Ortega, Dakota

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.

Heart disease continues to be the leading cause of death globally, even with the development and implementation of numerous pharmacological and surgical treatments. Transplanting cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs) shows potential for repairing heart damage. However, tracking and quantifying these cells after transplantation in large animals remains challenging. This study aimed to develop a hiPSC line that overexpresses ferritin heavy chain (FHC) to enable tracking of transplanted hiPSC-CMs via magnetic resonance imaging (MRI). Using the CRISPR/dCas9 activation system, we increased FHC expression in hiPSCs and hiPSC-CMs. Both mRNA and protein levels of FHC were significantly elevated following transfection. Cell viability was unaffected by iron chloride concentrations between 0 μM and 2000 μM. hiPSCs and hiPSC-CMs overexpressing FHC (hiPSC-FHC OE and hiPSC-CM-FHC OE ) showed enhanced iron chloride uptake without changes in their electrophysiological properties compared to control hiPSC-CMs. Additionally, hiPSC-CM-FHCOE cells provided strong contrast and lower T 2 * values, indicating their effectiveness for cardiac MRI. When hiPSC-CM-FHCOE cells were injected into mouse hearts and imaged three days later, MRI revealed distinct signals from these cells with lower T 2 * values and rapid signal decay. Overall, endogenous FHC labeling in hiPSC-CMs could significantly improve the precision of cardiac MRI, marking a crucial advancement in assessing the success of hiPSC-CM transplantation in large animal models and enhancing cardiac regenerative therapies.

AbstractThe objective of the current study is to develop a new method for tracking transplanted human induced pluripotent stem cells‐derived cardiomyocytes (hiPSC‐CMs) using magnetic resonance imaging (MRI). The CRISPR/dCas9 activation system is employed to overexpress ferritin heavy chain (FHC) in hiPSC‐CMs. The mRNA and protein expression of FHC in hiPSC and hiPSC‐CMs significantly increased after transfection. Iron chloride does not affect the cell viability in a concentration range from 0 to 2000 µm. hiPSCs overexpressing FHC (hiPSC‐ FHCOE) and hiPSC‐CMs overexpressing FHC (hiPSC‐CM‐FHCOE) significantly enhanced cellular uptake of iron chloride but with no changes in electrophysiological properties compared to hiPSC‐CM‐Control. Furthermore, hiPSC‐CM‐FHCOE presented robust contrast and lower T2* values, signifying their potential as highly effective candidates for cardiac MRI. Next, hiPSC‐CM‐FHCOE is injected into mouse hearts and after 3 days of transplantation, MR images are obtained. hiPSC‐CM‐FHCOE cells exhibited clear signals in the hearts with lower T2* and rapid signal decay. Collectively, data from this proof‐of‐concept study demonstrated that endogenous labeling with FHC in hiPSC‐CMs can be a potent strategy for enhancing the accuracy of cardiac MRI. This technology represents a significant step forward in tracking the transplanted hiPSC‐CMs in the hearts of live animals.