Efficacy and safety of flumatinib in the treatment of newly diagnosed chronic myeloid leukemia in the chronic phase: A real-world single-center retrospective study, with a focus on premature drug discontinuation.

PURPOSE: To assess the real-world efficacy and safety of flumatinib as first-line and post-line treatments for chronic myeloid leukemia in the chronic phase (CML-CP). RESULTS: Among 141 patients receiving flumatinib as first-line and post-line treatment, the 12-month major molecular response (MMR) rates were 69.4% and 67.6%, respectively. The median time to response was 6 and 10.5 months, respectively. In post-line treatment, the early molecular response (EMR) of flumatinib as second-line is significantly superior to that of third-line treatment (3-month EMR rate: 79.2% vs. 39.3%, P<0.001; 3-month MMR rate: 45.8% vs. 21.4%, P=0.033). Contrastively, patients who switched to flumatinib due to intolerance had significantly higher MMR rates at 3, 6, and 12 months compared to patients who switched due to inadequate response (60.6% vs. 24.2%, P=0.003; 66.7% vs. 36.0%, P=0.027; 84.2% vs. 50.0%, P=0.038). Premature drug discontinuation was observed in 28.4% of the patients. Grades 3-4 hematologic adverse events (AEs) were identified as independent risk factors for premature drug discontinuation. Patients who discontinued treatment and those who previously received only imatinib therapy had a poorer molecular response and failure-free survival. CONCLUSIONS: Flumatinib demonstrates favorable efficacy and safety. Treatment discontinuation can result in a poorer molecular response and long-term prognosis.

Development of a novel pyroptosis-related LncRNA signature with multiple significance in acute myeloid leukemia.

Background: Pyroptosis, a programmed cell death (PCD) with highly inflammatory form, has been recently found to be associated with the origin of hematopoietic malignancies. Long noncoding RNA (lncRNA) had emerged as an essential mediator to regulate gene expression and been involved in oncogenesis. However, the roles of pyroptosis-related lncRNA (PRlncRNA) in acute myeloid leukemia (AML) have not yet been completely clarified. Methods: We collected AML datasets from public databases to obtain PRlncRNA associated with survival and constructed a PRlncRNA signature using Lasso-Cox regression analysis. Subsequently, we employed RT-PCR to confirm its expression difference and internal training to further verify its reliability. Next, AML patients were classified into two subgroups by the median risk score. Finally, the differences between two groups in immune infiltration, enrichment analysis and drug sensitivity were further explored. Results: A PRlncRNA signature and an effective nomogram combined with clinicopathological variables to predict the prognosis of AML were constructed. The internal validations showed that the PRlncRNA risk score model was an accurate and productive indicator to predict the outcome of AML. Furthermore, this study indicated that higher inflammatory cell and immunosuppressive cells, and less sensitive to conventional chemotherapy drugs were highlighted in the high-risk group. Conclusion: Through comprehensive analysis of PRlncRNA model, our study may offer a valuable basis for future researches in targeting pyroptosis and tumor microenvironment (TME) and provide new measures for prevention and treatment in AML.

Fe3O4 Nanoparticles on 3D Porous Carbon Skeleton Derived from Rape Pollen for High-Performance Li-Ion Capacitors.

Herein, a three-dimensional (3D) Fe3O4@C composite with hollow porous structure is prepared by simple solution method and calcination treatment with biomass waste rape pollen (RP) as a carbon source, which is served as an anode of Li-ion capacitor (LIC). The 3D interconnected porous structure and conductive networks facilitate the transfer of ion/electron and accommodate the volume changes of Fe3O4 during the electrochemical reaction process, which leads to the excellent performance of the Fe3O4@C composite electrode. The electrochemical analysis demonstrates that the hybrid LIC fabricated with Fe3O4@C as the anode and activated carbon (AC) as the cathode can operate at a voltage of 4.0 V and exhibit a high energy density of 140.6 Wh kg-1 at 200 W kg-1 (52.8 Wh kg-1 at 10 kW kg-1), along with excellent cycling stability, with a capacity retention of 83.3% over 6000 cycles. Hence, these encouraging results indicate that Fe3O4@C has great potential in developing advanced LICs electrode materials for the next generation of energy storage systems.

Single-pass metal artifact reduction using a dual-layer flat panel detector.

