Adam Glaser

Adam Glaser
Allen Institute · Neural Dynamics

Ph.D.

About

121
Publications
32,624
Reads
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2,169
Citations
Citations since 2017
59 Research Items
1758 Citations
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20172018201920202021202220230100200300
20172018201920202021202220230100200300
20172018201920202021202220230100200300
Additional affiliations
July 2019 - present
University of Washington Seattle
Position
  • Instructor
July 2015 - July 2019
University of Washington Seattle
Position
  • PostDoc Position
September 2010 - June 2015
Dartmouth College
Position
  • PhD Student
Education
September 2010 - May 2014
Dartmouth College
Field of study
  • Engineering Science
September 2006 - May 2010
Tufts University
Field of study
  • Mechanical Engineering

Publications

Publications (121)
Article
Full-text available
For the 1.7 million patients per year in the US who receive a new cancer diagnosis, treatment decisions are largely based on histopathological specimen examinations. Unfortunately, the gold standard of slide-based microscopic pathology suffers from high inter-observer variability and limited prognostic value due to sampling limitations and the inab...
Article
Full-text available
Recent advances in optical clearing and light-sheet microscopy have provided unprecedented access to structural and molecular information from intact tissues. However, current light-sheet microscopes have imposed constraints on the size, shape, number of specimens, and compatibility with various clearing protocols. Here we present a multi-immersion...
Article
Full-text available
Light-sheet microscopy has emerged as the preferred means for high-throughput volumetric imaging of cleared tissues. However, there is a need for a flexible system that can address imaging applications with varied requirements in terms of resolution, sample size, tissue-clearing protocol, and transparent sample-holder material. Here, we present a ‘...
Article
Fluorescence microscopy is a vital tool in biomedical research but faces considerable challenges in achieving uniform or bright labeling. For instance, fluorescent proteins are limited to model organisms, and antibody conjugates can be inconsistent and difficult to use with thick specimens. To partly address these challenges, we developed a labelin...
Article
High-throughput methods for slide-free three-dimensional (3D) pathological analyses of whole biopsies and surgical specimens offer the promise of modernizing traditional histology workflows and delivering improvements in diagnostic performance. Advanced optical methods now enable the interrogation of orders of magnitude more tissue than previously...
Article
italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Objective: For tumor resections, margin status typically correlates with patient survival but positive margin rates are generally high (up to 45% for head and neck cancer). Frozen section analysis (FSA) is often used to intraoperatively assess the marg...
Article
Full-text available
Functional implication of stromal heterogeneity in the prostate remains incompletely understood. Using lineage tracing and light-sheet imaging, we show that some fibroblast cells at the mouse proximal prostatic ducts and prostatic urethra highly express Lgr5. Genetic ablation of these anatomically restricted stromal cells, but not nonselective abla...
Preprint
Full-text available
Prostate cancer treatment decisions are heavily reliant upon the subjective visual interpretation (assigning Gleason patterns, or ISUP grade groups) of limited numbers of 2D histology sections. Under this paradigm, inter-observer variance is high, with ISUP grades not correlating well with the outcomes of individual patients, which contributes to t...
Article
Significance: For breast cancer patients, the extent of regional lymph node (LN) metastasis influences the decision to remove all axillary LNs. Metastases are currently identified and classified with visual analysis of a few thin tissue sections with conventional histology that may underrepresent the extent of metastases. Aim: We sought to enabl...
Article
Full-text available
Prostate cancer treatment planning is largely dependent upon examination of core-needle biopsies. The microscopic architecture of the prostate glands forms the basis for prognostic grading by pathologists. Interpretation of these convoluted three-dimensional (3D) glandular structures via visual inspection of a limited number of two-dimensional (2D)...
Preprint
Full-text available
Prostate cancer treatment planning is largely dependent upon examination of core-needle biopsies. In current clinical practice, the microscopic architecture of the prostate glands is what forms the basis for prognostic grading by pathologists. Interpretation of these convoluted 3D glandular structures via visual inspection of a limited number of 2D...
Preprint
Full-text available
Light-sheet microscopy has emerged as the preferred means for high-throughput volumetric imaging of cleared tissues. However, there is a need for a user-friendly system that can address imaging applications with varied requirements in terms of resolution (mesoscopic to sub-micrometer), sample geometry (size, shape, and number), and compatibility wi...
