TAF2, within the TFIID complex, regulates the expression of a subset of protein-coding genes.

TFIID, one of the general transcription factor (GTF), regulates transcriptional initiation of protein-coding genes through direct binding to promoter elements and subsequent recruitment of other GTFs and RNA polymerase II. Although generally required for most protein-coding genes, accumulated studies have also demonstrated promoter-specific functions for several TFIID subunits in gene activation. Here, we report that TBP-associated factor 2 (TAF2) specifically regulates TFIID binding to a small subset of protein-coding genes and is essential for cell growth of multiple cancer lines. Co-immunoprecipitation assays revealed that TAF2 may be sub-stoichiometrically associated with the TFIID complex, thus indicating a minor fraction of TAF2-containing TFIID in cells. Consistently, integrated genome-wide profiles show that TAF2 binds to and regulates only a small subset of protein-coding genes. Furthermore, through the use of an inducible TAF2 degradation system, our results reveal a reduction of TBP/TFIID binding to several ribosomal genes upon selective ablation of TAF2. In addition, depletion of TAF2, as well as the TAF2-regulated ribosomal protein genes RPL30 and RPL39, decreases ribosome assembly and global protein translation. Collectively, this study suggests that TAF2 within the TFIID complex is of functional importance for TBP/TFIID binding to and expression of a small subset of protein-coding genes, thus establishing a previously unappreciated promoter-selective function for TAF2.

The Wave Sign Correlates with the Posterior Horn Medial Meniscus (PHMM) Tear in the Anterior Cruciate Ligament (ACL) Deficient Knee

@#Introduction: A posterior horn medial meniscus (PHMM) tear subjects the knee to pathological stresses, especially in the setting of a deficient anterior cruciate ligament (ACL). These PHMM tears have to be surgically addressed, however they remain a diagnostic challenge. Hence, this study aims to evaluate the wave sign as an arthroscopic diagnostic aid for the PHMM tear which may be occult. Materials and methods: This is a retrospective study of 61 consecutive patients (62 ACL-deficient knees) who underwent arthroscopic primary ACL reconstruction between September 2017 and August 2018. We defined PHMM tears as tears located in the posterior one-third of the medial meniscus. Root tears and ramp lesions were included in our analysis. The arthroscopic findings were recorded after a comprehensive arthroscopic survey. Results: In the sample of ACL-deficient knees, 44 (71.0%) had a concomitant medial meniscus tear. The most common location for the tear was in the posterior horn (81.8%). There were seven occult PHMM tears, not described by the radiologist or identified by the operating surgeon on the preoperative magnetic resonance imaging. The wave sign was identified in 10 (16.1%) knees, all confirming the presence of the PHMM tear. A positive correlation was found between the presence of the wave sign and the PHMM tear. Conclusions: The wave sign has a statistically significant but weak positive correlation with the presence of the PHMM. We view the wave sign as a valuable arthroscopic cue to rule-in the presence of the PHMM tear in the ACLdeficient knee.

Methylation of the tyrosine hydroxylase gene is dysregulated by cocaine dependence in the human striatum.

Cocaine dependence is a chronic, relapsing disorder caused by lasting changes in the brain. Animal studies have identified cocaine-related alterations in striatal DNA methylation; however, it is unclear how methylation is related to cocaine dependence in humans. We generated methylomic profiles of the nucleus accumbens using human postmortem brains from a cohort of individuals with cocaine dependence and healthy controls (n = 25 per group). We found hypermethylation in a cluster of CpGs within the gene body of tyrosine hydroxylase (TH), containing a putative binding site for the early growth response 1 (EGR1) transcription factor, which is hypermethylated in the caudate nucleus of cocaine-dependent individuals. We replicated this finding and found it to be specific to striatal neuronal nuclei. Furthermore, this locus demonstrates enhancer activity which is attenuated by methylation and enhanced by EGR1 overexpression. These results suggest that cocaine dependence alters the epigenetic regulation of dopaminergic signaling genes.

Volume-of-interest Imaging Using Multiple Aperture Devices.

