Training certified detectives to track down the intrinsic shortcuts in COVID-19 chest x-ray data sets.

Deep learning faces a significant challenge wherein the trained models often underperform when used with external test data sets. This issue has been attributed to spurious correlations between irrelevant features in the input data and corresponding labels. This study uses the classification of COVID-19 from chest x-ray radiographs as an example to demonstrate that the image contrast and sharpness, which are characteristics of a chest radiograph dependent on data acquisition systems and imaging parameters, can be intrinsic shortcuts that impair the model's generalizability. The study proposes training certified shortcut detective models that meet a set of qualification criteria which can then identify these intrinsic shortcuts in a curated data set.

Training certified detectives to track down the intrinsic shortcuts in COVID-19 chest x-ray data sets.

Deep learning faces a significant challenge wherein the trained models often underperform when used with external test data sets. This issue has been attributed to spurious correlations between irrelevant features in the input data and corresponding labels. This study uses the classification of COVID-19 from chest x-ray radiographs as an example to demonstrate that the image contrast and sharpness, which are characteristics of a chest radiograph dependent on data acquisition systems and imaging parameters, can be intrinsic shortcuts that impair the model's generalizability. The study proposes training certified shortcut detective models that meet a set of qualification criteria which can then identify these intrinsic shortcuts in a curated data set.

A quality-checked and physics-constrained deep learning method to estimate material basis images from single-kV contrast-enhanced chest CT scans.

BACKGROUND: Single-kV CT imaging is one of the primary imaging methods in radiology practices. However, it does not provide material basis images for some subtle lesion characterization tasks in clinical diagnosis. PURPOSE: To develop a quality-checked and physics-constrained deep learning (DL) method to estimate material basis images from single-kV CT data without resorting to dual-energy CT acquisition schemes. METHODS: Single-kV CT images are decomposed into two material basis images using a deep neural network. The role of this network is to generate a feature space with 64 template features with the same matrix dimensions of the input single-kV CT image. These 64 template image features are then combined to generate the desired material basis images with different sets of combination coefficients, one for each material basis image. Dual-energy CT image acquisitions with two separate kVs were curated to generate paired training data between a single-kV CT image and the corresponding two material basis images. To ensure the obtained two material basis images are consistent with the encoded spectral information in the actual projection data, two physics constraints, that is, (1) effective energy of each measured projection datum that characterizes the beam hardening in data acquisitions and (2) physical factors of scanners such as detector and tube characteristics, are incorporated into the end-to-end training. The entire architecture is referred to as Deep-En-Chroma in this paper. In the application stage, the generated material basis images are sent to a deep quality check (Deep-QC) network to assess the quality of estimated images and to report the pixel-wise estimation errors for users. The models were developed using 5592 training and validation pairs generated from 48 clinical cases. Additional 1526 CT images from another 13 patients were used to evaluate the quantitative accuracy of water and iodine basis images estimated by Deep-En-Chroma. RESULTS: For the iodine basis images estimated by Deep-En-Chroma, the mean difference with respect to dual-energy CT is -0.25 mg/mL, and the agreement limits are [-0.75 mg/mL, +0.24 mg/mL]. For the water basis images estimated by Deep-En-Chroma, the mean difference with respect to dual-energy CT is 0.0 g/mL, and the agreement limits are [-0.01 g/mL, 0.01 g/mL]. Across the test cohort, the median [25th, 75th percentiles] root mean square errors between the Deep-En-Chroma and dual-energy material images are 14 [12, 16] mg/mL for the water images and 0.73 [0.64, 0.80] mg/mL for the iodine images. When significant errors are present in the estimated material basis images, Deep-QC can capture these errors and provide pixel-wise error maps to inform users whether the DL results are trustworthy. CONCLUSIONS: The Deep-En-Chroma network provides a new pathway to estimating the clinically relevant material basis images from single-kV CT data and the Deep-QC module to inform end-users of the accuracy of the DL material basis images in practice.

