Dr. Shikhar Uttam Profile

Dr. Shikhar Uttam

Assistant Professor at Univ of Pittsburgh

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Publications (13)

SPIE Journal Paper | 26 March 2024 Open Access

Perspective on quantitative phase imaging to improve precision cancer medicine

Yang Liu, Shikhar Uttam

JBO, Vol. 29, Issue S2, S22705, (March 2024) https://doi.org/10.1117/12.10.1117/1.JBO.29.S2.S22705

KEYWORDS: Cancer, Refractive index, Reflection, Biological samples, Tissues, Phase imaging, Tumors, 3D image processing, Medicine, Oncology

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SignificanceQuantitative phase imaging (QPI) offers a label-free approach to non-invasively characterize cellular processes by exploiting their refractive index based intrinsic contrast. QPI captures this contrast by translating refractive index associated phase shifts into intensity-based quantifiable data with nanoscale sensitivity. It holds significant potential for advancing precision cancer medicine by providing quantitative characterization of the biophysical properties of cells and tissue in their natural states.AimThis perspective aims to discuss the potential of QPI to increase our understanding of cancer development and its response to therapeutics. It also explores new developments in QPI methods towards advancing personalized cancer therapy and early detection.ApproachWe begin by detailing the technical advancements of QPI, examining its implementations across transmission and reflection geometries and phase retrieval methods, both interferometric and non-interferometric. The focus then shifts to QPI’s applications in cancer research, including dynamic cell mass imaging for drug response assessment, cancer risk stratification, and in-vivo tissue imaging.ResultsQPI has emerged as a crucial tool in precision cancer medicine, offering insights into tumor biology and treatment efficacy. Its sensitivity to detecting nanoscale changes holds promise for enhancing cancer diagnostics, risk assessment, and prognostication. The future of QPI is envisioned in its integration with artificial intelligence, morpho-dynamics, and spatial biology, broadening its impact in cancer research.ConclusionsQPI presents significant potential in advancing precision cancer medicine and redefining our approach to cancer diagnosis, monitoring, and treatment. Future directions include harnessing high-throughput dynamic imaging, 3D QPI for realistic tumor models, and combining artificial intelligence with multi-omics data to extend QPI’s capabilities. As a result, QPI stands at the forefront of cancer research and clinical application in cancer care.

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Proceedings Article | 16 March 2023 Presentation

Nanoscale nuclear architecture mapping of early carcinogenesis (Conference Presentation)

Shikhar Uttam

Proceedings Volume PC12389, PC123890O (2023) https://doi.org/10.1117/12.2659388

KEYWORDS: Tumor growth modeling, Optical coherence tomography, Cancer, Animal model studies

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Proceedings Article | 5 March 2021 Presentation

Nanoscale nuclear architecture mapping captures chromatin reorganization in epithelial cells undergoing malignant transformation

Shikhar Uttam, Jianquan Xu, Yang Liu

Proceedings Volume 11653, 1165318 (2021) https://doi.org/10.1117/12.2583147

KEYWORDS: Tumor growth modeling, Tumors, Tissues, Super resolution, Refractive index, Optical coherence tomography, Mouse models, Image analysis, Computer simulations, Computational modeling

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Proceedings Article | 22 July 2019 Paper

Three-dimensional nanoscale nuclear architecture mapping for improved cancer risk stratification

Shikhar Uttam, Yang Liu

Proceedings Volume 11076, 1107611 (2019) https://doi.org/10.1117/12.2526469

KEYWORDS: Cancer, Surveillance, Refractive index, Tissues, Spatial frequencies, Visualization, Biopsy

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Proceedings Article | 24 April 2017 Presentation

Improved cancer risk stratification and diagnosis via quantitative phase microscopy (Conference Presentation)

Yang Liu, Shikhar Uttam, Hoa Pham, Douglas Hartman

Proceedings Volume 10074, 1007416 (2017) https://doi.org/10.1117/12.2252276

KEYWORDS: Cell biology, Animal model studies, Cancer, Microscopy, Tissues, Pathology, Microscopes, Gold, Phase imaging, Diagnostics

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Proceedings Article | 8 March 2016 Paper

Theory of Fourier phase within the framework of Fourier-domain optical coherence tomography

Shikhar Uttam, Yang Liu

Proceedings Volume 9697, 96972S (2016) https://doi.org/10.1117/12.2214821

KEYWORDS: Optical coherence tomography, Refractive index, Interfaces, Spatial frequencies, Microscopy, Interferometry, Fourier optics, Signal processing, Statistical analysis, Numerical simulations, Scattering, Fourier transforms, Correlation function

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Proceedings Article | 8 March 2016 Presentation + Paper

Depth-resolved nanoscale nuclear architecture mapping for early prediction of cancer progression

Shikhar Uttam, Hoa Pham, Justin LaFace, Douglas Hartman, Yang Liu

Proceedings Volume 9697, 969728 (2016) https://doi.org/10.1117/12.2214688

KEYWORDS: Cancer, Tissue optics, Refractive index, Tissues, Absorbance, Image segmentation, Mouse models, Microscopes, Interfaces, Phase contrast

