Effectiveness of the Spot tm Vision Screener With Variations in Ocular Pigments.

PURPOSE: To evaluate Spot in detecting American Association for Pediatric Ophthalmology and Strabismus (AAPOS) Amblyopia risk factors (ARF) and for ARF myopia and hyperopia with variations in ocular pigments. DESIGN: Diagnostic screening test evaluation. METHODS: Study population: Children presented for a complete eye examination in pediatric clinic. The study population included 1040 participants, of whom 273 had darkly pigmented eyes, 303 were medium pigmented, and 464 were light pigmented. INTERVENTION: Children were screened with the Spot vision screener before the complete eye examination. A pediatric ophthalmologist then completed an eye examination, including cycloplegic refraction. The pediatric ophthalmologist was blinded to the result of the Spot vision screener. MAIN OUTCOME: The association between Spot screening recommendation and meeting one or more ARF/ARF + Amblyopia criterion, Spot measured spherical equivalent, and ARF myopia and hyperopia detection. RESULTS: The area under the receiver operative characteristic curve (AUC) for myopia was excellent for all. The AUC for hyperopia was good (darker-pigmented: 0.92, medium-pigmented: 0.81, and lighter-pigmented: 0.86 eyes). The Spot was most sensitive for ARF myopia (lighter-pigmented: 0.78, medium-pigmented: 0.52, darker-pigmented: 0.49). The reverse was found for hyperopia; however, sensitivity was relatively poor. The Spot was found most sensitive for hyperopia in the darker-pigment group (0.46), 0.27 for medium-pigment, and 0.23 for the lighter-pigment cohort. CONCLUSIONS: While the Spot was confirmed as a sensitive screening test with good specificity in our large cohort, the sensitivity of the Spot in detecting AAPOS guidelines for myopia and hyperopia differed with variations in skin pigment. Our results support the consideration of ethnic and racial diversity in future advances in photorefractor technology.

Effectiveness of the Spot Vision Screener using updated 2021 AAPOS guidelines.

PURPOSE: To evaluate the Spot Vision Screener according to updated 2021 AAPOS Vision Screening Committee guidelines for instrument-based pediatric vision screen validation. METHODS: As part of an IRB-approved ongoing prospective study, children were screened with the Spot prior to a complete examination. RESULTS: Spot screening was successful in 1,036 of 1,090 children (95%). Forty-eight percent of participants were referred for further screening using the Spot manufacturer guidelines, and 40% of all children were found to have a 2021 amblyopia risk factor or visually significant refractive error by gold standard examination. The Spot recommendation compared reasonably well to the 2021 criteria, with an overall sensitivity of 0.88 and a specificity of 0.78. Applying updated guidelines to the Spot for hyperopia, anisometropia, and astigmatism yielded moderate-to-poor sensitivity (0.27-0.77) but excellent specificity (>0.9). The area under the curve of the receiver operating characteristic analysis demonstrates overall good prediction performance for the Spot for each diagnosis-myopia, hyperopia, astigmatism, anisometropia (range, 0.87-0.97). Results of our study suggest increasing the instrument referral criterion for astigmatism from 1.5 D (manufacturer thresholds of the screener used in this study) to 2 D in older children. Decreasing the anisometropia cut-off from 1 D to 0.75 D would improve sensitivity from 0.59 to >0.8. CONCLUSIONS: In our study population, the overall predictive ability of the Spot is good, with a sensitivity of 0.88 and a specificity of 0.78. We recommend specific device refractive referral criteria to maximize screening effectiveness using the updated AAPOS guidelines.

The blinq™ Vision Screener in Detection of Amblyopia and Strabismus.

PURPOSE: The blinq (Rebion Inc) is a new screening device designed to directly detect amblyopia and strabismus rather than amblyopia risk factors. We performed an independent assessment of the effectiveness of the blinq in detecting amblyopia and strabismus. DESIGN: Prospective clinical validity analysis of a screening device based on sensitivity and specificity. METHODS: Children presenting for examination in the pediatric ophthalmology clinic underwent screening with the blinq before examination by a pediatric ophthalmologist blinded to the screening results. Results of the blinq and examination findings of strabismus or amblyopia were compared. RESULTS: In our cohort of 267 children with an average age of 6.3 years, the sensitivity of the blinq to detect amblyopia or any constant strabismus was 87.5% (78.2%-93.8%) and specificity was 51.3% (43.9%-58.7%). Using the previously described "appropriate referral gold standard" criteria, including children with intermittent strabismus and high refractive error, the sensitivity increased to 91.3% and the specificity to 63.2%. We found a high number of children (44 [16%]) upon whom the blinq timed out and were included as automatic referrals. CONCLUSIONS: Our results support use of the blinq as a screening device to detect amblyopia and strabismus in children.