Quantitative lung perfusion blood volume using dual energy CT-based effective atomic number (Zeff ) imaging.

BACKGROUND: Iodine material images (aka iodine basis images) generated from dual energy computed tomography (DECT) have been used to assess potential perfusion defects in the pulmonary parenchyma. However, iodine material images do not provide the needed absolute quantification of the pulmonary blood pool, as materials with effective atomic numbers (Zeff ) different from those of basis materials may also contribute to iodine material images, thus confounding the quantification of perfusion defects. PURPOSE: (i) To demonstrate the limitations of iodine material images in pulmonary perfusion defect quantification and (ii) to develop and validate a new quantitative biomarker using effective atomic numbers derived from DECT images. METHODS: The quantitative relationship between the perfusion blood volume (PBV) in pulmonary parenchyma and the effective atomic number (Zeff ) spatial distribution was studied to show that the desired quantitative PBV maps are determined by the spatial maps of Zeff as PB V Z eff ( x ) = a Z eff ß ( x ) + b , where a, b, and ß are three constants. Namely, quantitative PB V Z eff is determined by Zeff images instead of the iodine basis images. Perfusion maps were generated for four human subjects to demonstrate the differences between conventional iodine material image-based PBV (PBViodine ) derived from two-material decompositions and the proposed PB V Z eff method. RESULTS: Among patients with pulmonary emboli, the proposed PB V Z eff maps clearly show the perfusion defects while the PBViodine maps do not. Additionally, when there are no perfusion defects present in the derived PBV maps, no pulmonary emboli were diagnosed by an experienced thoracic radiologist. CONCLUSION: Effective atomic number-based quantitative PBV maps provide the needed sensitive and specific biomarker to quantify pulmonary perfusion defects.

Diagnosis of Coronavirus Disease 2019 Pneumonia by Using Chest Radiography: Value of Artificial Intelligence.

Background Radiologists are proficient in differentiating between chest radiographs with and without symptoms of pneumonia but have found it more challenging to differentiate coronavirus disease 2019 (COVID-19) pneumonia from non-COVID-19 pneumonia on chest radiographs. Purpose To develop an artificial intelligence algorithm to differentiate COVID-19 pneumonia from other causes of abnormalities at chest radiography. Materials and Methods In this retrospective study, a deep neural network, CV19-Net, was trained, validated, and tested on chest radiographs in patients with and without COVID-19 pneumonia. For the chest radiographs positive for COVID-19, patients with reverse transcription polymerase chain reaction results positive for severe acute respiratory syndrome coronavirus 2 with findings positive for pneumonia between February 1, 2020, and May 30, 2020, were included. For the non-COVID-19 chest radiographs, patients with pneumonia who underwent chest radiography between October 1, 2019, and December 31, 2019, were included. Area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were calculated to characterize diagnostic performance. To benchmark the performance of CV19-Net, a randomly sampled test data set composed of 500 chest radiographs in 500 patients was evaluated by the CV19-Net and three experienced thoracic radiologists. Results A total of 2060 patients (5806 chest radiographs; mean age, 62 years ± 16 [standard deviation]; 1059 men) with COVID-19 pneumonia and 3148 patients (5300 chest radiographs; mean age, 64 years ± 18; 1578 men) with non-COVID-19 pneumonia were included and split into training and validation and test data sets. For the test set, CV19-Net achieved an AUC of 0.92 (95% CI: 0.91, 0.93). This corresponded to a sensitivity of 88% (95% CI: 87, 89) and a specificity of 79% (95% CI: 77, 80) by using a high-sensitivity operating threshold, or a sensitivity of 78% (95% CI: 77, 79) and a specificity of 89% (95% CI: 88, 90) by using a high-specificity operating threshold. For the 500 sampled chest radiographs, CV19-Net achieved an AUC of 0.94 (95% CI: 0.93, 0.96) compared with an AUC of 0.85 (95% CI: 0.81, 0.88) achieved by radiologists. Conclusion CV19-Net was able to differentiate coronavirus disease 2019-related pneumonia from other types of pneumonia, with performance exceeding that of experienced thoracic radiologists. © RSNA, 2021 Online supplemental material is available for this article.