Conference Paper
1. Purpose We developed an annotation-free image-translation-based approach for 3D segmentation of prostate glands within 3D-histology datasets of whole biopsies stained with a low-cost and rapid-diffusing fluorescent analog of H&E. 2. Introduction The current diagnostic gold standard of histopathology provides a limited 2D view of complex 3D gland...
Article
Significance: Processing and diagnosing a set of 12 prostate biopsies using conventional histology methods typically take at least one day. A rapid and accurate process performed while the patient is still on-site could significantly improve the patient's quality of life. Aim: We develop and assess the feasibility of a one-hour-to-diagnosis (1Hr...
Article
Open-top light-sheet (OTLS) microscopes have been developed for user-friendly and versatile high-throughput 3D microscopy of thick specimens. As with all imaging modalities, spatial resolution trades off with imaging and analysis times. A hierarchical multi-scale imaging workflow would therefore be of value for many volumetric microscopy applicatio...
Article
Full-text available
Slide-free digital pathology techniques, including nondestructive 3D microscopy, are gaining interest as alternatives to traditional slide-based histology. In order to facilitate clinical adoption of these fluorescence-based techniques, software methods have been developed to convert grayscale fluorescence images into color images that mimic the ap...
Article
Light-sheet microscopy (LSM) has emerged as a powerful tool for high-speed volumetric imaging of live model organisms and large optically cleared specimens. When designing cleared-tissue LSM systems with certain desired imaging specifications (e.g. resolution, contrast, and working distance), various design parameters must be taken into considerati...
Preprint
Full-text available
Light-sheet microscopy (LSM) has emerged as a powerful tool for high-speed volumetric imaging of live model organisms and large optically cleared specimens. When designing cleared-tissue LSM systems with certain desired imaging specifications (e.g. resolution, contrast, and working distance), various design parameters must be taken into considerati...
Preprint
Full-text available
Light-sheet microscopy has emerged as the preferred means for high-throughput volumetric imaging of cleared tissues. However, there is a need for a user-friendly system that can address diverse imaging applications with varied requirements in terms of resolution (mesoscopic to sub-micron), sample geometry (size, shape, and number), and compatibilit...
Preprint
Full-text available
Slide-free digital pathology techniques, including nondestructive 3D microscopy, are gaining interest as alternatives to traditional slide-based histology. In order to facilitate clinical adoption of these fluorescence-based techniques, software methods have been developed to convert grayscale fluorescence images into color images that mimic the ap...
Article
Full-text available
Fluorescence microscopy is a workhorse tool in biomedical imaging but often poses substantial challenges to practitioners in achieving bright or uniform labeling. In addition, while antibodies are effective specific labels, their reproducibility is often inconsistent, and they are difficult to use when staining thick specimens. We report the use of...
Article
Handheld and endoscopic optical‐sectioning microscopes are being developed for noninvasive screening and intraoperative consultation. Imaging a large extent of tissue is often desired, but miniature in vivo microscopes tend to suffer from limited fields of view. To extend the imaging field during clinical use, we have developed a real‐time video mo...
Conference Paper
In recent years we have developed open-top light-sheet microscopes for a variety of clinical applications. Here we present a new light-sheet micro-dissection microscope for improved molecular analysis of intact tissue specimens.
Conference Paper
We report the development of a solid immersion meniscus lens (SIMlens), a wavefront-matching optical element for open-top light sheet microscopy that increases numerical aperture and enables multi-resolution imaging with air objectives.
Conference Paper
An ~45-minute workflow, consisting of fluorescence labeling, tissue clearing, and 3D non-destructive, open-top light-sheet (OTLS) microscopy, has been developed for diagnosis of 12 human prostate needle cores within an hour after biopsy.
Article
Open-top light-sheet (OTLS) microscopy has been developed for rapid volumetric imaging of large pathology specimens. A challenge with OTLS microscopy is the transmission of oblique illumination and detection beams through a horizontal sample plate without introducing aberrations. Previous solutions prevented vertical sample movement, constrained th...
Article
Full-text available
Context.—: Ex vivo microscopy encompasses a range of techniques to examine fresh or fixed tissue with microscopic resolution, eliminating the need to embed the tissue in paraffin or produce a glass slide. One such technique is light-sheet microscopy, which enables rapid 3D imaging. Our pathology-engineering collaboration has resulted in an open-to...
