Optical coherence tomography of magnetically controllable photomagnetic nanoactuators for particle localization and background-free imaging

Introduction: : Optical coherence tomography (OCT) is an imaging technique that uses a near-infrared (NIR) light source to generate cross-sectional images of biological tissues with submicrometer spatial resolution and millimeter-scale depth. OCT captures backscattered light based on differences in tissue refractive indices, enabling noninvasive imaging of tissue microstructures. Thus, OCT is widely utilized in cancer diagnostics, ophthalmology, cardiology, and pulmonology. However, the ability of OCT to visualize specific biological processes is often hindered by the lack of effective contrast agents capable of generating noticeable imaging signals and contrast over background signals. To address this, designing contrast agents that respond to external stimuli and trigger changes in OCT signals can be utilized to identify the agent’s localization with specificity and minimal background signal via pixel-by-pixel subtraction of pre- and post-stimulus images. Here, we present photomagnetic nanoactuators (PMNAs) with approximately 90% scattering efficiency in the second NIR window, capable of magnetic field-mediated reversible modulation of optical scattering and, therefore, OCT signal. Each nanoactuator consists of a magnetite core and a gold shell, functioning as a magnetic driver and an optical scatterer, respectively. When exposed to an external magnetic field, PMNAs assemble into chain structures via magnetostatic interactions, reducing their optical scattering and OCT signal. Upon removal of the magnetic field, the nanoactuators disassemble, restoring the original OCT signal. We demonstrate that the magnetically controllable OCT response from the nanoactuators allows their specific localization and background-free imaging via subtraction of images before and after external magnetic field application both in vitro and in vivo settings.

Materials and

Methods: : PMNAs (~ 200 nm) were synthesized via seeded growth of gold nanospheres onto the surface of magnetite nanospheres, as demonstrated by transmission electron microscopy (TEM). The optical extinction of PMNAs was characterized by UV-vis-NIR spectroscopy. The scattering percentage of PMNAs was numerically calculated by a finite-difference time-domain simulation. The reversible chain assembly and disassembly of PMNAs upon controlled magnetic field applications were characterized by optical microscopy. Finally, OCT images acquired before (“OFF”) and during the magnetic field application (“ON”) were subtracted pixel-by-pixel to produce differential (“OFF” – “ON”) images of PMNAs placed in physiologically relevant environments, such as water, blood, or mouse subcutaneous tissue.

Results, Conclusions, and Discussions:: Results and

Discussion: We fabricated PMNAs by growing conformal gold shells on magnetite-silica core-shell nanospheres (Figs. 1a, b). The gold shell enabled strong optical responses, with ~90% scattering efficiency in the second NIR window (Figs. 1c, d). Under an external magnetic field, PMNAs reversibly assembled into chain constructs via magnetostatic interactions and disassembled upon field removal due to electrostatic repulsion (Figs. 1e, f). In the assembled state, optical scattering decreased due to interparticle plasmon coupling (Fig. 1g). This magnetically controllable optical behavior was leveraged to modulate OCT signals remotely and repeatedly (Fig. 1h). By comparing OCT images acquired with the magnetic field “OFF” and “ON”, PMNAs can be identified in differential (“OFF” – “ON”) images of water (Figs. 1i, j) and blood samples (Figs. 1k, l). Furthermore, subcutaneously injected PMNAs in mice produced significant OCT signal changes in response to the magnetic field application, enabling the localization of PMNAs with minimal signal interference from background tissue (Fig. 1m). Finally, we quantified contrast-to-noise ratio (CNR) in the differential “OFF” – “ON” images versus conventional OCT images (prior to image subtraction). The CNR in the differential images was approximately two-fold higher compared to conventional OCT images, demonstrating the enhanced detection sensitivity of PMNAs for background-free OCT imaging (Fig. 1n).

Conclusion: We present PMNAs as a platform for particle localization and background-free imaging in OCT under the control of an external magnetic field. The demonstrated nanoactuator platform offers a promising strategy to enhance OCT contrast and specificity, which could potentially broaden the applications of OCT, including non-invasive cell monitoring and molecular diagnostic imaging in preclinical models.

Acknowledgements and/or References (Optional)::