In Diffusion Weighted Magnetic Resonance Image (DW-MRI) processing, a 2 nd order tensor has been commonly used to approximate the diffusivity function at each lattice point of the DW-MRI data. From this tensor approximation, one can compute useful scalar quantities (e.g. anisotropy, mean diffusivity) which have been clinically used for monitoring encephalopathy, sclerosis, ischemia and other brain disorders. It is now well known that this 2 nd -order tensor approximation fails to capture complex local tissue structures, e.g. crossing fibers, and as a result, the scalar quantities derived from these tensors are grossly inaccurate at such locations. In this paper we employ a 4 th order symmetric positive-definite (SPD) tensor approximation to represent the diffusivity function and present a novel technique to estimate these tensors from the DW-MRI data guaranteeing the SPD property. Several articles have been reported in literature on higher order tensor approximations of the diffusivity function but none of them guarantee the positivity of the estimates, which is a fundamental constraint since negative values of the diffusivity are not meaningful. In this paper we represent the 4 th -order tensors as ternary quartics and then apply Hilbert's theorem on ternary quartics along with the Iwasawa parametrization to guarantee an SPD 4 th -order tensor approximation from the DW-MRI data. The performance of this model is depicted on synthetic data as well as real DW-MRIs from a set of excised control and injured rat spinal cords, showing accurate estimation of scalar quantities such as generalized anisotropy and trace as well as fiber orientations.
Malignant peripheral nerve sheath tumors (MPNST) are the most aggressive cancers associated with neurofibromatosis type 1 (NF1). Here we report a practical and reproducible model of intraneural NF1 MPNST, by orthotopic xenograft of an immortal human NF1 tumor-derived Schwann cell line into the sciatic nerves of female scid mice. Intraneural injection of the cell line sNF96.2 consistently produced MPNST-like tumors that were highly cellular and showed extensive intraneural growth. These xenografts had a high proliferative index, were angiogenic, had significant mast cell infiltration and rapidly dominated the host nerve. The histopathology of engrafted intraneural tumors was consistent with that of human NF1 MPNST. Xenograft tumors were readily examined by magnetic resonance imaging, which also was used to assess tumor vascularity. In addition, the intraneural proliferation of sNF96.2 cell tumors was decreased in ovariectomized mice, while replacement of estrogen or progesterone restored tumor cell proliferation. This suggests a potential role for steroid hormones in supporting tumor cell growth of this MPNST cell line in vivo. The controlled orthotopic implantation of sNF96.2 cells provides for the precise initiation of intraneural MPNST-like tumors in a model system suitable for therapeutic interventions, including inhibitors of angiogenesis and further study of steroid hormone effects on tumor cell growth. KEYWORDS: neurofibromatosis; malignant peripheral nerve sheath tumor; angiogenesis; xenografts; orthotopic; steroid hormone Malignant peripheral nerve sheath tumors (MPNST) are often associated with neurofibromatosis type 1 (NF1), and are thought to arise from plexiform neurofibromas. 1,2 In fact, neurofibromas coexisting with MPNSTs were found in 81% of patients with NF1 but only in 41% of non-NF1 patients. 3 Progression to malignancy from plexiform neurofibroma occurs in about 6% of NF1 patients, although the lifetime risk of MPNST in NF1 has been estimated as high as 8-13%, 4 and is associated with high mortality. 5 NF1 MPNSTs have distinctive characteristics. 6 They are densely hypercellular and composed of spindle-shaped cells. The clonal elements with Schwann cell (SC) characteristics have a high proliferative index (5-38% Ki67-positive cells) and exhibit nuclear hyperchromasia and nuclear enlargement. Their growth is characterized by abrupt variation in cellularity and tissue pattern. They are firm, gray-tan and opaque, may grow very large and can be surrounded by a pseudocapsule. They may have areas of localized necrosis and tend to extend intraneurally.A great deal of progress has been made developing cell lines and mouse models of NF1 tumors for experimental study and clinical testing. These cell lines and models have proven invaluable in furthering our understanding of the biology of NF1. Mice generated with a null mutation in the
The unscented Kalman filter (UKF) was recently introduced in literature for simultaneous multi-tensor estimation and tractography. This UKF however was not intrinsic to the space of diffusion tensors. Lack of this key property leads to inaccuracies in the multi-tensor estimation as well as in tractography. In this paper, we propose an novel intrinsic unscented Kalman filter (IUKF) in the space of symmetric positive definite matrices, which can be used for simultaneous recursive estimation of multi-tensors and tractography from diffusion weighted MR data. In addition to being more accurate, IUKF retains all the advantages of UKF for instance, multi-tensor estimation is only performed in the places where it is needed for tractography, which would be much more efficient than the two stage process involved in methods that do tracking post diffusion tensor estimation. The accuracy and effectiveness of the proposed method is demonstrated via real data experiments.
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