2021 BNAC Newsletter
Dear Friends and Colleagues: Growth can mean many things and I continue to believe that the growth we experience at the Buffalo Neuroimaging Analysis Center represents forward progress for all of you who have a stake in our work. During 2021, we grew as an educational center, introducing more aspiring research students and young professionals to insights and experiences that provide career opportunities for them as their work moves science, medicine, and learning ahead. We also grew as a partner to, academic, government, pharmaceutical, and philanthropic research sponsors by expanding and improving our core laboratory services to ensure accuracy and rigor in neuroimaging clinical trials. This included our portfolio of preclinical and clinical studies, using novel imaging techniques that expand our capabilities and accelerate research.
We undertook important new research in multiple sclerosis and other neurological disorders, continuing our pursuit of discoveries that move our entire research community closer to disease modifying therapies and elusive cures. We also focused on translating quantitative neuroimaging tools to real-world patient imaging. Our contributions to the literature remain prolific as we published 36 articles in high-impact, peer-reviewed journals. As for many of you, the pandemic brought hardships, challenges, and loss. However, it was also an opportunity to embrace new ways of working using hybrid onsite and virtual work settings and technology that prioritized the health and safety of our research subjects, employees, and students while staying focused on collaboration, quality, and efficiency throughout the pandemic. Many of these changes will be permanent, and allow us to much more directly collaborate in real time with our international colleagues. All of this takes place within our culture of continuous improvement that celebrates both achievement and curiosity, the growth mindset that fosters collaboration, process improvement, quality, ethics, and the personal growth to inspire our best efforts. We enter a new year with a strategic focus on the amazing opportunities ahead for patient-centered research, impactful clinical study partnerships, and the growth that benefits all of us. Thank you for your continuing confidence and interest in our work together. Sincerely,
Director, Buffalo Neuroimaging Analysis Center
Director, Center for Biomedical Imaging at the Clinical Translational Science Institute
Professor of Neurology, Department of Neurology,
Jacobs School of Medicine and Biomedical Sciences
University at Buffalo, SUNY
100 High Street, NY 14203
T: 1+.716.859.7040
2021 was a year of growth for BNAC.
In addition to sharing news with its many stakeholders on our website, on LinkedIn, and on Facebook, highlights of BNAC’s work can be found online through other media.
Neurology Live, May 25, 2021
Robert Zivadinov, MD, PhD, professor of neurology and director of the Buffalo Neuroimaging Analysis Center discusses the background of the ORATORIO study and the aT2-LV biomarker, presented at the American Academy of Neurology Annual Meeting.
Jacobs School of Medicine and Biomedical Sciences News, Jun. 8, 2021
Doctoral graduate Dejan Jakimovski, mentored by Robert Zivadinov, MD, PhD, received the Bishop Neuroscience Thesis Award, which recognizes demonstrated excellence in research. Jakimovski was honored for his dissertation, “The Effect of Cardiovascular Health on Multiple Sclerosis Disease Outcomes.”
Jacobs School of Medicine and Biomedical Sciences News, Jun. 9, 2021
Ralph H.B. Benedict, PhD, professor of neurology, has received the 2021 Stockton Kimball Award for outstanding scientific achievement and service.
NeurologyLive, Jul. 14, 2021
NeurologyLive®, a multimedia platform dedicated to providing health care professionals with direct access to expert-driven, practice-changing news and insights in neurology, welcomes Buffalo Neuroimaging Analysis Center and three other partners to its Strategic Alliance Partnership (SAP) program. The new partner organizations share a focus on innovation and advancements in neurology.
Neurology Live, Sep. 9, 2021
Dr. Michael Dwyer, director of IT and Neuroinformatics Development at the Buffalo Neuroimaging Analysis Center discussed the potential advantages AI-built neuroimaging brings to neurology.
