Adaptive Lung Radiation Therapy in the Era of Immunotherapy: A Single-Center Retrospective Study.

Purpose: Treatment for locally advanced non-small cell lung cancer consists of concurrent chemoradiation followed by immunotherapy. Though this combination has been shown to have a benefit in both progression-free survival and overall survival, treatment is often limited by the development of pneumonitis. One way to mitigate toxicity is through adaptive radiation therapy, which does not currently have a standardized implementation in clinical practice. Methods and Materials: A single-center retrospective review of patients with locally advanced stage III or oligometastatic stage IV non-small cell lung cancer who were treated with chemoradiation with concurrent or subsequent immunotherapy from 2015 to 2020 was performed. Patients were stratified based on having 1 or more offline adapted plan. The aim of this study was to evaluate the association between dose-volume histogram values and common toxicities experienced during this treatment, including pneumonitis and esophagitis. Results: Twenty-five patients were included in the final analysis: 10 with adapted plans (AP), and 15 with nonadapted plans (NAP). Mean age at onset was 74 years. The most common histology was adenocarcinoma (N = 13). Five patients experienced pneumonitis: 2 in AP and 3 in NAP. Mann-Whitney U test of gross tumor volume sizes between AP (346.2 ± 269.7 cm3) and NAP (153.1 ± 99.6 cm3) was significant (P = .019). Multiple linear regression analysis with adjustment for covariates of pneumonitis versus plan adaptation (P = .106) and esophagitis versus plan adaptation (P = .59) did not demonstrate a significant difference in toxicity between the adapted and nonadaptive patients. Conclusions: Despite similar toxicities in both groups, the gross tumor volume size in the AP was more than double compared with NAP, suggesting that adaptive techniques provide a method for patients with larger target volumes to be treated without an observed difference in pneumonitis rates. These results suggest adaptive radiation therapy may have a role in mitigating toxicity experience from chemoradiation and immunotherapy and warrants further investigation.

Combining natural and artificial intelligence for robust automatic anatomy segmentation: Application in neck and thorax auto-contouring.

BACKGROUND: Automatic segmentation of 3D objects in computed tomography (CT) is challenging. Current methods, based mainly on artificial intelligence (AI) and end-to-end deep learning (DL) networks, are weak in garnering high-level anatomic information, which leads to compromised efficiency and robustness. This can be overcome by incorporating natural intelligence (NI) into AI methods via computational models of human anatomic knowledge. PURPOSE: We formulate a hybrid intelligence (HI) approach that integrates the complementary strengths of NI and AI for organ segmentation in CT images and illustrate performance in the application of radiation therapy (RT) planning via multisite clinical evaluation. METHODS: The system employs five modules: (i) body region recognition, which automatically trims a given image to a precisely defined target body region; (ii) NI-based automatic anatomy recognition object recognition (AAR-R), which performs object recognition in the trimmed image without DL and outputs a localized fuzzy model for each object; (iii) DL-based recognition (DL-R), which refines the coarse recognition results of AAR-R and outputs a stack of 2D bounding boxes (BBs) for each object; (iv) model morphing (MM), which deforms the AAR-R fuzzy model of each object guided by the BBs output by DL-R; and (v) DL-based delineation (DL-D), which employs the object containment information provided by MM to delineate each object. NI from (ii), AI from (i), (iii), and (v), and their combination from (iv) facilitate the HI system. RESULTS: The HI system was tested on 26 organs in neck and thorax body regions on CT images obtained prospectively from 464 patients in a study involving four RT centers. Data sets from one separate independent institution involving 125 patients were employed in training/model building for each of the two body regions, whereas 104 and 110 data sets from the 4 RT centers were utilized for testing on neck and thorax, respectively. In the testing data sets, 83% of the images had limitations such as streak artifacts, poor contrast, shape distortion, pathology, or implants. The contours output by the HI system were compared to contours drawn in clinical practice at the four RT centers by utilizing an independently established ground-truth set of contours as reference. Three sets of measures were employed: accuracy via Dice coefficient (DC) and Hausdorff boundary distance (HD), subjective clinical acceptability via a blinded reader study, and efficiency by measuring human time saved in contouring by the HI system. Overall, the HI system achieved a mean DC of 0.78 and 0.87 and a mean HD of 2.22 and 4.53 mm for neck and thorax, respectively. It significantly outperformed clinical contouring in accuracy and saved overall 70% of human time over clinical contouring time, whereas acceptability scores varied significantly from site to site for both auto-contours and clinically drawn contours. CONCLUSIONS: The HI system is observed to behave like an expert human in robustness in the contouring task but vastly more efficiently. It seems to use NI help where image information alone will not suffice to decide, first for the correct localization of the object and then for the precise delineation of the boundary.