Quantification of lung function on CT images based on pulmonary radiomic filtering.

PURPOSE: To develop a radiomics filtering technique for characterizing spatial-encoded regional pulmonary ventilation information on lung computed tomography (CT). METHODS: The lung volume was segmented on 46 CT images, and a 3D sliding window kernel was implemented across the lung volume to capture the spatial-encoded image information. Fifty-three radiomic features were extracted within the kernel, resulting in a fourth-order tensor object. As such, each voxel coordinate of the original lung was represented as a 53-dimensional feature vector, such that radiomic features could be viewed as feature maps within the lungs. To test the technique as a potential pulmonary ventilation biomarker, the radiomic feature maps were compared to paired functional images (Galligas PET or DTPA-SPECT) based on the Spearman correlation (ρ) analysis. RESULTS: The radiomic feature maps GLRLM-based Run-Length Non-Uniformity and GLCOM-based Sum Average are found to be highly correlated with the functional imaging. The achieved ρ (median [range]) for the two features are 0.46 [0.05, 0.67] and 0.45 [0.21, 0.65] across 46 patients and 2 functional imaging modalities, respectively. CONCLUSIONS: The results provide evidence that local regions of sparsely encoded heterogeneous lung parenchyma on CT are associated with diminished radiotracer uptake and measured lung ventilation defects on PET/SPECT imaging. These findings demonstrate the potential of radiomics to serve as a complementary tool to the current lung quantification techniques and provide hypothesis-generating data for future studies.

Task Group 174 Report: Utilization of [18 F]Fluorodeoxyglucose Positron Emission Tomography ([18 F]FDG-PET) in Radiation Therapy.

The use of positron emission tomography (PET) in radiation therapy (RT) is rapidly increasing in the areas of staging, segmentation, treatment planning, and response assessment. The most common radiotracer is 18 F-fluorodeoxyglucose ([18 F]FDG), a glucose analog with demonstrated efficacy in cancer diagnosis and staging. However, diagnosis and RT planning are different endeavors with unique requirements, and very little literature is available for guiding physicists and clinicians in the utilization of [18 F]FDG-PET in RT. The two goals of this report are to educate and provide recommendations. The report provides background and education on current PET imaging systems, PET tracers, intensity quantification, and current utilization in RT (staging, segmentation, image registration, treatment planning, and therapy response assessment). Recommendations are provided on acceptance testing, annual and monthly quality assurance, scanning protocols to ensure consistency between interpatient scans and intrapatient longitudinal scans, reporting of patient and scan parameters in literature, requirements for incorporation of [18 F]FDG-PET in treatment planning systems, and image registration. The recommendations provided here are minimum requirements and are not meant to cover all aspects of the use of [18 F]FDG-PET for RT.

Impact of moving target on measurement accuracy in 3D and 4D PET imaging-a phantom study.

PURPOSE: The purpose of this study was to evaluate the impact of tumor motion on maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) measurements in both 3-dimensional and respiratory-correlated, 4-dimensional positron emission tomography (PET) imaging. We also evaluated the effect of implementing different attenuation correction methods in 4-dimensional PET image reconstruction on SUVmax and MTV. METHODS AND MATERIALS: An anthropomorphic thorax phantom with a spherical ball as a surrogate for a tumor was used. Different types of motion were imposed on the ball to mimic a patient's breathing motion. Three-dimensional PET imaging of the phantom without tumor motion was performed and used as the reference. The ball was then set in motion with different breathing motion traces and imaged with both 3- and 4-dimensional PET methods. The clinical 4-dimensional PET imaging protocol was modified so that 3 different types of attenuation correction images were used for reconstructions: the same free-breathing computed tomography (CT) for all PET phases, the same average intensity projection CT for all PET phases, and 4-dimensional CT for phase-matched attenuation correction. Tumor SUVmax and MTV values that were measured from the moving phantom were compared with the reference values. RESULTS: SUVmax that was measured in 3-dimensional PET imaging was different from the reference value by 20.4% on average for the motions that were investigated; this difference decreased to 2.6% with 4-dimensional PET imaging. The measurement of MTV in 4-dimensional PET also showed a similar magnitude of reduction of deviation compared with 3-dimensional PET. Four-dimensional PET with use of phase-matched 4-dimensional CT for attenuation correction showed less variation in SUVmax and MTV among phases compared with 4-dimensional PET with free-breathing CT or average intensity projection CT for attenuation correction. CONCLUSIONS: Four-dimensional PET imaging reduces the impact of motion on measured SUVmax and MTV when compared with 3-dimensional PET imaging. Clinical 4-dimensional PET imaging protocols should consider phase-matched 4-dimensional CT imaging for attenuation correction to achieve more accurate measurements.

