Abstract
Purpose
The activity of the glymphatic system is impaired in animal models of Alzheimer’s disease (AD). We evaluated the activity of the human glymphatic system in cases of AD with a diffusion-based technique called diffusion tensor image analysis along the perivascular space (DTI-ALPS).
Materials and methods
Diffusion tensor images were acquired to calculate diffusivities in the x, y, and z axes of the plane of the lateral ventricle body in 31 patients. We evaluated the diffusivity along the perivascular spaces as well as projection fibers and association fibers separately, to acquire an index for diffusivity along the perivascular space (ALPS-index) and correlated them with the mini mental state examinations (MMSE) score.
Results
We found a significant negative correlation between diffusivity along the projection fibers and association fibers. We also observed a significant positive correlation between diffusivity along perivascular spaces shown as ALPS-index and the MMSE score, indicating lower water diffusivity along the perivascular space in relation to AD severity.
Conclusion
Activity of the glymphatic system may be evaluated with diffusion images. Lower diffusivity along the perivascular space on DTI-APLS seems to reflect impairment of the glymphatic system. This method may be useful for evaluating the activity of the glymphatic system.
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References
Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta. Sci Transl Med. 2012;4(147):147ra11.
Iliff JJ, Lee H, Yu M, Feng T, Logan J, Nedergaard M, et al. Brain-wide pathway for waste clearance captured by contrast-enhanced MRI. J Clin Invest. 2013;123(3):1299–309.
Jessen NA, Munk AS, Lundgaard I, Nedergaard M. The glymphatic system: a beginner’s guide. Neurochem Res. 2015;40(12):2583–99.
Johnston M, Zakharov A, Papaiconomou C, Salmasi G, Armstrong D. Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates and other mammalian species. Cerebrospinal Fluid Res. 2004;1(1):2.
Murtha LA, Yang Q, Parsons MW, Levi CR, Beard DJ, Spratt NJ, et al. Cerebrospinal fluid is drained primarily via the spinal canal and olfactory route in young and aged spontaneously hypertensive rats. Fluids Barriers CNS. 2014;11:12.
Okudera T, Huang YP, Fukusumi A, Nakamura Y, Hatazawa J, Uemura K. Micro-angiographical studies of the medullary venous system of the cerebral hemisphere. Neuropathology. 1999;19(1):93–111.
Reisberg B, Prichep L, Mosconi L, John ER, Glodzik-Sobanska L, Boksay I, et al. The pre-mild cognitive impairment, subjective cognitive impairment stage of Alzheimer’s disease. Alzheimers Dement. 2008;4(1 Suppl 1):S98–108.
Masutani Y, Aoki S, Abe O, Hayashi N, Otomo K. MR diffusion tensor imaging: recent advance and new techniques for diffusion tensor visualization. Eur J Radiol. 2003;46(1):53–66.
Peng W, Achariyar TM, Li B, Liao Y, Mestre H, Hitomi E, et al. Suppression of glymphatic fluid transport in a mouse model of Alzheimer’s disease. Neurobiol Dis. 2016;93:215–25.
Achariyar TM, Li B, Peng W, Verghese PB, Shi Y, McConnell E, et al. Glymphatic distribution of CSF-derived apoE into brain is isoform specific and suppressed during sleep deprivation. Mol Neurodegener. 2016;11(1):74.
Zeppenfeld DM, Simon M, Haswell JD, D’Abreo D, Murchison C, Quinn JF, et al. Association of perivascular localization of aquaporin-4 with cognition and Alzheimer disease in aging brains. JAMA Neurol. 2016;74(1):91–9.
Tali ET, Ercan N, Krumina G, Rudwan M, Mironov A, Zeng QY, et al. Intrathecal gadolinium (gadopentetate dimeglumine) enhanced magnetic resonance myelography and cisternography: results of a multicenter study. Invest Radiol. 2002;37(3):152–9.
Oner AY, Barutcu B, Aykol S, Tali ET. Intrathecal contrast-enhanced magnetic resonance imaging-related brain signal changes: residual gadolinium deposition? Invest Radiol 2016. doi:10.1097/RLI.0000000000000327
Samardzic D, Thamburaj K. Magnetic resonance characteristics and susceptibility weighted imaging of the brain in gadolinium encephalopathy. J Neuroimaging. 2015;25(1):136–9.
Naganawa S, Nakane T, Kawai H, Taoka T. Gd-based contrast enhancement of the perivascular spaces in the basal ganglia. Magn Reson Med Sci. 2016;16(1):61–5.
Naganawa S, Suzuki K, Yamazaki M, Sakurai Y. Serial scans in healthy volunteers following intravenous administration of gadoteridol: time course of contrast enhancement in various cranial fluid spaces. Magn Reson Med Sci. 2014;13(1):7–13.
Taoka T, Fukusumi A, Miyasaka T, Kawai H, Nakane T, Kichikawa K, et al. Structure of the medullary veins of the cerebral hemisphere and related disorders. Radiographics. 2017;37(1):281–97.
Fellgiebel A, Yakushev I. Diffusion tensor imaging of the hippocampus in MCI and early Alzheimer’s disease. J Alzheimers Dis. 2011;26(Suppl 3):257–62.
Huang H, Fan X, Weiner M, Martin-Cook K, Xiao G, Davis J, et al. Distinctive disruption patterns of white matter tracts in Alzheimer’s disease with full diffusion tensor characterization. Neurobiol Aging. 2012;33(9):2029–45.
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Funding was provided by Grant-in-Aid for Scientific Research (Grant Nos. 16K10312 and 26461834).
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Taoka, T., Masutani, Y., Kawai, H. et al. Evaluation of glymphatic system activity with the diffusion MR technique: diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Alzheimer’s disease cases. Jpn J Radiol 35, 172–178 (2017). https://doi.org/10.1007/s11604-017-0617-z
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DOI: https://doi.org/10.1007/s11604-017-0617-z