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

  • Derek Dustin
    Translational Biology and Molecular Medicine Graduate Program, Baylor College of Medicine, Houston, Tex
    Search for articles by this author
  • Benjamin M. Hall
    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Tex
    Search for articles by this author
  • Ananth Annapragada
    Department of Radiology, Baylor College of Medicine, Houston, Tex

    Department of Radiology, Texas Children's Hospital, Houston, Tex
    Search for articles by this author
  • Robia G. Pautler
    Reprint requests: Robia G. Pautler, One Baylor Plaza Baylor College of Medicine, MC:335, Houston, TX, 77030.
    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
    Search for articles by this author
Published:March 12, 2016DOI:
      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.


      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)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Translational Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Weiner M.W.
        • Veitch D.P.
        • Aisen P.S.
        • et al.
        Impact of the Alzheimer’s Disease Neuroimaging Initiative, 2004 to 2014.
        Alzheimers Dement J Alzheimers Assoc. 2015; 11: 865-884
        • Duara R.
        • Loewenstein D.A.
        • Potter E.
        • et al.
        Medial temporal lobe atrophy on MRI scans and the diagnosis of Alzheimer disease.
        Neurology. 2008; 71: 1986-1992
        • Ferreira D.
        • Westman E.
        • Eyjolfsdottir H.
        • et al.
        Brain changes in Alzheimer's disease patients with implanted encapsulated cells releasing nerve growth factor.
        J Alzheimers Dis. 2015; 43: 1059-1072
        • Hsu P.J.
        • Shou H.
        • Benzinger T.
        • et al.
        Amyloid burden in cognitively normal elderly is associated with preferential hippocampal subfield volume loss.
        J Alzheimers Dis JAD. 2015; 45: 27-33
        • Trzepacz P.T.
        • Hochstetler H.
        • Yu P.
        • et al.
        Relationship of hippocampal volume to amyloid burden across diagnostic stages of Alzheimer's disease.
        Dement Geriatr Cogn Disord. 2015; 41: 68-79
        • Yin J.
        • Turner G.H.
        • Coons S.W.
        • Maalouf M.
        • Reiman E.M.
        • Shi J.
        Association of amyloid burden, brain atrophy and memory deficits in aged apolipoprotein ε4 mice.
        Curr Alzheimer Res. 2014; 11: 283-290
        • Bernard C.
        • Helmer C.
        • Dilharreguy B.
        • et al.
        Time course of brain volume changes in the preclinical phase of Alzheimer's disease.
        Alzheimers Dement J Alzheimers Assoc. 2014; 10: 143-151.e1
        • Firbank M.J.
        • Watson R.
        • Mak E.
        • et al.
        Longitudinal diffusion tensor imaging in dementia with Lewy bodies and Alzheimer's disease.
        Parkinsonism Relat Disord. 2016; 24: 76-80
        • Daianu M.
        • Mendez M.F.
        • Baboyan V.G.
        • et al.
        An advanced white matter tract analysis in frontotemporal dementia and early-onset Alzheimer's disease.
        Brain Imaging Behav. 2015; ([Epub ahead of print])
        • Hořínek D.
        • Štěpán-Buksakowska I.
        • Szabó N.
        • et al.
        Difference in white matter microstructure in differential diagnosis of normal pressure hydrocephalus and Alzheimer's disease.
        Clin Neurol Neurosurg. 2015; 140: 52-59
        • Delli Pizzi S.
        • Franciotti R.
        • Taylor J.P.
        • et al.
        Structural connectivity is differently altered in dementia with Lewy body and Alzheimer's disease.
        Front Aging Neurosci. 2015; 7: 208
        • Pautler R.G.
        Mouse MRI: concepts and applications in physiology.
        Physiol Bethesda Md. 2004; 19: 168-175
        • Liu J.
        • Zhang X.
        • Yu C.
        • et al.
        Impaired parahippocampus connectivity in mild cognitive impairment and Alzheimer's disease.
