Integrating local and distant radiation-induced lung injury: Development and validation of a predictive model for ventilation loss.

BACKGROUND: Investigations on radiation-induced lung injury (RILI) have predominantly focused on local effects, primarily those associated with radiation damage to lung parenchyma. However, recent studies from our group and others have revealed that radiation-induced damage to branching serial structures such as airways and vessels may also have a substantial impact on post-radiotherapy (RT) lung function. Furthermore, recent results from multiple functional lung avoidance RT trials, although promising, have demonstrated only modest toxicity reduction, likely because they were primarily focused on dose avoidance to lung parenchyma. These observations emphasize the critical need for predictive dose-response models that effectively incorporate both local and distant RILI effects. PURPOSE: We develop and validate a predictive model for ventilation loss after lung RT. This model, referred to as P+A, integrates local (parenchyma [P]) and distant (central and peripheral airways [A]) radiation-induced damage, modeling partial (narrowing) and complete (collapse) obstruction of airways. METHODS: In an IRB-approved prospective study, pre-RT breath-hold CTs (BHCTs) and pre- and one-year post-RT 4DCTs were acquired from lung cancer patients treated with definitive RT. Up to 13 generations of airways were automatically segmented on the BHCTs using a research virtual bronchoscopy software. Ventilation maps derived from the 4DCT scans were utilized to quantify pre- and post-RT ventilation, serving, respectively, as input data and reference standard (RS) in model validation. To predict ventilation loss solely due to parenchymal damage (referred to as P model), we used a normal tissue complication probability (NTCP) model. Our model used this NTCP-based estimate and predicted additional loss due radiation-induced partial or complete occlusion of individual airways, applying fluid dynamics principles and a refined version of our previously developed airway radiosensitivity model. Predictions of post-RT ventilation were estimated in the sublobar volumes (SLVs) connected to the terminal airways. To validate the model, we conducted a k-fold cross-validation. Model parameters were optimized as the values that provided the lowest root mean square error (RMSE) between predicted post-RT ventilation and the RS for all SLVs in the training data. The performance of the P+A and the P models was evaluated by comparing their respective post-RT ventilation values with the RS predictions. Additional evaluation using various receiver operating characteristic (ROC) metrics was also performed. RESULTS: We extracted a dataset of 560 SLVs from four enrolled patients. Our results demonstrated that the P+A model consistently outperformed the P model, exhibiting RMSEs that were nearly half as low across all patients (13 ± 3 percentile for the P+A model vs. 24 ± 3 percentile for the P model on average). Notably, the P+A model aligned closely with the RS in ventilation loss distributions per lobe, particularly in regions exposed to doses ≥13.5 Gy. The ROC analysis further supported the superior performance of the P+A model compared to the P model in sensitivity (0.98 vs. 0.07), accuracy (0.87 vs. 0.25), and balanced predictions. CONCLUSIONS: These early findings indicate that airway damage is a crucial factor in RILI that should be included in dose-response modeling to enhance predictions of post-RT lung function.

Combining Serial and Parallel Functionality in Functional Lung Avoidance Radiation Therapy.

PURPOSE: Functional lung avoidance (FLA) radiation therapy (RT) aims to minimize post-RT pulmonary toxicity by preferentially avoiding dose to high-functioning lung (HFL) regions. A common limitation is that FLA approaches do not consider the conducting architecture for gas exchange. We previously proposed the functionally weighted airway sparing (FWAS) method to spare airways connected to HFL regions, showing that it is possible to substantially reduce risk of radiation-induced airway injury. Here, we compare the performance of FLA and FWAS and propose a novel method combining both approaches. METHODS: We used breath-hold computed tomography (BHCT) and simulation 4-dimensional computed tomography (4DCT) from 12 lung stereotactic ablative radiation therapy patients. Four planning strategies were examined: (1) Conventional: no sparing other than clinical dose-volume constraints; (2) FLA: using a 4DCT-based ventilation map to delineate the HFL, plans were optimized to reduce mean dose and V13.50 in HFL; (3) FWAS: we autosegemented 11 to 13 generations of individual airways from each patient's BHCT and assigned priorities based on the relative contribution of each airway to total ventilation. We used these priorities in the optimization along with airway dose constraints, estimated as a function of airway diameter and 5% probability of collapse; and (4) FLA + FWAS: we combined information from the 2 strategies. We prioritized clinical dose constraints for organs at risk and planning target volume in all plans. We performed the evaluation in terms of ventilation preservation accounting for radiation-induced damage to both lung parenchyma and airways. RESULTS: We observed average ventilation preservation for FLA, FWAS, and FLA + FWAS as 3%, 8.5%, and 14.5% higher, respectively, than for Conventional plans for patients with ventilation preservation in Conventional plans <90%. Generalized estimated equations showed that all improvements were statistically significant (P ≤ .036). We observed no clinically relevant improvements in outcomes of the sparing techniques in patients with ventilation preservation in Conventional plans ≥90%. CONCLUSIONS: These initial results suggest that it is crucial to consider the parallel and the serial nature of the lung to improve post-radiation therapy lung function and, consequently, quality of life for patients.

