Search

Objective: High-intensity magnetic resonance-guided focused ultrasound (MRgFUS) is a non-invasive therapy to lesion brain tissue, used clinically in patients and pre-clinically in several animal models. Challenges with focused ablation in rodent brains can include skull and near-field heating and accurately targeting small and deep brain structures. We overcame these challenges by creating a novel method consisting of a craniectomy skull preparation, a high-frequency transducer (3 MHz) with a small ultrasound focal spot, a transducer positioning system with an added manual adjustment of ∼0.1 mm targeting accuracy, and MR acoustic radiation force imaging for confirmation of focal spot placement., Methods: The study consisted of two main parts. First, two skull preparation approaches were compared. A skull thinning approach (n = 7 lesions) was compared to a craniectomy approach (n = 22 lesions), which confirmed a craniectomy was necessary to decrease skull and near-field heating. Second, the two transducer positioning systems were compared with the fornix chosen as a subcortical ablation target. We evaluated the accuracy of targeting using histologic methods from a high-frequency transducer with a small ultrasound focal spot and MR acoustic radiation force imaging., Results: Comparing a motorized adjustment system (∼1 mm precision, n = 17 lesions) to the motorized system with an added micromanipulator (∼0.1 mm precision, n = 14 lesions), we saw an increase in the accuracy of targeting the fornix by 133%., Conclusions: The described work allows for repeatable and accurate targeting of small and deep structures in the rodent brain, such as the fornix, enabling the investigation of neurological disorders in chronic disease models., Competing Interests: Conflict of interest The authors declare no commercial or financial conflict of interest., (Copyright © 2024 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate numerical simulations of focused ultrasound (FUS) with a rabbit model, comparing simulated heating characteristics with magnetic resonance temperature imaging (MRTI) data collected during in vivo treatment., Methods: A rabbit model was treated with FUS sonications in the biceps femoris with 3D MRTI collected. Acoustic and thermal properties of the rabbit muscle were determined experimentally. Numerical models of the rabbits were created, and tissue-type-specific properties were assigned. FUS simulations were performed using both the hybrid angular spectrum (HAS) method and k-Wave. Simulated power deposition patterns were converted to temperature maps using a Pennes' bioheat equation-based thermal solver. Agreement of pressure between the simulation techniques and temperature between the simulation and experimental heating was evaluated. Contributions of scattering and absorption attenuation were considered., Results: Simulated peak pressures derived using the HAS method exceeded the simulated peak pressures from k-Wave by 1.6 ± 2.7%. The location and FWHM of the peak pressure calculated from HAS and k-Wave showed good agreement. When muscle acoustic absorption value in the simulations was adjusted to approximately 54% of the measured attenuation, the average root-mean-squared error between simulated and experimental spatial-average temperature profiles was 0.046 ± 0.019 °C/W. Mean distance between simulated and experimental COTMs was 3.25 ± 1.37 mm. Transverse FWHMs of simulated sonications were smaller than in in vivo sonications. Longitudinal FWHMs were similar., Conclusions: Presented results demonstrate agreement between HAS and k-Wave simulations and that FUS simulations can accurately predict focal position and heating for in vivo applications in soft tissue.

