Browsing by Author "Yeom, Kristen W"

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    ItemOpen Access
    An international study presenting a federated learning AI platform for pediatric brain tumors.
    (Nature communications, 2024-09) Lee, Edward H; Han, Michelle; Wright, Jason; Kuwabara, Michael; Mevorach, Jacob; Fu, Gang; Choudhury, Olivia; Ratan, Ujjwal; Zhang, Michael; Wagner, Matthias W; Goetti, Robert; Toescu, Sebastian; Perreault, Sebastien; Dogan, Hakan; Altinmakas, Emre; Mohammadzadeh, Maryam; Szymanski, Kathryn A; Campen, Cynthia J; Lai, Hollie; Eghbal, Azam; Radmanesh, Alireza; Mankad, Kshitij; Aquilina, Kristian; Said, Mourad; Vossough, Arastoo; Oztekin, Ozgur; Ertl-Wagner, Birgit; Poussaint, Tina; Thompson, Eric M; Ho, Chang Y; Jaju, Alok; Curran, John; Ramaswamy, Vijay; Cheshier, Samuel H; Grant, Gerald A; Wong, S Simon; Moseley, Michael E; Lober, Robert M; Wilms, Mattias; Forkert, Nils D; Vitanza, Nicholas A; Miller, Jeffrey H; Prolo, Laura M; Yeom, Kristen W
    While multiple factors impact disease, artificial intelligence (AI) studies in medicine often use small, non-diverse patient cohorts due to data sharing and privacy issues. Federated learning (FL) has emerged as a solution, enabling training across hospitals without direct data sharing. Here, we present FL-PedBrain, an FL platform for pediatric posterior fossa brain tumors, and evaluate its performance on a diverse, realistic, multi-center cohort. Pediatric brain tumors were targeted due to the scarcity of such datasets, even in tertiary care hospitals. Our platform orchestrates federated training for joint tumor classification and segmentation across 19 international sites. FL-PedBrain exhibits less than a 1.5% decrease in classification and a 3% reduction in segmentation performance compared to centralized data training. FL boosts segmentation performance by 20 to 30% on three external, out-of-network sites. Finally, we explore the sources of data heterogeneity and examine FL robustness in real-world scenarios with data imbalances.
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    GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas.
    (Nature, 2022-03) Majzner, Robbie G; Ramakrishna, Sneha; Yeom, Kristen W; Patel, Shabnum; Chinnasamy, Harshini; Schultz, Liora M; Richards, Rebecca M; Jiang, Li; Barsan, Valentin; Mancusi, Rebecca; Geraghty, Anna C; Good, Zinaida; Mochizuki, Aaron Y; Gillespie, Shawn M; Toland, Angus Martin Shaw; Mahdi, Jasia; Reschke, Agnes; Nie, Esther H; Chau, Isabelle J; Rotiroti, Maria Caterina; Mount, Christopher W; Baggott, Christina; Mavroukakis, Sharon; Egeler, Emily; Moon, Jennifer; Erickson, Courtney; Green, Sean; Kunicki, Michael; Fujimoto, Michelle; Ehlinger, Zach; Reynolds, Warren; Kurra, Sreevidya; Warren, Katherine E; Prabhu, Snehit; Vogel, Hannes; Rasmussen, Lindsey; Cornell, Timothy T; Partap, Sonia; Fisher, Paul G; Campen, Cynthia J; Filbin, Mariella G; Grant, Gerald; Sahaf, Bita; Davis, Kara L; Feldman, Steven A; Mackall, Crystal L; Monje, Michelle
    Diffuse intrinsic pontine glioma (DIPG) and other H3K27M-mutated diffuse midline gliomas (DMGs) are universally lethal paediatric tumours of the central nervous system1. We have previously shown that the disialoganglioside GD2 is highly expressed on H3K27M-mutated glioma cells and have demonstrated promising preclinical efficacy of GD2-directed chimeric antigen receptor (CAR) T cells2, providing the rationale for a first-in-human phase I clinical trial (NCT04196413). Because CAR T cell-induced brainstem inflammation can result in obstructive hydrocephalus, increased intracranial pressure and dangerous tissue shifts, neurocritical care precautions were incorporated. Here we present the clinical experience from the first four patients with H3K27M-mutated DIPG or spinal cord DMG treated with GD2-CAR T cells at dose level 1 (1 × 106 GD2-CAR T cells per kg administered intravenously). Patients who exhibited clinical benefit were eligible for subsequent GD2-CAR T cell infusions administered intracerebroventricularly3. Toxicity was largely related to the location of the tumour and was reversible with intensive supportive care. On-target, off-tumour toxicity was not observed. Three of four patients exhibited clinical and radiographic improvement. Pro-inflammatory cytokine levels were increased in the plasma and cerebrospinal fluid. Transcriptomic analyses of 65,598 single cells from CAR T cell products and cerebrospinal fluid elucidate heterogeneity in response between participants and administration routes. These early results underscore the promise of this therapeutic approach for patients with H3K27M-mutated DIPG or spinal cord DMG.
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    ItemOpen Access
    Intracranial Artery Morphology in Pediatric Moya Moya Disease and Moya Moya Syndrome.
    (Neurosurgery, 2022-11) Yedavalli, Vivek S; Quon, Jennifer L; Tong, Elizabeth; van Staalduinen, Eric K; Mouches, Pauline; Kim, Lily H; Steinberg, Gary K; Grant, Gerald A; Yeom, Kristen W; Forkert, Nils D

