All-digital histopathology by infrared-optical hybrid microscopy

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Optical microscopy for biomedical samples requires expertise in staining to visualize structure and composition. Midinfrared (mid-IR) spectroscopic imaging offers label-free molecular recording and virtual staining by probing fundamental vibrational modes of molecular components. This quantitative signal can be combined with machine learning to enable microscopy in diverse fields from cancer diagnoses to forensics. However, absorption of IR light by common optical imaging components makes mid-IR light incompatible with modern optical microscopy and almost all biomedical research and clinical workflows. Here we conceptualize an IR-optical hybrid (IR-OH) approach that sensitively measures molecular composition based on an optical microscope with wide-field interferometric detection of absorption-induced sample expansion. We demonstrate that IR-OH exceeds state-of-the-art IR microscopy in coverage (10-fold), spatial resolution (fourfold), and spectral consistency (by mitigating the effects of scattering). The combined impact of these advances allows full slide infrared absorption images of unstained breast tissue sections on a visible microscope platform. We further show that automated histopathologic segmentation and generation of computationally stained (stainless) images is possible, resolving morphological features in both color and spatial detail comparable to current pathology protocols but without stains or human interpretation. IR-OH is compatible with clinical and research pathology practice and could make for a cost-effective alternative to conventional stain-based protocols for stainless, all-digital pathology.

Related collections

Most cited references 63

Record: found
Abstract: found
Article: not found

Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy.

Christian W. Freudiger, Wei Min, Brian Saar … (2008)

Label-free chemical contrast is highly desirable in biomedical imaging. Spontaneous Raman microscopy provides specific vibrational signatures of chemical bonds, but is often hindered by low sensitivity. Here we report a three-dimensional multiphoton vibrational imaging technique based on stimulated Raman scattering (SRS). The sensitivity of SRS imaging is significantly greater than that of spontaneous Raman microscopy, which is achieved by implementing high-frequency (megahertz) phase-sensitive detection. SRS microscopy has a major advantage over previous coherent Raman techniques in that it offers background-free and readily interpretable chemical contrast. We show a variety of biomedical applications, such as differentiating distributions of omega-3 fatty acids and saturated lipids in living cells, imaging of brain and skin tissues based on intrinsic lipid contrast, and monitoring drug delivery through the epidermis.

0 comments Cited 442 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Using Fourier transform IR spectroscopy to analyze biological materials.

Matthew J Baker, Júlio Trevisan, Paul Bassan … (2014)

IR spectroscopy is an excellent method for biological analyses. It enables the nonperturbative, label-free extraction of biochemical information and images toward diagnosis and the assessment of cell functionality. Although not strictly microscopy in the conventional sense, it allows the construction of images of tissue or cell architecture by the passing of spectral data through a variety of computational algorithms. Because such images are constructed from fingerprint spectra, the notion is that they can be an objective reflection of the underlying health status of the analyzed sample. One of the major difficulties in the field has been determining a consensus on spectral pre-processing and data analysis. This manuscript brings together as coauthors some of the leaders in this field to allow the standardization of methods and procedures for adapting a multistage approach to a methodology that can be applied to a variety of cell biological questions or used within a clinical setting for disease screening or diagnosis. We describe a protocol for collecting IR spectra and images from biological samples (e.g., fixed cytology and tissue sections, live cells or biofluids) that assesses the instrumental options available, appropriate sample preparation, different sampling modes as well as important advances in spectral data acquisition. After acquisition, data processing consists of a sequence of steps including quality control, spectral pre-processing, feature extraction and classification of the supervised or unsupervised type. A typical experiment can be completed and analyzed within hours. Example results are presented on the use of IR spectra combined with multivariate data processing.

0 comments Cited 416 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

All-optical machine learning using diffractive deep neural networks

Mona Jarrahi, Yair Rivenson, Nezih. T. Yardimci … (2018)

Deep learning has been transforming our ability to execute advanced inference tasks using computers. We introduce a physical mechanism to perform machine learning by demonstrating an all-optical Diffractive Deep Neural Network (D2NN) architecture that can implement various functions following the deep learning-based design of passive diffractive layers that work collectively. We create 3D-printed D2NNs that implement classification of images of handwritten digits and fashion products as well as the function of an imaging lens at terahertz spectrum. Our all-optical deep learning framework can perform, at the speed of light, various complex functions that computer-based neural networks can implement, and will find applications in all-optical image analysis, feature detection and object classification, also enabling new camera designs and optical components that perform unique tasks using D2NNs.