Ning Lu

Ning Lu

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publications

Transcranial MR-Guided Histotripsy System

Published in IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control (Front Cover Article), 2021

Abstract: Histotripsy has been previously shown to treat a wide range of locations through excised human skulls in vitro. In this article, a transcranial magnetic resonance (MR)-guided histotripsy (tcMRgHt) system was developed, characterized, and tested in the in vivo pig brain through an excised human skull. A 700-kHz, 128-element MR-compatible phased-array ultrasound transducer with a focal depth of 15 cm was designed and fabricated in-house. Support structures were also constructed to facilitate transcranial treatment. The tcMRgHt array was acoustically characterized with a peak negative pressure up to 137 MPa in free field, 72 MPa through an excised human skull with aberration correction, and 48.4 MPa without aberration correction. The electronic focal steering range through the skull was 33.5 mm laterally and 50 mm axially, where a peak negative pressure above the 26-MPa cavitation intrinsic threshold can be achieved. The MR compatibility of the tcMRgHt system was assessed quantitatively using SNR, B0 field map, and B1 field map in a clinical 3T magnetic resonance imaging (MRI) scanner. Transcranial treatment using electronic focal steering was validated in red blood cell phantoms and in vivo pig brain through an excised human skull. In two pigs, targeted cerebral tissue was successfully treated through the human skull as confirmed by MRI. Excessive bleeding or edema was not observed in the peri-target zones by the time of pig euthanasia. These results demonstrated the feasibility of using this preclinical tcMRgHt system for in vivo transcranial treatment in a swine model.

Recommended citation: N. Lu, et al (2021). "Transcranial MR-Guided Histotripsy System." IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control. 68(9).
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Transcranial magnetic resonance-guided histotripsy for brain surgery: pre-clinical investigation

Published in Ultrasound in medicine & biology, 2022

Abstract: Histotripsy has been previously applied to target various cranial locations in vitro through an excised human skull. Recently, a transcranial magnetic resonance (MR)-guided histotripsy (tcMRgHt) system was developed, enabling pre-clinical investigations of tcMRgHt for brain surgery. To determine the feasibility of in vivo transcranial histotripsy, tcMRgHt treatment was delivered to eight pigs using a 700-kHz, 128-element, MR-compatible phased-array transducer inside a 3-T magnetic resonance imaging (MRI) scanner. After craniotomy to open an acoustic window to the brain, histotripsy was applied through an excised human calvarium to target the inside of the pig brain based on pre-treatment MRI and fiducial markers. MR images were acquired pre-treatment, immediately post-treatment and 2–4 h post-treatment to evaluate the acute treatment outcome. Successful histotripsy ablation was observed in all pigs. The MR-evident lesions were well confined within the targeted volume, without evidence of excessive brain edema or hemorrhage outside of the target zone. Histology revealed tissue homogenization in the ablation zones with a sharp demarcation between destroyed and unaffected tissue, which correlated well with the radiographic treatment zones on MRI. These results are the first to support the in vivo feasibility of tcMRgHt in the pig brain, enabling further investigation of the use of tcMRgHt for brain surgery.

Recommended citation: N. Lu, et al. (2022). "Transcranial magnetic resonance-guided histotripsy for brain surgery: pre-clinical investigation." Ultrasound in medicine & biology. 48(1).
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Two-step aberration correction: application to transcranial histotripsy

Published in Physics in Medicine & Biology, 2022

Abstract: Objective: Phase aberration correction is essential in transcranial histotripsy to compensate for focal distortion caused by the heterogeneity of the intact skull bone. This paper improves the 2-step aberration correction (AC) method that has been previously presented and develops an AC workflow that fits in the clinical environment, in which the computed tomography (CT)-based analytical approach was first implemented, followed by a cavitation-based approach using the shockwaves from the acoustic cavitation emission (ACE). Approach: A 700 kHz, 360-element hemispherical transducer array capable of transmit-and-receive on all channels was used to transcranially generate histotripsy-induced cavitation and acquire ACE shockwaves. For CT-AC, two ray-tracing models were investigated: a forward ray-tracing model (transducer-to-focus) in the open-source software Kranion, and an in-house backward ray-tracing model (focus-to-transducer) accounting for refraction and the sound speed variation in skulls. Co-registration was achieved by aligning the skull CT data to the skull surface map reconstructed using the acoustic pulse-echo method. For ACE-AC, the ACE signals from the collapses of generated bubbles were aligned by cross-correlation to estimate the corresponding time delays. Main results: The performance of the 2-step method was tested with 3 excised human calvariums placed at 2 different locations in the transducer array. Results showed that the 2-step AC achieved 90 ± 7% peak focal pressure compared to the gold standard hydrophone correction. It also reduced the focal shift from 0.84 to 0.30 mm and the focal volume from 10.6 to 2.0 mm3 on average compared to the no AC cases. Significance: The 2-step AC yielded better refocusing compared to either CT-AC or ACE-AC alone and can be implemented in real-time for transcranial histotripsy brain therapy.

