Henrik Odéen

Characterization and evaluation of tissue-mimicking gelatin phantoms for use with MRgFUS

BackgroundA tissue-mimicking phantom that accurately represents human-tissue properties is important for safety testing and for validating new imaging techniques. To achieve a variety of desired human-tissue properties, we have fabricated and tested several variations of gelatin phantoms. These phantoms are simple to manufacture and have properties in the same order of magnitude as those of soft tissues. This is important for quality-assurance verification as well as validation of magnetic resonance-guided focused ultrasound (MRgFUS) treatment techniques.MethodsThe phantoms presented in this work were constructed from gelatin powders with three different bloom values (125, 175, and 250), each one allowing for a different mechanical stiffness of the phantom. Evaporated milk was used to replace half of the water in the recipe for the gelatin phantoms in order to achieve attenuation and speed of sound values in soft tissue ranges. These acoustic properties, along with MR (T1 and T2*), mechanical (density and Young’s modulus), and thermal properties (thermal diffusivity and specific heat capacity), were obtained through independent measurements for all three bloom types to characterize the gelatin phantoms. Thermal repeatability of the phantoms was also assessed using MRgFUS and MR thermometry.ResultsAll the measured values fell within the literature-reported ranges of soft tissues. In heating tests using low-power (6.6 W) sonications, interleaved with high-power (up to 22.0 W) sonications, each of the three different bloom phantoms demonstrated repeatable temperature increases (10.4 ± 0.3 °C for 125-bloom, 10.2 ± 0.3 °C for 175-bloom, and 10.8 ± 0.2 °C for 250-bloom for all 6.6-W sonications) for heating durations of 18.1 s.ConclusionThese evaporated milk-modified gelatin phantoms should serve as reliable, general soft tissue-mimicking MRgFUS phantoms.

Toward Real-Time Availability of 3D Temperature Maps Created with Temporally Constrained Reconstruction

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.

Toward real-time temperature monitoring in fat and aqueous tissue during magnetic resonance–guided high-intensity focused ultrasound using a three-dimensional proton resonance frequency T1 method

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.

Treatment envelope evaluation in transcranial magnetic resonance-guided focused ultrasound utilizing 3D MR thermometry

BackgroundCurrent clinical targets for transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) are all located close to the geometric center of the skull convexity, which minimizes challenges related to focusing the ultrasound through the skull bone. Non-central targets will have to be reached to treat a wider variety of neurological disorders and solid tumors. Treatment envelope studies utilizing two-dimensional (2D) magnetic resonance (MR) thermometry have previously been performed to determine the regions in which therapeutic levels of FUS can currently be delivered. Since 2D MR thermometry was used, very limited information about unintended heating in near-field tissue/bone interfaces could be deduced.MethodsIn this paper, we present a proof-of-concept treatment envelope study with three-dimensional (3D) MR thermometry monitoring of FUS heatings performed in a phantom and a lamb model. While the moderate-sized transducer used was not designed for transcranial geometries, the 3D temperature maps enable monitoring of the entire sonication field of view, including both the focal spot and near-field tissue/bone interfaces, for full characterization of all heating that may occur. 3D MR thermometry is achieved by a combination of k-space subsampling and a previously described temporally constrained reconstruction method.ResultsWe present two different types of treatment envelopes. The first is based only on the focal spot heating—the type that can be derived from 2D MR thermometry. The second type is based on the relative near-field heating and is calculated as the ratio between the focal spot heating and the near-field heating. This utilizes the full 3D MR thermometry data achieved in this study.ConclusionsIt is shown that 3D MR thermometry can be used to improve the safety assessment in treatment envelope evaluations. Using a non-optimal transducer, it is shown that some regions where therapeutic levels of FUS can be delivered, as suggested by the first type of envelope, are not necessarily safely treated due to the amount of unintended near-field heating occurring. The results presented in this study highlight the need for 3D MR thermometry in tcMRgFUS.

Evaluation of a three-dimensional MR acoustic radiation force imaging pulse sequence using a novel unbalanced bipolar motion encoding gradient

MR guided focused ultrasound procedures require accurate focal spot localization in three dimensions. This study presents a three‐dimensional (3D) pulse sequence for acoustic radiation force imaging (ARFI) that efficiently localizes the focal spot by means of ultrasound induced tissue displacement over a large field‐of‐view.