Limb functional recovery is impaired in fibroblast growth factor-2 (FGF2) deficient mice despite chronic ischaemia-induced vascular growth.

FGF2 is a potent stimulator of vascular growth; however, even with a deficiency of FGF2 (Fgf2-/-), developmental vessel growth or ischaemia-induced revascularization still transpires. It remains to be elucidated as to what function, if any, FGF2 has during ischaemic injury. Wildtype (WT) or Fgf2-/- mice were subjected to hindlimb ischaemia for up to 42 days. Limb function, vascular growth, inflammatory- and angiogenesis-related proteins, and inflammatory cell infiltration were assessed in sham and ischaemic limbs at various timepoints. Recovery of ischaemic limb function was delayed in Fgf2-/- mice. Yet, vascular growth response to ischaemia was similar between WT and Fgf2-/- hindlimbs. Several angiogenesis- and inflammatory-related proteins (MCP-1, CXCL16, MMPs and PAI-1) were increased in Fgf2-/- ischaemic muscle. Neutrophil or monocyte recruitment/infiltration was elevated in Fgf2-/- ischaemic muscle. In summary, our study indicates that loss of FGF2 induces a pro-inflammatory microenvironment in skeletal muscle which exacerbates ischaemic injury and delays functional limb use.

Role of CT imaging in left atrial appendage occlusion for the WATCHMAN™ device.

Computed tomography (CT) plays a key role in the peri-procedural planning of left atrial appendage occlusion (LAAO) device placement and post-procedural evaluation. The geometric variability of the interatrial septum, left atrium, and the left atrial appendage morphology can be fully visualized and intuitively appreciated through CT-derived, patient-specific 3D model unique to each individual's anatomy. This review further defines the strengths and limitations of CT peri-procedural imaging in the planning of LAAO.

Purified PEGylated human glucagon-like peptide-2 reduces the severity of irradiation-induced acute radiation enteritis in rats.

Radiation-induced acute intestinal injury after abdominal and pelvic irradiation is a common and serious problem in the clinical setting. Glucagon-like peptide-2 (GLP-2), a 33-amino acid peptide, exerts diverse effects related to the regulation of gastrointestinal growth and function. However, GLP-2 is relatively unstable in vivo. The aim of the present study was to improve GLP-2 stability in vivo and to evaluate its therapeutic effect on acute radiation enteritis. We generated long-lasting intestinal protection peptides by conjugating human GLP-2 (hGLP-2) peptides to polyethyleneglycol (PEG) to produce mPEGylation hGLP-2 (Mono-PEG-hGLP-2) through an enzymatic site-specific transglutamination reaction. Mono-PEG-hGLP-2 synthesized under optimal reaction conditions and separated by one-step ion-exchange chromatography was found to be resistant to degradation in vitro. Pretreatment with Mono-PEG-hGLP-2 reduced the severity of radiation-induced intestinal injury, oxidative stress, and the expression of NF-κB in rats with irradiation-induced acute radiation enteritis. The enhanced biological potency of Mono-PEG-hGLP-2 highlights its potential as a therapeutic agent for intestinal diseases.

Transarterial radioembolization with yttrium-90 of unresectable primary hepatic malignancy in children.