Wiley Online Library, Nov. 14, 2021
Researchers including Cassondra Lyman, Dongchan Lee, Hannah Ferrari, Tom A. Fuchs, Niels Bergsland, Dejan Jakimovski, Bianca Weinstock-Guttmann, Robert Zivadinov, and Michael G. Dwyer provide this technology update in the Journal of Neuroimaging.
Buffalo Neuroimaging Analysis Center, Nov. 19, 2021
The U.S. National Institute of Neurological Disorders and Stroke will invest $1.4 million in a study to explore how brain iron status influences multiple sclerosis (MS) progression or remission. The four-year study will be led by Ferdinand Schweser, Ph.D., Director of Sequence Development at the Buffalo Neuroimaging Analysis Center (BNAC) and Associate Professor of Neurology, Radiology, and Biomedical Engineering at the University at Buffalo.
HMP Global Learning Network, Nov. 24, 2021
In a multi-part podcast, Robert Zivadinov MD, PhD, discusses his presentations at the Consortium for Multiple Sclerosis Centers Annual Meeting titled Detecting Demyelination and Remyelination by MRI in the CNS and Imaging Remyelination in Clinical Trials of Multiple Sclerosis.
Niagara Frontier Publications, Dec. 4, 2021
A study led by researchers Dejan Jakimovski and Weinstock-Guttman, plus co-authors from the UB Department of Neurology are Katelyn Kavak, Caila B. Vaughn, and Robert Zivadinov, shows evidence that discontinuing medications in older and previously stable patients results in new disease worsening/progression.
BNAC was involved in 36 publications in high-impact journals in 2021. Highlights include:
BNAC had 3 conference platform presentations and 11 posters featured at international scientific conferences in 2020 around the globe. Here are some highlighted presentations.
Throughout 2021, BNAC members’ accomplishments were acknowledged by a number of awards.
BNAC’s core lab activities focus on how to help patients with various diseases bring to the market new medications and interventional devices, using cutting edge imaging technologies. In order to do so, BNAC brings to every clinical trial a high degree of innovation, professionalism, and integrity that stipulates unequivocal respect for deadlines, commitments and scientific advances. As an ISO 9001:2015 certified organization, BNAC performs analysis of clinical trial imaging data following the highest academic and industry standards in the field, in order to truly understand the efficacy of drugs, interventions, and devices. BNAC has been involved in more than 100 clinical trials in multiple sclerosis, transaortic valve replacement (TAVR), stroke, and Parkinson’s disease and has experience collaborating with over 500 centers around the world, located on five continents in more than 70 countries. In 2021, BNAC continued to serve as a Core MRI Lab for several phase II, III, and IV multi-center clinical trials, as well as pivotal device approval studies for many industry partners both large and small, including Mapi Pharma, Novartis, Roche-Genentech, Bristol Myers Squibb, Keystone Heart, CorEvitas, Octave, Protembis and V-VAVE Medical.
On Nov 4, 2021, at the Transcatheter Cardiovascular Therapeutics (TCT) Connect 2021 meeting, PROTEMBIS GmbH presented compelling data regarding efficacy of their embolic protection device. This device (cerebral embolic protection) helps protect the brain from ischemic damage (including subtle "mini-strokes") that happen during cardiac surgeries when debris from vessels gets dislodged into the circulation and goes up into the brain. BNAC was the MRI core lab performing independent imaging reads for the study. The study was stopped early due to clear efficacy, based on imaging outcomes, and the company will be proceeding with a larger US regulatory study.
BNAC Validates Atrophied Lesion Volume as Imaging Biomarker of Treatment Efficacy in Primary-Progressive Multiple Sclerosis
A recent study presented at the 2021 American Academy of Neurology (AAN) Annual Meeting, by BNAC, suggested that ocrelizumab (Ocrevus; Genentech) reduced atrophied T2-lesion volume (aT2-LV) in patients with primary progressive multiple sclerosis (PPMS). Zivadinov and colleagues evaluated data from 732 patients with PPMS as part of a post-hoc analysis of the ORATORIO trial (NCT01194570), who were randomly assigned to ocrelizumab (n = 488) or placebo (n = 244). The researchers confirmed that accumulation of aT2-LV in patients receiving placebo (366.1mm3 in 120 weeks) was consistent with previous reports in PPMS and thus further validated the biomarker’s accuracy. They found that patients treated with ocrelizumab had significantly slower accumulation of aT2-LV. Including scanner model, software, protocol changes, and additional covariates further confirmed these results, demonstrating that aT2-LV is a robust predictor and response marker in PPMS.
