Rob H. Ireland

Functional image-based radiotherapy planning for non-small cell lung cancer: A simulation study

BACKGROUND AND PURPOSE To investigate the incorporation of data from single-photon emission computed tomography (SPECT) or hyperpolarized helium-3 magnetic resonance imaging ((3)He-MRI) into intensity-modulated radiotherapy (IMRT) planning for non-small cell lung cancer (NSCLC). MATERIAL AND METHODS Seven scenarios were simulated that represent cases of NSCLC with significant functional lung defects. Two independent IMRT plans were produced for each scenario; one to minimise total lung volume receiving >or=20Gy (V(20)), and the other to minimise only the functional lung volume receiving >or=20Gy (FV(20)). Dose-volume characteristics and a plan quality index related to planning target volume coverage by the 95% isodose (V(PTV95)/FV(20)) were compared between anatomical and functional plans using the Wilcoxon signed ranks test. RESULTS Compared to anatomical IMRT plans, functional planning reduced FV(20) (median 2.7%, range 0.6-3.5%, p=0.02), and total lung V(20) (median 1.5%, 0.5-2.7%, p=0.02), with a small reduction in mean functional lung dose (median 0.4Gy, 0-0.7Gy, p=0.03). There were no significant differences in target volume coverage or organ-at-risk doses. Plan quality index was improved for functional plans (median increase 1.4, range 0-11.8, p=0.02). CONCLUSIONS Statistically significant reductions in FV(20), V(20) and mean functional lung dose are possible when IMRT planning is supplemented by functional information derived from SPECT or (3)He-MRI.

Detection of radiation-induced lung injury in non-small cell lung cancer patients using hyperpolarized helium-3 magnetic resonance imaging

PURPOSE To compare hyperpolarized helium-3 magnetic resonance imaging ((3)He-MRI) acquired from non-small cell lung cancer (NSCLC) patients before and after external beam radiotherapy (EBRT). METHODS AND MATERIALS In an Ethics Committee-approved prospective study, five patients with histologically confirmed NSCLC gave written informed consent to undergo computed tomography (CT) and (3)He-MR ventilation imaging 1 week prior to and 3 months after radiotherapy. Images were registered to pre-treatment CT using anatomical landmark-based rigid registration to enable comparison. Emphysema was graded from examination of the CT. MRI-defined ventilation was calculated as the intersection of (3)He-MRI and CT lung volume as a percentage of the CT lung volume for the whole lung and regions of CT-defined pneumonitis. RESULTS On pre-treatment images, there was a significant correlation between the degree of CT-defined emphysema and (3)He-MRI whole lung ventilation (Spearmans rho=0.90, p=0.04). After radiation therapy, pneumonitis was evident on CT for 3/5 patients. For these cases, (3)He-MRI ventilation was significantly reduced within the regions of pneumonitis (pre: 94.1±2.2%, post: 73.7±4.7%; matched pairs Students t-test, p=0.02, mean difference=20.4%, 95% confidence interval 6.3-34.6%). CONCLUSIONS This work demonstrates the feasibility of detecting ventilation changes between pre- and post-treatment using hyperpolarized helium-3 MRI for patients with NSCLC. Pre-treatment, the degree of emphysema and (3)He-MRI ventilation were correlated. For three cases of radiation pneumonitis, (3)He-MRI ventilation changes between pre- and post-treatment imaging were consistent with CT evidence of radiation-induced lung injury.

Synchronous acquisition of hyperpolarised 3He and 1H MR images of the lungs – maximising mutual anatomical and functional information

The development of hybrid medical imaging scanners has allowed imaging with different detection modalities at the same time, providing different anatomical and functional information within the same physiological time course with the patient in the same position. Until now, the acquisition of proton MRI of lung anatomy and hyperpolarised gas MRI of lung function required separate breath‐hold examinations, meaning that the images were not spatially registered or temporally synchronised. We demonstrate the spatially registered concurrent acquisition of lung images from two different nuclei in vivo. The temporal and spatial registration of these images is demonstrated by a high degree of mutual consistency that is impossible to achieve in separate scans and breath holds. Copyright

An image acquisition and registration strategy for the fusion of hyperpolarized helium-3 MRI and x-ray CT images of the lung.