A pilot randomized clinical trial of intermittent occlusion therapy liquid crystal glasses versus traditional patching for treatment of moderate unilateral amblyopia.

PURPOSE: To compare the effectiveness of intermittent occlusion therapy (IO therapy) using liquid crystal glasses and continuous occlusion therapy using traditional adhesive patches for treating amblyopia. METHODS: Children 3-8 years of age with previously untreated, moderate, unilateral amblyopia (visual acuity of 20/40 to 20/100 in the amblyopic eye) were enrolled in this randomized controlled trial. Amblyopia was associated with strabismus, anisometropia, or both. All subjects had worn any optimal refractive correction for at least 12 weeks without improvement. Subjects were randomized into two treatment groups: a 4-hour IO therapy group with liquid crystal glasses (Amblyz), set at 30-second opaque/transparent intervals (occluded 50% of wear time), and a 2-hour continuous patching group (occluded 100% of wear time). For each patient, visual acuity was measured using ATS-HOTV before and after 12 weeks of treatment. RESULTS: Data from 34 patients were available for analysis. Amblyopic eye visual acuity improvement from baseline was 0.15 ± 0.12 logMAR (95% CI, 0.09-0.15) in the IO therapy group (n = 19) and 0.15 ± 0.11 logMAR (95% CI, 0.1-0.15) in the patching group (n = 15). In both groups improvement was significant, but the difference between groups was not (P = 0.73). No adverse effects were reported. CONCLUSIONS: In this pilot study, IO therapy with liquid crystal glasses is not inferior to adhesive patching and is a promising alternative treatment for children 3-8 years of age with moderate amblyopia.

A Case for Wide-Angle Breast Tomosynthesis.

RATIONALES AND OBJECTIVES: Conventional mammography is largely limited by superimposed anatomy. Digital breast tomosynthesis (DBT) and computed tomography (CT) alleviate this limitation but with added out-of-plane artifacts or limited chest wall coverage. This article presents a wide-angle breast tomosynthesis (WBT), aimed to provide a practical solution to these limitations, and offers an initial study of its utility in comparison with DBT and CT using a singular evaluation platform. MATERIALS AND METHODS: Using an anthropomorphic virtual breast phantom, a Monte Carlo code modeled a breast imaging system for three modalities of DBT, WBT, and breast CT (44°, 99°, and 198° total angle range, respectively) at four breast compression levels, all at a constant mean glandular dose level of 1.5 mGy. Reconstructed volumes were generated using iterative reconstruction methods. Lesion detectability was estimated using contrast-to-noise ratio and a channelized Hotelling observer model in terms of the area under the receiver operating characteristic (AUC). RESULTS: Results showed improved detection with increased angular span and compression. The estimated AUCs for WBT were similar to that of CT. Comparative performance averaged over all thicknesses between CT and WBT was 4.3 ± 3.0%, whereas that between WBT and DBT was 5.6 ± 1.0%. At compression levels reflective of the modality (7-, 5-, and 4-cm thickness for CT, WBT, and DBT, respectively), WBT yielded an AUC comparable to CT (performance difference of 1.2%) but superior to DBT (performance difference of 5.5%). CONCLUSIONS: The proposed imaging modality showed significant advantages over conventional DBT. WBT exhibited superior imaging performance over DBT at lower compression levels, highlighting further potential for reduced breast compression.

A hardware investigation of robotic SPECT for functional and molecular imaging onboard radiation therapy systems.