The impact of phantom design and material-dependence on repeatability and reproducibility of CT-based radiomics features.

PURPOSE: To understand the design of radiomics phantom and material-dependence on repeatability and reproducibility of computed tomography (CT) radiomics features. METHODS: A radiomics phantom consisting of various materials with uniformity, textural, and biological components, was constructed. The phantom was scanned with different manufacturer CT scanners and the scans were repeated multiple times on the same scanner with different acquisition settings as kVp, mAs, orientation, field of view (FOV), slice thickness, pitch, reconstruction kernels, and acquisition mode. A total of 72 phantom scans were included. For each scan, 18 different regions of interest (ROI) were contoured and 708 radiomics features were extracted from each ROI via an open source radiomics tool, IBEX. To relate the phantom data to patient data, the radiomics features from different phantom materials were compared with those extracted from 50 patients' images of five disease sites as brain, head-and-neck, breast, liver, and lung cases using box-plots comparison and principal component analysis (PCA). The temporal stability of imaging features was then evaluated with respect to a controlled scenario (test-retest) via the intra-class correlation coefficient (ICC). The reproducibility of radiomics features with respect to different scanners or acquisition settings were further evaluated with concordance correlation coefficients (CCC). RESULTS: Among all phantom materials, the biological component had feature values closest to human tissues, especially for tumors in brain and liver. The textural component showed similar ranges of variation to lung lesions, particularly for cartridges of rice, cereal, and the 3D-printed textural phantom with fine and rough grid. It also showed that certain materials, such as polystyrene foam, plaster, and peanuts, did not have comparable values to human tissue and could be excluded for future phantom design. High repeatability was observed in the test-retest study as indicated by an ICC value of 0.998 ± 0.020. All materials were used for feature stability analysis. For the inter-scanner study, shape-related features were the most-reliable category with 94% of features having CCC ≥ 0.9, while gradient orientation histogram (GOH) were the least-reliable with only 14.6% meeting the criteria. For the intra-scanner study, the reproducibility of CT-based radiomics features showed material-dependence. In general, the instability of radiomics features introduced by kVp, mAs, pitch, acquisition mode, and orientation were relatively mild. However, the homogeneous materials were more vulnerable to those changes compared to materials with textural patterns. Regardless of material compositions, resolution parameters like FOV and slice thickness, could have large impact on feature stability. Switching between standard and bone reconstruction kernels could also result significant changes to feature reproducibility. CONCLUSION: We have built a radiomics phantom using materials that cover a wide span of tumor textures seen in oncological CT images. The designed phantom presents a preliminary opportunity for investigating reproducibility of radiomics features and the reproducibility can be material dependent. Thus, in the radiomics quality assurance design, it is important to choose appropriate materials that can provide a close range of radiomics features to patients with specific disease sites dependency taken into consideration.

Adaptive Radiation Therapy in the Treatment of Lung Cancer: An Overview of the Current State of the Field.

Lung cancer treatment is constantly evolving due to technological advances in the delivery of radiation therapy. Adaptive radiation therapy (ART) allows for modification of a treatment plan with the goal of improving the dose distribution to the patient due to anatomic or physiologic deviations from the initial simulation. The implementation of ART for lung cancer is widely varied with limited consensus on who to adapt, when to adapt, how to adapt, and what the actual benefits of adaptation are. ART for lung cancer presents significant challenges due to the nature of the moving target, tumor shrinkage, and complex dose accumulation because of plan adaptation. This article presents an overview of the current state of the field in ART for lung cancer, specifically, probing topics of: patient selection for the greatest benefit from adaptation, models which predict who and when to adapt plans, best timing for plan adaptation, optimized workflows for implementing ART including alternatives to re-simulation, the best radiation techniques for ART including magnetic resonance guided treatment, algorithms and quality assurance, and challenges and techniques for dose reconstruction. To date, the clinical workflow burden of ART is one of the major reasons limiting its widespread acceptance. However, the growing body of evidence demonstrates overwhelming support for reduced toxicity while improving tumor dose coverage by adapting plans mid-treatment, but this is offset by the limited knowledge about tumor control. Progress made in predictive modeling of on-treatment tumor shrinkage and toxicity, optimizing the timing of adaptation of the plan during the course of treatment, creating optimal workflows to minimize staffing burden, and utilizing deformable image registration represent ways the field is moving toward a more uniform implementation of ART.