Volume-of-interest (VOI) imaging is a promising strategy for dose reduction in computed tomography (CT) while retaining image quality. However, implementation of VOI-CT has been challenged by the lack of adequate hardware and the interior tomography reconstruction problem. Multiple aperture devices (MAD) are a novel filtration scheme that can achieve x-ray fluence field modulation in a compact design with small translations. In this work, we propose a general approach for VOI imaging using MADs. MAD trajectories are designed to dynamically tailor the fluence for prescribed VOI. A penalized-likelihood reconstruction algorithm is proposed for fully truncated projections extended with scout views. Physical experiments were conducted to verify the feasibility for non-centered elliptic VOIs. Image quality and dose were estimated and compared with standard fullfield protocols. The ability of MAD-based VOI imaging to retain high image quality while significantly decreasing the total dose is demonstrated, suggesting the potential for dose reduction in clinical CT applications.

Spatial Resolution and Noise Prediction in Flat-Panel Cone-Beam CT Penalized-likelihood Reconstruction.

PURPOSE: Model based iterative reconstruction (MBIR) algorithms such as penalized-likelihood (PL) methods have data-dependent and shift-variant image properties. Predictors of local reconstructed noise and resolution have found application in a number of methods that seek to understand, control, and optimize CT data acquisition and reconstruction parameters in a prospective fashion (as opposed to studies based on exhaustive evaluation). However, previous MBIR prediction methods have relied on idealized system models. In this work, we develop and validate new predictors using accurate physical models specific to flat-panel CT systems. METHODS: Novel predictors for estimation of local spatial resolution and noise properties are developed for PL reconstruction that include a physical model for blur and correlated noise in flat-panel cone-beam CT (CBCT) acquisitions. Prospective predictions (e.g., without reconstruction) of local point spread function and and local noise power spectrum (NPS) model are applied, compared, and validated using a flat-panel CBCT test bench. RESULTS: Comparisons between prediction and physical measurements show excellent agreement for both spatial resolution and noise properties. In comparison, traditional prediction methods (that ignore blur/correlation found in flat-panel data) fail to capture important data characteristics and show significant mismatch. CONCLUSION: Novel image property predictors permit prospective assessment of flat-panel CBCT using MBIR. Such predictors enable standard and task-based performance assessments, and are well-suited to evaluation, control, and optimization of the CT imaging chain (e.g., x-ray technique, reconstruction parameters, novel data acquisition methods, etc.) for improved imaging performance and/or dose utilization.

Hydrogen deuterium exchange reveals changes to protein dynamics of recombinant human erythropoietin upon N- and O- desialylation.

Recombinant human erythropoietin (EPO) is a therapeutic glycoprotein widely used for treating anemia. EPO glycans carry extensive sialylation and the level of the modification is known to affect receptor binding, protein stability and pharmacokinetics. Nonetheless, a detailed understanding of the effects of sialylation on EPO conformation and dynamics is still lacking. Here we investigate the changes to EPO dynamics following enzymatic trimming of terminal sialic acid by amide hydrogen deuterium exchange mass spectrometry (HDX-MS). The results revealed that desialylation enhances structural flexibility near the glycosylation sites, with greater effects observed around the O-glycosylation site relative to the N-glycosylation sites. The affected regions are surface-exposed loops connecting the helix bundle, which do not appear to reduce the thermostability of the molecule as revealed from melting measurement. Our findings demonstrate the feasibility of HDX-MS technique in deciphering the function of specific type of glycosylation that can provide novel insights into the role of sialylation on protein therapeutics.

Association of a History of Child Abuse With Impaired Myelination in the Anterior Cingulate Cortex: Convergent Epigenetic, Transcriptional, and Morphological Evidence.

