Glymphatic system evaluation using diffusion tensor imaging in patients with traumatic brain injury

Park, Jung Hyun; Bae, Yun Jung; Kim, Ji Su; Jung, Woo Sang; Choi, Jin Wook; Roh, Tai Suk; You, Nam Kyu; Kim, Se-Hyuk; Han, Miran

doi:10.1007/s00234-022-03073-x

Cited by 31 publications

(38 citation statements)

References 28 publications

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“…The existence of brain parenchymal damage could aggravate the dysfunction of the glymphatic system. This result is also supported by a previous study reporting positive relationships between DTI‐ALPS and GCS 22 …”

Section: Discussionsupporting

confidence: 90%

“…At present, DTI‐ALPS has been proposed to be effective in reflecting the brain's glymphatic system, 18 and has been used in AD, 19 PD, 20 and multiple sclerosis (MS) 21 . As for TBI, only one study revealed impaired glymphatic system function in TBI using this method 22 . However, no previous study investigated the relationship between glymphatic system function and cognitive impairment after mTBI.…”

mentioning

confidence: 99%

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Associations of MRI‐Derived Glymphatic System Impairment With Global White Matter Damage and Cognitive Impairment in Mild Traumatic Brain Injury: A DTI‐ALPS Study

Yang

Sun

et al. 2023

Magnetic Resonance Imaging

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BackgroundAssessing the glymphatic function using diffusion tensor image analysis along the perivascular space (DTI‐ALPS) may be helpful for mild traumatic brain injury (mTBI) management.PurposeTo assess glymphatic function using DTI‐ALPS and its associations with global white matter damage and cognitive impairment in mTBI.Study TypeProspective.PopulationThirty‐four controls (44.1% female, mean age 49.2 years) and 58 mTBI subjects (43.1% female, mean age 48.7 years), including uncomplicated mTBI (N = 32) and complicated mTBI (N = 26).Field Strength/Sequence3‐T, single‐shot echo‐planar imaging sequence.AssessmentMagnetic resonance imaging (MRI) was done within 1 month since injury. DTI‐ALPS was performed to assess glymphatic function, and peak width of skeletonized mean diffusivity (PSMD) was used to assess global white matter damage. Cognitive tests included Auditory Verbal Learning Test and Digit Span Test (forward and backward).Statistical TestsNeuroimaging findings comparisons were done between mTBI and control groups. Partial correlation and multivariable linear regression assessed the associations between DTI‐ALPS, PSMD, and cognitive impairment. Mediation effects of PSMD on the relationship between DTI‐ALPS and cognitive impairment were explored. P‐value <0.05 was considered statistically significant, except for cognitive correlational analyses with a Bonferroni‐corrected P‐value set at 0.05/3 ≈ 0.017.ResultsmTBI showed lower DTI‐ALPS and higher PSMD, especially in complicated mTBI. DTI‐ALPS was significantly correlated with verbal memory (r = 0.566), attention abilities (r = 0.792), executive function (r = 0.618), and PSMD (r = −0.533). DTI‐ALPS was associated with verbal memory (β = 8.77, 95% confidence interval [CI] 5.00, 12.54), attention abilities (β = 5.67, 95% CI 4.56, 6.97), executive function (β = 2.34, 95% CI 1.49, 3.20), and PSMD (β = −0.79, 95% CI −1.15, −0.43). PSMD mediated 46.29%, 20.46%, and 24.36% of the effects for the relationship between DTI‐ALPS and verbal memory, attention abilities, and executive function.Data ConclusionGlymphatic function may be impaired in mTBI reflected by DTI‐ALPS. Glymphatic dysfunction may cause cognitive impairment related to global white matter damage after mTBI.Level of Evidence2Technical EfficacyStage 2

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Section: Discussionsupporting

confidence: 90%

mentioning

confidence: 99%

Associations of MRI‐Derived Glymphatic System Impairment With Global White Matter Damage and Cognitive Impairment in Mild Traumatic Brain Injury: A DTI‐ALPS Study

Yang

Sun

et al. 2023

Magnetic Resonance Imaging

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“…are in accord with one animal study 7 and one recent clinical study. 15 The correlation of ALPS index with plasma NfL -a biomarker of brain injury severity 16,17 and tau need to be cleared -would be expected to affect short term recovery after injury and contribute to later risk of proteinopathy and neurodegeneration. 19 Additional study of post-TBI clearance in humans and animal models is warranted to clarify relevant mechanisms and guide targeted therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Results are in accord with one animal study 7 and one recent clinical study. 15 The correlation of ALPS index with plasma NfL – a biomarker of brain injury severity 16, 17 – indicates that greater neuronal damage is associated with worse glymphatic function.…”