BACKGROUND: Primary malignant liver tumors are rare, accounting for 1% to 2% of all childhood cancers. When chemotherapy fails, transarterial radioembolization with yttrium-90 (TARE-Y90) may offer an alternative therapy as a bridge to surgical resection or liver transplant or for palliation. METHODS: We conducted a retrospective review of 10 pediatric patients with histologically confirmed primary liver malignancy who received treatment with TARE-Y90. RESULTS: The median age at treatment was 5.5 years (range, 2-18 years). Median patient survival from initial diagnosis was 12.5 months (range, 10-28 months), and median patient survival after TARE-Y90 was 4 months (range, 2-20 months). Retreatment was well tolerated in three of 10 patients, with these patients demonstrating the longest survival times (range, 17-20 months). One patient was transplanted 6 weeks after TARE-Y90. By RECIST 1.1 criteria of all target lesions, eight of nine patients had stable disease, and one of nine had progressive disease. By mRECIST criteria (requiring postcontrast arterial phase imaging), two of seven patients had a partial response, four of seven had stable disease, and one of seven had progressive disease. CONCLUSION: TARE-Y90 of unresectable primary liver malignancy is both technically feasible and demonstrates an anticancer effect, and retreatment is well tolerated. TARE-Y90 could be considered as adjunctive therapy in pediatric patients with unresectable hepatic malignancies and could be used as a bridge to surgical resection or liver transplant. More research is required to determine the efficacy of this treatment in children and to define the clinical scenarios where benefit is likely to be optimized.

A locus on chromosome 5 shows African ancestry-limited association with alloimmunization in sickle cell disease.

Red blood cell (RBC) transfusion remains a critical therapeutic intervention in sickle cell disease (SCD); however, the apparent propensity of some patients to regularly develop RBC alloantibodies after transfusion presents a significant challenge to finding compatible blood for so-called alloimmunization responders. Predisposing genetic loci have long been thought to contribute to the responder phenomenon, but to date, no definitive loci have been identified. We undertook a genome-wide association study of alloimmunization responder status in 267 SCD multiple transfusion recipients, using genetic estimates of ancestral admixture to bolster our findings. Analyses revealed single nucleotide polymorphisms (SNPs) on chromosomes 2 and 5 approaching genome-wide significance (minimum P = 2.0 × 10-8 and 8.4 × 10-8, respectively), with local ancestry analysis demonstrating similar levels of admixture in responders and nonresponders at implicated loci. Association at chromosome 5 was nominally replicated in an independent cohort of 130 SCD transfusion recipients, with meta-analysis surpassing genome-wide significance (rs75853687, P meta = 6.6 × 10-9), and this extended to individuals forming multiple (>3) alloantibodies (P meta = 9.4 × 10-5). The associated variant is rare outside of African populations, and orthogonal genome-wide haplotype analyses, contingent on local ancestry, revealed genome-wide significant sharing of a ∼60-kb haplotype of African ancestry at the chromosome 5 locus (Bayes Factor = 4.95). This locus overlaps a putative cis-acting enhancer predicted to regulate transcription of ADRA1B and the lncRNA LINC01847, both members of larger ontologies associated with immune regulation. Our findings provide potential insights to the pathophysiology underlying the development of alloantibodies and implicate non-RBC ancestry-limited loci in the susceptibility to alloimmunization.

Radiation dose reduction through combining positron emission tomography/computed tomography (PET/CT) and diagnostic CT in children and young adults with lymphoma.

BACKGROUND: Both [F-18]2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and diagnostic CT are at times required for lymphoma staging. This means some body segments are exposed twice to X-rays for generation of CT data (diagnostic CT + localization CT). OBJECTIVE: To describe a combined PET/diagnostic CT approach that modulates CT tube current along the z-axis, providing diagnostic CT of some body segments and localization CT of the remaining body segments, thereby reducing patient radiation dose. MATERIALS AND METHODS: We retrospectively compared total patient radiation dose between combined PET/diagnostic CT and separately acquired PET/CT and diagnostic CT exams. When available, we calculated effective doses for both approaches in the same patient; otherwise, we used data from patients of similar size. To confirm image quality, we compared image noise (Hounsfield unit [HU] standard deviation) as measured in the liver on both combined and separately acquired diagnostic CT images. We used t-tests for dose comparisons and two one-sided tests for image-quality equivalence testing. RESULTS: Mean total effective dose for the CT component of the combined and separately acquired diagnostic CT exams were 6.20±2.69 and 8.17±2.61 mSv, respectively (P<0.0001). Average dose savings with the combined approach was 24.8±17.8% (2.60±2.51 mSv [range: 0.32-4.72 mSv]) of total CT effective dose. Image noise was not statistically significantly different between approaches (12.2±1.8 HU vs. 11.7±1.5 HU for the combined and separately acquired diagnostic CT images, respectively). CONCLUSION: A combined PET/diagnostic CT approach as described offers dose savings at similar image quality for children and young adults with lymphoma who have indications for both PET and diagnostic CT examinations.