The combined use of 2D scout and 3D axial CT images to accurately determine the catheter tips for high-dose-rate brachytherapy plans.

PURPOSE: To develop a method combining CT scout images with axial images to improve the localization accuracy of catheter tips in high-dose-rate (HDR) brachytherapy treatments. MATERIALS AND METHODS: CT scout images were utilized along with conventionally reconstructed axial images to aid the localization of catheter tips used during HDR treatment planning. A method was developed to take advantage of the finer image resolution of the scout images to more precisely identify the tip coordinates. The accuracies of this method were compared with the conventional method based on the axial CT images alone, for various slice thicknesses, in a computed tomography dose index (CTDI) head phantom. A clinical case which involved multiple interstitial catheters was also selected for the evaluation of this method. Locations of the catheter tips were reconstructed with the conventional CT-based method and this newly developed method, respectively. Location coordinates obtained via both methods were quantitatively compared. RESULTS: Combination of the scout and axial CT images improved the accuracy of identification and reconstruction of catheter tips along the longitudinal direction (i.e., head-to-foot direction, more or less parallel to the catheter tracks), compared to relying on the axial CT images alone. The degree of improvement was dependent on CT slice thickness. For the clinical patient case, the coordinate differences of the reconstructed catheter tips were 2.6 mm ± 0.9 mm in the head-to-foot direction, 0.4 mm ± 0.2 mm in the left-to-right direction, and 0.6 mm ± 0.2 mm in the anterior-to-posterior direction, respectively. CONCLUSION: Combining CT scout and axial images demonstrates the ability to provide a more accurate identification and reconstruction of the interstitial catheter tips for HDR brachytherapy treatment, especially in the longitudinal direction. The method developed in this work has the potential to be implemented clinically together with automatic segmentation in modern brachytherapy treatment planning systems, in order to improve the reconstruction accuracy of HDR catheters.

Performance assessment of two motion management systems for frameless stereotactic radiosurgery.

BACKGROUND/PURPOSE: Frameless stereotactic radiosurgery (SRS) requires dedicated systems to monitor patient motion in order to avoid inaccurate radiation delivery due to involuntary shifts. The purpose of this study is to assess the accuracy and sensitivity of two distinct motion monitoring systems used for frameless SRS. METHODS: A surface image-guided system known as optical surface monitoring system (OSMS), and a fiducial marker-based system known as high definition motion management (HDMM) as part of the latest Gamma Knife Icon® were compared. A 3D printer-based cranial motion phantom was developed to evaluate the accuracy and sensitivity of these two systems in terms of: (1) the capability to recognize predefined shifts up to 3 cm, and (2) the capability to recognize predefined speeds up to 3 cm/s. The performance of OSMS, in terms of different reference surfaces, was also evaluated. RESULTS: Translational motion could be accurately detected by both systems, with an accuracy of 0.3 mm for displacement up to 1 cm, and 0.5 mm for larger displacements. The reference surface selection had an impact on OSMS performance, with flat surface resulting in less accuracy. HDMM was in general more sensitive when compared with OSMS in capturing the motion, due to its faster frame rate, but a delay in response was observed with faster speeds. Both systems were less sensitive in detection of superior-inferior motion when compared to lateral or vertical displacement directions. CONCLUSION: Translational motion can be accurately and sensitively detected by OSMS and HDMM real-time monitoring systems. However, performance variations were observed along different motion directions, as well as amongst the selection of reference images. Caution is needed when using real-time monitoring systems for frameless SRS treatment.

A novel approach to embed eye shields in customized bolus on nasal dorsum treatment for electron radiotherapy.

