Amir M. Owrangi

Hyperpolarized 3He and 129Xe MR Imaging in Healthy Volunteers and Patients with Chronic Obstructive Pulmonary Disease

PURPOSE To quantitatively compare hyperpolarized helium 3 (3He) and xenon 129 (129Xe) magnetic resonance (MR) images obtained within 5 minutes in healthy volunteers and patients with chronic obstructive pulmonary disease (COPD) and to evaluate the correlations between 3He and 129Xe MR imaging measurements and those from spirometry and plethysmography. MATERIALS AND METHODS This study was approved by an ethics board and compliant with HIPAA. Written informed consent was obtained from all subjects. Eight healthy volunteers and 10 patients with COPD underwent MR imaging, spirometry, and plethysmography. Ventilation defect percentages (VDPs) at 3He and 129Xe imaging were obtained by using semiautomated segmentation. Apparent diffusion coefficients (ADCs) were calculated from 3He (b=1.6 sec/cm2) and 129Xe (b=12 sec/cm2) diffusion-weighted images. VDPs at hyperpolarized 3He and 129Xe imaging were compared with a two-tailed Wilcoxon signed rank test and analysis of variance; Pearson correlation coefficients were used to evaluate the relationships among measurements. RESULTS 129Xe VDP was significantly greater than 3He VDP for patients with COPD (P<.0001) but not for healthy volunteers (P=.35), although 3He and 129Xe VDPs showed a significant correlation for all subjects (r=0.91, P<.0001). The forced expiratory volume in 1 second (FEV1) showed a similar and significant correlation with 3He VDP (r=-0.84, P<.0001) and 129Xe VDP (r=-0.89, P<.0001), although the correlation between the FEV1/forced vital capacity (FVC) ratio and 129Xe VDP (r=-0.95, P<.0001) was significantly greater (P=.01) than that for FEV1/FVC and 3He VDP (r=-0.84, P<.0001). A significant correlation was also observed for 3He and 129Xe ADC (r=0.97, P<.0001); 129Xe ADC was significantly correlated with diffusing capacity of lung for carbon monoxide (r=-0.79, P=.03) and computed tomographic emphysema measurements (areas with attenuation values in the 15th percentile: r=-0.91, P=.0003; relative areas with attenuation values of less than -950 HU: r=0.87, P=.001). CONCLUSION In patients with COPD, the VDP obtained with hyperpolarized 29Xe MR imaging was significantly greater than that with 3He MR imaging, suggesting incomplete or delayed filling of lung regions that may be related to the different properties of 129Xe gas and physiologic and/or anatomic abnormalities in COPD.

Pulmonary ventilation visualized using hyperpolarized helium-3 and xenon-129 magnetic resonance imaging: differences in COPD and relationship to emphysema

In subjects with chronic obstructive pulmonary disease (COPD), hyperpolarized xenon-129 ((129)Xe) magnetic resonance imaging (MRI) reveals significantly greater ventilation defects than hyperpolarized helium-3 ((3)He) MRI. The physiological and/or morphological determinants of ventilation defects and the differences observed between hyperpolarized (3)He and (129)Xe MRI are not yet understood. Here we aimed to determine the structural basis for the differences in ventilation observed between (3)He and (129)Xe MRI in subjects with COPD using apparent diffusion coefficients (ADC) and computed tomography (CT). Ten COPD ex-smokers provided written, informed consent and underwent MRI, CT, spirometry, and plethysmography. (3)He and (129)Xe MRI ventilation volume was generated using semiautomated segmentation, and ADC maps were registered to generate ADC values for lung regions of interest ventilated by both gases (ADCHX) and by (3)He gas only (ADCHO). CT wall area percentage and the lowest 15th percentile point of the CT lung density histogram (HU15%) were also evaluated. For lung regions accessed by (3)He gas only, mean (3)He ADCHO was significantly greater than for regions accessed by both gases (ADCHO = 0.503 ± 0.119 cm(2)/s, ADCHX = 0.470 ± 0.125 cm(2)/s, P < 0.0001). The difference between (3)He and (129)Xe ventilation volume was significantly correlated with CT HU15% (r = -65, P = 0.04) and (3)He ADCHO (r = 0.70, P = 0.02), but not CT wall area percentage (r = -0.34, P = 0.33). In conclusion, in this small study in COPD subjects, we observed significantly decreased (129)Xe MRI ventilation compared with (3)He MRI, and these regions of decreased (129)Xe ventilation were spatially and significantly correlated with regions of increased pulmonary emphysema, but not airway wall thickness.

