{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T06:28:41Z","timestamp":1763706521771,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T00:00:00Z","timestamp":1678320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Peach Bowl LegACy (BRE)","award":["U01 CA264039 (HS)","F31 CA247564 (KKR)"],"award-info":[{"award-number":["U01 CA264039 (HS)","F31 CA247564 (KKR)"]}]},{"name":"NIH","award":["U01 CA264039 (HS)","F31 CA247564 (KKR)"],"award-info":[{"award-number":["U01 CA264039 (HS)","F31 CA247564 (KKR)"]}]},{"name":"pre-doctoral fellowship","award":["U01 CA264039 (HS)","F31 CA247564 (KKR)"],"award-info":[{"award-number":["U01 CA264039 (HS)","F31 CA247564 (KKR)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Tomography"],"abstract":"<jats:p>Radiation therapy (RT) is a critical part of definitive therapy for pediatric high-grade glioma (pHGG). RT is designed to treat residual tumor defined on conventional MRI (cMRI), though pHGG lesions may be ill-characterized on standard imaging. Spectroscopic MRI (sMRI) measures endogenous metabolite concentrations in the brain, and Choline (Cho)\/N-acetylaspartate (NAA) ratio is a highly sensitive biomarker for metabolically active tumor. We provide a preliminary report of our study introducing a novel treatment approach of whole brain sMRI-guided proton therapy for pHGG. An observational cohort (c1 = 10 patients) receives standard of care RT; a therapeutic cohort (c2 = 15 patients) receives sMRI-guided proton RT. All patients undergo cMRI and sMRI, a high-resolution 3D whole-brain echo-planar spectroscopic imaging (EPSI) sequence (interpolated resolution of 12 \u00b5L) prior to RT and at several follow-up timepoints integrated into diagnostic scans. Treatment volumes are defined by cMRI for c1 and by cMRI and Cho\/NAA \u2265 2x for c2. A longitudinal imaging database is used to quantify changes in lesion and metabolite volumes. Four subjects have been enrolled (c1 = 1\/c2 = 3) with sMRI imaging follow-up of 4\u201318 months. Preliminary data suggest sMRI improves identification of pHGG infiltration based on abnormal metabolic activity, and using proton therapy to target sMRI-defined high-risk regions is safe and feasible.<\/jats:p>","DOI":"10.3390\/tomography9020051","type":"journal-article","created":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T03:35:42Z","timestamp":1678419342000},"page":"633-646","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Spectroscopic MRI-Guided Proton Therapy in Non-Enhancing Pediatric High-Grade Glioma"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3029-4700","authenticated-orcid":false,"given":"Vicki","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA 30332, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9273-0024","authenticated-orcid":false,"given":"Abinand","family":"Rejimon","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA 30332, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kartik","family":"Reddy","sequence":"additional","affiliation":[{"name":"Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Department of Radiology, Children\u2019s Healthcare of Atlanta, Atlanta, GA 30342, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3348-4529","authenticated-orcid":false,"given":"Anuradha G.","family":"Trivedi","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA 30332, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karthik K.","family":"Ramesh","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA 30332, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander S.","family":"Giuffrida","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA 30332, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Muiruri","sequence":"additional","affiliation":[{"name":"Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyunsuk","family":"Shim","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA 30332, USA"},{"name":"Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bree R.","family":"Eaton","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Department of Radiology, Children\u2019s Healthcare of Atlanta, Atlanta, GA 30342, USA"},{"name":"Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1093\/neuonc\/now038","article-title":"Phase 2 study of concurrent radiotherapy and temozolomide followed by temozolomide and lomustine in the treatment of children with high-grade glioma: A report of the Children\u2019s Oncology Group ACNS0423 study","volume":"18","author":"Jakacki","year":"2016","journal-title":"Neuro Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Buccoliero, A.M., Giunti, L., Moscardi, S., Castiglione, F., Provenzano, A., Sardi, I., Scagnet, M., Genitori, L., and Caporalini, C. (2022). Pediatric High Grade Glioma Classification Criteria and Molecular Features of a Case Series. Genes, 13.","DOI":"10.3390\/genes13040624"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Thorbinson, C., and Kilday, J.