Sample size calculation for clinical trials using magnetic resonance imaging for the quantitative assessment of carotid atherosclerosis.
OBJECTIVE
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 Tl-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.


CONCLUSIONS
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.
Saam
Tobias
T
Department of Radiology, University of Washington, Seattle, Washington 98195, USA.
Kerwin
William S
WS
Chu
Baocheng
B
Cai
Jianming
J
Kampschulte
Annette
A
Hatsukami
Thomas S
TS
Zhao
Xue-Qiao
XQ
Polissar
Nayak L
NL
Neradilek
Blazej
B
Yarnykh
Vasily L
VL
Flemming
Kelly
K
Huston
John
J
Insull
William
W
Morrisett
Joel D
JD
Rand
Scott D
SD
DeMarco
Kevin J
KJ
Yuan
Chun
C
D000368:Aged; D019412:Anatomy, Cross-Sectional; D002340:Carotid Artery Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000473:pathology*; D017536:Carotid Artery, Common / Q000033:anatomy & histology / Q000473:pathology*; D015986:Confounding Factors, Epidemiologic; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007089:Image Enhancement; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D018401:Sample Size