For many years, the Ultrasound Department has been conducting research to improve quality of methods supporting diagnostics and medical therapy. It is still one of the main topics being developed in the Department. In three laboratories, the research is conducted on ultrasound characteristics of tissues, thermal phenomena induced by ultrasound absorption, the modeling of ultrasound propagation in biological media, forming of the acoustic fields generated by multi-element transducers and methods of ultrasonic image reconstruction.

     Quantitative Ultrasound of breast tissue – application to lesions classification and prediction of cancer response to chemotherapy

     Ultrasonography (USG) is one of the basic medical examinations conducted for the purpose of breast disease diagnosis. Quantitative ultrasound (QU) imaging with RF signal analysis provides additional information on morphological features of breast tumors.
     The assessment of tumor malignancy degree is an important issue because an accurate diagnosis of breast tumors plays an important role in therapy planning, positively affects the patient’s prognosis and can improve the overall chance of survival. In turn, preoperative (neoadjuvant) chemotherapy is used in patients with clinically advanced breast cancer to improve the effectiveness of surgical treatment and to lower the risk of cancer recurrence. It also contributes to the increase in numbers of the breast-conserving procedures and reduces the mortality rate of patients. Monitoring the effectiveness of treatment in such patient groups is particularly important in order to individualise treatment and reduce its toxicity.

                        
Fig.1 QU images (distribution of weighted entropy) of the two types of breast lesions, malignant - cribriform breast carcinoma (left) and benign - breast adenocarcinoma (right). The red and blue colors correspond to high and low entropy values respectively.

     In cooperation with the Maria Skłodowska-Curie Memorial Cancer Centre, Institute of Oncology in Warsaw, we focused on the research of ultrasonic biomarkers of tumor changes and tumor response to chemotherapy. The physical parameters of the tumor tissue, texture parameters of tumor images and statistical parameters of ultrasonic backscatter were derived from ultrasonic echoes. Those parameters that best reflected changes in tissue were presented in the form of QU maps. Results demonstrated that QU imaging can differentiate between malignant and benign breast lesions and non-invasively monitor the response of the breast cancer patients to chemotherapy, following the treatment initiation.

                                           

Fig. 2 Patient with complete remission. QU imaging maps based on homodyned K distribution present a decrease in shape parameter for tumor treated with chemotherapy (from blue to red). Prior to treatment (a), after the third medicine dose (b) and after the NAC course (c).

     Heating by magnetic and ultrasonic fields of samples doped with iron oxide nanoparticles

     Magnetic nanoparticles (MNP) are now widely used in medicine, both in therapies and in diagnostics. Here, our main area of interest is the application of magnetic nanoparticles as thermal agents in the localized magnetic and ultrasonic hyperthermia due to hyperthermic effect observed when nanoparticles are exposed to the alternating magnetic field or to the ultrasound field. Magnetic hyperthermia uses the magnetization reversal losses of MNP in an alternating magnetic field whereas ultrasonic hyperthermia uses the effect of sound absorption to achieve local heating of the tissue to treat tumors. The main goal of our research is to find links between thermal effects of ultrasonic and magnetic hyperthermia. The ultrasonic and magnetic absorption rates, being the measures of hyperthermia efficiency, are obtained from experimentally measured rate of temperature variations at the starting time point of heating.
     The study of hyperthermia by simultaneous application of both, magnetic and ultrasound fields, needs dedicated equipment. To measure the magnetic hyperthermia by controlled alternating magnetic field, the dedicated system, was constructed (see Figure 3). With the help of the system, the first performed experiments confirmed the possibility of measuring the temperature increase, 8-10 °C, in the magnetic fluid located inside the coil during 5 minutes of application of an alternating magnetic field.
Further studies of the simultaneous use of magnetic and ultrasonic fields to improve hyperthermia performance are challenging both for basic research and the applications of its results in innovative hyperthermia for cancer treatment.


