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Shoko Hara^1,2,3, Junko Kikuta², Kaito Takabayashi², Koji Kamagata², Shihori Hayashi^1,4, Motoki Inaji^1,3, Yoji Tanaka¹, Masaaki Hori², Kenji Ishii⁴, Tadashi Nariai^1,4, Toshiaki Taoka⁵, Shinji Naganawa⁶, Shigeki Aoki², and Takeoshi Maehara^1
1Neurosurgery, Tokyo Medical and Dental University, Tokyo, Japan, ²Radiology, Juntendo University, Tokyo, Japan, ³Research Team of Neuroimaging, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan, ⁴Research Team for Neuroimaging, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan, ⁵Innovative Biomedical Visualization, Nagoya University Graduate School of Medicine, Nagoya, Japan, ⁶Radiology, Nagoya University, Nagoya, Japan

Keywords: Neurofluids, Diffusion/other diffusion imaging techniques, glymphatic system

We aimed to evaluate the glymphatic system of adult moyamoya disease (MMD) by measuring diffusion along the perivascular space (DTI-ALPS index). We evaluated 46 patients using diffusion MRI, perfusion parameters of ¹⁵O-gas PET, and cognitive tests, and 34 age-sex-matched normal controls. Compared to normal controls, patients with MMD showed significantly lower DTI-ALPS index. DTI-ALPS index in MMD revealed the correlation between perfusion and freewater parameters, and executive dysfunction, and suggested that dysfunction of the glymphatic system may exist, correlate with the degree of hemodynamic disturbance, lead to increased parenchymal free water, and relate to cognitive dysfunction in adult MMD.

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Adam M. Wright^1,2, Yunjie Tong¹, Yu-Chien Wu², and Qiuting Wen^2
1Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, United States, ²School of Medicine, Indiana University, Indianapolis, IN, United States

Keywords: Neurofluids, Neurofluids

We designed a non-invasive multimodal MRI approach to evaluate the relationship between cardiac pulsation and perivascular cerebrospinal fluid (pCSF) dynamics in humans. We utilized cardiac-aligned resting-state functional MRI and dynamic diffusion-weighted imaging to describe cerebral vascular events and pCSF motion, respectively. This approach revealed that changes in cerebral blood volume preceded an increase in pCSF motion, demonstrating the cardiac cycle’s effect on pCSF dynamics. Our results parallel preclinical two-photon imaging findings of perivascular CSF dynamics in mice. Our in-vivo assessment of cardiac pulsations influencing pCSF motion provides a non-invasive look into a crucial part of the human brain’s glymphatic system.

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Manon Roxanne Schipper¹, Arie-Tjerk Razoux-Schultz², Thijs W. van Harten¹, Jeroen van der Grond¹, Mark van Buchem¹, Steven M. Greenberg³, Marieke J.H. Wermer⁴, Matthias J.P. van Osch¹, Marianne A.A. van Walderveen¹, and Sanneke van Rooden^1
1Radiology, Leiden University Medical Center, Leiden, Netherlands, ²Leiden University Medical Center, Leiden, Netherlands, ³Neurology, Mass General Research Institute, Boston, MA, United States, ⁴Neurology, Leiden University Medical Center, Leiden, Netherlands

Keywords: Neurofluids, Neurofluids, Perivascular spaces

In this study we semi-automatically quantified MRI-visible perivascular space volume in the white matter (WM-PVS) and compared these volumes between (pre-)symptomatic Dutch-type hereditary Cerebral Amyloid Angiopathy (D-CAA) and matched controls. Main findings show that the WM-PVS volume was significantly higher in symptomatic D-CAA (median=19.9mL) compared with both presymptomatic D-CAA (median=3.5mL; U=19, p=.01) and matched controls (median=4.9mL; U=1, p<.001). Presymptomatic D-CAA carriers had a higher WM-PVS volume than the matched controls (median=2.3mL; U=27, p=.02). This indicates that WM-PVS volume, in contrast to the PVS-CSO visual rating scales, may be an early marker for D-CAA. 

