Chemical imaging, especially mid-infrared spectroscopic microscopy, enables label-free biomedical analyses while achieving expansive molecular sensitivity. However, its slow speed and poor image quality impede widespread adoption. We present a microscope that provides high-throughput recording, low noise, and high spatial resolution where the bottom-up design of its optical train facilitates dual-axis galvo laser scanning of a diffraction-limited focal point over large areas using custom, compound, infinity-corrected refractive objectives. We demonstrate whole-slide, speckle-free imaging in ~3 min per discrete wavelength at 10× magnification (2 μm/pixel) and high-resolution capability with its 20× counterpart (1 μm/pixel), both offering spatial quality at theoretical limits while maintaining high signal-to-noise ratios (>100:1). The data quality enables applications of modern machine learning and capabilities not previously feasible – 3D reconstructions using serial sections, comprehensive assessments of whole model organisms, and histological assessments of disease in time comparable to clinical workflows. Distinct from conventional approaches that focus on morphological investigations or immunostaining techniques, this development makes label-free imaging of minimally processed tissue practical.
Acousto-optic imaging (AOI) enables optical-contrast imaging deep inside scattering samples via localized ultrasound-modulation of scattered light. While AOI allows optical investigations at depths, its imaging resolution is inherently limited by the ultrasound wavelength, prohibiting microscopic investigations. Here, we propose a computational imaging approach that allows optical diffraction-limited imaging using a conventional AOI system. We achieve this by extracting diffraction-limited imaging information from speckle correlations in the conventionally detected ultrasound-modulated scattered-light fields. Specifically, we identify that since “memory-effect” speckle correlations allow estimation of the Fourier magnitude of the field inside the ultrasound focus, scanning the ultrasound focus enables robust diffraction-limited reconstruction of extended objects using ptychography (i.e., we exploit the ultrasound focus as the scanned spatial-gate probe required for ptychographic phase retrieval). Moreover, we exploit the short speckle decorrelation-time in dynamic media, which is usually considered a hurdle for wavefront-shaping- based approaches, for improved ptychographic reconstruction. We experimentally demonstrate noninvasive imaging of targets that extend well beyond the memory-effect range, with a 40-times resolution improvement over conventional AOI.
more » « less- Award ID(s):
- 1813848
- NSF-PAR ID:
- 10250620
- Publisher / Repository:
- Optical Society of America
- Date Published:
- Journal Name:
- Optica
- Volume:
- 8
- Issue:
- 6
- ISSN:
- 2334-2536
- Page Range / eLocation ID:
- Article No. 936
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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