Cell sonoporation enables the delivery of various exogenous molecules into the cells. To maximize the percentage of reversibly sonoporated cells and to increase cell viability we propose a model for implicit dosimetry for adjustment of ultrasound (US) exposure duration. The Chinese hamster ovary cell suspension was supplemented with microbubbles (MB) and exposed to US, operating at the frequency of 880kHz, with a 100% duty cycle and with an output peak negative pressure (PNP) of 500kPa for durations ranging from 0.5 to 30s. Using diagnostic B-scan imaging we showed that the majority of the MB at 500kPa US peak negative pressure undergo sonodestruction in less than a second. During this time maximal number of reversibly sonoporated cells was achieved. Increase of US exposure duration did not increase sonoporated cell number, however it induced additional cell viability decrease. Therefore aiming to achieve the highest level of reversibly sonoporated cells and also to preserve the highest level of cell viability, the duration of US exposure should not exceed the duration needed for complete MB sonodestruction.

These results show that the microbubble sonodestruction rate can be used to predict the percentage of reversible and irreversible sonoporation.

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Ultrasound induced microbubble (MB) cavitation is used to significantly enhance cell membrane permeabilization, thereby allowing delivery of various therapeutic agents into cells. In order to monitor and quantitatively control the extent of cavitation the uniform dosimetry model is needed. In present study we have simultaneously performed quantitative evaluation of three main sonoporation factors: (1) MB concentration, (2) MB cavitation extent, and (3) doxorubicin (DOX) sonotransfer into Chinese hamster ovary cells. MB concentration measurement results and passively recorded MB cavitation signals were used for MB sonodestruction rate and spectral root-mean-square (RMS) calculations, respectively. Subsequently, time to maximum value of RMS and inertial cavitation dose (ICD) quantifications were performed for every acoustic pressure value. This comprehensive research has led not only to explanation of relation of ICD and MB sonodestruction rate but also to the development of a new sonoporation metric: the inverse of time to maximum value of RMS (1/time to maximum value of RMS). ICD and MB sonodestruction rate intercorrelation and correlation with DOX sonotransfer suggest inertial cavitation to be the key mechanism for cell sonoporation. All these metrics were successfully used for doxorubicin sonotransfer prediction (R(2) > 0.9, p < 0.01) and therefore shows feasibility to be applied for future dosimetric applications for ultrasound-mediated drug and gene delivery.

Objectives-The paper presents the results of an initial clinical study, which were obtained using the strain elastography imaging method based on radio frequency ultrasound signal analysis.Methods-The technique employs endogenous motion of the liver induced by beating heart and vascular pulsatility as an excitation source of tissue microdisplacement. The potential for fibrotic tissue characterization was demonstrated using a clinical data set of radio frequency ultrasound signals (23 healthy controls, 21 subjects with hepatitis, and 16 subjects with liver cirrhosis). Parametric maps, which represent the tissue strain, were derived from the gradient of the integrated spectral coefficient parameter, and correlations with the stage of liver disease were evaluated. Average endogenous strain derived from the gradient of the integrated spectral coefficient parameter and variability (standard deviation) of the strain were evaluated in the rectangular regions of interest (sizes, 1 × 1 and 2 × 2 cm) defined by the observer. The assessment of strain was performed in different frequency subbands of endogenous motion (0-10 Hz and 10-20 Hz).Results-The best distinction between the groups was observed for the average strain derived from the gradient of the integrated spectral coefficient parameter: the controls, 13.30 AE 6.62; hepatitis, 7.12 AE 7.45; cirrhosis, 3.95 AE 2.44 μm/cm (region of interest, 1 × 1 cm; frequency subband 0-10 Hz), and 10.48 AE 6.02, 8.27 AE 5.41, 3.89 AE 2.07 μm/cm, respectively (2 × 2 cm, 0-10 Hz).Conclusion-The investigated strain parameters showed statistically significant differences (P < .001) for the different stages of liver fibrosis in most of the cases and proved this method to be feasible.

The purpose of this paper is a quantification of displacement parameters used in the imaging of brain tissue endogenous motion using ultrasonic radiofrequency (RF) signals. In a preclinical study, an ultrasonic diagnostic system with RF output was equipped with dedicated signal processing software and subject head–ultrasonic transducer stabilization. This allowed the use of RF scanning frames for the calculation of micrometer-range displacements, excluding sonographer-induced motions. Analysis of quantitative displacement estimates in dynamical phantom experiments showed that displacements of 55 µm down to 2 µm were quantified as confident according to Pearson correlation between signal fragments (minimum p ≤ 0.001). The same algorithm and scanning hardware were used in experiments and clinical imaging which allows translating phantom results to Alzheimer’s disease patients and healthy elderly subjects as examples. The confident quantitative displacement waveforms of six in vivo heart-cycle episodes ranged from 8 µm up to 263 µm (Pearson correlation p ≤ 0.01). Displacement time sequences showed promising possibilities to evaluate the morphology of endogenous displacement signals at each point of the scanning plane, while displacement maps—regional distribution of displacement parameters—were essential for tissue characterization.

This paper shows the results of a preliminary study on the performance of new methods based on ultrasonic images parametrization, to estimate the arterial wall movements used for the evaluation of arterial stiffness, considered to be a predictor of cardiovascular events. The well-known technique of motion tracking in ultrasound image sequences was applied on cine loops scanned from subjects with different risks of suffering from cardiovascular disease (CVD). The motion of arterial walls was traced using displacement signals: Diameter, intima-media thickness (IMT) and longitudinal intima-media (IM) complex movement. The new methods used for the parametrization of the displacement signals were the average value (AV), effective or root mean square (RMS) value, and peak-to-peak motion amplitude estimate. A total of 79 subjects were analyzed in the study with 30 considered at low risk and 49 included in a preventive program for monitoring high CVD risk subjects. The results show a statistically significant difference between healthy volunteers and at-risk patients according to the AV of IMT, RMS values of longitudinal and radial motions and peak-to-peak amplitude of radial motion.