BNAC provides comprehensive preclinical core lab services including overall leadership, project management, housing and induction of preclinical models, behavioral testing, creation and execution of image acquisition and analysis protocols, immunology and histology examinations, and quality control. In addition, we partner closely with the Center for Biomedical Imaging, a comprehensive core imaging facility at the University at Buffalo (UB) performing our imaging studies on a 9.4T ultra-high field MRI with unique cryogenically-cooled coil technology. 2021 was an extremely busy year for BNAC’s Pre-Clinical Core Lab. BNAC continued two large clinical trials investigating the safety and efficacy of siponimod and bruton tyrosine kinase inhibitor (BTK) in Theiler’s Murine Encephalomyelitis virus model of chronic demyelination. BNAC is using state of the art 9.4T MRI imaging techniques, as well as histopathological analyses to investigate the efficacy of these treatments on biomarkers of microglia activation.
BNAC Collaborates with Center for Biomedical Imaging at the University at Buffalo to Develop Unique Combined MRI-PET Integrated Acquisition System for Preclinical Trials
Positron emission tomography (PET) and its implementation in patient care have evolved rapidly with the development of new target-specific radiotracers for cancer and neurodegenerative diseases. Small animal PET instruments are being used increasingly to translate novel molecular radioactive tracers from bench to bedside, facilitating diagnosis and testing of new therapeutic interventions. Combining PET with MRI in research in preclinical models enables simultaneous structural and molecular information, without additional measurement time. This unique confluence of two powerful imaging modalities represents a major advance in diagnostic imaging. However, simultaneous PET and ultra-high field 9.4 Tesla MRI imaging are not yet commercially available. In partnership with the New York-based startup SynchroPET Inc., we are developing a miniature prototype PET detector that can be retrofitted into most pre-clinical MRI systems and integrates anesthesia and vital signs monitoring systems. This setup enables simultaneous PET and MRI acquisition, a significant advance in translational imaging. The first pilot projects have been recently presented at the scientific meetings, and it is anticipated that this technology will become available for use in preclinical trials by early 2023.
Translational research applies knowledge from basic biology and clinical trials to techniques and tools which address critical medical needs to improve health outcomes. BNAC is engaged in several new areas of translational research.
Ferdinand Schweser, Ph.D., BNAC’s Director of Sequence Development and UB Associate Professor of Neurology, Radiology, and Biomedical Engineering, will lead an international team exploring the link between deep gray matter iron and multiple sclerosis progression. The four-year, $1.4 million NIH-funded study will analyze thousands of MRI scans taken over 10 years to establish an objective means to assess brain iron status that could serve as part of a biomarker of MS disease progression and remission and could provide much deeper insight into the role of iron in MS.
BNAC Study and Novel Software Show Uncommon Insight About Multiple Sclerosis Progression from Common MRI Scans
There is no commonly-available way for clinical neurologists to use an “everyday” MRI to provide their multiple sclerosis (MS) patients with meaningful assessments of their disease progression, including brain tissue changes associated with physical and cognitive impairment, because conventional MRI methods in the vast majority of clinical settings are inadequate in creating scans that can be used to measure two of the most reliable known markers of MS progression. In August of this year, though, BNAC researchers published their NeuroSTREAM MSBase study. The study demonstrated that neurologists using a new, open-source software—NeuroSTREAM, recently co-developed by BNAC scientists—along with the widely-available T2-FLAIR MRI protocol, can perform and read scans that confidently assess reliable and clinically meaningful proxies of the two critical markers—salient central brain lesion volume (SCLV) and lateral ventricle volume (LVV)—in regular clinical routine settings and even in the face of complete scanner changes. This is a vital step in bringing the kind of quantitative markers that are standard in the academic field an in the FDA’s approval decisions within reach of normal clinical routine.
