Coherent Bistatic 3-D Ultrasound Imaging Using Two Sparse Matrix Arrays.

In the last decade, many advances have been made in high frame rate 3-D ultrasound imaging, including more flexible acquisition systems, transmit (TX) sequences, and transducer arrays. Compounding multiangle transmits of diverging waves has shown to be fast and effective for 2-D matrix arrays, where heterogeneity between transmits is key in optimizing the image quality. However, the anisotropy in contrast and resolution remains a drawback that cannot be overcome with a single transducer. In this study, a bistatic imaging aperture is demonstrated that consists of two synchronized matrix ( 32×32 ) arrays, allowing for fast interleaved transmits with a simultaneous receive (RX). First, for a single array, the aperture efficiency for high volume rate imaging was evaluated between sparse random arrays and fully multiplexed arrays. Second, the performance of the bistatic acquisition scheme was analyzed for various positions on a wire phantom and was showcased in a dynamic setup mimicking the human abdomen and aorta. Sparse array volume images were equal in resolution and lower in contrast compared to fully multiplexed arrays but can efficiently minimize decorrelation during motion for multiaperture imaging. The dual-array imaging aperture improved the spatial resolution in the direction of the second transducer, reducing the average volumetric speckle size with 72% and the axial-lateral eccentricity with 8%. In the aorta phantom, the angular coverage increased by a factor of 3 in the axial-lateral plane, raising the wall-lumen contrast with 16% compared to single-array images, despite accumulation of thermal noise in the lumen.

CDK4/6 inhibition presents as a therapeutic option for paediatric and adult germ cell tumours and induces cell cycle arrest and apoptosis via canonical and non-canonical mechanisms.

BACKGROUND: Germ cell tumours (GCTs) are the most common solid malignancies in young men. Although high cure rates can be achieved, metastases, resistance to cisplatin-based therapy and late toxicities still represent a lethal threat, arguing for the need of new therapeutic options. In this study, we analysed the potential of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors palbociclib and ribociclib (PaRi) as molecular drugs to treat cisplatin-resistant and -sensitive paediatric and adult GCTs. METHODS: Ten GCT cell lines, including cisplatin-resistant subclones and non-malignant controls, were treated with PaRi and screened for changes in viability (triphenyl tetrazolium chloride (XTT) assay), apoptosis rates (flow cytometry, caspase assay), the cell cycle (flow cytometry), the transcriptome (RNA-sequencing, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and on protein level (western blot). Expression profiling was performed on paediatric and adult GCT tissues (expression microarrays, qRT-PCR, immunohistochemistry, 'The Cancer Genome Atlas' database). RESULTS: We demonstrate that adult GCTs highly express CDK4, while paediatric GCTs strongly express CDK6 instead. Thus, both GCT types are potentially treatable by PaRi. GCTs presented as highly sensitive towards PaRi, which caused a decrease in viability, cell cycle arrest and apoptosis. Although GCTs mainly arrested in the G1/G0 phase, some embryonal carcinoma cell lines were able to bypass the G1/S checkpoint and progressed to the G2/M phase. We found that upregulation of CDK3 and downregulation of many mitosis regulation factors, like the HAUS genes, might be responsible for bypassing the G1/S checkpoint and termination of mitosis, respectively. We postulate that GCT cells do not tolerate these alterations in the cell cycle and eventually induce apoptosis. CONCLUSION: Our study highlights PaRi as therapeutic options for cisplatin-resistant and -sensitive paediatric and adult GCTs.