Dataset Information

A Gamma-Knife-Enabled Mouse Model of Cerebral Single-Hemisphere Delayed Radiation Necrosis.

ABSTRACT:

Purpose

To develop a Gamma Knife-based mouse model of late time-to-onset, cerebral radiation necrosis (RN) with serial evaluation by magnetic resonance imaging (MRI) and histology.

Methods and materials

Mice were irradiated with the Leksell Gamma Knife® (GK) PerfexionTM (Elekta AB; Stockholm, Sweden) with total single-hemispheric radiation doses (TRD) of 45- to 60-Gy, delivered in one to three fractions. RN was measured using T2-weighted MR images, while confirmation of tissue damage was assessed histologically by hematoxylin & eosin, trichrome, and PTAH staining.

Results

MRI measurements demonstrate that TRD is a more important determinant of both time-to-onset and progression of RN than fractionation. The development of RN is significantly slower in mice irradiated with 45-Gy than 50- or 60-Gy, where RN development is similar. Irradiated mouse brains demonstrate all of the pathologic features observed clinically in patients with confirmed RN. A semi-quantitative (0 to 3) histologic grading system, capturing both the extent and severity of injury, is described and illustrated. Tissue damage, as assessed by a histologic score, correlates well with total necrotic volume measured by MRI (correlation coefficient = 0.948, with p<0.0001), and with post-irradiation time (correlation coefficient = 0.508, with p<0.0001).

Conclusions

Following GK irradiation, mice develop late time-to-onset cerebral RN histology mirroring clinical observations. MR imaging provides reliable quantification of the necrotic volume that correlates well with histologic score. This mouse model of RN will provide a platform for mechanism of action studies, the identification of imaging biomarkers of RN, and the development of clinical studies for improved mitigation and neuroprotection.

SUBMITTER: Jiang X

PROVIDER: S-EPMC4595209 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

A Gamma-Knife-Enabled Mouse Model of Cerebral Single-Hemisphere Delayed Radiation Necrosis.

Jiang Xiaoyu X Yuan Liya L Engelbach John A JA Cates Jeremy J Perez-Torres Carlos J CJ Gao Feng F Thotala Dinesh D Drzymala Robert E RE Schmidt Robert E RE Rich Keith M KM Hallahan Dennis E DE Ackerman Joseph J H JJ Garbow Joel R JR

PloS one 20151006 10

<h4>Purpose</h4>To develop a Gamma Knife-based mouse model of late time-to-onset, cerebral radiation necrosis (RN) with serial evaluation by magnetic resonance imaging (MRI) and histology.<h4>Methods and materials</h4>Mice were irradiated with the Leksell Gamma Knife® (GK) PerfexionTM (Elekta AB; Stockholm, Sweden) with total single-hemispheric radiation doses (TRD) of 45- to 60-Gy, delivered in one to three fractions. RN was measured using T2-weighted MR images, while confirmation of tissue dam ...[more]

PMID: 26440791

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Dataset Information

A Gamma-Knife-Enabled Mouse Model of Cerebral Single-Hemisphere Delayed Radiation Necrosis.

Purpose

Methods and materials

Results

Conclusions

Publications

A Gamma-Knife-Enabled Mouse Model of Cerebral Single-Hemisphere Delayed Radiation Necrosis.

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