Nick Teller¹, Jordan A. Chad^1,2, Eugenie Roudaia¹, Ali Hashemi³, Haddas Grosbein¹, Asaf Gilboa^1,2, Maged Goubran^2,4, Ivy Cheng^2,4, Sandra E. Black^2,4, Robert Fowler^2,4, Chris Heyn^2,4, Fuqiang Gao⁴, Mario Masellis^2,4, Jennifer Rabin^2,4, Xiang Ji⁴, Aravinthan Jegatheesan^2,4, Benjamin Lam^2,4, Allison B. Sekuler^1,2,3, Bradley J. MacIntosh^2,4, Simon J. Graham^2,4, and J. Jean Chen^1,2
1Rotman Research Institute, North York, ON, Canada, ²University of Toronto, Toronto, ON, Canada, ³Psychology, Neuroscience & Behaviour, McMaster University, Hamilton, ON, Canada, ⁴Sunnybrook Research Institute, Toronto, ON, Canada

The impact of COVID19 on the brain’s microstructural integrity remains unclear.  In this study, we examine self-isolated COVID19 patients and controls using diffusion-tensor and free-water imaging, based on single- and multi-shell acquisitions, respectively. We identify several differences in spatial covariance among patients in fractional anisotropy (in cingulate-frontal and temporal-parietal regions), but not free water fraction. Our results indicate COVID19’s implications in long-term, measurable brain deficits.

Alexander D. Cohen¹, Laura Umfleet², Malgorzata Franczak², Sara Swanson², Jessica Pommy², Mohit Agarwal², Baolian Yang³, Suchandrima Banerjee³, and Yang Wang^1
1Radiology, Medical College of Wisconsin, Milwaukee, WI, United States, ²Medical College of Wisconsin, Milwaukee, WI, United States, ³GE Healthcare, Waukesha, WI, United States

Patients suffering from long COVID report cognitive symptoms months after disease onset, which may be related to neurovascular changes. Here, we evaluated functional connectivity in long COVID elderly patients and control subjects using a region of lower cerebrovascular reactivity (CVR) as the seed. We found significantly lower connectivity in long COVID patients that was widespread potentially linking alterations in CVR to functional connectivity and reduced cognitive ability in long COVID patients.

Emanuele Camerucci¹, Jose Thulasee¹, Matthew Bernstein¹, Steven Messina¹, Peter Kollasch¹, and John Huston^1
1Mayo Clinic, Rochester, MN, United States

We took advantage of the COVID-19-related decrease in clinical volume to conduct a quality improvement project; we established a panel of 24 experts for reviewing currently used brain MRI sequences and proposing ways to improve image quality and/or decrease acquisition time. The proposed sequences were integrated in existing protocols and compared with the standard ones. We were able to improve 14 of the most used brain MRI sequences with an equal or improved image quality and reduced acquisition time. Hence, we were able to reduce the acquisition time of our Brain protocol and Epilepsy protocol by 29.2% and 40%, respectively.

Chu-Yu Lee¹, Michael S Petronek², Cameron M Cushing³, Garry R Buettner², Joel J St-Aubin², Varun Monga⁴, John M Buatti², Joseph J Cullen⁵, Douglas R Spitz², Bryan G Allen², and Vincent A Magnotta^1
1Department of Radiology, The University of Iowa, Iowa City, IA, United States, ²Department of Radiation Oncology, Free Radical and Radiation Biology Program, The University of Iowa, Iowa City, IA, United States, ³Skope Magnetic Resonance Technologies AG, Zurich, Switzerland, ⁴Department of Internal Medicine, The University of Iowa, Iowa City, IA, United States, ⁵Department of Surgery, The University of Iowa, Iowa City, IA, United States

Pharmacological ascorbate (P-AscH^-), as an adjuvant to standard treatment for glioblastoma, may selectively enhance cancer cell killing. The mechanisms of P-AscH^- have been associated with redox changes in the labile iron pool. This study applies T₂* and QSM to assess the redox changes in 40 glioblastoma patients receiving standard treatment and adjuvant P-AscH^-. The results demonstrate an increase in T₂* values and a decrease in QSM values within contrast-enhancing lesions 1 hour after P-AscH^- infusion. These changes in T₂* and QSM may result from the redox changes by P-AscH^-, supporting the potential for imaging assessment of response to P-AscH^-.