On the role of abnormal DL CO in ex-smokers without airflow limitation: symptoms, exercise capacity and hyperpolarised helium-3 MRI

Background The functional effects of abnormal diffusing capacity for carbon monoxide (DLCO) in ex-smokers without chronic obstructive pulmonary disease (COPD) are not well understood. Objective We aimed to evaluate and compare well established clinical, physiological and emerging imaging measurements in ex-smokers with normal spirometry and abnormal DLCO with a group of ex-smokers with normal spirometry and DLCO and ex-smokers with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I COPD. Methods We enrolled 38 ex-smokers and 15 subjects with stage I COPD who underwent spirometry, plethysmography, St Georges Respiratory Questionnaire (SGRQ), 6 min Walk Test (6MWT), x-ray CT and hyperpolarised helium-3 (3He) MRI. The 6MWT distance (6MWD), SGRQ scores, 3He MRI apparent diffusion coefficients (ADC) and CT attenuation values below −950 HU (RA950) were evaluated. Results Of 38 ex-smokers without COPD, 19 subjects had abnormal DLCO with significantly worse ADC (p=0.01), 6MWD (p=0.008) and SGRQ (p=0.01) but not RA950 (p=0.53) compared with 19 ex-smokers with normal DLCO. Stage I COPD subjects showed significantly worse ADC (p=0.02), RA950 (p=0.0008) and 6MWD (p=0.005), but not SGRQ (p=0.59) compared with subjects with abnormal DLCO. There was a significant correlation for 3He ADC with SGRQ (r=0.34, p=0.02) and 6MWD (r=−0.51, p=0.0002). Conclusions In ex-smokers with normal spirometry and CT but abnormal DLCO, there were significantly worse symptoms, 6MWD and 3He ADC compared with ex-smokers with normal DLCO, providing evidence of the impact of mild or early stage emphysema and a better understanding of abnormal DLCO and hyperpolarised 3He MRI in ex-smokers without COPD.

Hyperpolarized 3He and 129Xe magnetic resonance imaging apparent diffusion coefficients: physiological relevance in older never‐ and ex‐smokers

Noble gas pulmonary magnetic resonance imaging (MRI) is transitioning away from 3He to 129Xe gas, but the physiological/clinical relevance of 129Xe apparent diffusion coefficient (ADC) parenchyma measurements is not well understood. Therefore, our objective was to generate 129Xe MRI ADC for comparison with 3He ADC and with well‐established measurements of alveolar structure and function in older never‐smokers and ex‐smokers with chronic obstructive pulmonary disease (COPD). In four never‐smokers and 10 COPD ex‐smokers, 3He (b = 1.6 sec/cm2) and 129Xe (b = 12, 20, and 30 sec/cm2) ADC, computed tomography (CT) density‐threshold measurements, and the diffusing capacity for carbon monoxide (DLCO) were measured. To understand regional differences, the anterior–posterior (APG) and superior–inferior (∆SI) ADC differences were evaluated. Compared to never‐smokers, COPD ex‐smokers showed greater 3He ADC (P = 0.006), 129Xe ADCb12 (P = 0.006), and ADCb20 (P = 0.006), but not for ADCb30 (P > 0.05). Never‐smokers and COPD ex‐smokers had significantly different APG for 3He ADC (P = 0.02), 129Xe ADCb12 (P = 0.006), and ADCb20 (P = 0.01), but not for ADCb30 (P > 0.05). ∆SI for never‐ and ex‐smokers was significantly different for 3He ADC (P = 0.046), but not for 129Xe ADC (P > 0.05). There were strong correlations for DLCO with 3He ADC and 129Xe ADCb12 (both r = −0.95, P < 0.05); in a multivariate model 129Xe ADCb12 was the only significant predictor of DLCO (P = 0.049). For COPD ex‐smokers, CT relative area <−950 HU (RA950) correlated with 3He ADC (r = 0.90, P = 0.008) and 129Xe ADCb12 (r = 0.85, P = 0.03). In conclusion, while 129Xe ADCb30 may be appropriate for evaluating subclinical or mild emphysema, in this small group of never‐smokers and ex‐smokers with moderate‐to‐severe emphysema, 129Xe ADCb12 provided a physiologically appropriate estimate of gas exchange abnormalities and alveolar microstructure.