Technical Report: Development and Implementation of an Open Source Template Interpretation Class Library for Automated Treatment Planning.

PURPOSE: Widespread implementation of automated treatment planning in radiation therapy remains elusive owing to variability in clinic and physician preferences, making it difficult to ensure consistent plan parameters. We have developed an open-source class library with the aim to improve efficiency and consistency for automated treatment planning in radiation therapy. METHODS AND MATERIALS: An open-source class library has been developed that interprets clinical templates within a commercial treatment planning system into a treatment plan for automated planning. This code was leveraged for the automated planning of 39 patients and retrospectively compared with the 78 clinically approved manual plans. RESULTS: From the initial 39 patients, 74 of 78 plans were successfully generated without manual intervention. The target dose was more homogeneous for automated plans, with an average homogeneity index of 3.30 for manual plans versus 3.11 for automated plans (P = .107). The generalized equivalent uniform dose (gEUD) was decreased in the femurs and rectum for automated plans, with a mean gEUD of 3746 cGy versus 3338 cGy (P ≤ 0.001) and 5761 cGy versus 5634 cGy (P ≤ 0.001) for the femurs and rectum, respectively. Dose metrics for the bladder and rectum (V6500 cGy and V4000 cGy) showed recognizable but insignificant improvements. All automated plans delivered for quality assurance passed a gamma analysis (>95%), with an average composite pass rate of 99.3% for pelvis plans and 98.8% for prostate plans. Deliverability parameters such as total monitor units and aperture complexity indicated deliverable plans. CONCLUSIONS: Prostate cancer and pelvic node radiation therapy can be automated using volumetric modulated arc therapy planning and clinical templates based on a standardized clinical workflow. The class library developed in this study conveniently interfaced between the plan template and the treatment planning system to automatically generate high-quality plans on customizable templates.

Optical emission-based phantom to verify coincidence of radiotherapy and imaging isocenters on an MR-linac.

PURPOSE: Demonstrate a novel phantom design using a remote camera imaging method capable of concurrently measuring the position of the x-ray isocenter and the magnetic resonance imaging (MRI) isocenter on an MR-linac. METHODS: A conical frustum with distinct geometric features was machined out of plastic. The phantom was submerged in a small water tank, and aligned using room lasers on a MRIdian MR-linac (ViewRay Inc., Cleveland, OH). The phantom physical isocenter was visualized in the MR images and related to the DICOM coordinate isocenter. To view the x-ray isocenter, an intensified CMOS camera system (DoseOptics LLC., Hanover, NH) was placed at the foot of the treatment couch, and centered such that the optical axis of the camera was coincident with the central axis of the treatment bore. Two or four 8.3mm x 24.1cm beams irradiated the phantom from cardinal directions, producing an optical ring on the conical surface of the phantom. The diameter of the ring, measured at the peak intensity, was compared to the known diameter at the position of irradiation to determine the Z-direction offset of the beam. A star-shot method was employed on the front face of the frustum to determine X-Y alignment of the MV beam. Known shifts were applied to the phantom to establish the sensitivity of the method. RESULTS: Couch translations, demonstrative of possible isocenter misalignments, on the order of 1mm were detectable for both the radiotherapy and MRI isocenters. Data acquired on the MR-linac demonstrated an average error of 0.28mm(N=10, R2 =0.997, σ=0.37mm) in established Z displacement, and 0.10mm(N=5, σ=0.34mm) in XY directions of the radiotherapy isocenter. CONCLUSIONS: The phantom was capable of measuring both the MRI and radiotherapy treatment isocenters. This method has the potential to be of use in MR-linac commissioning, and could be streamlined to be valuable in daily constancy checks of isocenter coincidence.

Evaluation of Motion Compensation Methods for Noninvasive Cardiac Radioablation of Ventricular Tachycardia.

