{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T15:09:51Z","timestamp":1791126591140,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2017,8,31]],"date-time":"2017-08-31T00:00:00Z","timestamp":1504137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81201149"],"award-info":[{"award-number":["81201149"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007567","name":"City University of Hong Kong","doi-asserted-by":"publisher","award":["7004425"],"award-info":[{"award-number":["7004425"]}],"id":[{"id":"10.13039\/100007567","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007567","name":"City University of Hong Kong","doi-asserted-by":"publisher","award":["7004617"],"award-info":[{"award-number":["7004617"]}],"id":[{"id":"10.13039\/100007567","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Physics"],"published-print":{"date-parts":[[2017,10]]},"abstract":"Purpose<\/jats:title>Vitamin B deficiency has been identified as a risk factor for vascular events. However, the reduction of vascular events was not shown in large randomized controlled trials evaluating B\u2010Vitamin therapy. There is an important requirement to develop sensitive biomarkers to be used as efficacy targets for B\u2010Vitamin therapy as well as other dietary treatments and lifestyle regimes that are being developed. Carotid vessel\u2010wall\u2010plus\u2010plaque thickness change (VWT<\/jats:styled-content>\u2010Change<\/jats:italic>) measured from 3D ultrasound has been shown to be sensitive to atorvastatin therapies in previous studies. However, B\u2010Vitamin treatment is expected to confer a smaller beneficial effect in carotid atherosclerosis than the strong dose of atorvastatin. This paper introduces a sensitive atherosclerosis biomarker based on the weighted mean VWT<\/jats:styled-content>\u2010Change<\/jats:italic> measurement from 3D ultrasound with a purpose to detect statistically significant effect of B\u2010Vitamin therapy.<\/jats:p><\/jats:sec>Methods<\/jats:title>Of the 56 subjects analyzed in this study, 27 were randomized to receive a B\u2010Vitamin tablet daily and 29 received a placebo tablet daily. Participants were scanned at baseline and 1.9 \u00b1 0.8 yr later. The 3D VWT<\/jats:styled-content><\/jats:italic> map at each scanning session was computed by matching the outer wall and lumen surfaces on a point\u2010by\u2010point basis. The 3D annual VWT<\/jats:styled-content>\u2010Change<\/jats:italic> maps were obtained by first registering the 3D VWT<\/jats:styled-content><\/jats:italic> maps obtained at the baseline and follow\u2010up scanning sessions, and then taking the point\u2010wise difference in VWT<\/jats:styled-content><\/jats:italic> and dividing the result by the years elapsed from the baseline to the follow\u2010up scanning session. The 3D VWT<\/jats:styled-content>\u2010Change<\/jats:italic> maps constructed for all patients were mapped to a 2D carotid template to adjust for the anatomic variability of the arteries. A weight at each point of the carotid template was assigned based on the degree of correlation between the VWT<\/jats:styled-content>\u2010Change<\/jats:italic> measurements exhibited at that point and the treatment received (i.e., B\u2010Vitamin or placebo) quantified by mutual information. The weighted mean of VWT<\/jats:styled-content>\u2010Change<\/jats:italic> for each patient, denoted by , was computed according to this weight. T<\/jats:italic>\u2010tests were performed to compare the sensitivity of with existing biomarkers in detecting treatment effects. These biomarkers included changes in intima\u2010media thickness (IMT<\/jats:styled-content>), total plaque area (TPA<\/jats:styled-content>), vessel wall volume (VWV<\/jats:styled-content>), unweighted average of VWT<\/jats:styled-content>\u2010Change<\/jats:italic> () and a previously described biomarker, denoted by , that quantifies the mean VWT<\/jats:styled-content>\u2010Change<\/jats:italic> specific to regions of interest identified by a feature selection algorithm.<\/jats:p><\/jats:sec>Results<\/jats:title>Among the six biomarkers evaluated, the effect of B Vitamins was detected only by in this cohort (). The sample sizes per treatment group required to detect an effect as large as exhibited in this study were 139, 178, 41 for \u0394VWV<\/jats:styled-content><\/jats:italic>, and respectively.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>The proposed weighted mean of VWT<\/jats:styled-content>\u2010Change<\/jats:italic> is more sensitive than existing biomarkers in detecting treatment effects. This measurement tool will allow for many proof\u2010of\u2010principal studies to be performed for various novel treatments before a more costly study involving a larger population is held to validate the results.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mp.12507","type":"journal-article","created":{"date-parts":[[2017,8,7]],"date-time":"2017-08-07T05:39:36Z","timestamp":1502084376000},"page":"5280-5292","source":"Crossref","is-referenced-by-count":19,"title":["Sensitive three\u2010dimensional ultrasound assessment of carotid atherosclerosis by weighted average of local vessel wall and plaque thickness change"],"prefix":"10.1002","volume":"44","author":[{"given":"Jieyu","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Electronic Engineering City University of Hong Kong Kowloon Tong Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eranga","family":"Ukwatta","sequence":"additional","affiliation":[{"name":"Department of Systems and Computer Engineering Carleton University Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shadi","family":"Shavakh","sequence":"additional","affiliation":[{"name":"Imaging Research Laboratories Robarts Research Institute London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommy W. 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