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Merel M. van der Thiel^1,2,3, Marieke van den Kerkhof^1,2, Alida A. Postma^1,2, Walter H. Backes^1,2,4, and Jacobus F.A. Jansen^1,2,5
1Department of Radiology & Nuclear Medicine, Maastricht University Medical Center, Maastricht, Netherlands, ²School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands, ³Department of Psychiatry & Neuropsychology, Maastricht University, Maastricht, Netherlands, ⁴Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Netherlands, ⁵Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands

Keywords: Neurofluids, Aging, Diffusion, pulsatility, waste clearance

Impaired cerebral waste clearance occurs in healthy ageing and various neurodegenerative diseases and is theorized to be due to compromised arterial pulsatility. Profiting from high-resolution 7 Tesla MRI, the current study investigated the association between pulsatility characteristics of a small artery in the basal ganglia (BG) with interstitial fluid (ISF) characteristics of the BG - as derived with intravoxel incoherent motion. This study found that an increased small vessel velocity pulsatility was related to higher ISF-diffusivity in the BG of an elderly sample. This increased ISF-diffusivity might represent increased perivascular fluid diffusivity, influencing the waste fluid transport out of these spaces.

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Keywords: Neurofluids, Parkinson's Disease, Glymphatic

The goal of this study was to use a novel diffusion weighted imaging (DWI) protocol with dynamic cycling of low b-values to test fundamental hypotheses regarding neurofluid movement along inflow and egress pathways of the suprasellar cisterns in older adults with and without Parkinson’s disease (PD). Contrast consistent with reduced neurofluid motion was observed in PD relative to healthy participants, with reduced fluid movement corresponding to choroid plexus hyperemia. Modeling of DWI signal decay as a function of b-value provides quantitative neurofluid kinetics and may present a candidate non-tracer technology for quantifying neurofluid flow non-invasively in vivo in humans.

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Naoya Kinota^1,2, Hiroyuki Kameda^3,4, Kazuyuki Minowa³, and Kohsuke Kudo^1,5
1Department of Diagnostic Imaging, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan, ²Department of Dental Radiology, Hokkaido University Hospital, Sapporo, Japan, ³Department of Radiology, Faculty of Dental Medicine, Hokkaido University, Sapporo, Japan, ⁴Department of Diagnostic and Interventional Radiology, Hokkaido University Hospital, Sapporo, Japan, ⁵Global Center for Biomedical Science and Engineering, Faculty of Medicine, Hokkaido University, Sapporo, Japan

Keywords: Neurofluids, Neurofluids, Glymphatic System

Previous reports showed that deep cervical lymph nodes (DCLNs) receive cerebrospinal fluid (CSF) outflow. DCLN ligation resulted in intracranial accumulation of waste proteins due to impaired CSF outflow; however, changes in extracranial outflow after DCLN ligation have not been directly observed. We examined extracranial CSF outflow in rats after DCLN ligation by using intrathecal gadolinium (Gd)-based dynamic contrast-enhanced MRI. DCLN ligation blocked CSF- tracer outflow into the nasal cavity. A weak trend towards CSF-tracer retention in the ventral cistern was also observed. These results suggest that DCLN ligation affects CSF outflow in rodents.

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Arash Nazeri¹, Taher Dehkharghanian², Pamela J. LaMontagne¹, Tammie L.S. Benzinger¹, and Aristeidis Sotiras^1,3
1Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO, United States, ²Faculty of Health Science, McMaster University, Hamilton, ON, Canada, ³Institute for Informatics, Washington University in St. Louis, St. Louis, MO, United States

Keywords: Neurofluids, Diffusion/other diffusion imaging techniques, cerebrospinal fluid

Alterations in CSF flow patterns have been implicated in various brain disorders. At low b-values, diffusion-weighted imaging is sensitive to pseudorandom CSF flow. Here, we present CSF pseudo-diffusion spatial statistics (CΨSS), a whole-brain multi-subject voxel-wise analysis framework that exploits low-b-value diffusion-weighted imaging to study regional patterns of CSF flow. Using this technique, we show how brain atrophy and ventricular volumes affect regional CSF pseudorandom flow. In conclusion, CΨSS is a simple and effective approach for characterizing determinants of regional CSF pseudorandom flow.