Article
Full-text available
Open-top light-sheet microscopy is a technique that can potentially enable rapid ex vivo inspection of large tissue surfaces and volumes. Here, we have optimized an open-top light-sheet (OTLS) microscope and image-processing workflow for the comprehensive examination of surgical margin surfaces, and have also developed a novel fluorescent analog of...
Preprint
Full-text available
Recent advances in optical clearing and light-sheet microscopy have provided unprecedented access to structural and molecular information from intact tissues. However, current light-sheet microscopes have imposed constraints on the size, shape, number of specimens, and compatibility with various clearing protocols. Here we present a multi-immersion...
Article
Full-text available
Intraoperative assessment of breast surgical margins will be of value for reducing the rate of re-excision surgeries for lumpectomy patients. While frozen-section histology is used for intraoperative guidance of certain cancers, it provides limited sampling of the margin surface (typically <1 % of the margin) and is inferior to gold-standard histol...
Conference Paper
Comprehensive pathology of fresh breast specimen surfaces has been achieved with a fluorescent analogue of H&E and a fully-automated MUSE system that incorporates 3D deconvolution to improve image quality.
Conference Paper
We present an easy-to-use multi-immersion open-top light-sheet microscope designed specifically for high-throughput imaging of tissues prepared with a variety of clearing protocols.
Conference Paper
A miniature line-scanned (LS) dual-axis confocal (DAC) microscope, with a 12-mm diameter distal tip, has been developed for high-speed (>15 Hz) microscopic imaging of tissue surfaces up to a depth of ~ 150 µm.
Conference Paper
Rapid and comprehensive surface microscopy of freshly excised breast specimens has been achieved with an optimized open-top light-sheet (OTLS) microscopy system in conjunction with an improved fluorescent analogue of H&E staining.
Article
Full-text available
Light-sheet fluorescence microscopy (LSFM) has emerged as a powerful method for rapid and optically efficient 3D microscopy. Initial LSFM designs utilized a static sheet of light, termed selective plane illumination microscopy (SPIM), which exhibited shadowing artifacts and deteriorated contrast due to light scattering. These issues have been addre...
Preprint
Light-sheet fluorescence microscopy (LSFM) has emerged as a powerful method for rapid and optically efficient 3D microscopy. Initial LSFM designs utilized a static sheet of light, termed selective plane illumination microscopy (SPIM), which exhibited shadowing artifacts and deteriorated contrast due to light scattering. These issues have been addre...
Conference Paper
We present the design of a pathology-optimized open-top light-sheet microscope for imaging fluorescently-labeled tissues. Initial imaging results from a variety of tissue types will be presented.
Article
Full-text available
In recent decades, various classes of nanoparticles have been developed for optical imaging of cancers. Many of these nanoparticles are designed to specifically target tumor sites, and specific cancer biomarkers, to facilitate the visualization of tumors. However, one challenge for accurate detection of tumors is that the molecular profiles of most...
Article
Intraoperative identification of carcinoma at lumpectomy margins would enable reduced re-excision rates, which are currently as high as 20-50%. While imaging of disease-associated biomarkers can identify malignancies with high specificity, multiplexed imaging of such biomarkers is necessary to detect molecularly heterogeneous carcinomas with high s...
Article
Full-text available
Cherenkov emission has a direct proportionality to the deposited dose at the local level, and capture of these emitted light signals allows visualization of real time maps of dose in vivo. Mapping the Cherenkov signals through water tanks illustrates how 3D Cherenkov can be achieved, either as 2D plus time, or 3D in static imaging. Imaging Cherenko...
Article
One of the main challenges for laser-scanning microscopy of biological tissues with refractive heterogeneities is the degradation in spatial resolution that occurs as a result of beam steering and distortion. This challenge is particularly significant for dual-axis confocal (DAC) microscopy, which achieves improved spatial-filtering and optical-sec...
Article
Full-text available
Current simulation methods for light transport in biological media have limited efficiency and realism when applied to three-dimensional microscopic light transport in biological tissues with refractive heterogeneities. We describe here a technique that combines a beam propagation method valid for modeling light transport in media with weak variati...