The thalamus is a key gray matter structure, and a sensitive marker of neurodegeneration in multiple sclerosis. A previously published BNAC study using DeepGRAI (Deep Gray Rating via Artificial Intelligence) has indicated that thalamic volumetry using AI on clinical-quality T2-FLAIR images alone is fast and reliable. To further investigate the feasibility and clinical validity of thalamic volume measurement using AI based on routine clinical scans from patients with multiple sclerosis, BNAC conducted a multi-center (30 USA sites), longitudinal, observational, retrospective, real-word, registry study of relapsing-remitting multiple sclerosis patients. Brain MRI exams acquired at baseline and follow-up on 1.5T or 3T scanners with no prior standardization were collected to resemble real-world situations. BNAC completed the study earlier this year, confirming the utility, clinical relevance, and robustness of these type of thalamic measurements. The study findings will be presented at upcoming scientific conferences in 2022.
BNAC Collaborates with the Jacobs Multiple Sclerosis Center for Treatment and Research at the University at Buffalo to Establish Individually Meaningful Cut-Offs for Cognitive Impairment in MS
The Symbol Digit Modalities Test (SDMT) is increasingly used in clinical trials to measure cognitive decline in patients with multiple sclerosis. An SDMT score change of 4 points is considered clinically important, based on association with employment anchors. In a prospective, case-control study that enrolled 166 patients with multiple sclerosis, BNAC researchers evaluated SDMT scores at baseline, relapse, and 3-month follow-up. Using data from the stable group and three previously published studies, candidate thresholds for reliable decline were calculated and validated against other tests and a clinically meaningful anchor-cognitive relapse. An SDMT change of 8 or more raw score points was deemed to offer the best balance of discriminatory power and external validity for estimating cognitive decline on an individual basis for clinical management. The study was performed by Zachary Weinstock, a Ph.D. candidate in BNAC, jointly mentored by Dr. Benedict and Dr. Dwyer.
The Comprehensive Assessment of Severely Affected Multiple Sclerosis (CASA-MS) study focuses on severely affected patients with multiple sclerosis, a population that is seldom studied despite their poor quality of life and the impact of their severe disability on caregivers. Careful evaluation of these patients is an unmet need that BNAC will address in collaboration with The Boston Home, a residential facility in Boston, Massachusetts for individuals living with advanced progressive neurological disorders, with a focus on MS. 
The central hypothesis of this study is that an evidence-based comparison of people whose MS has not progressed with a demographically matched group of severely affected people with MS (SAPwMS) will lead to better early identification of severe progression and better treatment and care for SAPwMS. The project's main goals are to:
The study enrollment of 60 patients in Boston Home, Boston, MA, and 60 age-, sex- and disease-duration matched MS patients, who are routinely followed at Jacobs MS Center, Buffalo, NY is expected to be completed in the first quarter of 2022, after which the study analyses will begin. The $1.2 million, multi-year, investigator-initiated study will be underwritten by gifts and grants from individuals and foundations. In December 2021, The Annette Funicello Research Fund for Neurological Diseases (AFRFND) awarded BNAC a $100,000 challenge grant in support of this groundbreaking study of people with advanced-stage progressive multiple sclerosis. Philip Holt, Chair of the Funicello fund, said the Board was pleased to make this grant, the largest in its history. “Our mission is to support clinical studies seeking the cause of MS and therapies that show promise of reversing the symptoms,” said Holt. “Annette Funicello first noticed her MS symptoms in 1987 when she was making the movie ‘Back to the Beach.’ As her MS progressed and her symptoms became increasingly pronounced, Annette decided to go public with her condition and commit herself to helping others. BNAC’s work and this study are perfectly aligned with her commitment.” Gifts to support CASA-MS during 2022 will generate a 1:1 match from Annette’s Fund. Donations to generate matching funds can be made on BNAC’s website.
