Yongsheng Chen¹, Jiani Hu², Yimin Shen², Lara M Fahmy^3,4, Li Zhang³, E. Mark Haacke^1,2, and Quan Jiang^1,3
1Department of Neurology, Wayne State University School of Medicine, Detroit, MI, United States, ²Department of Radiology, Wayne State University School of Medicine, Detroit, MI, United States, ³Department of Neurology, Henry Ford Health System, Detroit, MI, United States, ⁴Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, United States

The current understanding of cerebral waste clearance (CWC) involves CSF participation but lacks the direct participation of the parenchymal vascular system. We used SPIO-enhanced SWI on rats to simultaneously study parenchymal veins, arteries and their corresponding para-vascular spaces, and observed not only CSF participation, but also parenchymal venous participation in CWC following intra-cisterna magna infusion of CSF tracers. These results lead to the speculation of a new CWC mechanism with directional brain parenchyma-to-blood permeability. The substantial role of the parenchymal venous system in CWC raises intriguing questions on the differential contributions of parenchymal venous versus CSF pathways in neurodegenerative disease.

Junko Kikuta¹, Koji Kamagata¹, Kaito Takabayashi¹, Toshiaki Taoka², Hajime Yokota³, Yuki Someya⁴, Yoshifumi Tamura^4,5, Hirotaka Watada^4,5, Ryuzo Kawamori^4,5, Shinji Naganawa⁶, and Shigeki Aoki^1
1Department of Radiology, Juntendo University School of Medicine, Bunkyo-ku, Japan, ²Department of Innovative Biomedical Visualization, Graduate School of Medicine, Nagoya University, Nagoya, Japan, ³Department of Diagnostic Radiology and Radiation Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan, ⁴Sportology Center, Juntendo University School of Medicine, Bunkyo-ku, Japan, ⁵Department of Metabolism & Endocrinology, Juntendo University School of Medicine, Bunkyo-ku, Japan, ⁶Department of Radiology, Nagoya University Graduate School of Medicine, Nagoya, Japan

We used the analysis along the perivascular space (ALPS) index, which has been suggested as a noninvasive method to measure water diffusivity along the perivascular space in vivo. We assessed the change in water diffusivity in living patients with hypertension for the first time.

Meher R. Juttukonda^1,2, Randa Almaktoum¹, Kimberly A. Stephens¹, Kathryn Yochim¹, Essa Yacoub³, Randy L. Buckner⁴, and David H. Salat^1,2
1Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States, ²Radiology, Harvard Medical School, Boston, MA, United States, ³Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States, ⁴Psychology, Harvard University, Cambridge, MA, United States

Arterial spin labeling (ASL) approaches for measuring perfusion are challenging in white matter due in part to longer blood arrival times. We implemented a cross-correlation-based processing approach on multi-delay ASL data acquired in Human Connectome Project-Aging (HCP-A) to quantify white matter arterial transit time (ATT) and used these ATT values to analytically compute white matter CBF. Using this approach, we found that white matter CBF decreases (ρ=0.39) and white matter ATT elongates (ρ=0.42) with increasing age (p<0.001). We also found that CBF and ATT values are spatially heterogeneous, with periventricular white matter exhibiting the lowest CBF and longest ATT.

Xingfeng Shao¹, Chenyang Zhao¹, Matthew Borzage², Catherine Mark³, Elizabeth Joe⁴, Jonathan Russin^3,5, Charles Liu^3,4,5, Darrin Lee^3,5,6, and Danny JJ Wang^1,4
1Laboratory of FMRI Technology (LOFT), Mark & Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States, ²Fetal and Neonatal Institute, Division of Neonatology, Children's Hospital Los Angeles, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States, ³Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States, ⁴Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States, ⁵USC Neurorestoration Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States, ⁶Department of Psychiatry, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States

In this study we developed an arterial spin labeling (ASL) sequence with high spatial/temporal resolution and utilized a post-processing denoising method to measure dynamic choroid plexus (CP) perfusion signal. Quantified CP blood flow was evaluated in heathy subjects and one normal pressure hydrocephalus (NPH) patient and compared with water exchange rate across the blood-brain barrier (BBB). Our preliminary results show that CP blood flow may be altered in NPH and has a potential relation with water exchange rate across the BBB.

Ryo Yagawa¹, Naoki Ohno¹, Tosiaki Miyati¹, Mitsuhito Mase², Tomoshi Osawa², Harumasa Kasai², Yuta Shibamoto², and Satoshi Kobayashi^1
1Division of Health Sciences, Kanazawa University, Kanazawa, Japan, ²Nagoya City University Hospital, Nagoya, Japan

To assess the dynamic changes in the apparent diffusion coefficient (ADC) during the cardiac cycle (ΔADC) of the brain before and after the lumbar tap and shunt surgery for the purpose of determining changes in hydrodynamic and biomechanical properties in the brain after cerebrospinal fluid (CSF) drainage for iNPH. The frontal white matter ΔADC in iNPH decreased after the lumbar tap and shunt surgery. ΔADC analysis may provide detailed information regarding changes in the hydrodynamic and biomechanical properties through CSF drainage.

