Childhood Cancer Data Initiative Annual Symposium (Abstract Registration): Submission #37

serial: '37'
sid: '148228'
uuid: c739aad9-221a-44f5-ac78-1240feef0292
uri: /nci/ccdisymposium/abstract
created: '1754498060'
completed: '1754499212'
changed: '1754499212'
in_draft: '0'
current_page: ''
remote_addr: 10.208.24.36
uid: '0'
langcode: en
webform_id: ccdi_symposium_abstract
entity_type: node
entity_id: '2139'
locked: '0'
sticky: '0'
notes: ''
metatag: meta
data:
  authors_:
    - add_author_degree: B.Sc.
      add_author_first_name: Maya
      add_author_last_name: Teitz
      add_author_middle: ''
      add_author_organization: 'Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287'
    - add_author_degree: Ph.D.
      add_author_first_name: Saikat
      add_author_last_name: Maiti
      add_author_middle: ''
      add_author_organization: 'Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287'
    - add_author_degree: Ph.D.
      add_author_first_name: Santosh
      add_author_last_name: Yadav
      add_author_middle: ''
      add_author_organization: 'Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287'
    - add_author_degree: B.Sc.
      add_author_first_name: Esteban
      add_author_last_name: Velarde
      add_author_middle: ''
      add_author_organization: 'Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21231'
    - add_author_degree: Ph.D.
      add_author_first_name: Xiaoju
      add_author_last_name: Yang
      add_author_middle: ''
      add_author_organization: 'Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287'
    - add_author_degree: B.Sc.
      add_author_first_name: Shana
      add_author_last_name: Lee
      add_author_middle: ''
      add_author_organization: 'Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205'
    - add_author_degree: B.Sc.
      add_author_first_name: Kristen
      add_author_last_name: Lecksell
      add_author_middle: ''
      add_author_organization: 'Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287'
    - add_author_degree: Ph.D.
      add_author_first_name: Chantelle
      add_author_last_name: Terrilion
      add_author_middle: ''
      add_author_organization: 'Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287.'
    - add_author_degree: Ph.D.
      add_author_first_name: Adnan
      add_author_last_name: Bibic
      add_author_middle: ''
      add_author_organization: 'Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287;  F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205'
    - add_author_degree: Ph.D.
      add_author_first_name: Ethel
      add_author_last_name: Ngen
      add_author_middle: J.
      add_author_organization: 'Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287; Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287'
  abstract: |
    Introduction: Radiotherapy-induced brain injury (RIBI) affects up to 90% of brain tumor survivors treated with radiotherapy. Thus, there is a great need for imaging strategies capable of detecting RIBI early on, for its effective management.

    Objective: Here, we used multi-parametric magnetic resonance imaging (MRI) to identify translational and predictive biomarkers of RIBI in a preclinical mouse model. 

    Method: Mice were stereotactically irradiated with an X-ray beam at a dose of 80 Gy (1.7Gy/min), and longitudinally monitored using MRI, behavioral tests of learning and memory, positron emission tomography (PET), histology, and immunohistochemistry. The irradiated mice were studied in comparison to non-irradiated control mice.

    Results:  Contrast-enhanced T1-weighted MRI was best suited to detect the onset of injury, by detecting changes in the blood-brain barrier (BBB) permeability. Maximum BBB permeability was detected at one-month post-irradiation. This coincided with the detection of maximum neuroinflammation, using IBA1 and CD68 immunohistochemistry and 11C-CPPC and 11C-DPA PET radiotracers of neuroinflammation. This simultaneous maximum BBB permeability and neuroinflammation detection also coincided with the onset of transient cognitive impairment, detected using the fear-conditioning behavioral test of learning and memory. T2-weighted MRI was best suited to detect intermediate injury, while T2*-weighted MRI was best suited to detect late injury. This MRI biomarker of late injury preceded significant weight loss, severe cognitive impairment, and decreased survival outcomes in the irradiated mice compared to the non-irradiated mice. 

    Conclusion: We identified three translational and predictive MRI biomarkers of RIBI that could enable the better management of RIBI in brain tumor survivors. 
  abstract_title_: 'Developing predictive and translational magnetic resonance imaging biomarkers of neuroinflammation, cognitive impairment, and survival outcomes for radiotherapy-induced brain injury '
  email_address_: engen1@jhmi.edu
  institution_: 'Johns Hopkins University School of Medicine'
  presenting_author_: 'Ethel J. Ngen, Ph.D.'