Zongpai Zhang¹, Faizan Khan², Peter Novak², Christos Mantzoros³, Long Ngo³, Vera Novak², and Weiying Dai^1
1State University of New York at Binghamton, Binghamton, NY, United States, ²Department of Neurology, Harvard Medical School, Boston, ME, United States, ³Department of Medicine, Harvard Medical School, Boston, ME, United States

We aimed to investigate the effect of intranasal insulin (INI) on cognition, balance, and brain neurovascular activity in type 2 diabetes mellitus (T2DM) participants of the MemAID trial. Cognition, balance, and brain neurovascular fluctuations - amplitude of low-frequency fluctuations (ALFF) were measured in 11 subjects before and after 24-week treatment with INI or placebo. INI treatment significantly increased ALFF in the medial-frontal region. The ALFF increases at the end-of INI treatment were associated with improved balance. These findings suggest that INI may increase brain neurovascular activity in T2DM in the regions related to balance control and sustained attention.

Ping-Hong Yeh¹, J. Kent Werner, Jr^2,3, Chihwa Song¹, Rujirutana Srikanchana¹, Wei Liu¹, 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, ³Walter Reed National Military Medical Center, Bethesda, MD, United States

Sleep disturbances are common following traumatic brain injury (TBI). The intent of this study is to characterize the role of the noradrenergic locus coeruleus (LC) for sleep maintenance in service members following mild TBI by associating microstructural features, derived from diffusion MRI, of the LC–noradrenergic (NA) system with objective sleep measures. We found that severity of sleep apnea, particularly in rapid eye movement stage during sleep, significantly correlated with microstructural changes in the LC pathways to hypothalamus in mTBI participants. This result suggests sleep apnea following mild TBI may be modulated by sympathetic activity via pathways interconnecting LC and hypothalamus.

Elena Herranz^1,2, Valeria Barletta^1,2, Constantina A. Treaba^1,2, Ambica Mehendiratta¹, Russell Ouellette^1,3,4, Eric Klawiter^5,6, Jacob Sloane ^2,7, Carolina Ionette⁸, Suma Babu^2,5, Marco L. Loggia^1,2, Meena M Makary^1,2,9, Jacob M Hooker^1,2, Ciprian Catana^1,2, Revere Kinkel¹⁰, Roberta Magliozzi^11,12, and Caterina Mainero^1,2
1Radiology, Massachusetts General Hospital, Boston, MA, United States, ²Harvard Medical School, Boston, MA, United States, ³Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden, ⁴Department of Neurology, 4. Karolinska University Hospital, Stockholm, Sweden, ⁵Neurology, Massachusetts General Hospital, Boston, MA, United States, ⁶Massachusetts General Hospital, Boston, MA, United States, ⁷Beth Israel Deaconess Medical Center, Boston, MA, United States, ⁸Department of Neurology, UMass Memorial Medical Center, Worcester, MA, United States, ⁹Systems and Biomedical Engineering Department, Faculty of Engineering, Cairo University, Giza, Egypt, ¹⁰Department of Neuroscience, University of California, San Diego, CA, United States, ¹¹Neurology Section, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy, ¹²Division of Neuroscience, Department of Brain Sciences, Imperial College London, London, United Kingdom

In multiple sclerosis (MS), neuropathological studies suggest that meningeal inflammation involving T-, B-lymphocytes, plasma cells, macrophages may trigger underlying cortical neuroinflammation and demyelination. Using MR-PET targeting the18kDa mitochondrial translocator protein, which is overexpressed in activated glia/macrophages, we detected in 49 MS patients cortical inflammatory changes along with neuroinflammation in both meninges and juxtacortical white matter. Meningeal inflammation correlated with worse neurological disability and cognitive performance. Histochemistry performed in meningeal tissue from 40 post-mortem progressive MS cases confirmed in vivo findings. This study provides in vivo PET imaging evidence implicating meningeal neuroinflammation in the pathophysiology of MS.

