Report on the AAPM deep-learning spectral CT Grand Challenge.

BACKGROUND: This Special Report summarizes the 2022 AAPM Grand Challenge on Deep-Learning spectral Computed Tomography (DL-spectral CT) image reconstruction. PURPOSE: The purpose of the challenge is to develop the most accurate image reconstruction algorithm possible for solving the inverse problem associated with a fast kilovolt switching dual-energy CT scan using a three tissue-map decomposition. Participants could choose to use a deep-learning (DL), iterative, or a hybrid approach. METHODS: The challenge is based on a 2D breast CT simulation, where the simulated breast phantom consists of three tissue maps: adipose, fibroglandular, and calcification distributions. The phantom specification is stochastic so that multiple realizations can be generated for DL approaches. A dual-energy scan is simulated where the x-ray source potential of successive views alternates between 50 and 80 kilovolts (kV). A total of 512 views are generated, yielding 256 views for each source voltage. We generate 50 and 80 kV images by use of filtered back-projection (FBP) on negative logarithm processed transmission data. For participants who develop a DL approach, 1000 cases are available. Each case consists of the three 512 × 512 tissue maps, 50 and 80-kV transmission data sets and their corresponding FBP images. The goal of the DL network would then be to predict the material maps from either the transmission data, FBP images, or a combination of the two. For participants developing a physics-based approach, all of the required modeling parameters are made available: geometry, spectra, and tissue attenuation curves. The provided information also allows for hybrid approaches where physics is exploited as well as information about the scanned object derived from the 1000 training cases. Final testing is performed by computation of root-mean-square error (RMSE) for predictions on the tissue maps from 100 new cases. RESULTS: Test phase submission were received from 18 research groups. Of the 18 submissions, 17 were results obtained with algorithms that involved DL. Only the second place finishing team developed a physics-based image reconstruction algorithm. Both the winning and second place teams had highly accurate results where the RMSE was nearly zero to single floating point precision. Results from the top 10 also achieved a high degree of accuracy; and as a result, this special report outlines the methodology developed by each of these groups. CONCLUSIONS: The DL-spectral CT challenge successfully established a forum for developing image reconstruction algorithms that address an important inverse problem relevant for spectral CT.

Dopamine-Mediated Major Depressive Disorder in the Neural Circuit of Ventral Tegmental Area-Nucleus Accumbens-Medial Prefrontal Cortex: From Biological Evidence to Computational Models.

Major depressive disorder (MDD) is a serious psychiatric disorder, with an increasing incidence in recent years. The abnormal dopaminergic pathways of the midbrain cortical and limbic system are the key pathological regions of MDD, particularly the ventral tegmental area- nucleus accumbens- medial prefrontal cortex (VTA-NAc-mPFC) neural circuit. MDD usually occurs with the dysfunction of dopaminergic neurons in VTA, which decreases the dopamine concentration and metabolic rate in NAc/mPFC brain regions. However, it has not been fully explained how abnormal dopamine concentration levels affect this neural circuit dynamically through the modulations of ion channels and synaptic activities. We used Hodgkin-Huxley and dynamical receptor binding model to establish this network, which can quantitatively explain neural activity patterns observed in MDD with different dopamine concentrations by changing the kinetics of some ion channels. The simulation replicated some important pathological patterns of MDD at the level of neurons and circuits with low dopamine concentration, such as the decreased action potential frequency in pyramidal neurons of mPFC with significantly reduced burst firing frequency. The calculation results also revealed that NaP and KS channels of mPFC pyramidal neurons played key roles in the functional regulation of this neural circuit. In addition, we analyzed the synaptic currents and local field potentials to explain the mechanism of MDD from the perspective of dysfunction of excitation-inhibition balance, especially the disinhibition effect in the network. The significance of this article is that we built the first computational model to illuminate the effect of dopamine concentrations for the NAc-mPFC-VTA circuit between MDD and normal groups, which can be used to quantitatively explain the results of existing physiological experiments, predict the results for unperformed experiments and screen possible drug targets.

High-Resolution Full-3D Specimen Imaging for Lumpectomy Margin Assessment in Breast Cancer.

