Mohammadreza Negahdar

CT ventilation functional image-based IMRT treatment plans are comparable to SPECT ventilation functional image-based plans

PURPOSEnTo investigate the hypothesis that CT ventilation functional image-based IMRT plans designed to avoid irradiating highly-functional lung regions are comparable to single-photon emission CT (SPECT) ventilation functional image-based plans.nnnMETHODS AND MATERIALSnThree IMRT plans were created for eight thoracic cancer patients using: (1) CT ventilation functional images, (2) SPECT ventilation functional images, and (3) anatomic images (no functional images). CT ventilation images were created by deformable image registration of 4D-CT image data sets and quantitative analysis. The resulting plans were analyzed for the relationship between the deviations of CT-functional plan metrics from anatomic plan metrics (ΔCT-anatomic) and those of SPECT-functional plans (ΔSPECT-anatomic), and moreover for agreements of various metrics between the CT-functional and SPECT-functional plans.nnnRESULTSnThe relationship between ΔCT-anatomic and ΔSPECT-anatomic was strong (e.g., R=0.94; linear regression slope 0.71). The average differences and 95% limits of agreement between the CT-functional and SPECT-functional plan metrics (except for monitor units) for various structures were mostly less than 1% and 2%, respectively.nnnCONCLUSIONSnThis study demonstrated a reasonable agreement between the CT ventilation functional image-based IMRT plans and SPECT-functional plans, suggesting the potential for CT ventilation imaging to serve as a surrogate for SPECT ventilation in functional image-guided radiotherapy.

Noninvasive pulmonary nodule elastometry by CT and deformable image registration.

BACKGROUND AND PURPOSEnTo develop a noninvasive method for determining malignant pulmonary nodule (MPN) elasticity, and compare it against expert dual-observer manual contouring.nnnMETHODS AND MATERIALSnWe analyzed breath-hold images at extreme tidal volumes of 23 patients with 30 MPN treated with stereotactic ablative radiotherapy. Deformable image registration (DIR) was applied to the breath-hold images to determine the volumes of the MPNs and a ring of surrounding lung tissue (ring) in each state. MPNs were also manually delineated on deep inhale and exhale images by two observers. Volumes were compared between observers and DIR by Dice similarity. Elasticity was defined as the absolute value of the volume ratio of the MPN minus one normalized to that of the ring.nnnRESULTSnFor all 30 tumors the Dice coefficient was 0.79±0.07 and 0.79±0.06 between DIR with observers 1 and 2, respectively, close to the inter-observer Dice value, 0.81±0.1. The elasticity of MPNs was 1.24±0.26, demonstrating that volume change of the MPN was less than that of the surrounding lung.nnnCONCLUSIONnWe developed a noninvasive CT elastometry method based on DIR that measures the elasticity of biopsy-proven MPN. Our future direction would be to develop this method to distinguish malignant from benign nodules.

TU-A-12A-02: Novel Lung Ventilation Imaging with Single Energy CT After Single Inhalation of Xenon: Comparison with SPECT Ventilation Images

PURPOSEnWe propose a novel lung functional imaging method to determine the spatial distribution of xenon (Xe) gas in a single inhalation as a measure of regional ventilation. We compare Xe-CT ventilation to single-photon emission CT (SPECT) ventilation, which is the current clinical reference. Regional lung ventilation information may be useful for the diagnosis and monitoring of pulmonary diseases such as COPD, radiotherapy planning, and assessing the progression of toxicity after radiation therapy.nnnMETHODSnIn an IRB-approved clinical study, Xe-CT and SPECT ventilation scans were acquired for three patients including one patient with severe emphysema and two lung cancer patients treated with radiotherapy. For Xe- CT, we acquired two breath-hold single energy CT images of the entire lung with inspiration of 100% O2 and a mixture of 70% Xe and 30% O2, respectively. A video biofeedback system was used to achieve reproducible breath-holds. We used deformable image registration to align the breathhold images with each other to accurately subtract them, producing a map of the distribution of Xe as a surrogate of lung ventilation. We divided each lung into twelve parts and correlated the Hounsfield unit (HU) enhancement at each part with the SPECT ventilation count of the corresponding part of the lung.nnnRESULTSnThe mean of the Pearson linear correlation coefficient values between the Xe-CT and ventilation SPECT count for all three patients were 0.62 (p<0.01). The Xe-CT image had a higher resolution than SPECT, and did not show central airway deposition artifacts that were present in the SPECT image.nnnCONCLUSIONnWe developed a rapid, safe, clinically practical, and potentially widely accessible method for regional lung functional imaging. We demonstrated strong correlations between the Xe-CT ventilation image and SPECT ventilation image as the clinical reference. This ongoing study will investigate more patients to confirm this finding.

