Age-associated alterations in cortical gray and white matter signal intensity and gray to white matter contrast

Abstract

Prior studies have focused on patterns of brain atrophy with aging and age-associated cognitive decline. It is possible that changes in neural tissue properties could provide an important marker of more subtle changes compared to gross morphometry. However, little is known about how MRI tissue parameters are altered in aging. We created cortical surface models of 148 individuals and mapped regional gray and white matter T1-weighted signal intensities from 3D MPRAGE images to examine patterns of age-associated signal alterations. Gray matter intensity was decreased with aging with strongest effects in medial frontal, anterior cingulate, and inferior temporal regions. White matter signal intensity decreased with aging in superior and medial frontal, cingulum, and medial and lateral temporal regions. The gray/white ratio (GWR) was altered throughout a large portion of the cortical mantle, with strong changes in superior and inferior frontal, lateral parietal, and superior temporal and precuneus regions demonstrating decreased overall contrast. Statistical effects of contrast changes were stronger than those of cortical thinning. These results demonstrate that there are strong regional changes in neural tissue properties with aging and tissue intensity measures may serve as an important biomarker of degeneration.

Introduction

Prior studies have demonstrated the effect of aging on several neuroimaging parameters of tissue integrity, including reductions in brain volume (Jernigan et al., 1991, Jernigan et al., 2001, Lim et al., 1990, Pfefferbaum et al., 1994, Raz et al., 1997, Salat et al., 1999, Salat et al., 2001, Shear et al., 1995, Sullivan et al., 1995), cortical thickness (Fjell et al., 2009, Salat et al., 2004, Ziegler et al., 2008), density (Good et al., 2001, Sowell et al., 2003, Sowell et al., 2004) and variation (Thompson et al., 1998), and regional changes in tissue properties such as tissue microstructure measured by diffusion tensor imaging (DTI) (Head et al., 2004, Madden et al., 2009, Madden et al., 2004, Pfefferbaum et al., 2005, Pfefferbaum and Sullivan, 2003, Pfefferbaum et al., 2000, Salat et al., 2005a, Salat et al., 2005b, Sullivan et al., 2001, Sullivan et al., 2006, Ziegler et al., 2008). Less studied are the reported changes in tissue signal properties, such as T1 relaxation times (Cho et al., 1997, Ogg and Steen, 1998, Raz et al., 1990, Steen et al., 1995) and signal intensity. Similarly, the effect of tissue changes on the contrast properties of neural structures has been almost completely unexplored.

An early study by Raz et al. (1990) examined spin-lattice (T1) relaxation time and found a prolongation in temporal lobe white matter with increasing age. They additionally found that there was a reduction in the differentiation of gray and white matter T1, and this change in contrast was associated with cognitive performance (Raz et al., 1990). A subsequent study by Magnaldi et al. (1993) examined T1, spin density, and T2 values in gray and white matter of 22 individuals. They reported alterations in signal properties with a reduction in gray/white contrast with aging in regions measured. These findings demonstrated that there is a fundamental change in brain tissue with age that alters the imaging properties of brain structures. It is therefore critical to determine the clinical significance of such changes, and whether signal alterations are general or exhibit selective regional patterns. It is also important to understand how changes in tissue properties relate to alterations in neural morphometry to determine whether signal properties may provide a useful biomarker of age and disease-associated histological and pathological properties.

We created cortical surface models in 148 individuals and mapped gray and white matter signal intensities from 3D T1-weighted MPRAGE images to examine the regional patterns of age-associated signal alterations. This type of analysis was previously difficult to perform due to the need for precise representations of the gray/white matter and gray matter/cerebrospinal fluid (CSF) borders. Additionally, such an analysis requires accurate anatomical matching of data in homologous cortical regions across individuals due to the appreciable regional differences in premorbid gray/white matter signal properties across the cortical mantle, as well as appropriate procedures for the correction for signal nonuniformity. Along with individual tissue class signal intensities, we examined the ratio of gray to white matter signal intensity (GWR) at each point along the cortical surface to determine whether contrast properties were altered in a regionally specific manner throughout the brain. We found strong localized changes in tissue signal properties throughout the cortex and subjacent white matter. The GWR showed a considerable increase (towards a value of 1) with increasing age, demonstrating an overall decrease in the contrast between these tissue classes, mostly due to a decrease in white matter signal intensity approaching that of gray matter. These findings demonstrate that tissue signal properties are altered in nondemented aging in a regionally specific manner. Such changes may be an indirect marker of changes in the histological properties of the tissue that have a significant impact on neural and cognitive processes, and these findings may therefore have important clinical applications.