OBJECTIVE: Child abuse has devastating and long-lasting consequences, considerably increasing the lifetime risk of negative mental health outcomes such as depression and suicide. Yet the neurobiological processes underlying this heightened vulnerability remain poorly understood. The authors investigated the hypothesis that epigenetic, transcriptomic, and cellular adaptations may occur in the anterior cingulate cortex as a function of child abuse. METHOD: Postmortem brain samples from human subjects (N=78) and from a rodent model of the impact of early-life environment (N=24) were analyzed. The human samples were from depressed individuals who died by suicide, with (N=27) or without (N=25) a history of severe child abuse, as well as from psychiatrically healthy control subjects (N=26). Genome-wide DNA methylation and gene expression were investigated using reduced representation bisulfite sequencing and RNA sequencing, respectively. Cell type-specific validation of differentially methylated loci was performed after fluorescence-activated cell sorting of oligodendrocyte and neuronal nuclei. Differential gene expression was validated using NanoString technology. Finally, oligodendrocytes and myelinated axons were analyzed using stereology and coherent anti-Stokes Raman scattering microscopy. RESULTS: A history of child abuse was associated with cell type-specific changes in DNA methylation of oligodendrocyte genes and a global impairment of the myelin-related transcriptional program. These effects were absent in the depressed suicide completers with no history of child abuse, and they were strongly correlated with myelin gene expression changes observed in the animal model. Furthermore, a selective and significant reduction in the thickness of myelin sheaths around small-diameter axons was observed in individuals with history of child abuse. CONCLUSIONS: The results suggest that child abuse, in part through epigenetic reprogramming of oligodendrocytes, may lastingly disrupt cortical myelination, a fundamental feature of cerebral connectivity.

Joint Optimization of Fluence Field Modulation and Regularization in Task-Driven Computed Tomography.

PURPOSE: This work presents a task-driven joint optimization of fluence field modulation (FFM) and regularization in quadratic penalized-likelihood (PL) reconstruction. Conventional FFM strategies proposed for filtered-backprojection (FBP) are evaluated in the context of PL reconstruction for comparison. METHODS: We present a task-driven framework that leverages prior knowledge of the patient anatomy and imaging task to identify FFM and regularization. We adopted a maxi-min objective that ensures a minimum level of detectability index (d') across sample locations in the image volume. The FFM designs were parameterized by 2D Gaussian basis functions to reduce dimensionality of the optimization and basis function coefficients were estimated using the covariance matrix adaptation evolutionary strategy (CMA-ES) algorithm. The FFM was jointly optimized with both space-invariant and spatially-varying regularization strength (ß) - the former via an exhaustive search through discrete values and the latter using an alternating optimization where ß was exhaustively optimized locally and interpolated to form a spatially-varying map. RESULTS: The optimal FFM inverts as ß increases, demonstrating the importance of a joint optimization. For the task and object investigated, the optimal FFM assigns more fluence through less attenuating views, counter to conventional FFM schemes proposed for FBP. The maxi-min objective homogenizes detectability throughout the image and achieves a higher minimum detectability than conventional FFM strategies. CONCLUSIONS: The task-driven FFM designs found in this work are counter to conventional patterns for FBP and yield better performance in terms of the maxi-min objective, suggesting opportunities for improved image quality and/or dose reduction when model-based reconstructions are applied in conjunction with FFM.

Experimental evaluation of dual Multiple Aperture Devices for Fluence Field Modulated X-Ray Computed Tomography.

Acquisition of CT images with comparable diagnostic power can potentially be achieved with lower radiation exposure than the current standard of care through the adoption of hardware-based fluence-field modulation (e.g. dynamic bowtie filters). While modern CT scanners employ elements such as static bowtie filters and tube-current modulation, such solutions are limited in the fluence patterns that they can achieve, and thus are limited in their ability to adapt to broad classes of patient morphology. Fluence-field modulation also enables new applications such as region-of-interest imaging, task specific imaging, reducing measurement noise or improving image quality. The work presented in this paper leverages a novel fluence modulation strategy that uses "Multiple Aperture Devices" (MADs) which are, in essence, binary filters, blocking or passing x-rays on a fine scale. Utilizing two MAD devices in series provides the capability of generating a large number of fluence patterns via small relative motions between the MAD filters. We present the first experimental evaluation of fluence-field modulation using a dual-MAD system, and demonstrate the efficacy of this technique with a characterization of achievable fluence patterns and an investigation of experimental projection data.

Antitumor Activity of RXDX-105 in Multiple Cancer Types with RET Rearrangements or Mutations.

