Simultaneous cancer and tumor microenvironment subtyping using confocal infrared microscopy for all-digital molecular histopathology

Mittal, Shachi; Yeh, Kevin; Leslie, L. Suzanne; Kenkel, Seth; Kajdacsy-Balla, André; Bhargava, Rohit

doi:10.1073/pnas.1719551115

Cited by 119 publications

(129 citation statements)

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“…For a single image, we estimate that the presented upconversion system is in the order of 500 times faster than the FTIR system when using 4-8 mW of incoherent mid-IR light incident on the sample. The number of images needed for computer-assisted classification of biopsies may be as low as 10-20 [36], suggesting that a continuous spectrum is not required. A small number of images will, therefore, favor the upconversion system for this application.…”

Section: Experimental Setup and Resultsmentioning

confidence: 99%

“…Moreover, for HSI, large data storage and complex postprocessing software is currently needed to transform raw data into useful information [14]. Recent developments in mid-IR hyperspectral microscopy include tunable quantum cascade laser (QCL) illumination combined with either raster scanning [15] or microbolometer array detectors [16]. These systems have shown their potential to outperform FTIR systems for special applications; however, they still rely on direct detection of the mid-IR signal.…”

Section: Introductionmentioning

confidence: 99%

“…We report on the use of mid-IR upconversion imaging using a silicon-based camera, demonstrating unsupervised computerassisted classification of biopsy sections in the 3-4 μm wavelength range. It is generally recognized that the 5-12 μm range is preferred in terms of chemical specificity [15,16]; however, the 3-4 μm wavelength range has also shown relevant chemical features [26] and has the additional advantage of being compatible with existing glass substrates (microscope slides) used presently in clinics [27]. Using the k-means algorithm, an unsupervised spectral clustering method based on spectral similarity of different regions of the sample, each pixel acquired from the tissue sample were segmented into groups, comparable to the histotypes identified by an expert gastrointestinal histopathologist.…”

Section: Introductionmentioning

confidence: 99%

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Video-rate, mid-infrared hyperspectral upconversion imaging

Junaid¹,

Kumar²,

Mathez³

et al. 2019

Optica

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In this work we demonstrate, to the best of our knowledge, a novel wide field-of-view upconversion system, supporting upconversion of monochromatic mid-infrared (mid-IR) images, e.g., for hyperspectral imaging (HSI). An optical parametric oscillator delivering 20 ps pulses tunable in the 2.3-4 μm range acts as a monochromatic mid-IR illumination source. A standard CCD camera, in synchronism with the crystal rotation of the upconversion system, acquires in only 2.5 ms the upconverted mid-IR images containing 64 kpixels, thereby eliminating the need for postprocessing. This approach is generic in nature and constitutes a major simplification in realizing video-frame-rate mid-IR monochromatic imaging. A second part of this paper includes a proof-of-principle study on esophageal tissues samples, from a tissue microarray, in the 3-4 μm wavelength range. The use of mid-IR HSI for investigation of esophageal cancers is particularly promising as it allows for a much faster and possibly more observer-independent workflow than state-ofthe-art histology. Comparing histologically stained sections evaluated by a pathologist to images obtained by either Fourier transform IR or upconversion HSI based on machine learning shows great promise for further work pointing towards clinical translation using the presented mid-IR HSI upconversion system.

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Section: Experimental Setup and Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Video-rate, mid-infrared hyperspectral upconversion imaging

Junaid¹,

Kumar²,

Mathez³

et al. 2019

Optica

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“…IR spectroscopic imaging is based on the molecular vibration of materials and has been widely used for chemical identification and analysis based on the characteristic spectra of materials in the infrared frequency region. Because most materials show unique spectra in infrared range, IR spectral imaging has shown the great usefulness as an important analytical tool, especially in chemical and biological imaging . The advances of IR spectral imaging have thus been pushed over years, and as a mature technique, there are many types of Fourier‐transform infrared spectroscopy (FTIR)‐based commercial products.…”

