Ana-Maria Oros-Peusquens¹, Jonas Kielmann¹, and N. Jon Shah^1,2,3,4
1INM-4, Research Centre Juelich, Juelich, Germany, ²Faculty of Medicine, JARA, RWTH Aachen University, Aachen, Germany, ³INM-11, JARA, Research Centre Juelich, Juelich, Germany, ⁴Department of Neurology, RWTH Aachen University, Aachen, Germany

An increasing number of structural studies attempt identification of distinct structural regions based on their layer signature. Interestingly, water content quantitative contrast is little used in these attempts, despite being a fundamental contrast in MRI, based on the proton equilibrium magnetisation, and closely reflecting cell density on which modern cytoarchitectonic studies are based. In this contribution, we demonstrate the usefulness of water content contrast at 7T and propose it for layer-related studies and high-resolution brain anatomy.

Ahmadreza Attarpour¹, James Ward², and J. Jean Chen^1,2
1Medical Biophysics, University of Toronto, Toronto, ON, Canada, ²Rotman Research Institute, Baycrest, Toronto, ON, Canada

Due to its cardiogenic constituents, the cerebrospinal fluid (CSF) contribution to resting-state functional MRI (rs-fMRI) has been used for denoising. Recently, it has become increasingly used for characterizing CSF flow and glymphatic flow. However, the association between CSF and vascular oscillations in rs-fMRI remains to be fully understood. In this study, we quantify the relationship between rs-fMRI fluctuation in different CSF compartments and photoplethysmography (PPG) recordings, focusing on the frequency band around 0.1 Hz. We also quantify their relationship between the rs-fMRI signals (in CSF, tissue and vasculature) and other vascular measures derived from PPG traces.

Miller Fawaz¹, Sara Gharabaghi¹, Mojtaba Jokar¹, Ying Wang^1,2, Chao Chai³, and E. Mark Haacke^1,2
1Magnetic Resonance Innovations, Inc., Bingham Farms, MI, United States, ²Wayne State University, Detroit, MI, United States, ³Tianjin First Central Hospital, Tianjin, China

Automatic cerebral microbleed detection is attainable with our two step model for many disease states. We attributed previously shown lower performance in STAGE data to veins and edges, including some in the basal ganglia. We improved our existing pipeline for this detection by adding a false positive correction step to our pipeline using previously tested and new data. The results were improved overall, including on previously tested STAGE data, new STAGE data and our previously tested single echo data (multiple diseases). This makes our pipeline a viable and versatile real time automatic microbleed detection procedure.

Kathleen B Miller¹, Leonardo A Rivera-Rivera¹, Oliver Wieben¹, Kevin M Johnson¹, Sterling C Johnson¹, and Jill N Barnes^1
1University of Wisconsin-Madison, Madison, WI, United States

Low frequency oscillations (LFOs) of cerebral vessels may be important indicators of aging and disease related changes to cerebral autoregulation and glymphatic clearance. Assessing LFOs during a vasodilatory stimulus, such as hypercapnia, may reveal age-associated changes not apparent at rest. This study utilized 3D radial sampling and local low-rank reconstruction of 4D flow MRI scans to achieve real time temporal resolution to assess LFOs. Preliminary results suggest that there were no hypercapnia or age-associated changes in LFOs in the large intracranial arteries; however, there were both age and hypercapnia effects on LFOs in the venous circulation.  

Kayley Marchena-Romero^1,2, Xiang Ji², Andrew Centen², Joel Ramirez², Andrew Lim², Sandra E Black², and Bradley J MacIntosh^1,2
1Medical Biophysics, University of Toronto, Toronto, ON, Canada, ²Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada

Cerebrovascular reactivity (CVR) is assessed by dynamic MRI scanning, such as BOLD-fMRI during a hypercapnia gas challenge. Conventional CVR metrics do not account for individual vasoactive challenges in series. We study the relationship between vasoconstriction after the 1^st hypercapnia challenge and CVR during the 2^nd challenge, using a non-parametric method, Sen’s Slope, to estimate BOLD change. We show that vasoconstriction is directly proportional to the amplitude of CVR across a range of adult ages, as assessed by linear regression analysis. These results support our hypothesis that temporal features of a cerebrovascular challenge can provide additional insight on cerebrovascular physiology.

