Ultrathin monolithic 3D printed optical coherence tomography endoscopy for preclinical and clinical use

Fiber-optic endoscopes are indispensable clinical tools for diagnostic imaging of the internal lumen of hollow organs and real-time interventional guidance. OCT endoscopes, providing depth-resolved imaging, have been used on over 410,000 patients and are widely used in preclinical animal models. There remains an unmet need for miniaturized high-resolution probes to image delicate, narrow luminal organs and small animals while minimizing trauma from endoscope insertion. Achieving both high resolution (large NA) and large depth of focus in miniaturized probes is challenging due to traditional trade-offs: high NA yields shallow depth of focus, while low NA sacrifices resolution. In mouse cardiovascular models, previously reported ~483 μm probes were unable to image microstructures deeper than 100 μm due to short depth of focus and insufficient resolution to visualize features such as adipose cells, cholesterol crystals, and connective tissue. Existing fabrication techniques for highly miniaturized probes lead to spherical aberration, low resolution, or shallow depth of focus. Correcting spherical aberration typically requires aspherical profiles that are difficult to realize on fibers with melting-based lens formation. OCT catheter sheaths add further complexity by inducing astigmatism (negative cylindrical lens effect), necessitating correction to achieve desired performance. Current micro-optic fabrication methods (e.g., GRIN fibers with parabolic index profiles and fiber ball lenses) inherently introduce aberrations and limit astigmatism correction, constraining resolution and depth of focus. Ultrafast laser nanostructuring (two-photon lithography) can create complex, accurate micro-optics with low roughness and sub-micron alignment and has been preliminarily used to glue discrete optical elements to fibers for OCT, though without addressing aberration correction or scalable manufacture. The present work introduces an ultrathin, monolithic 3D microprinted freeform optic on fiber to correct nonchromatic aberrations, enabling a fully functional ultrathin, aberration-corrected OCT endoscopic probe.

Prior OCT and endoscopic probes face a fundamental resolution–depth-of-focus trade-off, exacerbated at miniature scales where small apertures limit feasible compromises. Traditional fiber-lens approaches (GRIN lenses/fibers with parabolic index profiles and fiber ball lenses) induce spherical aberrations and provide poor control over astigmatism, especially problematic within catheter sheaths that act as negative cylindrical lenses. Designs using discrete micro-optics (prisms, lenses) are constrained by assembly tolerances at small scales. Two-photon polymerization has emerged as a viable alternative for fabricating complex, accurate freeform micro-optics with sub-micron alignment; previous demonstrations glued discrete elements to fibers to enable OCT but did not exploit aberration correction and posed scalability challenges. Therefore, a gap remains for monolithic, on-fiber freeform micro-optics that can correct spherical aberration and sheath-induced astigmatism in ultrathin probes to simultaneously achieve high resolution and extended depth of focus.

Design and fabrication: A 450 μm length of no-core fiber was fusion spliced onto a 20 cm single-mode fiber (SMF-28) using an automated glass processor to allow beam expansion. A freeform beam-shaping micro-optic was directly 3D printed onto the distal end of the no-core fiber using two-photon lithography (Photonic Professional GT) with a fiber holder for precise alignment. The freeform surface functions as an off-axis total internal reflection (TIR) mirror to redirect and focus the beam, while phase-shaping to compensate for astigmatism introduced by the transparent polymer catheter sheath (inner diameter 0.386 mm, outer diameter 0.457 mm). The fiber assembly was integrated into a thin-walled torque coil (ID 0.26 mm, OD 0.36 mm) to transmit rotational and linear motion for helical 3D scanning; the probe rotates inside the stationary sheath to protect tissue. Characterization: Five replicate micro-optics were fabricated on fibers (100% print success). Surface profiles were measured with a noncontact confocal surface profiler (isurf export). RMS deviation from design was <34 ± 12 nm for the TIR mirror and <71 ± 52 nm for the planar surface (for a beam footprint NA = 0.14), with corresponding wavefront errors close to or below the diffraction limit (ΔW < 0.07λ). The assembled catheter’s beam profile was measured in water (to emulate in vivo refractive index) using custom mounts. Focal spot size (FWHM) and working distance were quantified along x and y to assess astigmatism and depth of focus. Effective depth of focus was defined as the axial range where FWHM < 2× minimum FWHM. Ex vivo and preclinical imaging: Human carotid artery (freshly excised from a 75-year-old male undergoing carotid endarterectomy; ethics approval R20170715 HREC/17/2A; informed consent obtained) was scanned and compared with matched histology based on anatomical landmarks. Mouse thoracic aortas were imaged in situ (ethics SAM188; tissue sharing protocols); blood was depleted via saline flushing to reduce scattering. The ultrathin probe was delivered through vessels and scanned via rotation and pullback to produce 3D OCT datasets.

