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Alper, J.

Publications and source records attributed to Alper, J..

2 recordsLinked to original sources

Frequency Shift Imaging Using an Adiabatic SLR Self-Refocused Pulse for Positive-Contrast SPION Imaging at 7T

Abstract: Purpose: Superparamagnetic iron oxide nanoparticles (SPION) are widely used as MRI contrast agents for cell tracking and molecular imaging. However, their detection using conventional T2/T2* weighted and susceptibility-weighted MRI relies on negative contrast (signal voids), which lacks specificity because similar hypointense signals can arise from other sources of magnetic susceptibility. This study introduces Frequency Shift Imaging (FSI), a positive-contrast technique based on an adiabatic Shinnar-Le Roux (SLR) self-refocused pulse that addresses the limited specificity of conventional SPION imaging. Methods: An adiabatic self-refocused RF pulse was designed using the SLR algorithm for frequency-selective positive-contrast imaging. The optimized pulse had a spectral bandwidth of 370 Hz, a peak RF amplitude of 14 T, and a duration of 15 ms. FSI data were acquired on a 7T MRI scanner. Phantom experiments used agarose-embedded 30 nm cell-labeled SPION at 0%, 25%, 75%, and 100% concentrations (pure). In vivo validation was performed following intramuscular SPION injection into the hind limb of a mouse. FSI images were compared with conventional acquisitions. Results: Quantitative phantom analysis showed normalized FSI signal intensities of 25.02% and 75.16% for samples containing 25% and 75% labeled cells, respectively, demonstrating an approximately proportional relationship between FSI signal and labeled-cell concentration. In vivo, FSI generated localized hyperintense positive contrast at the SPIO injection site, providing improved conspicuity and localization compared with the corresponding negative-contrast signal void. Discussion and Conclusion: FSI enables robust, B1-insensitive, positive-contrast SPION imaging at 7T with reduced echo time and SAR compared to paired adiabatic approaches, supporting its potential for quantitative cell tracking and molecular imaging applications.

bioengineering↗

Ensemble Switching Unveils a Kinetic Rheostat Mechanism of the Eukaryotic Thiamine PyrophosphateRiboswitch

Thiamine pyrophosphate (TPP) riboswitches regulate thiamine metabolism by inhibiting the translation of enzymes essential to thiamine synthesis pathways upon binding to thiamine pyrophosphate in cells across all domains of life. Recent work on the Arabidopsis thaliana TPP riboswitch suggests a multi-step TPP binding process involving multiple riboswitch conformational ensembles and that Mg2+ dependence underlies the mechanism of TPP recognition and subsequent transition to the translation-inhibiting state of the switching sequence followed by changes in the expression platform. However, details of the relationship between TPP riboswitch conformational changes and interactions with TPP and Mg2+ in the aptamer domain constituting this mechanism are unknown. Therefore, we integrated single-molecule multiparameter fluorescence and force spectroscopy with atomistic molecular dynamics simulations and found that conformational transitions within the aptamer domain associated with TPP and Mg2+ ligand binding occurred between at least five different ensembles on timescales ranging from s to ms. These dynamics are at least an order of magnitude faster than folding and unfolding kinetics associated with translation-state switching in the switching sequence. Moreover, we propose that two pathways exist for ligand recognition. Together, our results suggest a dynamic ensemble switching of the aptamer domain that may lead to the translation-inhibiting state of the riboswitch. Additionally, our results suggest that multiple configurations could enable inhibitory tuning manifested through ligand-dependent changes via ensemble switching and kinetic rheostat-like behavior of the Arabidopsis thaliana TPP riboswitch.

biophysics↗