Evaluation of Radiation Dose Effect on Lung Function Using Iodine Maps Derived From Dual-Energy Computed Tomography.

PURPOSE: There is interest in using dual-energy computed tomography (DECT) to evaluate organ function before and after radiation therapy (RT). The purpose of this study (trial identifier: NCT04863027) is to assess longitudinal changes in lung perfusion using iodine maps derived from DECT in patients with lung cancer treated with conventional or stereotactic RT. METHODS AND MATERIALS: For 48 prospectively enrolled patients with lung cancer, a contrast-enhanced DECT using a dual-source CT simulator was acquired pretreatment and at 6 and 12 months posttreatment. Pulmonary functions tests (PFT) were obtained at baseline and at 6 and 12 months posttreatment. Iodine maps were extracted from the DECT images using a previously described 2-material decomposition framework. Longitudinal iodine maps were normalized using a reference region defined as all voxels with perfusion in the top 10% outside of the 5 Gy isodose volume. Normalized functional responses (NFR) were calculated for 3 dose ranges: <5, 5 to 20, and >20 Gy. Mixed model analysis was used to assess the correlation between dose metrics and NFR. Pearson correlation was used to assess if NFRs were correlated with PFT changes. RESULTS: Out of the 48 patients, 21 (44%) were treated with stereotactic body RT and 27 (56%) were treated with conventionally fractionated intensity-modulated RT. Thirty-one out of these 48 patients were ultimately included in data analysis. It was found that NFR is linearly correlated with dose (P < .001) for both groups. The number of months elapsed post-RT was also found to correlate with NFR (P = .029), although this correlation was not observed for the stereotactic body RT subgroup. The NFR was not found to correlate with PFT changes. CONCLUSIONS: DECT-derived iodine maps are a promising method for detailed anatomic evaluation of radiation effect on lung function, including potentially subclinical changes.

Eliminating computed tomography imaging artifacts through 3D printed radiotherapy head supports.

PURPOSE: The geometry of an immobilization device such as a headrest can cause undesired computed tomography (CT) artifacts that may affect both volume definition and dosimetry in radiotherapy of the brain. The purpose of this work was to reduce CT artifacts caused by a standard hard plastic hollow radiotherapy headrest. This was to be achieved through design and prototyping of a custom-made head support. METHODS: A series of CT scans were acquired of both a water phantom and an anthropomorphic head phantom which were resting on custom-made three-dimensional (3D) printed supports. All custom-made supports were made of polylactic acid (PLA) plastic filament and printed by fused deposition modeling (FDM) 3D printing technology. Initial designs were studied with a water phantom using a simplified support with straight and curved shapes both at the edges and as infill patterns. Imaging of a 3D printed clinical prototype was then compared to our standard headrest using an anthropomorphic head phantom. RESULTS: The presence of dark streaks inside both phantoms was seen on the CT images for headrests involving supports with straight shapes at the edges or as infill patterns. Such artifacts were ascribed to the exponential edge-gradient effect (EEGE). No such artifact was observed when the support was designed with a combination of curved edges and infill patterns. CONCLUSION: When developing immobilization accessories for use in CT scanners, more attention could be paid to artifact attenuating design elements. This work illustrates the usefulness of 3D printing in prototyping radiotherapy accessories and solving concrete clinical problems.

Electron density and effective atomic number estimation in a maximum a posteriori framework for dual-energy computed tomography.