Romtheera Kamronritthisorn¹, Kritdipha Ningunha², Peeratat Suppapanya¹, Sunee Bovonsunthonchai³, Doonyaporn Wongsawaeng ¹, Yudthaphon Vichianin⁴, Theerapol Witthiwej⁵, Weerasak Muangpaisan⁶, Panida Charnchaowanish¹, Siriwan Piyapittayanan¹, Orasa Chawalparit¹, and Chanon Ngamsombat^1
1Department of Radiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, ²Department of TELE-Radiology, Bangkok Hospital Headquarters, Bangkok, Thailand, ³Faculty of Physical Therapy, Mahidol University, Bangkok, Thailand, ⁴Department of Radiological Technology, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand, ⁵Division of Neurosurgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, ⁶Department of Preventive and Social Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

      Shunt surgery is an effective treatment for iNPH, however some patients showed unsustainable response. We investigated how reduction of ventricular size after shunt surgery correlated with clinical outcome, as potential predictor of long-term shunt responsiveness using automated segmentation of ventricular volume from T1W sequence. A reduction of ventricular volume is found to negatively correlate with improved cognition. These findings might be one of helpful imaging predictors for the shunt responders in iNPH.  

Carles Javierre-Petit¹, Ashish A. Tamhane², Arnold M. Evia², Marinos Kontzialis², Nazanin Makkinejad¹, Gady Agam¹, David A. Bennett², Julie A. Schneider², and Konstantinos Arfanakis^1,2
1Illinois Institute of Technology, Chicago, IL, United States, ²Rush University Medical Center, Chicago, IL, United States

Perivascular spaces form a network that enables clearance of waste products from the brain. Abnormal enlargement of perivascular spaces is common in older adults and has been linked to cognitive impairment and dementia. However, the neuropathologic and cognitive correlates of enlarged perivascular spaces (EPVS) are not well understood yet. In this work, we first developed an algorithm to automatically segment and quantify EPVS in brain MR images, and then investigated the neuropathologic correlates of total and regional EPVS, as well as the contributions of EPVS on cognitive decline in a large community-based cohort of 817 older adults.

Lara M Fahmy¹, Yongsheng Chen², Stephanie Xuan³, E Mark Haacke³, Jiani M Hu³, and Quan Jiang^4
1Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, United States, ²Neurology, Wayne State University School of Medicine, Detroit, MI, United States, ³Radiology, Wayne State University School of Medicine, Detroit, MI, United States, ⁴Neurology, Henry Ford Health System, Detroit, MI, United States

It's well-established that the CNS is completely submerged in CSF; but to what extent is this true regarding the finer spaces within the CNS itself? We used MRI to simultaneously map the presence of CSF within all peri-neural and peri-vascular spaces in vivo in humans. Our findings indicated that all peri-neural spaces surrounding cranial and spinal nerves, as well as all peri-vascular spaces, were filled with CSF. These findings suggest that anatomically, substance exchange between the brain parenchyma and outside tissues (i.e. lymphatics) can only occur through CSF, warranting further investigation into its cerebral waste clearance and immunomodulation implications.

Ping-Hong Yeh¹, J. Kent Werner^2,3, Rujirutana Srikanchana¹, Kimbra Kenney^1,2, Treven Pickett^1,2, Grant Bonavia^1,2, Gerard Riedy^1,2, and John Ollinger^1
1National Intrepid Center of Excellence, Bethesda, MD, United States, ²Uniformed Services University of the Health Sciences, Bethesda, MD, United States, ³Center for Neuroscience and Regenerative Medicine, Bethesda, MD, United States

Sleep disturbances are common following traumatic brain injury (TBI). We sought to quantify changes in perivascular space (PVS) in combat-related mild TBI (mTBI) patients and explore the association between normalized PVS volume and sleep measures. We found mTBI patients with previous potential concussive event (PCE) (TBIPCE) had larger PVS fraction than controls.  A subjective sleep measure, The Pittsburgh Sleep Quality Index (PSQI), was positively associated with PVS in TBIPCE patients, which had mean higher PSQI than those of TBI patients who had only mTBI but no PCE. This result suggests enlarged PVS may be modulated by sleep and TBI.

