The major findings from this analysis were the following: 1) SWI, smaller section thickness, and higher magnetic field each yielded substantially increased lesion contrast for CMB, 2) identification of CMB by a trained rater was determined by lesion contrast and (to a lesser extent) diameter, and 3) the overall number of CMB detected depended markedly on the MR imaging technique, with thin-section SWI MR imaging demonstrating approximately 3 times as many lesions as conventional GRE MR imaging in concurrently imaged patients with CAA. SWI was also associated with a small increase in CMB diameter, whereas thin-section imaging yielded slightly decreased lesion diameter.
The additional CMB detected by thin-section SWI in these CAA subjects were almost exclusively (>98%) located in the same lobar brain regions as those detected by conventional GRE. Hemorrhages associated with CAA (both symptomatic macrobleeds and asymptomatic CMB) are characteristically located in these lobar regions.25
The current findings, therefore, suggest that the additional lesions identified by thin-section SWI are indeed CAA-related CMB rather than some type of non-CMB artifact. This is a reassuring observation given the a priori concern that highly sensitive MR imaging techniques might detect non-CMB lesions, potentially lowering their specificity for CMB.
Because the basis for the MR imaging contrast of these small hemosiderin-laden lesions is susceptibility-related signal-intensity loss due to their ferromagnetic composition, it is not surprising that a sequence designed to be sensitive to these signal-intensity properties (SWI) and a higher field strength (susceptibility effects scale increasingly with field strength) would increase their detection. Furthermore, partial voluming effects (reduction of specific signal intensity caused by combination with signal intensity from nearby tissue with different magnetic properties) are smaller at higher resolution; thus, as long as the signal-intensity-to-noise ratio is maintained, it is reasonable to predict that small lesions such as CMB would be better detected with higher resolution parameters. The major trade-off for both SWI and higher resolution GRE is longer scanning-acquisition time, which may be an issue of concern in patients who have difficulty remaining motionless in the scanner.
Previous reports have characterized the use of various SWI and high-resolution MR imaging techniques for diagnostic applications, such as venography,28
and vascular malformations.31,32
Recent studies focusing on microbleed detection have also indicated increased sensitivity.33,34
The Rotterdam Scan Study, by using a technique based on increased spatial resolution and prolonged TE without incorporation of phase information, demonstrated improved CMB detection relative to conventional GRE in a subset of 200 population-based subjects (prevalence of CMB, 35.5% versus 21.0%, P
< .001) with no change in overall spatial distribution.20
Another analysis of a single individual with hypertensive hemorrhage found that longer TEs resulted in an increased number and mean diameter of detected CMB.35
Studies comparing 3T with 1.5T GRE MR imaging in brain trauma21
and healthy aging have also demonstrated improved CMB detection.22
A specific strength of our study is its measurement of imaging characteristics of individual identified CMB across multiple scan types. There are also notable limitations. Although measurement of lesion contrast is relatively straightforward, lesion diameter is more difficult to measure with precision and required an indirect calculation. The imaging protocols developed and validated on our MR imaging systems include some differences in in-plane resolution and intersection gap () that could have contributed to the observed effects on CMB CI and diameter, though such effects are expected to be small. For practical reasons, we could not study every possible permutation of sequence, resolution, and field strength and instead chose to focus on the 6 combinations shown in . The comparison of CMB counts shown in involved 2 variations in MR imaging technique (SWI versus GRE and thin-versus-thick sections), each of which likely contributed to differences in CMB detection. Finally, the patients who participated in the present study were not (or only minimally) cognitively impaired, so it is not yet clear whether the scanning time of thin-section SWI (approximately 11 minutes) will be tolerable for patients with cognitive impairment, though our preliminary experience in such a population has been positive.
Recent studies have found CMB to be relatively common, not only in association with cerebrovascular disease, but also accompanying Alzheimer disease and normal aging.5,6,13,14
Together with results from the Rotterdam Scan cohort,6
our data suggest that implementation of more sensitive MR imaging techniques is likely to raise the estimated prevalence of CMB even further. Future studies will therefore be needed to define the clinical impact of these increasingly detectable lesions on questions such as risk of future hemorrhagic stroke,12,16
whether a patient can be safely anticoagulated,36
and risk of cognitive decline.16,18