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Biology subjects

Fletcher, S.-M.

Publications and source records attributed to Fletcher, S.-M..

2 recordsLinked to original sources

Spatial Profiling of Metals through Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging

The spatial-omic analysis of biomolecules such as nucleic acids, lipids, metabolites, and proteins is advancing the study of biological systems and processes in a physio-pathological context. Here, we describe an innovative matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) method to detect metals within biological tissues using instrumentation that is widely available in research and clinical laboratories. We characterize the spatial distribution of metals in diverse settings including mouse embryogenesis, genetic disorders leading to abnormal metal accumulation, and preclinical testing for improved platinum-based chemotherapy delivery through focused ultrasound across the blood-brain barrier. Spatial metal profiling will advance research studies and the clinical analysis of metal-related diseases, enabling more precise use of metal-based therapies and advances in diverse scientific fields beyond biomedicine. One-Sentence SummarySpatial metallomic profiling maps native metals or those coordinated to xenobiotics, antibodies, and biomolecules in tissues.

cancer biology↗

Non-invasive homogeneous targeted blood-brain barrier disruption using acoustic holography with a clinical focused ultrasound system

Holographic methods can be used with phased array transducers to shape an ultrasound field. We tested a simple method to create holograms with a 1024-element phased array transducer. With this method, individual acoustic simulations for each element of the transducer were simultaneously loaded into computer memory. Each elements phase was systematically modulated until the combined field matched a desired pattern. The method was evaluated with a 220 kHz hemispherical transducer being tested clinically to enhance drug delivery via blood-brain barrier disruption. The holograms were evaluated in a tissue-mimicking phantom and in vivo in experiments disrupting the blood-brain barrier in rats and in a macaque. This approach can enlarge the focal volume in a patient-specific manner and could reduce the number of sonication targets needed to disrupt large volumes, improve the homogeneity of the disruption, and improve our ability to detect microbubble activity in tissues with low vascular density. TeaserHolography can shape the focal region of a clinical focused ultrasound system developed for targeted drug delivery in the brain.

biophysics↗