Towards MRI Differentiation of Recurring Tumor from Delayed Radiation Necrosis
Carlos J Perez-Torres, John A Engelbach, Jeremy Cates, Dinesh K Thotala, Robert E Drzymala, Joseph JH Ackerman, and Joel R Garbow Department of Radiology, Washington University in Saint Louis, Saint Louis, Missouri, United States, Department of Radiation Oncology, Washington University in Saint Louis, Saint Louis, Missouri, United States, Department of Chemistry, Washington University in Saint Louis, Saint Louis, Missouri, United States
A novel murine model for localized radiation necrosis and its characterization using advanced magnetic resonance imaging.
PURPOSE
To develop a murine model of radiation necrosis using fractionated, subtotal cranial irradiation; and to investigate the imaging signature of radiation-induced tissue damage using advanced magnetic resonance imaging techniques.


METHODS AND MATERIALS
Twenty-four mice each received 60 Gy of hemispheric (left) irradiation in 10 equal fractions. Magnetic resonance images at 4.7 T were subsequently collected using T1-, T2-, and diffusion sequences at selected time points after irradiation. After imaging, animals were killed and their brains fixed for correlative histologic analysis.


RESULTS
Contrast-enhanced T1- and T2-weighted magnetic resonance images at months 2, 3, and 4 showed changes consistent with progressive radiation necrosis. Quantitatively, mean diffusivity was significantly higher (mean = 0.86, 1.13, and 1.24 microm(2)/ms at 2, 3, and 4 months, respectively) in radiated brain, compared with contralateral untreated brain tissue (mean = 0.78, 0.82, and 0.83 microm(2)/ms) (p < 0.0001). Histology reflected changes typically seen in radiation necrosis.


CONCLUSIONS
This murine model of radiation necrosis will facilitate investigation of imaging biomarkers that distinguish between radiation necrosis and tumor recurrence. In addition, this preclinical study supports clinical data suggesting that diffusion-weighted imaging may be helpful in answering this diagnostic question in clinical settings.
Detection of the Ischemic Penumbra Using pH-Weighted MRI
The classic definition of the ischemic penumbra is a hypoperfused region in which metabolism is impaired, but still sufficient to maintain cellular polarization. Perfusion- and diffusion-weighted MRI (PWI, DWI) can identify regions of reduced perfusion and cellular depolarization, respectively, but it often remains unclear whether a PWI—DWI mismatch corresponds to benign oligemia or a true penumbra. We hypothesized that pH-weighted MRI (pHWI) can subdivide the PWI—DWI mismatch into these regions. Twenty-one rats underwent permanent middle cerebral artery occlusion and ischemic evolution over the first 3.5 h post-occlusion was studied using multiparametric MRI. End point was the stroke area defined by T2-hyperintensity at 24 h. In the acute phase, areas of reduced pH were always larger than or equal to DWI deficits and smaller than or equal to PWI deficits. Group analysis showed that pHWI deficits during this phase coincided with the resulting infarct area at endpoint. Final infarcts were smaller than PWI deficits (range 65% to 90%, depending on the severity of the occlusion) and much larger than acute DWI deficits. These data suggest that the outer boundary of the hypoperfused area showing a decrease in pH without DWI abnormality may correspond to the outer boundary of the ischemic penumbra, while the hypoperfused region at normal pH may correspond to benign oligemia. These first results show that pHWI can provide information complementary to PWI and DWI in the delineation of ischemic tissue.