PURPOSE: Noninvasive cardiac radioablation is increasingly used for treatment of refractory ventricular tachycardia. Attempts to limit normal tissue exposure are important, including managing motion of the target. An interplay between cardiac and respiratory motion exists for cardiac radioablation, which has not been studied in depth. The objectives of this study were to estimate target motion during abdominal compression free breathing (ACFB) and respiratory gated (RG) deliveries and to investigate the quality of either implanted cardioverter defibrillator lead tip or the diaphragm as a gating surrogate. METHODS AND MATERIALS: Eleven patients underwent computed tomography (CT) simulation with an ACFB 4-dimensional CT (r4DCT) and an exhale breath-hold cardiac 4D-CT (c4DCT). The target, implanted cardioverter defibrillator lead tip and diaphragm trajectories were measured for each patient on the r4DCT and c4DCT using rigid registration of each 4D phase to the reference (0%) phase. Motion ranges for ACFB and exhale (40%-60%) RG delivery were estimated from the target trajectories. Surrogate quality was estimated as the correlation with the target motion magnitudes. RESULTS: Mean (range) target motion across patients from r4DCT was as follows: left/right (LR), 3.9 (1.7-6.9); anteroposterior (AP), 4.1 (2.2-5.4); and superoinferior (SI), 4.7 (2.2-7.9) mm. Mean (range) target motion from c4DCT was as follows: LR, 3.4 (1.0-4.8); AP, 4.3 (2.6-6.5); and SI, 4.1 (1.4-8.0) mm. For an ACFB, treatment required mean (range) margins to be 4.5 (3.1-6.9) LR, 4.8 (3-6.5) AP, and 5.5 (2.3-8.0) mm SI. For RG, mean (range) internal target volume motion would be 3.6 (1.1-4.8) mm LR, 4.3 (2.6-6.5) mm AP, and 4.2 (2.2-8.0) mm SI. The motion correlations between the surrogates and target showed a high level of interpatient variability. CONCLUSIONS: In ACFB patients, a simulated exhale-gated approach did not lead to large projected improvements in margin reduction. Furthermore, the variable correlation between readily available gating surrogates could mitigate any potential advantage to gating and should be evaluated on a patient-specific basis.

Dosimetric feasibility of brain stereotactic radiosurgery with a 0.35 T MRI-guided linac and comparison vs a C-arm-mounted linac.

PURPOSE: MRI is the gold-standard imaging modality for brain tumor diagnosis and delineation. The purpose of this work was to investigate the feasibility of performing brain stereotactic radiosurgery (SRS) with a 0.35 T MRI-guided linear accelerator (MRL) equipped with a double-focused multileaf collimator (MLC). Dosimetric comparisons were made vs a conventional C-arm-mounted linac with a high-definition MLC. METHODS: The quality of MRL single-isocenter brain SRS treatment plans was evaluated as a function of target size for a series of spherical targets with diameters from 0.6 cm to 2.5 cm in an anthropomorphic head phantom and six brain metastases (max linear dimension = 0.7-1.9 cm) previously treated at our clinic on a conventional linac. Each target was prescribed 20 Gy to 99% of the target volume. Step-and-shoot IMRT plans were generated for the MRL using 11 static coplanar beams equally spaced over 360° about an isocenter placed at the center of the target. Couch and collimator angles are fixed for the MRL. Two MRL planning strategies (VR1 and VR2) were investigated. VR1 minimized the 12 Gy isodose volume while constraining the maximum point dose to be within ±1 Gy of 25 Gy which corresponded to normalization to an 80% isodose volume. VR2 minimized the 12 Gy isodose volume without the maximum dose constraint. For the conventional linac, the TB1 method followed the same strategy as VR1 while TB2 used five noncoplanar dynamic conformal arcs. Plan quality was evaluated in terms of conformity index (CI), conformity/gradient index (CGI), homogeneity index (HI), and volume of normal brain receiving ≥12 Gy (V12Gy ). Quality assurance measurements were performed with Gafchromic EBT-XD film following an absolute dose calibration protocol. RESULTS: For the phantom study, the CI of MRL plans was not significantly different compared to a conventional linac (P > 0.05). The use of dynamic conformal arcs and noncoplanar beams with a conventional linac spared significantly more normal brain (P = 0.027) and maximized the CGI, as expected. The mean CGI was 95.9 ± 4.5 for TB2 vs 86.6 ± 3.7 (VR1), 88.2 ± 4.8 (VR2), and 88.5 ± 5.9 (TB1). Each method satisfied a normal brain V12Gy  ≤ 10.0 cm3 planning goal for targets with diameter ≤2.25 cm. The mean V12Gy was 3.1 cm3 for TB2 vs 5.5 cm3 , 5.0 cm3 and 4.3 cm3 , for VR1, VR2, and TB1, respectively. For a 2.5-cm diameter target, only TB2 met the V12Gy planning objective. The MRL clinical brain plans were deemed acceptable for patient treatment. The normal brain V12Gy was ≤6.0 cm3 for all clinical targets (maximum target volume = 3.51 cm3 ). CI and CGI ranged from 1.12-1.65 and 81.2-88.3, respectively. Gamma analysis pass rates (3%/1mm criteria) exceeded 97.6% for six clinical targets planned and delivered on the MRL. The mean measured vs computed absolute dose difference was -0.1%. CONCLUSIONS: The MRL system can produce clinically acceptable brain SRS plans for spherical lesions with diameter ≤2.25 cm. Large lesions (>2.25 cm) should be treated with a linac capable of delivering noncoplanar beams.

Influence of 0.35 T magnetic field on the response of EBT3 and EBT-XD radiochromic films.

