Signaling local non-credibility in an automatic segmentation pipeline

The advancing technology for automatic segmentation of medical images should be accompanied by techniques to inform the user of the local credibility of results. To the extent that this technology produces clinically acceptable segmentations for a significant fraction of cases, there is a risk that the clinician will assume every result is acceptable. In the less frequent case where segmentation fails, we are concerned that unless the user is alerted by the computer, she would still put the result to clinical use. By alerting the user to the location of a likely segmentation failure, we allow her to apply limited validation and editing resources where they are most needed. We propose an automated method to signal suspected non-credible regions of the segmentation, triggered by statistical outliers of the local image match function. We apply this test to m-rep segmentations of the bladder and prostate in CT images using a local image match computed by PCA on regional intensity quantile functions. We validate these results by correlating the non-credible regions with regions that have surface distance greater than 5.5mm to a reference segmentation for the bladder. A 6mm surface distance was used to validate the prostate results. Varying the outlier threshold level produced a receiver operating characteristic with area under the curve of 0.89 for the bladder and 0.92 for the prostate. Based on this preliminary result, our method has been able to predict local segmentation failures and shows potential for validation in an automatic segmentation pipeline

First-principles calculations of the phase stability of TiO2

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Retinoblastoma Loss Modulates DNA Damage Response Favoring Tumor Progression

Senescence is one of the main barriers against tumor progression. Oncogenic signals in primary cells result in oncogene-induced senescence (OIS), crucial for protection against cancer development. It has been described in premalignant lesions that OIS requires DNA damage response (DDR) activation, safeguard of the integrity of the genome. Here we demonstrate how the cellular mechanisms involved in oncogenic transformation in a model of glioma uncouple OIS and DDR. We use this tumor type as a paradigm of oncogenic transformation. In human gliomas most of the genetic alterations that have been previously identified result in abnormal activation of cell growth signaling pathways and deregulation of cell cycle, features recapitulated in our model by oncogenic Ras expression and retinoblastoma (Rb) inactivation respectively. In this scenario, the absence of pRb confers a proliferative advantage and activates DDR to a greater extent in a DNA lesion-independent fashion than cells that express only HRasV12. Moreover, Rb loss inactivates the stress kinase DDR-associated p38MAPK by specific Wip1-dependent dephosphorylation. Thus, Rb loss acts as a switch mediating the transition between premalignant lesions and cancer through DDR modulation. These findings may have important implications for the understanding the biology of gliomas and anticipate a new target, Wip1 phosphatase, for novel therapeutic strategies