Objective: Focused ultrasound (FUS) has become a non-invasive option for some surgical procedures, including tumor ablation and thalamotomy. Extension of magnetic resonance (MR) imaging-guided focused ultrasound for ablation of slowly perfused cerebrovascular lesions requires a novel treatment monitoring method that does not rely on thermometry or high-frequency Doppler methods. The goal of this study was to evaluate the sensitivity and specificity of strain estimates based on MR acoustic radiation force imaging (MR-ARFI) for differentiation of solids and liquids., Methods: Strain fields were estimated in gelatin-based tissue-mimicking focused ultrasound phantoms on the basis of apparent displacement fields measured by MR-ARFI. MR-ARFI and diffusion-weighted imaging (DWI) measurements were made before and after FUS-induced heating to evaluate the performance of displacement, strain and apparent diffusion coefficient (ADC) measurements for the discrimination of solid and liquid phases., Results: As revealed by receiver operating characteristic analyses, axial normal strain and shear strain components performed significantly better than axial displacement measurements alone when predicting whether a gelatin had melted. Additional measurements must be made to estimate certain strain components, so this trade-off must be considered when developing clinical strategies. ADC had the best overall performance, but DWI is vulnerable to signal dropouts and susceptibility artifacts near cerebrovascular lesions, so this metric may have limited clinical applicability., Conclusion: Strain components based on MR-ARFI apparent displacement measurements perform better than apparent displacement measurements alone at discriminating between solids and liquids. These methods are applicable to FUS treatment monitoring and evaluation of mechanical tissue properties in vivo., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Ultrasound beam aberration correction is vital when focusing ultrasound through the skull bone in transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) applications. Current methods make transducer element phase adjustments to compensate for the variation in skull properties (shape, thickness, and acoustic properties), but do not account for variations in the internal brain anatomy., Purpose: Our objective is to investigate the effect of cerebrospinal fluid (CSF) and brain anatomy on beam focusing in tcMRgFUS treatments., Methods: Simulations were conducted with imaging data from 20 patients previously treated with focused ultrasound for disabling tremor. The Hybrid Angular Spectrum (HAS) method was used to test the effect of including cerebral spinal fluid (CSF) and brain anatomy in determining the element phases used for aberration correction and beam focusing. Computer tomography (CT) and magnetic resonance imaging (MRI) images from patient treatments were used to construct a segmented model of each patient's head. The segmented model for treatment simulation consisted of water, skin, fat, brain, CSF, diploë, and cortical bone. Transducer element phases used for treatment simulation were determined using time reversal from the desired focus, generating a set of phases assuming a homogeneous brain in the intracranial volume, and a second set of phases assigning CSF acoustic properties to regions of CSF. In addition, for three patients, the relative effect of separately including CSF speed of sound values compared to CSF attenuation values was found., Results: We found that including CSF acoustic properties (speed of sound and attenuation) during phase planning compared to phase correction without considering CSF increased the absorbed ultrasound power density ratios at the focus over a range of 1.06 to 1.29 (mean of 17% ± 6%) for 20 patients. Separately considering the CSF speed of sound and CSF attenuation showed that the increase was due almost entirely to including the CSF speed of sound; considering only the CSF attenuation had a negligible effect., Conclusions: Based on HAS simulations, treatment planning phase determination using morphologically realistic CSF and brain anatomy yielded an increase of up to 29% in the ultrasound focal absorbed power density. Future work will be required to validate the CSF simulations., (© 2023 American Association of Physicists in Medicine.)

Real-time temperature monitoring is critical to the success of thermally ablative therapies. This work validates a 3D thermometry sequence with k-space field drift correction designed for use in magnetic resonance-guided focused ultrasound treatments for breast cancer. Fiberoptic probes were embedded in tissue-mimicking phantoms, and temperature change measurements from the probes were compared with the magnetic resonance temperature imaging measurements following heating with focused ultrasound. Precision and accuracy of measurements were also evaluated in free-breathing healthy volunteers (N = 3) under a non-heating condition. MR temperature measurements agreed closely with those of fiberoptic probes, with a 95% confidence interval of measurement difference from -2.0 °C to 1.4 °C. Field drift-corrected measurements in vivo had a precision of 1.1 ± 0.7 °C and were accurate within 1.3 ± 0.9 °C across the three volunteers. The field drift correction method improved precision and accuracy by an average of 46 and 42%, respectively, when compared to the uncorrected data. This temperature imaging sequence can provide accurate measurements of temperature change in aqueous tissues in the breast and support the use of this sequence in clinical investigations of focused ultrasound treatments for breast cancer., Competing Interests: Declaration of Competing Interest Authors AP and DLP have intellectual property relating to the breast MRgFUS technology used in the paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Advances in imaging and early cancer detection have increased interest in magnetic resonance (MR) guided focused ultrasound (MRgFUS) technologies for cancer treatment. MRgFUS ablation treatments could reduce surgical risks, preserve organ tissue and function, and improve patient quality of life. However, surgical resection and histological analysis remain the gold standard to assess cancer treatment response. For non-invasive ablation therapies such as MRgFUS, the treatment response must be determined through MR imaging biomarkers. However, current MR biomarkers are inconclusive and have not been rigorously evaluated against histology via accurate registration. Existing registration methods rely on anatomical features to directly register in vivo MR and histology. For MRgFUS applications in anatomies such as liver, kidney, or breast, anatomical features that are not caused by the treatment are often insufficient to drive direct registration. We present a novel MR to histology registration workflow that utilizes intermediate imaging and does not rely on anatomical MR features being visible in histology. The presented workflow yields an overall registration accuracy of 1.00 ± 0.13 mm. The developed registration pipeline is used to evaluate a common MRgFUS treatment assessment biomarker against histology. Evaluating MR biomarkers against histology using this registration pipeline will facilitate validating novel MRgFUS biomarkers to improve treatment assessment without surgical intervention. While the presented registration technique has been evaluated in a MRgFUS ablation treatment model, this technique could be potentially applied in any tissue to evaluate a variety of therapeutic options., (© 2021. The Author(s).)

