Chemogenetic Operation of iNTRacellular prOton Levels (pH-Control) is a novel substrate-based enzymatic method that enables precise spatio-temporal control of ultra-local acidification in cultured cell lines and primary neurons. The genetically encoded biosensor SypHer3s showed that pH-Control effectively acidifies cytosolic, mitochondrial, and nuclear pH exclusively in the presence of beta-Chloro-D-alanine in living cells in a concentra-tion-dependent manner. The pH-Control approach is promising for investigating the ultra-local pH imbalance associated with many diseases.

Gold nanoparticles (AuNPs) have attracted considerable interest as emerging CT contrast agents; however, the influence of reconstruction parameters on their quantitative detectability remains insufficiently characterized, limiting the optimization of quantitative CT imaging. This study quantitatively compared the CT imaging performance of citrate-stabilized AuNPs, PEGylated AuNPs (PEG-AuNPs), and a conventional iodinated contrast agent (BMX) under different reconstruction conditions. AuNPs were synthesized by citrate reduction and PEGylated with SH-PEG5K-COOH, followed by physicochemical characterization using dynamic light scattering, zeta potential analysis, and ICP-OES. Contrast samples (≤10 mg/mL) were imaged using a micro-CT system (50 kV, 0.43 mA) with two angular sampling intervals (0.750° and 0.500°), Gaussian and Hann reconstruction kernels, and voxel sizes of 100, 160, and 200 µm. Quantitative performance was evaluated using sensitivity, coefficient of determination (R²), background noise, limit of detection (LOD), and limit of quantification (LOQ). PEG-AuNPs exhibited the highest sensitivity (80.55 HU/mg/mL) and the lowest detection limits (LOD: 0.53 mg/mL; LOQ: 1.61 mg/mL), outperforming bare AuNPs and BMX. Voxel size was the dominant reconstruction parameter, with optimal detectability achieved at 160 µm due to an optimal balance between spatial resolution and image noise, whereas reconstruction kernel and angular sampling had comparatively minor effects. These findings provide a quantitative framework for optimizing reconstruction parameters in nanoparticle-enhanced quantitative CT imaging.

PurposeTo quantitatively evaluate the CT performance of gold nanoparticles (AuNP), polyethylene glycol-coated AuNP (PEG-AuNP), and an iodinated contrast agent (Biemexol, BMX) under varying reconstruction conditions, with emphasis on sensitivity and detectability metrics.MethodsAuNPs were synthesized via citrate reduction and PEGylated using SH-PEG5K-COOH. Physicochemical properties were characterized by DLS and zeta potential measurements, and gold concentration was determined by ICP-OES. Contrast samples (≤10 mg/mL) were scanned using a micro-CT system (50 kV, 0.43 mA) with angular sampling of 0.750° and 0.500°. Images were reconstructed using filtered back projection with Gaussian and Hann kernels at voxel sizes of 100, 160, and 200 µm. Quantitative analysis was performed by extracting mean Hounsfield Unit (HU) values, and sensitivity (HU per mg/mL), coefficient of determination (R²), background noise (σ), limit of detection (LOD), and limit of quantification (LOQ) were calculated.ResultsPEG-AuNP demonstrated the highest sensitivity (75.65 HU per mg/mL) and lowest detection limits (LOD: 0.40 mg/mL; LOQ: 1.23 mg/mL), outperforming both AuNP (12.02 HU per mg/mL; LOD: 2.55 mg/mL) and BMX (50.86 HU per mg/mL; LOD: 0.60 mg/mL). All agents exhibited strong linearity (R² ≥ 0.93). Voxel size was identified as the dominant factor influencing detectability, with optimal performance consistently observed at 160 µm. In contrast, reconstruction kernel (Gaussian vs. Hann) and angular sampling showed comparatively minor effects.ConclusionCT detectability is governed by the combined effects of contrast agent properties and reconstruction parameters. PEG-AuNP provides superior quantitative performance and may enable improved detectability at lower concentrations. Optimization of voxel size is critical for maximizing contrast performance, and further validation in clinical CT systems is warranted.