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Magnetic Resonance Materials in Physics, Biology and Medicine

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01-08-2020 | Research Article

Pilot study utilizing MRI 3D TGSE PASL (arterial spin labeling) differentiating clearance rates of labeled protons in the CNS of patients with early Alzheimer disease from normal subjects

Authors: Charles R Joseph, Christopher M Benhatzel, Logan J Stern, Olivia M Hopper, Michael D Lockwood

Published in: Magnetic Resonance Materials in Physics, Biology and Medicine | Issue 4/2020

Abstract

Objective

To determine the feasibility of 3D TGSE PASL MRI with long inversion times to estimate CNS perfusion clearance, comparing normals to Alzheimer disease patients.

Methods

This pilot study used 3D TGSE PASL MRI with long TIs to estimate the signal clearance of labeled blood/ultra-filtrate (CSF) from brain signal averages of seven inversion times (TI) from six regions of the brain in 18 normal subjects of ages 18–70 years before and after exercise. Arterial pulse corrected signal average per TI versus TI was plotted. The slope (linear regression) indicated the clearance rate. Three subjects with mild Alzheimer disease (AD) were studied pre-exercise only.

Results

In normals, signal decay rate variance among brain regions, age groups and post-exercise failed to demonstrate statistical significance except in middle-age group pre- to post-exercise-dominant temporal lobe. We found highly statistically significant reduced signal clearance rate in the AD group.

Discussion

Signal decay in normal age groups correlates with decay of T1_blood, thus CSF paravascular flow egresses and is inseparable from venous outflow. The AD group correlates with decay rate T1_CSF, indicating a proportion of labeled blood ultra-filtered within the brain (paravascular fluid) is retained. This provides indirect evidence of reduced paravascular clearance in AD. Further development may produce an efficient biomarker identifying neurodegenerative diseases and future treatment efficacy.

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Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, Derecki NC et al (2015) Structural and functional features of central nervous system lymphatic vessels. Nature. https://doi.org/10.1038/nature14432. (Nature Publishing Group) CrossRefPubMedPubMedCentral

Louveau A, Plog B, Antila S, Alitalo K, Nedergaard M, Kipnis J (2017) Understanding the functions and relationships of the glymphatic system and meningeal lymphatics. J Clin Invest 127(9):3210–3219. https://doi.org/10.1172/JCI90603 CrossRefPubMedPubMedCentral

Brinker T, Stopa E, Morrison J, Klinge P (2014) A new look at cerebrospinal fluid circulation. Fluids Barriers CNS 11:10. https://doi.org/10.1186/2045-8118-11-10 CrossRefPubMedPubMedCentral

Günther M, Oshio K, Feinberg DA (2005) Single-shot 3D imaging techniques improve arterial spin labeling perfusion measurements. Magn Reson Med 54(2):491–498. https://doi.org/10.1002/mrm.20580 CrossRefPubMed

Alsop DC, Detre JA, Golay X, Günther M, Hendrikse J, Hernandez-Garcia L, Zaharchuk G et al (2015) Recommended implementation of arterial spin-labeled perfusion MRI for clinical applications: a consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia. Magn Reson Med 73(1):102–116. https://doi.org/10.1002/mrm.25197 CrossRefPubMed

MacDonald ME et al (2018) Modeling hyperoxia-induced bold signal dynamics to estimate cerebral blood flow, volume and mean transit time. NeuroImage 178:461–474. https://doi.org/10.1016/J.NEUROIMAGE.2018.05.066. (Academic Press) CrossRefPubMed

Yan L, Liu CY et al (2016) Assessing Intracranial Vascular Compliance Using Dynamic Arterial Spin Labeling. Neuroimage 124(Pt A):433–41. doi:10.1016/j.neuroimage.2015.09.008 (NIH Public Access)

Holter KE, Kehlet B, Devor A et al (2017) Interstitial solute transport in 3D reconstructed neuropil occurs by diffusion rather than bulk flow. Proc Natl Acad Sci USA 114(37):9894–9899. https://doi.org/10.1073/pnas.1706942114 CrossRefPubMedPubMedCentral

Ohene Y, Harrison IF, Nahavandi P et al (2019) Non-invasive MRI of brain clearance pathways using multiple echo time arterial spin labelling: an aquaporin-4 study. NeuroImage 188:515–523. https://doi.org/10.1016/j.neuroimage.2018.12.026 CrossRefPubMed

10.