PURPOSE: Metal artifact remains a challenge in cone-beam CT images. Many image domain-based segmentation methods have been proposed for metal artifact reduction (MAR), which require two-pass reconstruction. Such methods first segment metal from a first-pass reconstruction and then forward-project the metal mask to identify them in projections. These methods work well in general but are limited when the metal is outside the scan field-of-view (FOV) or when the metal is moving during the scan. In the former, even reconstructing with a larger FOV does not guarantee a good estimate of metal location in the projections; and in the latter, the metal location in each projection is difficult to identify due to motion. Single-pass methods that detect metal in single-energy projections have also been developed, but often have imperfect metal detection that leads to residual artifacts. In this work, we develop a MAR method using a dual-layer (DL) flat panel detector, which improves performance for single-pass reconstruction. METHODS: In this work, we directly detect metal objects in projections using dual-energy (DE) imaging that generates material-specific images (e.g., soft tissue and bone), where the metal stands out in bone images when nonuniform soft tissue background is removed. Metal is detected via simple thresholding, and entropy filtration is further applied to remove false-positive detections. A DL detector provides DE images with superior temporal and spatial registration and was used to perform the task. Scatter correction was first performed on DE raw projections to improve the accuracy of material decomposition. One phantom mimicking a liver biopsy setup and a cadaver head were used to evaluate the metal reduction performance of the proposed method and compared with that of a standard two-pass reconstruction, a previously published sinogram-based method using a Markov random field (MRF) model, and a single-pass projection-domain method using single-energy imaging. The phantom has a liver steering setup placed in a hollow chest phantom, with embedded metal and a biopsy needle crossing the phantom boundary. The cadaver head has dental fillings and a metal tag attached to its surface. The identified metal regions in each projection were corrected by interpolation using surrounding pixels, and the images were reconstructed using filtered backprojection. RESULTS: Our current approach removes metal from the projections, which is robust to FOV truncation during imaging acquisition. In case of FOV truncation, the method outperformed the two-pass reconstruction method. The proposed method using DE renders better accuracy in metal segmentation than the MRF method and single-energy method, which were prone to false-positive errors that cause additional streaks. For the liver steering phantom, the average spatial nonuniformity was reduced from 0.127 in uncorrected images to 0.086 using a standard two-pass reconstruction and to 0.077 using the proposed method. For the cadaver head, the average standard deviation within selected soft tissue regions ( σ s ) was reduced from 209.1 HU in uncorrected images to 69.1 HU using a standard two-pass reconstruction and to 46.8 HU using our proposed method. The proposed method reduced the processing time by 31% as compared with the two-pass method. CONCLUSIONS: We proposed a MAR method that directly detects metal in the projection domain using DE imaging, which is robust to truncation and superior to that of single-energy imaging. The method requires only a single-pass reconstruction that substantially reduces processing time compared with the standard two-pass metal reduction method.

A modified McKinnon-Bates (MKB) algorithm for improved 4D cone-beam computed tomography (CBCT) of the lung.

PURPOSE: Four-dimensional (4D) cone-beam computed tomography (CBCT) of the lung is an effective tool for motion management in radiotherapy but presents a challenge because of slow gantry rotation times. Sorting the individual projections by breathing phase and using an established technique such as Feldkamp-Davis-Kress (FDK) to generate corresponding phase-correlated (PC) three-dimensional (3D) images results in reconstructions (FDK-PC) that often contain severe streaking artifacts due to the sparse angular sampling distributions. These can be reduced by further slowing down the gantry at the expense of incurring unwanted increases in scan times and dose. A computationally efficient alternative is the McKinnon-Bates (MKB) reconstruction algorithm that has shown promise in reducing view aliasing-induced streaking but can produce ghosting artifacts that reduce contrast and impede the determination of motion trajectories. The purpose of this work was to identify and correct shortcomings in the MKB algorithm. METHODS: In the general MKB approach, a time-averaged 3D prior image is first reconstructed. The prior is then forward-projected at the same angles as the original projection data creating time-averaged reprojections. These reprojections are subsequently subtracted from the original (unblurred) projections to create motion-encoded difference projections. The difference projections are reconstructed into PC difference images that are added to the well-sampled 3D prior to create the higher quality 4D image. The cause of the ghosting in the traditional 4D MKB images was studied and traced to motion-induced streaking in the prior that, when reprojected, has the undesirable effect of re-encoding for motion in what should be a purely time-averaged reprojection. A new method, designated as the modified McKinnon-Bates (mMKB) algorithm, was developed based on destreaking the prior. This was coupled with a postprocessing 4D bilateral filter for noise suppression and edge preservation (mMKBbf ). The algorithms were tested with the 4D XCAT phantom using four simulated scan times (57, 60, 120, 180 s) and with two in vivo thorax studies (acquisition time of 60 and 90 s). Contrast-to-noise ratios (CNRs) of the target lesions and overall visual quality of the images were assessed. RESULTS: Prior destreaking (mMKB algorithm) reduced ghosting artifacts and increased CNRs for all cases, with the biggest impacts seen in the end inhale (EI) and end exhale (EE) phases of the respiratory cycle. For the XCAT phantom, mMKB lesion CNR was 44% higher than the MKB lesion CNR and was 81% higher than the FDK-PC lesion CNR (EI and EE phases). The bilateral filter provided a further average CNR improvement of 87% with the highest increases associated with longer scan times. Across all phases and scan times, the maximum mMKBbf -to-FDK-PC CNR improvement was over 300%. In vivo results agreed with XCAT results. Significantly less ghosting was observed throughout the mMKB images including near the lesions-of-interest and the diaphragm allowing for, in one case, visualization of a small tumor with nearly 30 mm of motion. The maximum FDK-PC-to-MKBbf CNR improvement for Patient 1's lesion was 261% and for Patient 2's lesion was 318%. CONCLUSIONS: The 4D mMKB algorithm yields good quality coronal and sagittal images in the thorax that may provide sufficient information for patient verification.