BACKGROUND: Two-dimensional (2D) specimen radiography (SR) and tomosynthesis (DBT) for breast cancer yield data that lack high-depth resolution. A volumetric specimen imager (VSI) was developed to provide full-3D and thin-slice cross-sectional visualization at a 360° view angle. The purpose of this prospective trial was to compare VSI, 2D SR, and DBT interpretation of lumpectomy margin status with the final pathologic margin status of breast lumpectomy specimens. METHODS: The study enrolled 200 cases from two institutions. After standard imaging and interpretation was performed, the main lumpectomy specimen was imaged with the VSI device. Image interpretation was performed by three radiologists after surgery based on VSI, 2D SR, and DBT. A receiver operating characteristic (ROC) curve was created for each method. The area under the curve (AUC) was computed to characterize the performance of the imaging method interpreted by each user. RESULTS: From 200 lesions, 1200 margins were interpreted. The AUC values of VSI for the three radiologists were respectively 0.91, 0.90, and 0.94, showing relative improvement over the AUCs of 2D SR by 54%, 13%, and 40% and DBT by 32% and 11%, respectively. The VSI has sensitivity ranging from 91 to 94%, specificity ranging from 81 to 85%, a positive predictive value ranging from 25 to 30%, and a negative predicative value of 99%. CONCLUSIONS: The ROC curves of the VSI were higher than those of the other specimen imaging methods. Full-3D specimen imaging can improve the correlation between the main lumpectomy specimen margin status and surgical pathology. The findings from this study suggest that using the VSI device for intraoperative margin assessment could further reduce the re-excision rates for women with malignant disease.

A cortical model with multi-layers to study visual attentional modulation of neurons at the synaptic level.

Visual attention is a selective process of visual information and improves perceptual performance by modulating activities of neurons in the visual system. It has been reported that attention increased firing rates of neurons, reduced their response variability and improved reliability of coding relevant stimuli. Recent neurophysiological studies demonstrated that attention also enhanced the synaptic efficacy between neurons mediated through NMDA and AMPA receptors. Majority of computational models of attention usually are based on firing rates, which cannot explain attentional modulations observed at the synaptic level. To understand mechanisms of attentional modulations at the synaptic level, we proposed a neural network consisting of three layers, corresponding to three different brain regions. Each layer has excitatory and inhibitory neurons. Each neuron was modeled by the Hodgkin-Huxley model. The connections between neurons were through excitatory AMPA and NMDA receptors, as well as inhibitory GABAA receptors. Since the binding process of neurotransmitters with receptors is stochastic in the synapse, it is hypothesized that attention could reduce the variation of the stochastic binding process and increase the fraction of bound receptors in the model. We investigated how attention modulated neurons' responses at the synaptic level on the basis of this hypothesis. Simulated results demonstrated that attention increased firing rates of neurons and reduced their response variability. The attention-induced effects were stronger in higher regions compared to those in lower regions, and stronger for inhibitory neurons than for excitatory neurons. In addition, AMPA receptor antagonist (CNQX) impaired attention-induced modulations on neurons' responses, while NMDA receptor antagonist (APV) did not. These results suggest that attention may modulate neuronal activity at the synaptic level.

Spatial patterns and effects of air pollution and meteorological factors on hospitalization for chronic lung diseases in Beijing, China.

Chronic obstructive pulmonary disease (COPD), lung cancer (LC) and tuberculosis (TB) are common chronic lung diseases that generate a large disease burden and significant health care resource use in China. The aim of this study was to quantify spatial patterns and effects of air pollution and meteorological factors on hospitalization of COPD, LC and TB in Beijing. Daily counts of hospitalization for 2010 were obtained from the Beijing Urban Employees Basic Medical Insurance (UEBMI) system. Bayesian hierarchical Poisson regression models were applied to identify spatial patterns of hospitalization for COPD, LC and TB at the district level and explore associations with inhalable particulate matter (aerodynamic diameter <10 µm, PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), mean temperature and relative humidity. There were 18,882, 14,295 and 2,940 counts of hospitalizations for COPD, LC and TB respectively, in Beijing in 2010. Clusters of high relative risk were in different locations for the three diseases. The effect of relative humidity on COPD hospitalization was most significant with a relative risk (RR) of 1.070 (95%CI: 1.054, 1.086) per one percent increase. For lung cancer hospitalization, exposure to ambient SO2 was associated with a RR of 1.034 (95%CI: 1.011, 1.058) per µg m-3 increase. For tuberculosis, the effect of mean temperature was significant with a RR of 1.107 (95%CI: 1.038, 1.180) per °C increase. Risk factors and spatial patterns were different for hospitalization of non-infectious and infectious chronic lung disease in Beijing. Even over a short time period (one year), associations were apparent with air pollution and meteorological factors.