PURPOSE: To construct a robotic SPECT system and to demonstrate its capability to image a thorax phantom on a radiation therapy flat-top couch, as a step toward onboard functional and molecular imaging in radiation therapy. METHODS: A robotic SPECT imaging system was constructed utilizing a gamma camera detector (Digirad 2020tc) and a robot (KUKA KR150 L110 robot). An imaging study was performed with a phantom (PET CT Phantom(TM)), which includes five spheres of 10, 13, 17, 22, and 28 mm diameters. The phantom was placed on a flat-top couch. SPECT projections were acquired either with a parallel-hole collimator or a single-pinhole collimator, both without background in the phantom and with background at 1/10th the sphere activity concentration. The imaging trajectories of parallel-hole and pinhole collimated detectors spanned 180° and 228°, respectively. The pinhole detector viewed an off-centered spherical common volume which encompassed the 28 and 22 mm spheres. The common volume for parallel-hole system was centered at the phantom which encompassed all five spheres in the phantom. The maneuverability of the robotic system was tested by navigating the detector to trace the phantom and flat-top table while avoiding collision and maintaining the closest possible proximity to the common volume. The robot base and tool coordinates were used for image reconstruction. RESULTS: The robotic SPECT system was able to maneuver parallel-hole and pinhole collimated SPECT detectors in close proximity to the phantom, minimizing impact of the flat-top couch on detector radius of rotation. Without background, all five spheres were visible in the reconstructed parallel-hole image, while four spheres, all except the smallest one, were visible in the reconstructed pinhole image. With background, three spheres of 17, 22, and 28 mm diameters were readily observed with the parallel-hole imaging, and the targeted spheres (22 and 28 mm diameters) were readily observed in the pinhole region-of-interest imaging. CONCLUSIONS: Onboard SPECT could be achieved by a robot maneuvering a SPECT detector about patients in position for radiation therapy on a flat-top couch. The robot inherent coordinate frames could be an effective means to estimate detector pose for use in SPECT image reconstruction.

Onboard functional and molecular imaging: a design investigation for robotic multipinhole SPECT.

PURPOSE: Onboard imaging-currently performed primarily by x-ray transmission modalities-is essential in modern radiation therapy. As radiation therapy moves toward personalized medicine, molecular imaging, which views individual gene expression, may also be important onboard. Nuclear medicine methods, such as single photon emission computed tomography (SPECT), are premier modalities for molecular imaging. The purpose of this study is to investigate a robotic multipinhole approach to onboard SPECT. METHODS: Computer-aided design (CAD) studies were performed to assess the feasibility of maneuvering a robotic SPECT system about a patient in position for radiation therapy. In order to obtain fast, high-quality SPECT images, a 49-pinhole SPECT camera was designed which provides high sensitivity to photons emitted from an imaging region of interest. This multipinhole system was investigated by computer-simulation studies. Seventeen hot spots 10 and 7 mm in diameter were placed in the breast region of a supine female phantom. Hot spot activity concentration was six times that of background. For the 49-pinhole camera and a reference, more conventional, broad field-of-view (FOV) SPECT system, projection data were computer simulated for 4-min scans and SPECT images were reconstructed. Hot-spot localization was evaluated using a nonprewhitening forced-choice numerical observer. RESULTS: The CAD simulation studies found that robots could maneuver SPECT cameras about patients in position for radiation therapy. In the imaging studies, most hot spots were apparent in the 49-pinhole images. Average localization errors for 10-mm- and 7-mm-diameter hot spots were 0.4 and 1.7 mm, respectively, for the 49-pinhole system, and 3.1 and 5.7 mm, respectively, for the reference broad-FOV system. CONCLUSIONS: A robot could maneuver a multipinhole SPECT system about a patient in position for radiation therapy. The system could provide onboard functional and molecular imaging with 4-min scan times.

A line-source method for aligning on-board and other pinhole SPECT systems.

PURPOSE: In order to achieve functional and molecular imaging as patients are in position for radiation therapy, a robotic multipinhole SPECT system is being developed. Alignment of the SPECT system-to the linear accelerator (LINAC) coordinate frame and to the coordinate frames of other on-board imaging systems such as cone-beam CT (CBCT)-is essential for target localization and image reconstruction. An alignment method that utilizes line sources and one pinhole projection is proposed and investigated to achieve this goal. Potentially, this method could also be applied to the calibration of the other pinhole SPECT systems. METHODS: An alignment model consisting of multiple alignment parameters was developed which maps line sources in three-dimensional (3D) space to their two-dimensional (2D) projections on the SPECT detector. In a computer-simulation study, 3D coordinates of line-sources were defined in a reference room coordinate frame, such as the LINAC coordinate frame. Corresponding 2D line-source projections were generated by computer simulation that included SPECT blurring and noise effects. The Radon transform was utilized to detect angles (α) and offsets (ρ) of the line-source projections. Alignment parameters were then estimated by a nonlinear least squares method, based on the α and ρ values and the alignment model. Alignment performance was evaluated as a function of number of line sources, Radon transform accuracy, finite line-source width, intrinsic camera resolution, Poisson noise, and acquisition geometry. Experimental evaluations were performed using a physical line-source phantom and a pinhole-collimated gamma camera attached to a robot. RESULTS: In computer-simulation studies, when there was no error in determining angles (α) and offsets (ρ) of the measured projections, six alignment parameters (three translational and three rotational) were estimated perfectly using three line sources. When angles (α) and offsets (ρ) were provided by the Radon transform, estimation accuracy was reduced. The estimation error was associated with rounding errors of Radon transform, finite line-source width, Poisson noise, number of line sources, intrinsic camera resolution, and detector acquisition geometry. Statistically, the estimation accuracy was significantly improved by using four line sources rather than three and by thinner line-source projections (obtained by better intrinsic detector resolution). With five line sources, median errors were 0.2 mm for the detector translations, 0.7 mm for the detector radius of rotation, and less than 0.5° for detector rotation, tilt, and twist. In experimental evaluations, average errors relative to a different, independent registration technique were about 1.8 mm for detector translations, 1.1 mm for the detector radius of rotation (ROR), 0.5° and 0.4° for detector rotation and tilt, respectively, and 1.2° for detector twist. CONCLUSIONS: Alignment parameters can be estimated using one pinhole projection of line sources. Alignment errors are largely associated with limited accuracy of the Radon transform in determining angles (α) and offsets (ρ) of the line-source projections. This alignment method may be important for multipinhole SPECT, where relative pinhole alignment may vary during rotation. For pinhole and multipinhole SPECT imaging on-board radiation therapy machines, the method could provide alignment of SPECT coordinates with those of CBCT and the LINAC.