Three-dimensional lung tumor segmentation from x-ray computed tomography using sparse field active models.

PURPOSE Manual segmentation of lung tumors is observer dependent and time-consuming but an important component of radiology and radiation oncology workflow. The objective of this study was to generate an automated lung tumor measurement tool for segmentation of pulmonary metastatic tumors from x-ray computed tomography (CT) images to improve reproducibility and decrease the time required to segment tumor boundaries. METHODS The authors developed an automated lung tumor segmentation algorithm for volumetric image analysis of chest CT images using shape constrained Otsu multithresholding (SCOMT) and sparse field active surface (SFAS) algorithms. The observer was required to select the tumor center and the SCOMT algorithm subsequently created an initial surface that was deformed using level set SFAS to minimize the total energy consisting of mean separation, edge, partial volume, rolling, distribution, background, shape, volume, smoothness, and curvature energies. RESULTS The proposed segmentation algorithm was compared to manual segmentation whereby 21 tumors were evaluated using one-dimensional (1D) response evaluation criteria in solid tumors (RECIST), two-dimensional (2D) World Health Organization (WHO), and 3D volume measurements. Linear regression goodness-of-fit measures (r(2) = 0.63, p < 0.0001; r(2) = 0.87, p < 0.0001; and r(2) = 0.96, p < 0.0001), and Pearson correlation coefficients (r = 0.79, p < 0.0001; r = 0.93, p < 0.0001; and r = 0.98, p < 0.0001) for 1D, 2D, and 3D measurements, respectively, showed significant correlations between manual and algorithm results. Intra-observer intraclass correlation coefficients (ICC) demonstrated high reproducibility for algorithm (0.989-0.995, 0.996-0.997, and 0.999-0.999) and manual measurements (0.975-0.993, 0.985-0.993, and 0.980-0.992) for 1D, 2D, and 3D measurements, respectively. The intra-observer coefficient of variation (CV%) was low for algorithm (3.09%-4.67%, 4.85%-5.84%, and 5.65%-5.88%) and manual observers (4.20%-6.61%, 8.14%-9.57%, and 14.57%-21.61%) for 1D, 2D, and 3D measurements, respectively. CONCLUSIONS The authors developed an automated segmentation algorithm requiring only that the operator select the tumor to measure pulmonary metastatic tumors in 1D, 2D, and 3D. Algorithm and manual measurements were significantly correlated. Since the algorithm segmentation involves selection of a single seed point, it resulted in reduced intra-observer variability and decreased time, for making the measurements.

Computed tomography density histogram analysis to evaluate pulmonary emphysema in ex-smokers.

RATIONALE AND OBJECTIVES High-resolution computed tomography (CT) measurements of emphysema typically use Hounsfield unit (HU) density histogram thresholds or observer scores based on regions of low x-ray attenuation. Our objective was to develop an automated measurement of emphysema using principal component analysis (PCA) of the CT density histogram. MATERIALS AND METHODS Ninety-seven ex-smokers, including 53 subjects with chronic obstructive pulmonary disease (COPD) and 44 asymptomatic subjects (AEs), provided written informed consent to imaging as well as plethysmography and spirometry. We applied PCA to the CT density histogram to generate whole lung and regional density histogram principal components including the first and second components and the sum of both principal components (density histogram principal component score [DHPCS]). Significant relationships for DHPCS with single HU thresholds, pulmonary function measurements, an experts emphysema score, and hyperpolarized (3)He magnetic resonance imaging apparent diffusion coefficients (ADCs) were determined using linear regression and Pearson coefficients. Receiver operator characteristics analysis was performed using forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) as the independent diagnostic. RESULTS There was a significant difference (P < .0001) between AE and COPD subjects for DHPCS; FEV1/FVC; diffusing capacity of lung for carbon monoxide%predicted; attenuation values below -950, -910, and -856 HU; and (3)He ADCs. There were significant correlations for DHPCS with FEV1/FVC (r = -0.85, P < .0001); diffusing capacity of lung for carbon monoxide%predicted (r = -0.67, P < .0001); attenuation values below -950/-910/-856 HU (r = 0.93/0.96/0.76, P < .0001); and (3)He ADCs (r = 0.85, P < .0001). Receiver operator characteristics analysis showed a 91% classification rate for DHPCS. CONCLUSIONS We generated an automated emphysema score using PCA of the CT density histogram with a 91% COPD classification rate that showed strong and significant correlations with pulmonary function tests, single HU thresholds, and (3)He magnetic resonance imaging ADCs.