Imaging of fiber-like structures in digital breast tomosynthesis.

Fiber-like features are an important aspect of breast imaging. Vessels and ducts are present in all breast images, and spiculations radiating from a mass can indicate malignancy. Accordingly, fiber objects are one of the three types of signals used in the American College of Radiology digital mammography (ACR-DM) accreditation phantom. Our work focuses on the image properties of fiber-like structures in digital breast tomosynthesis (DBT) and how image reconstruction can affect their appearance. The impact of DBT image reconstruction algorithm and regularization strength on the conspicuity of fiber-like signals of various orientations is investigated in simulation. A metric is developed to characterize this orientation dependence and allow for quantitative comparison of algorithms and associated parameters in the context of imaging fiber signals. The imaging properties of fibers, characterized in simulation, are then demonstrated in detail with physical DBT data of the ACR-DM phantom. The characterization of imaging of fiber signals is used to explain features of an actual clinical DBT case. For the algorithms investigated, at low regularization setting, the results show a striking variation in conspicuity as a function of orientation in the viewing plane. In particular, the conspicuity of fibers nearly aligned with the plane of the x-ray source trajectory is decreased relative to more obliquely oriented fibers. Increasing regularization strength mitigates this orientation dependence at the cost of increasing depth blur of these structures.

Collision-avoiding imaging trajectories for linac mounted cone-beam CT.

BACKGROUND: Some patients cannot be imaged with cone-beam CT for image-guided radiation therapy because their size, pose, or fixation devices cause collisions with the machine. OBJECTIVE: To investigate imaging trajectories that avoid such collisions by using virtual isocenter and variable magnification during acquisition while yielding comparable image quality. METHODS: The machine components most likely to collide are the gantry and kV detector. A virtual isocenter trajectory continuously moves the patient during gantry rotation to maintain an increased separation between the two. With dynamic magnification, the kV detector is dynamically moved to increase clearance for an angular range around the potential collision point while acquiring sufficient data to maintain the field-of-view. Both strategies were used independently and jointly with the resultant image quality evaluated against the standard circular acquisition. RESULTS: Collision avoiding trajectories show comparable contrast and resolution to standard techniques. For an anthropomorphic phantom, the RMSE is <7×10- 4, multi-scale structural similarity index is >0.97, and visual image fidelity is >0.96 for all trajectories when compared to a standard circular scan. CONCLUSIONS: The proposed trajectories avoid machine-patient collisions while providing comparable image quality to the current standard thereby enabling CBCT imaging for patients that could not otherwise be scanned.

Reduction of Angularly-Varying-Data Truncation in C-Arm CBCT Imaging.

C-arm cone-beam computed tomography (CBCT) has been used increasingly as an imaging tool for yielding 3D anatomical information about the subjects in surgical and interventional procedures. In the clinical applications, the limited field-of-view (FOV) of C-arm CBCT can lead to significant data truncation, resulting in image artifacts that can obscure low contrast tumor embedded within soft-tissue background, thus limiting the utility of C-arm CBCT. The truncation issue can become serious as most of the surgical and interventional procedures would involve devices and tubes that are placed outside the FOV of C-arm CBCT and thus can engender angularly-varying-data truncation. Existing methods may not be adequately applicable to dealing with the angularly-varying truncation. In this work, we seek to reduce truncation artifacts by tailoring optimization-based reconstruction directly from truncated data, without performing pre-reconstruction data compensation, collected from physical phantoms and human subjects. The reconstruction problem is formulated as a constrained optimization program in which a data-derivative-ℓ2-norm fidelity is included for effectively suppressing image artifacts caused by the angularly-varying-data truncation, and the generic Chambolle-Pock algorithm is tailored to solve the optimization program. The results of the study suggest that an appropriately designed optimization-based reconstruction can be exploited for yielding images with reduced artifacts caused by angularly-varying-data truncation.