Anomaly Detection and Artifact Recovery in PET Attenuation-Correction Images Using the Likelihood Function.

In dual modality PET/CT, CT data are used to generate the attenuation correction applied in the reconstruction of the PET emission image. This requires converting the CT image into a 511-keV attenuation map. Algorithms for making this transformation require assumptions about the makeup of material within the patient. Anomalous material such as contrast agent administered to enhance the CT scan confounds conversion algorithms and has been observed to result in inaccuracies, i.e., inconsistencies with the true 511-keV attenuation present at the time of the PET emission scan. These attenuation artifacts carry through to the final attenuation-corrected PET emission image and can resemble diseased tissue. We propose an approach to correcting this problem that employs the attenuation information carried by the PET emission data. A likelihood-based algorithm for identifying and correcting of contrast is presented and tested. The algorithm exploits the fact that contrast artifacts manifest as too-high attenuation values in an otherwise high quality attenuation image. In a separate study, the performance of the loglikelihood as an objective-function component of a detection/correction algorithm, independent of any particular algorithm was mapped out for several imaging scenarios as a function of statistical noise. Both the full algorithm and the loglikelihood performed well in studies with simulated data. Additional studies including those with patient data are required to fully understand their capabilities.

Influence of filter choice on 18F-FDG PET segmentation accuracy determined using generalized estimating equations.

This study aims to quantify how filter choice affects several fluoro-deoxy-glucose (FDG)-positron emission tomography (PET) segmentation methods and present the use of model fitting via generalized estimating equations (GEEs) to appropriately account for the properties of a common segmentation quality metric (Dice similarity coefficient). Spherical and irregularly shaped 'hot' objects filled with 18F-FDG were placed in a medium with background activity and imaged for 1, 2 and 5 min durations at low and high contrasts. Images were filtered with Gaussian and bilateral filters of 5 and 7 mm full-width half maximum (FWHM), with and without 3 mm FWHM Gaussian pre-smoothing. Four segmentation methods were used: 40% thresholding, adaptive thresholding, k-means clustering and seeded region-growing. Segmentation accuracy was quantified by overlap (using Dice similarity coefficient (DSC)) and distance between surfaces (using symmetric-mean-absolute-surface-distance (SMASD)) of the ground truth and segmented volumes. All segmentation methods showed mean DSC values between 0.71-0.87 and mean SMASD values between 0.72-2.10 mm across filters. The bilateral filter with 3 mm FWHM Gaussian pre-smoothing had mean DSC 0.80 ± 0.17 and mean SMASD 1.17 ± 1.51 mm displaying approximately equal performance to a 5 mm Gaussian filter with mean DSC 0.79 ± 0.18 and mean SMASD 1.27 ± 1.52 mm. Results from models fit using GEE with a binomial distribution and exchangeable correlation structure estimated the correlation between DSC values as 0.118 and 0.290 for spheres and irregular objects, respectively. The GEE approach accounts for several factors specific to the DSC metric that simpler statistical approaches do not, providing more accurate estimations of experimental effects commonly associated with nuclear medicine segmentation studies.

Combining multiple FDG-PET radiotherapy target segmentation methods to reduce the effect of variable performance of individual segmentation methods.