        J Alzheimers Dis JAD. 2015; 49: 1051-1064
        • Hafkemeijer A.
        • Möller C.
        • Dopper E.G.
        • et al.
        Resting state functional connectivity differences between behavioral variant frontotemporal dementia and Alzheimer's disease.
        Front Hum Neurosci. 2015; 9: 474
        • Zippo A.G.
        • Castiglioni I.
        • Borsa V.M.
        • Biella G.E.
        The compression flow as a measure to estimate the brain connectivity changes in resting state fMRI and 18FDG-PET Alzheimer's disease connectomes.
        Front Comput Neurosci. 2015; 9: 148
        • Hanaoka T.
        • Kimura N.
        • Aso Y.
        • et al.
        Relationship between white matter lesions and regional cerebral blood flow changes during longitudinal follow up in Alzheimer's disease.
        Geriatr Gerontol Int. 2015; ([Epub ahead of print])
        • Wierenga C.E.
        • Hays C.C.
        • Zlatar Z.Z.
        Cerebral blood flow measured by arterial spin labeling MRI as a preclinical marker of Alzheimer's disease.
        J Alzheimers Dis JAD. 2014; 42: S411-S419
        • Klunk W.E.
        • Bacskai B.J.
        • Mathis C.A.
        • et al.
        Imaging Abeta plaques in living transgenic mice with multiphoton microscopy and methoxy-X04, a systemically administered Congo red derivative.
        J Neuropathol Exp Neurol. 2002; 61: 797-805
        • Klunk W.E.
        • Engler H.
        • Nordberg A.
        • et al.
        Imaging the pathology of Alzheimer's disease: amyloid-imaging with positron emission tomography.
        Neuroimaging Clin N Am. 2003; 13 (ix): 781-789
        • Clark C.M.
        • Pontecorvo M.J.
        • Beach T.G.
        • et al.
        Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-β plaques: a prospective cohort study.
        Lancet Neurol. 2012; 11: 669-678
        • Chien D.T.
        • Bahri S.
        • Szardenings A.K.
        • et al.
        Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807.
        J Alzheimers Dis JAD. 2013; 34: 457-468
        • Chien D.T.
        • Szardenings A.K.
        • Bahri S.
        • et al.
        Early clinical PET imaging results with the novel PHF-tau radioligand [F18]-T808.
        J Alzheimers Dis JAD. 2014; 38: 171-184
        • Small G.W.
        • Greenfield S.
        Current and future treatments for Alzheimer disease.
        Am J Geriatr Psychiatry. 2015; 23: 1101-1105
        • Benveniste H.
        • Einstein G.
        • Kim K.R.
        • Hulette C.
        • Johnson G.A.
        Detection of neuritic plaques in Alzheimer's disease by magnetic resonance microscopy.
        Proc Natl Acad Sci U S A. 1999; 96: 14079-14084
        • Dhenain M.
        • Privat N.
        • Duyckaerts C.
        • Jacobs R.E.
        Senile plaques do not induce susceptibility effects in T2*-weighted MR microscopic images.
        NMR Biomed. 2002; 15: 197-203
        • Dhenain M.
        • Delatour B.
        • Walczak C.
        • Volk A.
        Passive staining: a novel ex vivo MRI protocol to detect amyloid deposits in mouse models of Alzheimer's disease.
        Magn Reson Med. 2006; 55: 687-693
        • Chamberlain R.
        • Reyes D.
        • Curran G.L.
        • et al.
        Comparison of amyloid plaque contrast generated by T2-weighted, T2*-weighted, and susceptibility-weighted imaging methods in transgenic mouse models of Alzheimer's disease.
        Magn Reson Med. 2009; 61: 1158-1164
        • Pérez-Torres C.J.
        • Reynolds J.O.
        • Pautler R.G.
        Use of magnetization transfer contrast MRI to detect early molecular pathology in Alzheimer's disease.
