Brooks D. Lindsey

Percutaneous coronary intervention (PCI) treats myocardial ischemia by stenting stenotic coronary arteries. Wall shear stress (WSS) is an established indicator of plaque rupture risk and restenosis likelihood, yet is not currently used to guide stenting. To address this gap, we developed a forward-viewing intravascular ultrasound array and demonstrated 3D hemodynamic imaging in coronary artery phantoms. A 3 mm, 172 element forward-viewing 2D array was designed, simulated, and fabricated. Field II was used to simulate aperture performance, and finite element modeling was conducted to investigate element geometry effects on vibrational modes. The array was characterized electrically and acoustically, then used to acquire 3D color flow images in coronary artery-mimicking phantoms using plane wave compounding, SVD-based wall filtering, transverse oscillation velocity estimation, and Fourier sine series WSS estimation. The fabricated array achieved a center frequency of 31 MHz, a -6 dB bandwidth of 60%, and a single-element SNR of 20 ± 1 dB, with 164 of 172 elements operational. Lateral and axial resolutions of 170 μm and 150 μm, respectively, were measured at a depth of 5 mm. Peak velocities of 1 cm/s and 2.6 cm/s were measured in straight and stenotic phantoms, and WSS was derived from these 3D images. 3D finite element modeling provided new insights into element geometry effects on vibrational modes for IVUS 2D arrays, enabling a 31 MHz center frequency, 60% bandwidth, and 95% yield. This work represents the first demonstration of 3D imaging of WSS using a forward-viewing IVUS 2D array, a step toward IVUS-based hemodynamic guidance.

Percutaneous coronary intervention (PCI) is a common minimally-invasive procedure for treating coronary artery stenosis. However, 10% of patients with non-complex lesions experience restenosis within five years of initial PCI. Wall shear stress (WSS) is a physiological marker that provides additional predictive value for restenosis. The ability to estimate WSS during PCI could identify patients at high risk for restenosis. In order to assess the accuracy of intravascular ultrasound WSS imaging in coronary geometries, a high-frequency linear array was used to image three unique coronary phantom geometries before stenting and with partially- and fully-expanded stents. Acquired 2D WSS images were registered and compared with 3D in silico results. Finally, 3D images were acquired in a single geometry using a newly-developed intravascular ultrasound matrix array. Ultrasound-derived flow velocity maps demonstrated a mean absolute percentage error of 13.04 ± 4.82% relative to simulations, with a mean correlation of 81.91 ± 14.59%. Segments with partially-expanded stents exhibited decreased mean WSS (0.0800 ± 0.0233 Pa vs. 0.1328 ± 0.0265 Pa, p = 0.0479) and increased WSS spatial variance (0.0038 ± 0.0011 Pa ² vs. 0.00069 ± 0.000090 Pa ² , p = 0.0546) compared to segments with fully expanded stents. Accurate WSS imaging during PCI could stratify restenosis risk and inform long-term coronary modeling (i.e. digital twin system).

Coronary artery disease (CAD) is the third leading cause of disability and death globally. Intravascular ultrasound (IVUS) is the most commonly used imaging modality for the characterization of vulnerable plaques. The development of novel intravascular imaging and therapy devices requires dedicated open systems (e.g., for pulse sequences for imaging or thrombolysis), which are not currently available. This paper presents the development of a novel multifunctional FPGA-based pulser/receiver system for intravascular ultrasound imaging and therapy research. The open platform consists of a host PC with a Matlab-based software interface, an FPGA board, and a proprietary analog front-end board with state-of-the-art electronics for highly flexible transmission and reception schemes. The main features of the system include the capability to convert arbitrary waveforms into tristate bipolar pulses by using the PWM technique and by the direct acquisition of raw radiofrequency (RF) echo data. The results of a multicycle excitation pulse applied to a custom 550 kHz therapy transducer for acoustic characterization and a pulse-echo experiment conducted with a high-voltage, short-pulse excitation for a 19.48 MHz transducer are reported. Testing results show that the proposed system can be easily controlled to match the frequency and bandwidth required for different IVUS transducers across a broad class of applications.