Optimization-based image reconstruction from sparsely sampled data in electron paramagnetic resonance imaging.

Electron paramagnetic resonance imaging (EPRI) can yield information about the 3-dimensional (3D) spatial distribution of the unpaired-electron-spin density from which the spatial distribution of oxygen concentration within tumor tissue, referred to as the oxygen image or electron paramagnetic resonance (EPR) image in this work, can be derived. Existing algorithms for reconstruction of EPR images often require data collected at a large number of densely sampled projection views, resulting in a prolonged data-acquisition time and consequently numerous practical challenges especially to in vivo animal EPRI. Therefore, a strong interest exists in shortening data-acquisition time through reducing the number of data samples collected in EPRI, and one approach is to acquire data at a reduced number of sparsely distributed projection views from which existing algorithms may reconstruct images with prominent artifacts. In this work, we investigate and develop an optimization-based technique for image reconstruction from data collected at sparsely sampled projection views for reducing scanning time in EPRI. Specifically, we design a convex optimization program in which the EPR image of interest is formulated as a solution and then tailor the Chambolle-Pock (CP) primal-dual algorithm to reconstruct the image by solving the convex optimization program. Using computer-simulated EPRI data from numerical phantoms and real EPRI data collected from physical phantoms, we perform studies on the verification and characterization of the optimization-based technique for EPR image reconstruction. Results of the studies suggest that the technique may yield accurate EPR images from data collected at sparsely distributed projection views, thus potentially enabling fast EPRI with reduced acquisition time.

Investigating simulation-based metrics for characterizing linear iterative reconstruction in digital breast tomosynthesis.

PURPOSE: Simulation-based image quality metrics are adapted and investigated for characterizing the parameter dependences of linear iterative image reconstruction for DBT. METHODS: Three metrics based on a 2D DBT simulation are investigated: (1) a root-mean-square-error (RMSE) between the test phantom and reconstructed image, (2) a gradient RMSE where the comparison is made after taking a spatial gradient of both image and phantom, and (3) a region-of-interest (ROI) Hotelling observer (HO) for signal-known-exactly/background-known-exactly (SKE/BKE) and signal-known-exactly/background-known-statistically (SKE/BKS) detection tasks. Two simulation studies are performed using the aforementioned metrics, varying voxel aspect ratio, and regularization strength for two types of Tikhonov-regularized least-squares optimization. The RMSE metrics are applied to a 2D test phantom with resolution bar patterns at varying angles, and the ROI-HO metric is applied to two tasks relevant to DBT: lesion detection, modeled by use of a large, low-contrast signal, and microcalcification detection, modeled by use of a small, high-contrast signal. The RMSE metric trends are compared with visual assessment of the reconstructed bar-pattern phantom. The ROI-HO metric trends are compared with 3D reconstructed images from ACR phantom data acquired with a Hologic Selenia Dimensions DBT system. RESULTS: Sensitivity of the image RMSE to mean pixel value is found to limit its applicability to the assessment of DBT image reconstruction. The image gradient RMSE is insensitive to mean pixel value and appears to track better with subjective visualization of the reconstructed bar-pattern phantom. The ROI-HO metric shows an increasing trend with regularization strength for both forms of Tikhonov-regularized least-squares; however, this metric saturates at intermediate regularization strength indicating a point of diminishing returns for signal detection. Visualization with the reconstructed ACR phantom images appear to show a similar dependence with regularization strength. CONCLUSIONS: From the limited studies presented it appears that image gradient RMSE trends correspond with visual assessment better than image RMSE for DBT image reconstruction. The ROI-HO metric for both detection tasks also appears to reflect visual trends in the ACR phantom reconstructions as a function of regularization strength. We point out, however, that the true utility of these metrics can only be assessed after amassing more data.

Associations of PM2.5 and Black Carbon with Hospital Emergency Room Visits during Heavy Haze Events: A Case Study in Beijing, China.