Quantitative 1H and hyperpolarized 3He magnetic resonance imaging: Comparison in chronic obstructive pulmonary disease and healthy never-smokers

OBJECTIVE The aim of this study was to quantitatively evaluate the relationship between short echo time pulmonary (1)H magnetic resonance imaging (MRI) signal intensity (SI) and (3)He MRI apparent diffusion coefficients (ADC), high-resolution computed tomography (CT) measurements of emphysema, and pulmonary function measurements. MATERIALS AND METHODS Nine healthy never-smokers and 11 COPD subjects underwent same-day plethysmography, spirometry, short echo time ((TE)=1.2ms) (1)H and diffusion-weighted hyperpolarized (3)He MRI (b=1.6s/cm(2)) at 3.0T. In addition, for COPD subjects only, CT densitometry was also performed. RESULTS Mean (1)H SI was significantly greater for never-smokers (12.1 ± 1.1 arbitrary units (AU)) compared to COPD subjects (10.9 ± 1.3 AU, p=0.04). The (1)H SI AP-gradient was also significantly greater for never-smokers (0.40 AU/cm, R(2)=0.94) compared to COPD subjects (0.29 AU/cm, R(2)=0.968, p=0.05). There was a significant correlation between (1)H SI and (3)He ADC (r=-0.58, p=0.008) and significant correlations between (1)H MR SI and CT measurements of emphysema (RA950, r=-0.69, p=0.02 and HU15, r=0.66, p=0.03). CONCLUSIONS The significant and moderately strong relationship between (1)H SI and (3)He ADC, as well as between (1)H SI and CT measurements of emphysema suggests that these imaging methods and measurements may be quantifying similar tissue changes in COPD and that pulmonary (1)H SI may be used to monitor emphysema as a complement to CT and noble gas MRI.

Automated beam model optimization

PURPOSE The beam model in a three dimensional treatment planning system (TPS) defines virtually the mechanical and dosimetric characteristics of a treatment unit. The manual optimization of a beam model during commissioning can be a time consuming task due to its iterative nature. Furthermore, the quality of the beam model commissioning depends on the users ability to manage multiple parameters and assess their impact on the agreement between measured and calculated dose. The objective of this work is to develop and validate the performance of an automated beam model optimization system (ABMOS) based on intensity modulated radiotherapy (IMRT) beam measurements to improve beam model accuracy while streamlining the commissioning process. METHODS The ABMOS was developed to adjust selected TPS beam model parameters iteratively to maximize the agreement between measured and calculated 2D dose maps obtained for an IMRT beam pattern. A 2D diode array with high spatial resolution detectors was used to sample the entire IMRT beam pattern in a single dose measurement. The use of an IMRT beam pattern with large number of monitor units was selected to highlight the difference between planned and delivered dose and improve the signal to noise ratio in the low dose regions. ABMOS was applied to the optimization of a beam model for an Elekta Synergy S treatment unit. The optimized beam model was validated for two anatomical sites (25 paraspinal and 25 prostate cases) using two independent patient-specific IMRT quality control (QC) methods based on ion chamber and 2D diode array measurements, respectively. The conventional approach of comparing calculated and measured beam profiles and percent-depth dose curves was also used to assess improvement in beam model after ABMOS optimization. Elements of statistical process control were applied to the process of patient-specific QC performed with the ion chamber and the 2D array to complement the model comparison. RESULTS After beam model optimization with ABMOS, improvement in planned to delivered dose agreement was demonstrated with both patient-specific IMRT QC methods and the calculated to measured profile comparison. In terms of ion chamber measurements, the largest improvement was observed for the paraspinal cases with the mean measured to calculated dose difference at the low dose points decreasing from - 13.8% to 2.0% with the optimized beam model. The 2D diode array patient-specific QC also demonstrated clearly the improvement in beam model for both paraspinal and prostate cases with, on average, more than 96% of the diodes satisfying tolerances of 3% of dose difference or 2 mm of distance to agreement after ABMOS optimization. The capability index (C(pk)) for both patient-specific QC methods also increased with the optimized beam model. CONCLUSIONS In this work, ABMOS was developed to use 2D diode array measurements of an IMRT beam pattern for the automated multivariable optimization of a TPS beam model. Based on the observed improvements in patient-specific QC results for 25 paraspinal and 25 prostate plans, optimization of the remaining clinical beam models using ABMOS is now ongoing in the institution.