Prolonged hydrocephalus induced by intraventricular hemorrhage in rats is reduced by curcumin therapy.

Prolonged hydrocephalus is a major cause of severe disability and death of intraventricular hemorrhage (IVH) patients. However, the therapeutic options to minimize the detrimental effects of post-hemorrhagic hydrocephalus are limited. Curcumin has been reported to confer neuroprotective effects in numerous neurological diseases and injuries, but its role in IVH-induced hydrocephalus has not been determined. The aim of present study was to determine whether curcumin treatment ameliorates blood brain barrier (BBB) damage and reduces the incidence of post-hemorrhagic hydrocephalus in IVH rat model. Autologous blood intraventricular injection was used to establish the IVH model. Our results revealed that repeated intraperitoneal injection of curcumin ameliorated IVH-induced learning and memory deficits as determined by Morris water maze and reduced the incidence of post-hemorrhagic hydrocephalus in a dose-dependent manner at 28 d post-IVH induction. Further, the increased BBB permeability and brain edema induced by IVH were significantly reduced by curcumin administration. In summary, these findings highlighted the important role of curcumin in improving neurological function deficits and protecting against BBB disruption via promoting the neurovascular unit restoration, and thus it reduced the severity of post-hemorrhagic hydrocephalus in the long term. It is believed that curcumin might prove to be an effective therapeutic component in prevent the post-IVH hydrocephalus in the near future.

Radiation Dose to the Breast by 64-slice CT: Effects of Scanner Model and Study Protocol.

RATIONALE AND OBJECTIVES: This work aimed to study the effects of scanner model and study protocol on radiation dose received by breast tissues from 64-slice computed tomography (CT) studies. MATERIALS AND METHODS: Four scanner models and three study protocols were used in scanning an anthropomorphic phantom with breast modules. Each protocol follows recommendations or guidelines from the American Association of Physicists in Medicine and the American College of Radiology. Twenty thermoluminescent dosimeters were placed inside the breast modules to measure breast tissue doses. Both the absolute and the normalized breast tissue doses were analyzed. RESULTS: The mean glandular doses of a lung cancer screening CT, a chest/abdomen/pelvis CT, and a virtual colonoscopy CT are equivalent to less than 1, 5-7, and 1-3 two-view digital mammograms, respectively, for a standard-sized patient. The normalized breast dose differs significantly (P < 0.01) between lung cancer screening CT and chest/abdomen/pelvis CT; however, it shows less than ±10% variation among scanner models for the same protocol. In virtual colonoscopy CT, breast tissue dose decreases with the distance between local tissues to the edge of the x-ray field, although the decreasing trend varies for different scanner models and protocol settings. CONCLUSIONS: When breasts are entirely included in the primary x-ray field, breast dose by 64-slice CT is mainly protocol dependent, with the normalized breast dose about 15% lower for protocols with modulated mA than for those with constant mA; when breasts are only partially included in the primary beam field, breast dose by 64-slice CT is dependent on both the scanner model and the protocol settings.

Recombinant covalently closed circular hepatitis B virus DNA induces prolonged viral persistence in immunocompetent mice.