Purpose: While multikinase inhibitors with RET activity are active in RET-rearranged thyroid and lung cancers, objective response rates are relatively low and toxicity can be substantial. The development of novel RET inhibitors with improved potency and/or reduced toxicity is thus an unmet need. RXDX-105 is a small molecule kinase inhibitor that potently inhibits RET. The purpose of the preclinical and clinical studies was to evaluate the potential of RXDX-105 as an effective therapy for cancers driven by RET alterations.Experimental design: The RET-inhibitory activity of RXDX-105 was assessed by biochemical and cellular assays, followed by in vivo tumor growth inhibition studies in cell line- and patient-derived xenograft models. Antitumor activity in patients was assessed by imaging and Response Evaluation Criteria in Solid Tumors (RECIST).Results: Biochemically, RXDX-105 inhibited wild-type RET, CCDC6-RET, NCOA4-RET, PRKAR1A-RET, and RET M918T with low to subnanomolar activity while sparing VEGFR2/KDR and VEGFR1/FLT. RXDX-105 treatment resulted in dose-dependent inhibition of proliferation of CCDC6-RET-rearranged and RET C634W-mutant cell lines and inhibition of downstream signaling pathways. Significant tumor growth inhibition in CCDC6-RET, NCOA4-RET, and KIF5B-RET-containing xenografts was observed, with the concomitant inhibition of p-ERK, p-AKT, and p-PLCγ. Additionally, a patient with advanced RET-rearranged lung cancer had a rapid and sustained response to RXDX-105 in both intracranial and extracranial disease.Conclusions: These data support the inclusion of patients bearing RET alterations in ongoing and future molecularly enriched clinical trials to explore RXDX-105 efficacy across a variety of tumor types. Clin Cancer Res; 23(12); 2981-90. ©2016 AACR.

Task-Driven Tube Current Modulation and Regularization Design in Computed Tomography with Penalized-Likelihood Reconstruction.

PURPOSE: This work applies task-driven optimization to design CT tube current modulation and directional regularization in penalized-likelihood (PL) reconstruction. The relative performance of modulation schemes commonly adopted for filtered-backprojection (FBP) reconstruction were also evaluated for PL in comparison. METHODS: We adopt a task-driven imaging framework that utilizes a patient-specific anatomical model and information of the imaging task to optimize imaging performance in terms of detectability index (d'). This framework leverages a theoretical model based on implicit function theorem and Fourier approximations to predict local spatial resolution and noise characteristics of PL reconstruction as a function of the imaging parameters to be optimized. Tube current modulation was parameterized as a linear combination of Gaussian basis functions, and regularization was based on the design of (directional) pairwise penalty weights for the 8 in-plane neighboring voxels. Detectability was optimized using a covariance matrix adaptation evolutionary strategy algorithm. Task-driven designs were compared to conventional tube current modulation strategies for a Gaussian detection task in an abdomen phantom. RESULTS: The task-driven design yielded the best performance, improving d' by ~20% over an unmodulated acquisition. Contrary to FBP, PL reconstruction using automatic exposure control and modulation based on minimum variance (in FBP) performed worse than the unmodulated case, decreasing d' by 16% and 9%, respectively. CONCLUSIONS: This work shows that conventional tube current modulation schemes suitable for FBP can be suboptimal for PL reconstruction. Thus, the proposed task-driven optimization provides additional opportunities for improved imaging performance and dose reduction beyond that achievable with conventional acquisition and reconstruction.

Self-calibration of cone-beam CT geometry using 3D-2D image registration.

Robotic C-arms are capable of complex orbits that can increase field of view, reduce artifacts, improve image quality, and/or reduce dose; however, it can be challenging to obtain accurate, reproducible geometric calibration required for image reconstruction for such complex orbits. This work presents a method for geometric calibration for an arbitrary source-detector orbit by registering 2D projection data to a previously acquired 3D image. It also yields a method by which calibration of simple circular orbits can be improved. The registration uses a normalized gradient information similarity metric and the covariance matrix adaptation-evolution strategy optimizer for robustness against local minima and changes in image content. The resulting transformation provides a 'self-calibration' of system geometry. The algorithm was tested in phantom studies using both a cone-beam CT (CBCT) test-bench and a robotic C-arm (Artis Zeego, Siemens Healthcare) for circular and non-circular orbits. Self-calibration performance was evaluated in terms of the full-width at half-maximum (FWHM) of the point spread function in CBCT reconstructions, the reprojection error (RPE) of steel ball bearings placed on each phantom, and the overall quality and presence of artifacts in CBCT images. In all cases, self-calibration improved the FWHM-e.g. on the CBCT bench, FWHM = 0.86 mm for conventional calibration compared to 0.65 mm for self-calibration (p < 0.001). Similar improvements were measured in RPE-e.g. on the robotic C-arm, RPE = 0.73 mm for conventional calibration compared to 0.55 mm for self-calibration (p < 0.001). Visible improvement was evident in CBCT reconstructions using self-calibration, particularly about high-contrast, high-frequency objects (e.g. temporal bone air cells and a surgical needle). The results indicate that self-calibration can improve even upon systems with presumably accurate geometric calibration and is applicable to situations where conventional calibration is not feasible, such as complex non-circular CBCT orbits and systems with irreproducible source-detector trajectory.

