Radiation therapy (RT) is a major treatment modality for primary and metastatic brain neoplasms. Radiation-induced neurotoxicity is a limiting factor for brain RT. Clinical symptoms can occur acutely and subacutely after brain irradiation, but most devastated neurotoxicity manifests of late neurological sequelae, including neurocognitve dysfunction, and white matter degeneration and necrosis. Given the delayed nature of neurotoxicity, it would be important to develop biomarkers, including derived from in vivo functional and molecular imaging, for early assessment of individual sensitivity to radiation and prediction of late neurotoxicity. Radiation-induced cerebral tissue injury is a complex and dynamic process, and involves in multiple tissue compartments. Cerebral vascular injury, which has been long considered to be crucial important for the development of cerebral tissue toxicity, occurs early after irradiation. White matter degeneration, including demyelination and necrosis, is progressive over time after brain irradiation. In this study, using in vivo dynamic-contrast-enhanced magnetic resonance imaging and diffusion tensor imaging, we aim to detect early alternations in cerebral vasculature and white matter tissue in the patients who have low-grade glioma or benign tumors and undergo fractionated partial brain RT. Also, we aim to determine the bio-dosimetric effects, including total dose and dose-volume, on the alterations of cerebral vasculature and white matter.
We aim to assess neurocognitve function in the patients from pre RT up to 2 years post RT, and to determine correlative relationships of early cerebral vascular injury and early delayed white matter degradation with late neurocognitive dysfunction. We hypothesize that early monitoring of changes in cerebral microvessels and tissue degeneration in response to fractionated RT would allow us to predict late neurocognitive deficits.

Public Health Relevance

Radiation therapy is a major treatment modality for brain tumor. However, radiation can generate neurological complications after treatment. This study aims to identify early signs of complications using functional imaging, thereby to reduce radiation complications by advanced radiation technologies and/or therapeutic intervention.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Radiation Therapeutics and Biology Study Section (RTB)
Program Officer
Fountain, Jane W
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Michigan Ann Arbor
Schools of Medicine
Ann Arbor
United States
Zip Code
Tsien, Christina; Cao, Yue; Chenevert, Thomas (2014) Clinical applications for diffusion magnetic resonance imaging in radiotherapy. Semin Radiat Oncol 24:218-26
Farjam, Reza; Tsien, Christina I; Feng, Felix Y et al. (2014) Investigation of the diffusion abnormality index as a new imaging biomarker for early assessment of brain tumor response to radiation therapy. Neuro Oncol 16:131-9
Nazem-Zadeh, Mohammad-Reza; Chapman, Christopher H; Chenevert, Thomas et al. (2014) Response-driven imaging biomarkers for predicting radiation necrosis of the brain. Phys Med Biol 59:2535-47
Farjam, Reza; Tsien, Christina I; Lawrence, Theodore S et al. (2014) DCE-MRI defined subvolumes of a brain metastatic lesion by principle component analysis and fuzzy-c-means clustering for response assessment of radiation therapy. Med Phys 41:011708
Chapman, Christopher H; Nazem-Zadeh, Mohammad; Lee, Oliver E et al. (2013) Regional variation in brain white matter diffusion index changes following chemoradiotherapy: a prospective study using tract-based spatial statistics. PLoS One 8:e57768
Farjam, Reza; Tsien, Christina I; Feng, Felix Y et al. (2013) Physiological imaging-defined, response-driven subvolumes of a tumor. Int J Radiat Oncol Biol Phys 85:1383-90
Farjam, Reza; Parmar, Hemant A; Noll, Douglas C et al. (2012) An approach for computer-aided detection of brain metastases in post-Gd T1-W MRI. Magn Reson Imaging 30:824-36
Cao, Yue (2011) The promise of dynamic contrast-enhanced imaging in radiation therapy. Semin Radiat Oncol 21:147-56
Cao, Yue; Li, Diana; Shen, Zhou et al. (2010) Sensitivity of quantitative metrics derived from DCE MRI and a pharmacokinetic model to image quality and acquisition parameters. Acad Radiol 17:468-78