Acuros CTS: A fast, linear Boltzmann transport equation solver for computed tomography scatter - Part I: Core algorithms and validation.

PURPOSE: To describe Acuros® CTS, a new software tool for rapidly and accurately estimating scatter in x-ray projection images by deterministically solving the linear Boltzmann transport equation (LBTE). METHODS: The LBTE describes the behavior of particles as they interact with an object across spatial, energy, and directional (propagation) domains. Acuros CTS deterministically solves the LBTE by modeling photon transport associated with an x-ray projection in three main steps: (a) Ray tracing photons from the x-ray source into the object where they experience their first scattering event and form scattering sources. (b) Propagating photons from their first scattering sources across the object in all directions to form second scattering sources, then repeating this process until all high-order scattering sources are computed using the source iteration method. (c) Ray-tracing photons from scattering sources within the object to the detector, accounting for the detector's energy and anti-scatter grid responses. To make this process computationally tractable, a combination of analytical and discrete methods is applied. The three domains are discretized using the Linear Discontinuous Finite Elements, Multigroup, and Discrete Ordinates methods, respectively, which confer the ability to maintain the accuracy of a continuous solution. Furthermore, through the implementation in CUDA, we sought to exploit the parallel computing capabilities of graphics processing units (GPUs) to achieve the speeds required for clinical utilization. Acuros CTS was validated against Geant4 Monte Carlo simulations using two digital phantoms: (a) a water phantom containing lung, air, and bone inserts (WLAB phantom) and (b) a pelvis phantom derived from a clinical CT dataset. For these studies, we modeled the TrueBeam® (Varian Medical Systems, Palo Alto, CA) kV imaging system with a source energy of 125 kVp. The imager comprised a 600 µm-thick Cesium Iodide (CsI) scintillator and a 10:1 one-dimensional anti-scatter grid. For the WLAB studies, the full-fan geometry without a bowtie filter was used (with and without the anti-scatter grid). For the pelvis phantom studies, a half-fan geometry with bowtie was used (with the anti-scatter grid). Scattered and primary photon fluences and energies deposited in the detector were recorded. RESULTS: The Acuros CTS and Monte Carlo results demonstrated excellent agreement. For the WLAB studies, the average percent difference between the Monte Carlo- and Acuros-generated scattered photon fluences at the face of the detector was -0.7%. After including the detector response, the average percent differences between the Monte Carlo- and Acuros-generated scatter fractions (SF) were -0.1% without the grid and 0.6% with the grid. For the digital pelvis simulation, the Monte Carlo- and Acuros-generated SFs agreed to within 0.1% on average, despite the scatter-to-primary ratios (SPRs) being as high as 5.5. The Acuros CTS computation time for each scatter image was ~1 s using a single GPU. CONCLUSIONS: Acuros CTS enables a fast and accurate calculation of scatter images by deterministically solving the LBTE thus offering a computationally attractive alternative to Monte Carlo methods. Part II describes the application of Acuros CTS to scatter correction of CBCT scans on the TrueBeam system.

Continuous Blood Pressure Estimation Based on Two-Domain Fusion Model.

Blood pressure (BP) is one of the indispensable elements of physiological health characteristics and a significant indicator for predicting and diagnosing hypertension and cardiovascular diseases. This paper proposes a two-domain fusion model to estimate BP continuously from pulse wave acquired with a pressure sensor. Method. The optimal external pressure applied on the pressure sensor is first determined in order to capture pulse wave in the radial artery. The captured pulse wave is then processed in both the time and frequency domains via filtering and fast Fourier transform. Finally, a set of features are extracted from these two domains and input into a neural network along with blood pressure values measured by a commercial sphygmomanometer for training. The model is then tested on new data for accuracy evaluation. Results. The proposed two-domain fusion method achieved a high degree of accuracy in measuring blood pressure.

