Yexian Qin

Four-dimensional ultrasound current source density imaging of a dipole field.

Ultrasound current source density imaging (UCSDI) potentially transforms conventional electrical mapping of excitable organs, such as the brain and heart. For this study, we demonstrate volume imaging of a time-varying current field by scanning a focused ultrasound beam and detecting the acoustoelectric (AE) interaction signal. A pair of electrodes produced an alternating current distribution in a special imaging chamber filled with a 0.9% NaCl solution. A pulsed 1 MHz ultrasound beam was scanned near the source and sink, while the AE signal was detected on remote recording electrodes, resulting in time-lapsed volume movies of the alternating current distribution.

Optimizing frequency and pulse shape for ultrasound current source density imaging

Electric field mapping is commonly used to identify irregular conduction pathways in the heart (e.g., arrhythmia) and brain (e.g., epilepsy). A new technique, ultrasound current source density imaging (UCSDI) based on the acoustoelectric (AE) effect, provides an alternative method for current activity mapping in four-dimension with high resolution. The ultrasound transducer frequency and pulse shape significantly affect the sensitivity and spatial resolution of UCSDI. In this paper, we analyze the tradeoff between spatial resolution and sensitivity in UCSDI from two aspects: (1) ultrasound transducer frequency and (2) coded excitation pulses. For frequency dependence, we imaged an electric dipole using ultrasound transducers with different center frequencies (1 MHz and 2.25 MHz) and compared the sensitivity and resolution. For coded excitation, we measured AE signals with chirp excitation at 1 MHz and demonstrated improved sensitivity for chirps (3.5 μV/mA at 1 MHz) compared with square pulse excitation (1.6 μV/mA). Pulse compression was also applied to preserve spatial resolution, demonstrating enhanced detection while preserving spatial resolution.

An electrically coupled tissue-engineered cardiomyocyte scaffold improves cardiac function in rats with chronic heart failure

BACKGROUND Varying strategies are currently being evaluated to develop tissue-engineered constructs for the treatment of ischemic heart disease. This study examines an angiogenic and biodegradable cardiac construct seeded with neonatal cardiomyocytes for the treatment of chronic heart failure (CHF). METHODS We evaluated a neonatal cardiomyocyte (NCM)-seeded 3-dimensional fibroblast construct (3DFC) in vitro for the presence of functional gap junctions and the potential of the NCM-3DFC to restore left ventricular (LV) function in an in vivo rat model of CHF at 3 weeks after permanent left coronary artery ligation. RESULTS The NCM-3DFC demonstrated extensive cell-to-cell connectivity after dye injection. At 5 days in culture, the patch contracted spontaneously in a rhythmic and directional fashion at 43 ± 3 beats/min, with a mean displacement of 1.3 ± 0.3 mm and contraction velocity of 0.8 ± 0.2 mm/sec. The seeded patch could be electrically paced at nearly physiologic rates (270 ± 30 beats/min) while maintaining coordinated, directional contractions. Three weeks after implantation, the NCM-3DFC improved LV function by increasing (p < 0.05) ejection fraction 26%, cardiac index 33%, dP/dt(+) 25%, dP/dt(-) 23%, and peak developed pressure 30%, while decreasing (p < 0.05) LV end diastolic pressure 38% and the time constant of relaxation (Tau) 16%. At 18 weeks after implantation, the NCM-3DFC improved LV function by increasing (p < 0.05) ejection fraction 54%, mean arterial pressure 20%, dP/dt(+) 16%, dP/dt(-) 34%, and peak developed pressure 39%. CONCLUSIONS This study demonstrates that a multicellular, electromechanically organized cardiomyocyte scaffold, constructed in vitro by seeding NCM onto 3DFC, can improve LV function long-term when implanted in rats with CHF.

Ultrasound Current Source Density Imaging of the Cardiac Activation Wave Using a Clinical Cardiac Catheter

Ultrasound current source density imaging (UCSDI), based on the acoustoelectric (AE) effect, is a noninvasive method for mapping electrical current in 4-D (space + time). This technique potentially overcomes limitations with conventional electrical mapping procedures typically used during treatment of sustained arrhythmias. However, the weak AE signal associated with the electrocardiogram is a major challenge for advancing this technology. In this study, we examined the effects of the electrode configuration and ultrasound frequency on the magnitude of the AE signal and quality of UCSDI using a rabbit Langendorff heart preparation. The AE signal was much stronger at 0.5 MHz (2.99 μV/MPa) than 1.0 MHz (0.42 μV/MPa). Also, a clinical lasso catheter placed on the epicardium exhibited excellent sensitivity without penetrating the tissue. We also present, for the first time, 3-D cardiac activation maps of the live rabbit heart using only one pair of recording electrodes. Activation maps were used to calculate the cardiac conduction velocity for atrial (1.31 m/s) and apical (0.67 m/s) pacing. This study demonstrated that UCSDI is potentially capable of realtime 3-D cardiac activation wave mapping, which would greatly facilitate ablation procedures for treatment of arrhythmias.