Objective: We present the first multimodal deep learning framework combining ultrasound (US) and electrocardiography (ECG) data to predict cardiac quiescent periods (QPs) for optimized computed tomography angiography gating (CTA). Methods: The framework integrates a 3D convolutional neural network (CNN) for US data and an artificial neural network (ANN) for ECG data. A dynamic heart motion phantom, replicating diverse cardiac conditions, including arrhythmias, was used to validate the framework. Performance was assessed across varying QP lengths, cardiac segments, and motions to simulate real-world conditions. Results: The multimodal US-ECG 3D CNN-ANN framework demonstrated improved QP prediction accuracy compared to single-modality ECG-only gating, achieving 96.87% accuracy compared to 85.56%, including scenarios involving arrhythmic conditions. Notably, the framework shows higher accuracy for longer QP durations (100 ms - 200 ms) compared to shorter durations (<100 ms), while still outperforming single-modality methods, which often fail to detect shorter quiescent phases, especially in arrhythmic cases. Consistently outperforming single-modality approaches, it achieves reliable QP prediction across cardiac regions, including the whole phantom, interventricular septum, and cardiac wall regions. Analysis of QP prediction accuracy across cardiac segments demonstrated an average accuracy of 92% in clinically relevant echocardiographic views, highlighting the framework's robustness. Conclusion: Combining US and ECG data using a multimodal framework improves QP prediction accuracy under variable cardiac motion, particularly in arrhythmic conditions. Significance: Since even small errors in cardiac CTA can result in non-diagnostic scans, the potential benefits of multimodal gating may improve diagnostic scan rates in patients with high and variable heart rates and arrhythmias.

Large vessel occlusion (LVO) stroke, in which major cerebral arteries such as the internal carotid and middle cerebral arteries supplying the brain are occluded, is the most debilitating form of acute ischemic stroke (AIS). The current gold standard treatment for LVO stroke is mechanical thrombectomy, however, initial attempts to recanalize these large, proximal arteries supplying the brain fail in up to 75% of cases, leading to repeated passes that decrease the likelihood of success and affect patient outcomes. We report the design, fabrication, and testing of a 3 mm × 3 mm forward-treating US transducer with an acoustic metamaterial lens to dissolve blood clots recalcitrant to first pass mechanical thrombectomy in LVO stroke. Due to the lens with microscale features, the device was able to produce a 2.3× increase in peak negative pressure (4.3 MPa vs 1.8 MPa) and 2.4× increase in blood clot dissolution rate (5.43 ± 0.89 mg/min vs 2.23 ± 0.41 mg/min) with 90% mass reduction after 30 minutes of treatment. In this small endovascular form factor, the acoustic metamaterial lens increased the acoustic output from the transducer while minimizing the US energy delivered to the surrounding areas outside of the treatment volume.

Purpose The Wall Shear Stress (WSS) is the component tangential to the boundary of the normal stress tensor in an incompressible fluid, and it has been recognized as a quantity of primary importance in predicting possible adverse events in cardiovascular diseases, in general, and in coronary diseases, in particular. The quantification of the WSS in patient-specific settings can be achieved by performing a Computational Fluid Dynamics (CFD) analysis based on patient geometry, or it can be retrieved by a numerical approximation based on blood flow velocity data, e.g., ultrasound (US) Doppler measurements. This paper presents a novel method for WSS quantification from 2D vector Doppler measurements. Methods Images were obtained through unfocused plane waves and transverse oscillation to acquire both in-plane velocity components. These velocity components were processed using pseudo-spectral differentiation techniques based on Fourier approximations of the derivatives to compute the WSS. Results Our Pseudo-Spectral Method (PSM) is tested in two vessel phantoms, straight and stenotic, where a steady flow of 15 mL/min is applied. The method is successfully validated against CFD simulations and compared against current techniques based on the assumption of a parabolic velocity profile. The PSM accurately detected Wall Shear Stress (WSS) variations in geometries differing from straight cylinders, and is less sensitive to measurement noise. In particular, when using synthetic data (noise free, e.g., generated by CFD) on cylindrical geometries, the Poiseuille-based methods and PSM have comparable accuracy; on the contrary, when using the data retrieved from US measures, the average error of the WSS obtained with the PSM turned out to be 3 to 9 times smaller than that obtained by state-of-the-art methods. Conclusion The pseudo-spectral approach allows controlling the approximation errors in the presence of noisy data. This gives a more accurate alternative to the present standard and a less computationally expensive choice compared to CFD, which also requires high-quality data to reconstruct the vessel geometry.

