HOW CAN NEUROIMAGING HELP UNDERSTAND, DIAGNOSE, AND DEVELOP TREATMENTS FOR ALZHEIMER'S DISEASE? Part C – AD brain scans - anatomical NUCLEAR MEDICINE GRAND.

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HOW CAN NEUROIMAGING HELP UNDERSTAND, DIAGNOSE, AND DEVELOP TREATMENTS FOR ALZHEIMER'S DISEASE? Part C – AD brain scans - anatomical NUCLEAR MEDICINE GRAND ROUNDS Stanford University J. Wesson Ashford, M.D., Ph.D. Clinical Professor (affiliated), Department of Psychiatry and Behavioral Sciences Senior Research Scientist, Stanford / VA Aging Clinical Research Stanford University and VA Palo Alto Health Care System January 5, 2010 Slides at: www.medafile.com (Dr. Ashford’s lectures)

BRAIN SCANNING TECHNIQUES ANATOMICAL BRAIN IMAGING CT – cerebral tomography MRI – magnetic resonance imaging FUNCTIONAL BRAIN IMAGING SPECT – single photon emission computed tomography PET – FDG – Positron emission tomography BRAIN CHEMISTRY MEASUREMENT MRS (spectroscopy – NAA/Cr: estimate neuronal volume) BRAIN PATHOLOGY IMAGING PIB – amyloid (many compounds under development) FDDNP – neurofibrillary pathology

Evolution of Neuroimaging in AD 39 Evolution of Neuroimaging in AD Computed Tomography MRI Volumetric MRI Co-registration of MRI Functional MRI FDG Glucose PET Amyloid Imaging P-Tau imaging FDG Glucose PET Helmuth L. Science. 2002;297:1260-1262. Lab of Neuro Imaging UCLA School of Medicine. Brain Tissue Loss in Alzheimer’s Disease. Video Sequence. Available at: http://www.loni.ucla.edu/~thompson/AD_4D/dynamic.html. Accessed May 22, 2007. Helmuth L. New therapies. New Alzheimer's treatments that may ease the mind. Science. 2002;297:1260-1262. Alzheimer Disease Forum. Pittsburgh Compound-B Zooms into View. Available at: http://www.alzforum.org/new/detail.asp?id=948. Accessed May 22, 2007. Alzheimer Disease Forum. http://www.alzforum.org/new/detail.asp?id=948. Lab of Neuro Imaging UCLA School of Medicine. www.loni.ucla.edu/~thompson/AD_4D/dynamic.html. 3

NORMAL ALZHEIMER

Hippocampus outline Entorhinal Cortex outline

Braak and Braak stage vs normalized bilateral hippocampal formation (HF) volume in subjects with isolated AD pathology. Jack et al., 2002

Jack et al., 1992 HF/TIV = Hippocampal Formation / Total Intracranial Volume

Volumes already being done in some medical centers. AD-Designed Probability Atlas: Probabilistic Atlas of Hippocampal Volumes Mega et al. 2002 UCLA Medical Center Future MRIs will include estimates of disease probability based on volumes. Volumes already being done in some medical centers.