Quality Improvement of Thermoacoustic Imaging Based on Compressive Sensing

Thermoacoustic imaging (TAI) is a non-ionizing, high-contrast and high-resolution modality for biomedical applications. The resolution of the reconstructed image by traditional imaging algorithm, such as back-projection (BP), is dependent on the input microwave pulse width. In this work, it is experimentally demonstrated that the quality of images reconstructed based on compressive sensing (CS), a novel imaging algorithm that can reconstruct images using fewer measurements, is largely independent on the microwave pulse width which is taken into account when building the dictionary. Quantitative analysis reveals that the peak signal to noise ratio of the reconstructed images based on CS is at least 6 dB higher than those via BP, and the correlation coefficients of the images based on CS show higher correlation than those via BP.

Experimental Validation of a Numerical Model for Thermoacoustic Imaging Applications

Owing to its intrinsic advantages of favorable contrast and spatial resolution, microwave-induced thermoacoustic imaging (TAI) has drawn great attention in biomedical imaging applications, such as breast cancer detection. Many experimental studies have demonstrated the promising potential of TAI. Several TAI modeling studies have also been published that facilitate the design and optimization of TAI systems. However, experimental validation of the modeling results is rarely seen; thus it is highly desirable to prove the effectiveness of the modeling approach. In this letter, the TAI modeling approach previously described by our group is validated by experiments. A three-dimensional printed polymer slab with featured structures is used as the sample to be investigated by both the model and the experiment. Images are obtained to reveal the featured structures in the slab from both the modeling and experimental results. Rigorous comparisons between the modeling and experimental imaging results are carried out. The achieved good agreement between the images corroborates the validity of the TAI modeling approach and thereby encourages more applications of it.

4D acoustoelectric imaging of current sources in a human head phantom

Electrical brain mapping typically suffers from poor spatial resolution due to the uncertain spread of electric field lines through the brain and skull. To overcome this limitation, we propose 4D acoustoelectric brain imaging (ABI) for mapping current densities at a spatial resolution confined to the ultra-sound (US) focal spot. Acoustoelectric (AE) imaging exploits an interaction between a pressure wave and tissue resistivity. It has been used to dynamically map the cardiac activation wave in the live rabbit heart. Our long-term goal is to extend this technique for electrical mapping of the human brain. In this study, we developed a human-size head and brain phantom to test and optimize ABI for detecting an embedded “EEG-like” electrical current. Detection thresholds for current sources more than 15 mm below the surface of the brain phantom was less than 1 mA/cm2 using a 0.5-MHz or 1 MHz single element transducer and copper recording wires. Further optimization of ABI could enable detection of small neural currents in the brain and lead to a new modality for functional brain imaging.

Non-contact thermoacoustic imaging based on laser and microwave vibrometry

Microwave-induced thermoacoustic imaging (TAI), which exploits the high resolution of ultrasound imaging and high contrast of microwave imaging, is an emerging modality in medicine. Traditional TAI employs a relatively narrow-band ultrasound transducer to detect TA signals, which requires acoustic coupling and physical contact between the transducer and the sample. In certain applications, physical contact is either undesirable or not feasible. In this paper, we investigate non-contact TAI, employing either a laser or millimeter-wave (W-band) vibrometer, to remotely detect thermoacoustic-induced surface vibrations. The sensitivity of each vibrometer was first evaluated using a 1 MHz ultrasound transducer embedded inside an Agarose™ gel. The detection thresholds for the laser and microwave vibrometers were 0.02 and 1.3 nm, respectively. The sensitivity and bandwidth of the laser vibrometer were sufficient to detect TA signals from a saline gel and produce an image of embedded Rexolite™ samples. The amplitude and frequency of the surface vibrations depended on the thickness of the gel and depth of the sample. Unlike the laser vibrometer, the W-band vibrometer did not require an optically reflective surface, performing well even with a rough surface. The two types of vibrometers, therefore, are complementary and could be especially useful for non-contact applications in medical imaging or characterization of materials in high-water content media.

Mapping the ECG in the live rabbit heart using Ultrasound current source density imaging with coded excitation

Ultrasound current source density imaging (UCSDI) is a noninvasive technique for mapping electric current fields in 4D (space + time) with the resolution of ultrasound imaging. This approach can potentially overcome limitations of conventional electrical mapping procedures often used during treatment of cardiac arrhythmia or epilepsy. However, at physiologic currents, the detected acoustoelectric (AE) interaction signal in tissue is very weak. In this work, we evaluated coded ultrasound excitation (chirps) for improving the sensitivity of UCSDI for mapping the electrocardiogram (ECG) in a live rabbit heart preparation. Results confirmed that chirps improved detection of the AE signal by as much as 6.1 dB compared to a square pulse. We further demonstrated mapping the ECG using a clinical intracardiac catheter, 1 MHz ultrasound transducer and coded excitation. B-mode pulse echo and UCSDI revealed regions of high current flow in the heart wall during the peak of the ECG. These improvements to UCSDI are important steps towards translation of this new technology to the clinic for rapidly mapping the cardiac activation wave.

Performance of a transcranial ultrasound array designed for 4D acoustoelectric brain imaging in humans

Noninvasive electrical brain imaging in humans often suffers from poor spatial resolution due to the uncertain spread of electric fields through the head. To overcome this limitation, we propose 4D transcranial acoustoelectric brain imaging (tABI) for mapping current densities at a spatial resolution confined to the ultrasound (US) focus. Acoustoelectric (AE) imaging exploits an interaction between a pressure wave and tissue resistivity, which was demonstrated for mapping the cardiac activation wave in the rabbit heart. Our goal is to extend this modality for mapping the human brain noninvasively. This study describes the performance of a 2D US array designed for tABI in humans.