Purpose: Magnetic resonance guided focused ultrasound (MRgFUS) treatment of tumors uses inter-sonication delays to allow heat to dissipate from the skin and other near-field tissues. Despite inter-sonication delays, treatment of tumors close to the skin risks skin burns. This work has designed and evaluated an open-source, conformable, skin-cooling system for body MRgFUS treatments to reduce skin burns and enable ablation closer to the skin., Methods: A MR-compatible skin cooling system is described that features a conformable skin-cooling pad assembly with feedback control allowing continuous flow and pressure maintenance during the procedure. System performance was evaluated with hydrophone, phantom and in vivo porcine studies. Sonications were performed 10 and 5 mm from the skin surface under both control and forced convective skin-cooling conditions. 3D MR temperature imaging was acquired in real time and the accumulated thermal dose volume was measured. Gross analysis of the skin post-sonication was further performed. Device conformability was demonstrated at several body locations., Results: Hydrophone studies demonstrated no beam aberration, but a 5-12% reduction of the peak pressure due to the presence of the skin-cooling pad assembly in the acoustic near field. Phantom evaluation demonstrated there is no MR temperature imaging precision reduction or any other artifacts present due to the coolant flow during MRgFUS sonication. The porcine studies demonstrated skin burns were reduced in size or eliminated when compared to the control condition., Conclusion: An open-source design of an MRgFUS active skin cooling system demonstrates device conformability with a reduction of skin burns while ablating superficial tissues.

Purpose: To develop and characterize a tissue-mimicking phantom that enables the direct comparison of magnetic resonance (MR) and ultrasound (US) imaging techniques useful for monitoring high-intensity focused ultrasound (HIFU) treatments. With no additions, gelatin phantoms produce little if any scattering required for US imaging. This study characterizes the MR and US image characteristics as a function of psyllium husk concentration, which was added to increase US scattering. Methods: Gelatin phantoms were constructed with varying concentrations of psyllium husk. The effects of psyllium husk concentration on US B-mode and MR imaging were evaluated at nine different concentrations. T1, T2, and T2* MR maps were acquired. Acoustic properties (attenuation and speed of sound) were measured at frequencies of 0.6, 1.0, 1.8, and 3.0 MHz using a through-transmission technique. Phantom elastic properties were evaluated for both time and temperature dependence. Results: Ultrasound image echogenicity increased with increasing psyllium husk concentration while quality of gradient-recalled echo MR images decreased with increasing concentration. For all phantoms, the measured speed of sound ranged between 1567-1569 m/s and the attenuation ranged between 0.42-0.44 dB/(cm·MHz). Measured T1 ranged from 974-1051 ms. The T2 and T2* values ranged from 97-108 ms and 48-88 ms, respectively, with both showing a decreasing trend with increased psyllium husk concentration. Phantom stiffness, measured using US shear-wave speed measurements, increased with age and decreased with increasing temperature. Conclusions: The presented dual-use tissue-mimicking phantom is easy to manufacture and can be used to compare and evaluate US-guided and MR-guided HIFU imaging protocols.

Purpose: A novel and practical method for simultaneously performing MR acoustic radiation force imaging (ARFI) and proton resonance frequency (PRF)-shift thermometry has been developed and tested. This could be an important tool for evaluating the success of MR-guided focused ultrasound procedures for which MR-thermometry measures temperature and thermal dose and MR-ARFI detects changes in tissue mechanical properties., Methods: MR imaging was performed using a gradient recalled echo segmented echo-planar imaging pulse sequence with bipolar motion encoding gradients (MEG). Images with ultrasound pulses (ON) and without ultrasound pulses (OFF) during the MEG were interleaved at the repetition time (TR) level. ARFI displacements were calculated by complex subtraction of ON-OFF images, and PRF temperature maps were calculated by baseline subtraction. Evaluations in tissue-mimicking phantoms and ex vivo porcine brain tissue were performed. Constrained reconstruction improved the temporal resolution of dynamic measurements., Results: Simultaneous maps of displacement and temperature were acquired in 2D and 3D while keeping tissue heating < 1°C. Accuracy of the temperature maps was comparable to the standard PRF sequence. Using constrained reconstruction and subsampled k-space (R = 4.33), 3D simultaneous temperature and displacement maps can be acquired every 4.7 s., Conclusion: This new sequence acquires simultaneous temperature and displacement maps with minimal tissue heating, and can be applied dynamically for monitoring tissue mechanical properties during ablation procedures. Magn Reson Med 79:1515-1524, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

