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

Abstract Submission for Poster Presentation
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Abstract Title:: Developing predictive and translational magnetic resonance imaging biomarkers of neuroinflammation, cognitive impairment, and survival outcomes for radiotherapy-induced brain injury 
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. 


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Authors::
1. First Name: Maya
   Last Name: Teitz
   Degree(s): B.Sc.
   Organization: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287
2. First Name: Saikat
   Last Name: Maiti
   Degree(s): Ph.D.
   Organization: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287
3. First Name: Santosh
   Last Name: Yadav
   Degree(s): Ph.D.
   Organization: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287
4. First Name: Esteban
   Last Name: Velarde
   Degree(s): B.Sc.
   Organization: Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21231
5. First Name: Xiaoju
   Last Name: Yang
   Degree(s): Ph.D.
   Organization: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287
6. First Name: Shana
   Last Name: Lee
   Degree(s): B.Sc.
   Organization: Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205
7. First Name: Kristen
   Last Name: Lecksell
   Degree(s): B.Sc.
   Organization: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287
8. First Name: Chantelle
   Last Name: Terrilion
   Degree(s): Ph.D.
   Organization: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287.
9. First Name: Adnan
   Last Name: Bibic
   Degree(s): Ph.D.
   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
10. First Name: Ethel
    Middle Initial: J.
    Last Name: Ngen
    Degree(s): Ph.D.
    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

Presenting Author:: Ethel J. Ngen, Ph.D.
Institution:: Johns Hopkins University School of Medicine
Email Address:: engen1@jhmi.edu