A Breast-Specific MR Guided Focused Ultrasound Platform and Treatment Protocol: First-in-Human Technical Evaluation.

OBJECTIVE: This paper presents and evaluates a breast-specific magnetic resonance guided focused ultrasound (MRgFUS) system. A first-in-human evaluation demonstrates the novel hardware, a sophisticated tumor targeting algorithm and a volumetric magnetic resonance imaging (MRI) protocol. METHODS: At the time of submission, N = 10 patients with non-palpable T0 stage breast cancer have been treated with the breast MRgFUS system. The described tumor targeting algorithm is evaluated both with a phantom test and in vivo during the breast MRgFUS treatments. Treatments were planned and monitored using volumetric MR-acoustic radiation force imaging (MR-ARFI) and temperature imaging (MRTI). RESULTS: Successful technical treatments were achieved in 80 % of the patients. All patients underwent the treatment with no sedation and 60 % of participants had analgesic support. The total MR treatment time ranged from 73 to 114 minutes. Mean error between desired and achieved targeting in a phantom was 2.9 ±1.8 mm while 6.2 ±1.9 mm was achieved in patient studies, assessed either with MRTI or MR-ARFI measurements. MRTI and MR-ARFI were successful in 60 % and 70 % of patients, respectively. CONCLUSION: The targeting accuracy allows the accurate placement of the focal spot using electronic steering capabilities of the transducer. The use of both volumetric MRTI and MR-ARFI provides complementary treatment planning and monitoring information during the treatment, allowing the treatment of all breast anatomies, including homogeneously fatty breasts.

Technical Note: Effect of transducer position and ground plane configuration on image quality in MR-guided focused ultrasound therapies.

PURPOSE: To evaluate the effect of a focused ultrasound transducer position and ground plane configuration on magnetic resonance image quality. METHODS: The effect of transducer position with respect to the MRI B0 field and the radiofrequency receive coils was evaluated in a breast-specific MRgFUS system with an integrated RF phased-array coil. Image signal-to-noise ratio was evaluated at different transducer locations. The effect of ultrasound transducer ground plane configuration was evaluated using a replica transducer with 12 ground plane configurations. All evaluations were performed at 3 Tesla. RESULTS: Both transducer position and ground plane configuration were found to have a considerable effect on overall image SNR. A 67% increase in SNR was achieved by positioning the transducer face perpendicular to the B0 field. A 25% increase in SNR was achieved by segmenting the replica transducer ground plane from one continuous plane to nine individual segments. CONCLUSIONS: Advances in focused ultrasound hardware allow for integrated radiofrequency MRI coils as well as adjustable transducer positioning. The placement of the ultrasound transducer with respect to both the magnetic field and RF coils can have a considerable effect on image SNR and the resulting MR images that are used for MR-guided focused ultrasound treatment planning, monitoring and assessment.

Effect of applied energy in renal sympathetic denervation with magnetic resonance guided focused ultrasound in a porcine model.

BACKGROUND: Past catheter-based and focused ultrasound renal denervation studies have indicated that procedure efficacy is related to the number of ablations performed or the amount of energy used for the ablation. This study extends those prior results and investigates energy level effects on the efficacy of MR guided focused ultrasound renal denervation performed in a porcine model. METHODS: Twenty-four normotensive pigs underwent unilateral denervation at three intensity levels. The applied intensity level was retrospectively de-rated to account for variability in animal size. Efficacy was assessed through evaluating the norepinephrine present in the kidney medulla and through histological analysis. The treatment was performed under MRI guidance including pre- and post-procedure T1-weighted and quantitative T1 and T2 imaging. During treatment, the temperature in the near field of the ultrasound beam was monitored in real time with MR temperature imaging. Energy delivery in the regions surrounding the renal artery was independently confirmed through an invasive fiberoptic temperature probe placed in the right renal artery. RESULTS: Animals that underwent denervation at a de-rated acoustic intensity of greater than 1.2 kW/cm2 had a significantly lower norepinephrine concentration in the kidney indicating successful denervation. Images obtained during the treatment indicated no tissue changes in the kidneys as a function of the procedure but there were significant T1 changes present in the right lumbar muscles, although only one animal had indication of muscle damage at the time of necropsy. CONCLUSIONS: While MR guided focused ultrasound renal denervation was found to be safe and effective in this normotensive animal model, the results indicated the need to incorporate patient-specific details in the treatment planning of MRgFUS renal denervation procedure.

Renal sympathetic denervation using MR-guided high-intensity focused ultrasound in a porcine model.