        Magn Reson Med. 2014; 71: 333-338
        • Bigot C.
        • Vanhoutte G.
        • Verhoye M.
        • Van der Linden A.
        Magnetization transfer contrast imaging reveals amyloid pathology in Alzheimer's disease transgenic mice.
        Neuroimage. 2014; 87: 111-119
        • Park J.Y.
        • Baek M.J.
        • Choi E.S.
        • et al.
        Paramagnetic ultrasmall gadolinium oxide nanoparticles as advanced T1 MRI contrast agent: account for large longitudinal relaxivity, optimal particle diameter, and in vivo T1 MR images.
        ACS Nano. 2009; 3: 3663-3669
        • Faucher L.
        • Gossuin Y.
        • Hocq A.
        • Fortin M.-A.
        Impact of agglomeration on the relaxometric properties of paramagnetic ultra-small gadolinium oxide nanoparticles.
        Nanotechnology. 2011; 22: 295103
        • Stankiewicz J.
        • Panter S.S.
        • Neema M.
        • Arora A.
        • Batt C.E.
        • Bakshi R.
        Iron in chronic brain disorders: imaging and neurotherapeutic implications.
        Neurother J Am Soc Exp Neurother. 2007; 4: 371-386
        • Sperling R.A.
        • Jack Jr., C.R.
        • Black S.E.
        • et al.
        Amyloid related imaging abnormalities (ARIA) in amyloid modifying therapeutic trials: recommendations from the Alzheimer's Association Research Roundtable Workgroup.
        Alzheimers Dement J Alzheimers Assoc. 2011; 7: 367-385
        • Leike J.U.
        • Sachse A.
        • Rupp K.
        Characterization of continuously extruded iopromide-carrying liposomes for computed tomography blood-pool imaging.
        Invest Radiol. 2001; 36: 303-308
        • Sachse A.
        • Leike J.U.
        • Schneider T.
        • et al.
        Biodistribution and computed tomography blood-pool imaging properties of polyethylene glycol-coated iopromide-carrying liposomes.
        Invest Radiol. 1997; 32: 44-50
        • Sachse A.
        • Leike J.U.
        • Rössling G.L.
        • Wagner S.E.
        • Krause W.
        Preparation and evaluation of lyophilized iopromide-carrying liposomes for liver tumor detection.
        Invest Radiol. 1993; 28: 838-844
        • Burke S.J.
        • Annapragada A.
        • Hoffman E.A.
        • et al.
        Imaging of pulmonary embolism and t-PA therapy effects using MDCT and liposomal iohexol blood pool agent: preliminary results in a rabbit model.
        Acad Radiol. 2007; 14: 355-362
        • Karathanasis E.
        • Suryanarayanan S.
        • Balusu S.R.
        • et al.
        Imaging nanoprobe for prediction of outcome of nanoparticle chemotherapy by using mammography.
        Radiology. 2009; 250: 398-406
        • Karathanasis E.
        • Chan L.
        • Balusu S.R.
        • et al.
        Multifunctional nanocarriers for mammographic quantification of tumor dosing and prognosis of breast cancer therapy.
        Biomaterials. 2008; 29: 4815-4822
        • Ghaghada K.B.
        • Badea C.T.
        • Karumbaiah L.
        • et al.
        Evaluation of tumor microenvironment in an animal model using a nanoparticle contrast agent in computed tomography imaging.
        Acad Radiol. 2011; 18: 20-30
        • Ashton J.R.
        • Clark D.P.
        • Moding E.J.
        • et al.
        Dual-energy micro-CT functional imaging of primary lung cancer in mice using gold and iodine nanoparticle contrast agents: a validation study.
        PLoS One. 2014; 9: e88129
        • Bell R.C.
        • Rogith D.
        • Johnson C.W.
        • et al.
        Data analysis: evaluation of nanoscale contrast agent enhanced CT scan to differentiate between benign and malignant lung cancer in mouse model.
