David H. Salat
salat@nmr.mgh.harvard.edu
Athinoula A. Martinos Center for Biomedical Imaging
Massachusetts General Hospital Department of Radiology
Neuroimaging Research for Veterans (NeRVe) Center, VABoston Healthcare System
THE MANY FACETS OF BRAIN AGING ASASSESSED BY MRI (AND FREESURFER)
AGING
•US has added >20 years to normal life expectancy in the lastcentury
•Advancing age is a risk for several diseases (e.g. AD, CVD,cancer)
•Which of these changes are most detrimental to cognitivefunction, and what are the biological conditions that contributeto these detrimental processes?
THE US BABY BOOM
•Baby booms (increased rate ofbirths) signify good times andperiods of general economic growthand stability
•The number of births per thousandpeople in the United States
•The blue segment is the Post WorldWar II period; and is defined as theBaby Boom by the United Statesgovernment.
•~78 million Americans were bornduring this period
Image: Nicholas W. Beeson, University of Michigan
OVERVIEW OF MRI STUDIES OFAGING
•Age-associated alteration in:
•Brain macrostructure
•Structural MRI (sMRI)
•Brain microstructure
•Diffusion tensor imaging (DTI); Gray/white tissue
•Brain Vasculature: Cerebral blood flow
•Arterial spin labeling MRI (ASL)
BRIAN ATROPHY WITH AGING
•Postmortem studies have demonstratedsubstantial reduction in brain weight across theadult lifespan (5-10%)
•MRI can quantify the regional basis of thesechanges to determine whether certain regionsare particularly vulnerable
•Prior studies suggested vulnerability ofprefrontal and association cortex with relativesparing of primary cortices
CORTICAL THICKNESS (RECON-ALL)
Group Mean Thickness
Young
Old
Middle Aged
Salat et al., Cerebral Cortex, 2004
Salat et al., Cerebral Cortex, 2004
AGE-ASSOCIATED CORTICALTHINNING (MRI_GLMFIT)
•Thinning in primaryand associationcortices
•Regional thinningrelates toneuropsychologicalperformance
•Mechanisms ofthinning are unknown
CORTICAL SIGNATURE OF AD
Dickerson et al., Cerebral Cortex, 2008
GRAY MATTER MACROSTRUCTURESUMMARY
•There are substantial volumetric changesin cortical and subcortical gray matter withnondemented aging
•AD may accelerate, yet also presents withdistinct structural abnormalities comparedto aging
WMPARC: VOLUMETRIC ANALYSIS/DTI ROIANALYSIS (WMPARC.MGZ)
EFFECTS OF AGE AND AD ONREGIONAL WHITE MATTER
Salat et al., 2009
OVERVIEW OF MRI STUDIES OFAGING
•Age-associated alteration in:
•Brain macrostructure
•Structural MRI (sMRI)
•Brain microstructure
•Diffusion tensor imaging (DTI); Gray/white tissue
•Brain Vasculature: Cerebral blood flow
•Arterial spin labeling MRI (ASL)
FSL INTEGRATION: COMBINED TBSS/WMPARCELLATION ROI ANALYSIS
Leritz et al., under review
DIFFUSION MEASURES DEEP WHITE MATTER:WHAT ABOUT SUPERFICIALMICROSTRUCTURE?
High Contrast
Low Contrast
Salat et al., 2009
VARIATION IN SIGNAL INTENSITYACROSS THE CORTICAL MANTLE(PCTSURFCON)
Salat et al., 2009
STRONG ASSOCIATIONS BETWEENREGIONAL GWR AND AGE (MRI_GLMFIT)
Changes in Contrast (GWR) with Age
Salat et al., 2009
EFFECTS OF AD ON GWR REMAINSTRONG WHEN CONTROLLING FORCORTICAL THICKNESS (MRI_GLMFITW/-PVR)
Salat et al., 2011
OVERVIEW OF MRI STUDIES OFAGING
•Age-associated alteration in:
•Brain macrostructure
•Structural MRI (sMRI)
•Brain microstructure
•Diffusion tensor imaging (DTI); Gray/white tissue
•Brain Vasculature: Cerebral blood flow
•Arterial spin labeling MRI (ASL)
ARTERIAL SPIN LABELING (ASL)QUANTITATIVE CBF MAPS IN YOUNG, MIDDLE-AGED, AND OLDER ADULTS
<40 years
40-60 years
>60 years
Chen et al., 2011
MINIMAL OVERLAP: CBF & ATROPHY
overlap
atrophy only
CBF reduction only
Chen et al., 2011
CBF SUMMARY
•There is a regional decline in cerebralblood flow with advancing age
•Changes in blood flow are regionallydistinct from those of atrophy
OVERVIEW OF MRI STUDIES OFAGING
•Age-associated alteration in:
•Brain macrostructure
•Structural MRI (sMRI)
•Brain microstructure
•Diffusion tensor imaging (DTI); Gray/white tissue
•Brain Vasculature: Cerebral blood flow
•Arterial spin labeling MRI (ASL)
ACKNOWLEDGEMENTS
•H. Diana Rosas
•Bruce Fischl
•Randy Buckner
•Andre van der Kouwe
•Doug Greve
•Stephanie Lee
•Christina Onorato
•National Institutes of Health:
–NIA K01AG024898
–NINR R01NR10827
•Athinoula A. Martinos Center forBiomedical Imaging:
–National Center for ResearchResources: P41RR14075
–National Alliance for MedicalImage Computing: NIBIB U54EB005149
•Freesurfer Team:
–surfer.nmr.mgh.harvard.edu
•Open Access Series of ImagingStudies
–oasis-brains.org
•Bill Milberg
•Betsy Leritz
•Gina McGlinchey
•Jean Chen
•Tyler Triggs