Simultaneous MR thermometry and acoustic radiation force imaging using interleaved acquisition

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.

Model predictive filtering MR thermometry: Effects of model inaccuracies, k-space reduction factor, and temperature increase rate.

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.

Development and validation of a MRgHIFU non-invasive tissue acoustic property estimation technique

Abstract 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.

Magnetic resonance imaging-guided focused ultrasound to increase localized blood-spinal cord barrier permeability

Spinal cord injury (SCI) affects thousands of people every year in the USA, and most patients are left with some permanent paralysis. Therapeutic options are limited and only modestly affect outcome. To address this issue, we used magnetic resonance imaging-guided focused ultrasound (MRgFUS) as a non-invasive approach to increase permeability in the blood-spinal cord barrier (BSCB). We hypothesize that localized, controlled sonoporation of the BSCB by MRgFUS will aid delivery of therapeutics to the injury. Here, we report our preliminary findings for the ability of MRgFUS to increase BSCB permeability in the thoracic spinal cord of a normal rat model. First, an excised portion of normal rat spinal column was used to characterize the acoustic field and to estimate the insertion losses that could be expected in an MRgFUS blood spinal cord barrier opening. Then, in normal rats, MRgFUS was applied in combination with intravenously administered microbubbles to the spinal cord region. Permeability of the BSCB was indicated as signal enhancement by contrast administered prior to T1-weighted magnetic resonance imaging and verified by Evans blue dye. Neurological testing using the Basso, Beattie, and Breshnahan scale and the ladder walk was normal in 8 of 10 rats tested. Two rats showed minor impairment indicating need for further refinement of parameters. No gross tissue damage was evident by histology. In this study, we have opened successfully the blood spinal cord barrier in the thoracic region of the normal rat spine using magnetic resonance-guided focused ultrasound combined with microbubbles.

3D‐specific absorption rate estimation from high‐intensity focused ultrasound sonications using the Green's function heat kernel

Purpose To evaluate a numerical inverse Greens function method for deriving specific absorption rates (SARs) from high‐intensity focused ultrasound (HIFU) sonications using tissue parameters (thermal conductivity, specific heat capacity, and mass density) and three‐dimensional (3D) magnetic resonance imaging (MRI) temperature measurements. Methods SAR estimates were evaluated using simulations and MR temperature measurements from HIFU sonications. For simulations, a “true” SAR was calculated using the hybrid angular spectrum method for ultrasound simulations. This “true” SAR was plugged into a Pennes bioheat transfer equation (PBTE) solver to provide simulated temperature maps, which were then used to calculate the SAR estimate using the presented method. Zero mean Gaussian noise, corresponding to temperature precisions between 0.1 and 2.0°C, was added to the temperature maps to simulate a variety of in vivo situations. Experimental MR temperature maps from HIFU sonications in a gelatin phantom monitored with a 3D segmented echo planar imaging MRI pulse sequence were also used. To determine the accuracy of the simulated and phantom data, we reconstructed temperature maps by plugging in the estimated SAR to the PBTE solver. In both simulations and phantom experiments, the presented method was compared to two previously published methods of determining SAR, a linear and an analytical method. The presented numerical method utilized the full 3D data simultaneously, while the two previously published methods work on a slice‐by‐slice basis. Results In the absence of noise, SAR distribution estimates obtained from the simulated heating profiles match closely (within 10%) to the initial true SAR distribution. The resulting temperature distributions also match closely to the corresponding initial temperature distributions (<0.2°C RMSE). In the presence of temperature measurement noise, the SAR distributions have noise amplified by the inverse convolution process, while the resulting temperature distributions still match closely to the initial “true” temperature distributions. In general, temperature RMSE was observed to be approximately 20–30% higher than the level of the added noise. By contrast, the previously published linear method is less sensitive to noise, but significantly underpredicts the SAR. The analytic method is also less sensitive to noise and matches SAR in the central plane, but greatly underpredicts in the longitudinal direction. Similar observations are made from the phantom studies. The described numerical inverse Greens function method is very fast — at least two orders of magnitude faster than the compared methods. Conclusion The presented numerical inverse Greens function method is computationally fast and generates temperature maps with high accuracy. This is true despite generally overestimating the true SAR and amplifying the input noise.