Introduction: Hyperintense white matter (WM) lesions are frequently found in the elderly brain on T2-weighted MRI and may contribute to age-related cognitive decline. Two types of hyperintensities are generally recognized: small, focal lesions in the deep WM (dWMHs) and lesions adjacent to the ventricles (pWMHs). It has been suggested that vascular injury may play an important role in pWMHs, while demyelinating processes may contribute more to dWMHs. The goal of this study is to compare the blood volume (pb) of pWMHs and dWMHs in the elderly human brain using a gadolinium contrast reagent (CR).

Methods: 19 elderly subjects (11 male, 8 female; 70 ± 7 yrs) with no history of vascular disease were enrolled. MR data were obtained on a 7T Siemens MAGNETOM instrument. High resolution T1-weighted (IR-MPRAGE) and T2-weighted fluid-attenuated IR (FLAIR) images were acquired. Five 3D R1 (1/T1) maps centered on the lateral ventricles were prepared before and 12, 31, 45 and 57 min post CR injection using variable inversion time MPRAGE acquisitions. 1H2O R1 maps and FLAIR images were coregistered to the high resolution IR-MPRAGE image.3 Our previous work demonstrated that coregistration to FLAIR images provides superior conspicuity of WMHs. Blood volume maps were prepared by voxelwise fitting of tissue and blood R1 values to an equation for two-site (transendothelial) water exchange.5 Statistical analyses were performed in Stata (College Station, TX).

Results: Hyperintensities were present in the periventricular and deep WM in 15/19 and 17/19 subjects. No significant pb difference was found between normal-appearing and hyperintense WM regions. The mean pb was slightly (but not significantly) higher in pWMHs than dWMHs (2.0 ± 0.3% and 1.9 ± 0.5%, respectively).

Conclusions: These results suggest that vascular disturbances are minimal in both periventricular and deep WM hyperintensities and support an extravascular etiology for these common lesions.

Patient Care: As Alzheimer’s disease increases in prevalence with our aging population, an understanding of the underlying etiology is necessary to combat this major health concern. The use of advanced MR imaging has shed light onto the potential etiology of white matter hyperintensities (WMH) in the elderly brain. This study provides new knowledge of pathophysiology of these common lesions and supports the notion that the pathophysiology of periventricular and deep lesions may be different. As such, our study will advance the knowledge related to WMHs and further our understanding of their potential contribution to cognitive decline in the elderly.

Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the role of vascular changes in the etiology of white matter hyperintensities in the elderly brain and 2) Appreciate the role of advanced MR imaging on the study of Alzheimer’s disease.

References: 1. Fernando, et al., Stroke 37, 1391-98 (2006). 2. Rooney, et al., Magn Reson Med 57, 308-18 (2007). 3. Smith, et al., Neuroimage 17, 479-89 (2002). 4. Deichmann and Haase, J Magn Reson 96, 608-12 (1992). 5. Li, et al., Magn Reson Med 54, 1351-1359 (2005). 6. Rooney, et al PISMRM 11, 2188 (2003). 7. www.sci.utah.edu/cibc/software/42-seg3d.html. 8. Zhang, et al., IEEE Trans Med Imaging 20, 45-57 (2001). 9. Srour, et al., J Cerebr Blood Flow 31, 1272 (2011).