We aim to demonstrate the unique use of embedded lead eye shields in an electron wax bolus when treating the nasal dorsum. A patient presented to the clinic with squamous cell carcinoma of the nasal dorsum requiring treatment with en face electrons. A 3D customized wax bolus was designed and imported into the treatment planning system (TPS) to calculate the dose distribution. Due to high lens dose, the bolus was customized further to create 2 milled open slots in the wax, over the lens of eye, to allow lead sheets totaling 4 mm to be slid into the wax. The patient was brought back to the clinic to be scanned with the wax bolus fitting snugly over the nose, eyes, and cheek regions. The 3D milled insert holes were contoured on the CT in the TPS, assigned HU of 2758, to mimic the lead insertion. The lens dose with lead inserts was compared to the plan without lead insert. To further confirm the lens dose, EBT3 films were placed on the right and left eye under the bolus, and nose dorsum on the first day of treatment. The maximum dose of right lens, as calculated in the TPS with the simulated lead shields in place, decreased from 989.5cGy to 457cGy. The maximum dose of left lens decreased from 1085.4cGy to 501cGy. The dose readings from EBT3 films were in good agreement with the TPS, with deviation of 3.32%, 0.26%, and 3.44% for right lens, left lens, and nose, respectively. Daily positioning deviations compared to the plan were 0.65 ± 0.16cm and 0.63 ± 0.29cm for right eye and left eye, respectively. This novel device demonstrated the feasibility, in terms of dose calculation accuracy in the TPS and fabrication, of using customized bolus with lead inserts to conveniently shield the lens of the eyes in an electron treatment for the nose, enabling a streamlined daily setup.

Impact of computed tomography (CT) reconstruction kernels on radiotherapy dose calculation.

PURPOSE: To quantitatively evaluate the effect of computed tomography (CT) reconstruction kernels on various dose calculation algorithms with heterogeneity correction. METHODS: The gammex electron density (ED) Phantom was scanned with the Siemens PET/CT Biograph20 mCT and reconstructed with twelve different kernel options. Hounsfield unit (HU) vs electron density (ED) curves were generated to compare absolute differences. Scans were repeated under head and pelvis protocols and reconstructed per H40s (head) and B40s (pelvis) kernels. In addition, raw data from a full-body patient scan were also reconstructed using the four B kernels. Per reconstruction, photon (3D and VMAT), electron (18 and 20 MeV) and proton (single field) treatment plans were generated using Varian Eclipse dose calculation algorithms. Photon and electron plans were also simulated to pass through cortical bone vs liver plugs of the phantom for kernel comparison. Treatment field monitor units (MU) and isodose volumes were compared across all scenarios. RESULTS: The twelve kernels resulted in minor differences in HU, except at the extreme ends of the density curve with a maximum absolute difference of 55.2 HU. The head and pelvis scans of the phantom resulted in absolute HU differences of up to 49.1 HU for cortical bone and 45.1 HU for lung 300, which is a relative difference of 4.1% and 6.2%, respectively. MU comparisons across photon and proton calculation algorithms for the patient and phantom scans were within 1-2 MU, with a maximum difference of 5.4 MU found for the 20 MeV electron plan. The 20MeV electron plan also displayed maximum differences in isodose volumes of 20.4 cc for V90%. CONCLUSION: Clinically insignificant differences were found among the various kernel generated plans for photon and proton plans calculated on patient and phantom scan data. However, differences in isodose volumes found for higher energy electron plans amongst the kernels may have clinical implications for prescribing dose to an isodose level.

Association of Target Volume Margins With Locoregional Control and Acute Toxicities for Non-small cell lung cancer Treated With Concurrent Chemoradiation Therapy.