PURPOSE: Many approaches have been proposed to segment high uptake objects in 18F-fluoro-deoxy-glucose positron emission tomography images but none provides consistent performance across the large variety of imaging situations. This study investigates the use of two methods of combining individual segmentation methods to reduce the impact of inconsistent performance of the individual methods: simple majority voting and probabilistic estimation. METHODS: The National Electrical Manufacturers Association image quality phantom containing five glass spheres with diameters 13-37 mm and two irregularly shaped volumes (16 and 32 cc) formed by deforming high-density polyethylene bottles in a hot water bath were filled with 18-fluoro-deoxyglucose and iodine contrast agent. Repeated 5-min positron emission tomography (PET) images were acquired at 4:1 and 8:1 object-to-background contrasts for spherical objects and 4.5:1 and 9:1 for irregular objects. Five individual methods were used to segment each object: 40% thresholding, adaptive thresholding, k-means clustering, seeded region-growing, and a gradient based method. Volumes were combined using a majority vote (MJV) or Simultaneous Truth And Performance Level Estimate (STAPLE) method. Accuracy of segmentations relative to CT ground truth volumes were assessed using the Dice similarity coefficient (DSC) and the symmetric mean absolute surface distances (SMASDs). RESULTS: MJV had median DSC values of 0.886 and 0.875; and SMASD of 0.52 and 0.71 mm for spheres and irregular shapes, respectively. STAPLE provided similar results with median DSC of 0.886 and 0.871; and median SMASD of 0.50 and 0.72 mm for spheres and irregular shapes, respectively. STAPLE had significantly higher DSC and lower SMASD values than MJV for spheres (DSC, p < 0.0001; SMASD, p = 0.0101) but MJV had significantly higher DSC and lower SMASD values compared to STAPLE for irregular shapes (DSC, p < 0.0001; SMASD, p = 0.0027). DSC was not significantly different between 128 × 128 and 256 × 256 grid sizes for either method (MJV, p = 0.0519; STAPLE, p = 0.5672) but was for SMASD values (MJV, p < 0.0001; STAPLE, p = 0.0164). The best individual method varied depending on object characteristics. However, both MJV and STAPLE provided essentially equivalent accuracy to using the best independent method in every situation, with mean differences in DSC of 0.01-0.03, and 0.05-0.12 mm for SMASD. CONCLUSIONS: Combining segmentations offers a robust approach to object segmentation in PET. Both MJV and STAPLE improved accuracy and were robust against the widely varying performance of individual segmentation methods. Differences between MJV and STAPLE are such that either offers good performance when combining volumes. Neither method requires a training dataset but MJV is simpler to interpret, easy to implement and fast.

A dual cone-beam CT system for image guided radiotherapy: initial performance characterization.

PURPOSE: The purpose of this study is to evaluate the performance of a recently developed benchtop dual cone-beam computed tomography (CBCT) system with two orthogonally placed tube∕detector sets. METHODS: The benchtop dual CBCT system consists of two orthogonally placed 40 × 30 cm flat-panel detectors and two conventional x-ray tubes with two individual high-voltage generators sharing the same rotational axis. The x-ray source to detector distance is 150 cm and x-ray source to rotational axis distance is 100 cm for both subsystems. The objects are scanned through 200° of rotation. The dual CBCT system utilized 110° of projection data from one detector and 90° from the other while the two individual single CBCTs utilized 200° data from each detector. The system performance was characterized in terms of uniformity, contrast, spatial resolution, noise power spectrum, and CT number linearity. The uniformities, within the axial slice and along the longitudinal direction, and noise power spectrum were assessed by scanning a water bucket; the contrast and CT number linearity were measured using the Catphan phantom; and the spatial resolution was evaluated using a tungsten wire phantom. A skull phantom and a ham were also scanned to provide qualitative evaluation of high- and low-contrast resolution. Each measurement was compared between dual and single CBCT systems. RESULTS: Compared to single CBCT, the dual CBCT presented: (1) a decrease in uniformity by 1.9% in axial view and 1.1% in the longitudinal view, as averaged for four energies (80, 100, 125, and 150 kVp); (2) comparable or slightly better contrast (0∼25 HU) for low-contrast objects and comparable contrast for high-contrast objects; (3) comparable spatial resolution; (4) comparable CT number linearity with R(2) ≥ 0.99 for all four tested energies; (5) lower noise power spectrum in magnitude. Dual CBCT images of the skull phantom and the ham demonstrated both high-contrast resolution and good soft-tissue contrast. CONCLUSIONS: The performance of a benchtop dual CBCT imaging system has been characterized and is comparable to that of a single CBCT.

Successful transplantation of human hepatic stem cells with restricted localization to liver using hyaluronan grafts.

