Quantifying Local Radiation-Induced Lung Damage From Computed Tomography

doi:10.1016/j.ijrobp.2009.08.058

International Journal of Radiation OncologyBiologyPhysics

Volume 76, Issue 2, 1 February 2010, Pages 548-556

https://doi.org/10.1016/j.ijrobp.2009.08.058 Get rights and content

Purpose

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 and Materials

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-mm³ subvolumes. The relation of changes in S_L (ΔS_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 ΔS_L.

Results

In rats, a clear dose–response relationship of ΔS_L was observed at different time points after radiation. Furthermore, ΔS_L correlated strongly to histologic endpoints (infiltrates and inflammatory cells) and breathing rate. In the patient, progressive local dose-dependent increases in ΔS_L were observed.

Conclusion

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.

Introduction

In non–small-cell lung cancer (NSCLC), escalation of radiation dose to the tumor is expected to result in increased local control 1, 2. However, the tumor dose is limited by the risk of life-threatening complications, such as radiation-induced pneumonitis and fibrosis (3). Since dose and irradiated volume are risk factors for the development of pulmonary morbidity 4, 5, 6, modern radiation technologies, such as intensity-modulated radiotherapy and protons, are aimed at reducing dose and irradiated volume. However, optimal clinical application of these techniques requires detailed knowledge of the relationship between dose distribution and the risk of complications. Aggregative local radiation-induced damage determines the occurrence of symptomatic radiation-induced loss of lung function (SRILF) 7, 8. Thus, to elucidate the relationship between dose distributions and the risk of SRILF in clinical settings with inhomogeneous dose distribution, an objective measure for local lung tissue damage needs to be quantified and related to local dose.

Radiation-induced changes in the lung, such as edema, cell infiltration into air spaces, thickened alveolar walls, and fibrosis, cause density changes (9). These density changes can be noninvasively measured using computed tomography (CT) imaging. This imaging modality is generally used to image radiation-induced pulmonary injury in both humans and animal models 9, 10, 11, 12, 13, 14, 15. In most studies, the mean lung density in the whole lung or a large part of it was used to quantify tissue damage. However, in the irradiated lung combined local density increases and hyperinflation occur. These are not always detectable in the mean density 4, 5. Considering this, we recently developed a method that quantitatively measures regional structural changes in homogeneous irradiated rat lung from CT images (15) using a combination of mean density changes with the corresponding standard deviation. However, regional quantification cannot be used for measurement of dose–effect relationships for local changes occurring after irradiation in clinical practice using nonuniform dose distributions.

Therefore, the aim of the present study was to develop a method using CT to obtain local quantities of structural changes in very small subvolumes of lung tissue. To accurately determine the structural changes from CT images, it was necessary to study homogenous dose distributions using our rat lung model first 4, 5, 16. We showed that local structural changes quantified from CT images were representative of local damage as they related to local histologic damage. Functional relevance of these local measurements was shown by correlation with global lung function. In addition, the feasibility of this method in the clinical setting was demonstrated by applying the method to serial CT images of one patient.

Section snippets

Study design

Adult male albino Wistar rats (n = 211, Hsd/Cpb:WU strain) were used. Radiation portals were designed using planning CT images of 5 age-matched rats (4). Then, 100%, 75%, 50%, or 25% of the lung volumes were irradiated with 9–13 Gy, 12–17 Gy, 13–22 Gy, and 27–36 Gy, respectively (Fig. 1), using either proton or photon irradiation 4, 5, 14, 15, 16, 17. Since heart irradiation may influence the response of the lung to the irradiation, the dose distributions were chosen in such a manner that the

Dose–effect relations for local structural change

To test the capability of the method to measure radiation effects, the dose–effect relation was first determined in rats using homogenous dose distributions. A dose–response curve was created from rat lung CT images for ΔS_L at different time points after irradiation. First, to correct for growth of the thorax in time after irradiation, the irradiation field of 50% lateral (Fig. 1c) was reshaped to fit the lung size 8 and 26 weeks after irradiation.

Subsequently, these fields were projected on

Discussion

Radiation-induced lung damage is a major dose-limiting factor in radiotherapy for thoracic tumors (3). In models that are currently available to predict the risk of normal tissue complications, the only factor taken into account is either mean lung dose (23) or lung volume receiving more than a certain dose (i.e., V13 or V20 for 13 Gy or 20 Gy) (24). Even though these quantities correlate significantly to the risk of SRILF, correlations are generally weak 25, 26. Therefore, more accurate

Conclusion

A method was developed that is capable of measuring local damage to lung tissue in vivo. This local damage measurement correlated well with both histologic changes and global pulmonary function. The method provides essential information in elucidating the relation between the risk of complications and the dose distribution required for development of more accurate predictive models for normal tissue complication.

Acknowledgments

The authors thank H. Kiewiet and the accelerator crew of the Kernfysisch Versneller Instituut for their assistance in the present study.

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: Supported by the Dutch Cancer Society (Grant no. 2007-3890) and Grant no. 916.76.029 of the Innovational Research Incentives Scheme of the Netherlands Organization for Scientific Research (NWO). This work benefited from the use of Elastix software developed by S. Klein and M. Staring at the Image Sciences Institute (ISI) funded by NWO.

: Conflict of interest: none.

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Biology ContributionQuantifying Local Radiation-Induced Lung Damage From Computed Tomography

Purpose

Methods and Materials

Results

Conclusion

Introduction

Section snippets

Study design

Dose–effect relations for local structural change

Discussion

Conclusion

Acknowledgments

Lung Cancer

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Radiother Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Radiother Oncol

Int J Radiat Oncol Biol Phys

Radiother Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Biology Contribution
Quantifying Local Radiation-Induced Lung Damage From Computed Tomography