It remains crucial to develop a laboratory model for studying hepatitis B virus (HBV) chronic infection. We hereby produced a recombinant covalently closed circular DNA (rcccDNA) in view of the key role of cccDNA in HBV persistence. A loxP-chimeric intron was engineered into a monomeric HBV genome in a precursor plasmid (prcccDNA), which was excised using Cre/loxP-mediated DNA recombination into a 3.3-kb rcccDNA in the nuclei of hepatocytes. The chimeric intron was spliced from RNA transcripts without interrupting the HBV life cycle. In cultured hepatoma cells, cotransfection of prcccDNA and pCMV-Cre (encoding Cre recombinase) resulted in accumulation of nuclear rcccDNA that was heat stable and epigenetically organized as a minichromosome. A mouse model of HBV infection was developed by hydrodynamic injection of prcccDNA. In the presence of Cre recombinase, rcccDNA was induced in the mouse liver with effective viral replication and expression, triggering a compromised T-cell response against HBV. Significant T-cell hyporesponsiveness occurred in mice receiving 4 µg prcccDNA, resulting in prolonged HBV antigenemia for up to 9 weeks. Persistent liver injury was observed as elevated alanine transaminase activity in serum and sustained inflammatory infiltration in the liver. Although a T-cell dysfunction was induced similarly, mice injected with a plasmid containing a linear HBV replicon showed rapid viral clearance within 2 weeks. Collectively, our study provides an innovative approach for producing a cccDNA surrogate that established HBV persistence in immunocompetent mice. It also represents a useful model system in vitro and in vivo for evaluating antiviral treatments against HBV cccDNA. Importance: (i) Unlike plasmids that contain a linear HBV replicon, rcccDNA established HBV persistence with sustained liver injury in immunocompetent mice. This method could be a prototype for developing a mouse model of chronic HBV infection. (ii) An exogenous intron was engineered into the HBV genome for functionally seamless DNA recombination. This original approach could be also extended to other viral studies. (iii) rcccDNA was substantially induced in the nuclei of hepatocytes and could be easily distinguished by its exogenous intron using PCR. This convenient model system affords the opportunity to test antivirals directly targeting HBV cccDNA.

Molecular strategy to reduce in vivo collagen barrier promotes entry of NCX1 positive inducible pluripotent stem cells (iPSC(NCX¹âº)) into ischemic (or injured) myocardium.

OBJECTIVE: The purpose of this study was to assess the effect of collagen composition on engraftment of progenitor cells within infarcted myocardium. BACKGROUND: We previously reported that intramyocardial penetration of stem/progenitor cells in epicardial patches was enhanced when collagen was reduced in hearts overexpressing adenylyl cyclase-6 (AC6). In this study we hypothesized an alternative strategy wherein overexpression of microRNA-29b (miR-29b), inhibiting mRNAs that encode cardiac fibroblast proteins involved in fibrosis, would similarly facilitate progenitor cell migration into infarcted rat myocardium. METHODS: In vitro: A tri-cell patch (Tri-P) consisting of cardiac sodium-calcium exchanger-1 (NCX1) positive iPSC (iPSC(NCX1+)), endothelial cells (EC), and mouse embryonic fibroblasts (MEF) was created, co-cultured, and seeded on isolated peritoneum. The expression of fibrosis-related genes was analyzed in cardiac fibroblasts (CFb) by qPCR and Western blot. In vivo: Nude rat hearts were administered mimic miRNA-29b (miR-29b), miRNA-29b inhibitor (Anti-29b), or negative mimic (Ctrl) before creation of an ischemically induced regional myocardial infarction (MI). The Tri-P was placed over the infarcted region 7 days later. Angiomyogenesis was analyzed by micro-CT imaging and immunofluorescent staining. Echocardiography was performed weekly. RESULTS: The number of green fluorescent protein positive (GFP(+)) cells, capillary density, and heart function were significantly increased in hearts overexpressing miR-29b as compared with Ctrl and Anti-29b groups. Conversely, down-regulation of miR-29b with anti-29b in vitro and in vivo induced interstitial fibrosis and cardiac remodeling. CONCLUSION: Overexpression of miR-29b significantly reduced scar formation after MI and facilitated iPSC(NCX1+) penetration from the cell patch into the infarcted area, resulting in restoration of heart function after MI.

Interior tomography in x-ray differential phase contrast CT imaging.

