How can MSI enhance our understanding of ASO distribution?

In the dynamic field of drug discovery and development, a comprehensive understanding of drug absorption, distribution, metabolism, excretion, and toxicity is crucial. Mass spectrometry imaging (MSI) has become a key analytical tool in the pharmaceutical industry, allowing evaluation of drug biodistribution and molecular profiles. Antisense oligonucleotides (ASOs) are emerging drug candidates for treating neurologic diseases.

Lipid analysis of human primary dermal fibroblasts and epidermal keratinocytes after near-infrared exposure using mass spectrometry imaging.

Photobiomodulation (PBM) therapy is the application of near-infrared (NIR) exposure to injuries or lesions to (among others) improve wound healing, reduce inflammation, and decreases acute and chronic pain. However, the understanding of the molecular mechanism of PBM, more specifically the effects of NIR on skin cells is still lacking behind. Lipids are essential components of cellular membranes that are integral to skin structure and function.

Spatial omics reveals molecular changes in focal cortical dysplasia type II.

Focal cortical dysplasia (FCD) represents a group of diverse localized cortical lesions that are highly epileptogenic and occur due to abnormal brain development caused by genetic mutations, involving the mammalian target of rapamycin (mTOR). These somatic mutations lead to mosaicism in the affected brain, posing challenges to unravel the direct and indirect functional consequences of these mutations. To comprehensively characterize the impact of mTOR mutations on the brain, we employed here a multimodal approach in a preclinical mouse model of FCD type II (Rheb), focusing on spatial omics techniques to define the proteomic and lipidomic changes.

Sample preparation for lipid analysis of intra-articular adipose tissue by using matrix-assisted laser desorption/ionization imaging.

Mass spectrometry imaging (MSI) is a powerful technique enabling the visualization of the spatial distribution of different molecules in tissue biopsies with different pathologies. Sample handling and preparing adipose tissue for MSI is challenging and prone to molecular delocalization due to tissue melting. In this work, we developed a method for matrix-assisted laser desorption/ionization (MALDI)-MSI to study lipids in human infrapatellar fat pad (IPFP), a biomarker source in musculoskeletal pathologies, while preserving molecular spatial distribution.

Multimodal molecular imaging in drug discovery and development.

In addition to individual imaging techniques, the combination and integration of several imaging techniques, so-called multimodal imaging, can provide large amounts of anatomical, functional, and molecular information accelerating drug discovery and development processes. Imaging technologies aid in understanding the disease mechanism, finding new pharmacological targets, and assessment of new potential drug candidates and treatment response. Here, we describe how different imaging techniques can be used in different phases of drug discovery and development and highlight their strengths, related innovations, and future potential with a focus on the implementation of artificial intelligence (AI) and radiomics for imaging technologies.

Tumor classification with MALDI-MSI data of tissue microarrays: A case study.

With mass spectrometry imaging (MSI) on tissue microarrays (TMAs) a large number of biomolecules can be studied for many patients at the same time, making it an attractive tool for biomarker discovery. Here we investigate whether lymph node metastasis can be predicted from MALDI-MSI data. Measurements are performed on TMAs and then filtered based on spectral intensity and the percentage of tumor cells, after which the resulting data for 122 patients is further preprocessed.

Enhanced capabilities for imaging gangliosides in murine brain with matrix-assisted laser desorption/ionization and desorption electrospray ionization mass spectrometry coupled to ion mobility separation.

The increased interest in lipidomics calls for improved yet simplified methods of lipid analysis. Over the past two decades, mass spectrometry imaging (MSI) has been established as a powerful technique for the analysis of molecular distribution of a variety of compounds across tissue surfaces. Matrix-assisted laser desorption/ionization (MALDI) MSI is widely used to study the spatial distribution of common lipids.