PURPOSE: The stoichiometric calibration method for dual-energy CT (DECT) proposed by Bourque et al. (Phys Med Biol. 59:2059; 2014), which provides estimators of the electron density and the effective atomic number, is adapted to a maximum a posteriori (MAP) framework to increase the model's robustness to noise and biases in CT data, specifically for human tissues. Robust physical parameter estimation from noisy DECT scans is required to maximize the precision of quantities used for radiotherapy treatment planning such as the proton stopping power (SPR). METHODS: Estimation of electron density and effective atomic number is performed by constraining their variation to the natural range of values expected for human tissues, while maximizing attenuation data fidelity. The MAP framework is first compared against the original method using theoretical CT numbers with Gaussian noise. The quantitative accuracy of the MAP framework is then validated experimentally on the Gammex 467 phantom. Then, using two clinical datasets, the advantages of the approach are experimentally evaluated, qualitatively, and quantitatively. RESULTS: The theoretical study shows that the root-mean-square error on the electron density, the effective atomic number and the SPR are, respectively, reduced from 2.3 to 1.5, 5.7 to 3.2 and 2.8 to 1.7% with the adapted framework, when analyzing soft tissues and bone together. The experimental validation study shows that the standard deviation in Gammex inserts can be reduced, on average, by factors of 1.4 (electron density), 2.7 (effective atomic number), and 1.9 (SPR), while the quantitative accuracy of the three physical parameters is preserved, on average. Evaluation on clinical datasets show apparent noise reduction in maps of all estimated physical quantities, and suggests that the MAP framework has increased robustness to beam hardening and photon starvation artifacts. Mean values for the electron density, the effective atomic number, and the SPR averaged in four uniform regions of interest (brain, muscle, adipose, and cranium), respectively, differ by 0.7, 1.8, and 0.9% between both frameworks. The standard deviation in the same regions of interest is also reduced, on average, by factors of 1.8, 6.6, and 3.2 with the MAP framework. Differences in mean value and standard deviations are statistically significant. CONCLUSION: Theoretical and experimental results suggest that the MAP framework produces more accurate and precise estimates of the electron density and SPR. Thus, the present approach limits the propagation of noise in DECT attenuation data to radiotherapy-related parameters maps such as the SPR and the electron density. Using a MAP framework with DECT for radiotherapy treatment planning can help maximizing the precision of dose calculation. The method also provides more precise estimates of the effective atomic number. The MAP methodology is presented in a general way such that it can be adapted to any DECT image-based tissue characterization method.

Dual-energy computed tomography for prediction of loco-regional recurrence after radiotherapy in larynx and hypopharynx squamous cell carcinoma.

PURPOSE: To investigate the role of quantitative pre-treatment dual-energy computed tomography (DECT) for prediction of loco-regional recurrence (LRR) in patients with larynx/hypopharynx squamous cell cancer (L/H SCC). METHODS: Patients with L/H SCC treated with curative intent loco-regional radiotherapy and that underwent treatment planning with contrast-enhanced DECT of the neck were included. Primary and nodal gross tumor volumes (GTVp and GTVn) were contoured and transferred into a Matlab® workspace. Using a two-material decomposition, GTV iodine concentration (IC) maps were obtained. Quantitative histogram statistics (maximum, mean, standard deviation, kurtosis and skewness) were retrieved from the IC maps. Cox regression analysis was conducted to determine potential predictive factors of LRR. RESULTS: Twenty-five patients, including 20 supraglottic and 5 pyriform sinus tumors were analysed. Stage I, II, III, IVa and IVb constituted 4% (1 patient), 24%, 36%, 28% and 8% of patients, respectively; 44% had concurrent chemo-radiotherapy and 28% had neodjuvant chemotherapy. Median follow-up was 21 months. Locoregional control at 1 and 2 years were 75% and 69%, respectively. For the entire cohort, GTVn volume (HR 1.177 [1.001-1.392], p = 0.05), voxel-based maximum IC of GTVp (HR 1.099 [95% CI: 1.001-1.209], p = 0.05) and IC standard deviation of GTVn (HR 9.300 [95% CI: 1.113-77.725] p = 0.04) were predictive of LRR. On subgroup analysis of patients treated with upfront radiotherapy +/- chemotherapy, both voxel-based maximum IC of GTVp (HR 1.127 [95% CI: 1.010-1.258], p = 0.05) and IC kurtosis of GTVp (HR 1.088 [95% CI: 1.014-1.166], p = 0.02) were predictive of LRR. CONCLUSION: This exploratory study suggests that pre-radiotherapy DECT-derived IC quantitative analysis of tumoral volume may help predict LRR in L/H SCC.

In a Heartbeat: An Assessment of Dynamic Dose Variation to Cardiac Structures Using Dual Source Computed Tomography.