Section: Discussionmentioning

confidence: 99%

“…12,13 Decreased glymphatic function was very recently demonstrated using this method in subjects with AD 14 and TBI. 15 Here we apply DTI-ALPS to assessing glymphatic function in subacute TBI and in relation to blood levels of neurofilament light protein (NFL) -a robust biomarker of TBI severity. 16,17 Materials and methods TBI participants were recruited through inpatient rehabilitation units and trauma departments.…”

Section: Introductionmentioning

confidence: 99%

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Reduced glymphatic function after traumatic brain injury measured using diffusion MRI

Butler

Zhou

Ozhasin

et al. 2022

Preprint

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The glymphatic system is a perivascular fluid clearance system, most active during sleep, considered important for clearing the brain of waste products and toxins. Glymphatic failure is hypothesized to underlie brain protein deposition in neurodegenerative disorders like Alzheimers Disease. Preclinical evidence suggests that a functioning glymphatic system is also essential for recovery from traumatic brain injury (TBI), which involves release of debris and toxic proteins that need to be cleared from the brain. We estimated glymphatic clearance using Diffusion Tensor Imaging Along Perivascular Spaces (DTI-ALPS), an MRI-derived measure of water diffusivity surrounding veins, in 13 non-injured controls and 37 subjects with TBI (~5 months post). We additionally measured plasma concentrations of Neurofilament light chain (NfL), a biomarker of injury severity, in a subset of subjects. DTI-ALPS was significantly lower in TBI subjects compared to controls, after controlling for age, and significantly, negatively correlated with NfL. Glymphatic impairment after TBI could be due to mechanisms such as mis-localization of glymphatic water channels, inflammation, proteinopathy and/or sleep disruption. Additional work, including longitudinal studies, are needed to confirm results and assess glymphatic associations with outcome. Understanding post-TBI glymphatic functioning could inform novel therapies to improve short-term recovery and reduce later risk of neurodegeneration.

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Neurite orientation dispersion and density imaging reveals abnormal white matter and glymphatic function in active young boxers

Huang,

Ma,

Yan

et al. 2024

European Journal of Sport Science

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The neurological effects and underlying pathophysiological mechanisms of sports‐related concussion (SRC) in active young boxers remain poorly understood. This study aims to investigate the impairment of white matter microstructure and assess changes in glymphatic function following SRC by utilizing neurite orientation dispersion and density imaging (NODDI) on young boxers who have sustained SRC. A total of 60 young participants were recruited, including 30 boxers diagnosed with SRC and 30 healthy individuals engaging in regular exercise. The assessment of whole‐brain white matter damage was conducted using diffusion metrics, while the evaluation of glymphatic function was performed through diffusion tensor imaging (DTI) analysis along the perivascular space (DTI‐ALPS) index. A two‐sample t‐test was utilized to examine group differences in DTI and NODDI metrics. Spearman correlation and generalized linear mixed models were employed to investigate the relationship between clinical assessments of SRC and NODDI measurements. Significant alterations were observed in DTI and NODDI metrics among young boxers with SRC. Additionally, the DTI‐ALPS index in the SRC group exhibited a significantly higher value than that of the control group (left side: 1.58 vs. 1.48, PFDR = 0.009; right side: 1.61 vs. 1.51, PFDR = 0.02). Moreover, it was observed that the DTI‐ALPS index correlated with poorer cognitive test results among boxers in this study population. Repetitive SRC in active young boxers is associated with diffuse white matter injury and glymphatic dysfunction, highlighting the detrimental impact on brain health. These findings highlight the importance of long‐term monitoring of the neurological health of boxers.

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Glymphatic system evaluation using diffusion tensor imaging in patients with traumatic brain injury

Cited by 31 publications

References 28 publications

Associations of MRI‐Derived Glymphatic System Impairment With Global White Matter Damage and Cognitive Impairment in Mild Traumatic Brain Injury: A DTI‐ALPS Study

Associations of MRI‐Derived Glymphatic System Impairment With Global White Matter Damage and Cognitive Impairment in Mild Traumatic Brain Injury: A DTI‐ALPS Study

Reduced glymphatic function after traumatic brain injury measured using diffusion MRI

Neurite orientation dispersion and density imaging reveals abnormal white matter and glymphatic function in active young boxers

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