Coronary artery disease (CAD) is one of the leading causes of death globally. Currently, diagnosis and intervention in CAD are typically performed via minimally-invasive cardiac catheterization procedures. Using current diagnostic technology such as angiography and FFR, interventional cardiologists must decide which patients require intervention and which can be deferred. 10% of patients with stable CAD are incorrectly deferred using current diagnostic best practices. By developing a forward-viewing intravascular ultrasound (FV-IVUS) 2D array capable of simultaneously evaluating morphology, hemodynamics, and plaque composition, physicians would be better able to stratify risk of major adverse cardiac events in patients with intermediate stenosis. For this application, a forward-viewing, 16 MHz 2D array transducer was designed and fabricated. A 2 mm-diameter aperture consisting of 140 elements, with element dimensions of 98 μm × 98 μm × 70 μm (w × h × t) and a nominal inter-element spacing of 120 μm was designed for this application based on simulations. The acoustic stack for this array was developed with a designed center frequency of 16 MHz. A novel via-less interconnect was developed to enable electrical connections to fan out from a 140-element 2D array with 120 μm inter-element spacing. The fabricated array transducer had 96/140 functioning elements operating at a center frequency of 16 MHz with a -6 dB fractional bandwidth of 62 ± 7%. Single element SNR was 23 ± 3 dB, and the measured electrical crosstalk was -33 ± 3 dB. In imaging experiments, the measured lateral resolution was 0.231 mm and the measured axial resolution was 0.244 mm at a depth of 5 mm. Finally, the transducer was used to perform 3D B-mode imaging of a 3 mm-diameter spring and 3D B-mode and power Doppler imaging of a tissue-mimicking phantom.

Purpose Wall shear stress (WSS) is a critically important physical factor contributing to atherosclerosis. Mapping the spatial distribution of local, oscillatory WSS can identify important mechanisms underlying the progression of coronary artery disease. Methods In this study, blood flow velocity and time-varying WSS were estimated in the left anterior descending (LAD) coronary artery of an ex vivo beating porcine heart using ultrasound with an 18 MHz linear array transducer aligned with the LAD in a forward-viewing orientation. A pulsatile heart loop with physiologically-accurate flow was created using a pulsatile pump. The coronary artery wall motion was compensated using a local block matching technique. Next, 2D and 3D velocity magnitude and WSS maps in the LAD coronary artery were estimated at different time points in the cardiac cycle using an ultrafast Doppler approach. The blood flow velocity estimated using the presented approach was compared with a commercially-available, calibrated single element blood flow velocity measurement system. Results The resulting root mean square error (RMSE) of 2D velocity magnitude acquired from a high frequency, linear array transducer was less than 8% of the maximum velocity estimated by the commercial system. Conclusion When implemented in a forward-viewing intravascular ultrasound device, the presented approach will enable dynamic estimation of WSS, an indicator of plaque vulnerability in coronary arteries.

A novel transverse velocity spectral estimation method is proposed to estimate the velocity component in the direction transverse to the beam axis for ultrafast imaging. The transverse oscillation was introduced by filtering the envelope data after the axial oscillation was removed. The complex transverse oscillated signal was then used to estimate the transverse velocity spectrum and mean velocity. In simulations, both steady flow with a parabolic flow profile and temporally-varying flow were simulated to investigate the performance of the proposed method. Next, the proposed approach was used to estimate the flow velocity in a phantom with pulsatile flow, and finally this method was applied in vivo in a small animal model. Results of the simulation study indicate that the proposed method provided an accurate velocity spectrogram for beam-to-flow angles from 45° to 90°, without significant performance degradation as the angle decreased. For the simulation of temporally-varying flow, the proposed method had a reduced bias (< -11.7% vs. 73.3%) and higher peak-to-background ratio (> 15.6 dB vs. 10.5 dB) compared to previous methods. Results in a vessel phantom show that the temporally-varying flow velocity can be estimated in the transverse direction obtained using the spectrogram produced by the proposed method operating on the envelope data. Finally, the proposed method was used to map the microvascular blood flow velocity in the mouse spinal cord, demonstrating estimation of pulsatile blood flow in both the axial and transverse directions in vivo over several cardiac cycles.