled Reversible Photomagnetic Nanoactuators for Dynamic Contrast Enhancement in Optical Coherence Tomography,” Advanced Materials 37, no. 35 (2025)

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