Self-Calibration of Cone-Beam CT Geometry Using 3D-2D Image Registration: Development and Application to Task-Based Imaging with a Robotic C-Arm.

PURPOSE: Robotic C-arm systems are capable of general noncircular orbits whose trajectories can be driven by the particular imaging task. However obtaining accurate calibrations for reconstruction in such geometries can be a challenging problem. This work proposes a method to perform a unique geometric calibration of an arbitrary C-arm orbit by registering 2D projections to a previously acquired 3D image to determine the transformation parameters representing the system geometry. METHODS: Experiments involved a cone-beam CT (CBCT) bench system, a robotic C-arm, and three phantoms. A robust 3D-2D registration process was used to compute the 9 degree of freedom (DOF) transformation between each projection and an existing 3D image by maximizing normalized gradient information with a digitally reconstructed radiograph (DRR) of the 3D volume. The quality of the resulting "self-calibration" was evaluated in terms of the agreement with an established calibration method using a BB phantom as well as image quality in the resulting CBCT reconstruction. RESULTS: The self-calibration yielded CBCT images without significant difference in spatial resolution from the standard ("true") calibration methods (p-value >0.05 for all three phantoms), and the differences between CBCT images reconstructed using the "self" and "true" calibration methods were on the order of 10-3 mm-1. Maximum error in magnification was 3.2%, and back-projection ray placement was within 0.5 mm. CONCLUSION: The proposed geometric "self" calibration provides a means for 3D imaging on general non-circular orbits in CBCT systems for which a geometric calibration is either not available or not reproducible. The method forms the basis of advanced "task-based" 3D imaging methods now in development for robotic C-arms.

Task-driven imaging in cone-beam computed tomography.

PURPOSE: Conventional workflow in interventional imaging often ignores a wealth of prior information of the patient anatomy and the imaging task. This work introduces a task-driven imaging framework that utilizes such information to prospectively design acquisition and reconstruction techniques for cone-beam CT (CBCT) in a manner that maximizes task-based performance in subsequent imaging procedures. METHODS: The framework is employed in jointly optimizing tube current modulation, orbital tilt, and reconstruction parameters in filtered backprojection reconstruction for interventional imaging. Theoretical predictors of noise and resolution relates acquisition and reconstruction parameters to task-based detectability. Given a patient-specific prior image and specification of the imaging task, an optimization algorithm prospectively identifies the combination of imaging parameters that maximizes task-based detectability. Initial investigations were performed for a variety of imaging tasks in an elliptical phantom and an anthropomorphic head phantom. RESULTS: Optimization of tube current modulation and view-dependent reconstruction kernel was shown to have greatest benefits for a directional task (e.g., identification of device or tissue orientation). The task-driven approach yielded techniques in which the dose and sharp kernels were concentrated in views contributing the most to the signal power associated with the imaging task. For example, detectability of a line pair detection task was improved by at least three fold compared to conventional approaches. For radially symmetric tasks, the task-driven strategy yielded results similar to a minimum variance strategy in the absence of kernel modulation. Optimization of the orbital tilt successfully avoided highly attenuating structures that can confound the imaging task by introducing noise correlations masquerading at spatial frequencies of interest. CONCLUSIONS: This work demonstrated the potential of a task-driven imaging framework to improve image quality and reduce dose beyond that achievable with conventional imaging approaches.

Histone modifications change with age, dietary restriction and rapamycin treatment in mouse brain.

