An iterative algorithm, based on recent work in compressive sensing, is developed for volume image reconstruction from a circular cone-beam scan. The algorithm minimizes the total-variation (TV) of the image subject to the constraint that the estimated projection data is within a specified tolerance of the available data and that the values of the volume image are non-negative. The constraints are enforced by use of projection onto convex sets (POCS) and the TV objective is minimized by steepest descent with an adaptive step-size. The algorithm is referred to as adaptive-steepest-descent-POCS (ASD-POCS). It appears to be robust against cone-beam artifacts, and may be particularly useful when the angular range is limited or when the angular sampling rate is low. The ASD-POCS algorithm is tested with the Defrise disk and jaw computerized phantoms. Some comparisons are performed with the POCS and expectation-maximization (EM) algorithms. Although the algorithm is presented in the context of circular cone-beam image reconstruction, it can also be applied to scanning geometries involving other x-ray source trajectories.

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Bone morphogenetic protein 9 (BMP‐9) is a member of the transforming growth factor (TGF)‐β/BMP superfamily, and we have demonstrated that it is one of the most potent BMPs to induce osteoblast differentiation of mesenchymal stem cells (MSCs). Here, we sought to investigate if canonical Wnt/β‐catenin signalling plays an important role in BMP‐9‐induced osteogenic differentiation of MSCs. Wnt3A and BMP‐9 enhanced each other’s ability to induce alkaline phosphatase (ALP) in MSCs and mouse embryonic fibroblasts (MEFs). Wnt antagonist FrzB was shown to inhibit BMP‐9‐induced ALP activity more effectively than Dkk1, whereas a secreted form of LPR‐5 or low‐density lipoprotein receptor‐related protein (LRP)‐6 exerted no inhibitory effect on BMP‐9‐induced ALP activity. β‐Catenin knockdown in MSCs and MEFs diminished BMP‐9‐induced ALP activity, and led to a decrease in BMP‐9‐induced osteocalcin reporter activity and BMP‐9‐induced expression of late osteogenic markers. Furthermore, β‐catenin knockdown or FrzB overexpression inhibited BMP‐9‐induced mineralization in vitro and ectopic bone formation in vivo, resulting in immature osteogenesis and the formation of chondrogenic matrix. Chromatin immunoprecipitation (ChIP) analysis indicated that BMP‐9 induced recruitment of both Runx2 and β‐catenin to the osteocalcin promoter. Thus, we have demonstrated that canonical Wnt signalling, possibly through interactions between β‐catenin and Runx2, plays an important role in BMP‐9‐induced osteogenic differentiation of MSCs.

Despite major advances in x-ray sources, detector arrays, gantry mechanical design and especially computer performance, one component of computed tomography (CT) scanners has remained virtually constant for the past 25 years—the reconstruction algorithm. Fundamental advances have been made in the solution of inverse problems, especially tomographic reconstruction, but these works have not been translated into clinical and related practice. The reasons are not obvious and seldom discussed. This review seeks to examine the reasons for this discrepancy and provides recommendations on how it can be resolved. We take the example of field of compressive sensing (CS), summarizing this new area of research from the eyes of practical medical physicists and explaining the disconnection between theoretical and application-oriented research. Using a few issues specific to CT, which engineers have addressed in very specific ways, we try to distill the mathematical problem underlying each of these issues with the hope of demonstrating that there are interesting mathematical problems of general importance that can result from in depth analysis of specific issues. We then sketch some unconventional CT-imaging designs that have the potential to impact on CT applications, if the link between applied mathematicians and engineers/physicists were stronger. Finally, we close with some observations on how the link could be strengthened. There is, we believe, an important opportunity to rapidly improve the performance of CT and related tomographic imaging techniques by addressing these issues.

