A High-Resolution 3D Ultrasound Imaging System Oriented towards a Specific Application in Breast Cancer Detection Based on a 1 × 256 Ring Array.

This paper presents the design and development of a high-resolution 3D ultrasound imaging system based on a 1 × 256 piezoelectric ring array, achieving an accuracy of 0.1 mm in both ascending and descending modes. The system achieves an imaging spatial resolution of approximately 0.78 mm. A 256 × 32 cylindrical sensor array and a digital phantom of breast tissue were constructed using the k-Wave toolbox. The signal is acquired layer by layer using 3D acoustic time-domain simulation, resulting in the collection of data from each of the 32 layers. The 1 × 256 ring array moves on a vertical trajectory from the chest wall to the nipple at a constant speed. A data set was collected at intervals of 1.5 mm, resulting in a total of 32 data sets. Surface rendering and volume rendering algorithms were used to reconstruct 3D ultrasound images from the volume data obtained via simulation so that the smallest simulated reconstructed lesion had a diameter of 0.3 mm. The reconstructed three-dimensional image derived from the experimental data exhibits the contour of the breast model along with its internal mass. Reconstructable dimensions can be achieved up to approximately 0.78 mm. The feasibility of applying the system to 3D breast ultrasound imaging has been demonstrated, demonstrating its attributes of resolution, precision, and exceptional efficiency.

Cell membrane-anchored and tumor-targeted IL-12 T-cell therapy destroys cancer-associated fibroblasts and disrupts extracellular matrix in heterogenous osteosarcoma xenograft models.

BACKGROUND: The extracellular matrix (ECM) and cancer-associated fibroblasts (CAFs) play major roles in tumor progression, metastasis, and the poor response of many solid tumors to immunotherapy. CAF-targeted chimeric antigen receptor-T cell therapy cannot infiltrate ECM-rich tumors such as osteosarcoma. METHOD: In this study, we used RNA sequencing to assess whether the recently invented membrane-anchored and tumor-targeted IL-12-armed (attIL12) T cells, which bind cell-surface vimentin (CSV) on tumor cells, could destroy CAFs to disrupt the ECM. We established an in vitro model of the interaction between osteosarcoma CAFs and attIL12-T cells to uncover the underlying mechanism by which attIL12-T cells penetrate stroma-enriched osteosarcoma tumors. RESULTS: RNA sequencing demonstrated that attIL12-T cell treatment altered ECM-related gene expression. Immunohistochemistry staining revealed disruption or elimination of high-density CAFs and ECM in osteosarcoma xenograft tumors following attIL12-T cell treatment, and CAF/ECM density was inversely correlated with T-cell infiltration. Other IL12-armed T cells, such as wild-type IL-12-targeted or tumor-targeted IL-12-T cells, did not disrupt the ECM because this effect depended on the engagement between CSV on the tumor cell and its ligand on the attIL12-T cells. Mechanistic studies found that attIL12-T cell treatment elevated IFNγ production on interacting with CSV+ tumor cells, suppressing transforming growth factor beta secretion and in turn upregulating FAS-mediated CAF apoptosis. CAF destruction reshaped the tumor stroma to favor T-cell infiltration and tumor inhibition. CONCLUSIONS: This study unveiled a novel therapy-attIL12-T cells-for targeting CAFs/ECM. These findings are highly relevant to humans because CAFs are abundant in human osteosarcoma.