Using 4DCT‐ventilation to characterize lung function changes for pediatric patients getting thoracic radiotherapy

Abstract Purpose A form of lung functional imaging has been developed that uses 4DCT data to calculate ventilation (4DCT‐ventilation). Because 4DCTs are acquired as standard‐of‐care to manage breathing motion during radiotherapy, 4DCT‐ventilation provides functional information at no extra dosimetric or monetary cost. 4DCT‐ventilation has yet to be described in children. 4DCT‐ventilation can be used as a tool to help assess post‐treatment lung function and predict for future clinical thoracic toxicities for pediatric patients receiving radiotherapy to the chest. The purpose of this work was to perform a preliminary evaluation of 4DCT‐ventilation‐based lung function changes for pediatric patients receiving radiotherapy to the lungs. Methods The study used four patients with pre and postradiotherapy 4DCTs. The 4DCTs, deformable image registration, and a density‐change‐based algorithm were used to compute pre and post‐treatment 4DCT‐ventilation images. The post‐treatment 4DCT‐ventilation images were compared to the pretreatment 4DCT‐ventilation images for a global lung response and for an intrapatient dose–response (providing an assessment for dose‐dependent regional dose–response). Results For three of the four patients, a global ventilation decline of 7–37% was observed, while one patient did not demonstrate a global functional decline. Dose–response analysis did not reveal an intrapatient dose–response from 0 to 20 Gy for three patients while one patient demonstrated increased 4DCT‐ventilation decline as a function of increasing lung doses up to 50 Gy. Conclusions Compared to adults, pediatric patients have unique lung function, dosimetric, and toxicity profiles. The presented work is the first to evaluate spatial lung function changes in pediatric patients using 4DCT‐ventilation and showed lung function changes for three of the four patients. The early changes demonstrated with lung function imaging warrant further longitudinal work to determine whether the imaging‐based early changes can be predicted for long‐term clinical toxicity.

tion provides functional information at no extra dosimetric or monetary cost.
4DCT-ventilation has yet to be described in children. 4DCT-ventilation can be used as a tool to help assess post-treatment lung function and predict for future clinical thoracic toxicities for pediatric patients receiving radiotherapy to the chest. The purpose of this work was to perform a preliminary evaluation of 4DCT-ventilation-based lung function changes for pediatric patients receiving radiotherapy to the lungs.

Methods:
The study used four patients with pre and postradiotherapy 4DCTs. The 4DCTs, deformable image registration, and a density-change-based algorithm were used to compute pre and post-treatment 4DCT-ventilation images. The post-treatment 4DCT-ventilation images were compared to the pretreatment 4DCT-ventilation images for a global lung response and for an intrapatient dose-response (providing an assessment for dose-dependent regional dose-response).
Results: For three of the four patients, a global ventilation decline of 7-37% was observed, while one patient did not demonstrate a global functional decline. Doseresponse analysis did not reveal an intrapatient dose-response from 0 to 20 Gy for three patients while one patient demonstrated increased 4DCT-ventilation decline as a function of increasing lung doses up to 50 Gy.
Conclusions: Compared to adults, pediatric patients have unique lung function, dosimetric, and toxicity profiles. The presented work is the first to evaluate spatial lung function changes in pediatric patients using 4DCT-ventilation and showed lung function changes for three of the four patients. The early changes demonstrated with lung function imaging warrant further longitudinal work to determine whether the imaging-based early changes can be predicted for long-term clinical toxicity.

| INTRODUCTION
A form of functional imaging has been developed that uses 4-dimensional computed tomography (4DCT) data along with image processing techniques to calculate 4DCT-based lung ventilation maps. [1][2][3] 4DCT-ventilation has been gaining momentum in radiation oncology because 4DCT simulations are frequently acquired as part of the standard treatment planning process; which enables the calculation of 4DCT-ventilation-based lung function without burdening the patient with an extra imaging procedure. There have been two clinical applications of 4DCT-ventilation in radiation oncology: functional radiotherapy (designing radiation treatment plans that minimize dose to functional lung) and thoracic treatment assessment. [4][5][6][7] One clinical setting where 4DCT-ventilation has yet to be explored is children receiving radiotherapy to the lungs. Some common indications for radiation to the lungs in pediatric patients include whole lung radiation for metastatic solid tumors, total body irradiation, and focal radiation for primary or metastatic disease in the chest. As with adult patients, pulmonary complications are a serious clinical concern for pediatric patients that get dose to the thorax. 8 In this work, we evaluate the concept of using 4DCT-ventilation in the pediatric setting. Thoracic toxicity is an important clinical concern for pediatric patients getting lung radiotherapy. As with adult patients, 4DCT simulations are often used for pediatric patients where breathing motion management is needed. Therefore, acquiring baseline lung function with 4DCT-ventilation for pediatric patients would still come at minimal monetary, dosimetric, or time cost to the patients. 4DCT-ventilation can potentially be used to help assess post-treatment lung function and predict for subsequent long-term clinical thoracic toxicities. The purpose of this work was to evaluate 4DCT-ventilation-based spatial lung function changes for pediatric patients getting thoracic radiotherapy.

2.B | 4DCT-ventilation image calculation
Each patient's pre and post-treatment 4DCT scan was used to calculate 4DCT-ventilation maps using previously described methods. 1,2,9 The lungs are first segmented on the 0% (Inhale) and 50% (Exhale) phases of the 4DCT data set. Deformable image registration is used to register lung voxels from the inhale to the exhale data set. 10 Once the inhale and exhale voxels were linked, a density-change-based equation was applied to calculate ventilation: where V in and V ex are the inhale and exhale volumes and HU in and

| DISCUSSION
The results point to two distinct observations. The first observation is that in three out of four patients we demonstrated a global reduction in lung function, while in one patient there was no change in pre to post-treatment ventilation. The second finding was that we did not observe any regional reduction in ventilation as a function of isodose level for three out of the four patients, while for one patient