Characterization of late radiation effects in the rat thoracolumbar spinal cord by MR imaging using USPIO.
The aim of this study was to detect late radiation effects in the rat spinal cord using MR imaging with ultra-small particles of iron oxide (USPIO) contrast agent to better understand the development of late radiation damage with emphasis on the period preceding neurological signs. Additionally, the role of an inflammatory reaction was assessed by measuring macrophages that internalized USPIO. T2-weighted spin echo MR measurements were performed at 7T in six rats before paresis was expected (130-150 days post-irradiation, early group), and in six paretic rats (150-190 days post-irradiation, late group). Measurements were performed before, directly after and, only in the early group, 40 h after USPIO administration and compared with histology. In the early group, MR images showed focal regions in grey matter (GM) and white matter (WM) with signal intensity reduction after USPIO injection. Larger lesions with contrast enhancement were located in and around edematous GM of three animals of the early group and five of the late group. Forty hours after injection, additional lesions in WM, GM and nerve roots appeared in animals with GM edema. In the late paretic group, MR imaging showed WM necrosis adjacent to areas with large contrast enhancement. In conclusion, detection of early focal lesions was improved by contrast administration. In the animals with extended radiation damage, large hypo-intense regions appeared due to USPIO, which might be attributed to blood spinal cord barrier breakdown, but the involvement of blood-derived iron-loaded macrophages could not be excluded.
Philippens
M E P
ME
Department of Radiation Oncology, University Medical Center Nijmegen, 341 P.O. box 9101, 6500HB, Nijmegen, The Netherlands. m.philippens@rther.umcn.nl
Gambarota
G
G
Pikkemaat
J A
JA
Peeters
W J M
WJ
van der Kogel
A J
AJ
Heerschap
A
A
D000818:Animals; D003287:Contrast Media; D003911:Dextrans; D052203:Ferrosoferric Oxide; D007089:Image Enhancement / Q000379:methods; D007501:Iron; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D008297:Male; D009187:Myelitis / Q000209:etiology / Q000473:pathology*; D010087:Oxides; D011832:Radiation Injuries / Q000209:etiology / Q000473:pathology*; D011878:Radiotherapy / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000473:pathology* / Q000528:radiation effects*; D013904:Thoracic Vertebrae / Q000473:pathology / Q000528:radiation effects
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; D007501:Iron; D052203:Ferrosoferric Oxide