The BNAC is a multidisciplinary team of over 50 faculty, staff, students, fellows, as well as a broad group of collaborators and advisors. This section spotlights a few members and groups in depth.
The BNAC Advisory Council was formed in the spring of 2011 to provide guidance in addressing current challenges in neurological research, to help clarify directions for new research, and to provide education for those outside the neurological community about what BNAC’s research means to the understanding of multiple sclerosis and other neurological diseases.
The Advisory Council undertook a new initiative to provide resources for patients that help explain research outcomes in a meaningful way. The Council is also working with the research team to raise awareness and funding for new and important studies.
Mitch Sturgeon has joined the BNAC Advisory Council. Mitch is a writer and disability advocate living in South Portland, Maine, with his wife, Kim. He earned his chemical engineering degree and MBA from the University of Maine. In 2001 Mitch Sturgeon was diagnosed with primary progressive MS, and by 2009 he left the traditional workforce. With the help of fellow BNAC Advisory Council member Marc Stecker, he launched his disability advocacy blog, Enjoying the Ride, and later published a memoir of the same name. Today, Mitch is a regular contributor of personal essays at multiplesclerosis.net and an occasional public speaker wherever people will have him. He employs a mixture of humor, inspiration, and straight-talk to share his experiences as a disabled person.
Carol Schumacher and her husband, Scott, live in The San Francisco Bay Area where they enjoy gardening and making art glass in their home studio. An alumna of UC Berkeley with a degree in Entomology, Carol is a Registered Veterinary Technician (RVT) and a principal and president of a veterinary hospital. In addition to being a founding member of BNAC’s Advisory Council, Carol serves on the Executive Committee of the International Society of Neurovascular Diseases, and as a director at the Annette Funicello Research Fund for Neurological Diseases. Until 2011, she was chair of the RVT Committee of the California Veterinary Medical Board. Carol and Scott have three children and two grandchildren.
Ferdinand Schweser is the Director of Sequence Development at the BNAC, and Associate Professor of Neurology, Radiology, and Biomedical Engineering at the University at Buffalo. Dr. Schweser also serves as Technical Director for the Center for Biomedical Imaging, one of the Cores of UB’s Clinical and Translational Science Institute. Dr. Schweser is an internationally recognized expert in quantitative magnetic resonance imaging (MRI). He received his Ph.D. in MRI physics from the Friedrich Schiller University Jena in Germany (2012). Dr. Schweser co-developed a novel MRI method for the measurement of iron, calcium, and myelin in the brain that is used in numerous neuroimaging labs around the world (quantitative susceptibility mapping, QSM). Dr. Schweser’s team at BNAC works on the technological advancement of MRI to provide more accurate and reliable measurements of tissue pathology from mice to humans. A focus area of his team is the solution of physical equations that govern the MRI signal using cutting-edge computational techniques such as artificial intelligence (AI). His translational research at BNAC aims to improve the diagnosis and treatment of neurological diseases by providing novel insights on the biological underpinnings of pathology through the application of QSM and other advanced imaging techniques.
Alex Bartnik is a PhD candidate in the Neuroscience program at the University at Buffalo, and is completing his second year as a PhD student and fourth year with BNAC altogether. Alex’s work is focused on developing tools that facilitate the translation of academic research in neuroimaging to clinical science and aid collaboration in large-scale neuroimaging studies. Using his combined background in computer science and neuroscience, he is building a neuroinformatics platform that will automate scan classification and complex analysis pipelines and compiling and curating broad comparative and normative datasets that aid translational researchers in interpreting their data and asking new scientific questions. Alex and his team have developed an MRI ontology to help standardize the neuroimaging research process, working with an international consortium of biomedical ontologies to help ensure that neuroimaging research can be easily shared and reused across studies and sub-disciplines.
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