Mitsue Miyazaki¹, Vadim Malis¹, Asako Yamamoto², Jirach Kungsamutr³, Marin McDonald¹, Linda McEvoy¹, and Won Bae^1,4
1Radiology, University of California, San Diego, La Jolla, CA, United States, ²Radiology, Teikyo University, Tokyo, Japan, ³Bioengineer, University of California, San Diego, La Jolla, CA, United States, ⁴VA San Diego Healthcare System, San Diego, CA, United States

Keywords: Neurofluids, Neurofluids, CSF, glymphatic egress pathways, active and sedentary

Possible two intrinsic CSF egress pathways of dura mater and the lower parasagittal dura (PSD) are observed using non-contrast spin-labeling MRI. Intrinsic CSF outflow metrics increase in the adults with an active lifestyle than adults with sedentary lifestyle. However, after 3 weeks of increased physical activity, the sedentary group showed improved CSF outflow metrics. This improvement was notable at the lower PSD, where outflow metrics were highest among the active group. These quantitative CSF results indicate a new pathway of CSF flow from the lower PSD to the superior sagittal sinus that is most evident in physically active individuals.  

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Tekla Maria Kylkilahti^1,2, Max Wictor^1,2, David Berron³, Johannes Töger⁴, Karin Markenroth Bloch⁵, Niklas Mattson-Carlgren³, Oskar Hansson^3,6, and Iben Lundgaard^1,2
1Experimental medical science, Lund University, Lund, Sweden, ²Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden, ³Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden, ⁴Skåne University Hospital, Department of Clinical Sciences Lund, Diagnostic Radiology, Lund University, Lund, Sweden, ⁵Lund University Bioimaging Center, Lund University, Lund, Sweden, ⁶Neuropsychiatric Clinic, Malmö University Hospital, Malmö, Sweden

Keywords: Neurofluids, Velocity & Flow

Cerebrospinal fluid (CSF) circulation through the parenchyma by the glymphatic system has been suggested to play a role in the clearance of metabolic waste from the brain, including Amyloid β. In this 7T MRI study of CSF flow in the cerebral aqueduct, we find that ageing, cognitive status and amyloid status influence CSF dynamics and morphology of the aqueduct. These changes appear to precede major cognitive changes in Alzheimer’s disease. Disruption of  flow dynamics and anatomy of CSF flow pathways may reflect dysfunctional CSF circulation in downstream compartments of the glymphatic system, and contribute to amyloid accumulation in the brain.

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Aiqi Sun¹, Lekang Yin², Bingyi Wang¹, Hengfa Lu³, Peng Wu⁴, and Bo Zhao^3,5
1Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China, ²Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China, ³Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, United States, ⁴Philips Healthcare, Shanghai, China, ⁵Oden Institute for ComputationalEngineering and Sciences, University of Texas at Austin, Austin, TX, United States

Keywords: Neurofluids, Velocity & Flow

Quantification of cerebrospinal fluid (CSF) flow is critical for studying the physiological and pathological mechanisms of CSF dynamics and related neurological diseases. Conventional cine phase-contrast MRI provides an effective tool to quantify CSF flow, however, this method is not suitable for evaluating beat-by-beat flow variabilities associated with cardiac arrhythmia and/or respiratory regulation. This work presents a real-time flow MRI method at a spatial resolution of 0.5 mm and temporal resolution of 52 ms for assessment of CSF flow in cerebral aqueduct at 3T, which can well resolve beat-by-beat CSF flow variations. Its feasibility has been demonstrated in multiple healthy subjects.