Differential phase contrast computed tomography (DPC-CT) is an x-ray imaging method that uses the wave properties of imaging photons as the contrast mechanism. It has been demonstrated that DPC images can be obtained using a conventional x-ray tube and a Talbot-Lau-type interferometer. Due to the limited size of the gratings, current data acquisition systems only offer a limited field of view, and thus are prone to data truncation. As a result, the reconstructed DPC-CT image may suffer from image artifacts and increased inaccuracy in the reconstructed image values. In this paper, we demonstrate that a small region of interest (ROI) within a large object can be accurately and stably reconstructed using fully truncated projection datasets provided that a priori information on electron density is known for a small region inside the ROI. The method reconstructs an image iteratively to satisfy a group of physical conditions by using a projection onto convex set (POCS) approach. In this work, this POCS algorithm is validated using both numerical simulations and physical phantom experimental data. In both cases, the root mean square error is reduced by an order of magnitude with respect to the truncated analytic reconstructions. Truncation artifacts observed in the latter reconstructions are eliminated using the POCS algorithm.

Multicontrast x-ray computed tomography imaging using Talbot-Lau interferometry without phase stepping.

PURPOSE: The purpose of this work is to demonstrate that multicontrast computed tomography (CT) imaging can be performed using a Talbot-Lau interferometer without phase stepping, thus allowing for an acquisition scheme like that used for standard absorption CT. METHODS: Rather than using phase stepping to extract refraction, small-angle scattering (SAS), and absorption signals, the two gratings of a Talbot-Lau interferometer were rotated slightly to generate a moiré pattern on the detector. A Fourier analysis of the moiré pattern was performed to obtain separate projection images of each of the three contrast signals, all from the same single-shot of x-ray exposure. After the signals were extracted from the detector data for all view angles, image reconstruction was performed to obtain absorption, refraction, and SAS CT images. A physical phantom was scanned to validate the proposed data acquisition method. The results were compared with a phantom scan using the standard phase stepping approach. RESULTS: The reconstruction of each contrast mechanism produced the expected results. Signal levels and contrasts match those obtained using the phase stepping technique. CONCLUSIONS: Absorption, refraction, and SAS CT imaging can be achieved using the Talbot-Lau interferometer without the additional overhead of long scan time and phase stepping.

Time-resolved interventional cardiac C-arm cone-beam CT: an application of the PICCS algorithm.

Time-resolved cardiac imaging is particularly interesting in the interventional setting since it would provide both image guidance for accurate procedural planning and cardiac functional evaluations directly in the operating room. Imaging the heart in vivo using a slowly rotating C-arm system is extremely challenging due to the limitations of the data acquisition system and the high temporal resolution required to avoid motion artifacts. In this paper, a data acquisition scheme and an image reconstruction method are proposed to achieve time-resolved cardiac cone-beam computed tomography imaging with isotropic spatial resolution and high temporal resolution using a slowly rotating C-arm system. The data are acquired within 14 s using a single gantry rotation with a short scan angular range. The enabling image reconstruction method is the prior image constrained compressed sensing (PICCS) algorithm. The prior image is reconstructed from data acquired over all cardiac phases. Each cardiac phase is then reconstructed from the retrospectively gated cardiac data using the PICCS algorithm. To validate the method, several studies were performed. Both numerical simulations using a hybrid motion phantom with static background anatomy as well as physical phantom studies have been used to demonstrate that the proposed method enables accurate reconstruction of image objects with a high isotropic spatial resolution. A canine animal model scanned in vivo was used to further validate the method.

Performance studies of four-dimensional cone beam computed tomography.

