Moyamoya disease (MMD) causes cerebral arterial stenosis and hemodynamic disturbance, the latter of which may disrupt glymphatic system activity, the waste clearance system. We evaluated 46 adult patients with MMD and 33 age- and sex-matched controls using diffusivity along the perivascular space (ALPS) measured with diffusion tensor imaging (ALPS index), which may partly reflect glymphatic system activity, and multishell diffusion MRI to generate freewater maps. Twenty-three patients were also evaluated via 15O-gas positron emission tomography (PET), and all patients underwent cognitive tests. Compared to controls, patients (38.4 (13.2) years old, 35 females) had lower ALPS indices in the left and right hemispheres (1.94 (0.27) vs. 1.65 (0.25) and 1.94 (0.22) vs. 1.65 (0.19), P < 0.001). While the right ALPS index showed no correlation, the left ALPS index was correlated with parenchymal freewater (ρ = −0.47, P < 0.001); perfusion measured with PET (cerebral blood flow, ρ = 0.70, P < 0.001; mean transit time, ρ = −0.60, P = 0.003; and oxygen extraction fraction, ρ = −0.52, P = 0.003); and cognitive tests (trail making test part B for executive function; ρ = −0.37, P = 0.01). Adult patients with MMD may exhibit decreased glymphatic system activity, which is correlated with the degree of hemodynamic disturbance, increased interstitial freewater, and cognitive dysfunction, but further investigation is needed.
AgarwalNContarinoCToroEF.Neurofluids: a holistic approach to their physiology, interactive dynamics and clinical implications for neurological diseases. Veins and Lymphatics2019;
8: 8470.
2.
TaokaTItoRNakamichiR, et al.
Interstitial fluidopathy of the central nervous system: an umbrella term for disorders with impaired neurofluid dynamics. Magn Reson Med Sci2022;
23: 1–13.
3.
KlostranecJMVucevicDBhatiaKD, et al.
Current concepts in intracranial interstitial fluid transport and the glymphatic system: part I – anatomy and physiology. Radiology2021;
301: 502–514.
4.
KamagataKSaitoYAndicaC, et al.
Noninvasive magnetic resonance imaging measures of glymphatic system activity. J Magn Reson Imaging2023. DOI: 10.1002/jmri.28977.
5.
GaberelTGakubaCGoulayR, et al.
Impaired glymphatic perfusion after strokes revealed by contrast-enhanced MRI: a new target for fibrinolysis?Stroke2014;
45: 3092–3096.
6.
IliffJJWangMZeppenfeldDM, et al.
Cerebral arterial pulsation drives paravascular CSF-interstitial fluid exchange in the murine brain. J Neurosci2013;
33: 18190–18199.
7.
Guidelines for diagnosis and treatment of moyamoya disease (spontaneous occlusion of the circle of willis). Neurol Med Chir (Tokyo)2012;
52: 245–266.
8.
KuribaraTMikamiTKomatsuK, et al.
Prevalence of and risk factors for enlarged perivascular spaces in adult patients with moyamoya disease. BMC Neurol2017;
17: 149.
9.
ZouXLiaoYJiangC, et al.
Brain perfusion, cognition, and plasma Alzheimer's biomarkers in moyamoya disease. Alzheimer's & Dementia: The Journal of the Alzheimer's Association2023;
19: 3316–3326.
10.
JohnsonSEMcKnightCDLantsSK, et al.
Choroid plexus perfusion and intracranial cerebrospinal fluid changes after angiogenesis. J Cereb Blood Flow Metab2020;
40: 1658–1671.
11.
JohnsonSEMcKnightCDJordanLC, et al.
Choroid plexus perfusion in sickle cell disease and moyamoya vasculopathy: implications for glymphatic flow. J Cereb Blood Flow Metab2021;
41: 2699–2711.
12.
HaraSHoriMUedaR, et al.
Unraveling specific brain microstructural damage in moyamoya disease using diffusion magnetic resonance imaging and positron emission tomography. J Stroke Cerebrovasc Dis2019;
28: 1113–1125.
13.
HaraSHoriMKamagataK, et al.
Increased parenchymal free water may be decreased by revascularization surgery in patients with moyamoya disease. Magn Reson Med Sci2023. DOI: 10.2463/mrms.mp.2022-0146.
