Sample Size Calculation for Clinical Trials Using Magnetic Resonance Imaging for the Quantitative Assessment of Carotid Atherosclerosis

• Published in: Journal of cardiovascular magnetic resonance Vol. 7; no. 5; pp. 799 - 808
• Main Authors: Saam, Tobias, Kerwin, William S., Chu, Baocheng, Cai, Jianming, Kampschulte, Annette, Hatsukami, Thomas S., Zhao, Xue-Qiao, Polissar, Nayak L., Neradilek, Blazej, Yarnykh, Vasily L., Flemming, Kelly, Huston, John, Insull, William, Morrisett, Joel D., Rand, Scott D., DeMarco, Kevin J., Yuan, Chun
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 01.01.2005
• Subjects: Aged; Anatomy, Cross-Sectional; Carotid Artery Diseases - diagnosis; Carotid Artery Diseases - epidemiology; Carotid Artery Diseases - pathology; Carotid Artery, Common - anatomy & histology; Carotid Artery, Common - pathology; Confounding Factors (Epidemiology); Double-Blind Method; Female; Humans; Image Enhancement; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Observer Variation; Randomized Controlled Trials as Topic - methods; Sample Size
• ISSN: 1097-6647; 1532-429X
• DOI: 10.1080/10976640500287703

Purpose. To provide sample size calculation for the quantitative assessment of carotid atherosclerotic plaque using non-invasive magnetic resonance imaging in multi-center clinical trials. Methods. As part of a broader double-blind randomized trial of an experimental pharmaceutical agent, 20 asymptomatic placebo-control subjects were recruited from 5 clinical sites for a multi-center study. Subjects had 4 scans in 13 weeks on GE 1.5 T scanners, using TOF, T1-/PD-/T2- and contrast-enhanced T1-weighted images. Measurement variability was assessed by comparing quantitative data from the index carotid artery over the four time points. The wall/outer wall (W/OW) ratio was calculated as wall volume divided by outer wall volume. The percent lipid-rich/necrotic core (%LR/NC) and calcification (%Ca) were measured as a proportion of the vessel wall. For %LR/NC and %Ca, only those subjects that exhibited LR/NC or Ca components were used in the analysis. Results. Measurement error was 5.8% for wall volume, 3.2% for W/OW ratio, 11.1% for %LR/NC volume and 18.6% for %Ca volume. Power analysis based on these values shows that a study with 14 participants in each group could detect a 5% change in W/OW ratio, 10% change in wall volume, and 20% change in %LR/NC volume (power = 80%, p < .05). The calculated measurement errors presume any true biological changes were negligible over the 3 months that subjects received placebo. Conclusion. In vivo MRI is capable of quantifying plaque volume and plaque composition, such as %lipid-rich/necrotic core and %calcification, in the clinical setting of a multi-center trial with low inter-scan variability. This study provides the basis for sample size calculation of future MRI trials.