Recommended citation: N. Lu, et al. (2022). "Two-step aberration correction: application to transcranial histotripsy." Physics in Medicine & Biology. 67(12).
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Accurate and Robust Eye Tracking with Ultrasound: A Computational Study

Published in 2023 IEEE International Ultrasonics Symposium (IUS), 2023

Abstract: This paper introduces an ultrasound simulation platform for generating realistic eye-tracking data, accounting for transducer design, sensor noise, occlusions, and headset slippage. Using a face/eye model with adjustable gaze and eyelid opening, synthesized data were input into a machine learning algorithm to estimate gaze and slippage. The system achieved a gaze RMSE of 0.085° without slippage and 0.756° with slippage. This end-to-end pipeline supports the optimization of wearable ultrasound devices and explores ultrasound as a complementary technology to camera-based eye tracking for AR/VR applications.

Recommended citation: N. Lu, et al. (2023). "Accurate and Robust Eye Tracking with Ultrasound: A Computational Study." 2023 IEEE International Ultrasonics Symposium (IUS) Proceedings.
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Treatment envelope of transcranial histotripsy: challenges and strategies to maximize the treatment location profile

Published in Physics in Medicine & Biology, 2024

Abstract: A 750 kHz, 360-element ultrasound array has been built for transcranial histotripsy applications. This study aims to evaluate its performance to determine whether this array is adequate for treating a wide range of brain locations through a human skull. Treatment location profiles in 2 excised human skulls were experimentally characterized based on passive cavitation mapping. Full-wave acoustic simulations were performed in 8 human skulls to analyze the ultrasound propagation at shallow targets in skulls with different properties. Results showed that histotripsy successfully generated cavitation from deep to shallow targets within 5 mm from the skull surface in the skull with high SDR and small thickness, whereas in the skull with low SDR and large thickness, the treatment envelope was limited up to 16 mm from the skull surface. Simulation results demonstrated that the treatment envelope was highly dependent on the skull acoustic properties. Pre-focal pressure hotspots were observed in both simulation and experiments when targeting near the skull. For each skull, the acoustic pressure loss increases significantly for shallow targets compared to central targets due to high attenuation, large incident angles, and pre-focal pressure hotspots. Strategies including array design optimization, pose optimization, and amplitude correction, are proposed to broaden the treatment envelope. This study identifies the capabilities and limitations of the 360-element transcranial histotripsy array and suggests strategies for designing the next-generation transcranial histotripsy array to expand the treatment location profile for a future clinical trial.

Recommended citation: N. Lu, et al. (2024). "Treatment envelope of transcranial histotripsy: challenges and strategies to maximize the treatment location profile." Physics in Medicine & Biology. 69(22).
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Improving real-time ultrasound spine imaging with a large-aperture array

Published in Science Advances, 2025

Abstract: Ultrasound offers a safe, low-cost alternative to computed tomography (CT) and magnetic resonance imaging for spinal diagnostics and intervention by enabling real-time imaging. However, the complex structure of the spine and acoustic shadowing from bones present challenges for ultrasonography. This study addresses these limitations using an 8.8-centimeter 384-element large-aperture array and full aperture-based imaging protocols. Volumetric scanning across multiple vertebrae was accomplished in 5 seconds using ultrafast, diverging wave acquisition. In seven healthy volunteers, the large-aperture array and diverging wave transmission improved resolution, contrast, and visualization of the spinal canal, venous plexuses, and facet joints compared with conventional probes. A comparison between the coregistered CT and ultrasound scan confirmed the imaging accuracy. A simulated lumbar puncture demonstrated needle tip visualization throughout the trajectory into the spinal canal. The results suggest that large-aperture arrays, coupled with diverging wave imaging sequences, are a valuable tool for spine imaging and image-guided intervention.

Recommended citation: N. Lu, et al. (2025). "Improving real-time ultrasound spine imaging with a large-aperture array." Sci. Adv.. 11,eadw2601.
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talks

teaching

Guest Lecturer: 3D+ Imaging Sensors

EE 119/219 (undergraduate & graduate course), Stanford University, Department of Electrical Engineering, 2024

Lecture Preview

This lecture will introduce students to state-of-the-art topics in the field of ultrasound imaging. We will start with brief reviews of the ultrasound fundamentals, and then move on to discuss the hardware (transducer, array, and system), imaging sequences, and beamforming methods. We will conclude by discussing the real-world challenges, emerging applications, and advanced ultrasound techniques including ultrafast imaging, super-resolution imaging, aberration correction, etc. Live demo and hands-on experience using a commercial ultrasound system will be provided to the students. If time permits, we’ll also introduce ultrasound simulation software which can be helpful for students who are interested in ultrasound-related projects.