title: Mapping Radiation Injury and Recovery in Bone Marrow Using 18F-FLT PET/CT and USPIO MRI in a Rat Model.
abstract: We present and test the use of multimodality imaging as a topological tool to map the amount of the body exposed to ionizing radiation and the location of exposure, which are important indicators of survival and recovery. To achieve our goal, PET/CT imaging with 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) was used to measure cellular proliferation in bone marrow (BM), whereas MRI using ultra-small superparamagnetic iron oxide (USPIO) particles provided noninvasive information on radiation-induced vascular damage.
  
  
  METHODS
  Animals were x-ray-irradiated at a dose of 7.5 Gy with 1 of 3 radiation schemes-whole-body irradiation, half-body shielding (HBS), or 1-leg shielding (1LS)-and imaged repeatedly. The spatial information from the CT scan was used to segment the region corresponding to BM from the PET scan using algorithms developed in-house, allowing for quantification of proliferating cells, and BM blood volume was estimated by measuring the changes in the T2 relaxation rates (ΔR2) collected from MR scans.
  
  
  RESULTS
  (18)F-FLT PET/CT imaging differentiated irradiated from unirradiated BM regions. Two days after irradiation, proliferation of 1LS animals was significantly lower than sham (P = 0.0001, femurs; P < 0.0001, tibias) and returned to sham levels by day 10 (P = 0.6344, femurs; P = 0.3962, tibias). The degree of shielding affected proliferation recovery, showing an increase in the irradiated BM of the femurs, but not the tibias, of HBS animals when compared with 1LS (P = 0.0310, femurs; P = 0.5832, tibias). MRI of irradiated spines detected radiation-induced BM vascular damage, measured by the significant increase in ΔR2 2 d after whole-body irradiation (P = 0.0022) and HBS (P = 0.0003) with a decreasing trend of values, returning to levels close to baseline over 10 d. Our data were corroborated using γ-counting and histopathology.
  
  
  CONCLUSIONS
  We demonstrated that (18)F-FLT PET/CT and USPIO MRI are valuable tools in mapping regional radiation exposure and the effects of radiation on BM. Analysis of the (18)F-FLT signal allowed for a clear demarcation of exposed BM regions and elucidated the kinetics of BM recovery, whereas USPIO MRI was used to assess vascular damage and recovery.
authors: Hematology-Oncology Section, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors: David A
authors: DA
authors: Rendon
authors: Hematology-Oncology Section, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors: Khushali
authors: K
authors: Kotedia
authors: Department of Surgery, Houston Methodist Hospital Research Institute, Houston, Texas.
authors: Solmaz F
authors: SF
authors: Afshar
authors: Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; and.
authors: Jyotinder N
authors: JN
authors: Punia
authors: Department of Surgery, Houston Methodist Hospital Research Institute, Houston, Texas.
authors: Omaima M
authors: OM
authors: Sabek
authors: Center for Outcomes Research, Department of Surgery, Houston Methodist Hospital Research Institute, Houston, Texas.
authors: Beverly A
authors: BA
authors: Shirkey
authors: Hematology-Oncology Section, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors: Janice A
authors: JA
authors: Zawaski
authors: Hematology-Oncology Section, Department of Pediatrics, Baylor College of Medicine, Houston, Texas gaber@bcm.edu.
authors: M Waleed
authors: MW
authors: Gaber
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000473:pathology* / Q000528:radiation effects*; D001855:Bone Marrow Diseases / Q000000981:diagnostic imaging* / Q000473:pathology*; D015224:Dideoxynucleosides; D052203:Ferrosoferric Oxide; D006470:Hemorrhage / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D008297:Male; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography; D011833:Radiation Injuries, Experimental / Q000000981:diagnostic imaging* / Q000473:pathology*; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D014057:Tomography, X-Ray Computed; D014916:Whole-Body Irradiation; D014965:X-Rays
chemical_list: D015224:Dideoxynucleosides; D019275:Radiopharmaceuticals; C002854:alovudine; D052203:Ferrosoferric Oxide
keywords: 18F-FLT PET/CT; USPIO-MRI; bone marrow; proliferation; radiation