Thanh D Nguyen¹, Liangdong Zhou¹, Elizabeth Sweeney¹, Xiuyuan Wang¹, Susan A Gauthier¹, Yi Wang¹, Amy Kuceyeski¹, and Yi Li^1
1Weill Cornell Medicine, New York, NY, United States

Perivascular spaces (PVS) play a key role in the glial-lymphatic waste clearance pathway in the brain. We applied FAST-T2 multi-component T2 relaxometry to 20 healthy volunteers between 30 and 60 years old and found a significant relationship between CSF water fraction and age in the frontal and temporal cortex, while the brain tissue water content measured by T1 relaxation time remains stable over time. Our results suggest that CSF fraction may be a useful quantitative biomarker of PVS dilation in normal aging.

Shruti Agarwal¹, Jay J. Pillai^1,2, and Hanzhang Lu^3,4
1Division of Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ³Division of MR Research, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁴F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States

White matter hyperintensities (WMH) are white matter brain lesions found as areas of increased signals on T2-weighted and FLAIR MRI scans. A large majority of elderly individuals have a certain degree of WMH which may be associated with cognitive decline, decline in physical function and a higher risk of stroke and death. To date, neurobiological mechanisms underlying and predictive of WMH is not fully characterized. In this study, we aim to use a longitudinal design to elucidate hallmarks of brain tissue at baseline that will predict a “conversion” from normal-appearing WM (NAWM) to WMH over a four-year period.

Alexander Saunders^1,2, Stefan Bluml^1,2, Kevin S King³, and Matthew Borzage^2,4
1Radiology, Children's Hospital Los Angeles, Los Angeles, CA, United States, ²Rudi Schulte Research Insitute, Santa Barbara, CA, United States, ³Barrow Neurological Institute, Phenoix, AZ, United States, ⁴Children's Hospital Los Angeles, Los Angeles, CA, United States

Normal pressure hydrocephalus is a treatable dementia often misdiagnosed as Alzheimer’s Disease. Callosal angle measurement distinguish normal pressure hydrocephalus from other dementias but measurements are time-consuming and subjective. Therefore, we developed an algorithm for automatic callosal angle measurement and calculated callosal angles for 4,980 T1-weighted MRIs from databases of patients with purportedly healthy aging brains or Alzheimer’s. Based on the published guidelines, 1.8-4.3% of exams in these databases indicate patients likely have normal pressure hydrocephalus and thus a treatable form of dementia. Our automatic measurement of the callosal angle biomarker can rapidly and objectively screen patients for normal pressure hydrocephalus.

Corinne A. Donnay¹, Pauline Maillard¹, Charles DeCarli¹, and Audrey P. Fan^1,2
1Neurology, University of California Davis, Davis, CA, United States, ²Biomedical Engineering, University of California Davis, Davis, CA, United States

We investigated white matter (WM), cerebral blood flow (CBF) and free water content (FW) in the penumbra region surrounding white matter hyperintensities (WMH) in elderly participants. The tissue surrounding WMH clusters were defined as four 1mm concentric layers and compared to WM and WMHs. The findings of this study reveal that WMHs and adjacent layers have lower CBF than healthy WM and CBF increases from lower layers to higher layers. The opposite associations were found with FW.  

Chenyang Li^1,2, Marco Muccio¹, Dengrong Jiang³, Peiying Liu³, Jiangyang Zhang¹, Arjun Masurkar⁴, Thomas Wisniewski⁴, Hanzhang Lu³, and Yulin Ge^1
1Department of Radiology, Center for Biomedical Imaging, NYU Grossman School of Medicine, New York, NY, United States, ²Vilcek Institute of Graduate Biomedical Sciences, NYU Grossman School of Medicine, New York, NY, United States, ³Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States, ⁴Department of Neurology, NYU Grossman School of Medicine, New York City, NY, United States

Understanding of in vivo vascular pathophysiology in white matter hyperintensities (WMHs) is still incomplete. Compared to grey matter, white matter is considerably less vascularized and tends to have lower blood flow. Therefore, sensitive detection and accurate estimation for white matter hemodynamics is crucial for early prevention and mechanistic understanding of WMHs pathogenesis and progression. In this study, we implemented advanced neurovascular MRI techniques to evaluate the white matter hemodynamics including cerebral blood flow and cerebrovascular reactivity in patients with varying degrees of WMHs.