Smoothed l0 Norm Regularization for Sparse-View X-Ray CT Reconstruction.

Low-dose computed tomography (CT) reconstruction is a challenging problem in medical imaging. To complement the standard filtered back-projection (FBP) reconstruction, sparse regularization reconstruction gains more and more research attention, as it promises to reduce radiation dose, suppress artifacts, and improve noise properties. In this work, we present an iterative reconstruction approach using improved smoothed l0 (SL0) norm regularization which is used to approximate l0 norm by a family of continuous functions to fully exploit the sparseness of the image gradient. Due to the excellent sparse representation of the reconstruction signal, the desired tissue details are preserved in the resulting images. To evaluate the performance of the proposed SL0 regularization method, we reconstruct the simulated dataset acquired from the Shepp-Logan phantom and clinical head slice image. Additional experimental verification is also performed with two real datasets from scanned animal experiment. Compared to the referenced FBP reconstruction and the total variation (TV) regularization reconstruction, the results clearly reveal that the presented method has characteristic strengths. In particular, it improves reconstruction quality via reducing noise while preserving anatomical features.

Optical blood pressure estimation with photoplethysmography and FFT-based neural networks.

We introduce and validate a beat-to-beat optical blood pressure (BP) estimation paradigm using only photoplethysmogram (PPG) signal from finger tips. The scheme determines subject-specific contribution to PPG signal and removes most of its influence by proper normalization. Key features such as amplitudes and phases of cardiac components were extracted by a fast Fourier transform and were used to train an artificial neural network, which was then used to estimate BP from PPG. Validation was done on 69 patients from the MIMIC II database plus 23 volunteers. All estimations showed a good correlation with the reference values. This method is fast and robust, and can potentially be used to perform pulse wave analysis in addition to BP estimation.

A piecewise-focused high DQE detector for MV imaging.

PURPOSE: Electronic portal imagers (EPIDs) with high detective quantum efficiencies (DQEs) are sought to facilitate the use of the megavoltage (MV) radiotherapy treatment beam for image guidance. Potential advantages include high quality (treatment) beam's eye view imaging, and improved cone-beam computed tomography (CBCT) generating images with more accurate electron density maps with immunity to metal artifacts. One approach to increasing detector sensitivity is to couple a thick pixelated scintillator array to an active matrix flat panel imager (AMFPI) incorporating amorphous silicon thin film electronics. Cadmium tungstate (CWO) has many desirable scintillation properties including good light output, a high index of refraction, high optical transparency, and reasonable cost. However, due to the 0 1 0 cleave plane inherent in its crystalline structure, the difficulty of cutting and polishing CWO has, in part, limited its study relative to other scintillators such as cesium iodide and bismuth germanate (BGO). The goal of this work was to build and test a focused large-area pixelated "strip" CWO detector. METHODS: A 361 × 52 mm scintillator assembly that contained a total of 28 072 pixels was constructed. The assembly comprised seven subarrays, each 15 mm thick. Six of the subarrays were fabricated from CWO with a pixel pitch of 0.784 mm, while one array was constructed from BGO for comparison. Focusing was achieved by coupling the arrays to the Varian AS1000 AMFPI through a piecewise linear arc-shaped fiber optic plate. Simulation and experimental studies of modulation transfer function (MTF) and DQE were undertaken using a 6 MV beam, and comparisons were made between the performance of the pixelated strip assembly and the most common EPID configuration comprising a 1 mm-thick copper build-up plate attached to a 133 mg/cm(2) gadolinium oxysulfide scintillator screen (Cu-GOS). Projection radiographs and CBCT images of phantoms were acquired. The work also introduces the use of a lightweight edge phantom to generate MTF measurements at MV energies and shows its functional equivalence to the more cumbersome slit-based method. RESULTS: Measured and simulated DQE(0)'s of the pixelated CWO detector were 22% and 26%, respectively. The average measured and simulated ratios of CWO DQE(f) to Cu-GOS DQE(f) across the frequency range of 0.0-0.62 mm(-1) were 23 and 29, respectively. 2D and 3D imaging studies confirmed the large dose efficiency improvement and that focus was maintained across the field of view. In the CWO CBCT images, the measured spatial resolution was 7 lp/cm. The contrast-to-noise ratio was dramatically improved reflecting a 22 × sensitivity increase relative to Cu-GOS. The CWO scintillator material showed significantly higher stability and light yield than the BGO material. CONCLUSIONS: An efficient piecewise-focused pixelated strip scintillator for MV imaging is described that offers more than a 20-fold dose efficiency improvement over Cu-GOS.

