Background and Purpose-Measurement of carotid plaque volume and its progression are important tools for research and patient management. In this study, we investigate the observer variability in the measurement of plaque volume as determined by 3-dimensional (3D) ultrasound (US). We also investigate the effect of interslice distances (ISD) and repeated 3D US scans on measurement variability. Materials and Methods-Forty 3D US patient images of plaques (range, 37.43 to 604.1 mm 3 ) were measured by manual planimetry. We applied ANOVA to determine plaque volume measurement variability and reliability. Plaque volumes were measured with 9 ISDs to determine the effect of ISD on measurement variability. Additional plaque volumes were also measured from multiple 3D US scans to investigate repeated scan acquisition variability. Results-Intraobserver and interobserver measurement reliabilities were 94% and 93.2%, respectively. Plaque volume measurement variability decreased with increasing plaque volume (range, 27.1% to 2.2%). Measurement precision was constant for ISDs between 1.0 and 3.0 mm, whereas plaque volume measurement variability increased with ISD. Repeated 3D US scan measurements were not different from single-scan measurements (Pϭ0.867). Conclusions-The coefficient of variation in the measurement of plaque volume decreased with plaque size. The volumetric change that must be observed to establish with 95% confidence that a plaque has undergone change is Ϸ20% to 35% for plaques Ͻ100 mm 3 and Ϸ10% to 20% for plaques Ͼ100 mm 3 . Measurement precision was unchanged for ISDs Ͻ3.0 mm, whereas measurement variability increased with ISD. Repeated 3D US scans did not affect plaque volume measurement variability.

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An accurate technique that exhibits low variability has practical importance for the quantification of carotid plaque volume. Such a technique is necessary to monitor plaque progression or regression that may result in response to nonsurgical therapy. In this study, we investigate the accuracy and variability of plaque volume measurement by three-dimensional ultrasound using vascular plaque phantoms over a range of 68.2 mm3 to 285.5 mm3. The agar plaques maintained a consistent cylindrical geometry with variations in the height, length, and echogenicity. The volume of each plaque was determined by water displacement. The three-dimensional (3D) ultrasound (US) images were acquired with a mechanical scanning system which creates a 3D US Cartesian volume, that was manipulated and viewed in any orientation, from a collection of conventional parallel two-dimensional (2D) US images. The plaque volumes were measured by serial 2D manual planimtery. The mean accuracy in plaque volume measurement was 3.1+/-0.9%. Variability in plaque volume measurement was calculated to be 4.0+/-1.0% and 5.1+/-1.4% for intraobserver and interobserver measurements, respectively. We have also developed a theoretical description for the variance in measurement of plaque volume using manual planimetry. Root-mean-square difference between experimentally and theoretically determined values of plaque volume fractional variance was 9%.

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Neutron exposure poses a unique radiation protection concern because neutrons have a large, energy-dependent relative biological effectiveness (RBE) for stochastic effects. Recent computational studies on the microdosimetric properties of neutron dose deposition have implicated clustered DNA damage as a likely contributor to this marked energy dependence. So far, publications have focused solely on neutron RBE for inducing clusters of DNA damage containing two or more DNA double strand breaks (DSBs). In this study, we have conducted a novel assessment of neutron RBE for inducing all types of clustered DNA damage that contain two or more lesions, stratified by whether the clusters contain DSBs (complex DSB clusters) or not (non-DSB clusters). This assessment was conducted for eighteen initial neutron energies between 1 eV and 10 MeV as well as a reference radiation of 250 keV x-rays. We also examined the energy dependence of cluster length and cluster complexity because these factors are believed to impact the DNA repair process. To carry out our investigation, we developed a user-friendly TOPAS-nBio application that includes a custom nuclear DNA model and a novel algorithm for recording clustered DNA damage. We found that neutron RBE for inducing complex DSB clusters exhibited similar energy dependence to the canonical neutron RBE for stochastic radiobiological effects, at multiple depths in human tissue. Qualitatively similar results were obtained for non-DSB clusters, although the quantitative agreement was lower. Additionally we identified a significant neutron energy dependence in the average length and complexity of clustered lesions. These results support the idea that many types of clustered DNA damage contribute to the energy dependence of neutron RBE for stochastic radiobiological effects and imply that the size and constituent lesions of individual clusters should be taken into account when modeling DNA repair. Our results were qualitatively consistent for (i) multiple radiation doses (including a low-dose 0.1 Gy irradiation), (ii) variations in the maximal lesion separation distance used to define a cluster, and (iii) two distinct collections of physics models used to govern particle transport. Our complete TOPAS-nBio application has been released under an open-source license to enable others to independently validate our work and to expand upon it.