Constantina Treaba¹, Allegra Conti², Ambica Mehndiratta¹, Valeria Barletta^1,3, Caterina Mainero^1,3, and Nicola Toschi^1,2
1Radiology, Massachusetts General Hospital; A. Martinos Center for Biomedical Imaging, Boston, MA, United States, ²Department of Biomedicine and Prevention, University of Rome “Tor Vergata", Rome, Italy, ³Harvard Medical School, Boston, MA, United States

In multiple sclerosis (MS), cortical atrophy could result from extensive axonal transection from distant white matter lesion and/or local cortical demyelination. The destructive potential of MS white matter lesions, however, seem to differ across lesion types, being higher for chronic active lesions detectable on susceptibility weighted images by their characteristic paramagnetic rim. Using 7T MRI that has shown increased sensitivity to cortical lesions and modern machine learning algorithms, we demonstrate that both white matter and cortical lesions are main determinants of cortical thinning. Despite their destructive capacity, chronic active lesions are not major contributors of cortical tissue loss.

Joan Brewer¹, Ilena George², Gale Edison¹, Joy Zhang², Sarah King², James Sumowski², Priti Balchandani², Gaurav Verma², Rebecca Feldman¹, and Sam Horng^2
1University of British Columbia Okanagan, Kelowna, BC, Canada, ²Icahn School of Medicine at Mount Sinai, New York, NY, United States

Multiple Sclerosis (MS) is an autoimmune disease; disease can be measured on MRI by the appearance or enlargement of lesions. PVS measurements on MRI may represent a more predictive biomarker of disease. Because manual measurement of PVSs is time intensive, our collaborators developed a tool to automatically segment PVSs. Here, we investigated the utility of the automatic segmentations. We correlated the automated PVS counts with manual segmentations (0.66), as well as the PVS areas (0.55). Differences between healthy control and MS groups in this preliminary analysis were not statistically significant. Future work will expand from 45 to 300 patients.

Valeria Barletta¹, Elena Herranz¹, Constantina Andrada Treaba¹, Ambica Mehndiratta², Russell Ouellette³, Tobias Granberg⁴, Eric Klawiter⁵, Carolina Ionete⁶, Jacob Sloane⁷, and Caterina Mainero^1
1Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA, United States, ²Department of Radiology, Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA, United States, ³Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden, ⁴Karolinska University Hospital, Department of Neuroradiology, Stockholm, Sweden, ⁵Department of Neurology, Massachusetts General Hospital, Boston, MA, United States, ⁶Umass Memorial Medical Center, Worcester, MA, United States, ⁷Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, United States

We combined 11C-PBR28 magnetic resonance-positron emission tomography, marking activated microglia, with synthetic MRI to measure myelin content, on a group of 33 patients affected by multiple sclerosis, to quantify neuroinflammation in the brain white matter and assess its relation to myelin content and disease burden. Microglia activation was higher in the white matter of multiple sclerosis patients compared to 16 healthy volunteers. Microglia activation within perilesional WM correlated the most with worse disease outcomes. Peripherally active lesions were related to higher disability and progressive disease. Perilesional myelin content was lower for higher inflammation and correlated with disease burden.

Constantina Treaba¹, Ciprian Catana^1,2, Eric Klawiter^2,3, Susie Huang^1,2, Grae Arabasz¹, Valeria Barletta^1,2, Elena Herranz^1,2, Jacob Sloane⁴, Peter Caravan^1,2, and Caterina Mainero^1,2
1Radiology, Massachusetts General Hospital; A. Martinos Center for Biomedical Imaging, Boston, MA, United States, ²Harvard Medical School, Boston, MA, United States, ³Neurology, Massachusetts General Hospital, Boston, MA, United States, ⁴Neurology, Beth Israel Deaconess Medical Center, Boston, MA, United States

In multiple sclerosis, experimental and histopathological studies point to fibrinogen as a link between a damaged brain blood barrier and the initiation of the inflammatory demyelination and neurodegeneration in both cortex and white matter. Nevertheless, although the widespread accumulation of fibrinogen as fibrin deposits within multiple sclerosis lesions is well documented on postmortem brain tissue, in vivo evidence is still lacking. Using a novel fibrin-specific positron emission tomography probe, ⁶⁴Cu-FBP8, we were able to demonstrate in vivo fibrin deposition not only in active white matter multiple sclerosis lesions but also in the cortex of a few multiple sclerosis patients.

Risavarshni Thevakumaran ^1,2, Adam Groh ^3,4, Jo Anne Stratton^3,4, and David Rudko ^1,2,3
1Biological and Biomedical Engineering, McGill University, Montreal, QC, Canada, ²McConnell Brain Imaging Centre, Montreal, QC, Canada, ³Neurology and Neurosurgery, McGill University, Montreal, QC, Canada, ⁴Montreal Neurological Institute-Hospital, Montreal, QC, Canada

Quantitative T₂^* and T₁ relaxometry metrics calculated at 7T have high sensitivity to myelin and can be jointly used to identify dirty-appearing white matter (DAWM) and normal-appearing white matter (NAWM) pathology in post-mortem, multiple sclerosis (MS) brain tissue. Relaxometry mapping was performed on fixed, cerebral brain samples from MS patients and healthy donors. T₂^* and T₁ distributions in WM from MS tissue exhibited bimodality and were shifted to higher relaxation time values compared to healthy tissue. Using k-means clustering applied to 2D T₂^* and T₁ MS tissue data, regions of DAWM were detected in periventricular WM for MS tissue samples.

