Analytical validation of innovative magneto-inertial outcomes: a controlled environment study.

peer reviewe

Inhibition of Nek2 by Small Molecules Affects Proteasome Activity

Background. Nek2 is a serine/threonine kinase localized to the centrosome. It promotes cell cycle progression from G2 to M by inducing centrosome separation. Recent studies have shown that high Nek2 expression is correlated with drug resistance in multiple myeloma patients. Materials and Methods. To investigate the role of Nek2 in bortezomib resistance, we ectopically overexpressed Nek2 in several cancer cell lines, including multiple myeloma lines. Small-molecule inhibitors of Nek2 were discovered using an in-house library of compounds. We tested the inhibitors on proteasome and cell cycle activity in several cell lines. Results. Proteasome activity was elevated in Nek2-overexpressing cell lines. The Nek2 inhibitors inhibited proteasome activity in these cancer cell lines. Treatment with these inhibitors resulted in inhibition of proteasome-mediated degradation of several cell cycle regulators in HeLa cells, leaving them arrested in G2/M. Combining these Nek2 inhibitors with bortezomib increased the efficacy of bortezomib in decreasing proteasome activity in vitro. Treatment with these novel Nek2 inhibitors successfully mitigated drug resistance in bortezomib-resistant multiple myeloma. Conclusion. Nek2 plays a central role in proteasome-mediated cell cycle regulation and in conferring resistance to bortezomib in cancer cells. Taken together, our results introduce Nek2 as a therapeutic target in bortezomib-resistant multiple myeloma

SmartPulse, a machine learning approach for calibration-free dynamic RF shimming: preliminary study in a clinical environment

International audiencePurpose: A calibration-free pulse design method is introduced to alleviate B$_1$$^+$ artifacts in clinical routine with parallel transmission at high field, dealing with significant inter-subject variability, found for instance in the abdomen.Theory and Methods: From a dual-transmit 3T scanner, a database of B$_1$$^+$ and off resonance abdominal maps from 50 subjects was first divided into three clusters based on mutual affinity between their respective tailored kT-points pulses. For each cluster, a kT-points pulse was computed, minimizing normalized root-mean-square flip angle (FA) deviations simultaneously for all subjects comprised in it. Using 30 additional subjects’ field distributions, a machine learning classifier was trained on this 80-labelled-subject database to recognize the best pulse from the three ones available, relying only on patient features accessible from the preliminary localizer sequence present in all protocols. This so-called SmartPulse process was experimentally tested on an additional 53-subject set and compared with other pulse types: vendor’s hard calibration-free dual excitation, tailored static RF shimming, universal and tailored kT-points pulses.Results: SmartPulse outperformed both calibration-free approaches. Tailored static RF shimming yielded similar FA homogeneity for most patients but broke down for some while SmartPulse remained robust. Although FA homogeneity was systematically better with tailored kT-points, the difference was barely noticeable on in-vivo images.Conclusion: The proposed method paves the way towards an efficient trade-off between tailored and universal pulse design approaches for large inter-subject variability. With no need for on-line field mapping or pulse design, it can fit seamlessly into a clinical protocol

Z-segmentation of a transmit array head coil improves RF ramp pulse design at 7T

International audienceIn Time-Of-Flight sequences, ramp pulses such as TONE's are frequently used to compensate for thru-slab blood flow saturation in cerebral MRA. At Ultra High Field, fast-kz spokes in parallel transmission allow to mitigate B1 + heterogeneities in the slab selection process. Here we extend their use for TONE pulses and show improvement of the flip angle ramp fidelity with a homemade z-segmented head array in comparison to a purely azimuthally-distributed commercial coil

Value of biomarkers for predicting immunoglobulin A vasculitis nephritis outcome in an adult prospective cohort

International audienc