PURPOSE: To investigate the inconsistency of recent literature on the effect of magnetic field on the response of radiochromic films, we studied the influence of 0.35 T magnetic field on dosimetric response of EBT3 and EBT-XD GafchromicTM films. METHODS: Two different models of radiochromic films, EBT3 and EBT-XD, were investigated. Pieces of films samples from two different batches for each model were irradiated at different dose levels ranging from 1 to 20 Gy using 6 MV flattening filter free (FFF) x-rays generated by a clinical MR-guided radiotherapy system (B = 0.35 T). Film samples from the same batch were irradiated at corresponding dose levels using 6 MV FFF beam from a conventional linac (B = 0) for comparison. The net optical density was measured 48 h postirradiation using a flatbed scanner. The absorbance spectra were also measured over 500-700 nm wavelength range using a fiber-coupled spectrometer with 2.5 nm resolution. To study the effect of fractionated dose delivery to EBT3 (/EBT-XD) films, 8 (/16) Gy dose was delivered in four 2 (/4) Gy fractions with 24 h interval between fractions. RESULTS: No significant difference was found in the net optical density and net absorbance of the films irradiated with or without the presence of magnetic field. No dependency on the orientation of the film during irradiation with respect to the magnetic field was observed. The fractionated dose delivery resulted in the same optical density as delivering the whole dose in a single fraction. CONCLUSIONS: The 0.35 T magnetic field employed in the ViewRay® MR-guided radiotherapy system did not show any significant influence on the response of EBT3 and EBT-XD GafchromicTM films.

Optical imaging method to quantify spatial dose variation due to the electron return effect in an MR-linac.

PURPOSE: Treatment planning systems (TPSs) for MR-linacs must employ Monte Carlo-based simulations of dose deposition to model the effects of the primary magnetic field on dose. However, the accuracy of these simulations, especially for areas of tissue-air interfaces where the electron return effect (ERE) is expected, is difficult to validate due to physical constraints and magnetic field compatibility of available detectors. This study employs a novel dosimetric method based on remotely captured, real-time optical Cherenkov and scintillation imaging to visualize and quantify the ERE. METHODS: An intensified CMOS camera was used to image two phantoms with designed ERE cavities. Phantom A was a 40 cm × 10 cm × 10 cm clear acrylic block drilled with five holes of increasing diameters (0.5, 1, 2, 3, 4 cm). Phantom B was a clear acrylic block (25 cm × 20 cm × 5 cm) with three cavities of increasing diameter (3, 2, 1 cm) split into two halves in the transverse plane to accommodate radiochromic film. Both phantoms were imaged while being irradiated by 6 MV flattening filter free (FFF) beams within a MRIdian Viewray (Viewray, Cleveland, OH) MR-linac (0.34 T primary field). Phantom A was imaged while being irradiated by 6 MV FFF beams on a conventional linac (TrueBeam, Varian Medical Systems, San Jose, CA) to serve as a control. Images were post processed in Matlab (Mathworks Inc., Natick, MA) and compared to TPS dose volumes. RESULTS: Control imaging of Phantom A without the presence of a magnetic field supports the validity of the optical image data to a depth of 6 cm. In the presence of the magnetic field, the optical data shows deviations from the commissioned TPS dose in both intensity and localization. The largest air cavity examined (3 cm) indicated the largest dose differences, which were above 20% at some locations. Experiments with Phantom B illustrated similar agreement between optical and film dosimetry comparisons with TPS data in areas not affected by ERE. CONCLUSION: There are some appreciable differences in dose intensity and spatial dose distribution observed between the novel experimental data set and the dose models produced by the current clinically implemented MR-IGRT TPS.

Dosimetric Feasibility of Utilizing the ViewRay Magnetic Resonance Guided Linac System for Image-guided Spine Stereotactic Body Radiation Therapy.

INTRODUCTION: Spine stereotactic body radiation therapy (SBRT) achieves favorable outcomes compared to conventional radiotherapy doses/fractionation. The spinal cord is the principal dose-limiting organ-at-risk (OAR), and safe treatment requires precise immobilization/localization. Therefore, image guidance is paramount to successful spine SBRT. Conventional X-ray imaging and alignment to surrogate bony anatomy may be inadequate, whereas magnetic resonance imaging (MRI) directly visualizes the dose-limiting cord. This work assessed the dosimetric capability of the ViewRay (ViewRay Inc. Oakwood Village, OH) magnetic resonance (MR) guided linac (MR-Linac) for spine SBRT. METHODS: Eight spine SBRT patients without orthopedic hardware who were previously treated on a TrueBeam using volumetric modulated arc therapy (VMAT) were re-planned using MR-Linac fixed-field intensity-modulated radiation therapy (IMRT). Phantom measurements using film, ionization chamber, and a commercial diode-array assessed feasibility. Plans included a variety of prescriptions (30-50 Gy in 3-10 fractions). RESULTS: MR-Linac plans satisfied all clinical goals. Compared to VMAT plans, both entrance dose and heterogeneity increased (Dmax: 134±3% vs. 120±2%, p=0.0270), while conformality decreased (conformity index: 1.28±0.06 vs. 1.06±0.06, p=0.0005), and heterogeneity increased. However, while not statistically significant, MR-linac cord sparing improved (cord Dmax: 16.1±2.7Gy vs. 19.5±1.6Gy, p=0.2066; cord planning organ at risk volume (cord PRV) Dmax: 20.0±2.6Gy vs. 24.5±2.0Gy, p=0.0996). Delivery time increased but was acceptable (14.39±1.26min vs. 9.57±1.19min). Ionization chamber measurements agreed with planned dose to within 2.5%. Film and diode measurements demonstrated accurate/precise delivery of dose gradients between the target and the cord. CONCLUSION: Spine SBRT with the MR-Linac is feasible as verified via re-planning eight clinical cases followed by delivery verification in phantoms using film, diodes, and an ionization chamber. Real-time visualization of the dose-limiting cord during spine SBRT may enable cord-based gating, reduced margins, alternate dose schemas, and/or adaptive therapy.

