In-vitro sonothrombolysis using thick-shelled polymer microbubbles - a comparison with thin-shelled microbubbles.

BACKGROUND: Vascular thrombosis can be treated pharmacologically, however, serious shortcomings such as bleeding may occur. Several studies suggest that sonothrombolysis can induce lysis of the clots using ultrasound. Moreover, intravenously injected thin-shelled microbubbles (MBs) combined with ultrasound can further improve clot lysis. Thick-shelled MBs have been used for drug delivery, targeting and multimodal imaging. However, their capability to enhance sonothrombolysis is unknown. In this study, using an in-vitro set-up, the enhancement of clot lysis using ultrasound and thick-shelled MBs was investigated. Thin-shelled MBs was used for comparison. METHOD: The main components in the in-vitro set-up was a vessel mimicking phantom, a pressure mearing system and programmable ultrasound machine. Blood clots were injected and entrapped on a pore mesh in the vessel phantom. Four different protocols for ultrasound transmission and MB exposure (7 blood clots/protocol) were considered together with a control test were no MBs and ultrasound were used. For each protocol, ultrasound exposure of 20 min was used. The upstream pressure of the partially occluded mesh was continuously measured to assess clot burden. At the end of each protocol blood clots were removed from the phantom and the clot mass loss was computed. RESULTS: For the thick-shelled MBs no difference in clot mass loss compared with the control tests was found. A 10% increase in the clot mass loss compared with the control tests was found when using thin-shelled MBs and low pressure/long pulses ultrasound exposure. Similarly, in terms of upstream pressure over exposure time, no differences were found when using the thick-shelled MBs, whereas thin-shelled MBs showed a 15% decrease achieved within the first 4 min of ultrasound exposure. CONCLUSION: No increase in clot lysis was achieved using thick-shelled MBs as demonstrated by no significant change in clot mass or upstream pressure. Although thick-shelled MBs are promising for targeting and drug delivery, they do not enhance clot lysis when considering the ultrasound sequences used in this study. On the other hand, ultrasound in combination with thin-shelled MBs can facilitate thrombolysis when applying long ultrasound pulses with low pressure.

Sparse Ultrasound Image Reconstruction From a Shape-Sensing Single-Element Forward-Looking Catheter.

OBJECTIVE: Minimally invasive procedures, such as intravascular and intracardiac interventions, may benefit from guidance with forward-looking (FL) ultrasound. In this work, we investigate FL ultrasound imaging using a single-element transducer integrated in a steerable catheter, together with an optical shape sensing (OSS) system. METHODS: We tested the feasibility of the proposed device by imaging the surface of a tissue-mimicking (TM) phantom and an ex vivo human carotid plaque. While manually steering the catheter tip, ultrasound A-lines are acquired at 60 Hz together with the catheter shape from the OSS system, resulting in a two-dimensional sparse and irregularly sampled data set. We implemented an adaptive Normalized Convolution (NC) algorithm to interpolate the sparse data set by applying an anisotropic Gaussian kernel that is rotated according to the local direction of the catheter scanning pattern. To choose the Gaussian widths tangential ( ${\sigma _t}$) and normal ( ${\sigma _n}$) to the scanning pattern, an exhaustive search was implemented based on RMSE computation on simulated data. RESULTS: Simulations showed that the sparse data set contains only 5% of the original information. The chosen widths, ${\sigma _n} = \text{250}\;\mu {\textrm{m}}$ and ${\sigma _t} = \text{100}\;\mu{\textrm{m}}$, are used to successfully reconstruct the surface of the phantom with a contrast ratio of 0.9. The same kernel is applied successfully to the carotid plaque data. CONCLUSION: The proposed approach enables FL imaging with a single ultrasound element, mounted on a steerable device. SIGNIFICANCE: This principle may find application in a variety of image-guided interventions, such as chronic total occlusion (CTO) recanalization.

A 2-D Ultrasound Transducer With Front-End ASIC and Low Cable Count for 3-D Forward-Looking Intravascular Imaging: Performance and Characterization.

Intravascular ultrasound (IVUS) is an imaging modality used to visualize atherosclerosis from within the inner lumen of human arteries. Complex lesions like chronic total occlusions require forward-looking IVUS (FL-IVUS), instead of the conventional side-looking geometry. Volumetric imaging can be achieved with 2-D array transducers, which present major challenges in reducing cable count and device integration. In this work, we present an 80-element lead zirconium titanate matrix ultrasound transducer for FL-IVUS imaging with a front-end application-specific integrated circuit (ASIC) requiring only four cables. After investigating optimal transducer designs, we fabricated the matrix transducer consisting of 16 transmit (TX) and 64 receive (RX) elements arranged on top of an ASIC having an outer diameter of 1.5 mm and a central hole of 0.5 mm for a guidewire. We modeled the transducer using finite-element analysis and compared the simulation results to the values obtained through acoustic measurements. The TX elements showed uniform behavior with a center frequency of 14 MHz, a -3-dB bandwidth of 44%, and a transmit sensitivity of 0.4 kPa/V at 6 mm. The RX elements showed center frequency and bandwidth similar to the TX elements, with an estimated receive sensitivity of /Pa. We successfully acquired a 3-D FL image of three spherical reflectors in water using delay-and-sum beamforming and the coherence factor method. Full synthetic-aperture acquisition can be achieved with frame rates on the order of 100 Hz. The acoustic characterization and the initial imaging results show the potential of the proposed transducer to achieve 3-D FL-IVUS imaging.

Improving the Performance of a 1-D Ultrasound Transducer Array by Subdicing.

In medical ultrasound transducer design, the geometry of the individual elements is crucial since it affects the vibration mode of each element and its radiation impedance. For a fixed frequency, optimal vibration (i.e., uniform surface motion) can be achieved by designing elements with very small width-to-thickness ratios. However, for optimal radiation impedance (i.e., highest radiated power), the width should be as large as possible. This leads to a contradiction that can be solved by subdicing wide elements. To systematically examine the effect of subdicing on the performance of a 1-D ultrasound transducer array, we applied finite-element simulations. We investigated the influence of subdicing on the radiation impedance, on the time and frequency response, and on the directivity of linear arrays with variable element widths. We also studied the effect of varying the depth of the subdicing cut. The results show that, for elements having a width greater than 0.6 times the wavelength, subdicing improves the performance compared with that of nonsubdiced elements: the emitted pressure may be increased up to a factor of three, the ringing time may be reduced by up to 50%, the bandwidth increased by up to 77%, and the sidelobes reduced by up to 13 dB. Moreover, this simulation study shows that all these improvements can already be achieved by subdicing the elements to a depth of 70% of the total element thickness. Thus, subdicing can improve important transducer parameters and, therefore, help in achieving images with improved signal-to-noise ratio and improved resolution.