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SPIE Journal Paper | 4 June 2012 Open Access

Investigation of nuclear nano-morphology marker as a biomarker for cancer risk assessment using a mouse model

Rajan Bista, Shikhar Uttam, Douglas Hartman, Wei Qiu, Jian Yu, Lin Zhang, Randall Brand, Yang Liu

JBO, Vol. 17, Issue 06, 066014, (June 2012) https://doi.org/10.1117/12.10.1117/1.JBO.17.6.066014

KEYWORDS: Cancer, Tumors, Intestine, Mouse models, Statistical analysis, Oncology, Animal model studies, Microscopy, Tissues, Medicine

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The development of accurate and clinically applicable tools to assess cancer risk is essential to define candidates to undergo screening for early-stage cancers at a curable stage or provide a novel method to monitor chemoprevention treatments. With the use of our recently developed optical technology—spatial-domain low-coherence quantitative phase microscopy (SL-QPM), we have derived a novel optical biomarker characterized by structure-derived optical path length (OPL) properties from the cell nucleus on the standard histology and cytology specimens, which quantifies the nano-structural alterations within the cell nucleus at the nanoscale sensitivity, referred to as nano-morphology marker. The aim of this study is to evaluate the feasibility of the nuclear nano-morphology marker from histologically normal cells, extracted directly from the standard histology specimens, to detect early-stage carcinogenesis, assess cancer risk, and monitor the effect of chemopreventive treatment. We used a well-established mouse model of spontaneous carcinogenesis—ApcMin mice, which develop multiple intestinal adenomas (Min) due to a germline mutation in the adenomatous polyposis coli (Apc) gene. We found that the nuclear nano-morphology marker quantified by OPL detects the development of carcinogenesis from histologically normal intestinal epithelial cells, even at an early pre-adenomatous stage (six weeks). It also exhibits a good temporal correlation with the small intestine that parallels the development of carcinogenesis and cancer risk. To further assess its ability to monitor the efficacy of chemopreventive agents, we used an established chemopreventive agent, sulindac. The nuclear nano-morphology marker is reversed toward normal after a prolonged treatment. Therefore, our proof-of-concept study establishes the feasibility of the SL-QPM derived nuclear nano-morphology marker OPL as a promising, simple and clinically applicable biomarker for cancer risk assessment and evaluation of chemopreventive treatment.

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SPIE Journal Paper | 1 November 2011 Open Access

Correction of stain variations in nuclear refractive index of clinical histology specimens

Shikhar Uttam, Rajan Bista, Yang Liu, Douglas Hartman, Randall Brand

JBO, Vol. 16, Issue 11, 116013, (November 2011) https://doi.org/10.1117/12.10.1117/1.3650306

KEYWORDS: Refractive index, Tissues, Absorption, Pathology, Cancer, Animal model studies, Breast, Statistical modeling, Microscopy, Intestine

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SPIE Journal Paper | 1 July 2011 Open Access

Quantification of nanoscale nuclear refractive index changes during the cell cycle

Rajan Bista, Shikhar Uttam, Pin Wang, Kevin Staton, Randall Brand, Yang Liu, Serah Choi, Christopher Bakkenist, Douglas Hartman

JBO, Vol. 16, Issue 07, 070503, (July 2011) https://doi.org/10.1117/12.10.1117/1.3597723

KEYWORDS: Refractive index, Cancer, Microscopy, Flow cytometry, Medicine, Confocal microscopy, Diagnostics, Luminescence, Statistical analysis, Scattering

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SPIE Journal Paper | 1 November 2010 Open Access

Nanoscale nuclear architecture for cancer diagnosis beyond pathology via spatial-domain low-coherence quantitative phase microscopy

Pin Wang, Rajan Bista, Walid Khalbuss, Wei Qiu, Shikhar Uttam, Kevin Staton, Lin Zhang, Teresa Brentnall, Randall Brand, Yang Liu

JBO, Vol. 15, Issue 06, 066028, (November 2010) https://doi.org/10.1117/12.10.1117/1.3523618

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Proceedings Article | 19 August 2008 Paper

Direct reconstruction of difference images from optimal spatial-domain projections

Shikhar Uttam, Nathan Goodman, Mark Neifeld

Proceedings Volume 7096, 709608 (2008) https://doi.org/10.1117/12.795380

KEYWORDS: Imaging systems, Image restoration, Transmittance, Error analysis, Video, Performance modeling, Feature extraction, Sensors, Matrices, Computer engineering

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Proceedings Article | 19 August 2008 Paper

Optically multiplexed imaging with superposition space tracking

Shikhar Shikhar, Nathan Goodman, Mark Neifeld, Changsoon Kim, Jungsang Kim, David Brady

Proceedings Volume 7096, 709607 (2008) https://doi.org/10.1117/12.795150

KEYWORDS: Superposition, Computer programming, Multiplexing, Camera shutters, Imaging systems, Staring arrays, Optical tracking, Compressive imaging, Cameras, Sensors

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Showing 5 of 13 publications

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