The risk of developing neurodegenerative disorders such as Alzheimer's disease (AD) increases dramatically with age. Understanding the underlying mechanisms of brain aging is crucial for developing preventative and/or therapeutic approaches for age-associated neurological diseases. Recently, it has been suggested that epigenetic factors, such as histone modifications, maybe be involved in brain aging and age-related neurodegenerations. In this study, we investigated 14 histone modifications in brains of a cohort of young (3 months), old (22 months), and old age-matched dietary restricted (DR) and rapamycin treated BALB/c mice. Results showed that 7 out of all measured histone markers were changed drastically with age. Intriguingly, histone methylations in brain tissues, including H3K27me3, H3R2me2, H3K79me3 and H4K20me2 tend to disappear with age but can be partially restored by both DR and rapamycin treatment. However, both DR and rapamycin treatment also have a significant impact on several other histone modifications such as H3K27ac, H4K16ac, H4R3me2, and H3K56ac, which do not change as animal ages. This study provides the first evidence that a broad spectrum of histone modifications may be involved in brain aging. Besides, this study suggests that both DR and rapamycin may slow aging process in mouse brain via these underlying epigenetic mechanisms.

Cascaded systems analysis of photon counting detectors.

PURPOSE: Photon counting detectors (PCDs) are an emerging technology with applications in spectral and low-dose radiographic and tomographic imaging. This paper develops an analytical model of PCD imaging performance, including the system gain, modulation transfer function (MTF), noise-power spectrum (NPS), and detective quantum efficiency (DQE). METHODS: A cascaded systems analysis model describing the propagation of quanta through the imaging chain was developed. The model was validated in comparison to the physical performance of a silicon-strip PCD implemented on an experimental imaging bench. The signal response, MTF, and NPS were measured and compared to theory as a function of exposure conditions (70 kVp, 1-7 mA), detector threshold, and readout mode (i.e., the option for coincidence detection). The model sheds new light on the dependence of spatial resolution, charge sharing, and additive noise effects on threshold selection and was used to investigate the factors governing PCD performance, including the fundamental advantages and limitations of PCDs in comparison to energy-integrating detectors (EIDs) in the linear regime for which pulse pileup can be ignored. RESULTS: The detector exhibited highly linear mean signal response across the system operating range and agreed well with theoretical prediction, as did the system MTF and NPS. The DQE analyzed as a function of kilovolt (peak), exposure, detector threshold, and readout mode revealed important considerations for system optimization. The model also demonstrated the important implications of false counts from both additive electronic noise and charge sharing and highlighted the system design and operational parameters that most affect detector performance in the presence of such factors: for example, increasing the detector threshold from 0 to 100 (arbitrary units of pulse height threshold roughly equivalent to 0.5 and 6 keV energy threshold, respectively), increased the f50 (spatial-frequency at which the MTF falls to a value of 0.50) by ∼30% with corresponding improvement in DQE. The range in exposure and additive noise for which PCDs yield intrinsically higher DQE was quantified, showing performance advantages under conditions of very low-dose, high additive noise, and high fidelity rejection of coincident photons. CONCLUSIONS: The model for PCD signal and noise performance agreed with measurements of detector signal, MTF, and NPS and provided a useful basis for understanding complex dependencies in PCD imaging performance and the potential advantages (and disadvantages) in comparison to EIDs as well as an important guide to task-based optimization in developing new PCD imaging systems.

Noise, sampling, and the number of projections in cone-beam CT with a flat-panel detector.

PURPOSE: To investigate the effect of the number of projection views on image noise in cone-beam CT (CBCT) with a flat-panel detector. METHODS: This fairly fundamental consideration in CBCT system design and operation was addressed experimentally (using a phantom presenting a uniform medium as well as statistically motivated "clutter") and theoretically (using a cascaded systems model describing CBCT noise) to elucidate the contributing factors of quantum noise (σ(Q)), electronic noise (σ(E)), and view aliasing (σ(view)). Analysis included investigation of the noise, noise-power spectrum, and modulation transfer function as a function of the number of projections (N(proj)), dose (D(tot)), and voxel size (b(vox)). RESULTS: The results reveal a nonmonotonic relationship between image noise and N(proj) at fixed total dose: for the CBCT system considered, noise decreased with increasing N(proj) due to reduction of view sampling effects in the regime N(proj) <~200, above which noise increased with N(proj) due to increased electronic noise. View sampling effects were shown to depend on the heterogeneity of the object in a direct analytical relationship to power-law anatomical clutter of the form κ/f(ß)--and a general model of individual noise components (σ(Q), σ(E), and σ(view)) demonstrated agreement with measurements over a broad range in N(proj), D(tot), and b(vox). CONCLUSIONS: The work elucidates fairly basic elements of CBCT noise in a manner that demonstrates the role of distinct noise components (viz., quantum, electronic, and view sampling noise). For configurations fairly typical of CBCT with a flat-panel detector (FPD), the analysis reveals a "sweet spot" (i.e., minimum noise) in the range N(proj) ~ 250-350, nearly an order of magnitude lower in N(proj) than typical of multidetector CT, owing to the relatively high electronic noise in FPDs. The analysis explicitly relates view aliasing and quantum noise in a manner that includes aspects of the object ("clutter") and imaging chain (including nonidealities of detector blur and electronic noise) to provide a more rigorous basis for commonly held intuition and heurism in CBCT system design and operation.