BACKGROUND: Initial catheter-based renal sympathetic denervation (RSD) studies demonstrated promising results in showing a significant reduction of blood pressure, while recent data were less successful. As an alternative approach, the objective of this study was to evaluate the feasibility of using magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) to perform RSD in a porcine model. METHODS: An intravascular fiber optic temperature probe was used to confirm energy delivery during MRgHIFU. This technique was evaluated both in a vascular phantom and in a normotensive pig model. Five animals underwent unilateral RSD using MRgHIFU, and both safety and efficacy were assessed. MRI was used to evaluate the acoustic window, target sonications, monitor the near-field treatment region using MR thermometry imaging, and assess the status of tissues post-procedure. An intravascular fiber optic temperature probe verified energy delivery. Animals were sacrificed 6 to 9 days post-treatment, and pathological analysis was performed. The norepinephrine present in the kidney medulla was assessed post-mortem. RESULTS: All animals tolerated the procedure well with no observed complications. The fiber optic temperature probe placed in the target renal artery confirmed energy delivery during MRgHIFU, measuring larger temperature rises when the MRgHIFU beam location was focused closer to the tip of the probe. Following ablation, a significant reduction (p = 0.04) of cross-sectional area of nerve bundles between the treated and untreated renal arteries was observed in all of the animals with treated nerves presenting increased cellular infiltrate and fibrosis. A reduction of norepinephrine (p = 0.14) in the kidney medulla tissue was also observed. There was no indication of tissue damage in arterial walls. CONCLUSIONS: Performing renal denervation non-invasively with MRgHIFU was shown to be both safe and effective as determined by norepinephrine levels in a porcine model. This approach may be a promising alternative to catheter-based strategies.

Sampling strategies for subsampled segmented EPI PRF thermometry in MR guided high intensity focused ultrasound.

PURPOSE: To investigate k-space subsampling strategies to achieve fast, large field-of-view (FOV) temperature monitoring using segmented echo planar imaging (EPI) proton resonance frequency shift thermometry for MR guided high intensity focused ultrasound (MRgHIFU) applications. METHODS: Five different k-space sampling approaches were investigated, varying sample spacing (equally vs nonequally spaced within the echo train), sampling density (variable sampling density in zero, one, and two dimensions), and utilizing sequential or centric sampling. Three of the schemes utilized sequential sampling with the sampling density varied in zero, one, and two dimensions, to investigate sampling the k-space center more frequently. Two of the schemes utilized centric sampling to acquire the k-space center with a longer echo time for improved phase measurements, and vary the sampling density in zero and two dimensions, respectively. Phantom experiments and a theoretical point spread function analysis were performed to investigate their performance. Variable density sampling in zero and two dimensions was also implemented in a non-EPI GRE pulse sequence for comparison. All subsampled data were reconstructed with a previously described temporally constrained reconstruction (TCR) algorithm. RESULTS: The accuracy of each sampling strategy in measuring the temperature rise in the HIFU focal spot was measured in terms of the root-mean-square-error (RMSE) compared to fully sampled "truth." For the schemes utilizing sequential sampling, the accuracy was found to improve with the dimensionality of the variable density sampling, giving values of 0.65 °C, 0.49 °C, and 0.35 °C for density variation in zero, one, and two dimensions, respectively. The schemes utilizing centric sampling were found to underestimate the temperature rise, with RMSE values of 1.05 °C and 1.31 °C, for variable density sampling in zero and two dimensions, respectively. Similar subsampling schemes with variable density sampling implemented in zero and two dimensions in a non-EPI GRE pulse sequence both resulted in accurate temperature measurements (RMSE of 0.70 °C and 0.63 °C, respectively). With sequential sampling in the described EPI implementation, temperature monitoring over a 192×144×135 mm3 FOV with a temporal resolution of 3.6 s was achieved, while keeping the RMSE compared to fully sampled "truth" below 0.35 °C. CONCLUSIONS: When segmented EPI readouts are used in conjunction with k-space subsampling for MR thermometry applications, sampling schemes with sequential sampling, with or without variable density sampling, obtain accurate phase and temperature measurements when using a TCR reconstruction algorithm. Improved temperature measurement accuracy can be achieved with variable density sampling. Centric sampling leads to phase bias, resulting in temperature underestimations.

Reducing morphological variability of the cervical carotid artery in serial magnetic resonance imaging using a head and neck immobilization device.

PURPOSE: To evaluate how well a head and neck immobilization device performed in reducing lumen morphology variability in repeated MR imaging of the carotid artery. MATERIALS AND METHODS: Quantitative measures of lumen and plaque characteristics may be important for longitudinal management of carotid atherosclerotic disease. However, quantitative measurements of the carotid artery are limited by their dependence on patient positioning, which can be quite variable. We created a head and neck immobilization device to reduce the variability of patient positioning during MR imaging of the carotid artery. In this article we describe the design and use of the immobilization device and assess how well its use reduced variability in vascular orientation and measurements of the carotid lumen cross-sectional area. Evaluation was based on 15 subjects who were repeatedly imaged without the immobilization device and 14 subjects who were repeatedly imaged with the device. RESULTS: Use of the immobilization device decreased the orientation variability from 9.1 degrees to 5.3 degrees (P = 0.0006) and the variability (defined as the standard deviation divided by the mean) of the cross-sectional area decreased from 0.24 to 0.18 (P = 0.04). CONCLUSION: Using the immobilization device effectively reduces variability in repeated imaging of the carotid arteries.