        AMIA Annu Symp Proc. 2012; 2012: 27-35
        • Bhavane R.
        • Badea C.
        • Ghaghada K.B.
        • et al.
        Dual-energy computed tomography imaging of atherosclerotic plaques in a mouse model using a liposomal-iodine nanoparticle contrast agent.
        Circ Cardiovasc Imaging. 2013; 6: 285-294
        • Starosolski Z.
        • Villamizar C.A.
        • Rendon D.
        • et al.
        Ultra high-resolution in vivo computed tomography imaging of mouse cerebrovasculature using a long circulating blood pool contrast agent.
        Sci Rep. 2015; 5: 10178
        • Tanifum E.A.
        • Starosolski Z.A.
        • Fowler S.W.
        • Jankowsky J.L.
        • Annapragada A.V.
        Cerebral vascular leak in a mouse model of amyloid neuropathology.
        J Cereb Blood Flow Metab. 2014; 34: 1646-1654
        • Barsky D.
        • Pütz B.
        • Schulten K.
        • Magin R.L.
        Theory of paramagnetic contrast agents in liposome systems.
        Magn Reson Med. 1992; 24: 1-13
        • Mulder W.J.
        • Strijkers G.J.
        • van Tilborg G.A.
        • Griffioen A.W.
        • Nicolay K.
        Lipid-based nanoparticles for contrast-enhanced MRI and molecular imaging.
        NMR Biomed. 2006; 19: 142-164
        • Gløgård C.
        • Stensrud G.
        • Hovland R.
        • Fossheim S.L.
        • Klaveness J.
        Liposomes as carriers of amphiphilic gadolinium chelates: the effect of membrane composition on incorporation efficacy and in vitro relaxivity.
        Int J Pharm. 2002; 233: 131-140
        • Ghaghada K.B.
        • Ravoori M.
        • Sabapathy D.
        • Bankson J.
        • Kundra V.
        • Annapragada A.
        New dual mode gadolinium nanoparticle contrast agent for magnetic resonance imaging.
        PLoS One. 2009; 4: e7628
        • Howles G.P.
        • Ghaghada K.B.
        • Qi Y.
        • Mukundan S.
        • Johnson G.A.
        High-resolution magnetic resonance angiography in the mouse using a nanoparticle blood-pool contrast agent.
        Magn Reson Med. 2009; 62: 1447-1456
        • Ayyagari A.L.
        • Zhang X.
        • Ghaghada K.B.
        • Annapragada A.
        • Hu X.
        • Bellamkonda R.V.
        Long-circulating liposomal contrast agents for magnetic resonance imaging.
        Magn Reson Med. 2006; 55: 1023-1029
        • Ghaghada K.B.
        • Bockhorst K.H.
        • Mukundan S.
        • Annapragada A.V.
        • Narayana P.A.
        High-resolution vascular imaging of the rat spine using liposomal blood pool MR agent.
        AJNR Am J Neuroradiol. 2007; 28: 48-53
        • Bucholz E.
        • Ghaghada K.
        • Qi Y.
        • Mukundan S.
        • Johnson G.A.
        Four-dimensional MR microscopy of the mouse heart using radial acquisition and liposomal gadolinium contrast agent.
        Magn Reson Med. 2008; 60: 111-118
        • Bucholz E.
        • Ghaghada K.
        • Qi Y.
        • Mukundan S.
        • Rockman H.A.
        • Johnson G.A.
        Cardiovascular phenotyping of the mouse heart using a 4D radial acquisition and liposomal Gd-DTPA-BMA.
        Magn Reson Med. 2010; 63: 979-987
        • Karathanasis E.
        • Park J.
        • Agarwal A.
        • et al.
        MRI mediated, non-invasive tracking of intratumoral distribution of nanocarriers in rat glioma.
        Nanotechnology. 2008; 19: 315101
        • Aime S.
        • Castelli D.D.
        • Crich S.G.
        • Gianolio E.
        • Terreno E.
