Multimodal exploration of the intracranial aneurysm wall.

PURPOSE: Intracranial aneurysms (IAs) are pathological changes of the intracranial vessel wall, although clinical image data can only show the vessel lumen. Histology can provide wall information but is typically restricted to ex vivo 2D slices where the shape of the tissue is altered. METHODS: We developed a visual exploration pipeline for a comprehensive view of an IA. We extract multimodal information (like stain classification and segmentation of histologic images) and combine them via 2D to 3D mapping and virtual inflation of deformed tissue. Histological data, including four stains, micro-CT data and segmented calcifications as well as hemodynamic information like wall shear stress (WSS), are combined with the 3D model of the resected aneurysm. RESULTS: Calcifications were mostly present in the tissue part with increased WSS. In the 3D model, an area of increased wall thickness was identified and correlated to histology, where the Oil red O (ORO) stained images showed a lipid accumulation and the alpha-smooth muscle actin (aSMA) stained images showed a slight loss of muscle cells. CONCLUSION: Our visual exploration pipeline combines multimodal information about the aneurysm wall to improve the understanding of wall changes and IA development. The user can identify regions and correlate how hemodynamic forces, e.g. WSS, are reflected by histological structures of the vessel wall, wall thickness and calcifications.

High miR-30 Expression Associates with Improved Breast Cancer Patient Survival and Treatment Outcome.

Deregulated miRNA expression has been suggested in several stages of breast cancer pathogenesis. We have studied the miR-30 family, in particular miR-30d, in relation to breast cancer patient survival and treatment outcomes. With tumor specimens from 1238 breast cancer patients, we analyzed the association of miR-30d expression with tumor characteristics with the 5-year occurrence of breast cancer-specific death or distant metastasis (BDDM), and with 10-year breast cancer survival (BCS). We conducted a two-stage drug-screen to investigate the impact of miR-30 family members (miR-30a-30e) on sensitivity to doxorubicin and lapatinib in six breast cancer cell lines HCC1937, HCC1954, MDA-MB-361, MCF7, MDA-MB-436 and CAL-120, using drug sensitivity scores (DSS) to compare the miR-30 family mimics to their specific inhibitors. The study was complemented with Ingenuity Pathway Analysis (IPA) with the METABRIC data. We found that while high miR-30d expression is typical for aggressive tumors, it predicts better metastasis-free (pBDDM = 0.035, HR = 0.63, 95% CI = 0.4-0.9) and breast cancer-specific survival (pBCS = 0.018, HR = 0.61, 95% CI = 0.4-0.9), especially in HER2-positive (pBDDM = 0.0009), ER-negative (pBDDM = 0.003), p53-positive (pBDDM = 0.011), and highly proliferating (pBDDM = 0.0004) subgroups, and after adjuvant chemotherapy (pBDDM = 0.035). MiR-30d predicted survival independently of standard prognostic markers (pBDDM = 0.0004). In the drug-screening test, the miR-30 family sensitized the HER2-positive HCC1954 cell line to lapatinib (p < 10-2) and HCC1937, MDA-MB-361, MDA-MB-436 and CAL120 to doxorubicin (p < 10-4) with an opposite impact on MCF7. According to the pathway analysis, the miR-30 family has a suppressive effect on cell motility and metastasis in breast cancer. Our results suggest prognostic and predictive potential for the miR-30 family, which warrants further investigation.