PURPOSE: This study aimed to investigate the association between target volume margins and clinical outcomes for patients with inoperable non-small cell lung cancer (NSCLC) treated with concurrent chemoradiation therapy. METHODS AND MATERIALS: We reviewed the records of 82 patients with inoperable NSCLC treated between 2009 and 2016 with concurrent chemoradiation. All patients received positron emission tomography-based treatment planning, 4-dimensional computed tomography simulation to define an internal target volume, and daily cone beam computed tomography. We quantified variations in target volume margins with a margin deviation index (MDI), calculated as the percentage change in equivalent uniform dose between the original planning target volume (PTV) and a standard reference PTV 10 mm beyond the original gross tumor volume, consistent with the minimum margins mandated by recent NSCLC trials. Greater MDIs equated to smaller effective target volume margins. We dichotomized patients by the upper tercile MDI value (5.8%). Endpoints included time to locoregional progression and time to grade ≥ 3 radiation esophagitis (RE3) or radiation pneumonitis (RP3), modelled with the Fine-Gray method. RESULTS: Median follow-up was 37.8 months (range, 5.9-58.1 months). Larger MDIs correlated with smaller clinical target volume (CTV) + PTV margins, larger gross tumor volumes, later treatment year, and intensity modulated radiation therapy use. The risk of locoregional progression did not differ for MDI ≥5.8% versus <5.8% (adjusted hazard ratio: 0.88; P = .76), but the risk of RE3 or RP3 was decreased for MDI ≥5.8% (adjusted hazard ratio: 0.27; P = .027). Patients with MDI ≥5.8% were treated with smaller CTV + PTV margins (median, 5.6 vs 8 mm; P < .0001) and a marginally lower volume of esophagus receiving ≥50 Gy (median, 31.1% vs 35.3%; P = .069). CONCLUSIONS: Smaller margins were used for larger tumors but were not associated with an increase in locoregional failures. Additional studies could clarify whether smaller margins, when used alongside modern radiation therapy techniques, decrease treatment-related toxicity for inoperable NSCLC.

Dosimetric Predictors of Symptomatic Cardiac Events After Conventional-Dose Chemoradiation Therapy for Inoperable NSCLC.

INTRODUCTION: We hypothesized that higher cardiac doses correlates with clinically significant cardiotoxicity after standard-dose chemoradiation therapy (CRT) (∼60 Gy) for inoperable NSCLC. METHODS: We retrospectively reviewed the records of 140 patients with inoperable NSCLC treated with concurrent CRT from 2007 to 2015. Extracted data included baseline cardiac status, dosimetric parameters to the whole heart (WH) and cardiac substructures, and the development of post-CRT symptomatic cardiac events (acute coronary syndrome [ACS], arrhythmia, pericardial effusion, pericarditis, and congestive heart failure [CHF]). Competing risks analysis was used to estimate time to cardiac events. RESULTS: Median follow-up was 47.4 months. Median radiation therapy dose was 61.2 Gy (interquartile range, 60 to 66 Gy). Forty patients (28.6%) developed 47 symptomatic cardiac events at a median of 15.3 months to first event. On multivariate analysis, higher WH doses and baseline cardiac status were associated with an increased risk of symptomatic cardiac events. The 4-year cumulative incidence of symptomatic cardiac events was 48.6% versus 18.5% for mean WH dose ≥ 20 Gy versus < 20 Gy, respectively (p = 0.0002). Doses to the WH, ventricles, and left anterior descending artery were associated with ACS/CHF, whereas doses to the WH and atria were not associated with supraventricular arrhythmias. Symptomatic cardiac events (p = 0.0001) were independently associated with death. CONCLUSIONS: Incidental cardiac irradiation was associated with subsequent symptomatic cardiac events, particularly ACS/CHF, and symptomatic cardiac events were associated with inferior survival. These results support the minimization of cardiac doses among patients with inoperable NSCLC receiving standard-dose CRT.

Daily Image Guidance With Cone Beam Computed Tomography May Reduce Radiation Pneumonitis in Unresectable Non-Small Cell Lung Cancer.

