title: Monochromatic minibeams radiotherapy: from healthy tissue-sparing effect studies toward first experimental glioma bearing rats therapy.
abstract: OBJECTIVE
  The purpose of this study was to evaluate high-dose single fraction delivered with monochromatic X-rays minibeams for the radiotherapy of primary brain tumors in rats.
  
  
  METHODS
  Two groups of healthy rats were irradiated with one anteroposterior minibeam incidence (four minibeams, 123 Gy prescribed dose at 1 cm depth in the brain) or two interleaved incidences (54 Gy prescribed dose in a 5 × 5 × 4.8 mm(3) volume centered in the right hemisphere), respectively. Magnetic resonance imaging (MRI) follow-up was performed over 1 year. T2-weighted (T2w) images, apparent diffusion coefficient (ADC), and blood vessel permeability maps were acquired. F98 tumor bearing rats were also irradiated with interleaved minibeams to achieve a homogeneous dose of 54 Gy delivered to an 8 × 8 × 7.8 mm(3) volume centered on the tumor. Anatomic and functional MRI follow-up was performed every 10 days after irradiation. T2w images, ADC, and perfusion maps were acquired.
  
  
  RESULTS
  All healthy rats were euthanized 1 year after irradiation without any clinical alteration visible by simple examination. T2w and ADC measurements remain stable for the single incidence irradiation group. Localized Gd-DOTA permeability, however, was observed 9 months after irradiation for the interleaved incidences group. The survival time of irradiated glioma bearing rats was significantly longer than that of untreated animals (49 ± 12.5 days versus 23.3 ± 2 days, p < 0.001). The tumoral cerebral blood flow and blood volume tend to decrease after irradiation.
  
  
  CONCLUSIONS
  This study demonstrates the sparing effect of minibeams on healthy tissue. The increased life span achieved for irradiated glioma bearing rats was similar to the one obtained with other radiotherapy techniques. This experimental tumor therapy study shows the feasibility of using X-ray minibeams with high doses in brain tumor radiotherapy.
authors.affiliation: INSERM, Grenoble, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Deman
authors.forename: Mathias
authors.initials: M
authors.lastname: Vautrin
authors.forename: Magali
authors.initials: M
authors.lastname: Edouard
authors.forename: Vasile
authors.initials: V
authors.lastname: Stupar
authors.forename: Laure
authors.initials: L
authors.lastname: Bobyk
authors.forename: Régine
authors.initials: R
authors.lastname: Farion
authors.forename: Hélène
authors.initials: H
authors.lastname: Elleaume
authors.forename: Chantal
authors.initials: C
authors.lastname: Rémy
authors.forename: Emmanuel L
authors.initials: EL
authors.lastname: Barbier
authors.forename: François
authors.initials: F
authors.lastname: Estève
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Adam
mesh_terms: D000818:Animals; D001810:Blood Volume / Q000528:radiation effects; D001932:Brain Neoplasms / Q000098:blood supply / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D016371:Cranial Irradiation / Q000295:instrumentation / Q000379:methods*; D005240:Feasibility Studies; D005910:Glioma / Q000098:blood supply / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008279:Magnetic Resonance Imaging; D008297:Male; D023421:Models, Animal; D059351:Organ Sparing Treatments / Q000295:instrumentation / Q000379:methods*; D058958:Organs at Risk; D011878:Radiotherapy / Q000379:methods; D011879:Radiotherapy Dosage; D051381:Rats; D011916:Rats, Inbred F344; D016019:Survival Analysis; D017356:Synchrotrons / Q000295:instrumentation