Depth dependence of electron backscatter: An energy spectral and dosimetry study using Monte Carlo simulation

This study investigated the depth dependence of electron backscatter from a layer of lead (Pb) for clinical electron beams. The change in the electron backscatter with variation in the water depth above the Pb was determined. Electron energy spectra and relative depth doses as a function of depth in water over the Pb layer were calculated using a Monte Carlo simulation and studied. Phase-space files for 4 and 9 MeV electron beams (10 x 10 cm2 applicator and cutout) based on the Varian 21 EX linear accelerator were generated using the EGSnrc-based BEAMNRC code. 3 mm of Pb, at depths of 0.5 and 1 cm in water, was irradiated with electrons. The source-to-surface distance is equal to 100 cm. Electron energy spectra and relative depth doses with and without the presence of the Pb layer at different depths in water were determined using the BEAMNRC code. For the 4 MeV electron energy spectra at a depth of 0.5 cm in water, electron backscatter was found to originate at the Pb-water interface and extend to 0.5 cm above the Pb insert. However, at a depth of 1 cm in water, electron backscatter almost disappeared at 0.5 and 1 cm above th ePb insert. This is due to the increased attenuation of the incident 4 MeV electron beam in a thicker layer of water as well as increased attenuation of the electron backscatter above the Pb. This resulted in a 23% decrease in relative dose at a measurement point of 0.5 cm depth, when the depth of the Pb insert was changed from 1 to 0.5 cm. For the electron energy spectra of the 9 MeV beams with a 0.5 cm depth of water, only a small amount of electron backscatter was observed. However, more electron backscatter was found when the water depth was increased to 1 cm. This is because the electron beam energy was decreased more due to the increase in attenuation from the increased depth of water compared to 0.5 cm. Since the electron energy spectrum and relative depth dose above the Pb layer vary with depth of water on top of the Pb, the electron backscatter depends significantly on the thickness of water, or water equivalent bolus, or critical tissue over the Pb shield in electron radiotherapy.

Semi-automated scoring of pulmonary emphysema from X-ray CT: Trainee reproducibility and accuracy

OBJECTIVE We developed a semi-automated tool to quantify emphysema from thoracic X-ray multi-detector (64-slice) computed tomography (CT) for training purposes and multi-reader studies. MATERIALS AND METHODS Thoracic X-ray CT was acquired in 93 ex-smokers, who were evaluated by six trainees with little or no expertise (trainees) and a single experienced thoracic radiologist (expert). A graphic user interface (GUI) was developed for emphysema quantification based on the percentile of lung where a score of 0=no abnormalities, 1=1-25%, 2=26-50%, 3=51-75% and 4=76-100% for each lung side/slice. Trainees blinded to subject characteristics scored randomized images twice; accuracy was determined by comparison to expert scores, density histogram 15th percentile (HU 15), relative area at -950 HU (RA(950)), low attenuation clusters at -950 HU (LAC(950)), -856 HU (LAC(856)) and the diffusing capacity for carbon monoxide (DL(CO%pred)). Intra- and inter-observer reproducibility was evaluated using coefficients-of-variation (COV), intra-class (ICC) and Pearson correlations. RESULTS Trainee-expert correlations were significant (r=0.85-0.97, p<0.0001) and a significant trainee bias (0.15 ± 0.22) was observed. Emphysema score was correlated with RA(950) (r=0.88, p<0.0001), HU 15 (r=-0.77, p<0.0001), LAC(950) (r=0.76, p<0.0001), LAC(856) (r=0.74, p=0.0001) and DLCO%pred (r=-0.71, p<0.0001). Intra-observer reproducibility (COV=4-27%; ICC=0.75-0.94) was moderate to high for trainees; intra- and inter-observer COV were negatively and non-linearly correlated with emphysema score. CONCLUSION We developed a GUI for rapid and interactive emphysema scoring that allows for comparison of multiple readers with clinical and radiological standards.