A prior-based metal artifact reduction algorithm for x-ray CT.

In computed tomography (CT), metal objects in the scanning filed are accompanied by physical phenomenon that causes projections to be inconsistent. These inconsistencies produce bright and dark shadows or streaks in analytically reconstructed images. Interpolation-based metal artifact reduction (MAR) algorithms usually replace the inconsistent projection data by estimating surrogate data based on the surrounding uncorrupted projections. In such cases, secondary artifacts will be generated when the data estimates are inaccurate. Therefore, better projection estimation is critical. This paper proposes an image post-processing strategy to create an intermediate image, named the prior image and better estimates of the surrogate data by forward projecting this prior image. The proposed method consists of three steps based on the forward projection MAR framework. First, metallic implants in the uncorrected images are segmented using a Markov random field model (MRF). Then a prior image is generated via an edge-preserving filter and a recovery procedure of the adjacent anatomical structures. Finally, the projection is completed via forward projecting this prior image and the corrected image is reconstructed by the filtered backprojection (FBP) method. Studies on both phantom and clinical data are carried out to verify the performance of the proposed method. The comparisons with other previous MAR algorithms demonstrate that the proposed MAR method performs better in metal artifact suppression and anatomical structure preservation.

Rapid Monte Carlo simulation of detector DQE(f).

PURPOSE: Performance optimization of indirect x-ray detectors requires proper characterization of both ionizing (gamma) and optical photon transport in a heterogeneous medium. As the tool of choice for modeling detector physics, Monte Carlo methods have failed to gain traction as a design utility, due mostly to excessive simulation times and a lack of convenient simulation packages. The most important figure-of-merit in assessing detector performance is the detective quantum efficiency (DQE), for which most of the computational burden has traditionally been associated with the determination of the noise power spectrum (NPS) from an ensemble of flood images, each conventionally having 10(7) - 10(9) detected gamma photons. In this work, the authors show that the idealized conditions inherent in a numerical simulation allow for a dramatic reduction in the number of gamma and optical photons required to accurately predict the NPS. METHODS: The authors derived an expression for the mean squared error (MSE) of a simulated NPS when computed using the International Electrotechnical Commission-recommended technique based on taking the 2D Fourier transform of flood images. It is shown that the MSE is inversely proportional to the number of flood images, and is independent of the input fluence provided that the input fluence is above a minimal value that avoids biasing the estimate. The authors then propose to further lower the input fluence so that each event creates a point-spread function rather than a flood field. The authors use this finding as the foundation for a novel algorithm in which the characteristic MTF(f), NPS(f), and DQE(f) curves are simultaneously generated from the results of a single run. The authors also investigate lowering the number of optical photons used in a scintillator simulation to further increase efficiency. Simulation results are compared with measurements performed on a Varian AS1000 portal imager, and with a previously published simulation performed using clinical fluence levels. RESULTS: On the order of only 10-100 gamma photons per flood image were required to be detected to avoid biasing the NPS estimate. This allowed for a factor of 10(7) reduction in fluence compared to clinical levels with no loss of accuracy. An optimal signal-to-noise ratio (SNR) was achieved by increasing the number of flood images from a typical value of 100 up to 500, thereby illustrating the importance of flood image quantity over the number of gammas per flood. For the point-spread ensemble technique, an additional 2× reduction in the number of incident gammas was realized. As a result, when modeling gamma transport in a thick pixelated array, the simulation time was reduced from 2.5 × 10(6) CPU min if using clinical fluence levels to 3.1 CPU min if using optimized fluence levels while also producing a higher SNR. The AS1000 DQE(f) simulation entailing both optical and radiative transport matched experimental results to within 11%, and required 14.5 min to complete on a single CPU. CONCLUSIONS: The authors demonstrate the feasibility of accurately modeling x-ray detector DQE(f) with completion times on the order of several minutes using a single CPU. Convenience of simulation can be achieved using GEANT4 which offers both gamma and optical photon transport capabilities.

Acquisition of MV-scatter-free kilovoltage CBCT images during RapidArc™ or VMAT.

