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Pivovarov, Misha

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Pivovarov

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Misha

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Pivovarov, Misha
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    Holographic Assessment of Lymphoma Tissue (HALT) for Global Oncology Field Applications
    (Ivyspring International Publisher, 2016) Pathania, Divya; Im, Hyungsoon; Kilcoyne, Aoife; Sohani, Aliyah R.; Fexon, Lioubov; Pivovarov, Misha; Abramson, Jeremy; Randall, Thomas; Chabner, Bruce; Weissleder, Ralph; Lee, Hakho; Castro, Cesar
    Low-cost, rapid and accurate detection technologies are key requisites to cope with the growing global cancer challenges. The need is particularly pronounced in resource-limited settings where treatment opportunities are often missed due to the absence of timely diagnoses. We herein describe a Holographic Assessment of Lymphoma Tissue (HALT) system that adopts a smartphone as the basis for molecular cancer diagnostics. The system detects malignant lymphoma cells labeled with marker-specific microbeads that produce unique holographic signatures. Importantly, we optimized HALT to detect lymphomas in fine-needle aspirates from superficial lymph nodes, procedures that align with the minimally invasive biopsy needs of resource-constrained regions. We equipped the platform to directly address the practical needs of employing novel technologies for “real world” use. The HALT assay generated readouts in <1.5 h and demonstrated good agreement with standard cytology and surgical pathology.
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    Sparsity-Based Pixel Super Resolution for Lens-Free Digital In-line Holography
    (Nature Publishing Group, 2016) Song, Jun; Leon Swisher, Christine; Im, Hyungsoon; Jeong, Sangmoo; Pathania, Divya; Iwamoto, Yoshiko; Pivovarov, Misha; Weissleder, Ralph; Lee, Hakho
    Lens-free digital in-line holography (LDIH) is a promising technology for portable, wide field-of-view imaging. Its resolution, however, is limited by the inherent pixel size of an imaging device. Here we present a new computational approach to achieve sub-pixel resolution for LDIH. The developed method is a sparsity-based reconstruction with the capability to handle the non-linear nature of LDIH. We systematically characterized the algorithm through simulation and LDIH imaging studies. The method achieved the spatial resolution down to one-third of the pixel size, while requiring only single-frame imaging without any hardware modifications. This new approach can be used as a general framework to enhance the resolution in nonlinear holographic systems.
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    The global cardiovascular magnetic resonance registry (GCMR) of the society for cardiovascular magnetic resonance (SCMR): its goals, rationale, data infrastructure, and current developments
    (BioMed Central, 2017) Kwong, Raymond; Petersen, Steffen E.; Schulz-Menger, Jeanette; Arai, Andrew E.; Bingham, Scott E.; Chen, Yucheng; Choi, Yuna L.; Cury, Ricardo C.; Ferreira, Vanessa M.; Flamm, Scott D.; Steel, Kevin; Bandettini, W. Patricia; Martin, Edward T.; Nallamshetty, Leelakrishna; Neubauer, Stefan; Raman, Subha V.; Schelbert, Erik B.; Valeti, Uma S.; Cao, Jie Jane; Reichek, Nathaniel; Young, Alistair A.; Fexon, Lyuba; Pivovarov, Misha; Ferrari, Victor A.; Simonetti, Orlando P.
    Background: With multifaceted imaging capabilities, cardiovascular magnetic resonance (CMR) is playing a progressively increasing role in the management of various cardiac conditions. A global registry that harmonizes data from international centers, with participation policies that aim to be open and inclusive of all CMR programs, can support future evidence-based growth in CMR. Methods: The Global CMR Registry (GCMR) was established in 2013 under the auspices of the Society for Cardiovascular Magnetic Resonance (SCMR). The GCMR team has developed a web-based data infrastructure, data use policy and participation agreement, data-harmonizing methods, and site-training tools based on results from an international survey of CMR programs. Results: At present, 17 CMR programs have established a legal agreement to participate in GCMR, amongst them 10 have contributed CMR data, totaling 62,456 studies. There is currently a predominance of CMR centers with more than 10 years of experience (65%), and the majority are located in the United States (63%). The most common clinical indications for CMR have included assessment of cardiomyopathy (21%), myocardial viability (16%), stress CMR perfusion for chest pain syndromes (16%), and evaluation of etiology of arrhythmias or planning of electrophysiological studies (15%) with assessment of cardiomyopathy representing the most rapidly growing indication in the past decade. Most CMR studies involved the use of gadolinium-based contrast media (95%). Conclusions: We present the goals, mission and vision, infrastructure, preliminary results, and challenges of the GCMR. Trial registration Identification number on ClinicalTrials.gov: NCT02806193. Registered 17 June 2016. Electronic supplementary material The online version of this article (doi:10.1186/s12968-016-0321-7) contains supplementary material, which is available to authorized users.
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    PepBank - A Database of Peptides Based on Sequence Text Mining and Public Peptide Data Sources
    (BioMed Central, 2007) Shtatland, Timur; Guettler, Daniel; Kossodo, Misha; Pivovarov, Misha; Weissleder, Ralph