        Pushing the sensitivity envelope of lanthanide-based magnetic resonance imaging (MRI) contrast agents for molecular imaging applications.
        Acc Chem Res. 2009; 42: 822-831
        • Aime S.
        • Delli Castelli D.
        • Lawson D.
        • Terreno E.
        Gd-loaded liposomes as T1, susceptibility, and CEST agents, all in one.
        J Am Chem Soc. 2007; 129: 2430-2431
        • Opina A.C.
        • Ghaghada K.B.
        • Zhao P.
        • Kiefer G.
        • Annapragada A.
        • Sherry A.D.
        TmDOTA-tetraglycinate encapsulated liposomes as pH-sensitive LipoCEST agents.
        PLoS One. 2011; 6: e27370
        • Haris M.
        • Singh A.
        • Cai K.
        • et al.
        MICEST: a potential tool for non-invasive detection of molecular changes in Alzheimer's disease.
        J Neurosci Methods. 2013; 212: 87-93
        • Lee R.J.
        • Low P.S.
        Folate-mediated tumor cell targeting of liposome-entrapped doxorubicin in vitro.
        Biochim Biophys Acta. 1995; 1233: 134-144
        • Caravan P.
        • Ellison J.J.
        • McMurry T.J.
        • Lauffer R.B.
        Gadolinium(III) chelates as MRI contrast agents: structure, dynamics, and applications.
        Chem Rev. 1999; 99: 2293-2352
        • Caravan P.
        • Farrar C.T.
        • Frullano L.
        • Uppal R.
        Influence of molecular parameters and increasing magnetic field strength on relaxivity of gadolinium- and manganese-based T1 contrast agents.
        Contrast Media Mol Imaging. 2009; 4: 89-100
        • Bertini I.
        • Bianchini F.
        • Calorini L.
        • et al.
        Persistent contrast enhancement by sterically stabilized paramagnetic liposomes in murine melanoma.
        Magn Reson Med. 2004; 52: 669-672
        • Jaruszewski K.M.
        • Curran G.L.
        • Swaminathan S.K.
        • et al.
        Multimodal nanoprobes to target cerebrovascular amyloid in Alzheimer's disease brain.
        Biomaterials. 2014; 35: 1967-1976
        • Jacoby C.
        • Temme S.
        • Mayenfels F.
        • et al.
        Probing different perfluorocarbons for in vivo inflammation imaging by 19F MRI: image reconstruction, biological half-lives and sensitivity.
        NMR Biomed. 2014; 27: 261-271
        • Balducci A.
        • Helfer B.M.
        • Ahrens E.T.
        • O'Hanlon C.F.
        • Wesa A.K.
        Visualizing arthritic inflammation and therapeutic response by fluorine-19 magnetic resonance imaging (19F MRI).
        J Inflamm Lond Engl. 2012; 9: 24
        • Temme S.
        • Bönner F.
        • Schrader J.
        • Flögel U.
        19F magnetic resonance imaging of endogenous macrophages in inflammation.
        Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2012; 4: 329-343
        • Weise G.
        • Basse-Lüsebrink T.C.
        • Kleinschnitz C.
        • Kampf T.
        • Jakob P.M.
        • Stoll G.
        In vivo imaging of stepwise vessel occlusion in cerebral photothrombosis of mice by 19F MRI.
        PLoS One. 2011; 6: e28143
        • Hertlein T.
        • Sturm V.
        • Kircher S.
        • et al.
        Visualization of abscess formation in a murine thigh infection model of Staphylococcus aureus by 19F-magnetic resonance imaging (MRI).
        PLoS One. 2011; 6: e18246
        • Ebner B.
        • Behm P.
        • Jacoby C.
        • et al.
        Early assessment of pulmonary inflammation by 19F MRI in vivo.
        Circ Cardiovasc Imaging. 2010; 3: 202-210
        • Kim J.G.
        • Zhao D.
        • Song Y.
        • Constantinescu A.
