Beeman, Scott C.

Background/Objectives: White matter (WM) tract detection is critical in the presurgical planning of tumor resection. However, standard-of-care imaging techniques including T1-weighted, T2-weighted, and Diffusion Tensor Imaging (DTI) often fail to identify WM tracts within edematous regions. In T1/T2-weighted imaging, edema increases extracellular water and reduces tissue contrast, and in diffusion-weighted imaging, edema elevates isotropic diffusion, reducing sensitivity to anisotropic diffusion along WM tracts. Advanced biophysical diffusion modeling techniques such as Neurite Orientation Dispersion and Density Imaging (NODDI) and the Standard Model (SM) address this limitation by compartmentalizing the diffusion signal into free-water, intra-neurite, and extra-neurite contributions. Here, we test if biophysical multi-compartment models can robustly identify WM tracts and recover tractography streamlines within edematous regions. Methods: In this study, we use multi-shell diffusion-weighted MRI data obtained from patients with meningiomas—a pathology allowing for isolation of the effects of edema without the confounding effects of tumor cell invasion. We compared FA from standard and free-water-corrected DTI, the orientation dispersion index (ODI) from NODDI, and P2 (a scalar descriptor of fiber orientation coherence) from the SM fODF in edematous and unaffected contralateral WM regions. As a proof of concept, we visually evaluated the tractography performance across models. Results: Our results show that (1 − ODI) and P2 values in edema remained close to within-subject contralateral measurements, contrasting with substantial reductions in FA and FW-FA. (1 − ODI) showed a small but statistically significant increase in edema (~8%, p = 0.02), while P2 was unchanged. Conclusions: These results highlight the potential of biophysical diffusion models for preoperative mapping in edema.

Background: The potential long-term effects of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection on the brain structure have not yet been fully elucidated. Even though existing studies have reported structural changes in the post-COVID-19 period, the results remain highly inconsistent and controversial. As such, identifying an imaging biomarker for post-COVID brains is still under investigation. This review aims to comprehensively summarize the structural MRI (sMRI) studies that focus on volumetric brain changes at least two weeks following COVID-19 infection. Methods: A systematic literature search was conducted on PubMed, SCOPUS, Web of Science, EMBASE, and Google Scholar up to 9 September 2025. Studies that utilized sMRI to assess volumetric brain changes post-COVID at greater than two weeks following infection were included. Exclusion criteria encompassed research involving pediatric or adolescent populations and imaging modalities other than sMRI. Preprints, reviews, case reports, case series and post-mortem studies were also excluded. Results: Forty-one studies satisfied the inclusion criteria and consisted of 2895 patients and 1729 healthy controls. Despite the wide variability in image acquisition protocols, data processing methods, and comorbidities between studies, multiple studies reported statistically significant volumetric reductions in the hippocampus, amygdala, thalamus, basal ganglia, nucleus accumbens and the cerebellum months to years after infection, especially in older hospitalized patients with severe COVID-19. Conclusions: The emerging literature reports long-term volume changes across various brain regions in individuals previously infected with COVID-19; however, the evidence is inconsistent. Specific imaging biomarkers following exposure to SARS-CoV-2 infection and the underlying mechanisms of these changes are yet to be identified. Future studies with harmonized imaging protocols, longitudinal designs, and integrated biomarker and clinical data are needed to define robust biomarkers and elucidate the pathophysiology of these findings.