PURPOSE: To assess radiation dose variation to the left anterior descending artery (LAD), left main coronary artery (LMCA), left ventricle (LV), and whole heart (WH) during the cardiac cycle using dual source computed tomography (DSCT). METHODS AND MATERIALS: The present prospective study included patients with left-side breast cancer planned to undergo tangential radiation therapy. An electrocardiogram-synchronized contrast-injected DSCT scan was obtained with the patient in the treatment position, in deep-inspiration breath-hold, using retrospective sequential acquisition. The WH, LV, LMCA, and proximal, middle, and distal LAD segments were contoured on each phase of the cardiac cycle. The maximum, minimum, and mean Hausdorff distance between each structure and the tangential fields was assessed in ventricular systole and diastole. Four-dimensional dose-volume histograms were used to compare the systolic and diastolic dosimetric data. RESULTS: Ten patients were enrolled. The average maximum, minimum, and mean Hausdorff distance variation from systole to diastole was ≤4 mm for the LV and LMCA and ≤3 mm for the WH and LAD segments. WH maximum dose and volume receiving 5 Gy were decreased in systole compared with diastole (42.9 Gy versus 44.5 Gy, P = .03, and 21.7 cm3 versus 27.7 cm3, P = .01), but the mean dose remained similar throughout the cycle. The maximum and mean dose to the distal LAD was 21.2 Gy versus 26.6 Gy (P = .005) and 8.6 Gy versus 13.2 Gy (P = .006) in systole versus diastole, respectively. The maximum and mean dose to the middle LAD was 18.4 Gy versus 25.1 Gy (P = .005) and 8.5 Gy versus 10.2 Gy in systole versus diastole (P = .005). The maximum dose to the LV was lower in systole than in diastole (21.5 Gy vs 26.7 Gy; P = .005). CONCLUSIONS: In addition to deep-inspiration breath-hold, systolic irradiation is associated with a reduction in dose to the LAD, LV, and WH. In addition to its potential use in radiation planning for cardiac gating, DSCT imaging can be used to help define a planning organ at risk volume for clinically important cardiac substructures.

Phase 1-2 Study of Dual-Energy Computed Tomography for Assessment of Pulmonary Function in Radiation Therapy Planning.

PURPOSE: To quantify lung function according to a dual-energy computed tomography (DECT)-derived iodine map in patients treated with radiation therapy for lung cancer, and to assess the dosimetric impact of its integration in radiation therapy planning. METHODS AND MATERIALS: Patients treated with stereotactic ablative radiation therapy for early-stage or intensity modulated radiation therapy for locally advanced lung cancer were prospectively enrolled in this study. A DECT in treatment position was obtained at time of treatment planning. The relative contribution of each voxel to the total lung function was based on iodine distribution. The composition of each voxel was determined on the basis of a 2-material decomposition. The DECT-derived lobar function was compared with single photon emission computed tomography/computed tomography (SPECT/CT). A functional map was integrated in the treatment planning system using 6 subvolumes of increasing iodine distribution levels. Percent lung volume receiving 5 Gy (V5), V20, and mean dose (MLD) to whole lungs (anatomic) versus functional lungs were compared. RESULTS: Twenty-five patients with lung cancer, including 18 patients treated with stereotactic ablative radiation therapy and 7 patients with intensity modulated radiation therapy (locally advanced), were included. Eighty-four percent had chronic obstructive pulmonary disease. Median (range) forced expiratory volume in 1 second was 62% of predicted (29%-113%), and median diffusing capacity of the lung for carbon monoxide was 56% (39%-91%). There was a strong linear correlation between DECT- and SPECT/CT-derived lobar function (Pearson coefficient correlation r=0.89, P<.00001). Mean (range) differences in V5, V20, and MLD between anatomic and functional lung volumes were 16% (0%-48%, P=.03), 5% (1%-15%, P=.12), and 15% (1%-43%, P=.047), respectively. CONCLUSIONS: Lobar function derived from a DECT iodine map correlates well with SPECT/CT, and its integration in lung treatment planning is associated with significant differences in V5 and MLD to functional lungs. Future work will involve integration of the weighted functional volume in the treatment planning system, along with integration of an iodine map for functional lung-sparing IMRT.