Fernández-Seara MA, Wang Z, Wang J, Rao H-Y, Guenther M, Feinberg DA, Detre JA (2005) Continuous arterial spin labeling perfusion measurements using single shot 3D GRASE at 3 T. Magn Reson Med. https://doi.org/10.1002/mrm.20674 CrossRefPubMed

11.

Feinberg DA, Beckett A, Chen L (2013) Arterial spin labeling with simultaneous multi-slice echo planar imaging. Magn Reson Med 70:1500–1506. https://doi.org/10.1002/mrm.24994 CrossRefPubMedPubMedCentral

12.

Chao LL, Buckley S, Kornak J, Schuff N, Madison C, Yaffe K, Miller BL (2010) ASL perfusion MRI predicts cognitive decline and conversion from mci to dementia. Alzheimer Dis Assoc Disord 24:19–27. https://doi.org/10.1097/WAD.0b013e3181b4f736 CrossRefPubMedPubMedCentral

13.

Yan L, Liu CY, Smith RX, Jog M, Langham M, Krasileva K, Wang DJJ (2016) Assessing intracranial vascular compliance using dynamic arterial spin labeling. NeuroImage 124(Pt A):433–441. https://doi.org/10.1016/j.neuroimage.2015.09.008 CrossRefPubMed

14.

Smith AJ, Yao X, Dix JA, Jin B, Verkman AS (2017) Test of the “glymphatic” hypothesis demonstrates diffusive and aquaporin-4-independent solute transport in rodent brain parenchyma. ELife 2017:6. https://doi.org/10.7554/eLife.27679 CrossRef

15.

Abbott J (2004) Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathology. Neurochem Int 45:545–552. https://doi.org/10.1016/j.neuint.2003.11.006 CrossRefPubMed

16.

Fisher JP, Hartwich D, Seifert T, Olesen ND, Mcnulty CL, Nielsen HB, Secher NH (2013) Cerebral perfusion, oxygenation and metabolism during exercise in young and elderly individuals. J Physiol 591(7):1859–1870. https://doi.org/10.1113/jphysiol.2012.244905 CrossRefPubMed

17.

Tanaka H, Monahan K, Seals D (2001) Age-predicted maximal heart rate revisited. J Am Coll Cardiol 37:153–156. https://www.ncbi.nlm.nih.gov/pubmed/11153730

18.

Lu H, Clingman C, X Golay, MR Peter (2019) Determining the longitudinal relaxation time (T1) of blood at 3.0 Tesla. Wiley Online Library. https://onlinelibrary.wiley.com/doi/abs/10.1002/mrm.20178

19.

Bipin M, Coppo B, Frances S, McGivney D, Ian HJ, Chen Y, Jiang Y, Alan GM et al (2019) Magnetic resonance fingerprinting: a technical review. Magn Reson Med 81(1):25–46. https://doi.org/10.1002/mrm.27403 CrossRef

20.

Ringstad G, Vatnehol S, Eide P (2017) Glymphatic MRI in idiopathic normal pressure hydrocephalus. Brain 140:2691–2705. https://doi.org/10.1093/brain/awx191 CrossRefPubMedPubMedCentral

21.

Lefferts WK, Augustine JA, Heffernan KS (2014) Effect of acute resistance exercise on carotid artery stiffness and cerebral blood flow pulsatility. Front Physiol 5:101. https://doi.org/10.3389/fphys.2014.0010121 CrossRefPubMedPubMedCentral

22.