Feng Han¹, Jing Chen¹, Aaron Belkin-Rosen¹, Yameng Gu¹, Liying Luo^2,3, Orfeu M Buxton⁴, and Xiao Liu^1,5
1Department of Biomedical Engineering, The Pennsylvania State University, State College, PA, United States, ²Department of Sociology & Criminology, The Pennsylvania State University, State College, PA, United States, ³Population Research Institute, The Pennsylvania State University, State College, PA, United States, ⁴Department of Biobehavioral Health, The Pennsylvania State University, State College, PA, United States, ⁵Institute for Computational and Data Sciences, The Pennsylvania State University, State College, PA, United States

Glymphatic system responsible for brain waste clearance may play an important role in the development of Alzheimer's disease (AD). However, this possibility has not been sufficiently studied in AD patients due to a lack of non-invasive tools for gauging glymphatic function. Low-frequency (<0.1 Hz) fMRI signals have been recently linked to glymphatic function, and its global signal was found to be coupled with CSF flow known to be essential for glymphatic clearance. Here, we used the coupling of global BOLD signal and CSF to quantify glymphatic function and found this BOLD-CSF coupling metric is significantly correlated with various AD pathologies.

Safa Sanami¹, Brittany Intzandt^2,3,4, Fatemeh Razavipour¹, Julia Huck¹, Richard D Hoge⁵, Louis Bherer^3,4,6,7, and Claudine J Gauthier^1,4,6
1Physics, Concordia University, Montreal, QC, Canada, ²INDI, Concordia University, Montreal, QC, Canada, ³Centre de Recherche de l'Institut Universitaire de Geriatrie, Montreal, QC, Canada, ⁴Centre de Recherche, l'Institut de Cardiologie de Montréal, Montreal, QC, Canada, ⁵Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada, ⁶PERFORM Centre, Concordia University, Montreal, QC, Canada, ⁷Départment de Médicine, Université de Montréal, Montreal, QC, Canada

Aging is associated with cerebrovascular impairments in males and females, yet this impairment  develops nearly one decade later in females. Although cerebral blood flow (CBF) is consistently reported as higher in females, results on cerebrovascular reactivity (CVR) have not been uniform in studies comparing females to males. Here, given that much less is known about cerebrovascular changes in females than males, we examined CBF and CVR during aging in healthy females only. Our results revealed that both CBF and CVR decline across the lifespan in females. Future work should include hormone levels, arterial stiffness, other vascular risk factors, and males.

Li Zhao¹, Xue Feng², Yueqin Hu³, Dan Wu¹, Craig H. Meyer², and David C. Alsop^4
1College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, China, ²Biomedical Engineering, University of Virginia, Charlottesville, VA, United States, ³Psychology, Beijing Normal University, Beijing, China, ⁴Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States

Choroid plexus volume was investigated using a deep learning segmentation method, which has demonstrated higher accuracy than the previous atlas-based method. Therefore, a higher sensitivity was expected with the new method. MR images of 733 subjects were selected retrospectively, including healthy volunteers, MCI and AD patients. The results show that 1) the choroid plexus volume increases with age; 2) is smaller in the female subjects; and 3) is larger in the MCI and AD patients compared to the healthy volunteers. Our preliminary results suggest that the choroid plexus volume changes with brain aging.

Tae Kim¹, Howard J Aizenstein¹, and James T Becker^1
1University of Pittsburgh, Pittsburgh, PA, United States

The effect of white matter hyperintensities (WMHs) on 50 major WM tractometries was investigated. Elevated WMHs load on white matter tract was associated with lower apparent fiber density (AFD) on tractometery, showing the co-localization of WMH with AFD change. Reduced AFD is associated with lower connectivity of the WM tract. Differences in these metrics between lower WMH and higher WMH groups, and between lower WMH and MCI groups are significant. Moreover, AFD is lower in individuals with MCI, supporting a role of white matter microstructure in cognitive decline.

Olivier Baledent¹, Pan Liu¹, Serge Metanbou¹, Cyrille Capel¹, Sidy Fall¹, and Roger Bouzerar^1
1university hospital Jules Verne, Amiens, France

it is still debated how breathing interact with the CSF. New Phase contrast MRI sequence based on Echo Planar imaging (EPI-PC) can now produce continuously during minutes a velocity map, more or less every 100 ms. We did not found in the literature quantitative evaluation of the CSF stroke volume change during breathing. The aim of this work is to quantify CSF dynamics change in the aqueduct and in the spinal canal during the breathing and cardiac period using EPI-PC. 

Haoyu Lan¹ and Farshid Sepehrband^1
1USC Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, CA, United States

Automatic perivascular spaces (PVS) segmentation from magnetic resonance images enables whole brain morphometric assessment of glia-lymphatic network. While conventional deep learning segmentations are shown to produce reliable results, they heavily rely on the presence of ground truth for training. In this work we introduce an unsupervised learning method for PVS segmentation, by combining a rule-based image processing approach with a deep learning algorithm. The experiment results showed that the proposed method increased segmentation accuracy by effectively increasing the true positive rate compared to the rule-based method and decreasing false positive rate compared to the deep learning method.