Assessing lung function using contrast-enhanced dual-energy computed tomography for potential applications in radiation therapy.

PURPOSE: There is an increasing interest in the evaluation of lung function from physiological images in radiation therapy treatment planning to reduce the extent of postradiation toxicities. The purpose of this work was to retrieve reliable functional information from contrast-enhanced dual-energy computed tomography (DECT) for new applications in radiation therapy. The functional information obtained by DECT is also compared with other methods using single-energy CT (SECT) and single-photon emission computed tomography (SPECT) with CT. The differential function between left and right lung, as well as between lobes is computed for all methods. METHODS: Five lung cancer patients were retrospectively selected for this study; each underwent a SPECT/CT scan and a contrast-injected DECT scan, using 100 and 140 Sn kVp. The DECT images are postprocessed into iodine concentration maps, which are further used to determine the perfused blood volume. These maps are calculated in two steps: (a) a DECT stoichiometric calibration adapted to the presence of iodine and followed by (b) a two-material decomposition technique. The functional information from SECT is assumed proportional to the HU numbers from a mixed CT image. The functional data from SPECT/CT are considered proportional to the number of counts. A radiation oncologist segmented the entire lung volume into five lobes on both mixed CT images and low-dose CT images from SPECT/CT to allow a regional comparison. The differential function for each subvolume is computed relative to the entire lung volume. RESULTS: The differential function per lobe derived from SPECT/CT correlates strongly with DECT (Pearson's coefficient r = 0.91) and moderately with SECT (r = 0.46). The differential function for the left lung shows a mean difference of 7% between SPECT/CT and DECT; and 17% between SPECT/CT and SECT. The presence of nonfunctional areas, such as localized emphysema or a lung tumor, is reflected by an intensity drop in the iodine concentration maps. Functional dose volume histograms (fDVH) are also generated for two patients as a proof of concept. CONCLUSION: The extraction of iodine concentration maps from a contrast-enhanced DECT scan is achieved to compute the differential function for each lung subvolume and good agreement is found in respect to SPECT/CT. One promising avenue in radiation therapy is to include such functional information during treatment planning dose optimization to spare functional lung tissues.

Larynx motion considerations in partial larynx volumetric modulated arc therapy for early glottic cancer.

INTRODUCTION: To assess laryngeal motion in early glottic cancer in order to determine safe margins for partial larynx volumetric modulated arc therapy (PL-VMAT), and to quantify dosimetric advantages of PL-VMAT. METHODS: This prospective study included T1-2N0 glottic cancers treated with whole larynx VMAT (WL-VMAT). Pre- and mid-treatment 4D-computed tomography (4D-CT) and dynamic magnetic resonance imaging (MRI) allowed for assessment of larynx swallowing and respiratory motion. For 10 patients with lateralized lesions, PL-VMAT plans were calculated using margins derived from 4D-CT analysis. RESULTS: Twenty patients were accrued from 2014 to 2016. Mean amplitude of larynx swallowing excursion was 23 mm and 6 mm in the superior and anterior directions, respectively. Mean respiratory motion reached 4 mm and 2 mm in superior-inferior and antero-posterior directions, respectively. Pre-treatment 4D-CT analysis identified one patient with planning CT acquired during swallowing. Mid-treatment 4D-CT revealed larynx shift relative to vertebrae in 30% of cases. PL-VMAT allowed for significant reduction of mean doses to ipsilateral carotid, contralateral carotid, thyroid gland, contralateral arytenoid and larynx. Using 8 mm internal margin for PL-VMAT, swallowing resulted in clinical target volume excursion beyond 95% isodose line during ≤1.5% of total treatment time in all patients. CONCLUSION: Although swallowing motion is rare, rapid and easily suppressed by patients, there is a risk of systematic miss-targeting if planning CT is acquired during swallowing. Larynx position shift relative to vertebrae occurs in 1/3 of patients over the course of radiotherapy. With soft-tissue image guidance and margins accounting for respiratory motion, PL-VMAT allows safe reduction of dose to organs at risk.

Analysis of Pulmonary Vein Antrums Motion with Cardiac Contraction Using Dual-Source Computed Tomography.

