eScholarship@UMassChan

eScholarship@UMassChan is a digital archive for UMass Chan Medical School's research and scholarship, including journal articles, theses, datasets and more. We welcome submissions from our faculty, staff, and students. eScholarship@UMassChan is a service of the Lamar Soutter Library, Worcester, MA, USA. See also our open access journal publishing services.

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Recent Publications

  • Publication
    Applications of spectral CT in emergency department imaging, with a focus on neuroimaging
    (2025-06-14) Lowenthal, Jonathan M; Choi, David; Dundamadappa, Sathish Kumar; Radiology
    Multi-energy detector spectral CT is a specialized form of dual-energy CT, an imaging technique that takes full advantage of the entire X-ray spectrum applied during CT scans, enabling superior differentiation of materials that may be indistinguishable on traditional CT. Contrary to source-based dual-energy CT, the benefits of detector-based spectral CT are always available with every scan, without needing to preemptively manually select dual source technique at the time of scanning. In cases of questionable findings on conventional CT images that require enhanced material differentiation, "spectral" data collected alongside CT images scanned utilizing this technique can be instantly analyzed to improve diagnostic confidence, without needing to re-scan the patient. While applicable to various patient populations and clinical scenarios, spectral CT is particularly useful for neuroradiology in the often fast-paced emergency department. The authors' facility uses the Philips Healthcare IQon Spectral CT in its own emergency department. This paper strives to briefly introduce some ways that spectral CT can be utilized to improve patient care in this setting.
  • Publication
    Multicenter evaluation of the safety and efficacy of varying doses of cangrelor used in acute cerebrovascular stenting in patients with acute ischemic stroke
    (2025-06-12) Holden, Devin N; Dingman, James Spencer; Sutton, Lauren H; Ramos-Estebanez, Ciro; El Ammar, Faten; Warinpramote, Jirapuck; Siddiqui, Raffe; Choi, Richard; Schneider, Laura; Baker, Richard; Bonderski, Veronica; Morsi, Rami Z; Desai, Harsh; Kass-Hout, Tareq; Singh, Jasmeet; Kuhn, Anna Luisa; Puri, Ajit S; Gutierrez-Aguirre, Salvador F; Hanel, Ricardo A; Zaidat, Osama O; Ashouri, Yazan; Al Majli, Mohammed; Anderson, Eve; Wetmore, Lori; Barats, Michael; Kimmons, Lauren; Scott, Whitney; Webb, Andrew; Johnson, Riley; O'Donnell, J Nicholas; Entezami, Pouya; Radiology
    Background: Acute ischemic stroke often necessitates neuroendovascular interventions such as thrombectomy and, occasionally, stenting for large vessel occlusions or intracranial atherosclerotic disease. Effective antiplatelet therapy is essential during stenting to mitigate thrombosis risks, but consensus on optimal cangrelor dosing remains elusive. This study evaluates the safety and efficacy of various cangrelor doses used in acute cerebrovascular stenting. Methods: A multicenter, retrospective cohort study was conducted across 11 comprehensive stroke centers. Patients aged 18-85 with ischemic stroke who underwent emergent cerebrovascular stenting with cangrelor were included. Patients were categorized into low-dose cangrelor (<2 mcg/kg/min; LDC) and high-dose cangrelor (≥2 mcg/kg/min; HDC) cangrelor groups. Outcomes included thrombotic and bleeding complications both intra-procedurally and within 48 hours post-procedure. Results: A total of 230 patients were included in the analysis (LDC: 68; HDC: 162). Baseline characteristics were similar between groups. Thrombotic outcomes, including intraprocedural thrombosis (13% LDC vs 6% HDC; P=0.078) and thrombosis within 48 hours of the procedure (9% LDC vs 4% HDC; P=0.093), showed no statistical differences. Similarly, intraprocedural bleeding (6% LDC vs 5% HDC; P=0.753) and intracranial hemorrhage within 48 hours of the procedure (19% LDC vs 25% HDC; P=0.360) were not statistically different. Conclusion: Different cangrelor dosing regimens demonstrated no significant differences in thrombotic or bleeding complications during acute neuroendovascular stenting for ischemic stroke. Larger, prospective studies are warranted to refine optimal dosing strategies for cangrelor in this population.
  • Publication
    Suppression of binge alcohol drinking by an inhibitory neuronal ensemble in the mouse medial orbitofrontal cortex
    (2025-06-10) Gimenez-Gomez, Pablo; Le, Timmy; Zinter, Max; M'Angale, Peter; Duran-Laforet, Violeta; Freels, Timothy G; Pavchinskiy, Rebecca; Molas, Susanna; Schafer, Dorothy P; Tapper, Andrew R; Thomson, Travis; Martin, Gilles E; Brudnick Neuropsychiatric Research Institute; Neurobiology; Morningside Graduate School of Biomedical Sciences; Schafer Lab; Tapper Lab; Thomson Lab; Martin Lab