MR-guided high-intensity focussed ultrasound (MRgHIFU) non-invasive ablative surgeries have advanced into clinical trials for treating many pathologies and cancers. A remaining challenge of these surgeries is accurately planning and monitoring tissue heating in the face of patient-specific and dynamic acoustic properties of tissues. Currently, non-invasive measurements of acoustic properties have not been implemented in MRgHIFU treatment planning and monitoring procedures. This methods-driven study presents a technique using MR temperature imaging (MRTI) during low-temperature HIFU sonications to non-invasively estimate sample-specific acoustic absorption and speed of sound values in tissue-mimicking phantoms. Using measured thermal properties, specific absorption rate (SAR) patterns are calculated from the MRTI data and compared to simulated SAR patterns iteratively generated via the Hybrid Angular Spectrum (HAS) method. Once the error between the simulated and measured patterns is minimised, the estimated acoustic property values are compared to the true phantom values obtained via an independent technique. The estimated values are then used to simulate temperature profiles in the phantoms, and compared to experimental temperature profiles. This study demonstrates that trends in acoustic absorption and speed of sound can be non-invasively estimated with average errors of 21% and 1%, respectively. Additionally, temperature predictions using the estimated properties on average match within 1.2 °C of the experimental peak temperature rises in the phantoms. The positive results achieved in tissue-mimicking phantoms presented in this study indicate that this technique may be extended to in vivo applications, improving HIFU sonication temperature rise predictions and treatment assessment., Competing Interests: Declarations of Interest The authors report no conflicts of interest.

Purpose: Evaluate effects of model parameter inaccuracies (thermal conductivity, k, and ultrasound power deposition density, Q), k-space reduction factor (R), and rate of temperature increase ( T˙) in a thermal model-based reconstruction for MR-thermometry during focused-ultrasound heating., Methods: Simulations and ex vivo experiments were performed to investigate the accuracy of the thermal model and the model predictive filtering (MPF) algorithm for varying R and T˙, and their sensitivity to errors in k and Q. Ex vivo data was acquired with a segmented EPI pulse sequence to achieve large field-of-view (192 × 162 × 96 mm) four-dimensional temperature maps with high spatiotemporal resolution (1.5 × 1.5 × 2.0 mm, 1.7 s)., Results: In the simulations, 50% errors in k and Q resulted in maximum temperature root mean square errors (RMSE) of 6 °C for model only and 3 °C for MPF. Using recently developed methods, estimates of k and Q were accurate to within 3%. The RMSE between MPF and true temperature increased with R and T˙. In the ex vivo study the RMSE remained below 0.7 °C for R ranging from 4 to 12 and T˙ of 0.28-0.75 °C/s., Conclusion: Errors in MPF temperatures occur due to errors in k and Q. These MPF temperature errors increase with increase in R and T˙, but are smaller than those obtained using the thermal model alone., (© 2015 Wiley Periodicals, Inc.)

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.

Purpose: To present a three-dimensional (3D) segmented echoplanar imaging (EPI) pulse sequence implementation that provides simultaneously the proton resonance frequency shift temperature of aqueous tissue and the longitudinal relaxation time (T1 ) of fat during thermal ablation., Methods: The hybrid sequence was implemented by combining a 3D segmented flyback EPI sequence, the extended two-point Dixon fat and water separation, and the double flip angle T1 mapping techniques. High-intensity focused ultrasound (HIFU) heating experiments were performed at three different acoustic powers on excised human breast fat embedded in ex vivo porcine muscle. Furthermore, T1 calibrations with temperature in four different excised breast fat samples were performed, yielding an estimate of the average and variation of dT1 /dT across subjects., Results: The water only images were used to mask the complex original data before computing the proton resonance frequency shift. T1 values were calculated from the fat-only images. The relative temperature coefficients were found in five fat tissue samples from different patients and ranged from 1.2% to 2.6%/°C., Conclusion: The results demonstrate the capability of real-time simultaneous temperature mapping in aqueous tissue and T1 mapping in fat during HIFU ablation, providing a potential tool for treatment monitoring in organs with large fat content, such as the breast., (Copyright © 2013 Wiley Periodicals, Inc.)

Purpose: To extend the previously developed temporally constrained reconstruction (TCR) algorithm to allow for real-time availability of three-dimensional (3D) temperature maps capable of monitoring MR-guided high intensity focused ultrasound applications., Methods: A real-time TCR (RT-TCR) algorithm is developed that only uses current and previously acquired undersampled k-space data from a 3D segmented EPI pulse sequence, with the image reconstruction done in a graphics processing unit implementation to overcome computation burden. Simulated and experimental data sets of HIFU heating are used to evaluate the performance of the RT-TCR algorithm., Results: The simulation studies demonstrate that the RT-TCR algorithm has subsecond reconstruction time and can accurately measure HIFU-induced temperature rises of 20°C in 15 s for 3D volumes of 16 slices (RMSE = 0.1°C), 24 slices (RMSE = 0.2°C), and 32 slices (RMSE = 0.3°C). Experimental results in ex vivo porcine muscle demonstrate that the RT-TCR approach can reconstruct temperature maps with 192 × 162 × 66 mm 3D volume coverage, 1.5 × 1.5 × 3.0 mm resolution, and 1.2-s scan time with an accuracy of ±0.5°C., Conclusion: The RT-TCR algorithm offers an approach to obtaining large coverage 3D temperature maps in real-time for monitoring MR-guided high intensity focused ultrasound treatments., (Copyright © 2013 Wiley Periodicals, Inc.)