PURPOSE: The purpose of the study was to determine the extent of displacement of the pulmonary vein antrums resulting from the intrinsic motion of the heart using 4D cardiac dual-source computed tomography (DSCT). METHODS: Ten consecutive female patients were enrolled in this prospective planning study. In breath-hold, a contrast-injected cardiac 4-dimensional (4D) computed tomography (CT) synchronized to the electrocardiogram was obtained using a prospective sequential acquisition method including the extreme phases of systole and diastole. Right and left atrial fibrillation target volumes (CTVR and CTVL) were defined, with each target volume containing the antral regions of the superior and inferior pulmonary veins. Four points of interest were used as surrogates for the right superior and inferior pulmonary vein antrum (RSPVA and RIPVA) and the left superior and inferior pulmonary vein antrum (LSPVA and LIPVA). On our 4D post-processing workstation (MIM Maestro™, MIM Software Inc.), maximum displacement of each point of interest from diastole to systole was measured in the mediolateral (ML), anteroposterior (AP), and superoinferior (SI) directions. RESULTS: Median age of the enrolled patients was 60 years (range, 56-71 years). Within the CTVR, the mean displacements of the superior and inferior surrogates were 3 mm vs. 1 mm (p=0.002), 2 mm vs. 0 mm (p= 0.001), and 3 mm vs. 0 mm (p=0.00001), in the ML, AP, and SI directions, respectively. On the left, mean absolute displacements of the LSPVA vs. LIPVA were similar at 4 mm vs. 1 mm (p=0.0008), 2 mm vs. 0 mm (p= 0.001), and 3 mm vs. 1 mm (p=0.00001) in the ML, AP, and SI directions. CONCLUSION: When isolated from breathing, cardiac contraction is associated with minimal inferior pulmonary veins motion and modest (1-6 mm) motion of the superior veins. Target deformation was thus of a magnitude similar or greater than target motion, limiting the potential gains of cardiac tracking. Optimal strategies for cardiac radiosurgery should thus either incorporate the generation of an internal target or cardiac gating. In either case, cardiac 4D DSCT would allow for personalized margin definition.

Turn down the noise--a blinded evaluation of iterative image reconstruction in radiation therapy computed tomography simulation.

PURPOSE: The current standard reconstruction algorithm for computed tomography (CT) scans is filtered back projection. Alternative algorithms using iterative reconstruction (IR)-in our case, "sinogram affirmed iterative reconstruction"-have been increasingly implemented in diagnostic CT imaging. We studied its potential in improving radiation therapy planning images. METHODS AND MATERIALS: Raw planning CT data sets of patients from varied disease sites were reconstructed using filtered back projection and IR levels 1, 3, and 5 with equal radiation dose. For each site, 2-7 patient scans were selected; 2-3 physicians blindly evaluated the 4 3-dimensional image sets. Using a visual analogue scale, they rated the sharpness, noise, perceived ease in delineating gross tumor/clinical target volume and organs at risk, and overall appreciation of the images. Interobserver correlation was calculated with the Spearman correlation coefficient (ρ). Generalized estimating equations assessed the differences in the mean score for each criterion between reconstructions. When significant differences existed, pairwise comparisons compared the least-squares means. The preference for each reconstruction was rank ordered for each observer. The rank occurrences were computed; generalized estimating equations and pairwise comparisons were again calculated. RESULTS: Sixteen physicians reviewed 548 image sets. The sharpness had a ρ = -0.22-0.53, noise ρ = -0.34-0.38, delineating gross tumor/clinical target volume ρ = -0.28-0.53, delineating organs at risk ρ = -0.47-0.42, and overall appreciation ρ = -0.17-0.38, suggesting a low level of agreement among observers. IR 3 and 5 had consistently higher scores and ranks than filtered back projection (P = .02 and P = .015, respectively). Paradoxically, IR 5 scored both highest and worst the most frequently. IR 3 was more consistently well-ranked for all criteria. CONCLUSIONS: This report is the first to clinically evaluate IR in radiation therapy planning. When used to reduce noise in current CT simulation protocols, IR images were generally preferred. Although highly processed images polarized observers, the use of moderate IR was appreciated for most disease sites.