In January 2013, severe haze events over northeastern China sparked substantial health concerns. This study explores the associations of fine particulate matter less than 2.5 µm (PM2.5) and black carbon (BC) with hospital emergency room visits (ERVs) during a haze season in Beijing. During that period, daily counts of ERVs for respiratory, cardiovascular and ocular diseases were obtained from a Level-3A hospital in Beijing from 1 December 2012 to 28 February 2013, and associations of which with PM2.5 and BC were estimated by time-stratified case-crossover analysis in single- and two-pollutant models. We found a 27.5% (95% confidence interval (CI): 13.0, 43.9%) increase in respiratory ERV (lag02), a 19.4% (95% CI: 2.5, 39.0%) increase in cardiovascular ERV (lag0), and a 12.6% (95% CI: 0.0, 26.7%) increase in ocular ERV (lag0) along with an interquartile range (IQR) increase in the PM2.5. An IQR increase of BC was associated with 27.6% (95% CI: 9.6, 48.6%) (lag02), 18.8% (95% CI: 1.4, 39.2%) (lag0) and 11.8% (95% CI: -1.4, 26.8%) (lag0) increases for changes in these same health outcomes respectively. Estimated associations were consistent after adjusting SO2 or NO2 in two-pollutant models. This study provides evidence that improving air quality and reducing haze days would greatly benefit the population health.

Dynamic intensity-weighted region of interest imaging for conebeam CT.

BACKGROUND: Patient dose from image guidance in radiotherapy is small compared to the treatment dose. However, the imaging beam is untargeted and deposits dose equally in tumor and healthy tissues. It is desirable to minimize imaging dose while maintaining efficacy. OBJECTIVE: Image guidance typically does not require full image quality throughout the patient. Dynamic filtration of the kV beam allows local control of CT image noise for high quality around the target volume and lower quality elsewhere, with substantial dose sparing and reduced scatter fluence on the detector. METHODS: The dynamic Intensity-Weighted Region of Interest (dIWROI) technique spatially varies beam intensity during acquisition with copper filter collimation. Fluence is reduced by 95% under the filters with the aperture conformed dynamically to the ROI during cone-beam CT scanning. Preprocessing to account for physical effects of the collimator before reconstruction is described. RESULTS: Reconstructions show image quality comparable to a standard scan in the ROI, with higher noise and streak artifacts in the outer region but still adequate quality for patient localization. Monte Carlo modeling shows dose reduction by 10-15% in the ROI due to reduced scatter, and up to 75% outside. CONCLUSIONS: The presented technique offers a method to reduce imaging dose by accepting increased image noise outside the ROI, while maintaining full image quality inside the ROI.

Noise properties of CT images reconstructed by use of constrained total-variation, data-discrepancy minimization.

PURPOSE: The authors develop and investigate iterative image reconstruction algorithms based on data-discrepancy minimization with a total-variation (TV) constraint. The various algorithms are derived with different data-discrepancy measures reflecting the maximum likelihood (ML) principle. Simulations demonstrate the iterative algorithms and the resulting image statistical properties for low-dose CT data acquired with sparse projection view angle sampling. Of particular interest is to quantify improvement of image statistical properties by use of the ML data fidelity term. METHODS: An incremental algorithm framework is developed for this purpose. The instances of the incremental algorithms are derived for solving optimization problems including a data fidelity objective function combined with a constraint on the image TV. For the data fidelity term the authors, compare application of the maximum likelihood principle, in the form of weighted least-squares (WLSQ) and Poisson-likelihood (PL), with the use of unweighted least-squares (LSQ). RESULTS: The incremental algorithms are applied to projection data generated by a simulation modeling the breast computed tomography (bCT) imaging application. The only source of data inconsistency in the bCT projections is due to noise, and a Poisson distribution is assumed for the transmitted x-ray photon intensity. In the simulations involving the incremental algorithms an ensemble of images, reconstructed from 1000 noise realizations of the x-ray transmission data, is used to estimate the image statistical properties. The WLSQ and PL incremental algorithms are seen to reduce image variance as compared to that of LSQ without sacrificing image bias. The difference is also seen at few iterations--short of numerical convergence of the corresponding optimization problems. CONCLUSIONS: The proposed incremental algorithms prove effective and efficient for iterative image reconstruction in low-dose CT applications particularly with sparse-view projection data.