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Dengrong Jiang¹, Yifan Gou², Zhiliang Wei¹, Xirui Hou¹, Vivek Yedavalli¹, and Hanzhang Lu^1
1Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²Department of Biomedical Engineering, Johns Hopkins University School of Engineering, Baltimore, MD, United States

Keywords: Neurofluids, Neurofluids

It has been suggested that the brain’s waste clearance system involves water exchange between brain tissue and CSF in perivascular spaces, which are part of the subarachnoid space (SAS). In this work, we found CSF T₁ and T₂ in SAS were shorter than corresponding values in the frontal-horns of lateral ventricle, which have minimal exchange. Numerical simulations showed that a higher brain-CSF water exchange rate was associated with lower apparent relaxation time in SAS, providing a potential means to estimate brain-CSF water exchange rate in vivo.

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Jun-Hee Kim¹, Suhong Kim¹, Jae-Geun Im¹, Seok Jong Chung², Phil Hyu Lee², Yong Jeong¹, and Sung-Hong Park^1
1Korea Advanced Institute of Science and Technology, Daejeon, Korea, Republic of, ²Yonsei University Colledge of Medicine, Seoul, Korea, Republic of

Keywords: Neurofluids, Parkinson's Disease

The fMRI dataset for Parkinson’s disease with mild cognitive impairment (PD-MCI) was studied using a recently-proposed method of simultaneous CSF pulsation and BOLD activity imaging. The PD group was classified to dementia (PDD) high-risk and low-risk groups. The CSF pulsation of both PDD high-risk and low-risk groups was higher than that of healthy control. Opposite to the tendency of CSF pulsation, coefficient of variation of CSF pulsation was reduced in PD group compared to healthy control. These results indicate association of CSF pulsation with brain waste clearance in these patients, which requires further investigations for elucidation.

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Yuran Zhu¹, Guanhua Wang², Kihwan Kim¹, Chris A. Flask^1,3,4, and Xin Yu^1,3,5
1Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States, ²Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, United States, ³Department of Radiology, Case Western Reserve University, Cleveland, OH, United States, ⁴Department of Pediatrics, Case Western Reserve University, Cleveland, OH, United States, ⁵Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, United States

Keywords: Neurofluids, Contrast Agent, Glymphatic system

This study evaluated the impact of infusion rate on tracer transport in mouse glymphatic system. Gd-DTPA was administered via cisterna magna at a rate either comparable to the CSF production rate in mouse brain (0.33 μL/min) or three-fold higher (1 μL/min). The kinetics and distribution of Gd-DTPA were assessed by DCE-MRI for 2 hours. Our results show a significantly increased transport along the dorsal brain regions and penetration into the deep brain regions at a slow infusion rate, suggesting that the infusion rate may alter the pressure gradient and affect tracer transport and distribution in the brain.

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Jun-Hee Kim¹, Roh-Eul Yoo^2,3, Seung-Hong Choi^2,3, and Sung-Hong Park^1
1Korea Advanced Institute of Science and Technology, Daejeon, Korea, Republic of, ²Department of Radiology, Seoul National University College of Medicine, Seoul, Korea, Republic of, ³Seoul National University Hospital, Seoul, Korea, Republic of

Keywords: Neurofluids, Machine Learning/Artificial Intelligence

In this study, we proposed non-invasive brain lymphatic region mapping by synthesizing contrast-enhancement maps (CEM) from non-contrast enhanced black blood imaging (non-CEBB). T1 images were used as secondary input along with non-CEBB, which helped the network to better distinguish lymphatic regions from blood vessels. From the reconstructed 3D CEM segmentation, enhancement was mainly distributed in dorsal parasagittal dura, parasagittal regions, brain basal region and around choroid plexus, consistent with previous studies. This study could be applied to the segmentation of the brain lymphatic region with less ambiguity and may help automatic segmentation rather than intensity-based segmentation by adapting self-supervised learning.

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Keywords: Neurofluids, Brain

The choroid plexus (CP) plays a key role in brain homeostasis and waste clearance as the main source of CSF production in the brain. However, this small structure sitting in the lateral ventricles is not well characterized, including its dysfunction or impairment in several pathologies or just normal aging. Water exchange measurement using various methods has been proposed to evaluate structural but also functional properties of the CP such as ASL or other spin labeling strategies mainly in rodents. In this work, we propose a new look into water exchange between CP and CSF using T2-prepared, long TE Fluid-Attenuated-Inversion-Recovery (FLAIR).