Experimental and Clinical Therapeutics

Monday, October 17, 2005 3:00 PM-5:00 PM Exhibit Hall

(PP135) The relation between structural and functional changes in the rat lung after irradiation.

Luijk, P.*,1, Novakova-Jiresova, A.2, Steneker, M.N.J.1, Faber, H.2, Meertens, H.1, Kampinga, H.H.2, Coppes, R.P.1, 2, 1 Radiation Oncology, Groningen, Groningen, The Netherlands2 Radiation and Stress Cell Biology, Groningen, Groningen, The Netherlands

ABSTRACT- Radiation-induced pulmonary toxicity is characterized by severe changes in lung morphology and function. In recent studies, we showed that irradiation of the heart enhances early and very late radiation-induced lung function morbidity. The relation between lung function and structure changes after irradiation of the heart is not known. This study aims to determine this relation in the irradiated rat lung at three different times after irradiation. Six groups of animals were irradiated on different lung regions (left, right, apex, base, mediastinal and lateral.) All regions contained 50% of the total lung volume and were irradiated with 16-22 Gy. At 8, 26 and 38 weeks after irradiation, next to breathing rate (BR) measurements to assess lung function, CT scans were made to assess structural changes. In the CT scans the lungs were delineated using a computerized algorithm to ensure objectivity. The separation between irradiated and non-irradiated tissue was reconstructed using volume information of age-matched, non-irradiated controls. Changes of the mean and standard deviation of the density (in hounsfield units) within the delineated lung were combined to yield one quantitative measure for structural change, with respect to values obtained in the same region in non-irradiated controls. Subsequently, this was correlated to the BR. In the mediastinal region no BR and structural changes were observed. In all other regions, structural changes correlated significantly (r=0.58-0.64, p<0.05) to the BR in the intermediate week 26, but not early in week 8 and late in week 38. Therefore, it is concluded that for early and late radiation-induced lung damage structural changes do not correlate with the functional outcome since the latter is also influenced by early (pre-clinical) and late heart damage. In the intermediate phase when heart damage is compensated for, however, CT density change is a good measure for radiation-induced lung damage.

Key words: lung, heart, radiation pneumonitis, radiotherapy

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2005 RRS