Article
This study's goal was to determine how Cherenkov radiation emission observed in radiotherapy is affected by predictable factors expected in patient imaging. Factors such as tissue optical properties, radiation beam properties, thickness of tissues, entrance/exit geometry, curved surface effects, curvature and imaging angles were investigated throug...
Article
Purpose:The irradiation of photodynamic agents with radiotherapy beams has been demonstrated to enhance tumor killing in various studies, and one proposed mechanism is the optical fluence of Cherenkov emission activating the photosensitizer. This mechanism is explored in Monte Carlo simulations of fluence as well as laboratory measurements of fluen...
Conference Paper
External beam radiotherapy utilizes high energy radiation to target cancer with dynamic, patient-specific treatment plans. The otherwise invisible radiation beam can be observed via the optical Cherenkov photons emitted from interaction between the high energy beam and tissue. Using a specialized camera-system, the Cherenkov emission can thus be us...
Conference Paper
Cherenkov imaging during radiotherapy is a method by which an optical analog for the high-energy radiation beam can be observed directly on the surface of the patient. While simple geometries and volumes demonstrate a strong correlation between Cherenkov emission intensity and surface dose, in vivo data collected from 14 whole-breast patients has n...
Article
Full-text available
There is a need for miniature optical-sectioning microscopes to enable in vivo interrogation of tissues as a real-time and noninvasive alternative to gold-standard histopathology. Such devices could have a transformative impact for the early detection of cancer as well as for guiding tumor-resection procedures. Miniature confocal microscopes have b...
Article
Full-text available
Light sheet microscopy (LSM) has emerged as an optical-imaging method for high spatiotemporal volumetric imaging of relatively transparent samples. While this capability has allowed the technique to be highly impactful in fields such as developmental biology, applications involving highly scattering thick tissues have been largely unexplored. Herei...
Article
Purpose: A method was developed utilizing Cherenkov imaging for rapid and thorough determination of the two gantry angles that produce the most uniform treatment plane during dual-field total skin electron beam therapy (TSET).
Conference Paper
A novel simulation method for light scattering in heterogeneous biological tissue based on the beam propagation method (BPM) in a fractal continuous medium is presented, with implications for a variety of biophotonics applications.
Conference Paper
We employ Monte Carlo simulations to assess the performance of light sheet microscopy (LSM) in large, highly scattering tissues, and present a novel system design which addresses logistical challenges in using LSM for non-transparent samples.
Article
Full-text available
Cherenkov radiation has recently emerged as an interesting phenomenon for a number of applications in the biomedical sciences. Its unique properties, including broadband emission spectrum, spectral weight in the ultraviolet and blue wavebands, and local generation of light within a given tissue, have made it an attractive new source of light within...
Article
Full-text available
To test the use of a three-dimensional (3D) optical cone beam computed tomography reconstruction algorithm, for estimation of the imparted 3D dose distribution from megavoltage photon beams in a water tank for quality assurance, by imaging the induced Cherenkov-excited fluorescence (CEF). An intensified charge-coupled device coupled to a standard n...
Article
A new imaging modality Cherenkov-excited luminescence scanned imaging (CELSI) is demonstrated illustrating that LINAC beams induce Cherenkov emission within tissue, and that in-turn can excite luminescence of optical probes. This is achieved in a highly spatially confined fashion thereby allowing scanned imaging of distributions of luminescent sour...
Article
To determine the feasibility of using real-time imaging of Cherenkov light emission from an object's surface for the qualitative identification of radiation 'mistakes'. A highly sensitive camera was used to image the Cherenkov light emitted for a solid water phantom. A Varian 2100CD was used to deliver 500 MU for a 6 MV photon beam operating a dose...
Article
To investigate the positional accuracy possible with real time Cherenkov video imaging based patient positioning and movement tracking during EBRT. In a phase 1 clinical trial, including 12 patients undergoing post-lumpectomy whole breast irradiation, Cherenkov emission was imaged with a time-gated ICCD camera synchronized to the LINAC pulse output...
Article
To evaluate treatment field heterogeneity resulting from gantry angle choice in total skin electron beam therapy (TSEBT) following a modified Stanford dual-field technique, and determine a relationship between source to surface distance (SSD) and optimized gantry angle spread. Cherenkov imaging was used to image 62 treatment fields on a sheet of 1....