Magnetic Resonance Thermometry Targeting for Magnetic Resonance-Guided Histotripsy Treatments.

OBJECTIVE: The potential of transcranial magnetic resonance (MR)-guided histotripsy for brain applications has been described in prior in vivo studies in the swine brain through an excised human skull. The safety and accuracy of transcranial MR-guided histotripsy (tcMRgHt) rely on pre-treatment targeting guidance. In the work described here, we investigated the feasibility and accuracy of using ultrasound-induced low-temperature heating and MR thermometry for histotripsy pre-treatment targeting in ex vivo bovine brain. METHODS: A 15-element, 750-kHz MRI-compatible ultrasound transducer with modified drivers that can deliver both low-temperature heating and histotripsy acoustic pulses was used to treat seven bovine brain samples. The samples were first heated to an approximately 1.6°C temperature increase at the focus, and MR thermometry was used to localize the target. Once the targeting was confirmed, a histotripsy lesion was generated at the focus and visualized on post-histotripsy MR images. DISCUSSION: The accuracy of MR thermometry targeting was evaluated with the mean/standard deviation of the difference between the locus of peak heating identified by MR thermometry and the center of mass of the post-treatment histotripsy lesion, which was 0.59/0.31 mm and 1.31/0.93 mm in the transverse and longitudinal directions, respectively. CONCLUSION: This study determined that MR thermometry could provide reliable pre-treatment targeting for transcranial MR-guided histotripsy treatment.

Effects of phase aberration on transabdominal focusing for a large aperture, lowf-number histotripsy transducer.

Objective. Soft tissue phase aberration may be particularly severe for histotripsy due to large aperture and lowf-number transducer geometries. This study investigated how phase aberration from human abdominal tissue affects focusing of a large, strongly curved histotripsy transducer.Approach.A computational model (k-Wave) was experimentally validated withex vivoporcine abdominal tissue and used to simulate focusing a histotripsy transducer (radius: 14.2 cm,f-number: 0.62, central frequencyfc: 750 kHz) through the human abdomen. Abdominal computed tomography images from 10 human subjects were segmented to create three-dimensional acoustic property maps. Simulations were performed focusing at 3 target locations in the liver of each subject with ideal phase correction, without phase correction, and after separately matching the sound speed of water and fat to non-fat soft tissue.Main results.Experimental validation in porcine abdominal tissue showed that simulated and measured arrival time differences agreed well (average error, ∼0.10 acoustic cycles atfc). In simulations with human tissue, aberration created arrival time differences of 0.65µs (∼0.5 cycles) at the target and shifted the focus from the target by 6.8 mm (6.4 mm pre-focally along depth direction), on average. Ideal phase correction increased maximum pressure amplitude by 95%, on average. Matching the sound speed of water and fat to non-fat soft tissue decreased the average pre-focal shift by 3.6 and 0.5 mm and increased pressure amplitude by 2% and 69%, respectively.Significance.Soft tissue phase aberration of large aperture, lowf-number histotripsy transducers is substantial despite low therapeutic frequencies. Phase correction could potentially recover substantial pressure amplitude for transabdominal histotripsy. Additionally, different heterogeneity sources distinctly affect focusing quality. The water path strongly affects the focal shift, while irregular tissue boundaries (e.g. fat) dominate pressure loss.

Transcranial Magnetic Resonance-Guided Histotripsy for Brain Surgery: Pre-clinical Investigation.

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.

Transcranial MR-Guided Histotripsy System.

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.

Generation of Synthetic CT Images From MRI for Treatment Planning and Patient Positioning Using a 3-Channel U-Net Trained on Sagittal Images.

A novel deep learning architecture was explored to create synthetic CT (MRCT) images that preserve soft tissue contrast necessary for support of patient positioning in Radiation therapy. A U-Net architecture was applied to learn the correspondence between input T1-weighted MRI and spatially aligned corresponding CT images. The network was trained on sagittal images, taking advantage of the left-right symmetry of the brain to increase the amount of training data for similar anatomic positions. The output CT images were divided into three channels, representing Hounsfield Unit (HU) ranges of voxels containing air, soft tissue, and bone, respectively, and simultaneously trained using a combined Mean Absolute Error (MAE) and Mean Squared Error (MSE) loss function equally weighted for each channel. Training on 9192 image pairs yielded resulting synthetic CT images on 13 test patients with MAE of 17.6+/-3.4 HU (range 14-26.5 HU) in soft tissue. Varying the amount of training data demonstrated a general decrease in MAE values with more data, with the lack of a plateau indicating that additional training data could further improve correspondence between MRCT and CT tissue intensities. Treatment plans optimized on MRCT-derived density grids using this network for 7 radiosurgical targets had doses recalculated using the corresponding CT-derived density grids, yielding a systematic mean target dose difference of 2.3% due to the lack of the immobilization mask on the MRCT images, and a standard deviation of 0.1%, indicating the consistency of this correctable difference. Alignment of MRCT and cone beam CT (CBCT) images used for patient positioning demonstrated excellent preservation of dominant soft tissue features, and alignment comparisons of treatment planning CT scans to CBCT images vs. MRCT to CBCT alignment demonstrated differences of -0.1 (σ 0.2) mm, -0.1 (σ 0.3) mm, and -0.2 (σ 0.3) mm about the left-right, anterior-posterior and cranial-caudal axes, respectively.