Four-dimensional cone beam computed tomography (4DCBCT) has been proposed to characterize the breathing motion of tumors before radiotherapy treatment. However, when the acquired cone beam projection data are retrospectively gated into several respiratory phases, the available data to reconstruct each phase is under-sampled and thus causes streaking artifacts in the reconstructed images. To solve the under-sampling problem and improve image quality in 4DCBCT, various methods have been developed. This paper presents performance studies of three different 4DCBCT methods based on different reconstruction algorithms. The aims of this paper are to study (1) the relationship between the accuracy of the extracted motion trajectories and the data acquisition time of a 4DCBCT scan and (2) the relationship between the accuracy of the extracted motion trajectories and the number of phase bins used to sort projection data. These aims will be applied to three different 4DCBCT methods: conventional filtered backprojection reconstruction (FBP), FBP with McKinnon-Bates correction (MB) and prior image constrained compressed sensing (PICCS) reconstruction. A hybrid phantom consisting of realistic chest anatomy and a moving elliptical object with known 3D motion trajectories was constructed by superimposing the analytical projection data of the moving object to the simulated projection data from a chest CT volume dataset. CBCT scans with gantry rotation times from 1 to 4 min were simulated, and the generated projection data were sorted into 5, 10 and 20 phase bins before different methods were used to reconstruct 4D images. The motion trajectories of the moving object were extracted using a fast free-form deformable registration algorithm. The root mean square errors (RMSE) of the extracted motion trajectories were evaluated for all simulated cases to quantitatively study the performance. The results demonstrate (1) longer acquisition times result in more accurate motion delineation for each method; (2) ten or more phase bins are necessary in 4DCBCT to ensure sufficient temporal resolution in tumor motion and (3) to achieve the same performance as FBP-4DCBCT with a 4 min data acquisition time, MB-4DCBCT and PICCS-4DCBCT need about 2- and 1 min data acquisition times, respectively.

Extraction of tumor motion trajectories using PICCS-4DCBCT: a validation study.

PURPOSE: As a counterpart of 4DCT in the treatment planning stage of radiotherapy treatment, 4D cone beam computed tomography (4DCBCT) method has been proposed to verify tumor motion trajectories before radiation therapy treatment delivery. Besides 4DCBCT acquisition using slower gantry rotation speed or multiple rotations, a new method using the prior image constrained compressed sensing (PICCS) image reconstruction method and the standard 1-min data acquisition were proposed. In this paper, the PICCS-4DCBCT method was combined with deformable registration to validate its capability in motion trajectory extraction using physical phantom data, simulated human subject data from 4DCT and in vivo human subject data. METHODS: Two methods were used to validate PICCS-4DCBCT for the purpose of respiratory motion delineation. The standard 1-min gantry rotation Cone Beam CT acquisition was used for both methods. In the first method, 4DCBCT projection data of a physical motion phantom were acquired using an on-board CBCT acquisition system (Varian Medical Systems, Palo Alto, CA). Using a deformable registration method, the object motion trajectories were extracted from both FBP and PICCS reconstructed 4DCBCT images, and compared against the programmed motion trajectories. In the second method, using a clinical 4DCT dataset, Cone Beam CT projections were simulated by forward projection. Using a deformable registration method, the tumor motion trajectories were extracted from the reconstructed 4DCT and PICCS-4DCBCT images. The performance of PICCS-4DCBCT is assessed against the 4DCT ground truth. The breathing period was varied in the simulation to study its effect on motion extraction. For both validation methods, the root mean square error (RMSE) and the maximum of the errors (MaxE) were used to quantify the accuracy of the extracted motion trajectories. After the validation, a clinical dataset was used to demonstrate the motion delineation capability of PICCS-4DCBCT for human subjects. RESULTS: In both validation studies, the RMSEs of the extracted motion trajectories from PICCS-4DCBCT images are less than 0.7 mm, and their MaxEs are less than 1 mm, for all three directions. In comparison, FBP-4DCBCT shows considerably larger RMSEs in the physical phantom based validation. PICCS-4DCBCT also shows insensitivity to the breathing period in the 4DCT based validation. For the in vivo human subject study, high quality 3D motion trajectory of the tumor was obtained from PICCS-4DCBCT images and showed consistency with visual observation. CONCLUSIONS: These results demonstrate accurate delineation of tumor motion trajectory can be achieved using PICCS-4DCBCT and the standard 1-min data acquisition.