14.
TaokaTMasutaniYKawaiH, 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 Radiol2017;
35: 172–178.
15.
ZhangWZhouYWangJ, et al.
Glymphatic clearance function in patients with cerebral small vessel disease. NeuroImage2021;
238: 118257.
16.
TaokaTItoRNakamichiR, et al.
Reproducibility of diffusion tensor image analysis along the perivascular space (DTI-ALPS) for evaluating interstitial fluid diffusivity and glymphatic function: CHanges in alps index on multiple conditiON acquIsition eXperiment (CHAMONIX) study. Jpn J Radiol2022;
40: 147–158.
17.
KamagataKAndicaCTakabayashiK, et al.
Association of MRI indices of glymphatic system with amyloid deposition and cognition in mild cognitive impairment and Alzheimer disease. Neurology2022;
99: e2648–e2660.
18.
ChenHLChenPCLuCH, et al.
Associations among cognitive functions, plasma DNA, and diffusion tensor image along the perivascular space (DTI-ALPS) in patients with Parkinson's disease. Oxid Med Cell Longev2021;
2021: 4034509.
19.
BaeYJChoiBSKimJM, et al.
Altered glymphatic system in idiopathic normal pressure hydrocephalus. Parkinsonism Relat Disord2021;
82: 56–60.
20.
MoritaYKamagataKAndicaC, et al.
Glymphatic system impairment in nonathlete older male adults who played contact sports in their youth associated with cognitive decline: a diffusion tensor image analysis along the perivascular space study. Front Neurol2023;
14: 1100736.
21.
KikutaJKamagataKTakabayashiK, et al.
An investigation of water diffusivity changes along the perivascular space in elderly subjects with hypertension. AJNR Am J Neuroradiol2022;
43: 48–55.
22.
YangGDengNLiuY, et al.
Evaluation of glymphatic system using diffusion MR technique in T2DM cases. Front Hum Neurosci2020;
14: 300.
23.
AndicaCKamagataKTakabayashiK, et al.
Neuroimaging findings related to glymphatic system alterations in older adults with metabolic syndrome. Neurobiol Dis2023;
177: 105990–20230105.
24.
ZhangHSchneiderTWheeler-KingshottCA, et al.
NODDI: practical in vivo neurite orientation dispersion and density imaging of the human brain. Neuroimage2012;
61: 1000–1016.
25.
HaraSHoriMMurataS, et al.
Microstructural damage in normal-appearing brain parenchyma and neurocognitive dysfunction in adult moyamoya disease. Stroke2018;
49: 2504–2507.
26.
HaraSHoriMHagiwaraA, et al.
Myelin and axonal damage in normal-appearing white matter in patients with moyamoya disease. AJNR Am J Neuroradiol2020;
41: 1618–1624.
27.
van SwietenJCHijdraAKoudstaalPJ, et al.
Grading white matter lesions on CT and MRI: a simple scale. J Neurol Neurosurg Psychiatry1990;
53: 1080–1083.
28.
HaraSTanakaYInajiM, et al.
Spatial coefficient of variation of arterial spin labeling MRI for detecting hemodynamic disturbances measured with (15)O-gas PET in patients with moyamoya disease. Neuroradiology2022;
64: 675–684.
29.
NariaiTMatsushimaYImaeS, et al.
Severe haemodynamic stress in selected subtypes of patients with moyamoya disease: a positron emission tomography study. J Neurol Neurosurg Psychiatry2005;
76: 663–669.
30.
HoukinKNakayamaNKurodaS, et al.
How does angiogenesis develop in pediatric moyamoya disease after surgery? A prospective study with MR angiography. Childs Nerv Syst2004;
20: 734–741.
31.
ShidaharaMWatabeHKimKM, et al.
Optimal scan time of oxygen-15-labeled gas inhalation autoradiographic method for measurement of cerebral oxygen extraction fraction and cerebral oxygen metabolic rate. Ann Nucl Med2008;
22: 667–675.
32.
KudomiNChoiEYamamotoS, et al.
Development of a GSO detector assembly for a continuous blood sampling system. Ieee Trans Nucl Sci2003;
50: 70–73.