PURPOSE: To investigate the impact of daily image-guided radiation therapy technique on clinical outcomes in patients with inoperable non-small cell lung cancer treated with definitive chemoradiation therapy. METHODS AND MATERIALS: We compared patients with inoperable non-small cell lung cancer receiving daily cone beam computed tomography (CBCT) after an initial 4-dimensional computed tomography (4DCT) simulation (n = 76) with those receiving daily 2-dimensional orthogonal kilovoltage (kV) imaging (n = 48). The primary endpoint was time to grade ≥2 radiation pneumonitis (RP2), estimated with the cumulative incidence method, compared with Gray's test, and modeled with the Fine-Gray method. RESULTS: Median follow-up was 40.6 months (range, 5.9-58.1 months) for the CBCT group and 75.8 months (range, 9.9-107.8 months) for the orthogonal kV group. Four-dimensional computed tomography simulation was used in 100% (n = 76) of the CBCT group and 56% (n = 27) of the orthogonal kV group (P < .0001). The 1-year cumulative incidence of RP2 was lower in the CBCT group than in the orthogonal kV group (24% vs 44%, P = .020). On multivariate analysis, daily imaging with CBCT after an initial 4DCT simulation was associated with a decreased risk of RP2 (adjusted hazard ratio 0.43, 95% confidence interval 0.22-0.82, P = .011), a finding that persisted among only patients who received 4DCT simulation (adjusted hazard ratio 0.48, 95% confidence interval 0.23-0.98, P = .045). There was no difference in locoregional progression, distant metastasis, any progression, or overall survival between groups. CONCLUSIONS: Daily image guided radiation therapy with CBCT compared with 2-dimensional orthogonal kV imaging was associated with a decreased risk of RP2. Clinicians could consider the implications of localization methods during curative intent radiation therapy.

Effect of beam profile measurement on arc therapy plan quality assurance: a case study.

We present an example when profile measurement and modeling of an Elekta Agility multileaf collimator (MLC) had a large effect specifically on arc therapy plan quality assurance (QA) results using ArcCheck. ArcCheck absolute dose measurements of these plans were systematically lower than planned by 3-10%. Failing QA results were seen even with unmodulated static and conformal arcs. Furthermore, the effect was found to be dependent on collimator angle, with worse results associated with near-zero collimator angles. In contrast, step-and-shoot QA results were not affected. Changing the beam model to match steeper profile measurements obtained using a different measurement device resolved the problem. This case study demonstrates that conventional gamma index analysis can be sensitive to small profile modeling changes.

Effect of free-breathing on left ventricular rotational mechanics in healthy subjects and patients with duchenne muscular dystrophy.

PURPOSE: Cardiovascular magnetic resonance imaging exams can be performed during free-breathing. This may be especially important for boys with Duchenne muscular dystrophy (DMD) given their frequently limited breath-hold abilities. The impact of the respiratory compensation method on quantitative measurements of left ventricular (LV) rotational mechanics is incompletely understood. The purpose of this study was to evaluate differences in LV rotational mechanics acquired during breath-holding (BH), free-breathing with averaging (AVG), and free-breathing with respiratory bellows gating (BEL). METHODS: LV short-axis tagged images from healthy subjects (N = 16) and DMD patients (N = 5) were acquired with BH, AVG, and BEL. LV twist and circumferential-longitudinal shear (CL-shear) angle were measured using the Fourier Analysis of STimulated echoes (FAST) method. RESULTS: Peak LV twist estimates using BEL were significantly lower compared with BH in both healthy subjects (10.2 ± 3.6 ° versus 12.9 ± 2.3 °, P = 0.003) and patients with DMD (8.6 ± 3.6 ° versus 10.5 ± 3.6 °, P = 0.004). AVG results were in between BEL and BH. No significant differences in CL-shear were detected between BEL and BH. CONCLUSION: Breath-holding directly affects estimates of peak LV twist, but not CL-shear. Using a free-breathing strategy for the evaluation of cardiac function is important for intrasubject longitudinal studies, intersubject comparisons, and multicenter trials for patients with DMD. Magn Reson Med 77:864-869, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Characterization of the effect of MRI on Gafchromic film dosimetry.

Magnetic resonance (MR) imaging of Gafchromic film causes perturbation to absolute dosimetry measurements; the purpose of this work was to characterize the perturbation and develop a correction method for it. Three sets of Gafchromic EBT2 film were compared: radiation (control), radiation followed by MR imaging (RAD + B), and MR imaging followed by radiation (B + RAD). The T1-weighted and T2-weighted MR imaging was performed using a 1.5T scanner with the films wedged between two chicken legs. Doses from 0 to 800 cGy were delivered with a 6MV linac. The time interval between radiation and MR imaging was less than 10 min. Film calibration was generated from the red channel. Microscopic imaging was performed on two pieces of film. The effect of specific absorption rate (SAR) was determined by exposing another three sets of films to low, medium, and high levels of SAR through a series of pulse sequences. No discernible preferential alignment was detected on the microscopic images of the irradiated film exposed to MRI. No imaging artifacts were introduced by Gafchromic film on any MR images. On average, 4% dose difference was observed between B + RAD or RAD + B and the control, using the same calibration curve. The pixel values between the B + RAD or RAD + B and the control films were found to follow a linear relationship pixel(Control) = 1.02 × pixel(B + RAD or RAD + B). By applying this correction, the average dose error was reduced to approximately 2%. The SAR experiment revealed a dose overestimation with increasing SAR even when the correction was applied. It was concluded that MR imaging introduces perturbation on Gafchromic film dose measurements by 4% on average, compared to calibrating the film without the presence of MRI. This perturbation can be corrected by applying a linear correction to the pixel values. Additionally, Gafchromic film did not introduce any imaging artifacts in any of the MR images acquired.

