Rytis Jurkonis

Investigation of intracranial media ultrasonic monitoring model.

The objectives are to investigate the peculiarities of the ultrasound pulse propagation through human extra/intracranial media by mathematical simulation and to confirm the simulation results experimentally by proving the suitability of the ultrasonic time-of-flight measurement method for human intracranial media (IM) physiological non-invasive monitoring. The mathematical model of ultrasound pulse propagation through the human extra/intracranial media is described. The simulation of various physiological phenomena were performed to determine the relationship between the characteristics of the transmitted ultrasound pulse through the human head and the acoustic properties of the IM. It is shown that non-invasive monitoring of the IM acoustic properties is possible by measuring the changes of the ultrasonic signal time-of-flight and the oscillation period. The influence made by variations in acoustic parameters of the external tissue/skull bones on the non-invasive measurement data is investigated and methods of compensation of that influence are presented. The models were applied for developing of a new non-invasive sonographic intracranial pressure (ICP) monitor (Vittamed). Comparative studies of this monitor with the invasive ICP monitor (Camino) have shown the possibility of achieving clinically acceptable accuracy of the long term non-invasive ICP monitoring of head injured patients in intensive care units.

Adjustment of ultrasound exposure duration to microbubble sonodestruction kinetics for optimal cell sonoporation in vitro.

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 880 kHz, with a 100% duty cycle and with an output peak negative pressure (PNP) of 500 kPa for durations ranging from 0.5 to 30 s. Using diagnostic B-scan imaging we showed that the majority of the MB at 500 kPa 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.

Microbubble Sonodestruction Rate as a Metric to Evaluate Sonoporation Efficiency

The efficiency of sonoporation is directly related to microbubble cavitation and can be dependent on the microbubble sonodestruction rate. The objective of this study was to investigate whether the rate of microbubble sonodestruction can be used as a parameter to develop an implicit dosimetric method for sonoporation efficiency evaluation.

New method of spatial superposition of attenuated waves for ultrasound field modelling

The objective of this work is the contrary issues of ultrasonic diagnostics in medicine when modern requirements for resolution are in conflict with strict safety issues. There is only one way to make progress by starting to take into account the attenuation in biological tissues and the wave diffraction phenomena. The aim of this work is to develop the flexible ultrasound field model implemented in routine algorithms of digital signal processing. The method consists of the calculation of plane wave propagation and the calculation of an ultrasound signal field. On the basis of the spatial impulse response of an aperture for calculation of space-spread ultrasound signals and the spectrum decomposition method for modelling plane wave propagation in lossy media, the modified method of spatial superposition of attenuated waves was developed. Using the method of equidistant line calculation the time and frequency features of the ultrasound signal field caused by the geometry and dynamics of the aperture, the attenuation and velocity dispersion in the medium are determined. The method was successfully applied to the investigation of the system for intracranial media monitoring, where a new measurement channel based on the changes of attenuation and dispersion in intracranial medium has been implemented.

Ultrasound Medical Diagnostics Laboratory for Remote Learning in EVICAB*Campus

The aim of this paper is to present the development of remote learning laboratory for ultrasound medical diagnostics. We demonstrate the implementation of such laboratory using virtual instrument that is built by using standard PC, ultrasonic transducer with tissue like phantom, digitizer (Picoscope ADC 212/100, Picotech Ltd.), function generator (Hameg HM8131-2, Hameg Instruments GmbH) and popular software package LabView (National Instruments Inc.). By controlling the virtual instrument it is possible to excite and receive ultrasound waves in pulse echo mode then process the received echographic signal and get the characteristics of tissue like phantom. The tissue like phantom is characterized with thickness and density also with the speed of waves propagation and attenuation coefficient. The students are motivated by the assignment of the clear task - to identify the material from which the phantom is made. The implemented virtual instrument is based on NI Remote panel technology. This technology allows to access the virtual instrument remotely using internet browse. The lab preparation materials: goal, theory, quizzes are available from e-learning platform Moodle. We expect the students will improve their knowledge of ultrasound tissue characterization using our remote hands-on labwork.

