Sensitive three-dimensional ultrasound assessment of carotid atherosclerosis by weighted average of local vessel wall and plaque thickness change

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

18 Scopus Citations
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Author(s)

  • Eranga Ukwatta
  • Shadi Shavakh
  • Grace Parraga
  • J. David Spence

Related Research Unit(s)

Detail(s)

Original languageEnglish
Pages (from-to)5280–5292
Journal / PublicationMedical Physics
Volume44
Issue number10
Online published31 Aug 2017
Publication statusPublished - Oct 2017

Abstract

Purpose: 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-Vitamin therapy. There is an important requirement to develop sensitive biomarkers to be used as efficacy targets for B-Vitamin therapy as well as other dietary treatments and lifestyle regimes that are being developed. Carotid vessel-wall-plus-plaque thickness change (VWT-Change) measured from 3D ultrasound has been shown to be sensitive to atorvastatin therapies in previous studies. However, B-Vitamin 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-Change measurement from 3D ultrasound with a purpose to detect statistically significant effect of B-Vitamin therapy.

Methods: Of the 56 subjects analyzed in this study, 27 were randomized to receive a B-Vitamin tablet daily and 29 received a placebo tablet daily. Participants were scanned at baseline and 1.9 ± 0.8 yr later. The 3D VWT map at each scanning session was computed by matching the outer wall and lumen surfaces on a point-by-point basis. The 3D annual VWT-Change maps were obtained by first registering the 3D VWT maps obtained at the baseline and follow-up scanning sessions, and then taking the point-wise difference in VWT and dividing the result by the years elapsed from the baseline to the follow-up scanning session. The 3D VWT-Change 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-Change measurements exhibited at that point and the treatment received (i.e., B-Vitamin or placebo) quantified by mutual information. The weighted mean of VWT-Change for each patient, denoted by ΔVWTWeighted, was computed according to this weight. T-tests were performed to compare the sensitivity of ΔVWTWeighted with existing biomarkers in detecting treatment effects. These biomarkers included changes in intima-media thickness (IMT), total plaque area (TPA), vessel wall volume (VWV), unweighted average of VWT-ChangeVWT) and a previously described biomarker, denoted by ΔVWTs, that quantifies the mean VWT-Change specific to regions of interest identified by a feature selection algorithm.

Results: Among the six biomarkers evaluated, the effect of B Vitamins was detected only by ΔVWTWeighted in this cohort (P = 4.4 × 10-3). The sample sizes per treatment group required to detect an effect as large as exhibited in this study were 139, 178, 41 for ΔVWV, ΔVWT and ΔVWTWeighted respectively.

Conclusion: The proposed weighted mean of VWT-Change is more sensitive than existing biomarkers in detecting treatment effects. This measurement tool will allow for many proof-of-principal studies to be performed for various novel treatments before a more costly study involving a larger population is held to validate the results.

Citation Format(s)

Sensitive three-dimensional ultrasound assessment of carotid atherosclerosis by weighted average of local vessel wall and plaque thickness change. / Cheng, Jieyu; Ukwatta, Eranga; Shavakh, Shadi et al.
In: Medical Physics, Vol. 44, No. 10, 10.2017, p. 5280–5292.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review