CT-based surrogates of pulmonary ventilation in lung cancer: A voxel-level comparison with HP gas MRI Tahir BA1,2, Hughes PJ2, Hart KA1, Marshall H2, Swinscoe JA1, Wild JM2, Ireland RH1,2 and Hatton MQ1, 1Academic Unit of Clinical Oncology and 2Academic Radiology, University of Sheffield, UK www.shef.ac.uk/polaris Image Acquisition Introduction Deformation vector fields for shallow and large respiratory differences for 4D-CT reference dataset CT and MRI immobilisation and patient positioning CT MRI Although dose escalation can be employed to improve local control, it is limited by the incidence of radiation induced pneumonitis. Potentially localised measures of lung function can assist in preferential sparing of functional lung during the treatment planning process. This ‘functional lung avoidance planning’ concept has been applied using several pulmonary functional imaging modalities including single photon emission computed tomography [1] and helium-3 magnetic resonance imaging (3He-MRI) [2]. As an alternative, a novel computed tomography (CT) method, (‘ventilation CT’), has been proposed which could provide lung ventilation information directly from CT treatment planning scans, acquired at two different respiratory states, solely by image processing [3]. Before clinical use, the physiological accuracy of ventilation CT must be validated against established modalities such as hyperpolarised 3He-MRI. Previously, Mathew et al. attempted to validate ventilation derived from 4D-CT against 3He-MRI [4]. Their study was limited by significant differences in acquisition settings between CT and MRI including breathing manoeuvres (tidal breathing vs breath-hold), patient couch positioning and time interval between scans (1.5 weeks). 6 NSCLC patients due to have radiotherapy underwent expiration and inspiration breath-hold CT. On the same day, 3He-MRI and 1H-MRI were acquired in the same breath and at the same inflation state as the inspiratory CT, acquired using a 1L bag of room air [5]. Both CT and MRI were acquired supine, arms raised. CT and MRI acquisition Shallow difference Large difference Inspiration CT Expiration CT 3He MRI 1H MRI Ventilation CT   Registration CT vs 3He MRI comparison Expiration CT Warped expiration CT Inspiration CT Same-breath 1H & 3He MRI Warped 3He MRI Ventilation CT computation (Apply transform of 1H MRI to CT to 3He MRI) Workflow of comparison method of ventilation CT and 3He MRI Objectives To present an imaging protocol for acquiring pulmonary CT that can be used to calculate ventilation surrogates for direct comparison with hyperpolarised gas 3He-MRI. To compare the spatial correlation of ventilation CT & 3He MRI in a cohort of lung cancer patients. Image Registration and Processing Corresponding anatomical landmark identified on inspiration and expiration CT Methods Theory – Computation of CT-based surrogates of ventilation Inspiration Expiration Results Expiration CT was registered to inspiration CT via an initial pre-alignment affine stage followed by a diffeomorphic transform using Advanced Normalization Tools (ANTs) registration software [6]. To reduce computational time and improve the spatial alignment of the lungs by avoiding high contrast structures such as the ribs, the registration was limited to voxels within the lungs. The lungs were contoured using the Eclipse treatment planning system (Varian Medical Systems, Palo Alto, CA, USA). Registration accuracy was validated using a reference 4D-CT data set consisting of end-inhale and end-exhale phases for 6 patients with 100 expert anatomical landmarks defined on both images [7]. Ventilation CT images were calculated from voxel-wise intensity differences in Hounsfield unit (HU) values [3]. 1. Acquire inspiration & expiration CT Can be from 4DCT or breath-hold 2. Perform deformable image registration   3. Calculate a ventilation metric (Other methods are available!) 4. Apply post-processing Visual examination indicated accurate registration of inspiratory and expiratory breath-hold CT. Quantitative results demonstrated registration error of 1.1±0.2mm (mean±SD) for the reference dataset. Successful registration enabled computation of ventilation CT images at the inspiratory state and direct comparison with 3He-MRI. The median (range) Spearman’s coefficient was 0.65 (0.45-0.76). CT vs 3He 0.650.15  p < 0.05 CT 3He MRI Conclusions This work demonstrates the feasibility of acquiring CT and 1H / 3He-MRI in similar breath-holds and posture such that registered data can be used to compare CT ventilation and 3He-MRI ventilation maps. Initial results show moderate correlation between ventilation CT & 3He MRI, suggesting that ventilation CT may also be influenced by non-ventilatory factors. To ensure that 3He-MRI was in the same spatial domain and inflation state as the CT ventilation surrogate, the former was registered to the inspiratory CT data via same-breath anatomical 1H-MRI, also using ANTs [8]. The transformation from 1H-MRI to CT was applied directly to 3He-MRI allowing direct comparison of 3He-MRI and CT ventilation in corresponding regions of interest located within the lungs as defined by a 1H MRI lung mask. Spearman coefficients were used to assess voxel-level correlation. Acknowledgements: References: [1] Lavrenkov K, et al. Radiother Oncol 2009;91:349-52 [2] Ireland RH, et al. Int J Radiat Oncol Biol Phys 2007;68:273-81 [3] Guerrero TM, et al. Int J Radiat Oncol Biol Phys 2005;62:630-34 [4] Mathew L, et al. Acad Radiol 2012;19:1546-53 [5] Ireland RH, Phys Med Biol, 2008;53:6055-63 [6] Avants BB, et al. Neuroimage 2011;54:2033-44 [7] Vandemeulebroucke J, et al. Med Phys 2011;38:166-78 [8] Tahir BA, et al. Phys Med Biol 2014;59: 7267-77