Jianing Tang¹, Soroush Heidari Pahlavian¹, Helena Chui², and Lirong Yan^1,2
1USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States, ²Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States

Characterization of cerebral vascular compliance (VC) could offer more insights into the vascular contribution to cognitive impairment. Cerebral VC can be measured using ASL methods but with a long scan time. A recent study introduced a fast MRI technique to assess global cerebral VC by measuring carotid pulse wave velocity (cPWV) using a single-slice oblique-sagittal PC-MRI. In this study, the robustness of cPWV measurement to the variations of ROI selection has been demonstrated. The results from a pilot study on an aged cohort suggests elevated cPWV is associated with cognitive decline and could be a potential marker for cognitive impairment.  

KowsalyaDevi Pavuluri¹, Jonathan M. Scott², John Huston III¹, Richard L. Ehman¹, Armando Manduca^1,3, Clifford R. Jack¹, Rodolfo Savica⁴, Bradley F Boeve⁵, Kejal Kantarci¹, Ronald C. Petersen⁴, and Matthew C. Murphy^1
1Department of Radiology, Mayo Clinic, Rochester, MN, United States, ²Mayo Clinic Medical Scientist Training Program, Mayo Clinic, Rochester, MN, United States, ³Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, United States, ⁴Department of Neurology, Mayo Clinic, Rochester, MN, United States, ⁵Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, United States

Dementia is a progressive neurodegenerative syndrome characterized by impairment in memory and activities of daily living, altered behavior, personality, and other cognitive dysfunctions. Around 50 million people have dementia worldwide, and there are nearly 10 million new cases every year. MR elastography is a non-invasive imaging technique to measure the mechanical properties of tissues and has demonstrated sensitivity to neurodegenerative processes. In this study we utilized two neural network inversions to investigate the viscoelastic property changes in cortical regions with both tissue- and environment-weighting in various etiologies of dementia including Alzheimer’s, frontotemporal dementia, and dementia with Lewy bodies.

Liangdong Zhou¹, Thanh Nguyen¹, and Yi Li^1
1Radiology, Weill Cornell Medicine, New York, NY, United States

We demonstrated that, our proposed T2 relaxometry-based free water mapping, CSFF, could be an imaging biomarker of dilated PVS and CSF clearance function by correlating it with multiple brain clearance-related measures including PVS score, PC-MRI based aqueduct CSF flow, dynamic PET based ventricle CSF clearance, amyloid beta and tau deposits. Our results show that CSFF is positively associated with PVS score, aging, amyloid beta and tau deposits. And it negatively correlates with net aqueduct CSF flow, ventricle CSF flow, and cognitive score.

Junjie Wu¹, Qixiang Lin², Benjamin B. Risk³, Aditya S. Bisht², David W. Loring², Felicia C. Goldstein², Allan I. Levey², James J. Lah², and Deqiang Qiu^1,4
1Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, United States, ²Department of Neurology, Emory University School of Medicine, Atlanta, GA, United States, ³Department of Biostatistics and Bioinformatics, Emory University Rollins School of Public Health, Atlanta, GA, United States, ⁴Joint Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, United States

We systematically studied alterations in 14 resting-state functional networks due to normal aging and AD pathology in the asymptomatic phase, as well as their relationship with CSF biomarkers for AD and neuropsychological assessments. We found disrupted functional connectivity in most of the functional networks with normal aging and compromised left executive control network (LECN) due to asymptomatic AD pathology. Furthermore, LECN is associated with overall cognition. Tau closely correlates with functional networks in asymptomatic AD.

Wingchi Edmund Kwok¹, Molly Brady², Akib Rahman³, Alexander Solorzano³, Ronald Wood³, and Rashid Deane^3
1Imaging Sciences, University of Rochester Medical Center, Rochester, NY, United States, ²Tufts University, Boston, MA, United States, ³University of Rochester, Rochester, NY, United States

Study of CSF flow can be used to assess CSF clearance pathways for the better understanding of neurological diseases, such as Alzheimer's disease. We developed a technique for macromolecular gadolinium enhanced dynamic MRI of CSF in mice on a whole-body 3T system. A specially designed 4-channel RF receive coil was developed, and a high-resolution 3D spoiled gradient-echo T1 sequence was used. Gadolinium-albumin contrast was injected into the cisterna magna. Contrast enhancement was detected in various locations including the olfactory lobe, nasal cavity, lymphatic system and spine cord. Lower contrast elimination rates were observed in old mice than in young mice.

Chenyang Li¹, Li Jiang¹, Marco Muccio¹, Sagar Buch², Hanzhang Lu³, E.Mark Haacke², and Yulin Ge^1
1Department of Radiology, NYU Grossman School of Medicine, New York, NY, United States, ²Department of Radiology, Wayne State University School of Medicine, Detroit, MI, United States, ³Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States

In this study, we reconstructed the venous drainage course of Basal vein of Rosenthal (BVR) and its tributaries using dual-echo SWI/QSM. Consistent with existing knowledge of venous anatomy, our results show that BVR drains blood from multiple tissue structures such as insula, amygdala and hippocampus. Inferior ventricular vein (IVV) and medial atrial vein (MAV), two tributaries of BVR, are anatomically relevant to the venous drainage in hippocampus. With the proposed technique, we extracted the venous blood susceptibility value in BVR and IVV/MAV to examine its feasibility in characterizing changes of venous oxygenation level related to hippocampal neurodegeneration.