Advanced hardware for fine-tuning and optimization of sonoporation efficiency in vitro

To our knowledge current achievements in tuning the sonoporations bio-efficiency is limited by the inflexibility of the ultrasound excitation hardware. Advanced instrumentation for fine-tuning and optimization of sonoporation efficiency in-vitro has been developed. The advantages of developed hardware are: the fine tuning of center frequency of the burst; the fine tuning of amplitude of the burs from 50 V to 500 V; the programmable number of burst periods, duty cycle of series of bursts and repetition frequency, and total time of excitation. Our hardware together with wideband focused transducer has specified parameters in space, and ability to control the acoustic pressure amplitude with digital precision. Operation range is 500 kHz to 5 MHz; length of burst variable up to 100 periods; pulse repetition frequency up to 5 kHz. The linear RF power amplifier with matched output impedance was replaced by the low output impedance square wave generator. Such hardware solution allows having better output amplitude stability and digital programmability, yet at increased economy: both power consumption and cost of equipment. Instrumentation structure and operation principles are presented.1

Courseware for ultrasonic medical diagnostics curriculum: system for on-site and remote laboratory experiments

The aim of this paper is to present the implementation approach of on-site and remote experimenting laboratory for ultrasound medical diagnostics curriculum. We demonstrate the implementation of such laboratory using virtual instrument that is built by using a standard computer, a ultrasonic transducer with a tissue like phantom, digitizer, function generator and the software package LabView. By controlling the virtual instrument it is possible to excite and receive ultrasound waves in the pulse echo mode, then process the received echographic signal and get the characteristics of the tissue like phantom. The tissue like phantom is characterized with thickness and density also with the speed of wave’s propagation and attenuation coefficient. The students are motivated by the assignment of the precise task - to identify the material from which the phantom is made. The implemented on-site experiments system is based on a virtual instrument, the remote experiments system and is tested using the LabView remote panel technology as well. This technology allows accessing the experiment system remotely using an internet browser. We expect the students will improve their knowledge of ultrasound medical diagnostics using our hands-on lab experiment system.

Analysis of Metrics for Molecular Sonotransfer in Vitro.

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.

Algorithms and Results of Eye Tissues Differentiation Based on RF Ultrasound

Algorithms and software were developed for analysis of B-scan ultrasonic signals acquired from commercial diagnostic ultrasound system. The algorithms process raw ultrasonic signals in backscattered spectrum domain, which is obtained using two time-frequency methods: short-time Fourier and Hilbert-Huang transformations. The signals from selected regions of eye tissues are characterized by parameters: B-scan envelope amplitude, approximated spectral slope, approximated spectral intercept, mean instantaneous frequency, mean instantaneous bandwidth, and parameters of Nakagami distribution characterizing Hilbert-Huang transformation output. The backscattered ultrasound signal parameters characterizing intraocular and orbit tissues were processed by decision tree data mining algorithm. The pilot trial proved that applied methods are able to correctly classify signals from corpus vitreum blood, extraocular muscle, and orbit tissues. In 26 cases of ocular tissues classification, one error occurred, when tissues were classified into classes of corpus vitreum blood, extraocular muscle, and orbit tissue. In this pilot classification parameters of spectral intercept and Nakagami parameter for instantaneous frequencies distribution of the 1st intrinsic mode function were found specific for corpus vitreum blood, orbit and extraocular muscle tissues. We conclude that ultrasound data should be further collected in clinical database to establish background for decision support system for ocular tissue noninvasive differentiation.

RF Ultrasound Based Estimation of Pulsatile Flow Induced Microdisplacements in Phantom

Mechanical stimulus is key component to estimate tissue stiffness. Few techniques have been developed to induce external mechanical stimulus into tissues. We hypothesize that the natural tissue motion due to cardiovascular activity could be employed for this purpose and with decrease of tissue stiffness increase their motion amplitude. The assessment of elastic sub-millimeter tissue displacements is one of the leading developments for ultrasonic characterization of tissue stiffness. The objective of this study was to investigate the feasibility to parametrize the phantom material response to pulsatile flow. The displacements were evaluated in tissue-mimicking phantoms with known stiffness. The two agar phantoms, having vessel imitating channel with controlled pulsatile flow inside, were manufactured (agar concentrations 6 and 3 g/l in distilled water, predicted Young modulus was 10 and 7 kPa respectively). The pulse water flow in channel was produced by centrifugal pump MultiFlow (Gampt) with period of 1 s. The length of channel was 19 cm embedded in the tissue mimicking agarose gel. Linear array transducer L14-5 (5–14 MHz) driven by scanner SonixTouch (Ultrasonix) was used for the echoscopy of phantom and ultrasound (US) radiofrequency (RF) data acquisition. The collected beam formed B-mode RF data (120 fps) were used for the displacements estimation applying phase-correlation and sub-sample techniques. The pulsation of channel diameter and displacements of material were estimated at a few distances from channel border in all phantoms. The pulsation of diameter and displacements of material were parametrized extracting double amplitudes. Amplitudes of displacements of material were normalized respective to pulsation amplitude of channel diameter. The relation of amplitude parameters with concentration of agar was evaluated. It was determined that displacement is correlated with stiffness: with decrease of tissue stiffness the motion amplitude is increasing. The method may provide the technological background for future studies characterizing in vivo tissue stiffness from vascular pulsations generated displacements.