Improving treatment geometries in total skin electron therapy: Experimental investigation of linac angles and floor scatter dose contributions using Cherenkov imaging.

PURPOSE: The purpose of this study was to identify the optimal treatment geometry for total skin electron therapy (TSET) using a new optimization metric from Cherenkov image analysis, and to investigate the sensitivity of the Cherenkov imaging method to floor scatter effects in this unique treatment setup. METHODS: Cherenkov imaging using an intensified charge coupled device (ICCD) was employed to measure the relative surface dose distribution as a 2D image in the total skin electron treatment plane. A 1.2 m × 2.2 m × 1 cm white polyethylene sheet was placed vertically at a source to surface distance (SSD) of 300 cm, and irradiated with 6 MeV high dose rate TSET beams. The linear accelerator coordinate system used stipulates 0° is the bottom of the gantry arc, and progresses counterclockwise so that gantry angle 270° produces a horizontal beam orthogonal to the treatment plane. First, all unique pairs of treatment beams were analyzed to determine the performance of the currently recommended symmetric treatment angles (±20° from the horizontal), compared to treatment geometries unconstrained to upholding gantry angle symmetry. This was performed on two medical linear accelerators (linacs). Second, the extent of the floor scatter contributions to measured surface dose at the extended SSD required for TSET were imaged using three gantry angles of incidence: 270° (horizontal), 253° (-17°), and 240° (-30°). Images of the surface dose profile at each angle were compared to the standard concrete floor when steel plates, polyvinyl chloride (PVC), and solid water were placed on the ground at the base of the treatment plane. Postprocessing of these images allowed for comparison of floor material-based scatter profiles with previously published simulation results. RESULTS: Analysis of the symmetric treatment geometry (270 ± 20°) and the identified optimal treatment geometry (270 + 23° and 270 - 17°) showed a 16% increase in the 90% isodose area for the latter field pair on the first linac. The optimal asymmetric pair for the second linac (270 + 25° and 270 - 17°) provided a 52% increase in the 90% isodose area when compared to the symmetric geometry. Difference images between Cherenkov images captured with test materials (steel, PVC, and solid water) and the control (concrete floor) demonstrated relative changes in the two-dimensional (2D) dose profile over a 1 × 1.9 m region of interest (ROI) that were consistent with published simulation data. Qualitative observation of the residual images demonstrates localized increases and decreases with respect to the change in floor material and gantry angle. The most significant changes occurred when the beam was most directly impinging the floor (gantry angle 240°, horizontal -30°), where the PVC floor material decreased scatter dose by 1-3% in 7.2% of the total ROI area, and the steel plate increased scatter dose by 1-3% in 7.0% of the total ROI area. CONCLUSIONS: An updated Cherenkov imaging method identified asymmetric, machine-dependent TSET field angle pairs that provided much larger 90% isodose areas than the commonly adopted symmetric geometry suggested by Task Group 30 Report 23. A novel demonstration of scatter dose Cherenkov imaging in the TSET field was established.

Metal artifact reduction in MRI-based cervical cancer intracavitary brachytherapy.

