Biology subjects

Sakuma, I.

Publications and source records attributed to Sakuma, I..

3 recordsLinked to original sources

bioRxiv2026

Real-time ultrafast holography of focused ultrasound wave fields using an ultrasound scanner

Acoustic pressure field measurements are required for marketing clearance of medical ultrasound instruments, but the gold standard method, hydrophone scanning, is time consuming. The objective of this work was to develop an ultrafast holographic method for real-time imaging of focused ultrasound fields. The technique is based on parallel acquisition with a sensor array, and FUS field reconstruction based on time reversal assuming a homogeneous lossless medium. The geometric characteristics of the sensor to enable accurate reconstruction were evaluated through numerical modelling. A practical example involving a commercially-available 128-element linear-array ultrasound imaging probe is presented. Finally, preliminary experiments were conducted on in-vitro soft tissues to validate the concept of simultaneous dual-mode imaging, combining conventional B-mode tissue imaging with FUS field holography. In modelling of ideal sensor characteristics (2D matrix; intercepted energy > 99%), parallel holography allowed reconstructing wave fields with excellent agreement with the Rayleigh Integral reference (errors << 0.01%). Successfully experimental demonstration of real-time ultrafast wave field holography was achieved with the commercial imaging probe (7-10% error in the -6dB focus vs hydrophone measurements, acquisition time: 100 microseconds, display rate: 15 frames/s), despite a suboptimal intercepted energy (44%). Real-time dual-mode imaging of continuous wave fields allowed targeting localized tissues regions, while holographic movies highlighted the propagation of transient waves. Overall, real-time ultrafast holography offers a practical way to perform metrology and guidance of ultrasonic devices, by visualising waves fields typically used for ultrasound imaging, or those used during thermal or non-thermal ultrasound therapy.

bioengineering↗

bioRxiv2025

Liver lipid droplet cholesterol content is a key determinant of metabolic dysfunction-associated steatohepatitis

Metabolic dysfunction-associated steatohepatitis (MASH) represents a progressive form of steatotic liver disease which increases the risk for fibrosis and advanced liver disease. The accumulation of discrete species of bioactive lipids has been postulated to activate signaling pathways that promote inflammation and fibrosis. However, the key pathogenic lipid species is a matter of debate. We explored candidates using various dietary, molecular, and genetic models. Mice fed a choline-deficient L-amino acid-defined high-fat diet (CDAHFD) developed steatohepatitis and manifested early markers of liver fibrosis associated with increased cholesterol content in liver lipid droplets within 5 days without any changes in total liver cholesterol content. Treating mice with antisense oligonucleotides (ASOs) against Coenzyme A synthase (Cosay) or treatment with bempedoic acid or atorvastatin decreased liver lipid droplet cholesterol content and prevented CDAHFD-induced MASH and the fibrotic response. All these salutary effects were abrogated with dietary cholesterol supplementation. Analysis of human liver samples demonstrated that cholesterol in liver lipid droplets was increased in humans with MASH and liver fibrosis and was higher in PNPLA3 I148M (variants rs738409) than in HSD17B13 variants (rs72613567). Together, these data identify cholesterol in liver lipid droplets as a critical mediator of MASH and demonstrate that COASY knockdown and bempedoic acid are novel therapeutic approaches to reduce liver lipid droplet cholesterol content and thereby prevent the development of MASH and liver fibrosis. Significance StatementMetabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease linked to fibrosis. The role of specific lipid species in its pathogenesis remains debated. Using dietary, molecular, and genetic models, we found that mice on a choline-deficient, high-fat diet (CDAHFD) developed steatohepatitis and early fibrosis, marked by increased cholesterol in liver lipid droplets within five days. Targeting COASY with antisense oligonucleotides or treating with bempedoic acid or atorvastatin reduced lipid droplet cholesterol and prevented MASH. However, dietary cholesterol supplementation negated these effects. Human liver samples confirmed elevated lipid droplet cholesterol in MASH and fibrosis, especially in PNPLA3 I148M carriers. These findings highlight cholesterol reduction as a potential MASH therapy.

pathology↗

bioRxiv2021

Acoustic light-sheet microscopy

Light-sheet imaging of 3D objects with high spatial resolution remains an open challenge because of the trade-off between field-of-view (FOV) and axial resolution originating from the diffraction of light. We developed acoustic light-sheet microscopy (acoustic LSM), which actively manipulates the light propagation inside a large sample to obtain wide-field microscopic images deep inside a target. By accurately coupling a light-sheet illumination pulse into a planar acoustic pulse, the light-sheet can be continuously guided over large distances. We imaged a fluorescence-labeled transparent mouse brain for the FOVs of 19.3 x 12.4 mm2 and 9.7 x 5.9 mm2 with resolved microstructures and single cells deep inside the brain. Acoustic LSM creates new opportunities for the application of light-sheet in the field of industry to basic science. One Sentence SummaryAn acoustic-optical method overcomes a trade-off between field-of-view and axial resolution in light-sheet microscopy.

bioengineering↗