Point-of-Care Pathology with Miniature Microscopes

Liu, Jonathan; Loewke, Nathan O.; Mandella, Michael J.; Levenson, Richard M.; Crawford, James M.; Contag, Christopher H.

doi:10.1155/2011/657403

Cited by 49 publications

(33 citation statements)

References 0 publications

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“…Fluorescence endomicroscopy provides high resolution images of tissue in vivo via flexible probes 41,42 and is one of the most widely used and clinically validated optical biopsy techniques (FIG. 3).…”

Section: Biomarkers For Eedmentioning

confidence: 99%

The potential role of optical biopsy in the study and diagnosis of environmental enteric dysfunction

Thompson

Hughes

Anastasova

et al. 2017

Nat Rev Gastroenterol Hepatol

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| Environmental enteric dysfunction (EED) is a disease of the small intestine affecting children and adults in low and middle income countries. Arising as a consequence of repeated infections, gut inflammation results in impaired intestinal absorptive and barrier function, leading to poor nutrient uptake and ultimately to stunting and other developmental limitations. Progress towards new biomarkers and interventions for EED is hampered by the practical and ethical difficulties of cross-validation with the gold standard of biopsy and histology. Optical biopsy techniques -which can provide minimally invasive or noninvasive alternatives to biopsy -could offer other routes to validation and could potentially be used as point-of-care tests among the general population. This Consensus Statement identifies and reviews the most promising candidate optical biopsy technologies for applications in EED, critically assesses them against criteria identified for successful deployment in developing world settings, and proposes further lines of enquiry. Importantly, many of the techniques discussed could also be adapted to monitor the impaired intestinal barrier in other settings such as IBD, autoimmune enteropathies, coeliac disease, graft-versus-host disease, small intestinal transplantation or critical care. Members of the board and experts met to discuss the horizon scan in London, UK, in November 2015 and San Francisco, USA, in February 2016. Literature searches were performed using Web of Science, as well as through the advice of the advisory board and experts. The results of the horizon scan are presented in this Consensus Statement, which entails a review of EED, a discussion of technologies deemed relevant to EED (based on literature searches and the opinions of the advisory board and experts), and a series of recommendations for the future application of the rele vant technologies to the study and diagnosis of EED. In the Recommendations section, each technology has been assessed according to its suitability for application to EED and this assessment includes an evaluation of the cost, invasiveness and appropriateness for developing countries of each device and/or technique. This assessment was performed in a qualitative manner based on currently available information (for example, the present cost and size of the devices) and the opinions of the authors as to feasible future develop ment. Technique suitability for use in developing countries was determined in a qualitative manner after consideration of the need for advanced infrastructure and high levels of training for either system use or data analysis. Probable deployment time scales have also been assigned to each technique based on the current states of development and the degree of valid ation work that will be required before application to EED. These timescales have been tentatively defined as short-term (suitable for deployment immediately or within ~1 year), mediumterm (suit able for deployment within ~1-3 years) and long-term (suitable for deployme...

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Section: Biomarkers For Eedmentioning

confidence: 99%

The potential role of optical biopsy in the study and diagnosis of environmental enteric dysfunction

Thompson

Hughes

Anastasova

et al. 2017

Nat Rev Gastroenterol Hepatol

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“…3 and summarized in Table 1. For the PS-DAC geometry, NA i and NA c of 0.20 were used, similar to previous reports [9][10][11][12][13]. The LS-DAC geometry was identical to the PS-DAC geometry, except that in this case (as described previously) a line of illumination was used, i.e.…”

Section: Dac and Lsm Imaging Geometriesmentioning

confidence: 99%

“…al. [8]), which have successfully been utilized for reflectance and fluorescence imaging of thick, highly scattering tissues in a number of ex-vivo and in-vivo studies [9][10][11][12][13][14]. Furthermore, recent reports have demonstrated LSM in novel "open-top" or "inverted" imaging geometries that are more compatible for the imaging of conventionally mounted specimens of arbitrary size [15][16][17], as well as the use of confocal line detection for improved contrast in scattering samples [18].…”

Section: Introductionmentioning

confidence: 99%

Assessing the imaging performance of light sheet microscopies in highly scattering tissues

Glaser

Wang

Liu

2016

Biomed. Opt. Express

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Light sheet microscopy (LSM) has emerged as an opticalimaging 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. Herein, we employ Monte Carlo simulations to explore the use of LSM for imaging turbid media. In particular, due to its similarity to dual-axis confocal (DAC) microscopy, we compare LSM performance to pointscanned (PS-DAC) and line-scanned (LS-DAC) dual-axis confocal microscopy techniques that have been previously shown to produce highquality images at round-trip optical lengths of ~9 -10 and ~3 -4 respectively. The results of this study indicate that LSM using widefield collection (WF-LSM) provides comparable performance to LS-DAC in thick tissues, due to the fact that they both utilize an illumination beam focused in one dimension (i.e. a line or sheet). On the other hand, LSM using confocal line detection (CL-LSM) is more analogous to PS-DAC microscopy, in which the illumination beam is focused in two dimensions to a point. The imaging depth of LSM is only slightly inferior to DAC (~2 -3 and ~6 -7 optical lengths for WF-LSM and CL-LSM respectively) due to the use of a lower numerical aperture (NA) illumination beam for extended imaging along the illumination axis. Therefore, we conclude that the ability to image deeply is dictated most by the confocality of the microscope technique. In addition, we find that imaging resolution is mostly dependent on the collection NA, and is relatively invariant to imaging depth in a homogeneous scattering medium. Our results indicate that superficial imaging of highly scattering tissues using light sheet microscopy is possible.

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“…To enable noninvasive real-time pathology (optical biopsy) of fresh tissues [1][2][3], improving the depth of optical sectioning is of high priority and would provide a broad clinical impact. For example, 90% of cancers originate in epithelial tissues and metastasize by invading into the underlying stroma [4].…”

Section: Introductionmentioning

confidence: 99%

Modulated-alignment dual-axis (MAD) confocal microscopy for deep optical sectioning in tissues

Leigh¹,

Chen²,

Liu³

2014

Biomed. Opt. Express

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Abstract:A strategy is presented to enable optical-sectioning microscopy with improved contrast and imaging depth using low-power (0.5 -1 mW) diode laser illumination. This technology combines the inherent strengths of focal-modulation microscopy and dual-axis confocal (DAC) microscopy for rejecting out-of-focus and multiply scattered background light in tissues. The DAC architecture is unique in that it utilizes an intersecting pair of illumination and collection beams to improve the spatial-filtering and optical-sectioning performance of confocal microscopy while focal modulation selectively 'labels' in-focus signals via amplitude modulation. Simulations indicate that modulating the spatial alignment of dual-axis beams at a frequency f generates signals from the focal volume of the microscope that are modulated at 2f with minimal modulation of background signals, thus providing nearly an order-of-magnitude improvement in optical-sectioning contrast compared to DAC microscopy alone. Experiments show that 2f lock-in detection enhances contrast and imaging depth within scattering phantoms and fresh tissues.

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Point-of-Care Pathology with Miniature Microscopes

Cited by 49 publications

References 0 publications

The potential role of optical biopsy in the study and diagnosis of environmental enteric dysfunction

The potential role of optical biopsy in the study and diagnosis of environmental enteric dysfunction

Assessing the imaging performance of light sheet microscopies in highly scattering tissues

Modulated-alignment dual-axis (MAD) confocal microscopy for deep optical sectioning in tissues

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