Rachel Bitton¹, Angela Fast², Gina Hesley³, Steven Raman⁴, Alan Matsumoto⁵, Eric Dolan⁶, Maureen Kohi⁷, Thomas Price⁸, Fiona Fenessey⁹, and Pejman Ghanouni^1
1Radiology, Stanford University, Stanford, CA, United States, ²Allegheny Health Network, Pittsburgh, PA, United States, ³Radiology, Mayo Clinic, Rochester, MN, United States, ⁴Radiology, UCLA, Los Angeles, CA, United States, ⁵Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, United States, ⁶Interventional Radiology, Ohio Health, Columbus, OH, United States, ⁷Radiology, UCSF, San Francisco, CA, United States, ⁸Obstetrics and Gynecology, Duke University, Durham, NC, United States, ⁹Radiology, Brigham and Women's Hospital, Boston, MA, United States

This study presents results of a prospective multicenter clinical trial of 99 women treated with MR guided focused ultrasound (MRgFUS) for symptomatic uterine leiomyomas to assess treatment durability and to evaluate potential demographic, imaging, and technical characteristics associated with lasting clinical outcomes. Following treatment, there was an improvement in symptoms, with a significant decrease in mean symptom severity score at the 6, 12, 24 and 36 month follow up (p<0.001). In a multivariate model, a new parameter of interest, the ratio of non-perfused volume to total fibroid volume (NPV/TFV) was found to be predictive of durable clinical success (p=0.03).

Stanley Chu¹, Mitchell Collins¹, Maurice H Pradella², Rachel Davids ³, Martin Kramer ³, Mathis Zimmerman³, Sarah Fopma², Alexander Korutz², Ryan Avery², Michael Markl², Bradley Allen², Blair Faber², and James Carr^2
1Radiology, Northwestern University, Chicago, IL, United States, ²Northwestern University, Chicago, IL, United States, ³Siemens Medical Solutions, Chicago, IL, United States

The impact of the first wave of COVID-19 (Feb-Apr. 2020) on imaging volumes has been widely explored, but responses to a subsequent wave (Oct-Dec. 2020) remain to be investigated. In this study, a cloud-based analytics tool (CBAT) collected monthly CT/MRI scan volumes at a large tertiary center from Oct 2019 to Aug 2021. The first wave of COVID-19 significantly lowered all forms of CT/MRI imaging. The second COVID-19 wave did not significantly impact CT/MRI scan volumes, which remained at pre-pandemic levels during/afterwards. CBAT has the ability to assess impact/response towards two waves of COVID-19 at a large tertiary center.

Alejandro Santos-Díaz^1,2, Berenice Sanchez-Alvarado³, Oscar Marrufo Melendez⁴, Roger Carrillo Mezo⁴, Antonio Arauz Gongora⁴, and Monica Rodriguez^5
1School of Engineering and Science, Tecnologico de Monterrey, Mexico City, Mexico, ²School of Medicine and Health Sciences, Tecnologico de Monterrey, Monterrey, Mexico, ³School of Engineering and Science, Tecnologico de Monterrey, Monterrey, Mexico, ⁴Neuroimaging, Instituto Nacional de Neurologia y Neurocirugía, Mexico City, Mexico, ⁵Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico

Evidence supports that the virus SARS-CoV-2 has a potential neuroinvasion causing neurological symptoms, even after recovery. Diffusion Weighted Imaging (DWI) allows us to detect the microstructural changes in white matter tissue integrity. In this work, we studied the neurological manifestations of COVID-19 in apparent diffusion coeficient (ADC), fractional anisotropy (FA), and metrics derived from fixel-based analysis (FBA) such as fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC). We found statistically significant differences in 34/43 fiber bundle regions from the IIT Human Brain Atlas in the five different metrics studied.

Huajun Liang¹, Thomas Ernst^1,2, Kenichi Oishi³, Meghann Ryan¹, Eleanor Wilson⁴, Andrea Levine⁵, Eric Cunningham¹, Shyamasundaran Kottilil⁴, and Linda Chang^1,2,6
1Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, United States, ²Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ³Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁴Institute of Human Virology, Department of Medicine, Division of Infectious Disease, University of Maryland School of Medicine, Baltimore, MD, United States, ⁵Department of Medicine, Division of Pulmonary & Critical Care Medicine, University of Maryland School of Medicine, Baltimore, MD, United States, ⁶Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, United States

Diffusion tensor imaging (DTI), a sensitive method to detect inflammatory or cytotoxic tissue changes, has been used to study brain microstructure in patients with COVID-19. At 2-3 months post-acute sequelae SARS-CoV-2 infection (PASC), prior reports found both higher or lower than normal white matter diffusivity in participants who had variable severity of clinical manifestations. We performed DTI and neuropsychiatric assessments in 20 participants with PASC. Individuals with PASC had lower diffusivity 6 months after the diagnosis, which correlated with greater fatigue. These diffusion findings may be due to glial proliferation and immune-response related cytotoxic edema. 