Querido JS, Sheel W (2007) Regulation of cerebral blood flow during exercise. Sports Med 37:765–782. https://doi.org/10.2165/00007256-200737090-00002 CrossRefPubMed

23.

Ogoh S, Ainslie PN (2009) Cerebral blood flow during exercise: Mechanisms of regulation. J Appl Physiol 107:371380. https://doi.org/10.1152/japplphysiol.00573.2009 CrossRef

24.

Bering E (1952) Water exchange of central nervous system and cerebrospinal fluid. J Neurosurg 9:275–287. https://thejns.org/view/journals/j-neurosurg/9/3/j-neurosurg.9.issue-3.xml

25.

Plog BA, Nedergaard M (2018) The glymphatic system in central nervous system health disease: past, present, and future. Annu Rev Pathol Mech Dis 13(1):379–394. https://doi.org/10.1146/annurev-pathol-051217-111018 CrossRef

26.

Igarshi H, Tsujita M, Kwee IL, Nakada T (2014) Water influx into cerebrospinal fluid is primarily controlled by aquaporin-4, not aquaporin-1. NeuroReport 25:39–43. https://doi.org/10.1097/WNR.0000000000000042 CrossRef

27.

Papadopoulos MC, Verkman AS (2013) Aquaporin water channels in the nervous system. Nature Rev Neurosci 14:265–277. https://doi.org/10.1038/nrn3468 CrossRef

28.

Da Mesquita S, Louveau A, Vaccari A, Smirnov I, Cornelison C, Kingsmore K, Contarino C (2018) Functional aspects of meningeal lymphatics in aging and Alzheimer's disease. Nature 560:185–191. https://doi.org/10.1038/s41586-018-0368-8 CrossRefPubMedPubMedCentral

29.

Billinger SA, Vidoni ED, Greer CS, Graves RS, Mattlage AE, Burns JM (2014) Cardiopulmonary exercise testing is well tolerated in people with Alzheimer-related cognitive impairment. Arch Phys Med Rehabil 95:1714–1718. https://doi.org/10.1016/j.apmr.2014.04.007 CrossRefPubMedPubMedCentral

30.

Femminella G, Rengo G, Komici K, Iacotucci P, Petraglia L, Pagano G, De Lucia C (2014) Autonomic dysfunction in Alzheimer's disease: tools for assessment and review of the literature. J Alzheimer's Dis 42:369–377. https://doi.org/10.3233/JAD-140513 CrossRef

31.

Shen Z, Lei J, Li X, Wang Z, Bao X, Wang R (2018) Multifaceted assessment of the APP/PS1 mouse model for Alzheimer’s disease: applying MRS, DTI, and ASL. Brain Res 1698:114–120. https://doi.org/10.1016/j.brainres.2018.08.001 CrossRefPubMed

32.

Wolk DA, Detre JA (2012) Arterial spin labeling MRI: an emerging biomarker for Alzheimer’s disease and other neurodegenerative conditions. Curr Opin Neurol 25(4):421–428. https://doi.org/10.1097/WCO.0b013e328354ff0a CrossRefPubMedPubMedCentral

Title: Pilot study utilizing MRI 3D TGSE PASL (arterial spin labeling) differentiating clearance rates of labeled protons in the CNS of patients with early Alzheimer disease from normal subjects
Authors: Charles R Joseph
Christopher M Benhatzel
Logan J Stern
Olivia M Hopper
Michael D Lockwood
Publication date: 01-08-2020
Publisher: Springer International Publishing
Published in: Magnetic Resonance Materials in Physics, Biology and Medicine / Issue 4/2020
Print ISSN: 0968-5243
Electronic ISSN: 1352-8661
DOI: https://doi.org/10.1007/s10334-019-00818-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Pilot study utilizing MRI 3D TGSE PASL (arterial spin labeling) differentiating clearance rates of labeled protons in the CNS of patients with early Alzheimer disease from normal subjects

Abstract

Objective

Methods

Results

Discussion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Methods

Results

Discussion

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