Purpose: Burgess et al. have shown that the power-spectral density of mammographic breast tissue P(f) follows a power-law, P(f) ¼ c=f b . 1 Due to the complexity of the breast anatomy, breast phantoms often make use of power-law backgrounds to approximate the irregular texture of breast images. However, the current methodology of estimating power-law coefficients assumes that the breast structure is isotropic. The purpose of this letter is to demonstrate that breast anatomic structure is not isotropic, but in fact has a preferred orientation. Further, we present a formalism to estimate power-law coefficients b and c while accounting for tissue orientation in mammographic regions-of-interests (ROIs). We then show the effect of structure orientation on b and c, as well as on the appearance of simulated power-law backgrounds. Methods: When breast tissue exhibits a preferred orientation, the radial symmetry in the associated power spectrum is broken. The new symmetry was fit by an ellipsoidal model. Ellipse tilt angle and axis ratio were accounted for in the power-law fit. Results: On average, breast structure was found to point toward the nipple: the average orientation in MLO views was 22.5 , while it was 5 for CC views, and the mean orientation for left breasts was negative while it was positive for right breasts. For both power-law magnitude and exponent, the mean difference was statistically significant ( ¼ À0.096, ¼À0.192). Conclusions: A formalism for quantification of breast structure and structure orientation is provided. The difference in power-law coefficient estimates when accounting for orientation was found to be statistically significant. Examples of statistically defined backgrounds indicate that breast structure is mimicked more closely when structure orientation is accounted for.

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Purpose: Epigenetic alterations in hepatocellular carcinoma (HCC) may facilitate cell survival under transarterial chemoembolization-induced ischemia by potentiating the function of canonical stress response pathways including the unfolded protein response (UPR), Hypoxia-Inducible Factor (HIF), and Autophagy. Moreover, the redundancy in function of these pathways makes inhibition of any single pathway insufficient to abrogate their function entirely. We hypothesize that HCC cells surviving severe TACE-like ischemia are susceptible to inhibition of these pathways and that combination of the inhibition of these pathways would lead to synergistic effects. Materials: Viability assays and cytotoxicity profiles of Huh-7, SNU-387 and SNU-449 HCC cell lines were studied under standard (21% O 2 with complete medium) and compared to severely ischemic conditions (1% O 2 , 1% serum, 1 mM glucose) with an inhibitor of the UPR (GSK2606141), a HIF-1 alpha inhibitor (PX-478 or BAY87-2243) and an inhibitor of autophagy (Hydroxychloroquine). Cytotoxicity measurements were derived from measured dose-response curves using the WST-1 cytotoxicity assay. The t-test was used to compare standard to severely ischemic conditions. Results: Each of the cell lines tested demonstrated decreased cellular viability with incubation of either of the inhibitory agents (EC50 GSK2606141, PX-478, BAY87-2243, Hydroxcychloroquine of 75-150μM, 50-100 μM, 300-600uM, and 100-200μM respectively). Ischemia potentiated the cytotoxicity (EC50 GSK2606141, PX-478, BAY87-2243, Hydroxcychloroquine of 25-50μM, 50-75 μM, 200-400uM, and 50-80μM respectively; with p<0.05 except for BAY87-2243). Combination inhibition of the three pathways under TACE-like ischemia lead to a synergistic response showing cell death at concentrations below any single drug alone (EC50 of BAY87-2243 in combination of 100-200uM compared to 400-500uM as a single agent). Conclusions: Inhibition of the UPR, HIF, and autophagy independently lead to cytotoxicity of HCC cells. Combination of the three drugs under TACE-like ischemia lead to a synergistic response and should be considered as potential chemotherapeutics for TACE.