Rachel W. Chan¹, Mark Ruschin², Liam S.P. Lawrence³, James Stewart², Sten Myrehaug², Chia-Lin Tseng², Jay Detsky², Pejman J. Maralani⁴, Mary Jane Lim-Fat², Hany Soliman², Greg J. Stanisz^1,3,5, Arjun Sahgal², and Angus Z. Lau^1,3
1Physical Sciences Platform, Sunnybrook Research Institute, Toronto, ON, Canada, ²Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ³Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada, ⁴Department of Medical Imaging, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada, ⁵Department of Neurosurgery and Pediatric Neurosurgery, Medical University of Lublin, Lublin, Poland

Hybrid MR/radiotherapy MR-Linac devices enable dose adaptation based on daily  imaging. Saturation transfer MRI, including quantitative magnetization transfer (qMT) and chemical exchange saturation transfer (CEST), have been shown to predict treatment response in glioblastoma. Here, in a proof-of-principle study, we demonstrated the feasibility of retrospectively generating dose-escalated radiation plans based on qMT semi-solid fraction maps acquired on the MR-Linac. Treatment plans with a 115-120% boost dose were successfully generated in all four patients and adhered to clinical organs-at-risk dose constraints.

Shraddha Pandey^1,2, Tugce Kutuk³, Matthew N Mills³, Mahmoud Abdalah⁴, Olya Stringfield⁴, Kujtim Latifi³, Timothy J Robinson³, Wilfrido Moreno¹, Kamran A Ahmed³, and Natarajan Raghunand^2,5
1Electrical Engineering, University of South Florida, Tampa, FL, United States, ²Department of Cancer Physiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States, ³Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States, ⁴Quantitative Imaging Shared Service, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States, ⁵Department of Oncologic Sciences, University of South Florida, Tampa, FL, United States

Stereotactic Radiosurgery (SRS) of asymptomatic brain metastases provides lasting tumor control with only minor side effects to healthy brain. An active research area is the development of models to predict tumor response to a given dose of Radiation Treatment (RT) from analysis of pre-RT and post-RT MR images (i.e., the forward problem). Here we propose an approach to train a deep neural net on pre-RT MR images of patients with Breast Cancer Metastases to the Brain (BCMB), for predicting RT dose maps that will yield desired/target tumor voxel intensities on post-RT MR images (i.e., the inverse problem).

Ho-Ching Yang¹, Kelly Naugle², Qiuting Wen¹, Fletcher A White^3,4,5, and Yu-Chien Wu^1
1Departments of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United States, ²Department of Kinesiology, School of Health and Human Sciences, Indiana University Purdue University Indianapolis, Indianapolis, IN, United States, ³Department of Anesthesia, School of Medicine, Indiana University School of Medicine, Indianapolis, IN, United States, ⁴Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN, United States, ⁵Research and Development Services, Richard L. Roudebush VA Medical Center, Indianapolis, IN, United States

To investigate the neuropathogenesis of post-traumatic headache following mild traumatic brain injuries (mTBI), this study applied diffusion tensor imaging and functional magnetic resonance imaging to explore relationships between brain structural and functional changes and sensitization, pain inhibitory capacity, psychological factors and headache pain in mTBI subjects. The results found structural and functional alterations in mTBI. Also, the results showed that DTI metric differences between mTBI subjects and controls can be used to predict pain/psychological measurements, which indicated the relationship between white matter disruption and measurements of endogenous pain modulation and psychological distress in mTBI.

Isaac Vicente Manzanera Esteve¹, Adam Evans¹, Brian Johnson², Ryan Robinson³, Saikat Sengupta¹, Alonda Pollins¹, Wesley Thayer¹, and Salam Al Kassis^1
1Vanderbilt University Medical Center, Nashville, TN, United States, ²Philips Healthcare, Gainesville, FL, United States, ³Philips Healthcare, Nashville, TN, United States

Migraine Headaches (MH) are the 6th leading cause of years lived with disability worldwide, affect 15% of the US population, and are nearly twice as prevalent in veterans who have been deployed. Our study focuses on pathology of the greater occipital nerve (GON), which occurs with a high prevalence in individuals with a history of trauma (i.e. traffic accidents, explosions, falls). In our pilot MRI scans and operative experience, migraines associated with GON pathology displayed a pathologic thickening of the nerve validated intraoperatively. These results present MRI as a potential biomarker of headache pathologies of MH associated with GON pathology.