Strain as a novel index of regional pulmonary function from thoracic 4D CT images: in-vivo validation with tomographic SPECT ventilation and perfusion

Since many diseases or injuries can cause biomechanical or structural property changes that can alter lung function, there is great interest in measuring regional lung function by measurement of regional mechanical changes. To date, the most prevalent approach for assessing regional lung function from 4-D X-ray CT data has been a measure of Jacobian of deformation. However, although the Jacobian describes regional volume changes of the lung during deformation, it lacks any consideration of directional changes of local compressions and expansions during respiration. Herein, we propose the use of strain as a measure of regional lung function from 4-D thoracic CT and we perform correlation of principal strains of calculated deformation by s recently proposed 3-D optical flow technique (MOFID) computed from radiotherapy treatment planning 4-D X-ray CT data sets collected in seven subjects suffering from non-small cell primary lung cancer. In addition to 4-D CT data, both SPECT ventilation (VSPECT), and SPECT perfusion (QSPECT) data were acquired in all subjects. For each subject, we performed voxel-wise statistical correlation of the Jacobian as well as principal strains of deformation (CT-derived pulmonary function images) with both ventilation and perfusion SPECT. For all subjects, the maximum principal strain resulted in a higher correlation with both SPECT ventilation and SPECT perfusion than other indices including the previously established Jacobian metric.

Dynamic CT imaging of volumetric changes in pulmonary nodules correlates with physical measurements of stiffness

BACKGROUND AND PURPOSEnA major challenge in CT screening for lung cancer is limited specificity when distinguishing between malignant and non-malignant pulmonary nodules (PN). Malignant nodules have different mechanical properties and tissue characteristics (stiffness) from non-malignant nodules. This study seeks to improve CT specificity by demonstrating in rats that measurements of volumetric ratios in PNs with varying composition can be determined by respiratory-gated dynamic CT imaging and that these ratios correlate with direct physical measurements of PN stiffness.nnnMETHODS AND MATERIALSnRespiratory-gated MicroCT images acquired at extreme tidal volumes of 9 rats with PNs from talc, matrigel and A549 human lung carcinoma were analyzed and their volumetric ratios (δ) derived. PN stiffness was determined by measuring the Youngs modulus using atomic force microscopy (AFM) for each nodule excised immediately after MicroCT imaging.nnnRESULTSnThere was significant correlation (p=0.0002) between PN volumetric ratios determined by respiratory-gated CT imaging and the physical stiffness of the PNs determined from AFM measurements.nnnCONCLUSIONnWe demonstrated proof of concept that PN volume changes measured non-invasively correlate with direct physical measurements of stiffness. These results may translate clinically into a means of improving the specificity of CT screening for lung cancer and/or improving individual prognostic assessments based on lung tumor stiffness.

Comparison of indices of regional lung function from 4-D X-ray CT: Jacobian vs. strain of deformation

In the literature, a widely adopted approach for assessing the regional lung function in patients undergoing radiation therapy for lung cancer from 4-D X-ray CT data is the Jacobian of deformation. The Jacobian which describes regional lung volume changes however lacks consideration of directional length changes during respiration. Previously, we proposed the use of strain for measurement of regional deformation in the Lung [1]. In this paper, we perform physiologic validation of lung strain and compare the results with those from the Jacobian measure. Lung deformation fields were computed through application of a recently proposed 3-D optical flow technique (MOFID) [2] to 4-D X-ray CT data sets collected in seven subjects diagnosed with non-small cell primary lung cancer. In addition to 4-D CT data, both SPECT ventilation (VSPECT), and SPECT perfusion (QSPECT) data were acquired in all subjects. For each case, voxel-wise statistical correlation of the Jacobian as well as principal strains of deformation (CT-derived pulmonary function images) with both ventilation and perfusion SPECT was performed. The results indicate that the maximum principal strain has a higher correlation with both SPECT ventilation and SPECT perfusion than other indices including the Jacobian.

A Feasibility Study of Single-inhalation, Single-energy Xenon-enhanced CT for High-resolution Imaging of Regional Lung Ventilation in Humans

RATIONALE AND OBJECTIVESnThe objective of this study was to assess the feasibility of single-inhalation xenon-enhanced computed tomography (XeCT) to provide clinically practical, high-resolution pulmonary ventilation imaging to clinics with access to only a single-energy computed tomography scanner, and to reduce the subjects overall exposure to xenon by utilizing a higher (70%) concentration for a much shorter time than has been employed in prior studies.nnnMATERIALS AND METHODSnWe conducted an institutional review board-approved prospective feasibility study of XeCT for 15 patients undergoing thoracic radiotherapy. For XeCT, we acquired two breath-hold single-energy computed tomography images of the entire lung with a single inhalation each of 100% oxygen and a mixture of 70% xenon and 30% oxygen, respectively. A video biofeedback system for coached patient breathing was used to achieve reproducible breath holds. We assessed the technical success of XeCT acquisition and side effects. We then used deformable image registration to align the breath-hold images with each other to accurately subtract them, producing a map of lung xenon distribution. Additionally, we acquired ventilation single-photon emission computed tomography-computed tomography (V-SPECT-CT) images for 11 of the 15 patients. For a comparative analysis, we partitioned each lung into 12 sectors, calculated the xenon concentration from the Hounsfield unit enhancement in each sector, and then correlated this with the corresponding V-SPECT-CT counts.nnnRESULTSnXeCT scans were tolerated well overall, with a mild (grade 1) dizziness as the only side effect in 5 of the 15 patients. Technical failures in five patients occurred because of inaccurate breathing synchronization with xenon gas delivery, leaving seven patients analyzable for XeCT and single-photon emission computed tomography correlation. Sector-wise correlations were strong (Spearman coefficient >0.75, Pearson coefficient >0.65, P value <.002) for two patients for whom ventilation deficits were visibly pronounced in both scans. Correlations were nonsignificant for the remaining five who had more homogeneous XeCT ventilation maps, as well as strong V-SPECT-CT imaging artifacts attributable to airway deposition of the aerosolized imaging agent. Qualitatively, XeCT demonstrated higher resolution and no central airway deposition artifacts compared to V-SPECT-CT.nnnCONCLUSIONSnIn this pilot study, single-breath XeCT ventilation imaging was generally feasible for patients undergoing thoracic radiotherapy, using an imaging protocol that is clinically practical and potentially widely available. In the future, the xenon delivery failures can be addressed by straightforward technical improvements to the patient biofeedback coaching system.

