Molecularly targeted photoacoustic endoscopy with fiber-scanning side-view probe for in vivo staging of early mucosal tumors

Tse-Shao Chang; Shuo Feng; Gaoming Li; Haijun Li; Xiaoli Wu; Sangeeta Jaiswal; Guan Xu; Hui Jiang; Eun-Young K Choi; Kenn R Oldham; Thomas D Wang

doi:10.1016/j.bios.2025.117757

Molecularly targeted photoacoustic endoscopy with fiber-scanning side-view probe for in vivo staging of early mucosal tumors

Biosens Bioelectron. 2025 Jul 4:288:117757. doi: 10.1016/j.bios.2025.117757. Online ahead of print.

Authors

Tse-Shao Chang¹, Shuo Feng², Gaoming Li², Haijun Li², Xiaoli Wu², Sangeeta Jaiswal², Guan Xu³, Hui Jiang⁴, Eun-Young K Choi⁵, Kenn R Oldham¹, Thomas D Wang⁶

Affiliations

¹ Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
² Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.
³ Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48109, USA.
⁴ Department of Biostatistics, University of Michigan, Ann Arbor, MI, 48109, USA.
⁵ Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
⁶ Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: thomaswa@umich.edu.

PMID: 40651392
DOI: 10.1016/j.bios.2025.117757

Abstract

Accurate in vivo staging of early gastrointestinal (GI) cancers is critical for selecting between local and systemic therapy. We present a molecularly targeted photoacoustic endoscopy (PAE) system that combines a compact, fiber-scanning side-view probe with a HER2-targeted near-infrared (NIR) contrast agent (KSP∗-IRDye800) to assess mucosal and submucosal tumor invasion in vivo. The 4.2 mm diameter probe uses a piezoelectric (PZT) bender to steer a laser beam laterally (±16°) and achieve high-resolution imaging. The system provides 363 μm lateral and 119 μm axial resolution at a depth of 3.1 mm and supports 3D volumetric image acquisition via rotational scanning and linear pullback. In vivo imaging was performed in CPC;Apc mice that spontaneously develop colonic adenomas. The targeted contrast agent demonstrated a significantly higher peak target-to-background (T/B) ratio (3.0 ± 0.3, RSD = 10 %) than indocyanine green (ICG, 1.37 ± 0.1), with peak uptake at 1.5 h post-injection. Adenoma dimensions measured by PAE correlated strongly with histology (ρ = 0.97 for width, ρ = 0.90 for depth), and 3D reconstructions accurately delineated tumor margins. Ex vivo validation confirmed imaging performance and molecular specificity. This work demonstrates the feasibility of targeted PAE for high-resolution, minimally invasive staging of early GI tumors. The system's resolution and depth performance are sufficient to distinguish between T1_a and T1_b lesions. Integration of molecular contrast with miniaturized photoacoustic imaging enables real-time assessment of tumor invasion depth and has potential to improve diagnostic accuracy and therapeutic decision-making during endoscopy.

Keywords: Cancer; Contrast; Endoscopy; Molecular; Photoacoustics; Staging.