Depth dose perturbation by a hydrogel fiducial marker in a proton beam.

The purpose of this study was to evaluate proton depth dose perturbation caused by a radio-opaque hydrogel fiducial marker. Electronic proton stopping powers in the hydrogel were calculated for energies 0.5-250 MeV, and Monte Carlo simulations were generated of hydrogel vs. gold markers placed at various water phantom depths in a generic proton beam. Across the studied energy range, the gel/water stopping power ratio was 1.0146 to 1.0160. In the Monte Carlo simulation, the hydrogel marker caused no discernible perturbation of the proton percent depth-dose (PDD) curve. In contrast, the gold marker caused dose reductions of as much as 20% and dose shadowing regions as long as 6.5 cm. In contrast to gold markers, the radio-opaque hydrogel marker causes negligible proton depth dose perturbation. This factor may be taken into consideration for image-guided proton therapy at facilities with suitable imaging modalities.

Left ventricular twist and shear in patients with primary mitral regurgitation.

PURPOSE: To evaluate the relationship between left ventricular (LV) twist, shear, and twist-per-volume and the severity of mitral regurgitation (MR). Primary MR is a valvular disorder that induces LV dysfunction. There exist several measures of LV rotational mechanics, but it remains unclear which measure of LV dysfunction best accords with the severity of MR. We hypothesized that LV systolic twist-per-volume slope would decrease with increasing severity of MR because of both decreases in rotational mechanics and increases in stroke volumes. MATERIALS AND METHODS: Normal subjects (n = 54), moderate MR patients (n = 29), and severe MR patients (n = 54) were studied. Magnetic resonance imaging (MRI) was performed on a 1.5T scanner and grid-tagged LV images were collected at the LV base and LV apex. Measures of LV rotational mechanics were derived from tagged images using Fourier Analysis of STimulated echoes (FAST). RESULTS: Peak systolic twist-per-volume slope was significantly different for all pairwise comparisons (P < 0.0001) and compared to normal subjects (-0.14 ± 0.05°/mL) was decreased in moderate MR (-0.12 ± 0.04°/mL) and further decreased in severe MR (-0.07 ± 0.03°/mL). CONCLUSION: Peak systolic twist-per-volume slope significantly decreased with increasing severity of MR and is therefore a suitable quantitative imaging biomarker for LV dysfunction in patients with MR.

Complementary radial tagging for improved myocardial tagging contrast.

PURPOSE: To develop and evaluate complementary radial tagging (CRT) for improved myocardial tagging contrast. METHODS: We sought to develop and evaluate CRT, which aims to preserve the radial tag contrast throughout the cardiac cycle. Similar to complementary spatial modulation of magnetization, CRT acquires two sets of images with a phase shift in the tag pattern. The combination of a ramped imaging flip angle and image subtraction enhances tag contrast throughout the cardiac cycle. The proposed CRT technique uses a small table shift away from the isocenter to improve the uniformity of the radial tag pattern. We provide a mathematical solution for the optimal table shift and validate the solution in using a retrospective analysis of images from 500 patients in the Cardiac Atlas Project database. RESULTS: CRT simulations, phantom experiments, and in vivo images all demonstrate the improved tag contrast of CRT compared to RT. The retrospective evaluation demonstrated that acceptable CRT images could be acquired in over 98% of the clinical exams. CONCLUSION: The CRT technique improves radial tag contrast throughout the cardiac cycle and should produce high quality tag patterns in nearly all patients.