SU-F-207-13: Comparison of Four Dimensional Computed Tomography (4D CT) Versus Breath Hold Images to Determine Pulmonary Nodule Elasticity

Purpose: Elasticity may distinguish malignant from benign pulmonary nodules. To compare determining of malignant pulmonary nodule (MPN) elasticity from four dimensional computed tomography (4D CT) images versus inhale/exhale breath-hold CT images. Methods: We analyzed phase 00 and 50 of 4D CT and deep inhale and natural exhale of breath-hold CT images of 30 MPN treated with stereotactic ablative radiotherapy (SABR). The radius of the smallest MPN was 0.3 cm while the biggest one was 2.1 cm. An intensity based deformable image registration (DIR) workflow was applied to the 4D CT and breath-hold images to determine the volumes of the MPNs and a 1 cm ring of surrounding lung tissue (ring) in each state. Next, an elasticity parameter was derived by calculating the ratio of the volume changes of MPN (exhale:inhale or phase50:phase00) to that of a 1 cm ring of lung tissue surrounding the MPN. The proposed formulation of elasticity enables us to compare volume changes of two different MPN in two different locations of lung. Results: The calculated volume ratio of MPNs from 4D CT (phase50:phase00) and breath-hold images (exhale:inhale) was 1.00±0.23 and 0.95±0.11, respectively. It shows the stiffness of MPN and comparably bigger volume changes of MPN in breath-hold images because of the deeper degree of inhalation. The calculated elasticity of MPNs from 4D CT and breath-hold images was 1.12±0.22 and 1.23±0.26, respectively. For five patients who have had two MPN in their lung, calculated elasticity of tumor A and tumor B follows same trend in both 4D CT and breath-hold images. Conclusion: We showed that 4D CT and breath-hold images are comparable in the ability to calculate the elasticity of MPN. This study has been supported by Department of Defense LCRP 2011 #W81XWH-12-1-0286.

WE‐C‐103‐08: Automated Tool for Determining Pulmonary Nodule Elasticity to Distinguish Malignant Nodules

PURPOSEnTo develop and validate an automated method of determining pulmonary nodule (PN) elasticity against a manual contouring method, and preliminarily assess its ability to distinguish malignant tissue by comparing the elasticities of malignant PNs treated with stereotactic ablative radiotherapy (SABR) with those of the lung.nnnMETHODSnWe analyzed breath-hold images of 30 patients with malignant PNs who underwent SABR in our department. A parametric nonrigid transformation model based on multilevel B-spline guided by Sum of Squared Differences similarity metric was applied on breath-hold images to determine the deformation map. The Jacobian of the calculated deformation map, which is directly related to the volume changes between the two respiratory phases, was calculated. Next, elasticity parameter will be derived by calculating the ratio of the Jacobian of the PN to the Jacobian of a 1cm region of lung tissue surrounding the tumor (E-ROI) as well as the Jacobian of the whole lung (E-Lung).nnnRESULTSnFor the first group of 15 patients we evaluated the volumetric changes of PNs and the lung from the maximum exhale phase to the maximum inhale phase, whereas the reverse was done for the second group of 15 patients. For the first group, mean and standard deviation for E-ROI and E-Lung were 0.91±0.09 and 0.86±0.18, respectively, which was verified by the manual method. For the second group, E-ROI and E-Lung were 1.34±0.27 and 1.57±0.51, respectively. These results demonstrate that the elasticity of the PNs was less than that of the surrounding lung (p<0.0037).nnnCONCLUSIONnWe developed an automated tool to determine the elasticity of PNs based on deformable image registration of breath-hold images. The tool was validated against manual contouring. Preliminarily, PN elastometry distinguishes proven malignant PNs from normal tissue of lung, suggesting its potential utility as a non-invasive diagnostic tool to differentiate malignant from benign PN. This Study is suuported by DoD LCRP 2011, Grant# W81XWH-12-1-0286.