33.
ShidaharaMWatabeHKimKM, et al.
Evaluation of a commercial PET tomograph-based system for the quantitative assessment of rCBF, rOEF and rCMRO2 by using sequential administration of 15O-labeled compounds. Ann Nucl Med2002;
16: 317–327.
34.
MiwaKUmedaTMurataT, et al.
Evaluation of scatter limitation correction: a new method of correcting photopenic artifacts caused by patient motion during whole-body PET/CT imaging. Nucl Med Commun2016;
37: 147–154.
35.
IimaMBihanDL.Clinical intravoxel incoherent motion and diffusion MR imaging: past, present, and future. Radiology2016;
278: 13–32.
36.
DaducciACanales-RodríguezEJZhangH, et al.
Accelerated microstructure imaging via convex optimization (AMICO) from diffusion MRI data. Neuroimage2015;
105: 32–44.
37.
HagiwaraAHoriMKamagataK, et al.
Myelin measurement: comparison between simultaneous tissue relaxometry, magnetization transfer saturation index, and T(1)w/T(2)w ratio methods. Sci Rep2018;
8: 10554.
38.
SahaGB.Performance characteristics of PET scanners. Basics of PET imaging: physics, chemistry, and regulations.
Cham:
Springer International Publishing, 2016, pp.121–142.
39.
HaraSHoriMUedaR, et al.
Intravoxel incoherent motion perfusion in patients with moyamoya disease: comparison with (15)O-gas positron emission tomography. Acta Radiol Open2019;
8: 2058460119846587.
40.
ToyokuraMTanakaHFurukawaT, et al.
Normal aging effect on cognitive task performance of information-processing speed: analysis of paced auditory serial addition task and trail making test. Brain Science and Mental Disorders1996;
7: 401–409.
41.
IharaMYamamotoYHattoriY, et al.
Moyamoya disease: diagnosis and interventions. Lancet Neurol2022;
21: 747–758.
42.
PowersWJGrubbRLJr.andRaichleME.Physiological responses to focal cerebral ischemia in humans. Ann Neurol1984;
16: 546–552.
KazumataKThaKKNaritaH, et al.
Chronic ischemia alters brain microstructural integrity and cognitive performance in adult moyamoya disease. Stroke2015;
46: 354–360.
46.
HaraSHoriMInajiM, et al.
Regression of white matter hyperintensity after indirect bypass surgery in a patient with moyamoya disease. Magn Reson Med Sci2019;
18: 247–248.
47.
SuzukiHMikamiTKuribaraT, et al.
Pathophysiological consideration of medullary streaks on FLAIR imaging in pediatric moyamoya disease. J Neurosurg Pediatr2017;
19: 560–566.
48.
KazumataKThaKKTokairinK, et al.
Brain structure, connectivity, and cognitive changes following revascularization surgery in adult moyamoya disease. Neurosurgery2019;
85: E943–E952.
49.
YamauchiHKagawaSKusanoK, et al.
Misery perfusion and tau deposition in atherosclerotic major cerebral artery disease: A (18)F-Florzolotau positron emission tomography study. Stroke2022;
53: e500–e503.
50.
OgasawaraKFujiwaraSChidaK, et al.
Reduction in amyloid β deposition on (18)F-florbetapir positron emission tomography with correction of cerebral hypoperfusion after endarterectomy for carotid stenosis. Am J Nucl Med Mol Imaging2019;
9: 316–320.
51.
ZouXYuanYLiaoY, et al.
Moyamoya disease: a human model for chronic hypoperfusion and intervention in Alzheimer's disease. Alzheimers Dement (N Y)2022;
8: e1228520220406.
52.
WangXPathakSStefaneanuL, et al.
Subcomponents and connectivity of the superior longitudinal fasciculus in the human brain. Brain Struct Funct2016;
221: 2075–2092.
53.
FujiiMMoriK.An introduction of fiber dissection.
Osaka, Japan:
MEDICUS SHUPPAN, Publisher Co. Ltd, 2019.
54.
StewardCEVenkatramanVKLuiE, et al.
Assessment of the DTI-ALPS parameter along the perivascular space in older adults at risk of dementia. J Neuroimaging2021;
31: 569–578.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
