KEYWORDS: Digital signal processing, Profiling, Breast cancer, Tumors, Resistance, Antibodies, Ultraviolet radiation, Tissues, Optical signal processing, Optical imaging
NanoString GeoMX Digital Spatial Profiling (DSP) is an emerging optical technology for spatial multi-omics. DSP utilizes probes attached to UV-photocleavable, fluorescent oligonucleotide barcodes indicating target identity and location. These barcodes are counted to quantify gene expression. This high-throughput, single-cell resolution tool exemplifies how optics can elucidate disease mechanisms. Our study employed DSP to understand T-DXd resistance in metastatic breast cancer (mBC). T-DXd is an antibody-drug conjugate that is standard of care in mBC. Patients have few options if T-DXd fails; uncovering resistance mechanisms is crucial for developing life-saving therapies. We used GeoMX DSP to investigate tumor-immune interactions in T-DXd responsive and resistant patient samples. We captured spatially diverse tumor-dense and tumor-sparse regions of interest for proteomics analysis. We found that local stromal remodeling and decreased killer T-cell infiltration are T-DXd resistance characteristics. These results show promise for helping T-DXd resistant-patients and highlight the importance of optical imaging in drug discovery.
Significant challenges such as a high proportion of indeterminate results, inadequate sampling, and false positives remain prevalent in the diagnosis of thyroid cancer when using fine needle aspiration biopsy or core needle biopsy. Second harmonic generation (SHG) imaging is a label-free, nonlinear optical imaging method that selectively uses fibrillar collagen arrangement to provide endogenous contrast. We investigated applications of SHG-specific feature extraction methods such as anisotropy, and more broadly applied gray-level co-occurrence matrices to generate quantitative metrics that describe either the structural or physical properties of the imaged thyroid samples. The features differed significantly between thyroid cancer and normal thyroid samples, thus independently possessing the capability to differentiate between cancerous and normal thyroid tissue.
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