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Neuroimaging in Alzheimer's disease: preclinical challenges toward clinical efficacy

  • Derek Dustin
    Affiliations
    Translational Biology and Molecular Medicine Graduate Program, Baylor College of Medicine, Houston, Tex
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  • Benjamin M. Hall
    Affiliations
    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Tex
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  • Ananth Annapragada
    Affiliations
    Department of Radiology, Baylor College of Medicine, Houston, Tex

    Department of Radiology, Texas Children's Hospital, Houston, Tex
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  • Robia G. Pautler
    Correspondence
    Reprint requests: Robia G. Pautler, One Baylor Plaza Baylor College of Medicine, MC:335, Houston, TX, 77030.
    Affiliations
    Translational Biology and Molecular Medicine Graduate Program, Baylor College of Medicine, Houston, Tex

    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Tex

    Department of Radiology, Baylor College of Medicine, Houston, Tex

    Department of Neuroscience, Baylor College of Medicine, Houston, Tex

    Small Animal Imaging Facility, Texas Children's Hospital, Houston, Tex
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Published:March 12, 2016DOI:https://doi.org/10.1016/j.trsl.2016.03.005
      The scope of this review focuses on recent applications in preclinical and clinical magnetic resonance imaging (MRI) toward accomplishing the goals of early detection and responses to therapy in animal models of Alzheimer's disease (AD). Driven by the outstanding efforts of the Alzheimer's Disease Neuroimaging Initiative (ADNI), a truly invaluable resource, the initial use of MRI in AD imaging has been to assess changes in brain anatomy, specifically assessing brain shrinkage and regional changes in white matter tractography using diffusion tensor imaging. However, advances in MRI have led to multiple efforts toward imaging amyloid beta plaques first without and then with the use of MRI contrast agents. These technological advancements have met with limited success and are not yet appropriate for the clinic. Recent developments in molecular imaging inclusive of high-power liposomal–based MRI contrast agents as well as fluorine 19 (19F) MRI and manganese enhanced MRI have begun to propel promising advances toward not only plaque imaging but also using MRI to detect perturbations in subcellular processes occurring within the neuron. This review concludes with a discussion about the necessity for the development of novel preclinical models of AD that better recapitulate human AD for the imaging to truly be meaningful and for substantive progress to be made toward understanding and effectively treating AD. Furthermore, the continued support of outstanding programs such as ADNI as well as the development of novel molecular imaging agents and MRI fast scanning sequences will also be requisite to effectively translate preclinical findings to the clinic.

      Abbreviations:

      AD (Alzheimer’s disease), ADNI (Alzheimer’s Disease Neuroimaging Initiative), (amyloid beta), BBB (blood-brain barrier), BC (betweenness), BOLD (blood oxygen level detection), CEST (chemical exchange saturation transfer), CF (compression flow), CSF (cerebrospinal fluid), CT (computed tomography), DC (degree centrality), DTI (diffusion tensor imaging), DTPA (diethylenetriamine pentaacetic acid), EBC (edge betweenness), FA (fractional anisotropy), fMRI (functional MRI), FWE (familywise error correction), Gd (gadolinium), GM (gray matter), MEMRI (manganese enhanced MRI), MICEST (multi-ion chemical exchange saturation transfer), MR (magnetic resonance), MRI (magnetic resonance imaging), MRS (magnetic resonance spectroscopy), NGF (nerve growth factor), NMR (nuclear magnetic resonance), PEG (polyethylene glycol), PET (positron emission tomography), PFC (perfluorocarbon), PS1/APP (presenilin-1/amyloid precursor protein), SPECT (single photon emission computed tomography), USPIO (ultra small paramagnetic iron oxide), τR (correlation time)
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