Section: Spectroscopic Imagingmentioning

confidence: 99%

Microscale Spectroscopic Mapping of 2D Optical Materials

Dong

Yetisen

Köhler

et al. 2019

Advanced Optical Materials

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be used for flexible touch screens and displays, printable electronics, and thinfilm photovoltaics, [4] while FETs made of graphene can be used for highly sensitive biosensors. [5] Another 2D material MoS 2 , a direct-bandgap semiconductor, has applications in ultrasensitive photodetectors, transistors, and gas-sensing devices. [6][7][8][9] Other 2D materials have also shown potential in photovoltaic devices, memory, and light-emitting diodes (LEDs). [10,11] Broad application potential of 2D materials in optoelectronic devices, photonic devices, and optical sensors is mainly based on their unique optical performances. [12] 2D materials can be fabricated based on their layered structure. In the molecular structures of these materials, the atoms are bonded hard in the same plane, but the bond effect between two lateral layers is weak due to van der Waals forces. [13] 2D materials can be roughly categorized as semimetal like graphene, semiconductor like transition metal dichalcogenides (TMDs), and insulator like hexagonal boron nitride (hBN) from the aspect of bandgap differences. [14] Due to the experimentally practical manipulation of monolayer and multilayer 2D materials, remarkable optical performances can be realized for a wide range of optical applications. For example, the number of layers of 2D materials can strongly influence the photoluminescence performance. [15] The unconventional optical performances including adsorption and emission, light sensitivity, as well as plasmonic effects of 2D materials are closely related to their inner physical properties such as carrier mobility, density of states, and band structure based on the interaction of atoms, structural symmetry, and stacking patterns. [16,17] Through the control of layer number which could influence the bandgap value, 2D materials could react to different spectrum ranging from ultraviolet to infrared light. [18] Doping strategies are also effective to modify intrinsic 2D semiconductors and improve the response with respect to an extended range of spectrum. [19,20] The assessment of the optical properties of 2D materials is indispensable for device and sensor development. [21] Based on detailed surface mapping and spectral information, the suitability of 2D materials for optical devices or sensor applications can be thoroughly studied. [22,23] Microscopy, direct 2D mapping of materials, can provide basic spatial information, [24] while spectroscopy can offer one more dimensional spectral information which is 2D materials have unique optical properties due to their ultrathin layered structures, and are emerging as promising materials for optoelectronic devices. To characterize and evaluate these properties, diffraction-limited spectroscopic mapping, also known as microscale spectroscopic imaging, has been developed to provide abundant spatial and spectral information. The usefulness of microscale spectroscopic mapping for unique property study of 2D optical materials is addressed. Advances in both mature and growing microscale spectroscopic mapping...

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“…By tuning to a molecular absorbance wavelength of interest, real-time molecular imaging can be utilized for immediate unstained tissue analysis. Furthermore, for advanced spectral predication of disease, the Bhargava group has shown that using a confocal Agilent microscope with a QCL source coupled to a Mercury Cadmium Telluride (MCT) detector it was possible to screen automatically breast tissue biopsies (1 mm diameter) in ~1 hour, in High Definition [21].…”

Section: Introductionmentioning

confidence: 99%

Upconversion raster scanning microscope for long-wavelength infrared imaging of breast cancer microcalcifications

Tseng¹,

Bouzy²,

Pedersen³

et al. 2018

Biomed. Opt. Express

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Long-wavelength identification of microcalcifications in breast cancer tissue is demonstrated using a novel upconversion raster scanning microscope. The system consists of quantum cascade lasers (QCL) for illumination and an upconversion system for efficient, high-speed detection using a silicon detector. Absorbance spectra and images of regions of ductal carcinoma in situ (DCIS) from the breast have been acquired using both upconversion and Fourier-transform infrared (FTIR) systems. The spectral images are compared and good agreement is found between the upconversion and the FTIR systems.

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Simultaneous cancer and tumor microenvironment subtyping using confocal infrared microscopy for all-digital molecular histopathology

Cited by 119 publications

References 56 publications

Video-rate, mid-infrared hyperspectral upconversion imaging

Video-rate, mid-infrared hyperspectral upconversion imaging

Microscale Spectroscopic Mapping of 2D Optical Materials

Upconversion raster scanning microscope for long-wavelength infrared imaging of breast cancer microcalcifications

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