Cell therapies are potential alternatives to organ transplantation for liver failure or dysfunction but are compromised by inefficient engraftment, cell dispersal to ectopic sites, and emboli formation. Grafting strategies have been devised for transplantation of human hepatic stem cells (hHpSCs) embedded into a mix of soluble signals and extracellular matrix biomaterials (hyaluronans, type III collagen, laminin) found in stem cell niches. The hHpSCs maintain a stable stem cell phenotype under the graft conditions. The grafts were transplanted into the livers of immunocompromised murine hosts with and without carbon tetrachloride treatment to assess the effects of quiescent versus injured liver conditions. Grafted cells remained localized to the livers, resulting in a larger bolus of engrafted cells in the host livers under quiescent conditions and with potential for more rapid expansion under injured liver conditions. By contrast, transplantation by direct injection or via a vascular route resulted in inefficient engraftment and cell dispersal to ectopic sites. Transplantation by grafting is proposed as a preferred strategy for cell therapies for solid organs such as the liver.

Interleaved acquisition for cross scatter avoidance in dual cone-beam CT.

PURPOSE: Cone-beam x-ray imaging with flat panel detectors is used for target localization in image guided radiation therapy. This imaging includes cone-beam computed tomography (CBCT) and planar imaging. Use of two orthogonal x-ray systems could reduce imaging time for CBCT, provide simultaneous orthogonal views in planar imaging, facilitate dual-energy methods, and be useful in alleviating cone-beam artifacts by providing two axially offset focal-spot trajectories. However, the potential advantages of a second cone-beam system come at the cost of cross scatter, i.e., scatter of photons originating from one tube into the noncorresponding detector. Herein, cross scatter is characterized for dual cone-beam imaging, and a method for avoiding cross scatter is proposed and evaluated. METHODS: A prototype dual-source CBCT system has been developed that models the geometry of a gantry-mounted kV imaging device used in radiation therapy. Cross scatter was characterized from 70 to 145 kVp in projections and reconstructed images using this system and three cylindrical phantoms (15, 20, and 30 cm) with a common Catphan core. A novel strategy for avoiding cross scatter in dual CBCT was developed that utilized interleaved data acquisition on each imaging chain. Interleaving, while maintaining similar angular sampling, can be achieved by either doubling the data acquisition rate or, as presented herein, halving the rotation speed. RESULTS: The ratio of cross scatter to the total detected signal was found to be as high as 0.59 in a 30 cm diameter phantom. The measured scatter-to-primary ratio in some cases exceeded 4. In the 30 cm phantom, reconstructed contrast was reduced across all ROIs by an average of 48.7% when cross scatter was present. These cross-scatter degradations were almost entirely avoided by the method of interleaved exposures. CONCLUSIONS: Cross scatter is substantial in dual cone-beam imaging, but its effects can be largely removed by interleaved acquisition, which can be achieved at the same angular sampling rate either by doubling the data acquisition rate or halving the rotation speed.

Commissioning and dosimetric characteristics of TrueBeam system: composite data of three TrueBeam machines.

PURPOSE: A TrueBeam linear accelerator (TB-LINAC) is designed to deliver traditionally flattened and flattening-filter-free (FFF) beams. Although it has been widely adopted in many clinics for patient treatment, limited information is available related to commissioning of this type of machine. In this work, commissioning data of three units were measured, and multiunit comparison was presented to provide valuable insights and reliable evaluations on the characteristics of the new treatment system. METHODS: The TB-LINAC is equipped with newly designed waveguide, carousel assembly, monitoring control, and integrated imaging systems. Each machine in this study has 4, 6, 8, 10, 15 MV flattened photon beams, and 6 MV and 10 MV FFF photon beams as well as 6, 9, 12, 16, 20, and 22 MeV electron beams. Dosimetric characteristics of the three new TB-LINAC treatment units are systematically measured for commissioning. High-resolution diode detectors and ion chambers were used to measure dosimetric data for a range of field sizes from 10 × 10 to 400 × 400 mm(2). The composite dosimetric data of the three units are presented in this work. The commissioning of intensity modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), image-guided radiation therapy, and gating systems are also illustrated. Critical considerations of P(ion) of FFF photon beams and small field dosimetric measurements were investigated. RESULTS: The authors found all PDDs and profiles matched well among the three machines. Beam data were quantitatively compared and combined through average to yield composite beam data. The discrepancies among the machines were quantified using standard deviation (SD). The mean SD of the PDDs among the three units is 0.12%, and the mean SD of the profiles is 0.40% for 10 MV FFF open fields. The variations of P(ion) of the chamber CC13 is 1.2 ± 0.1% under 6 MV FFF and 2.0 ± 0.5% under 10 MV FFF from dmax to the 18 cm-off-axis point at 35 cm depth under 40 × 40 cm(2). The mean penumbra of crossplane flattened photon beams at collimator angle of 0° is measured from 5.88 ± 0.09 to 5.99 ± 0.13 mm from 4 to 15 MV at 10 cm depth of 100 × 100 mm(2). The mean penumbra of crossplane beams at collimator angle of 0° is measured as 3.70 ± 0.21 and 4.83 ± 0.04 mm for 6 MV FFF and 10 MV FFF, respectively, at 10 cm depth with a field size of 5 × 5 cm(2). The end-to-end test procedures of both IMRT and VMAT were performed for various energy modes. The mean ion chamber measurements of three units showed less than 2% between measurement and calculation; the mean MultiCube ICA measurements demonstrated over 90% pixels passing gamma analysis (3%, 3 mm, 5% threshold). The imaging dosimetric data of KV planar imaging and CBCT demonstrated improved consistency with vendor specifications and dose reduction for certain imaging protocols. The gated output verification showed a discrepancy of 0.05% or less between gating radiation delivery and nongating radiation delivery. CONCLUSIONS: The commissioning data indicated good consistency among the three TB-LINAC units. The commissioning data provided us valuable insights and reliable evaluations on the characteristics of the new treatment system. The systematically measured data might be useful for future reference.