PURPOSE: To perform kilovoltage (kV) cone beam computed tomography (CBCT) imaging concomitant with the delivery of megavoltage (MV) RapidArc treatment, and demonstrate the feasibility of obtaining MV-scatter-free kV CBCT images. METHODS AND MATERIALS: RapidArc/CBCT treatment and imaging plans are designed, and delivered on the Varian TrueBeam, using its Developer Mode. The plan contains 250 control points for MV-radiation delivery, each over an arc of 0.4-0.7(o). Interlaced between successive MV delivery control points are imaging control points, each over an arc of 0.7-1.1(o). During the 360(o) gantry rotation for the RapidArc delivery, CBCT projections of a phantom are acquired at 11 frames per second. The kV projections with minimal MV-scatter are selected, based on gantry angle, and the CBCT(s) image reconstructed. For comparison, a reference CBCT(r) image is acquired in the normal way. In addition, to examine the effect of MV-scatter we acquire CBCT(c) using the same treatment plan without the imaging control points, i.e. with continuous MV delivery during the 360(o) rotation. Quantitative evaluation of image qualities is performed based on the concepts of CNR (contrast-to-noise ratio) and NSTD (normalized standard deviation). RESULTS: The different types of CBCT images were reconstructed, evaluated, and compared. Visual comparison indicates that the image quality of CBCT(s) is similar to that of the reference CBCT(r), and that the quality of CBCT(c) is significantly degraded by the MV-scatter. Quantitative evaluation of the image quality indicates that MV-scatter significantly decreases the CNR of CBCT (from ∼7 to ∼3.5 in one comparison). Similarly, MV-scatter significantly increases the inhomogeneity of image intensity, e.g. from ∼0.03 to ∼0.06 in one comparison. CONCLUSION: We have developed a method to acquire MV-scatter-free kV CBCT images concomitant with the delivery of RapidArc treatment. Engineering development is necessary to improve the process, e.g. by synchronization of the MV and kV beams.

Correction for patient table-induced scattered radiation in cone-beam computed tomography (CBCT).

PURPOSE: In image-guided radiotherapy, an artifact typically seen in axial slices of x-ray cone-beam computed tomography (CBCT) reconstructions is a dark region or "black hole" situated below the scan isocenter. The authors trace the cause of the artifact to scattered radiation produced by radiotherapy patient tabletops and show it is linked to the use of the offset-detector acquisition mode to enlarge the imaging field-of-view. The authors present a hybrid scatter kernel superposition (SKS) algorithm to correct for scatter from both the object-of-interest and the tabletop. METHODS: Monte Carlo simulations and phantom experiments were first performed to identify the source of the black hole artifact. For correction, a SKS algorithm was developed that uses separate kernels to estimate scatter from the patient tabletop and the object-of-interest. Each projection is divided into two regions, one defined by the shadow cast by the tabletop on the imager and one defined by the unshadowed region. The region not shadowed by the tabletop is processed using the recently developed fast adaptive scatter kernel superposition (fASKS) method which employs asymmetric kernels that best model scatter transport through bodylike objects. The shadowed region is convolved with a combination of slab-derived symmetric SKS kernels and asymmetric fASKS kernels. The composition of the hybrid kernels is projection-angle-dependent. To test the algorithm, pelvis phantom and in vivo data were acquired using a CBCT test stand, a Varian Acuity simulator, and a Varian On-Board Imager, all of which have similar geometries and components. Artifact intensities and Hounsfield unit (HU) accuracies in the reconstructions were assessed before and after the correction. RESULTS: The hybrid kernel algorithm provided effective correction and produced substantially better scatter estimates than the symmetric SKS or asymmetric fASKS methods alone. HU nonuniformities in the reconstructed pelvis phantom were reduced from 220 to 50 HU (i.e., 22%-5%). In the in vivo scans, the black hole artifact was reduced by up to 147 HU, a 73% improvement, and anatomical details in the prostate and rectum areas were made considerably more visible. CONCLUSIONS: Radiotherapy tabletops, which are generally flatter and larger than those used for diagnostic CT, can produce significant scatter-related artifacts. The proposed hybrid SKS algorithm accurately estimates scatter from both the object-of-interest and the patient tabletop, and resulting image uniformities and HU accuracies are greatly improved.

Shading correction for on-board cone-beam CT in radiation therapy using planning MDCT images.