    Alcohol consumption remains a significant global health challenge, directly and indirectly causing millions of deaths annually. Alcohol abuse causes dysregulated activity of the prefrontal cortex, yet effects on specific prefrontal circuits remain to be elucidated. Here, we identify a discrete GABAergic neuronal ensemble in the mouse medial orbitofrontal cortex (mOFC) that is selectively recruited in response to binge alcohol drinking and limits further drinking behavior. Optogenetic silencing of this population, or its ablation, results in uncontrolled binge alcohol consumption. This neuronal ensemble is specific to alcohol and is not recruited by other rewarding substances. Neurons in this ensemble project widely throughout the brain, but projections specifically to the mediodorsal thalamus regulate binge alcohol drinking. Together, these results identify a brain circuit in the mOFC that serves to protect against binge drinking by reducing alcohol intake, which may offer avenues for the development of mOFC neuronal ensemble-targeted interventions.
  • Publication
    Characterization of the genomic landscape of canine oral osteosarcoma reveals similarities with appendicular osteosarcoma
    (2025-06-10) Husted, Christopher; Adrianowycz, Sarah; Peterson, Cornelia; DeWitt, Suzanne Bartholf; Karlsson, Elinor K; Eward, William; Somarelli, Jason A; Megquier, Kate; Gardner, Heather L; Genomics and Computational Biology
    Osteosarcoma (OS) is the most common bone tumor in both dogs and humans. It predominantly occurs in the appendicular skeleton, with about 25% of cases occurring within the axial skeleton. Progression of local disease is often the life-limiting factor for patients with axial OS, in contrast to appendicular OS, where local disease is addressed surgically, and metastatic disease remains the primary obstacle. While OS is a rare human cancer, limiting the availability of samples, its higher incidence in dogs provides a valuable comparative model for study. Both canines and humans share commonalities in clinical presentation, but dogs have an accelerated progression. Similarly, complex structural genetic changes define appendicular OS in both dogs and people, but it is unclear whether the genomic landscape of axial OS exhibits different alterations that may separate it from appendicular OS. We performed pilot whole genome sequencing of canine primary oral (maxillary or mandibular) OS tumors (n = 8) and matched normal tissue. We found that the genetics of canine oral OS largely parallel the genetics of canine appendicular OS, including an overall low number of recurrent point mutations affecting the same gene (TP53 and SETD2, 3/8 samples). Structural variants dominated the landscape of mutational changes, with recurrent variants in DMD (4/8) and DLG2 (3/8) found at a similar incidence to appendicular OS. This pilot suggests genomic similarities between oral and appendicular OS.
  • Publication
    Cerebrospinal Fluid Flow Enhancement (CFE) Increases the Spatial Distribution of Methotrexate after Intracerebroventricular Administration in a Sheep Model
    (2025-06-10) Benatti, Hector Ribeiro; Taghian, Toloo; Mihalek, Olivia; Nath, Sarah; Gallagher, Jillian; McElroy, Abigail; Hall, Erin F; Daci, Rrita; Yingling, Nathan K; Baker, William C; Tuominen, Susan; Bierfeldt, Lindsey; Jiang, Xuntian; Gray-Edwards, Heather L; Sirianni, Rachael W; Radiology
    For the treatment of central nervous system (CNS) neoplasias, achieving widespread chemotherapy distribution throughout the brain remains a major challenge. Direct infusion of substances into the cerebrospinal fluid (CSF) is one method to bypass the blood-brain barrier (BBB) and increase the exposure of CNS tissues to therapeutic molecules. As of 2024, only a handful of drugs are FDA-approved for CSF administration, including morphine, baclofen, ziconotide, and methotrexate. However, despite the use of these approaches in clinical practice, relatively little is understood regarding the spatial distribution of CSF-administered agents, and these distributions remain to be optimized. Here, we focus on methotrexate (MTX), which is an antifolate antineoplastic agent that has been administered intrathecally to treat numerous conditions, including inflammatory and oncologic diseases. We examined the time course of the distribution of MTX to gain insight into the flow dynamics and hypothesized that CSF flow enhancement (CFE), i.e., manipulation of the pattern by which CSF moves within the CNS, would alter the spatial distribution of MTX in the CNS following CSF administration. This hypothesis was tested with a recirculating device, which we used to continuously recirculate fluid from the intracerebral lateral ventricles (ICV) to the cisterna magna (CM). Our experimental results provide detailed maps of the spatial distribution of MTX following CSF administration in sheep and support our expectation that CFE is an effective method to manipulate CNS drug distribution.