Satoshi Yatsushiro¹, Tomohiko Horie², Mitsunori Matsumae³, and Kagayaki Kuroda^1
1Department of Human and Information Science, Tokai University, Hiratsuka, Japan, ²Department of Radiological Technology, Tokai University Hospital, Isehara, Japan, ³Department of Neurosurgery, Tokai University, Isehara, Japan

To investigate cardiac- and respiratory-driven CSF motions in the intracranial space, asynchronous phase contrast (Async-PC) imaging with Stockwell transform (ST) and power mapping was conducted for 3 healthy volunteers under free breathing. ST can separate the cardiac- and respiratory-driven CSF motions as spectrogram. Power mapping visualizes the power of the spectrum voxel-by-voxel. Async-PC with ST presented the time-frequency property of the cardiac- and respiratory-driven CSF motions, while that with the power mapping technique visualized the spatial distribution of both the motion contributions. Combination of those techniques may provide new findings related with CSF dynamics.

Yoshitaka Bito^1,2, Hisaaki Ochi^1,2, Kuniaki Harada², and Kohsuke Kudo^2
1Healthcare Business Unit, Hitachi, Ltd., Tokyo, Japan, ²Department of Diagnostic Imaging, Hokkaido University Graduate School of Medicine, Sapporo, Japan

Low b-value DTI (Low-b DTI) has been recently proposed for investigating the CSF physiology, and was reported to reflect the covariance of velocity distribution of the pseudo-random flow. The purpose of this study was to analyze diffusion properties of Low-b DTI (i.e. diffusion tensor, mean diffusivity, and fractional anisotropy) for normal volunteers. The diffusion properties show statistically high and anisotropic values at some ROIs such as around the foramen of Monro, the aqueduct, the prepontine cistern and the Sylvian fissure. It demonstrates that Low-b DTI can be used for evaluating the pseudo-random flow of CSF.

Toshiaki Taoka^1,2, Rintaro Ito^1,2, Rei Nakamichi², Takashi Abe², Toshiki Nakane², Hisashi Kawai², Mayuko Sakai³, and Shinji Naganawa^2
1Department of Innovative Biomedical Visualization (iBMV), Nagoya University, Nagoya, Japan, ²Radiology, Nagoya University, Nagoya, Japan, ³Canon Medical Systems Corporation, Otawara, Japan

We conducted water peak MRS without water suppression, in which the water peak itself is evaluated, to determine if the water peak is altered by the existence of solutes and to evaluate the feasibility of water peak MRS for detecting pathologic changes in CSF. The water peaks were modified by the solute concentrations of NaCl, Glu, and Alb. Differences in water peaks were observed among the CSF phantom simulating normal CSF, CSF with bacterial meningitis, and CSF with obstruction of the subarachnoid space.

Tiago Martins¹, Tales Santini¹, Minjie Wu¹, Kristine Wilckens¹, Davneet Minhas¹, James W. Ibinson¹, Howard J. Aizenstein¹, and Tamer S. Ibrahim^1
1University of Pittsburgh, Pittsburgh, PA, United States

In this work, we investigated the oscillations on the flow cerebrospinal fluid in the human brain using ultra-high field magnetic resonance imaging with a homogeneous head coil. Acquisition and analysis of images from 5 human volunteers results in identification of different frequency bands around 0.3, 0.8, 1.2, 2.3 and 3.4Hz. The analysis of the frequency spectrum and spatial localization of the signal yield results that could be correlated with physiological processes and CSF clearances.

Masatoshi Kojima^1,2, Yohsuke Makino^1,3, and Hirotarou Iwase^1,3
1Department of legal of medicine, graduate school of medicine, Chiba university, Chiba, Japan, ²Department of radiology, Chiba medical center, Chiba, Japan, ³Department of forensic medicine, graduate school of medicine, Tokyo university, Tokyo, Japan

The purpose of this study was to investigate the variation of cerebral temperature and T1 and T2 values by varying the temperature of the formalin-fixed brain, assuming various temperatures during postmortem MRI. The T1 and T2 values were calculated by varying the temperature of the formalin-fixed brain in a thermostatic bath from 5°C to 40°C. THe T2 value prolonged with increasing temperature, and the T1 value was highest at 20°C and decreased at lower and higher temperatures. The results of this study will be useful for setting conditions for postmortem MRI imaging and image interpretation.

Celine Berger^1,2, Melanie Bauer^1,2, Eva Scheurer^1,2, and Claudia Lenz^1,2
1Institute of Forensic Medicine, Department of Biomedical Engineering, Basel, Switzerland, ²Institute of Forensic Medicine, Health Department Basel-Stadt, Basel, Switzerland

The temperature sensitivity of the relaxation parameters represents a major issue in post-mortem MRI due to the passive cooling of the deceased. This study proposes a real-time non-invasive temperature correction method of MR neuroimaging parameters based on an MRI compatible forehead temperature probe. The observed significant linear relations between the forehead temperature and the relaxation times indicate that this real-time non-invasive temperature correction method is suitable for in situ post mortem MR neuroimaging.