Magnetic resonance imaging (MRI) plays an increasingly important role in brachytherapy planning for cervical cancer. Yet, metal tandem, ovoid intracavitary applicators, and fiducial markers used in brachytherapy cause magnetic susceptibility artifacts in standard MRI. These artifacts may impact the accuracy of brachytherapy treatment and the evaluation of tumor response by misrepresenting the size and location of the metal implant, and distorting the surrounding anatomy and tissue. Metal artifact reduction sequences (MARS) with high bandwidth RF selective excitations and turbo spin-echo readouts were developed for MRI of orthopedic implants. In this study, metal artifact reduction was applied to brachytherapy of cervical cancer using the orthopedic metal artifact reduction (O-MAR) sequence. O-MAR combined MARS features with view angle tilting and slice encoding for metal artifact correction (SEMAC) to minimize in-plane and through-plane susceptibility artifacts. O-MAR improved visualization of the tandem tip on T2 and proton density weighted (PDW) imaging in phantoms and accurately represented the diameter of the tandem. In a pilot group of cervical cancer patients (N = 7), O-MAR significantly minimized the blooming artifact at the tip of the tandem in PDW MRI. There was no significant difference observed in artifact reduction between the weak (5 kHz, 7 z-phase encodes) and medium (10 kHz, 13 z-phase encodes) SEMAC settings. However, the weak setting allowed a significantly shorter acquisition time than the medium setting. O-MAR also reduced susceptibility artifacts associated with metal fiducial markers so that they appeared on MRI at their true dimensions.

Proton computed tomography using a 1D silicon diode array.

PURPOSE: Proton radiography (PR) and proton computed tomography (PCT) can be used to measure proton stopping power directly. However, practical and cost effective proton imaging detectors are not widely available. In this study, the authors investigated the feasibility of proton imaging using a silicon diode array. METHODS: A one-dimensional silicon diode detector array (1DSDA) was aligned with the central axis (CAX) of the proton beam. Polymethyl methacrylate (PMMA) slabs were used to find the correspondence between the water equivalent thickness (WET) and 1DSDA channel number. Two-dimensional proton radiographs were obtained by translation and rotation of a phantom relative to CAX while the proton nozzle and 1DSDA were kept stationary. A PCT image of one slice of the phantom was reconstructed using filtered backprojection. RESULTS: PR and PCT images of the PMMA cube were successfully acquired using the 1DSDA. The WET of the phantom was measured using PR data. The resolution and maximum error in WET measurement are 2.0 and 1.5 mm, respectively. Structures down to 2.0 mm in size could be resolved completely. Reconstruction of a PCT image showed very good agreement with simulation. Limitations in spatial resolution are attributed to limited spatial sampling, beam collimation, and proton scatter. CONCLUSIONS: The results demonstrate the feasibility of using silicon diode arrays for proton imaging. Such a device can potentially offer fast image acquisition and high spatial and energy resolution for PR and PCT.

Evaluation of models of spectral distortions in photon-counting detectors for computed tomography.

A semi-analytical model describing spectral distortions in photon-counting detectors (PCDs) for clinical computed tomography was evaluated using simulated data. The distortions were due to count rate-independent spectral response effects and count rate-dependent pulse-pileup effects and the model predicted both the mean count rates and the spectral shape. The model parameters were calculated using calibration data. The model was evaluated by comparing the predicted x-ray spectra to Monte Carlo simulations of a PCD at various count rates. The data-model agreement expressed as weighted coefficient of variation [Formula: see text] was better than [Formula: see text] for dead time losses up to 28% and [Formula: see text] or smaller for dead time losses up to 69%. The accuracy of the model was also tested for the purpose of material decomposition by estimating material thicknesses from simulated projection data. The estimated attenuator thicknesses generally agreed with the true values within one standard deviation of the statistical uncertainty obtained from multiple noise realizations.

Regional function analysis of left atrial appendage using motion estimation CT and risk of stroke in patients with atrial fibrillation.

AIMS: The aim of this article is to determine the association between left atrial appendage (LAA) regional dysfunction using image-based motion-estimation computed tomography (CT) (iME) and a prior history of stroke or transient ischaemic attack (TIA) in patients with atrial fibrillation (AF). METHODS AND RESULTS: In this single-centre retrospective case-control study, among patients referred for AF ablation who underwent pre-ablation cardiac CT with retrospective ECG gating, we identified 18 patients with a prior history of stroke or TIA at the time of CT scan and 18 age- and gender-matched controls. All the patients were in sinus rhythm at the time of CT scan. Four-dimensional motion vector field was estimated from the CT images using iME. To assess myocardial deformation, area change ratio (A) and area change rate (AR) were calculated over the endocardial surface of the LAA. There was no significant difference in the baseline patient characteristics between the stroke/TIA group and the control group (67.6 ± 8.1 years old, 66.7% male, 16.7% persistent AF). LAA maximum (Amax; 23.8 ± 33.0 vs. 52.9 ± 41.2%, P = 0.02) and pre-atrial contraction area change ratio (ApreA; 13.7 ± 17.7 vs. 30.9 ± 29.2%, P = 0.04) were significantly lower in the stroke/TIA group than in the control group, respectively. The difference in LAA Amax and ApreA remained significant in multivariate analysis (P = 0.03 and P = 0.04, respectively). CONCLUSION: LAA regional dysfunction is associated with stroke/TIA in AF patients. Our results offer a basis for a prospective study to determine the role of LAA regional dysfunction by iME in predicting cerebrovascular events such as stroke or TIA.

A new redundancy weighting scheme for nonstationary data for computed tomography.

