title: A brain stress test: Cerebral perfusion during memory encoding in mild cognitive impairment.
abstract: Arterial spin labeled perfusion magnetic resonance imaging (ASL MRI) provides non-invasive quantification of cerebral blood flow, which can be used as a biomarker of brain function due to the tight coupling between cerebral blood flow (CBF) and brain metabolism. A growing body of literature suggests that regional CBF is altered in neurodegenerative diseases. Here we examined ASL MRI CBF in subjects with amnestic mild cognitive impairment (n = 65) and cognitively normal healthy controls (n = 62), both at rest and during performance of a memory-encoding task. As compared to rest, task-enhanced ASL MRI improved group discrimination, which supports the notion that physiologic measures during a cognitive challenge, or "stress test", may increase the ability to detect subtle functional changes in early disease stages. Further, logistic regression analysis demonstrated that ASL MRI and concomitantly acquired structural MRI provide complementary information of disease status. The current findings support the potential utility of task-enhanced ASL MRI as a biomarker in early Alzheimer's disease.
authors.affiliation: Penn Image Computing and Science Laboratory (PICSL), Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: lxie@seas.upenn.edu.
authors.forename: Long
authors.initials: L
authors.lastname: Xie
authors.affiliation: Center for Functional Neuroimaging, Department of Neurology, Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA; Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA; Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Sudipto
authors.initials: S
authors.lastname: Dolui
authors.affiliation: Penn Image Computing and Science Laboratory (PICSL), Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA; Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Sandhitsu R
authors.initials: SR
authors.lastname: Das
authors.affiliation: Penn Memory Center, University of Pennsylvania, Philadelphia, PA, USA; Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Grace E
authors.initials: GE
authors.lastname: Stockbower
authors.affiliation: Penn Memory Center, University of Pennsylvania, Philadelphia, PA, USA; Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Molly
authors.initials: M
authors.lastname: Daffner
authors.affiliation: Center for Functional Neuroimaging, Department of Neurology, Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA; Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Hengyi
authors.initials: H
authors.lastname: Rao
authors.affiliation: Penn Image Computing and Science Laboratory (PICSL), Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA; Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Yushkevich
authors.affiliation: Center for Functional Neuroimaging, Department of Neurology, Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA; Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA; Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Detre
authors.affiliation: Penn Memory Center, University of Pennsylvania, Philadelphia, PA, USA; Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Wolk
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000098:blood supply / Q000000981:diagnostic imaging*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D060825:Cognitive Dysfunction / Q000175:diagnosis* / Q000503:physiopathology*; D005260:Female; D006624:Hippocampus / Q000098:blood supply / Q000000981:diagnostic imaging; D006801:Humans; D007091:Image Processing, Computer-Assisted; D018810:Magnetic Resonance Angiography; D008297:Male; D008568:Memory / Q000502:physiology*; D008875:Middle Aged; D010775:Photic Stimulation; D011594:Psychometrics
keywords: AAL, Anatomical Automatic Labeling; ASL, arterial spin labeled; Alzheimer's disease; Arterial spin labeling; BOLD, blood oxygen level dependent; Biomarker; CBF, cerebral blood flow; CSF, cerebrospinal fluid; FDG PET, flourodeoyglucose positron emission tomography; FWER, familywise error rate; HC, health control; MCI, mild cognitive impairment; MMSE, mini-mental status exam; MNI, Montreal Neurological Institute; MTL, medial temporal lobe; Medial temporal lobe; PASL, pulsed ASL; PCC, posterior cingulate cortex; ROI, region of interest; SCORE, structural correlation based outlier rejection; Scene-encoding memory task; a-MCI, amnestic mild cognitive impairment; aCBF, absolute cerebral blood flow; pCASL, pseudo-continuous ASL; rCBF, relative cerebral blood flow