        • Mason R.P.
        • Liu H.
        Interplay of tumor vascular oxygenation and tumor pO2 observed using near-infrared spectroscopy, an oxygen needle electrode, and 19F MR pO2 mapping.
        J Biomed Opt. 2003; 8: 53-62
        • Hitchens T.K.
        • Ye Q.
        • Eytan D.F.
        • Janjic J.M.
        • Ahrens E.T.
        • Ho C.
        19F MRI detection of acute allograft rejection with in vivo perfluorocarbon labeling of immune cells.
        Magn Reson Med. 2011; 65: 1144-1153
        • Ahrens E.T.
        • Helfer B.M.
        • O'Hanlon C.F.
        • Schirda C.
        Clinical cell therapy imaging using a perfluorocarbon tracer and fluorine-19 MRI.
        Magn Reson Med. 2014; 72: 1696-1701
        • Higuchi M.
        • Iwata N.
        • Matsuba Y.
        • Sato K.
        • Sasamoto K.
        • Saido T.C.
        19F and 1H MRI detection of amyloid beta plaques in vivo.
        Nat Neurosci. 2005; 8: 527-533
        • Flaherty D.P.
        • Walsh S.M.
        • Kiyota T.
        • Dong Y.
        • Ikezu T.
        • Vennerstrom J.L.
        Polyfluorinated bis-styrylbenzene beta-amyloid plaque binding ligands.
        J Med Chem. 2007; 50: 4986-4992
        • Yanagisawa D.
        • Taguchi H.
        • Ibrahim N.F.
        • et al.
        Preferred features of a fluorine-19 MRI probe for amyloid detection in the brain.
        J Alzheimers Dis JAD. 2014; 39: 617-631
        • Tooyama I.
        • Yanagisawa D.
        • Taguchi H.
        • et al.
        Amyloid imaging using fluorine-19 magnetic resonance imaging ((19)F-MRI).
        Ageing Res Rev. 2016; ([Epub ahead of print])
        • Pautler R.G.
        In vivo, trans-synaptic tract-tracing utilizing manganese-enhanced magnetic resonance imaging (MEMRI).
        NMR Biomed. 2004; 17: 595-601
        • Massaad C.A.
        • Pautler R.G.
        Manganese-enhanced magnetic resonance imaging (MEMRI).
        Methods Mol Biol Clifton NJ. 2011; 711: 145-174
        • Smith K.D.
        • Paylor R.
        • Pautler R.G.
        R-flurbiprofen improves axonal transport in the Tg2576 mouse model of Alzheimer's disease as determined by MEMRI.
        Magn Reson Med. 2011; 65: 1423-1429
        • Serrano F.
        • Deshazer M.
        • Smith K.D.
        • Ananta J.S.
        • Wilson L.J.
        • Pautler R.G.
        Assessing transneuronal dysfunction utilizing manganese-enhanced MRI (MEMRI).
        Magn Reson Med. 2008; 60: 169-175
        • Pautler R.G.
        • Mongeau R.
        • Jacobs R.E.
        In vivo trans-synaptic tract tracing from the murine striatum and amygdala utilizing manganese enhanced MRI (MEMRI).
        Magn Reson Med. 2003; 50: 33-39
        • Inoue T.
        • Majid T.
        • Pautler R.G.
        Manganese enhanced MRI (MEMRI): neurophysiological applications.
        Rev Neurosci. 2011; 22: 675-694
        • Pautler R.G.
        • Silva A.C.
        • Koretsky A.P.
        In vivo neuronal tract tracing using manganese-enhanced magnetic resonance imaging.
        Magn Reson Med. 1998; 40: 740-748
        • Murray R.C.
        • Calof A.L.
        Neuronal regeneration: lessons from the olfactory system.
        Semin Cell Dev Biol. 1999; 10: 421-431
        • Pautler R.G.
        Biological applications of manganese-enhanced magnetic resonance imaging.