Dual-energy cone-beam CT with a flat-panel detector: effect of reconstruction algorithm on material classification.

PURPOSE: Cone-beam CT (CBCT) with a flat-panel detector (FPD) is finding application in areas such as breast and musculoskeletal imaging, where dual-energy (DE) capabilities offer potential benefit. The authors investigate the accuracy of material classification in DE CBCT using filtered backprojection (FBP) and penalized likelihood (PL) reconstruction and optimize contrast-enhanced DE CBCT of the joints as a function of dose, material concentration, and detail size. METHODS: Phantoms consisting of a 15 cm diameter water cylinder with solid calcium inserts (50-200 mg/ml, 3-28.4 mm diameter) and solid iodine inserts (2-10 mg/ml, 3-28.4 mm diameter), as well as a cadaveric knee with intra-articular injection of iodine were imaged on a CBCT bench with a Varian 4343 FPD. The low energy (LE) beam was 70 kVp (+0.2 mm Cu), and the high energy (HE) beam was 120 kVp (+0.2 mm Cu, +0.5 mm Ag). Total dose (LE+HE) was varied from 3.1 to 15.6 mGy with equal dose allocation. Image-based DE classification involved a nearest distance classifier in the space of LE versus HE attenuation values. Recognizing the differences in noise between LE and HE beams, the LE and HE data were differentially filtered (in FBP) or regularized (in PL). Both a quadratic (PLQ) and a total-variation penalty (PLTV) were investigated for PL. The performance of DE CBCT material discrimination was quantified in terms of voxelwise specificity, sensitivity, and accuracy. RESULTS: Noise in the HE image was primarily responsible for classification errors within the contrast inserts, whereas noise in the LE image mainly influenced classification in the surrounding water. For inserts of diameter 28.4 mm, DE CBCT reconstructions were optimized to maximize the total combined accuracy across the range of calcium and iodine concentrations, yielding values of ∼ 88% for FBP and PLQ, and ∼ 95% for PLTV at 3.1 mGy total dose, increasing to ∼ 95% for FBP and PLQ, and ∼ 98% for PLTV at 15.6 mGy total dose. For a fixed iodine concentration of 5 mg/ml and reconstructions maximizing overall accuracy across the range of insert diameters, the minimum diameter classified with accuracy >80% was ∼ 15 mm for FBP and PLQ and ∼ 10 mm for PLTV, improving to ∼ 7 mm for FBP and PLQ and ∼ 3 mm for PLTV at 15.6 mGy. The results indicate similar performance for FBP and PLQ and showed improved classification accuracy with edge-preserving PLTV. A slight preference for increased smoothing of the HE data was found. DE CBCT discrimination of iodine and bone in the knee was demonstrated with FBP and PLTV at 6.2 mGy total dose. CONCLUSIONS: For iodine concentrations >5 mg/ml and detail size ∼ 20 mm, material classification accuracy of >90% was achieved in DE CBCT with both FBP and PL at total doses <10 mGy. Optimal performance was attained by selection of reconstruction parameters based on the differences in noise between HE and LE data, typically favoring stronger smoothing of the HE data, and by using penalties matched to the imaging task (e.g., edge-preserving PLTV in areas of uniform enhancement).

Fatty acid biosynthesis and lipogenic enzyme activities in subcutaneous adipose tissue of feedlot steers fed supplementary palm oil or soybean oil.