Khin Khin Tha^1,2, Yuta Urushibata³, Hiroyuki Hamaguchi², and Hideki Hyodoh^4
1Global Center for Biomedical Science and Engineering, Hokkaido University Faculty School of Medicine, Sapporo, Japan, ²Department of Biomarker Imaging Science, Hokkaido University Graduate School of Biomedical Science and Engineering, Sapporo, Japan, ³Siemens Healthcare K.K., Tokyo, Japan, ⁴Department of Forensic Medicine, Hokkaido University Faculty of Medicine, Sapporo, Japan

This prospective study aimed to evaluate if CEST MRI can detect the biochemical composition of CSF. Fifty-two cadaveric CSF samples were tested for any correlation between the compounds detected by CEST MRI and the CSF biochemical analysis reports. The normalized area for intermediate exchanging amines showed a moderate positive correlation with protein concentration (r= 0.436, P= 0.001), a weak positive correlation with specific gravity (r=0.369, P=0.007), and a weak negative correlation with pH (r= -0.290, P= 0.037). The normalized area for intermediate exchanging amines may be sensitive to detect a change in CSF proteins.

Kwok-Shing Chan¹ and José P. Marques^1
1Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands

In this study, we optimise the variable flip angle acquisition protocol for GRE-based myelin water imaging using MCR model. We show numerically and via in vivo imaging that MCR-MWI can be performed with as few as 3 flip angles and still be able to achieve similar measurement performance as with 7 flip angles. We also conduct an analysis to investigate the usefulness of an image denoising method to improve MWI. Preliminary results suggest that MCR-MWI is very robust to noise and higher resolution data is needed to have a better insight. 

Feng Han¹, Gregory L Brown^2,3, Yalin Zhu¹, Aaron Belkin-Rosen¹, Mechelle M Lewis^3,4, Guangwei Du³, Yameng Gu¹, Paul J Eslinger^3,5, Richard B Mailman^3,4, Xuemei Huang^3,4,5,6,7,8, and Xiao Liu^1,8
1Department of Biomedical Engineering, The Pennsylvania State University, State College, PA, United States, ²Department of Engineering Science and Mechanics, The Pennsylvania State University, State College, PA, United States, ³Department of Neurology, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA, United States, ⁴Department of Pharmacology, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA, United States, ⁵Department of Radiology, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA, United States, ⁶Department of Neurosurgery, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA, United States, ⁷Department of Kinesiology, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA, United States, ⁸Institute for Computational and Data Sciences, The Pennsylvania State University, State College, PA, United States

Deposition and spreading of misfolded proteins have been linked to cognitive dysfunction in Parkinson’s disease (PD). The glymphatic system responsible for removing brain wastes thus may play a role in cognitive impairment in PD. This hypothesis is however difficult to test in clinical populations due to the lack of non-invasive measurements of glymphatic function. Low-frequency (< 0.1 Hz) resting-state fMRI (rsfMRI) signal was recently linked to glymphatic function primarily based on its sleep-dependent coupling with CSF flows. This study found early evidence that the coupling of global rsfMRI and CSF signals is indeed related to cognitive decline in PD.

Ivan Maximov^1,2, Oliver Geier³, Elias Kellner⁴, Helle Pfeiffer³, Valerij G Kiselev⁴, and Marco Reisert^4
1Western Norway University of Applied Sciences, Bergen, Norway, ²NORMENT, University of Oslo, Oslo, Norway, ³Oslo University Hospital, Oslo, Norway, ⁴University Medical Center Freiburg, Freiburg, Germany

Myelin water imaging (MWI) is a useful tool to probe and provide a quantitative measure of myelin content in the human brain in vivo. The most common MRI technique for MWI is based on multi-echo T₂ measurements allowing one to estimate different T₂ contributions into the signal decay. However, the conventional non-negative least squares algorithm is computationally very challenging and vulnerable to image artefacts. In the present work we developed an optimised framework for MWI enabling improved pipeline and fast metric estimations using Bayesian regression.