Fig.3 The system consists of a coil, Generator Agilent Technologies 33250A, Amplifier ENI.INC Model 3100LA RF and water circulation cooling system used to obtain the thermally insulated space inside the coil in which homogeneous magnetic field appears.

    Novel method for improvement of quality of ultrasound echoes visualisation

      The purpose of the study is to develop methods with low computational complexity, improving the quality of ultrasound signals obtained from periodic transceivers. Such transceivers are commonly used in ultrasonic scanners and generate the noise by the grating lobes. The foundations of the phenomenon of this structural noise is described by the diffraction grating theory. Without reduction, the noise from grating lobes occupies signifivant imaging areas and change the image of an object or hides the details of its structure below the noise level — red rectangles in Fig.4. A new method of Virtual Receiving Subaperture for the suppression of the influence of grating lobes noise has been developed. It consists of generating virtual signals, non-existing physically, in real transceivers. Virtual Receiving Subaperture method is a kind of a spatial filter that effectively increases the density of detectors. During reconstruction, the Virtual Receiving Subaperture also creates a grating lobes signal,  however, with a phase opposite to that generated by the real aperture. As a consequence, both signals perform self cancelation. The use of Virtual Receiving Subaperture is highly noise-suppressing and thus enable early detection and improvement of the diagnosis of tissue with emerging pathology or material structure. Objects previously barely visible or invisible become visible — yellow rectangle in Fig.(a,b).

      
Fig.4. Images of tissue-mimicking phantom obtained using an transceiver array of various sizes: (a) - 64 elements, (b) - 128 elements; Effect of grating lobes noise on imaging quality — red rectangles and the result of Virtual Receiving Subaperture application — yellow rectangles.

     Destruction of solid tumors by means of pulsed focused ultrasonic beams

     In recent years, new therapeutic approaches have been proposed for the treatment of solid cancers by means of focused ultrasound (FUS). The technology utilizing pulsed focused ultrasound waves is a non-invasive technique to destroy primary solid tumors or their metastases localized deep beneath the skin. Therefore, it produces significantly less complications and side effects than conventional treatments (surgery, radio- and/or chemotherapy).
     Therapy using FUS beams with low local intensity (in the focal area) rely on tumor hyperthermia (40-43 ^oC). During the process, thermo-sensitive liposomes filled with a cytotoxic drug are selectively delivered to the tumor and release the drug locally due to their cracking induced by ultrasonic waves. The therapy which uses FUS with high local intensity relies on the thermo-ablative destruction of the tumor volume without damaging the surrounding healthy tissue.
     The research objectives were to design an automated device dedicated to small animal studies and capable of simultaneous:
     - guiding the focus of the heating beam on the interior of an implanted tumor;
     - heating a small volume inside the tumor to a suitable temperature;
     - automatic spatial scanning of the entire tumor volume by the heating beam focus.

Fig.5 Automated bimodal ultrasonic device designed for thermal destruction of solid tumors in preclinical studies.

     Estimation and Measurement of the Streaming Velocity

      The aim of the project was to use the streaming phenomena to assist clots dissolution in blood vessels. Such treatment is called sonothrombolysis. Acoustic streaming is a steady flow in a fluid driven by the acoustic wave propagating in a lossy medium. The streaming depends on the intensity and absorption of ultrasound in the media. For high frequencies exceeding 20 MHz the speed of streaming in blood is also affected by scattering effects on the blood cells and the contrast agent microbubbles. We have modified the theoretical description of streaming by adding the scattering coefficient to equations describing the radiation force and the streaming velocity.
     Theoretical calculations confirmed the increase in streaming velocity for the blood-mimicking starch concentration, very similar to the experimental results. The theory has also shown the ability to reduce the streaming velocity by low-density scatterers. It was experimentally proved using BR14 ultrasonic contrast agent.


Fig.6 Doppler velocity spectrum of the signal scattered on blood-mimicking starch in concentrations of 0.01 and 1 - 4 g/l (a), and scattered on BR14 contrast in concentration of 1 - 4·10³ microbubbles /mm³ (b).