Pluripotent mesenchymal stem cells (MSCs) are bone marrow stromal progenitor cells that can differentiate into osteogenic, chondrogenic, adipogenic, and myogenic lineages. We previously demonstrated that bone morphogenetic protein (BMP) 9 is one of the most potent and yet least characterized BMPs that are able to induce osteogenic differentiation of MSCs both in vitro and in vivo. Here, we conducted gene expression-profiling analysis and identified that Hey1 of the hairy/Enhancer of splitrelated repressor protein basic helix-loop-helix family was among the most significantly up-regulated early targets in BMP9-stimulated MSCs. We demonstrated that Hey1 expression was up-regulated at the immediate early stage of BMP9-induced osteogenic differentiation. Chromatin immunoprecipitation analysis indicated that Hey1 may be a direct target of the BMP9-induced Smad signaling pathway. Silencing Hey1 expression diminished BMP9-induced osteogenic differentiation both in vitro and in vivo and led to chondrogenic differentiation. Likewise, constitutive Hey1 expression augmented BMP9-mediated bone matrix mineralization. Hey1 and Runx2 were shown to act synergistically in BMP9-induced osteogenic differentiation, and Runx2 expression significantly decreased in the absence of Hey1, suggesting that Runx2 may function downstream of Hey1. Accordingly, the defective osteogenic differentiation caused by Hey1 knockdown was rescued by exogenous Runx2 expression. Thus, our findings suggest that Hey1, through its interplay with Runx2, may play an important role in regulating BMP9-induced osteoblast lineage differentiation of MSCs. Mesenchymal stem cells (MSCs)5 represent a very small fraction of the total population of nucleated cells in bone marrow (1) and are adherent multipotent marrow stromal cells (1-6). Although primarily located within the bone marrow compartment (5, 7, 8), MSCs have been isolated from periosteum, trabecular bone, adipose tissue, synovium, skeletal muscle, and deciduous teeth (9). As members of the transforming growth factor-␤ superfamily, BMPs play an important role in stem cell biology (10, 11) and regulate cell proliferation and differentiation during development (12, 13). Several BMPs have been shown to regulate osteoblast differentiation and subsequent bone formation (12-15). Genetic disruptions of BMPs result in various skeletal and extraskeletal abnormalities during development (14, 16). We have recently conducted a comprehensive analysis of the osteogenic activity of 14 human BMPs and demonstrated that BMP9 is one of the most potent BMPs promoting osteogenic differentiation of MSCs both in vitro and in vivo (17,18). We also demonstrated that osteogenic BMPs regulate a distinct set of downstream targets in MSCs (6,[19][20][21].BMP9 (also known as GDF2) was originally identified from fetal mouse liver cDNA libraries and is a relatively uncharacterized member of the BMP family. BMP9 is highly expressed in the developing mouse liver, and recombinant human BMP9 stimulates hepatocyte proliferation (22,23). BMP9 ha...

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. Mesenchymal stem cells (MSCs),2 representing a very small fraction of the total population of nucleated cells in bone marrow are adherent marrow stromal cells that can self-renew and differentiate into osteogenic, chondrogenic, adipogenic, and myogenic lineages (1-4). Bone morphogenetic proteins (BMPs), members of the TGF␤ superfamily, play an important role in stem cell biology (5, 6) and function to regulate cell proliferation and differentiation during development (7, 8). Several BMPs have been shown to regulate osteoblast differentiation and subsequent bone formation (3, 4, 7-9) and genetic disruptions of these factors have resulted in various skeletal and extraskeletal abnormalities during development (9, 10). We have conducted a comprehensive analysis of the osteogenic activity of 14 human BMPs and demonstrated that BMP9 is one of the most potent BMPs in promoting osteogenic differentiation of MSCs (3,11,12). We also demonstrated that osteogenic BMP9 regulates a distinct set of downstream targets in MSCs (13-16).BMP9 (a.k.a., GDF2) was originally identified from fetal mouse liver cDNA libraries, and is a relatively uncharacterized member of the BMP family (17). BMP9 is highly expressed in the developing mouse liver, and recombinant human BMP9 stimulates hepatocyte proliferation (17,18). It has been reported that BMP9 may play role in regulating glucose and iron homeostasis in liver (19,20). BMP9 has been shown to be a potent synergistic factor for hematopoietic progenitor generation and colony formation (21) and may play a role in the induction and main...

Knowledge of the x-ray spectrum in diagnostic imaging is important for dose calculations, correction for beam-hardening artifacts, and dual-energy computed tomography. One way to determine the x-ray source spectrum is to estimate it from transmission data of a known phantom. Although such an approach is experimentally simple, spectrum estimation from transmission data is known to be an ill-conditioned problem. The contribution of this work is twofold. First, we present a systematic method of designing the transmission measurements to reduce the mathematical instability of spectrum estimation. Second, we apply the expectation-maximization (EM) method, which is known to yield robust solutions to positive, linear integral equations such as the one that describes spectrum estimation from transmission data. The proposed EM method is compared to other algorithms in the literature on simulated data from x-ray spectra typical to mammography and computed tomography. The EM method appears to outperform existing algorithms for spectrum estimation.

Exact methods of inverting the two-dimensional (2-D) exponential Radon transform have been proposed by Bellini et al. (1979) and by Inouye et al. (1989), both of whom worked in the spatial-frequency domain to estimate the 2-D Fourier transform of the unattenuated sinogram; by Hawkins et al. (1988), who worked with circularly harmonic Bessel transforms; and by Tretiak and Metz (1980), who followed filtering of appropriately-modified projections by exponentially-weighted backprojection. With perfect sampling, all four of these methods are exact in the absence of projection-data noise, but empirical studies have shown that they propagate noise differently, and no underlying theoretical relationship among the methods has been evident. Here, an analysis of the 2-D Fourier transform of the modified sinogram reveals that all previously-proposed linear methods can be interpreted as special cases of a broad class of methods, and that each method in the class can be implemented, in principle, by any one of four distinct techniques. Moreover, the analysis suggests a new member of the class that Is predicted to have noise properties better than those of previously-proposed members.