TuNet: End-to-end Hierarchical Brain Tumor Segmentation using Cascaded Networks

Glioma is one of the most common types of brain tumors; it arises in the glial cells in the human brain and in the spinal cord. In addition to having a high mortality rate, glioma treatment is also very expensive. Hence, automatic and accurate segmentation and measurement from the early stages are critical in order to prolong the survival rates of the patients and to reduce the costs of the treatment. In the present work, we propose a novel end-to-end cascaded network for semantic segmentation that utilizes the hierarchical structure of the tumor sub-regions with ResNet-like blocks and Squeeze-and-Excitation modules after each convolution and concatenation block. By utilizing cross-validation, an average ensemble technique, and a simple post-processing technique, we obtained dice scores of 88.06, 80.84, and 80.29, and Hausdorff Distances (95th percentile) of 6.10, 5.17, and 2.21 for the whole tumor, tumor core, and enhancing tumor, respectively, on the online test set.Comment: Accepted at MICCAI BrainLes 201

Hole concentration in a diluted ferromagnetic semiconductor

We consider a mean-field approach to the hole-mediated ferromagnetism in III-V Mn-based semiconductor compounds to discuss the dependence of the hole density on that of Mn sites in Ga_{1-x}Mn_xAs. The hole concentration, p, as a function of the fraction of Mn sites, x, is parametrized in terms of the product m*J_{pd}^2 (where m* is the hole effective mass and J_{pd} is the Kondo-like hole/local-moment coupling), and the critical temperature Tc. By using experimental data for these quantities, we have established the dependence of the hole concentration with x, which can be associated with the occurrence of a reentrant metal-insulator transition taking place in the hole gas. We also calculate the dependence of the Mn magnetization with x, for different temperatures (T), and found that as T increases, the width of the composition-dependent magnetization decreases drammatically, and that the magnetization maxima also decreases, indicating the need for quality-control of Mn-doping composition in diluted magnetic semiconductor devices.Comment: 4 pages, 3 figures, RevTeX 3; Fig. 1 changed, new references adde

Electronic structure and magnetism of Mn doped GaN

Mn doped semiconductors are extremely interesting systems due to their novel magnetic properties suitable for the spintronics applications. It has been shown recently by both theory and experiment that Mn doped GaN systems have a very high Curie temperature compared to that of Mn doped GaAs systems. To understand the electronic and magnetic properties, we have studied Mn doped GaN system in detail by a first principles plane wave method. We show here the effect of varying Mn concentration on the electronic and magnetic properties. For dilute Mn concentration, $d$ states of Mn form an impurity band completely separated from the valence band states of the host GaN. This is in contrast to the Mn doped GaAs system where Mn $d$ states in the gap lie very close to the valence band edge and hybridizes strongly with the delocalized valence band states. To study the effects of electron correlation, LSDA+U calculations have been performed. Calculated exchange interaction in (Mn,Ga)N is short ranged in contrary to that in (Mn,Ga)As where the strength of the ferromagnetic coupling between Mn spins is not decreased substantially for large Mn-Mn separation. Also, the exchange interactions are anisotropic in different crystallographic directions due to the presence or absence of connectivity between Mn atoms through As bonds.Comment: 6 figures, submitted to Phys. Rev.

Single-Band Model for Diluted Magnetic Semiconductors: Dynamical and Transport Properties and Relevance of Clustered States

Dynamical and transport properties of a simple single-band spin-fermion lattice model for (III,Mn)V diluted magnetic semiconductors (DMS) is here discussed using Monte Carlo simulations. This effort is a continuation of previous work (G. Alvarez, Phys. Rev. Lett. 89, 277202 (2002)) where the static properties of the model were studied. The present results support the view that the relevant regime of J/t (standard notation) is that of intermediate coupling, where carriers are only partially trapped near Mn spins, and locally ordered regions (clusters) are present above the Curie temperature T_C. This conclusion is based on the calculation of the resistivity vs. temperature, that shows a soft metal to insulator transition near T_C, as well on the analysis of the density-of-states and optical conductivity. In addition, in the clustered regime a large magnetoresistance is observed in simulations. Formal analogies between DMS and manganites are also discussed.Comment: Revtex4, 20 figures. References updated, minor changes to figures and tex

Recombinant AAV-mediated HSVtk gene transfer with direct intratumoral injections and Tet-On regulation for implanted human breast cancer