The purpose of this ethics committee approved prospective study was to evaluate an image acquisition and registration protocol for hyperpolarized helium-3 magnetic resonance imaging ((3)He-MRI) and x-ray computed tomography. Nine patients with non-small cell lung cancer (NSCLC) gave written informed consent to undergo a free-breathing CT, an inspiration breath-hold CT and a 3D ventilation (3)He-MRI in CT position using an elliptical birdcage radiofrequency (RF) body coil. (3)He-MRI to CT image fusion was performed using a rigid registration algorithm which was assessed by two observers using anatomical landmarks and a percentage volume overlap coefficient. Registration of (3)He-MRI to breath-hold CT was more accurate than to free-breathing CT; overlap 82.9 +/- 4.2% versus 59.8 +/- 9.0% (p < 0.001) and mean landmark error 0.75 +/- 0.24 cm versus 1.25 +/- 0.60 cm (p = 0.002). Image registration is significantly improved by using an imaging protocol that enables both (3)He-MRI and CT to be acquired with similar breath holds and body position through the use of a birdcage (3)He-MRI body RF coil and an inspiration breath-hold CT. Fusion of (3)He-MRI to CT may be useful for the assessment of patients with lung diseases.

Lung ventilation volumetry with same-breath acquisition of hyperpolarized gas and proton MRI.

The purpose of this work was to assess the reproducibility of percentage of ventilated lung volume (PV) measured from hyperpolarized (HP) 3He and 1H anatomical images acquired in the same breath‐hold when compared with PV measured from 3He and 1H images from separate breath‐holds.

A method for quantitative analysis of regional lung ventilation using deformable image registration of CT and hybrid hyperpolarized gas/1H MRI

Hyperpolarized gas magnetic resonance imaging (MRI) generates highly detailed maps of lung ventilation and physiological function while CT provides corresponding anatomical and structural information. Fusion of such complementary images enables quantitative analysis of pulmonary structure-function. However, direct image registration of hyperpolarized gas MRI to CT is problematic, particularly in lungs whose boundaries are difficult to delineate due to ventilation heterogeneity. This study presents a novel indirect method of registering hyperpolarized gas MRI to CT utilizing (1)H-structural MR images that are acquired in the same breath-hold as the gas MRI. The feasibility of using this technique for regional quantification of ventilation of specific pulmonary structures is demonstrated for the lobes.The direct and indirect methods of hyperpolarized gas MRI to CT image registration were compared using lung images from 15 asthma patients. Both affine and diffeomorphic image transformations were implemented. Registration accuracy was evaluated using the target registration error (TRE) of anatomical landmarks identified on (1)H MRI and CT. The Wilcoxon signed-rank test was used to test statistical significance.For the affine transformation, the indirect method of image registration was significantly more accurate than the direct method (TRE = 14.7 ± 3.2 versus 19.6 ± 12.7 mm, p = 0.036). Using a deformable transformation, the indirect method was also more accurate than the direct method (TRE = 13.5 ± 3.3 versus 20.4 ± 12.8 mm, p = 0.006).Accurate image registration is critical for quantification of regional lung ventilation with hyperpolarized gas MRI within the anatomy delineated by CT. Automatic deformable image registration of hyperpolarized gas MRI to CT via same breath-hold (1)H MRI is more accurate than direct registration. Potential applications include improved multi-modality image fusion, functionally weighted radiotherapy planning, and quantification of lobar ventilation in obstructive airways disease.

Dosimetric evaluation of inspiration and expiration breath-hold for intensity-modulated radiotherapy planning of non-small cell lung cancer.