Gerhard Drenthen¹, Jacobus Jansen¹, Paulien Voorter¹, Joost de Jong¹, and Walter Backes^1
1Maastricht University Medical Center, Maastricht, Netherlands

Recently, it was shown that besides the parenchymal diffusion and microvascular perfusion an additional, intermediate, component can be observed in the IVIM signal. The fraction of this intermediate diffusion ($$$f_{int}$$$) is suggested to be related to interstitial fluid in the perivascular spaces (PVS). In this study we examine several b-value sampling strategies for measuring the ($$$f_{int}$$$) using simulated IVIM data. When a large intermediate diffusion component is present in the IVIM signal (eg. white matter hyperintensities), b-value sampling strategies specifically aimed to quantify this component can provide better estimates of $$$f_{int}$$$ compared to linear or logarithmic spaced b-values.

Isabelle Heukensfeldt Jansen¹, Luca Marinelli¹, J Kevin DeMarco², Robert Y Shih^2,3, Vincent B Ho^2,3, and Thomas TK Foo^1
1GE Global Research Center, Niskayuna, NY, United States, ²Walter Reed National Military Medical Center, Bethesda, MD, United States, ³Uniformed Services University of the Health Sciences, Bethesda, MD, United States

We use retrospective cardiac gating with phase-sensitive reconstruction of diffusion tensor data to create a 4D profile of motion in brain parenchyma with velocity encoding value (VENC) of 0.18 mm/s. We imaged the brain of a healthy volunteer in regions surrounding the ventricles with synchronized recording of a PPG signal. We created a velocity profile for the volume spanning the full cardiac cycle by binning individual images according to the local cardiac phase. Results show coherent periodic motion with distinct systolic/diastolic phases. This motion is thought to comprise of both tissue movement and interstitial fluid flow (ISF) in the region.

Dennis Thomas^1,2, Ana-Maria Oros-Peusquens¹, Dirk Poot³, and N. Jon Shah^1,4,5,6
1Institute of Neuroscience and Medicine-4, Forschungszentrum Jülich, Jülich, Germany, ²RWTH Aachen University, Aachen, Germany, ³Department of Radiology and Nuclear medicine, Erasmus Medical Center, Rotterdam, Netherlands, ⁴Department of Neurology, RWTH Aachen University, Aachen, Germany, ⁵Institute of Neuroscience and Medicine 11, INM-11, JARA, Forschungszentrum Jülich, Jülich, Germany, ⁶JARA - BRAIN - Translational Medicine, Aachen, Germany

Tissue water content is highly regulated in the healthy brain, and even small changes are indicative of pathology. It also constitutes an important source of anatomic MRI contrast. However, this contrast remains insufficiently explored, partly due to lengthy measurement times and relatively low resolution. Super-resolution reconstruction techniques offer a trade-off between resolution, scan time and SNR.The goal of this work was to develop a technique to achieve high resolution, whole-brain water content maps by employing super-resolution reconstruction techniques. Results from the developed technique were evaluated with a carrageenan phantom and whole-brain water content maps acquired from a healthy volunteer.

Claire Kelly^1,2, Thijs Dhollander², Ian Harding^3,4, Wasim Khan³, Richard Beare², Jeanie Cheong^1,5,6, Lex Doyle^1,5,6,7, Marc Seal^2,7, Deanne Thompson^1,2,7, and Peter Anderson^1,8
1Victorian Infant Brain Studies (VIBeS), Murdoch Children's Research Institute, Melbourne, Australia, ²Developmental Imaging, Murdoch Children's Research Institute, Melbourne, Australia, ³Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia, ⁴Monash Biomedical Imaging, Monash University, Melbourne, Australia, ⁵Newborn Research, The Royal Women's Hospital, Melbourne, Australia, ⁶Department of Obstetrics and Gynaecology, The University of Melbourne, Melbourne, Australia, ⁷Department of Paediatrics, The University of Melbourne, Melbourne, Australia, ⁸Turner Institute for Brain and Mental Health and School of Psychological Sciences, Monash University, Melbourne, Australia

We investigated the microstructural composition of the brain tissue in 130 adolescents born very preterm (VP) compared with 45 full-term (FT)-born controls. This involved a novel voxel-based analysis of white matter-like, grey matter-like, and fluid-like (free-water) diffusion tissue signal fractions derived by Single-Shell 3-Tissue Constrained Spherical Deconvolution. VP adolescents showed widespread, diverse microstructural alterations and increased free-water content across the brain parenchyma compared with FT controls, which were associated with perinatal risk factors and adverse neurodevelopmental outcomes. This study expands knowledge of the neurobiological mechanisms by which VP birth adversely affects brain development in the long-term.