PURPOSE: The same projection data (or line integrals) are often measured multiple times, e.g., twice from opposite directions during one gantry rotation. The redundant data must be normalized by applying redundancy weighting such as the halfscan algorithm, which assumes that the noise of the data is uniform. This assumption, however, is not correct when a tube current modulation technique is employed. The variance of line integrals, which is inversely related to the tube current, could vary significantly. The purpose of this work is to improve how the projection data are used during analytical reconstruction when the tube current is modulated during the scan. METHODS: The authors developed a new redundancy weighting scheme. It not only takes into account the data statistics but also can control how much to weigh the statistics from 100% (αs = 1.0) to 0% (αs = 0.0) by a parameter αs. The proposed weighting scheme reduces to the conventional redundancy weighting scheme when αs = 0.0. The authors evaluated the performance of the proposed scheme using computer simulations targeting at myocardial perfusion CT imaging. The image quality was evaluated in terms of the image noise and halfscan artifacts, and perfusion defect detection performance was evaluated by the positive predictive value (PPV) and the area-under-the-receiver operating characteristic-curve (AUC) value. RESULTS: Results showed a tradeoff between the image noise and halfscan artifacts. The normalized noise standard deviation was 1.00 with halfscan, 0.89 with αs = 1.0, 0.97 with αs = 0.5, and 1.20 with αs = 0.0 when projections over one rotation (75% of projections are acquired with full dose, 25% with 1/10 of the full dose) are used. The halfscan artifacts were 13.4 Hounsfield unit (HU) with halfscan, 8.2 HU with αs = 1.0, 4.5 HU with αs = 0.5, and 3.1 HU with αs = 0.0. Both the PPVs and AUCs were improved from the halfscan method: PPV, 69.0%-70.6% vs 58.0%, P < 0.003; AUC, 0.935-0.938 vs 0.908, P < 0.003. CONCLUSIONS: The new redundancy weight allows for decreasing the image noise and controlling the tradeoff between the image noise and artifacts.

Quantitative assessment of atrial regional function using motion estimation computed tomography.

OBJECTIVES: We validated a novel image-based motion estimation computed tomographic (CT) technique (iME) to quantify atrial regional function in swine in vivo. MATERIALS AND METHODS: Domestic swine (n = 8) underwent CT scan with intravenous contrast before and after median sternotomy where 15 to 30 glass beads were sutured to the atria to calculate the motion estimation error. Four-dimensional motion vector field was estimated using iME. Area change ratio (%AC) was calculated over the atrial endocardium to assess the surface deformation. RESULTS: The error between the measured and the calculated coordinates based on motion vector field was 0.76 ± 0.43 mm. The %AC was regionally heterogeneous. The %AC time course was significantly different between the right and the left atriums (P < 0.001) as well as between the right atrial appendage and the right atrial chamber (P = 0.004). CONCLUSIONS: Quantitative assessment of atrial regional function using iME is highly accurate. Image-based motion estimation computed tomographic (CT) technique can quantify subtle regional dysfunction that is not apparent in global functional indices such as ejection fraction.

A cascaded model of spectral distortions due to spectral response effects and pulse pileup effects in a photon-counting x-ray detector for CT.

PURPOSE: Energy discriminating, photon-counting detectors (PCDs) are an emerging technology for computed tomography (CT) with various potential benefits for clinical CT. The photon energies measured by PCDs can be distorted due to the interactions of a photon with the detector and the interaction of multiple coincident photons. These effects result in distorted recorded x-ray spectra which may lead to artifacts in reconstructed CT images and inaccuracies in tissue identification. Model-based compensation techniques have the potential to account for the distortion effects. This approach requires only a small number of parameters and is applicable to a wide range of spectra and count rates, but it needs an accurate model of the spectral distortions occurring in PCDs. The purpose of this study was to develop a model of those spectral distortions and to evaluate the model using a PCD (model DXMCT-1; DxRay, Inc., Northridge, CA) and various x-ray spectra in a wide range of count rates. METHODS: The authors hypothesize that the complex phenomena of spectral distortions can be modeled by: (1) separating them into count-rate independent factors that we call the spectral response effects (SRE), and count-rate dependent factors that we call the pulse pileup effects (PPE), (2) developing separate models for SRE and PPE, and (3) cascading the SRE and PPE models into a combined SRE+PPE model that describes PCD distortions at both low and high count rates. The SRE model describes the probability distribution of the recorded spectrum, with a photo peak and a continuum tail, given the incident photon energy. Model parameters were obtained from calibration measurements with three radioisotopes and then interpolated linearly for other energies. The PPE model used was developed in the authors' previous work [K. Taguchi et al., "Modeling the performance of a photon counting x-ray detector for CT: Energy response and pulse pileup effects," Med. Phys. 38(2), 1089-1102 (2011)]. The agreement between the x-ray spectra calculated by the cascaded SRE+PPE model and the measured spectra was evaluated for various levels of deadtime loss ratios (DLR) and incident spectral shapes, realized using different attenuators, in terms of the weighted coefficient of variation (COVW), i.e., the root mean square difference weighted by the statistical errors of the data and divided by the mean. RESULTS: At low count rates, when DLR < 10%, the distorted spectra measured by the DXMCT-1 were in agreement with those calculated by SRE only, with COVW's less than 4%. At higher count rates, the measured spectra were also in agreement with the ones calculated by the cascaded SRE+PPE model; with PMMA as attenuator, COVW was 5.6% at a DLR of 22% and as small as 6.7% for a DLR as high as 55%. CONCLUSIONS: The x-ray spectra calculated by the proposed model agreed with the measured spectra over a wide range of count rates and spectral shapes. The SRE model predicted the distorted, recorded spectra with low count rates over various types and thicknesses of attenuators. The study also validated the hypothesis that the complex spectral distortions in a PCD can be adequately modeled by cascading the count-rate independent SRE and the count-rate dependent PPE.