        Methods Mol Med. 2006; 124: 365-386
        • Sharma R.
        • Buras E.
        • Terashima T.
        • et al.
        Hyperglycemia induces oxidative stress and impairs axonal transport rates in mice.
        PLoS One. 2010; 5: e13463
        • Smith K.D.
        • Kallhoff V.
        • Zheng H.
        • Pautler R.G.
        In vivo axonal transport rates decrease in a mouse model of Alzheimer's disease.
        Neuroimage. 2007; 35: 1401-1408
        • Smith K.D.
        • Peethumnongsin E.
        • Lin H.
        • Zheng H.
        • Pautler R.G.
        Increased human wild type tau attenuates axonal transport deficits caused by loss of APP in mouse models.
        Magn Reson Insights. 2010; 4: 11-18
        • Hu T.C.
        • Pautler R.G.
        • MacGowan G.A.
        • Koretsky A.P.
        Manganese-enhanced MRI of mouse heart during changes in inotropy.
        Magn Reson Med. 2001; 46: 884-890
        • Pautler R.G.
        • Koretsky A.P.
        Tracing odor-induced activation in the olfactory bulbs of mice using manganese-enhanced magnetic resonance imaging.
        Neuroimage. 2002; 16: 441-448
        • Saar G.
        • Cheng N.
        • Belluscio L.
        • Koretsky A.P.
        Laminar specific detection of APP induced neurodegeneration and recovery using MEMRI in an olfactory based Alzheimer's disease mouse model.
        Neuroimage. 2015; 118: 183-192
        • Gallagher J.J.
        • Zhang X.
        • Ziomek G.J.
        • Jacobs R.E.
        • Bearer E.L.
        Deficits in axonal transport in hippocampal-based circuitry and the visual pathway in APP knock-out animals witnessed by manganese enhanced MRI.
        Neuroimage. 2012; 60: 1856-1866
        • Kim J.
        • Choi I.-Y.
        • Michaelis M.L.
        • Lee P.
        Quantitative in vivo measurement of early axonal transport deficits in a triple transgenic mouse model of Alzheimer's disease using manganese-enhanced MRI.
        Neuroimage. 2011; 56: 1286-1292
        • Massaad C.A.
        • Amin S.K.
        • Hu L.
        • Mei Y.
        • Klann E.
        • Pautler R.G.
        Mitochondrial superoxide contributes to blood flow and axonal transport deficits in the Tg2576 mouse model of Alzheimer's disease.
        PLoS One. 2010; 5: e10561
        • Majid T.
        • Ali Y.O.
        • Venkitaramani D.V.
        • Jang M.K.
        • Lu H.C.
        • Pautler R.G.
        In vivo axonal transport deficits in a mouse model of fronto-temporal dementia.
        Neuroimage Clin. 2014; 4: 711-717
        • Massaad C.A.
        • Washington T.M.
        • Pautler R.G.
        • Klann E.
        Overexpression of SOD-2 reduces hippocampal superoxide and prevents memory deficits in a mouse model of Alzheimer's disease.
        Proc Natl Acad Sci U S A. 2009; 106: 13576-13581
        • Pipe J.G.
        • Zwart N.
        Turboprop: improved PROPELLER imaging.
        Magn Reson Med. 2006; 55: 380-385
        • Bhavsar P.S.
        • Zwart N.R.
        • Pipe J.G.
        Fast, variable system delay correction for spiral MRI.
        Magn Reson Med. 2014; 71: 773-782
        • Li Z.
        • Pipe J.G.
        • Lee C.Y.
        • Debbins J.P.
        • Karis J.P.
        • Huo D.
        X-PROP: a fast and robust diffusion-weighted propeller technique.
        Magn Reson Med. 2011; 66: 341-347
        • Barthel H.
        • Schroeter M.L.
        • Hoffmann K.-T.
        • Sabri O.
        PET/MR in dementia and other neurodegenerative diseases.
        Semin Nucl Med. 2015; 45: 224-233