The reasons why fractional flow reserve and instantaneous wave-free ratio are similar using wave separation analysis.

BACKGROUND AND OBJECTIVES: Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are the two most commonly used coronary indices of physiological stenosis severity based on pressure. To minimize the effect of wedge pressure (Pwedge), FFR is measured during hyperemia conditions, and iFR is calculated as the ratio of distal and aortic pressures (Pd/Pa) in the wave-free period. The goal of this study was to predict Pwedge using the backward wave (Pback) through wave separation analysis (WSA) and to reflect the effect of Pwedge on FFR and iFR to identify the relationship between the two indices. METHODS: An in vitro circulation system was constructed to calculate Pwedge. The measurements were performed in cases with stenosis percentages of 48, 71, and 88% and with hydrostatic pressures of 10 and 30 mmHg. Then, the correlation between Pback by WSA and Pwedge was calculated. In vivo coronary flow and pressure were simultaneously measured for 11 vessels in all patients. The FFR and iFR values were reconstructed as the ratios of forward wave at distal and proximal sites during hyperemia and at rest, respectively. RESULTS: Based on the in vitro results, the correlation between Pback and Pwedge was high (r = 0.990, p < 0.0001). In vivo results showed high correlations between FFR and reconstructed FFR (r = 0.992, p < 0.001) and between iFR and reconstructed iFR (r = 0.930, p < 0.001). CONCLUSIONS: Reconstructed FFR and iFR were in good agreement with conventional FFR and iFR. FFR and iFR can be expressed as the variation of trans-stenotic forward pressure, indicating that the two values are inferred from the same formula under different conditions.

Characterization of the shock pulse-induced cavitation bubble activities recorded by an optical fiber hydrophone.

A shock pressure pulse used in an extracorporeal shock wave treatment has a large negative pressure (<-5 MPa) which can produce cavitation. Cavitation cannot be measured easily, but may have known therapeutic effects. This study considers the signal recorded for several hundred microseconds using an optical hydrophone submerged in water at the focus of shock pressure field. The signal is characterized by shock pulse followed by a long tail after several microseconds; this signal is regarded as a cavitation-related signal (CRS). An experimental investigation of the CRS was conducted in the shock pressure field produced in water using an optical hydrophone (FOPH2000, RP Acoustics, Germany). The CRS was found to contain characteristic information about the shock pulse-induced cavitation. The first and second collapse times (t1 and t2) were identified in the CRS. The collapse time delay (tc = t2 - t1) increased with the driving shock pressures. The signal amplitude integrated for time from t1 to t2 was highly correlated with tc (adjusted R(2) = 0.990). This finding suggests that a single optical hydrophone can be used to measure shock pulse and to characterize shock pulse-induced cavitation.

A Novel Method for Angiographic Contrast-Based Diagnosis of Stenosis in Coronary Artery Disease: In Vivo and In Vitro Analyses.

BACKGROUND: The existing diagnostic methods for coronary artery disease (CAD), such as coronary angiography and fractional flow reserve (FFR), have limitations regarding their invasiveness, cost, and discomfort. We explored a novel diagnostic approach, coronary contrast intensity analysis (CCIA), and conducted a comparative analysis between it and FFR. METHODS: We used an in vitro coronary-circulation-mimicking system with nine stenosis models representing various stenosis lengths (6, 18, and 30 mm) and degrees (30%, 50%, and 70%). The angiographic brightness values were analyzed for CCIA. The in vivo experiments included 15 patients with a normal sinus rhythm. Coronary angiography was performed, and arterial movement was tracked, enabling CCIA derivation. The CCIA values were compared with the FFR (n = 15) and instantaneous wave-free ratio (iFR; n = 11) measurements. RESULTS: In vitro FFR showed a consistent trend related to the length and severity of stenosis. The CCIA was related to stenosis but had a weaker correlation with length, except for with 70% stenosis (6 mm: 0.82 ± 0.007, 0.68 ± 0.007, 0.61 ± 0.004; 18 mm: 0.78 ± 0.052, 0.69 ± 0.025, 0.44 ± 0.016; 30 mm: 0.80 ± 0.018, 0.64 ± 0.006, 0.40 ± 0.026 at 30%, 50%, and 70%, respectively). In vitro CCIA and FFR were significantly correlated (R = 0.9442, p < 0.01). The in vivo analysis revealed significant correlations between CCIA and FFR (R = 0.5775, p < 0.05) and the iFR (n = 11, R = 0.7578, p < 0.01). CONCLUSIONS: CCIA is a promising alternative for diagnosing stenosis in patients with CAD. The initial in vitro validation and in vivo confirmation in patients demonstrate the feasibility of applying CCIA during coronary angiography. Further clinical studies are warranted to fully evaluate the diagnostic accuracy and potential impact of CCIA on CAD management.

Preparation of fragmented polyethylene nanoplastics using a focused ultrasonic system and assessment of their cytotoxic effects on human cells.

With the growing prevalence of plastic use, the environmental release of plastic waste is escalating, and fragmented nanoscale plastic particles are emerging as significant environmental threats. This study aimed to evaluate the cytotoxic effects of fragmented polyethylene nanoplastics (PE NPs) manufactured using a focused ultrasonic system. The ultrasonic irradiation process generated fragmented PE NPs with a geometric mean diameter of 85.14 ± 5.37 nm and a size range of 25-350 nm. To assess cytotoxicity, we conducted a series of tests on various human cell lines, including stomach, blood, colon, lung, skin, liver, and brain-derived cells. The testing involved MTS-based cell viability assays to evaluate direct impacts on cell viability, lactate dehydrogenase (LDH) leakage assays to measure membrane damage, and ELISA to quantify TNF-α release as an indicator of inflammation. Although PE-NPs did not immediately induce apoptosis, significant LDH leakage and elevated TNF-α levels were observed across all cell lines, indicating membrane damage and inflammatory responses. Additionally, flow cytometry and TEM analyses revealed the intracellular accumulation of PE-NPs, further supporting their cytotoxic potential. These results demonstrate that fragmented PE-NPs can disrupt cellular membranes and induce inflammatory responses through accumulation within cells. The findings suggest that these NPs pose potential hazards to cell viability and underscore the need for further research into their environmental and health impacts.

