Fingerprint multiplex CARS at high speed based on supercontinuum generation in bulk media and deep learning spectral denoising

Abstract

We introduce a broadband coherent anti-Stokes Raman scattering (CARS) microscope based on a 2-MHz repetition rate ytterbium laser generating 1035-nm high-energy (≈µJ level) femtosecond pulses. These features of the driving laser allow producing broadband red-shifted Stokes pulses, covering the whole fingerprint region (400–1800 cm−1), employing supercontinuum generation in a bulk crystal. Our system reaches state-of-the-art acquisition speed (<1 ms/pixel) and unprecedented sensitivity of ≈14.1 mmol/L when detecting dimethyl sulfoxide in water. To further improve the performance of the system and to enhance the signal-to-noise ratio of the CARS spectra, we designed a convolutional neural network for spectral denoising, coupled with a post-processing pipeline to distinguish different chemical species of biological tissues.

Computational coherent Raman scattering imaging: breaking physical barriers by fusion of advanced instrumentation and data science

“…The authors further applied a k-means clustering algorithm after denoising to yield chemical segmentation maps in an automatic and unsupervised manner. Denoising of hyperspectral CARS images with a 1D spectral network has also been achieved [101] for high-speed fingerprint CARS imaging.…”

“…Compressive sensing Berto [68] Takizawa [69] Matrix completion Lin [59] Supervised spectral sub-sampling Freudiger [71], Bae [72], Pence [74] Masia [73] Digital holography Shi [78], Cocking [79] Projection tomography Chen [80], Lin [81], Gong [85] Deep learning denoising Manifold [97], Lin [36], Abdolghader [100] Yamato [98], Vernuccio [101] Deep learning segmentation & Clinical decision making Orringer [104], Hollon [105], Zhang [106], Feizpour [107] Manuscu [108], Aljakouch [109], Weng [110] Deep learning background removal Bresci [114] Houhou [111], Valensise [112], Wang [113] Deep learning chemical maps prediction Zhang [56], Liu [118], Manifold [115] as existing methods remain viable to boost the newly established design space, and new methods may arise to achieve breakthroughs in aspects such as field of view, imaging depth, and spatial resolution.…”

Full-Spectrum CARS Microscopy of Cells and Tissues with Ultrashort White-Light Continuum Pulses

“…28 We recently introduced a new approach to high-speed multiplex CARS microscopy based on a 2 MHz repetition rateamplified ytterbium laser system, producing the broadband Stokes pulses through white-light continuum (WLC) generation in bulk media. 29 Compared to previous multiplex CARS systems operating with a higher repetition rate (≈40− 80 MHz) and nJ energy pulses, our platform employs much higher pulse energies (≈ 2 μJ), thus enabling us to replace the PCFs used for the broadband Stokes beam generation with a bulk yttrium aluminum garnet (YAG) crystal. This solution leads to a setup that is more robust, compact, and alignment insensitive.…”

Pulse-Picking Multimodal Nonlinear Optical Microscopy

“…One approach is to use lasers with lower repetition rates and higher pulse energy, which gives higher peak power at the same average power. − A tunable repetition rate would provide better flexibility for different imaging requirements. One way to reduce the repetition rate is using Pockels cells.…”