PURPOSE: Applications of cone-beam CT (CBCT) to image-guided radiationtherapy (IGRT) are hampered by shading artifacts in the reconstructed images. These artifacts are mainly due to scatter contamination in the projections but also can result from uncorrected beam hardening effects as well as nonlinearities in responses of the amorphous silicon flat panel detectors. While currently, CBCT is mainly used to provide patient geometry information for treatment setup, more demanding applications requiring high-quality CBCT images are under investigation. To tackle these challenges, many CBCT correction algorithms have been proposed; yet, a standard approach still remains unclear. In this work, we propose a shading correction method for CBCT that addresses artifacts from low-frequency projection errors. The method is consistent with the current workflow of radiation therapy. METHODS: With much smaller inherent scatter signals and more accurate detectors, diagnostic multidetector CT (MDCT) provides high quality CT images that are routinely used for radiation treatment planning. Using the MDCT image as "free" prior information, we first estimate the primary projections in the CBCT scan via forward projection of the spatially registered MDCT data. Since most of the CBCT shading artifacts stem from low-frequency errors in the projections such as scatter, these errors can be accurately estimated by low-pass filtering the difference between the estimated and raw CBCT projections. The error estimates are then subtracted from the raw CBCT projections. Our method is distinct from other published correction methods that use the MDCT image as a prior because it is projection-based and uses limited patient anatomical information from the MDCT image. The merit of CBCT-based treatment monitoring is therefore retained. RESULTS: The proposed method is evaluated using two phantom studies on tabletop systems. On the Catphan 600 phantom, our approach reduces the reconstruction error from 348 Hounsfield unit (HU) without correction to 4 HU around the object center after correction, and from 375 HU to 17 HU in the high-contrast regions. In the selected regions of interest (ROIs), the average image contrast is increased by a factor of 3.3. When noise suppression is implemented, the proposed correction substantially improves the contrast-to-noise ratio (CNR) and therefore the visibility of low-contrast objects, as seen in a more challenging pelvis phantom study. Besides a significant improvement in image uniformity, a low-contrast object of approximately 25 HU, which is otherwise buried in the shading artifacts, can be clearly identified after the proposed correction due to a CNR increase of 3.1. Compared to a kernel-based scatter correction method coupled with an analytical beam hardening correction, our approach also shows an overall improved performance with some residual artifacts. CONCLUSIONS: By providing effective shading correction, our approach has the potential to improve the accuracy of more advanced CBCT-based clinical applications for IGRT, such as tumor delineation and dose calculation.

Scatter correction method for x-ray CT using primary modulation: phantom studies.

PURPOSE: Scatter correction is a major challenge in x-ray imaging using large area detectors. Recently, the authors proposed a promising scatter correction method for x-ray computed tomography (CT) using primary modulation. Proof of concept was previously illustrated by Monte Carlo simulations and physical experiments on a small phantom with a simple geometry. In this work, the authors provide a quantitative evaluation of the primary modulation technique and demonstrate its performance in applications where scatter correction is more challenging. METHODS: The authors first analyze the potential errors of the estimated scatter in the primary modulation method. On two tabletop CT systems, the method is investigated using three phantoms: A Catphan 600 phantom, an anthropomorphic chest phantom, and the Catphan 600 phantom with two annuli. Two different primary modulators are also designed to show the impact of the modulator parameters on the scatter correction efficiency. The first is an aluminum modulator with a weak modulation and a low modulation frequency, and the second is a copper modulator with a strong modulation and a high modulation frequency. RESULTS: On the Catphan 600 phantom in the first study, the method reduces the error of the CT number in the selected regions of interest (ROIs) from 371.4 to 21.9 Hounsfield units (HU); the contrast to noise ratio also increases from 10.9 to 19.2. On the anthropomorphic chest phantom in the second study, which represents a more difficult case due to the high scatter signals and object heterogeneity, the method reduces the error of the CT number from 327 to 19 HU in the selected ROIs and from 31.4% to 5.7% on the overall average. The third study is to investigate the impact of object size on the efficiency of our method. The scatter-to-primary ratio estimation error on the Catphan 600 phantom without any annulus (20 cm in diameter) is at the level of 0.04, it rises to 0.07 and 0.1 on the phantom with an elliptical annulus (30 cm in the minor axis and 38 cm in the major axis) and with a circular annulus (38 cm in diameter). CONCLUSIONS: On the three phantom studies, good scatter correction performance of the proposed method has been demonstrated using both image comparisons and quantitative analysis. The theory and experiments demonstrate that a strong primary modulation that possesses a low transmission factor and a high modulation frequency is preferred for high scatter correction accuracy.

Correction of photon attenuation and collimator response for a body-contouring SPECT/CT imaging system.