The purpose of this study was to compare target coverage and lung tissue sparing between inspiration and expiration breath-hold intensity-modulated radiotherapy (IMRT) plans for patients with non-small cell lung cancer (NSCLC). In a prospective study, seven NSCLC patients gave written consent to undergo both moderate deep inspiration and end-expiration breath-hold computed tomography (CT), which were used to generate five-field IMRT plans. Dose was calculated with a scatter and an inhomogeneity correction algorithm. The percentage of the planning target volume (PTV) receiving 90% of the prescription dose (PTV(90)), the volume of total lung receiving >or=10 Gy (V(10)) and >or=20 Gy (V(20)) and the mean lung dose (MLD) were compared by the Students paired t-test. Compared with the expiration plans, the mean +/- SD reductions for V(10), V(20) and MLD on the inspiration plans were 4.0 +/- 3.7% (p = 0.031), 2.5 +/- 2.3% (p = 0.028) and 1.1 +/- 0.7 Gy (p = 0.007), respectively. Conversely, a mean difference of 1.1 +/- 1.1% (p = 0.044) in PTV(90) was demonstrated in favour of expiration. When using IMRT, inspiration breath-hold can reduce the dose to normal lung tissue while expiration breath-hold can improve the target coverage. The improved lung sparing at inspiration may outweigh the modest improvements in target coverage at expiration.

Functional Image-guided Radiotherapy Planning for Normal Lung Avoidance

For patients with lung cancer undergoing curative intent radiotherapy, functional lung imaging can be incorporated into treatment planning to modify the dose distribution within non-target volume lung by differentiation of lung regions that are functionally defective or viable. This concept of functional image-guided lung avoidance treatment planning has been investigated with several imaging modalities, primarily single photon emission computed tomography (SPECT), but also hyperpolarised gas magnetic resonance (MR) imaging, positron emission tomography (PET) and computed tomography (CT)-based measures of lung biomechanics. Here, we review the application of each of these modalities, review practical issues of lung avoidance implementation, including image registration and the role of both ventilation and perfusion imaging, and provide guidelines for reporting of future lung avoidance planning studies.

Comparison of 3He and 129Xe MRI for evaluation of lung microstructure and ventilation at 1.5T: 3He and 129Xe Lung MRI at 1.5T

To support translational lung MRI research with hyperpolarized 129Xe gas, comprehensive evaluation of derived quantitative lung function measures against established measures from 3He MRI is required. Few comparative studies have been performed to date, only at 3T, and multisession repeatability of 129Xe functional metrics have not been reported.

Impact of field number and beam angle on functional image-guided lung cancer radiotherapy planning

To investigate the effect of beam angles and field number on functionally-guided intensity modulated radiotherapy (IMRT) normal lung avoidance treatment plans that incorporate hyperpolarised helium-3 magnetic resonance imaging (3He MRI) ventilation data. Eight non-small cell lung cancer patients had pre-treatment 3He MRI that was registered to inspiration breath-hold radiotherapy planning computed tomography. IMRT plans that minimised the volume of total lung receiving  ⩾20 Gy (V20) were compared with plans that minimised 3He MRI defined functional lung receiving  ⩾20 Gy (fV20). Coplanar IMRT plans using 5-field manually optimised beam angles and 9-field equidistant plans were also evaluated. For each pair of plans, the Wilcoxon signed ranks test was used to compare fV20 and the percentage of planning target volume (PTV) receiving 90% of the prescription dose (PTV90). Incorporation of 3He MRI led to median reductions in fV20 of 1.3% (range: 0.2-9.3%; p  =  0.04) and 0.2% (range: 0 to 4.1%; p  =  0.012) for 5- and 9-field arrangements, respectively. There was no clinically significant difference in target coverage. Functionally-guided IMRT plans incorporating hyperpolarised 3He MRI information can reduce the dose received by ventilated lung without comprising PTV coverage. The effect was greater for optimised beam angles rather than uniformly spaced fields.