    Background

    Moya Moya disease (MMD) and Moya Moya syndrome (MMS) are cerebrovascular disorders, which affect the internal carotid arteries (ICAs). Diagnosis and surveillance of MMD/MMS in children mostly rely on qualitative evaluation of vascular imaging, especially MR angiography (MRA).

    Objective

    To quantitatively characterize arterial differences in pediatric patients with MMD/MMS compared with normal controls.

    Methods

    MRA data sets from 17 presurgery MMD/MMS (10M/7F, mean age = 10.0 years) patients were retrospectively collected and compared with MRA data sets of 98 children with normal vessel morphology (49 male patients; mean age = 10.6 years). Using a level set segmentation method with anisotropic energy weights, the cerebral arteries were automatically extracted and used to compute the radius of the ICA, middle cerebral artery (MCA), anterior cerebral artery (ACA), posterior cerebral artery (PCA), and basilar artery (BA). Moreover, the density and the average radius of all arteries in the MCA, ACA, and PCA flow territories were quantified.

    Results

    Statistical analysis revealed significant differences comparing children with MMD/MMS and those with normal vasculature ( P < .001), whereas post hoc analyses identified significantly smaller radii of the ICA, MCA-M1, MCA-M2, and ACA ( P < .001) in the MMD/MMS group. No significant differences were found for the radii of the PCA and BA or any artery density and average artery radius measurement in the flow territories ( P > .05).

    Conclusion

    His study describes the results of an automatic approach for quantitative characterization of the cerebrovascular system in patients with MMD/MMS with promising preliminary results for quantitative surveillance in pediatric MMD/MMS management.
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    Spatiotemporal changes in along-tract profilometry of cerebellar peduncles in cerebellar mutism syndrome.
    (NeuroImage. Clinical, 2022-01) Toescu, Sebastian M; Bruckert, Lisa; Jabarkheel, Rashad; Yecies, Derek; Zhang, Michael; Clark, Christopher A; Mankad, Kshitij; Aquilina, Kristian; Grant, Gerald A; Feldman, Heidi M; Travis, Katherine E; Yeom, Kristen W
    Cerebellar mutism syndrome, characterised by mutism, emotional lability and cerebellar motor signs, occurs in up to 39% of children following resection of medulloblastoma, the most common malignant posterior fossa tumour of childhood. Its pathophysiology remains unclear, but prior studies have implicated damage to the superior cerebellar peduncles. In this study, the objective was to conduct high-resolution spatial profilometry of the cerebellar peduncles and identify anatomic biomarkers of cerebellar mutism syndrome. In this retrospective study, twenty-eight children with medulloblastoma (mean age 8.8 ± 3.8 years) underwent diffusion MRI at four timepoints over one year. Forty-nine healthy children (9.0 ± 4.2 years), scanned at a single timepoint, served as age- and sex-matched controls. Automated Fibre Quantification was used to segment cerebellar peduncles and compute fractional anisotropy (FA) at 30 nodes along each tract. Thirteen patients developed cerebellar mutism syndrome. FA was significantly lower in the distal third of the left superior cerebellar peduncle pre-operatively in all patients compared to controls (FA in proximal third 0.228, middle and distal thirds 0.270, p = 0.01, Cohen's d = 0.927). Pre-operative differences in FA did not predict cerebellar mutism syndrome. However, post-operative reductions in FA were highly specific to the distal left superior cerebellar peduncle, and were most pronounced in children with cerebellar mutism syndrome compared to those without at the 1-4 month follow up (0.325 vs 0.512, p = 0.042, d = 1.36) and at the 1-year follow up (0.342, vs 0.484, p = 0.038, d = 1.12). High spatial resolution cerebellar profilometry indicated a site-specific alteration of the distal segment of the superior cerebellar peduncle seen in cerebellar mutism syndrome which may have important surgical implications in the treatment of these devastating tumours of childhood.