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

Jiang X, Yuan L, Engelbach JA, Cates J, Perez-Torres CJ, Gao F, Thotala D, Drzymala RE, Schmidt RE, Rich KM, Hallahan DE, Ackerman JJ, Garbow JR - PLoS ONE (2015)

Bottom Line: MRI measurements demonstrate that TRD is a more important determinant of both time-to-onset and progression of RN than fractionation.A semi-quantitative (0 to 3) histologic grading system, capturing both the extent and severity of injury, is described and illustrated.MR imaging provides reliable quantification of the necrotic volume that correlates well with histologic score.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Washington University, St. Louis, Missouri, United States of America.

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 KnifeĀ® (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.

No MeSH data available.


Related in: MedlinePlus

MRI can monitor radiation necrosis in irradiated mouse brain.Representative contrast-enhanced, transaxial T2-weighted spin-echo images of irradiated mice at 1, 4, 8, and 13 weeks following a single 50-Gy (50% isodose) of radiation. Slices are chosen to display the same anatomic region of the brain at all four time points.
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pone.0139596.g002: MRI can monitor radiation necrosis in irradiated mouse brain.Representative contrast-enhanced, transaxial T2-weighted spin-echo images of irradiated mice at 1, 4, 8, and 13 weeks following a single 50-Gy (50% isodose) of radiation. Slices are chosen to display the same anatomic region of the brain at all four time points.

Mentions: Representative contrast-enhanced T2-weighted spin-echo images of irradiated mice, covering the same anatomic region of the brain and collected at 1, 4, 8, and 13 weeks following a single 50-Gy dose of radiation, are shown in Fig 2. Though not included in the volume measurements, some mice were imaged as early as one day post-irradiation, with no lesion observed. Hyperintense areas in these images, due to edema, correspond with regions of radiation necrosis in the brain. MR images begin to show hyperintense regions at ~4 weeks post irradiation, and these regions expand significantly in extent by 13 weeks, indicating late onset and rapid progression of radiation necrosis.


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

Jiang X, Yuan L, Engelbach JA, Cates J, Perez-Torres CJ, Gao F, Thotala D, Drzymala RE, Schmidt RE, Rich KM, Hallahan DE, Ackerman JJ, Garbow JR - PLoS ONE (2015)

MRI can monitor radiation necrosis in irradiated mouse brain.Representative contrast-enhanced, transaxial T2-weighted spin-echo images of irradiated mice at 1, 4, 8, and 13 weeks following a single 50-Gy (50% isodose) of radiation. Slices are chosen to display the same anatomic region of the brain at all four time points.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4595209&req=5

pone.0139596.g002: MRI can monitor radiation necrosis in irradiated mouse brain.Representative contrast-enhanced, transaxial T2-weighted spin-echo images of irradiated mice at 1, 4, 8, and 13 weeks following a single 50-Gy (50% isodose) of radiation. Slices are chosen to display the same anatomic region of the brain at all four time points.
Mentions: Representative contrast-enhanced T2-weighted spin-echo images of irradiated mice, covering the same anatomic region of the brain and collected at 1, 4, 8, and 13 weeks following a single 50-Gy dose of radiation, are shown in Fig 2. Though not included in the volume measurements, some mice were imaged as early as one day post-irradiation, with no lesion observed. Hyperintense areas in these images, due to edema, correspond with regions of radiation necrosis in the brain. MR images begin to show hyperintense regions at ~4 weeks post irradiation, and these regions expand significantly in extent by 13 weeks, indicating late onset and rapid progression of radiation necrosis.

Bottom Line: MRI measurements demonstrate that TRD is a more important determinant of both time-to-onset and progression of RN than fractionation.A semi-quantitative (0 to 3) histologic grading system, capturing both the extent and severity of injury, is described and illustrated.MR imaging provides reliable quantification of the necrotic volume that correlates well with histologic score.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Washington University, St. Louis, Missouri, United States of America.

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 KnifeĀ® (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.

No MeSH data available.


Related in: MedlinePlus