In Situ Stimulated Raman Scattering (SRS) Microscopy Study of the Dissolution of Sustained-Release Implant Formulation

Stimulated Raman scattering (SRS) microscopy is a label-free quantitative chemical imaging technique that has demonstrated great utility in biomedical imaging applications ranging from real-time stain-free histopathology to live animal imaging. However, similar to many other nonlinear optical imaging techniques, SRS images often suffer from low signal to noise ratio (SNR) due to absorption and scattering of light in tissue as well as the limitation in applicable power to minimize photodamage. We present the use of a deep learning algorithm to significantly improve the SNR of SRS images. Our algorithm is based on a U-Net convolutional neural network (CNN) and significantly outperforms existing denoising algorithms. More importantly, we demonstrate that the trained denoising algorithm is applicable to images acquired at different zoom, imaging power, imaging depth, and imaging geometries that are not included in the training. Our results identify deep learning as a powerful denoising tool for biomedical imaging at large, with potential towards in vivo applications, where imaging parameters are often variable and ground-truth images are not available to create a fully supervised learning training set.

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“…SRS images were acquired using a homebuilt SRS microscope as described previously [29][30][31] and as shown in Fig. 1.…”

Section: Srs Imagingmentioning

confidence: 99%

Denoising of stimulated Raman scattering microscopy images via deep learning

Manifold¹,

Thomas²,

Francis³

et al. 2019

Biomed. Opt. Express

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“…Fu group made use of SRS microscopy for chemical mapping of entecavir, a hepatitis B antiviral drug, embedded in a slow release poly (D,L-lactic acid) formulation. High spatial resolution of SRS microscopy allowed quantitative profiling of dissolution of single crystalline particles in implant formulations in situ (Francis et al, 2018). Their later work demonstrated chemical imaging of salt disproportionation reaction of pioglitazone hydrochloride (PIO-HCl) at a very low drug loading (1% w/w) by SRS microscopy (Figueroa et al, 2019).…”

Section: Anti-cancer Drug Stability and Dissolution In The Solid Statementioning

confidence: 99%

Coherent Raman Scattering Microscopy in Oncology Pharmacokinetic Research

2021

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The high attrition rates of anti-cancer drugs during clinical development remains a bottleneck problem in pharmaceutical industry. This is partially due to the lack of quantitative, selective, and rapid readouts of anti-cancer drug activity in situ with high resolution. Although fluorescence microscopy has been commonly used in oncology pharmacological research, fluorescent labels are often too large in size for small drug molecules, and thus may disturb the function or metabolism of these molecules. Such challenge can be overcome by coherent Raman scattering microscopy, which is capable of chemically selective, highly sensitive, high spatial resolution, and high-speed imaging, without the need of any labeling. Coherent Raman scattering microscopy has tremendously improved the understanding of pharmaceutical materials in the solid state, pharmacokinetics of anti-cancer drugs and nanocarriers in vitro and in vivo. This review focuses on the latest applications of coherent Raman scattering microscopy as a new emerging platform to facilitate oncology pharmacokinetic research.

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“…[ 50 ] Chemical mapping of entecavir embedded in a poly( d,l ‐lactic acid) release formulation was obtained by SRS microscopy to quantitatively analyze the dissolution of single crystal particles in implant formulations. [ 117 ] The drug distribution on the skin surface and efficiency of drug delivery into the skin are vital for the treatment of dermatologic diseases, and a high‐speed 3D SRS imaging technique may be a promising solution. Relevant demonstrations include mapping the distribution of vitamin E on the skin of mice, [ 23 ] investigating the transmission pathway of an antifungal skin drug (terbinafine hydrochloride) in the ear tissue of mice [ 88 ] and comparing the different permeation pathways and velocities of two drugs (ketoprofen and ibuprofen) in the skin tissue of mice.…”

Section: Applicationsmentioning

confidence: 99%

Review of Stimulated Raman Scattering Microscopy Techniques and Applications in the Biosciences

Shen

et al. 2020

Advanced Biology

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elastically scattered photons) featuring time-consuming spectral integration and hence a poor acquisition speed (several seconds per line or minutes per frame). This weakness constitutes a large obstacle for real-time monitoring of dynamic events in organisms. Recently, several variations of Raman spectroscopy have been developed to enhance the sensitivity of Raman spectroscopy and dynamic processes of biological samples, including coherent Raman scattering (CRS) spectroscopy and surfaceenhanced Raman spectroscopy (SERS). SERS involves a plasmonic effect where molecules absorbed on a rough metal surface can result in high Raman scattering intensities by increasing the incident electric field. [5] For SERS technology, a SERS substrate must be introduced to enhance the detection sensitivity, and the properties of the substrate (the composition, size, shape and aggregation degree of nanoparticles) affect the shape of the SERS spectra. In addition, only gold, silver, copper, and a few rare alkali metals (such as lithium and sodium) have strong SERS effects, and it is necessary to effectively solve the biocompatibility and safety issues in the preparation of nanomaterials. With the development of laser and nonlinear optics, CRS microscopy has also been demonstrated to break the speed limit for vibrational imaging. [6] CRS has two major forms: coherent anti-Stokes Raman scattering (CARS) and stimulated Raman scattering (SRS); [7] both techniques can dramatically increase the Raman signal by a few orders of magnitude and hence are able to achieve video-rate molecular imaging in vivo. [8,9] CARS and SRS processes often exist in a sample concurrently because of the same excitation conditions (spatiotemporal overlap of the pump and Stokes beam) with a frequency difference (Raman shift) matching the molecular vibrational frequency. However, CARS is an optical parametric process accompanied by a nonresonant part originating from fourwave mixing processes. This intrinsic nonresonant background results in a deviation or even distortion of the Raman spectrum. SRS is a direct process of photon-vibration energy transfer: in brief, the interaction between the electron cloud of a sample and the photons of two lasers creates an induced dipole moment within the molecule based on its polarizability, resulting in a pump energy loss (stimulated Raman loss, SRL) and a Stokes energy increase (stimulated Raman gain, SRG). The Raman signal can, therefore, be deduced from SRL or SRG, resulting in a high-fidelity Raman spectrum free from the nonresonant background. Moreover, the SRS signal exhibits Stimulated Raman scattering (SRS) microscopy is a nonlinear optical imaging method for visualizing chemical content based on molecular vibrational bonds. Featuring high speed, high resolution, high sensitivity, high accuracy, and 3D sectioning, SRS microscopy has made tremendous progress toward biochemical information acquisition, cellular function investigation, and label-free medical diagnosis in the biosciences. In this review, the principle of ...

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In Situ Stimulated Raman Scattering (SRS) Microscopy Study of the Dissolution of Sustained-Release Implant Formulation

Cited by 32 publications

References 46 publications

Denoising of stimulated Raman scattering microscopy images via deep learning

Denoising of stimulated Raman scattering microscopy images via deep learning

Coherent Raman Scattering Microscopy in Oncology Pharmacokinetic Research

Review of Stimulated Raman Scattering Microscopy Techniques and Applications in the Biosciences

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