Implementation of dual-energy technique for virtual monochromatic and linearly mixed CBCTs.

PURPOSE: To implement dual-energy imaging technique for virtual monochromatic (VM) and linearly mixed (LM) cone beam CTs (CBCTs) and to demonstrate their potential applications in metal artifact reduction and contrast enhancement in image-guided radiation therapy (IGRT). METHODS: A bench-top CBCT system was used to acquire 80 kVp and 150 kVp projections, with an additional 0.8 mm tin filtration. To implement the VM technique, these projections were first decomposed into acrylic and aluminum basis material projections to synthesize VM projections, which were then used to reconstruct VM CBCTs. The effect of VM CBCT on the metal artifact reduction was evaluated with an in-house titanium-BB phantom. The optimal VM energy to maximize contrast-to-noise ratio (CNR) for iodine contrast and minimize beam hardening in VM CBCT was determined using a water phantom containing two iodine concentrations. The LM technique was implemented by linearly combining the low-energy (80 kVp) and high-energy (150 kVp) CBCTs. The dose partitioning between low-energy and high-energy CBCTs was varied (20%, 40%, 60%, and 80% for low-energy) while keeping total dose approximately equal to single-energy CBCTs, measured using an ion chamber. Noise levels and CNRs for four tissue types were investigated for dual-energy LM CBCTs in comparison with single-energy CBCTs at 80, 100, 125, and 150 kVp. RESULTS: The VM technique showed substantial reduction of metal artifacts at 100 keV with a 40% reduction in the background standard deviation compared to a 125 kVp single-energy scan of equal dose. The VM energy to maximize CNR for both iodine concentrations and minimize beam hardening in the metal-free object was 50 keV and 60 keV, respectively. The difference of average noise levels measured in the phantom background was 1.2% between dual-energy LM CBCTs and equivalent-dose single-energy CBCTs. CNR values in the LM CBCTs of any dose partitioning are better than those of 150 kVp single-energy CBCTs. The average CNR for four tissue types with 80% dose fraction at low-energy showed 9.0% and 4.1% improvement relative to 100 kVp and 125 kVp single-energy CBCTs, respectively. CNRs for low-contrast objects improved as dose partitioning was more heavily weighted toward low-energy (80 kVp) for LM CBCTs. CONCLUSIONS: Dual-energy CBCT imaging techniques were implemented to synthesize VM CBCT and LM CBCTs. VM CBCT was effective at achieving metal artifact reduction. Depending on the dose-partitioning scheme, LM CBCT demonstrated the potential to improve CNR for low contrast objects compared to single-energy CBCT acquired with equivalent dose.

Imaging system QA of a medical accelerator, Novalis Tx, for IGRT per TG 142: our 1 year experience.

American Association of Physicists in Medicine (AAPM) task group (TG) 142 has recently published a report to update recommendations of the AAPM TG 40 report and add new recommendations concerning medical accelerators in the era of image-guided radiation therapy (IGRT). The recommendations of AAPM TG 142 on IGRT are timely. In our institute, we established a comprehensive imaging QA program on a medical accelerator based on AAPM TG 142 and implemented it successfully. In this paper, we share our one-year experience and performance evaluation of an OBI capable linear accelerator, Novalis Tx, per TG 142 guidelines.