Abstract High grade glioma (HGG) represents a group of devastating diseases with dismal prognosis. Surgical resection of the contrast enhancing (CE) region of HGG remains the mainstay of treatment, but recurrence inevitably arises from the unresected non-contrast enhancing (NE) region, surgically inaccessible due to cancer cell invasion into healthy brain tissue. Due to its critical role in recurrence, understanding of the NE region is central to the improvement of clinical outcomes. We reveal the biological characteristics of this region through image localized multi-regional sampling. We linked microenvironmental characteristics measured by multi-parametric MRI to genomic mutations and transcriptional phenotypes using mixed effect modeling which allowed us to control for individualized patient effects. We first confirmed that T2 is a significant indicator of IDH mutation status in the NE region, being the first description of such a relationship in a HGG cohort. We found the combination of EGFR amplification and CDKN2A homozygous loss was associated with a significantly lower mean diffusivity (MD) compared to double wild type tumors in the NE region, indicating the presence of greater cellular packing and proliferation in EGFR amplification/CDKN2A loss regions. Finally, using single cell pathway based tumor classifications, we showed that nK2, a DSC-MRI metric representing cell size heterogeneity, correlated positively with neuronal signature and negatively with glycolytic/plurimetabolic signature within the NE tumor, indicating that glycolytic/plurimetobolic tumors possessed a high amount of cell size heterogeneity compared to neuronal samples. This hypothesis was supported using digital reference object (DRO) modeling which confirmed that cell size and heterogeneity drove the differential nK2 signal between neuronal and glycolytic/plurimetabolic samples. We identified immune cell infiltrate as one possible mechanism of increased cell size heterogeneity using transcriptomic signature analysis which found more immune cell signatures within glycolytic/plurimetobolic tumors compared to neuronal. Collectively this study demonstrates the central role of multi-parametric MRI as a non-invasive measure of tumor biology and a tool for understanding the clinically critical NE region which can then inform new therapies targeting this region of HGG recurrence. Citation Format: Matthew Flick, Taylor Weiskittel, Kevin Meng-Lin, Fulvio D'Angelo, Francesca Caruso, Shannon Ensign, Mylan Blomquist, Luija Wang, Christopher Sereduk, Gustavo De Leon, Ashley Nespodzany, Javier Urcuyo, Ashlynn Gonzalez, Lee Curtin, Kyle Singleton, Aliya Anil, Natenael Simmineh, Erika Lewis, Teresa Noviello, Reyna Patel, Panwen Wang, Junwen Wang, Jennifer Eschbacher, Andrea Hawkins-Daarud, Pamela Jackson, Kris Smith, Peter Nakaji, Bernard Bendok, Richard Zimmerman, Chandan Krishna, Devi Patra, Naresh Patel, Mark Lyons, Matthew Neal, Kliment Donev, Maciej Mrugala, Alyx Porter, Scott Beeman, Yuxiang Zhou, Leslie Baxter, Christopher Plaisier, Jing Li, Hu Li, Anna Lasorella, Chad Quarles, Kristin Swanson, Michele Ceccarelli, Antonio Iavarone, Nhan Tran, Leland Hu. Multi-parametric MRI maps regional heterogeneity of high grade glioma phenotypes. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5621.

PurposeThe goal of this work was to detect disease‐related microstructural changes to the liver using magnetic resonance imaging. Chronic liver disease can cause microstructural changes in the liver that reduce plasma access to the perisinusoidal space—the site of exchange between the blood plasma and the hepatic parenchyma. The reduced plasma access to the perisinusoidal space inhibits hepatic function and contributes to the ∼30,000 chronic liver disease‐related deaths per year.MethodsThe extracellular matrix‐specific cationized ferritin magnetic resonance imaging probe was injected intravenously into healthy rats and a rat model of the chronic liver disease non‐alcoholic steatohepatitis. Rats were subsequently imaged with ‐weighted magnetic resonance imaging.ResultsThis work demonstrates that the binding of cationized ferritin to the perisinusoidal extracellular matrix is reduced by 55% in a rat model of non‐alcoholic steatohepatitis compared to healthy controls. This reduced binding is detectable in vivo with magnetic resonance imaging. Immunofluorescence and electron microscopy indicated that the reduced binding is due to inhibited macromolecular access to the perisinusoidal space caused by non‐alcoholic steatohepatitis‐related microstructural changes.ConclusionsThe reduced accumulation of intravenously injected cationized ferritin may report on changes in macromolecular access to the liver parenchyma in chronic liver disease. Magn Reson Med 70:1728–1738, 2013. © 2013 Wiley Periodicals, Inc.