Objective

Atherosclerosis is a chronic immuno-inflammatory condition emerging in arteries and considered the cause of a myriad of cardiovascular diseases. Atherosclerotic lesion characterization through invasive imaging modalities is essential in disease evaluation and determining intervention strategy. Recently, electrical properties of the lesions have been utilized in assessing its vulnerability mainly owing to its capability to differentiate lipid content existing in the lesion, albeit with limited detection resolution. Electrical impedance tomography is the natural extension of conventional spectrometric measurement by incorporating larger number of interrogating electrodes and advanced algorithm to achieve imaging of target objects and thus provides significantly richer information. It is within this context that we develop Outward Electrical Impedance Tomography (OEIT), aimed at intravascular imaging for atherosclerotic lesion characterization.

Methods

We utilized flexible electronics to establish the 32-electrode OEIT device with outward facing configuration suitable for imaging of vessels. We conducted comprehensive studies through simulation model and ex vivo setup to demonstrate the functionality of OEIT.

Results

Quantitative characterization for OEIT regarding its proximity sensing and conductivity differentiation was achieved using well-controlled experimental conditions. Imaging capability for OEIT was further verified with phantom setup using porcine aorta to emulate in vivo environment.

Conclusion

We have successfully demonstrated a novel tool for intravascular imaging, OEIT, with unique advantages for atherosclerosis detection.

Significance

This study demonstrates for the first time a novel electrical tomography-based platform for intravascular imaging, and we believe it paves the way for further adaptation of OEIT for intravascular detection in more translational settings and offers great potential as an alternative imaging tool for medical diagnosis.

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.