-P. (2021). Childhood Malignant Brain Tumors: Balancing the Bench and Bedside. Cancers, 13.","DOI":"10.3390\/cancers13236099"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.ccell.2017.08.017","article-title":"Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma","volume":"32","author":"Mackay","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1056\/NEJMoa043330","article-title":"Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma","volume":"352","author":"Stupp","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.ijrobp.2014.06.058","article-title":"Critical Combinations of Radiation Dose and Volume Predict IQ and Academic Achievement Scores after Craniospinal Irradiation in Children with Medulloblastoma","volume":"90","author":"Merchant","year":"2014","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1093\/neuonc\/noq178","article-title":"Survival and long-term health and cognitive outcomes after low-grade glioma","volume":"13","author":"Armstrong","year":"2011","journal-title":"Neuro Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1056\/NEJMsa060185","article-title":"Chronic Health Conditions in Adult Survivors of Childhood Cancer","volume":"355","author":"Oeffinger","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1200\/JCO.2008.21.1425","article-title":"Late Mortality Among 5-Year Survivors of Childhood Cancer: A Summary From the Childhood Cancer Survivor Study","volume":"27","author":"Armstrong","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"102209","DOI":"10.1016\/j.ctrv.2021.102209","article-title":"Proton beam therapy for children and adolescents and young adults (AYAs): JASTRO and JSPHO Guidelines","volume":"98","author":"Mizumoto","year":"2021","journal-title":"Cancer Treat. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1093\/neuonc\/noz085","article-title":"Proton beam therapy in pediatric brain tumor patients: Improved radiation delivery techniques improve neurocognitive outcomes","volume":"21","author":"Jalali","year":"2019","journal-title":"Neuro Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1093\/neuonc\/noz070","article-title":"Improved neuropsychological outcomes following proton therapy relative to X-ray therapy for pediatric brain tumor patients","volume":"21","author":"Gross","year":"2019","journal-title":"Neuro Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/S1470-2045(15)00167-9","article-title":"Long-term toxic effects of proton radiotherapy for paediatric medulloblastoma: A phase 2 single-arm study","volume":"17","author":"Yock","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1200\/JCO.2015.62.1383","article-title":"Comparing Intelligence Quotient Change After Treatment With Proton Versus Photon Radiation Therapy for Pediatric Brain Tumors","volume":"34","author":"Kahalley","year":"2016","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.ijrobp.2004.09.027","article-title":"Longitudinal multivoxel MR spectroscopy study of pediatric diffuse brainstem gliomas treated with radiotherapy","volume":"62","author":"Laprie","year":"2005","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Poussaint, T.Y., and Rodriguez, D. (2006). Advanced neuroimaging of pediatric brain tumors: MR diffusion, MR perfusion, and MR spectroscopy. Neuroimaging Clin. N. Am., 16.","DOI":"10.1016\/j.nic.2005.11.005"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.21037\/tp-20-445","article-title":"MR spectroscopy in pediatric neuroradiology","volume":"10","author":"Liserre","year":"2021","journal-title":"Transl. Pediatr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1093\/neuonc\/now036","article-title":"Whole-brain spectroscopic MRI biomarkers identify infiltrating margins in glioblastoma patients","volume":"18","author":"Cordova","year":"2016","journal-title":"Neuro Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"vdac006","DOI":"10.1093\/noajnl\/vdac006","article-title":"A multi-institutional pilot clinical trial of spectroscopic MRI-guided radiation dose escalation for newly diagnosed glioblastoma","volume":"4","author":"Ramesh","year":"2022","journal-title":"Neuro Oncol. Adv."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"184","DOI":"10.18383\/j.tom.2018.00028","article-title":"The Brain Imaging Collaboration Suite (BrICS): A Cloud Platform for Integrating Whole-Brain Spectroscopic MRI into the Radiation Therapy Planning Workflow","volume":"5","author":"Gurbani","year":"2019","journal-title":"Tomography"},{"key":"ref_21","unstructured":"Goryawala, M., Han, H., Hosseini, Z., Ahn, S., Moran, G.R., and Shim, H. (2020). Siemens Healthineers World Magazine: Magnetom Flash, Siemens Healthineers."