Scalable production of siRNA-encapsulated extracellular vesicles for the inhibition of KRAS-mutant cancer using acoustic shock waves.

Extracellular vesicles (EVs) have emerged as a potential delivery vehicle for nucleic-acid-based therapeutics, but challenges related to their large-scale production and cargo-loading efficiency have limited their therapeutic potential. To address these issues, we developed a novel "shock wave extracellular vesicles engineering technology" (SWEET) as a non-genetic, scalable manufacturing strategy that uses shock waves (SWs) to encapsulate siRNAs in EVs. Here, we describe the use of the SWEET platform to load large quantities of KRASG12C-targeting siRNA into small bovine-milk-derived EVs (sBMEVs), with high efficiency. The siRNA-loaded sBMEVs effectively silenced oncogenic KRASG12C expression in cancer cells; they inhibited tumour growth when administered intravenously in a non-small cell lung cancer xenograft mouse model. Our study demonstrates the potential for the SWEET platform to serve as a novel method that allows large-scale production of cargo-loaded EVs for use in a wide range of therapeutic applications.

High-resolution photoacoustic/ultrasound imaging of the porcine stomach wall: an ex vivo feasibility study.

Photoacoustic (PA) imaging has become invaluable in preclinical and clinical research. Endoscopic PA imaging in particular has been explored as a noninvasive imaging modality to view vasculature and diagnose cancers in the digestive system. However, these feasibility studies are still limited to rodents or rabbits. Here, we develop a fully synchronized simultaneous ultrasound and photoacoustic microscopy system using two spectral bands (i.e., the visible and near-infrared) in both optical- and acoustic-resolution modes. We investigate the feasibility of imaging gastric vasculature in an ex vivo porcine model. The entire gastric wall, including the mucosa, submucosa, muscularis propria, and serosa, was excised from fresh porcine stomachs immediately followed by ultrasound and PA imaging being performed within a few hours of sacrifice. PA images of the mucosal vasculature were obtained at depths of 1.90 mm, which is a clinically significant accomplishment considering that the average thickness of the human mucosa is 1.26 mm. The layer structure of the stomach wall could be clearly distinguished in the overlaid PA and US images. Because gastric cancer starts from the mucosal surface and infiltrates into the submucosa, PA imaging can cover a clinically relevant depth in early gastric cancer diagnosis. We were able to detect mucosal vasculature in the entire mucosal layer, suggesting the potential utility of combined PA/US imaging in gastroenterology.

Geometrical characterization of the cavitation bubble clouds produced by a clinical shock wave device.

This study was to optically visualize the cavitation bubbles produced by a clinical shock wave and to look into their geometric features of the resulting cavitation bubbles in relation to the driving shock wave field. A clinical shock wave therapeutic system was taken for shock wave production. The shock wave induced cavitation bubbles were captured by a professional camera under the illumination of a micro-pulse LED light. The light exposure was set to last for the whole life time of bubbles from formation to subsequent collapses. It was shown that the cavitation bubbles appeared mostly in the vicinity of the focus. The bubbles became more and larger as approaching to the focus. The cavitation bubbles formed jet streams which became enlarged (stronger) as the shock wave device output setting increased. The bubble cloud boundary was reasonably fitted to an elongated ellipsoid characteristically similar to the acoustic focal area. The bubble clouds were enlarged as the output setting increased. The geometric features of the cavitation bubbles characteristically similar to those of the focusing acoustic field have potential to provide the therapeutic focal information without time consuming hydrophone measurements of the shock wave field causing damages of the expensive sensor. The present study is limited to the static afterimages of the cavitation bubbles and investigation including the bubble dynamics is suggested to deliver the more realistic therapeutic area of the shock wave therapy.

The role of the acoustic radiation force in color Doppler twinkling artifacts.

PURPOSE: The aim of this experimental study was to evaluate whether the acoustic radiation force (ARF) is a potential source of twinkling artifacts in color Doppler images. METHODS: Color Doppler images were obtained using a clinical ultrasonic scanner (Voluson e, GE Healthcare) for a high contrast (+15 dB) circular scattering phantom at pulse repetition frequencies (PRFs) ranging from 0.1 to 13 kHz. Ultrasound transmissions resulting in ARF were measured using a hydrophone at the various PRFs considered. The influence of ARF on the appearance of twinkling colors was examined via the common parameter PRF. This methodology is based on the fact that alternating positive and negative Doppler shifts induced by the ARF are centered at a PRF twice the maximum Doppler frequency on the color scale bar, whereas the twinkling color aliasing is expected to remain similar regardless of PRF. RESULTS: Color twinkling artifacts were observed to be most conspicuous at the lowest PRF of 0.1 kHz. The extent of twinkling rapidly decreased as the PRF increased, eventually disappearing when the PRF ≥0.6 kHz. The measured ultrasound transmissions, however, were found to be insensitive to the PRF, and therefore it can be inferred that the PRF was insensitive to the ARF. CONCLUSION: Based on our experimental observations, the ARF may not be a source of color Doppler twinkling artifacts.