Intra- and interscan reproducibility using Fourier Analysis of STimulated Echoes (FAST) for the rapid and robust quantification of left ventricular twist.

PURPOSE: To assess the intra- and interscan reproducibility of LV twist using FAST. Assessing the reproducibility of the measurement of new MRI biomarkers is an important part of validation. Fourier Analysis of STimulated Echoes (FAST) is a new MRI tissue tagging method that has recently been shown to compare favorably with conventional estimates of left ventricular (LV) twist from cardiac tagged images, but with significantly reduced user interaction time. MATERIALS AND METHODS: Healthy volunteers (N = 10) were scanned twice using FAST over 1 week. On day 1, two measurements of LV twist were collected for intrascan comparisons. Measurements for LV twist were again collected on day 8 for interscan assessment. LV short-axis tagged images were acquired on a 3 Tesla (T) scanner to ensure detectability of tags during early and mid-diastole. Peak LV twist is reported as mean ± SD. Reproducibility was assessed using the concordance correlation coefficient (CCC) and the repeatability coefficient (RC) (95% confidence interval [CI] range). RESULTS: Mean peak twist measurements were 13.4 ± 4.3° (day 1, scan 1), 13.6 ± 3.7° (day 1, scan 2), and 13.0 ± 2.7° (day 8). Bland-Altman analysis resulted in intra- and interscan bias and 95% CI of -0.6° [-1.0°, 1.6°] and 1.4° (-1.0°, 3.0°), respectively. The Bland-Altman RC for peak LV twist was 2.6° and 4.0° for intra- and interscan, respectively. The CCC was 0.9 and 0.6 for peak LV twist for intra- and interscan, respectively. CONCLUSION: FAST is a semi-automated method that provides a quick and quantitative assessment of LV systolic and diastolic twist that demonstrates high intrascan and moderate interscan reproducibility in preliminary studies.

Off-resonance insensitive complementary SPAtial Modulation of Magnetization (ORI-CSPAMM) for quantification of left ventricular twist.

PURPOSE: To evaluate Off Resonance Insensitive Complementary SPAtial Modulation of Magnetization (ORI-CSPAMM) and Fourier Analysis of STimulated echoes (FAST) for the quantification of left ventricular (LV) systolic and diastolic function and compare it with the previously validated FAST+SPAMM technique. MATERIALS AND METHODS: LV short-axis tagged images were acquired with ORI-CSPAMM and SPAMM in healthy volunteers (n = 13). The FAST method was used to automatically estimate LV systolic and diastolic twist parameters from rotation of the stimulated echo and stimulated anti-echo about the middle of k-space subsequent to ∼3 min of user interaction. RESULTS: There was no significant difference between measures obtained for FAST+ORI-CSPAMM and FAST+SPAMM for mean peak twist (12.9 ± 3.4° versus 11.9 ± 4.0°; P = 0.4), torsion (3.3 ± 0.9°/cm versus 2.9 ± 1.0°/cm, P = 0.3), circumferential-longitudinal shear angle (9.1 ± 3.0° versus 8.2 ± 3.4°, P = 0.3), twisting rate (79.6 ± 20.2°/s versus 68.2 ± 23.4°/s, P = 0.1), untwisting rate (-117.5 ± 31.4°/s versus -106.6 ± 32.4°/s, P = 0.3), normalized untwisting rate (-9.3 ± 2.0/s versus -9.9 ± 4.4/s, P = 0.7), and time of peak twist (281 ± 18 ms versus 293 ± 25 ms, P = 0.04). FAST+ORI-CSPAMM also provided measures of duration of untwisting (148 ± 21 ms) and the ratio of rapid untwisting to peak twist (0.9 ± 0.3). Bland-Altman analysis of FAST+ORI-CSPAMM and FAST+SPAMM twist data demonstrates excellent agreement with a bias of -0.1° and 95% confidence intervals of (-1.0°, 3.2°). CONCLUSION: FAST+ORI-CSPAMM is a semi-automated method that provides a quick and quantitative assessment of LV systolic and diastolic twist and torsion. ORI-CSPAMM corrects off-resonance accrued during tagging preparation and readout and visibly removes chemical shift from the tagging pattern, which confers greater robustness to the derived quantitative measures.