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1111\/jon.12685","article-title":"The Association between Whole-Brain MR Spectroscopy and IDH Mutation Status in Gliomas","volume":"30","author":"Goryawala","year":"2020","journal-title":"J. Neuroimaging"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1002\/nbm.3575","article-title":"Regional Distributions of Brain Glutamate and Glutamine in Normal Subjects","volume":"29","author":"Goryawala","year":"2016","journal-title":"NMR Biomed."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2886","DOI":"10.1002\/mrm.26991","article-title":"Spectral decomposition for resolving partial volume effects in MRSI","volume":"79","author":"Goryawala","year":"2018","journal-title":"Magn. Reson. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1002\/mrm.25510","article-title":"Multi-Vendor Implementation and Comparison of Volumetric Whole-Brain Echo-Planar MR Spectroscopic Imaging","volume":"74","author":"Sabati","year":"2015","journal-title":"Magn. Reson. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1002\/nbm.1025","article-title":"Comprehensive processing, display and analysis for in vivo MR spectroscopic imaging","volume":"19","author":"Maudsley","year":"2006","journal-title":"NMR Biomed."},{"key":"ref_27","first-page":"93","article-title":"The Longitudinal Imaging Tracker (BrICS-LIT):A Cloud Platform for Monitoring Treatment Response in Glioblastoma Patients","volume":"6","author":"Ramesh","year":"2020","journal-title":"Tomogr. Ann Arbor Mich"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.jacr.2018.01.022","article-title":"Management-Based Structured Reporting of Posttreatment Glioma Response With the Brain Tumor Reporting and Data System","volume":"15","author":"Weinberg","year":"2018","journal-title":"J. Am. Coll. Radiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1016\/j.acra.2018.12.023","article-title":"Institutional Implementation of a Structured Reporting System: Our Experience with the Brain Tumor Reporting and Data System","volume":"26","author":"Gore","year":"2019","journal-title":"Acad. Radiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.acra.2019.07.028","article-title":"Quantitative Improvement in Brain Tumor MRI Through Structured Reporting (BT-RADS)","volume":"27","author":"Zhang","year":"2020","journal-title":"Acad. Radiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1111\/jon.13044","article-title":"A brain tumor reporting and data system to optimize imaging surveillance and prognostication in high-grade gliomas","volume":"32","author":"Kim","year":"2022","journal-title":"J. Neuroimaging"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1067\/j.cpradiol.2020.01.006","article-title":"Using a Website to Teach a Structured Reporting System, the Brain Tumor Reporting and Data System","volume":"50","author":"Kim","year":"2021","journal-title":"Curr. Probl. Diagn. Radiol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Haase, S., Nu\u00f1ez, F.M., Gauss, J.C., Thompson, S., Brumley, E., Lowenstein, P., and Castro, M.G. (2020). Hemispherical Pediatric High-Grade Glioma: Molecular Basis and Therapeutic Opportunities. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249654"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"iv1","DOI":"10.1093\/neuonc\/noy131","article-title":"CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2011-2015","volume":"20","author":"Ostrom","year":"2018","journal-title":"Neuro Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2370","DOI":"10.1200\/JCO.2017.73.0242","article-title":"Pediatric Gliomas: Current Concepts on Diagnosis, Biology, and Clinical Management","volume":"35","author":"Sturm","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1002\/mrm.1910300405","article-title":"Development of the human brain: In vivo quantification of metabolite and water content with proton magnetic resonance spectroscopy","volume":"30","author":"Kreis","year":"1993","journal-title":"Magn. Reson. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1093\/neuros\/nyx103","article-title":"Current Clinical Brain Tumor Imaging","volume":"81","author":"Mabray","year":"2017","journal-title":"Neurosurgery"}],"container-title":["Tomography"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2379-139X\/9\/2\/51\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:51:52Z","timestamp":1760122312000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2379-139X\/9\/2\/51"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,9]]},"references-count":37,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["tomography9020051"],"URL":"https:\/\/doi.org\/10.3390\/tomography9020051","relation":{},"ISSN":["2379-139X"],"issn-type":[{"type":"electronic","value":"2379-139X"}],"subject":[],"published":{"date-parts":[[2023,3,9]]}}}