- Fabrication and fidelity: Direct 3D microprinting of freeform optics on fiber achieved 100% success across five replicates, with RMS surface deviations of <34 ± 12 nm (TIR mirror) and <71 ± 52 nm (planar surface) for NA = 0.14 footprints, corresponding to near-diffraction-limited wavefront errors (ΔW < 0.07λ). - Ultrathin probe dimensions: Complete catheter OD 0.457 mm (smallest aberration-corrected intravascular OCT probe reported), with on-fiber freeform optic <130 μm diameter. - Optical performance in water: Measured focal spot size ~12.4 μm FWHM; working distance ~513 μm (simulated 12.8 μm FWHM, 500 μm WD). Effective depths of focus: 760 μm (x) and 1100 μm (y), with negligible astigmatism. - Mechanical performance: Smooth rotation and pullback within sheath; probe flexibility enabled effortless delivery through a severely stenotic human carotid artery. - Imaging results: Ex vivo human carotid artery imaging visualized an internal thrombus and fibroatheroma with necrotic core and fibrous cap, consistent with corresponding histology. In situ mouse thoracic aorta imaging preserved anatomical configuration with blood cleared by saline, enabling imaging without obvious rotational distortion. - Significance: Demonstrated high-resolution, extended-depth imaging with an ultrathin, aberration-corrected OCT catheter suitable for preclinical and potential clinical applications.

The work addresses the central challenge in ultraminiaturized OCT endoscopy: achieving high resolution with extended depth of focus while correcting nonchromatic aberrations introduced by both miniaturized optics and catheter sheaths. By monolithically 3D printing a freeform TIR surface directly on a fiber, the design corrects spherical aberration and sheath-induced astigmatism that limit GRIN and ball-lens approaches. Measured optical performance closely matches simulations, confirming effective aberration control and beam shaping in a clinically relevant medium (water). The combination of a ~12.4 μm focal spot with 0.76–1.1 mm effective DOF at sub-0.5 mm catheter OD enables visualization of plaque microarchitecture, including thrombus, fibrous cap, and necrotic core, in human carotid tissue, as validated by histology. In situ mouse imaging further shows that the ultrathin footprint and flexible mechanical design allow navigation and stable rotational scanning in small vessels. Collectively, these results indicate that monolithic 3D printed freeform micro-optics can overcome longstanding trade-offs in miniature OCT probes, expanding applicability to delicate, narrow lumens in both preclinical models and potential clinical use.

This study introduces the smallest aberration-corrected intravascular OCT probe to date by leveraging monolithic 3D microprinted freeform optics on fiber. The ultrathin catheter (0.457 mm OD) delivers near-diffraction-limited beam shaping with negligible astigmatism, achieving a ~12.4 μm focal spot and up to 1.1 mm effective depth of focus in water. High-fidelity fabrication (nanometer-scale surface deviations, 100% print success) and robust mechanical operation enable high-quality imaging of atherosclerotic features in human and mouse arteries with histological concordance. These advances open a pathway for minimally invasive imaging in delicate and small luminal organs. Potential future directions include translating the technology to additional preclinical and clinical applications requiring ultrathin catheters and further optimizing manufacturing scalability and device integration for broader deployment.