Algorithm-enabled exploration of image-quality potential of cone-beam CT in image-guided radiation therapy.

Kilo-voltage (KV) cone-beam computed tomography (CBCT) unit mounted onto a linear accelerator treatment system, often referred to as on-board imager (OBI), plays an increasingly important role in image-guided radiation therapy. While the FDK algorithm is currently used for reconstructing images from clinical OBI data, optimization-based reconstruction has also been investigated for OBI CBCT. An optimization-based reconstruction involves numerous parameters, which can significantly impact reconstruction properties (or utility). The success of an optimization-based reconstruction for a particular class of practical applications thus relies strongly on appropriate selection of parameter values. In the work, we focus on tailoring the constrained-TV-minimization-based reconstruction, an optimization-based reconstruction previously shown of some potential for CBCT imaging conditions of practical interest, to OBI imaging through appropriate selection of parameter values. In particular, for given real data of phantoms and patient collected with OBI CBCT, we first devise utility metrics specific to OBI-quality-assurance tasks and then apply them to guiding the selection of parameter values in constrained-TV-minimization-based reconstruction. The study results show that the reconstructions are with improvement, relative to clinical FDK reconstruction, in both visualization and quantitative assessments in terms of the devised utility metrics.

Constrained TpV Minimization for Enhanced Exploitation of Gradient Sparsity: Application to CT Image Reconstruction.

Exploiting sparsity in the image gradient magnitude has proved to be an effective means for reducing the sampling rate in the projection view angle in computed tomography (CT). Most of the image reconstruction algorithms, developed for this purpose, solve a nonsmooth convex optimization problem involving the image total variation (TV). The TV seminorm is the ℓ1 norm of the image gradient magnitude, and reducing the ℓ1 norm is known to encourage sparsity in its argument. Recently, there has been interest in employing nonconvex ℓp quasinorms with 0

Task-based optimization of dedicated breast CT via Hotelling observer metrics.

PURPOSE: The purpose of this work is to develop and demonstrate a set of practical metrics for CT systems optimization. These metrics, based on the Hotelling observer (HO) figure of merit, are task-based. The authors therefore take the specific example of optimizing a dedicated breast CT system, including the reconstruction algorithm, for two relevant tasks, signal detection and Rayleigh discrimination. METHODS: A dedicated breast CT system is simulated using specifications in the literature from an existing prototype. The authors optimize configuration and image reconstruction algorithm parameters for two tasks: the detection of simulated microcalcifications and the discrimination of two adjacent, high-contrast signals, known as the Rayleigh discrimination task. The effects on task performance of breast diameter, signal location, image grid size, projection view number, and reconstruction filter were all investigated. Two HO metrics were evaluated: the percentage of correct decisions in a two-alternative forced choice experiment (equivalent to area under the ROC curve or AUC), and the HO efficiency, defined as the squared ratio of HO signal-to-noise ratio (SNR) in the reconstructed image to HO SNR in the projection data. RESULTS: The ease and efficiency of the HO metric computation allows a rapid high-resolution survey of many system parameters. Optimization of a range of system parameters using the HO results in images that subjectively appear optimal for the tasks investigated. Further, the results of assessment through the HO reproduce closely many existing results in the literature regarding the impact of parameter selection on image quality. CONCLUSIONS: This study demonstrates the utility of a task-based approach to system design, evaluation, and optimization. The methodology presented is equally applicable to determining the impact of a wide range of factors, including patient parameters, system and acquisition design, and the reconstruction algorithm. The results demonstrate the versatility of the proposed HO formalism by not only generating a set of parameters that are optimal for a given task but also by qualitatively reproducing many existing results from the breast CT literature. Meanwhile, the implementation of the proposed methodology is straightforward and entirely simulation-based. This is an attractive feature for many system optimization problems, where the goal is to analyze the individual system components such as the image reconstruction algorithm. Final assessment of the system as a whole should be based also on real data studies.

Investigation of iterative image reconstruction in low-dose breast CT.

