Joshua de Bever

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.

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.

High intensity focused ultrasound hyperthermia for enhanced macromolecular delivery

Mild hyperthermia has been used in combination with polymer therapeutics to further increase delivery to solid tumors and enhance efficacy. An attractive method for generating heat is through non-invasive high intensity focused ultrasound (HIFU). HIFU is often used for ablative therapies and must be adapted to produce uniform mild hyperthermia in a solid tumor. In this work a magnetic resonance imaging guided HIFU (MRgHIFU) controlled feedback system was developed to produce a spatially uniform 43°C heating pattern in a subcutaneous mouse tumor. MRgHIFU was employed to create hyperthermic conditions that enhance macromolecular delivery. Using a mouse model with two subcutaneous tumors, it was demonstrated that MRgHIFU enhanced delivery of both Evans blue dye (EBD) and Gadolinium-chelated N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers. The EBD accumulation in the heated tumors increased by nearly 2-fold compared to unheated tumors. The Gadolinium-chelated HPMA copolymers also showed significant enhancement in accumulation over control as evaluated through MRI T1-mapping measurements. Results show the potential of HIFU-mediated hyperthermia for enhanced delivery of polymer therapeutics.

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.

Adaptive model-predictive controller for magnetic resonance guided focused ultrasound therapy

Abstract Purpose: Minimising treatment time and protecting healthy tissues are conflicting goals that play major roles in making magnetic resonance image-guided focused ultrasound (MRgFUS) therapies clinically practical. We have developed and tested in vivo an adaptive model-predictive controller (AMPC) that reduces treatment time, ensures safety and efficacy, and provides flexibility in treatment set-up. Materials and methods: The controller realises time savings by modelling the heated treatment cell’s future temperatures and thermal dose accumulation in order to anticipate the optimal time to switch to the next cell. Selected tissues are safeguarded by a configurable temperature constraint. Simulations quantified the time savings realised by each controller feature as well as the trade-offs between competing safety and treatment time parameters. In vivo experiments in rabbit thighs established the controller’s effectiveness and reliability. Results: In all in vivo experiments the target thermal dose of at least 240 CEM43 was delivered everywhere in the treatment volume. The controller’s temperature safety limit reliably activated and constrained all protected tissues to <9 CEM43. Simulations demonstrated the path independence of the controller, and that a path which successively proceeds to the hottest untreated neighbouring cell leads to significant time savings, e.g. when compared to a concentric spiral path. Use of the AMPC produced a compounding time-saving effect; reducing the treatment cells’ heating times concurrently reduced heating of normal tissues, which eliminated cooling periods. Conclusions: Adaptive model-predictive control can automatically deliver safe, effective MRgFUS treatments while significantly reducing treatment times.

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.

A full-wave phase aberration correction method for transcranial high-intensity focused ultrasound brain therapies

Transcranial high-intensity focused ultrasound has recently been used to noninvasively treat several types of brain disorders. However, due to the large differences in acoustic properties of skulls and the surrounding soft tissue, it can be a challenge to adequately focus an ultrasonic beam through the skull. We present a novel, fast, full-wave method of correcting the aberrations caused by the skull by phasing the elements of a phased-array transducer to create constructive interference at the target. Because the method is full-wave, it also allows for trajectory planning by determining the phases required for multiple target points with negligible additional computational costs. Experimental hydrophone scans with an ex vivo skull sample using a 256-element 1-MHz transducer show an improvement of 6.2% in peak pressure at the focus and a reduction of side-lobe pressure by a factor of 2.31. Additionally, mispositioning of the peak pressure from the intended treatment location is reduced from 2.3 to 0.5 mm.

Focal point determination in magnetic resonance-guided focused ultrasound using tracking coils

To develop a method for rapid prediction of the geometric focus location in MR coordinates of a focused ultrasound (US) transducer with arbitrary position and orientation without sonicating.

The effect of electronically steering a phased array on proximal tissue heating

This study presents results, obtained from both simulation and experimental techniques that show the effect of mechanically and electronically steering a phased‐array transducer on proximal tissue heating between the transducer and focal zone. The thermal response of a nine‐position, single‐plane, scanning trajectory executed through both electronic and mechanical scanning was evaluated in a homogeneous tissue‐mimicking phantom. Simulations were performed by applying a finite‐difference approximation of the Pennes’ bioheat transfer equation. The power deposition was modeled using the Hybrid Angular Spectrum (HAS) method. Experiments were conducted in a 3T Siemens MRI with a 256‐randomized element phased‐array transducer HIFU system that has both electronic and mechanical steering capabilities. Temperatures were obtained using the proton resonance frequency method. Both simulation and experimental results show that electronically steering the ultrasound beam using a 256‐element randomized phased‐array sign...

Multiple-point magnetic resonance acoustic radiation force imaging

To implement and evaluate an efficient multiple‐point MR acoustic radiation force imaging pulse sequence that can volumetrically measure tissue displacement and evaluate tissue stiffness using focused ultrasound (FUS) radiation force.