UNLABELLED: (111)In-Capromab pendetide imaging is indicated for postprostatectomy patients at risk for residual or recurrent disease. However, this study is complicated by relatively long times for tumor uptake and background washout that require imaging to be performed several days after radiopharmaceutical administration. In addition, (111)In-capromab pendetide demonstrates uptake in normal structures that produce images that are interpreted best using correlation with anatomic imaging. Finally, the visual quality of radionuclide imaging can be improved with corrections for photon attenuation and for the geometric response of the radionuclide collimator. Therefore, we have evaluated the advantages of using a commercially available dual-modality SPECT/CT system. In this article, we evaluate a novel iterative reconstruction algorithm using the SPECT/CT data obtained from phantoms and (111)In-capromab pendetide patient studies. METHODS: Phantom data acquired with the dual-head SPECT camera were reconstructed using both filtered backprojection (FBP) and an iterative maximum-likelihood expectation maximization (MLEM) algorithm incorporating corrections for (a) attenuation coefficient at the effective energy of the radionuclide (either (99m)Tc or (111)In) and (b) collimator response based on experimentally measured depth-dependent spatial resolution of the camera. The collimator response model used the coregistered CT image to estimate the source-target distances produced by the patient-contouring logic of the SPECT camera. Spatial resolution was measured using SPECT images of 2 line sources and uniformity from a uniform cylindric tank. Clinical (111)In-capromab pendetide SPECT/CT data were acquired according to the radiopharmaceutical manufacturer's protocol. Region-of-interest (ROI) analysis of a transverse slice at the level of the sacral base produced mean, median, maximum, and minimum counts per pixel for bone marrow and surrounding soft-tissue ROIs. Ratios of the mean capromab pendetide uptake within marrow to uptake within soft tissue were compared for images reconstructed with FBP versus that obtained from the MLEM method with photon attenuation and collimator response corrections. RESULTS: The source-target distances reconstructed from the patient-specific CT image agreed well with the corresponding values recorded manually from the camera display unit. This information was incorporated into the iterative reconstruction algorithms and improved the quality of SPECT images from phantoms and patients versus SPECT images reconstructed without the depth-dependent collimator response model. Qualitatively, SPECT images reconstructed with corrections for photon attenuation and collimator response showed less background activity and improved target contrast compared with those images reconstructed with FBP. The target-to-background ratio (marrow uptake-to-soft-tissue uptake) was significantly better using MLEM reconstruction than with FBP when mean uptake values were measured. CONCLUSION: A priori anatomic data can be used to enhance the quality of the SPECT image when reconstructed using iterative techniques (e.g., MLEM) that use the CT data to produce a patient-specific attenuation map and a collimator response model based on the body contour produced during the SPECT acquisition.

Radiation dose estimate in small animal SPECT and PET.

Calculations of radiation dose are important in assessing the medical and biological implications of ionizing radiation in medical imaging techniques such as SPECT and PET. In contrast, radiation dose estimates of SPECT and PET imaging of small animals are not very well established. For that reason we have estimated the whole-body radiation dose to mice and rats for isotopes such as 18F, 99mTc, 201Tl, (111)In, 123I, and 125I that are used commonly for small animal imaging. We have approximated mouse and rat bodies with uniform soft tissue equivalent ellipsoids. The mouse and rat sized ellipsoids had a mass of 30 g and 300 g, respectively, and a ratio of the principal axes of 1:1:4 and 0.7:1:4. The absorbed fractions for various photon energies have been calculated using the Monte Carlo software package MCNP. Using these values, we then calculated MIRD S-values for two geometries that model the distribution of activity in the animal body: (a) a central point source and (b) a homogeneously distributed source, and compared these values against S-value calculations for small ellipsoids tabulated in MIRD Pamphlet 8 to validate our results. Finally we calculated the radiation dose taking into account the biological half-life of the radiopharmaceuticals and the amount of activity administered. Our calculations produced S-values between 1.06 x 10(-13) Gy/Bq s and 2.77 x 10(-13) Gy/Bq s for SPECT agents, and 15.0 x 10(-13) Gy/Bq s for the PET agent 18F, assuming mouse sized ellipsoids with uniform source distribution. The S-values for a central point source in an ellipsoid are about 10% higher than the values obtained for the uniform source distribution. Furthermore, the S-values for mouse sized ellipsoids are approximately 10 times higher than for the rat sized ellipsoids reflecting the difference in mass. We reviewed published data to obtain administered radioactivity and residence times for small animal imaging. From these values and our computed S-values we estimated that the whole body dose in small animals ranges between 6 cGy and 90 cGy for mice and between about 1 cGy and 27 cGy for rats. The whole body dose in small animal imaging can be very high in comparison to the lethal dose to mice (LD50/30 approximately 7 Gy). For this reason the dose in small animal imaging should be monitored carefully and the administered activity should be kept to a minimum. These results also underscore the need of further development of instrumentation that improves detection efficiency and reduces radiation dose in small animal imaging.