There is interest in developing computed tomography (CT) dedicated to breast-cancer imaging. Because breast tissues are radiation-sensitive, the total radiation exposure in a breast-CT scan is kept low, often comparable to a typical two-view mammography exam, thus resulting in a challenging low-dose-data-reconstruction problem. In recent years, evidence has been found that suggests that iterative reconstruction may yield images of improved quality from low-dose data. In this work, based upon the constrained image total-variation minimization program and its numerical solver, i.e., the adaptive steepest descent-projection onto the convex set (ASD-POCS), we investigate and evaluate iterative image reconstructions from low-dose breast-CT data of patients, with a focus on identifying and determining key reconstruction parameters, devising surrogate utility metrics for characterizing reconstruction quality, and tailoring the program and ASD-POCS to the specific reconstruction task under consideration. The ASD-POCS reconstructions appear to outperform the corresponding clinical FDK reconstructions, in terms of subjective visualization and surrogate utility metrics.

Convex optimization problem prototyping for image reconstruction in computed tomography with the Chambolle-Pock algorithm.

The primal-dual optimization algorithm developed in Chambolle and Pock (CP) (2011 J. Math. Imag. Vis. 40 1-26) is applied to various convex optimization problems of interest in computed tomography (CT) image reconstruction. This algorithm allows for rapid prototyping of optimization problems for the purpose of designing iterative image reconstruction algorithms for CT. The primal-dual algorithm is briefly summarized in this paper, and its potential for prototyping is demonstrated by explicitly deriving CP algorithm instances for many optimization problems relevant to CT. An example application modeling breast CT with low-intensity x-ray illumination is presented.

Evaluation of sparse-view reconstruction from flat-panel-detector cone-beam CT.

Flat-panel-detector x-ray cone-beam computed tomography (CBCT) is used in a rapidly increasing host of imaging applications, including image-guided surgery and radiotherapy. The purpose of the work is to investigate and evaluate image reconstruction from data collected at projection views significantly fewer than what is used in current CBCT imaging. Specifically, we carried out imaging experiments using a bench-top CBCT system that was designed to mimic imaging conditions in image-guided surgery and radiotherapy; we applied an image reconstruction algorithm based on constrained total-variation (TV)-minimization to data acquired with sparsely sampled view-angles and conducted extensive evaluation of algorithm performance. Results of the evaluation studies demonstrate that, depending upon scanning conditions and imaging tasks, algorithms based on constrained TV-minimization can reconstruct images of potential utility from a small fraction of the data used in typical, current CBCT applications. A practical implication of the study is that the optimization of algorithm design and implementation can be exploited for considerably reducing imaging effort and radiation dose in CBCT.

TGFbeta/BMP type I receptors ALK1 and ALK2 are essential for BMP9-induced osteogenic signaling in mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are bone marrow stromal cells that can differentiate into multiple lineages. We previously demonstrated that BMP9 is one of the most potent BMPs to induce osteogenic differentiation of MSCs. BMP9 is one of the least studied BMPs. Whereas ALK1, ALK5, and/or endoglin have recently been reported as potential BMP9 type I receptors in endothelial cells, little is known about type I receptor involvement in BMP9-induced osteogenic differentiation in MSCs. Here, we conduct a comprehensive analysis of the functional role of seven type I receptors in BMP9-induced osteogenic signaling in MSCs. We have found that most of the seven type I receptors are expressed in MSCs. However, using dominant-negative mutants for the seven type I receptors, we demonstrate that only ALK1 and ALK2 mutants effectively inhibit BMP9-induced osteogenic differentiation in vitro and ectopic ossification in MSC implantation assays. Protein fragment complementation assays demonstrate that ALK1 and ALK2 directly interact with BMP9. Likewise, RNAi silencing of ALK1 and ALK2 expression inhibits BMP9-induced BMPR-Smad activity and osteogenic differentiation in MSCs both in vitro and in vivo. Therefore, our results strongly suggest that ALK1 and ALK2 may play an important role in mediating BMP9-induced osteogenic differentiation. These findings should further aid us in understanding the molecular mechanism through which BMP9 regulates osteogenic differentiation of MSCs.