A fully four-dimensional, iterative motion estimation and compensation method for cardiac CT.

PURPOSE: To develop a new fully four-dimensional (4D), iterative image reconstruction algorithm for cardiac CT that alternates the following two methods: estimation of a time-dependent motion vector field (MVF) of the heart from image data and reconstruction of images using the estimated MVF and projection data. METHODS: Volumetric image data at different cardiac phase points were obtained using electrocardiogram-gated CT. Motion estimation (ME) and motion-compensated image reconstruction (MCR) were performed alternately until convergence was achieved. The ME method estimated the cardiac MVF using 4D nonrigid image registration between a cardiac reference phase and all the other phases. The nonrigid deformation of the heart was modeled using cubic B-splines. The cost function consisted of a sum of squared weighted differences and spatial and temporal regularization terms. A nested conjugate gradient optimization algorithm was applied to minimize the cost function and estimate the MVFs. Cardiac images were reconstructed using a motion-tracking algorithm that utilized the MVFs estimated by the ME method. The reconstructed images supplied the input to the ME of the next iteration. The performance of the proposed method was evaluated using four patient data sets acquired with a 64-slice CT scanner. The heart rates of the patients ranged from 52 to 71 beats/min. RESULTS: Motion artifacts were significantly reduced, and the image quality increased with the number of iterations. Without MCR, the right coronary artery (RCA) was deformed into an arc in axial images of rapid phases. With the proposed method the RCA appeared sharper and was reconstructed similar in shape to the reconstruction at the quiescent phase at mid-diastole. The boundary between the interventricular septum and the right ventricle was also clearer and sharper using the proposed algorithm. The steepness of the transition range at a rapid phase (35% R-R) was increased from 6.8 HU∕pixel to 11.5 HU∕pixel. The ME-MCR algorithm converged in just four iterations. CONCLUSION: We developed a fully 4D image reconstruction method that alternates ME and MCR algorithms in an iterative fashion. Performance tests using clinical patient data resulted in reduced motion artifacts.

Interior region-of-interest reconstruction using a small, nearly piecewise constant subregion.

PURPOSE: To develop a method to reconstruct an interior region-of-interest (ROI) image with sufficient accuracy that uses differentiated backprojection (DBP) projection onto convex sets (POCS) [H. Kudo et al., "Tiny a priori knowledge solves the interior problem in computed tomography," Phys. Med. Biol. 53, 2207-2231 (2008)] and a tiny knowledge that there exists a nearly piecewise constant subregion. METHODS: The proposed method first employs filtered backprojection to reconstruct an image on which a tiny region P with a small variation in the pixel values is identified inside the ROI. Total variation minimization [H. Yu and G. Wang, "Compressed sensing based interior tomography," Phys. Med. Biol. 54, 2791-2805 (2009); W. Han et al., "A general total variation minimization theorem for compressed sensing based interior tomography," Int. J. Biomed. Imaging 2009, Article 125871 (2009)] is then employed to obtain pixel values in the subregion P, which serve as a priori knowledge in the next step. Finally, DBP-POCS is performed to reconstruct f(x,y) inside the ROI. Clinical data and the reconstructed image obtained by an x-ray computed tomography system (SOMATOM Definition; Siemens Healthcare) were used to validate the proposed method. The detector covers an object with a diameter of approximately 500 mm. The projection data were truncated either moderately to limit the detector coverage to Ø 350 mm of the object or severely to cover Ø199 mm. Images were reconstructed using the proposed method. RESULTS: The proposed method provided ROI images with correct pixel values in all areas except near the edge of the ROI. The coefficient of variation, i.e., the root mean square error divided by the mean pixel values, was less than 2.0% or 4.5% with the moderate or severe truncation cases, respectively, except near the boundary of the ROI. CONCLUSIONS: The proposed method allows for reconstructing interior ROI images with sufficient accuracy with a tiny knowledge that there exists a nearly piecewise constant subregion.