    Background: Peptides are important molecules with diverse biological functions and biomedical uses. To date, there does not exist a single, searchable archive for peptide sequences or associated biological data. Rather, peptide sequences still have to be mined from abstracts and full-length articles, and/or obtained from the fragmented public sources. Description: We have constructed a new database (PepBank), which at the time of writing contains a total of 19,792 individual peptide entries. The database has a web-based user interface with a simple, Google-like search function, advanced text search, and BLAST and Smith-Waterman search capabilities. The major source of peptide sequence data comes from text mining of MEDLINE abstracts. Another component of the database is the peptide sequence data from public sources (ASPD and UniProt). An additional, smaller part of the database is manually curated from sets of full text articles and text mining results. We show the utility of the database in different examples of affinity ligand discovery. Conclusion: We have created and maintain a database of peptide sequences. The database has biological and medical applications, for example, to predict the binding partners of biologically interesting peptides, to develop peptide based therapeutic or diagnostic agents, or to predict molecular targets or binding specificities of peptides resulting from phage display selection. The database is freely available on http://pepbank.mgh.harvard.edu, and the text mining source code (Peptide::Pubmed) is freely available above as well as on CPAN (http://www.cpan.org/).
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    Enhancing Navigation in Biomedical Databases by Community Voting and Database-Driven Text Classification
    (BioMed Central, 2009) Duchrow, Timo; Shtatland, Timur; Guettler, Daniel; Pivovarov, Misha; Kramer, Stefan; Weissleder, Ralph
    Background: The breadth of biological databases and their information content continues to increase exponentially. Unfortunately, our ability to query such sources is still often suboptimal. Here, we introduce and apply community voting, database-driven text classification, and visual aids as a means to incorporate distributed expert knowledge, to automatically classify database entries and to efficiently retrieve them. Results: Using a previously developed peptide database as an example, we compared several machine learning algorithms in their ability to classify abstracts of published literature results into categories relevant to peptide research, such as related or not related to cancer, angiogenesis, molecular imaging, etc. Ensembles of bagged decision trees met the requirements of our application best. No other algorithm consistently performed better in comparative testing. Moreover, we show that the algorithm produces meaningful class probability estimates, which can be used to visualize the confidence of automatic classification during the retrieval process. To allow viewing long lists of search results enriched by automatic classifications, we added a dynamic heat map to the web interface. We take advantage of community knowledge by enabling users to cast votes in Web 2.0 style in order to correct automated classification errors, which triggers reclassification of all entries. We used a novel framework in which the database "drives" the entire vote aggregation and reclassification process to increase speed while conserving computational resources and keeping the method scalable. In our experiments, we simulate community voting by adding various levels of noise to nearly perfectly labelled instances, and show that, under such conditions, classification can be improved significantly. Conclusion: Using PepBank as a model database, we show how to build a classification-aided retrieval system that gathers training data from the community, is completely controlled by the database, scales well with concurrent change events, and can be adapted to add text classification capability to other biomedical databases. The system can be accessed at .
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    Born Normalization for Fluorescence Optical Projection Tomography for Whole Heart Imaging
    (MyJove Corporation, 2009) Vinegoni, Claudio; Razansky, Daniel; Figueiredo, Jose-Luiz; Fexon, Lyuba; Pivovarov, Misha; Nahrendorf, Matthias; Ntziachristos, Vasilis; Weissleder, Ralph
    Optical projection tomography is a three-dimensional imaging technique that has been recently introduced as an imaging tool primarily in developmental biology and gene expression studies. The technique renders biological sample optically transparent by first dehydrating them and then placing in a mixture of benzyl alcohol and benzyl benzoate in a 2:1 ratio (BABB or Murray s Clear solution). The technique renders biological samples optically transparent by first dehydrating them in graded ethanol solutions then placing them in a mixture of benzyl alcohol and benzyl benzoate in a 2:1 ratio (BABB or Murray s Clear solution) to clear. After the clearing process the scattering contribution in the sample can be greatly reduced and made almost negligible while the absorption contribution cannot be eliminated completely. When trying to reconstruct the fluorescence distribution within the sample under investigation, this contribution affects the reconstructions and leads, inevitably, to image artifacts and quantification errors.. While absorption could be reduced further with a permanence of weeks or months in the clearing media, this will lead to progressive loss of fluorescence and to an unrealistically long sample processing time. This is true when reconstructing both exogenous contrast agents (molecular contrast agents) as well as endogenous contrast (e.g. reconstructions of genetically expressed fluorescent proteins).