title: Quantifying local radiation-induced lung damage from computed tomography.
abstract: OBJECTIVE
  Optimal implementation of new radiotherapy techniques requires accurate predictive models for normal tissue complications. Since clinically used dose distributions are nonuniform, local tissue damage needs to be measured and related to local tissue dose. In lung, radiation-induced damage results in density changes that have been measured by computed tomography (CT) imaging noninvasively, but not yet on a localized scale. Therefore, the aim of the present study was to develop a method for quantification of local radiation-induced lung tissue damage using CT.
  
  
  METHODS
  CT images of the thorax were made 8 and 26 weeks after irradiation of 100%, 75%, 50%, and 25% lung volume of rats. Local lung tissue structure (S(L)) was quantified from local mean and local standard deviation of the CT density in Hounsfield units in 1-mm(3) subvolumes. The relation of changes in S(L) (DeltaS(L)) to histologic changes and breathing rate was investigated. Feasibility for clinical application was tested by applying the method to CT images of a patient with non-small-cell lung carcinoma and investigating the local dose-effect relationship of DeltaS(L).
  
  
  RESULTS
  In rats, a clear dose-response relationship of DeltaS(L) was observed at different time points after radiation. Furthermore, DeltaS(L) correlated strongly to histologic endpoints (infiltrates and inflammatory cells) and breathing rate. In the patient, progressive local dose-dependent increases in DeltaS(L) were observed.
  
  
  CONCLUSIONS
  We developed a method to quantify local radiation-induced tissue damage in the lung using CT. This method can be used in the development of more accurate predictive models for normal tissue complications.
authors.affiliation: Department of Radiation Oncology, University Medical Center Groningen/University of Groningen, Groningen, The Netherlands.
authors.forename: Ghazaleh
authors.initials: G
authors.lastname: Ghobadi
authors.forename: Laurens E
authors.initials: LE
authors.lastname: Hogeweg
authors.forename: Hette
authors.initials: H
authors.lastname: Faber
authors.forename: Wim G J
authors.initials: WG
authors.lastname: Tukker
authors.forename: Jacobus M
authors.initials: JM
authors.lastname: Schippers
authors.forename: Sytze
authors.initials: S
authors.lastname: Brandenburg
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Langendijk
authors.forename: Robert P
authors.initials: RP
authors.lastname: Coppes
authors.forename: Peter
authors.initials: P
authors.lastname: van Luijk
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000532:radiotherapy; D004307:Dose-Response Relationship, Radiation; D005240:Feasibility Studies; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000528:radiation effects*; D008175:Lung Neoplasms / Q000532:radiotherapy; D008297:Male; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000000981:diagnostic imaging* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D056152:Respiratory Rate; D014057:Tomography, X-Ray Computed