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dc.contributor.authorYabusaki, Katsumien_US
dc.contributor.authorHutcheson, Joshua D.en_US
dc.contributor.authorVyas, Payalen_US
dc.contributor.authorBertazzo, Sergioen_US
dc.contributor.authorBody, Simon C.en_US
dc.contributor.authorAikawa, Masanorien_US
dc.contributor.authorAikawa, Elenaen_US
dc.date.accessioned2016-12-02T15:25:02Z
dc.date.issued2016en_US
dc.identifier.citationYabusaki, Katsumi, Joshua D. Hutcheson, Payal Vyas, Sergio Bertazzo, Simon C. Body, Masanori Aikawa, and Elena Aikawa. 2016. “Quantification of Calcified Particles in Human Valve Tissue Reveals Asymmetry of Calcific Aortic Valve Disease Development.” Frontiers in Cardiovascular Medicine 3 (1): 44. doi:10.3389/fcvm.2016.00044. http://dx.doi.org/10.3389/fcvm.2016.00044.en
dc.identifier.issn2297-055Xen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:29626118
dc.description.abstractRecent studies indicated that small calcified particles observable by scanning electron microscopy (SEM) may initiate calcification in cardiovascular tissues. We hypothesized that if the calcified particles precede gross calcification observed in calcific aortic valve disease (CAVD), they would exhibit a regional asymmetric distribution associated with CAVD development, which always initiates at the base of aortic valve leaflets adjacent to the aortic outflow in a region known as the fibrosa. Testing this hypothesis required counting the calcified particles in histological sections of aortic valve leaflets. SEM images, however, do not provide high contrast between components within images, making the identification and quantification of particles buried within tissue extracellular matrix difficult. We designed a new unique pattern-matching based technique to allow for flexibility in recognizing particles by creating a gap zone in the detection criteria that decreased the influence of non-particle image clutter in determining whether a particle was identified. We developed this flexible pattern particle-labeling (FpPL) technique using synthetic test images and human carotid artery tissue sections. A conventional image particle counting method (preinstalled in ImageJ) did not properly recognize small calcified particles located in noisy images that include complex extracellular matrix structures and other commonly used pattern-matching methods failed to detect the wide variation in size, shape, and brightness exhibited by the particles. Comparative experiments with the ImageJ particle counting method demonstrated that our method detected significantly more (p < 2 × 10−7) particles than the conventional method with significantly fewer (p < 0.0003) false positives and false negatives (p < 0.0003). We then applied the FpPL technique to CAVD leaflets and showed a significant increase in detected particles in the fibrosa at the base of the leaflets (p < 0.0001), supporting our hypothesis. The outcomes of this study are twofold: (1) development of a new image analysis technique that can be adapted to a wide range of applications and (2) acquisition of new insight on potential early mediators of calcification in CAVD.en
dc.language.isoen_USen
dc.publisherFrontiers Media S.A.en
dc.relation.isversionofdoi:10.3389/fcvm.2016.00044en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095138/pdf/en
dash.licenseLAAen_US
dc.subjectparticle labelingen
dc.subjectimage analysisen
dc.subjectcalcificationen
dc.subjectparticlesen
dc.subjectmicrocalcificationen
dc.subjectatherosclerosisen
dc.subjectcalcific aortic valve diseaseen
dc.titleQuantification of Calcified Particles in Human Valve Tissue Reveals Asymmetry of Calcific Aortic Valve Disease Developmenten
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalFrontiers in Cardiovascular Medicineen
dash.depositing.authorHutcheson, Joshua D.en_US
dc.date.available2016-12-02T15:25:02Z
dc.identifier.doi10.3389/fcvm.2016.00044*
dash.authorsorderedfalse
dash.contributor.affiliatedBody, Simon
dash.contributor.affiliatedAikawa, Masanori
dash.contributor.affiliatedHutcheson, Joshua
dash.contributor.affiliatedAikawa, Elena


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