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.
Amide proton transfer (APT) contrast for imaging of brain tumors
In this work we demonstrate that specific MR image contrast can be produced in the water signal that reflects endogenous cellular protein and peptide content in intracranial rat 9L gliosarcomas. Although the concentration of these mobile proteins and peptides is only in the millimolar range, a detection sensitivity of several percent on the water signal (molar concentration) was achieved. This was accomplished with detection sensitivity enhancement by selective radiofrequency (RF) labeling of the amide protons, and by utilizing the effective transfer of this label to water via hydrogen exchange. Brain tumors were also assessed by conventional T1‐weighted, T2‐weighted, and diffusion‐weighted imaging. Whereas these commonly‐used approaches yielded heterogeneous images, the new amide proton transfer (APT) technique showed a single well‐defined region of hyperintensity that was assigned to brain tumor tissue. Magn Reson Med 50:1120–1126, 2003. © 2003 Wiley‐Liss, Inc.