BACKGROUND: HSVtk/ganciclovir (GCV) gene therapy has been extensively studied in tumors and relies largely on the gene expression of HSVtk. Most studies, however, have failed to demonstrate any significant benefit of a controlled gene expression strategy in cancer treatment. The Tet-On system is commonly used to regulate gene expression following Dox induction. We have evaluated the antitumor effect of HSVtk/ganciclovir gene therapy under Tet-On regulation by means of adeno-associated virus-2 (AAV-2)-mediated HSVtk gene transfer with direct intratumoral injections in mice bearing breast cancer tumors. METHODS: Recombinant adeno-associated virus-2 (rAAV) was constructed and transduced into MCF-7 cell line. GCV treatment to the rAAV infected MCF-7 cells was performed by MTT assay under the doxycycline (Dox) induction or without Dox induction at a vp (viral particle) number of ≥10(4 )/cell. The virus was administered intratumorally to nude mice that had also received GCV intraperitoneally. The antitumor effects were evaluated by measuring tumor regression and histological analysis. RESULTS: We have demonstrated that GCV treatment to the infected MCF-7 cells under the Dox induction was of more inhibited effects than those without Dox induction at ≥10(4 )vp/cell. In ex vivo experiments, tumor growth of BALB/C nude mice breast cancer was retarded after rAAV-2/HSVtk/Tet-On was injected into the tumors under the Dox induction. Infiltrating cells were also observed in tumors after Dox induction followed by GCV treatment and cells were profoundly damaged. The expression of HSVtk gene in MCF-7 cells and BALB/C nude mice tumors was up-regulated by Tet-On under Dox induction with reverse transcription-PCR (RT-PCR) analysis. CONCLUSION: The antitumor effect of rAAV-mediated HSVtk/GCV gene therapy under the Dox induction with direct intratumoral injections may be a useful treatment for breast cancer and other solid tumors

Complementary effects of HDAC inhibitor 4-PB on gap junction communication and cellular export mechanisms support restoration of chemosensitivity of PDAC cells

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease and one of the cancer entities with the lowest life expectancy. Beside surgical therapy, no effective therapeutic options are available yet. Here, we show that 4-phenylbutyrate (4-PB), a known and well-tolerable inhibitor of histone deacetylases (HDAC), induces up to 70% apoptosis in all cell lines tested (Panc 1, T4M-4, COLO 357, BxPc3). In contrast, it leads to cell cycle arrest in only half of the cell lines tested. This drug increases gap junction communication between adjacent T3M-4 cells in a concentration-dependent manner and efficiently inhibits cellular export mechanisms in Panc 1, T4M-4, COLO 357 and BxPc3 cells. Consequently, in combination with gemcitabine 4-PB shows an overadditive effect on induction of apoptosis in BxPc3 and T3M-4 cells (up to 4.5-fold compared to single drug treatment) with accompanied activation of Caspase 8, BH3 interacting domain death agonist (Bid) and poly (ADP-ribose) polymerase family, member 1 (PARP) cleavage. Although the inhibition of the mitogen-activated protein kinase-pathway has no influence on fulminant induction of apoptosis, the inhibition of the JNK-pathway by SP600125 completely abolishes the overadditive effect induced by the combined application of both drugs, firstly reported by this study

Impact of therapy on quality of life, neurocognitive function and their correlates in glioblastoma multiforme: a review

The maintenance of quality of life (QoL) in patients with high-grade glioma is an important endpoint during treatment, particularly in those with glioblastoma multiforme (GBM) given its dismal prognosis despite limited advances in standard therapy. It has proven difficult to identify new therapies that extend survival in patients with recurrent GBM, so one of the primary aims of new therapies is to reduce morbidity, restore or preserve neurologic functions, and the capacity to perform daily activities. Apart from temozolomide, cytotoxic chemotherapeutic agents do not appear to significantly impact response or survival, but produce toxicity that is likely to negatively impact QoL. New biological agents, such as bevacizumab, can induce a clinically meaningful proportion of durable responses among patients with recurrent GBM with an acceptable safety profile. Emerging evidence suggests that bevacizumab produces an improvement or preservation of neurocognitive function in GBM patients, suggestive of QoL improvement, in most poor-prognosis patients who would otherwise be expected to show a sudden and rapid deterioration in QoL