We hypothesized that supplementing finishing diets with palm oil would promote adipocyte differentiation in subcutaneous adipose tissue of feedlot steers, and that soybean oil supplementation would depress adipocyte differentiation. Twenty-eight Angus steers were assigned randomly to 3 groups of 9 or 10 steers and fed a basal diet without additional fat (control), with 3% palm oil (rich in palmitic acid), or with 3% soybean oil (rich in polyunsaturated fatty acids), for 10 wk, top-dressed daily. Palm oil had no effect (P > 0.05) on ADG, food intake, or G:F, whereas soybean oil depressed ADG (P = 0.02), food intake (P = 0.04), and G:F (P = 0.05). Marbling scores tended (P = 0.09) to be greater in palm oil-fed steers (Modest(09)) than in soybean oil-fed steers (Small(55)). Subcutaneous adipocyte mean volume was greater in palm oil-fed steers (515.9 pL) than in soybean-supplemented cattle (395.6 pL; P = 0.01). Similarly, glucose and acetate incorporation into total lipids in vitro was greater in subcutaneous adipose tissue of palm oil-fed steers (119.9 and 242.8 nmol·3h(-1)·10(5) cells, respectively) than adipose tissue of soybean oil-fed steers in (48.9 and 95.8 nmol·3h(-1)·10(5) cells, respectively). Glucose-6-phosphate dehydrogenase and NADP-malate dehydrogenase activities were greater (P ≤ 0.05) in subcutaneous adipose tissue of palm oil-fed steers than in adipose tissue of control steers. Palm oil did not increase palmitic acid or decrease oleic acid in subcutaneous adipose tissue or LM, but decreased (P ≤ 0.05) myristoleic, palmitoleic, and cis-vaccenic acid in adipose tissue, indicating a depression in stearoyl-coenzyme A desaturase activity. Soybean oil increased the proportion of α-linolenic acid in adipose tissue and muscle and increased linoleic acid and 18:1trans-10 in muscle. We conclude that palm oil supplementation promoted lipid synthesis in adipose tissue without depressing feed efficiency or increasing the palmitic acid content of beef.

Noise Reduction in Material Decomposition for Low-Dose Dual-Energy Cone-Beam CT.

PURPOSE: Dual-energy cone-beam CT (DE-CBCT) is an emerging technology with potential application in diagnostic imaging and image-guided interventions. This paper reports DE-CBCT feasibility and investigates decomposition algorithms for maximizing low-dose performance for reconstruction-based DE decomposition. A framework of binary decision theory is used to examine the accuracy of DE decompositions obtained from analytical reconstructions of differentially filtered low-energy (LE) and high-energy (HE) data and from penalized likelihood (PL) reconstructions with differential regularization using quadratic and total variation penalties. METHODS: Accurate DE-CBCT decomposition benefits from consideration of all system noise components. Filtered backprojection (FBP) reconstruction-based decomposition was investigated with differential filtering of LE and HE data. Penalized likelihood reconstruction-based decomposition with differential regularization was hypothesized to further improve low-dose performance, especially when coupled with regularization through a total variation edge preserving penalty that encourages piecewise smooth images. Performance of decomposition was assessed in terms of a binary hypothesis framework of sensitivity, specificity, and accuracy. Studies involved experiments on a DE-CBCT testbench, phantoms of variable material type and concentration, and cadavers (knee arthrography). RESULTS: Studies support the overall feasibility of accurate, low-dose DE-CBCT at concentration down to 5 mg/ml (iodine), dose ~3-6 mGy, and accuracy of material classification ~90%. Reconstruction-based decomposition with quadratic PL performed comparably to FBP. PL with a total variation penalty provided edge preservation and piecewise smooth images that aided DE classification and achieved improved performance over FBP and quadratic PL, reaching accuracy of ~0.98 for 2 mg/mL iodine at 3.2 mGy, compared to approx. 0.9 for FBP and quadratic PL. CONCLUSIONS: Accurate material decomposition with DE-CBCT is feasible at low dose and benefits from a rigorous assessment of noise mechanisms among various reconstruction-based techniques. The work points to the potential for non-linear iterative reconstruction methods for high-quality decomposition at low material concentration and dose.