Viola Rieke

Clinical applications for magnetic resonance guided high intensity focused ultrasound (MRgHIFU): Present and future

It has been well known for decades that high intensity focused ultrasound (HIFU) generates heat in tissues resulting in coagulative necrosis. Implementation, however, has been slow, due to difficulties with finding an appropriate imaging modality that could not only guide treatment, but also provide real‐time thermal feedback. These problems have been overcome with the newest magnetic resonance‐guided high intensity focused ultrasound systems (MRgHIFU). With its superior spatial resolution enabling accurate image guidance coupled with its ability to provide real‐time thermography during treatments, MRI is moving further into the realm of therapeutics for oncologic patient care.

International consensus on use of focused ultrasound for painful bone metastases: Current status and future directions

Abstract Focused ultrasound surgery (FUS), in particular magnetic resonance guided FUS (MRgFUS), is an emerging non-invasive thermal treatment modality in oncology that has recently proven to be effective for the palliation of metastatic bone pain. A consensus panel of internationally recognised experts in focused ultrasound critically reviewed all available data and developed consensus statements to increase awareness, accelerate the development, acceptance and adoption of FUS as a treatment for painful bone metastases and provide guidance towards broader application in oncology. In this review, evidence-based consensus statements are provided for (1) current treatment goals, (2) current indications, (3) technical considerations, (4) future directions including research priorities, and (5) economic and logistical considerations.

Comparison of temperature processing methods for monitoring focused ultrasound ablation in the brain

To investigate the performance of different reconstruction methods for monitoring temperature changes during transcranial magnetic resonance imaging (MRI)‐guided focused ultrasound (MRgFUS).

PROMISe trial: a pilot, randomized, placebo-controlled trial of magnetic resonance guided focused ultrasound for uterine fibroids

OBJECTIVEnTo evaluate the feasibility of a full-scale placebo-controlled trial of magnetic resonance-guided focused ultrasound for fibroids (MRgFUS) and obtain estimates of safety and efficacy.nnnDESIGNnPilot, randomized, placebo-controlled trial.nnnSETTINGnUniversity medical center.nnnPATIENT(S)nPremenopausal women with symptomatic uterine fibroids.nnnINTERVENTION(S)nParticipants randomized in a 2:1 ratio to receive MRgFUS or placebo procedure.nnnMAIN OUTCOME MEASURE(S)nnnnPRIMARY OUTCOMEnchange in fibroid symptoms from baseline to 4 and 12 weeks after treatment assessed by the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QOL); secondary outcome: incidence of surgery or procedures for recurrent symptoms at 12 and 24 months.nnnRESULT(S)nTwenty women with a mean age of 44 years (±standard deviation 5.4 years) were enrolled, and 13 were randomly assigned to MRgFUS and 7 to placebo. Four weeks after treatment, all participants reported improvement in the UFS-QOL: a mean of 10 points in the MRgFUS group and 9 points in the placebo group (for difference in change between groups). By 12 weeks, the MRgFUS group had improved more than the placebo group (mean 31 points and 13 points, respectively). The mean fibroid volume decreased 18% in the MRgFUS group with no decrease in the placebo group at 12 weeks. Two years after MRgFUS, 4 of 12 women who had a follow-up evaluation (30%) had undergone another fibroid surgery or procedure.nnnCONCLUSION(S)nWomen with fibroids were willing to enroll in a randomized, placebo-controlled trial of MRgFUS. A placebo effect may explain some of the improvement in fibroid-related symptoms observed in the first 12 weeks after MRgFUS.nnnCLINICAL TRIAL REGISTRATION NUMBERnNCT01377519.

Model-based feasibility assessment and evaluation of prostate hyperthermia with a commercial MR-guided endorectal HIFU ablation array

PURPOSEnFeasibility of targeted and volumetric hyperthermia (40-45u2009°C) delivery to the prostate with a commercial MR-guided endorectal ultrasound phased array system, designed specifically for thermal ablation and approved for ablation trials (ExAblate 2100, Insightec Ltd.), was assessed through computer simulations and tissue-equivalent phantom experiments with the intention of fast clinical translation for targeted hyperthermia in conjunction with radiotherapy and chemotherapy.nnnMETHODSnThe simulations included a 3D finite element method based biothermal model, and acoustic field calculations for the ExAblate ERUS phased array (2.3 MHz, 2.3 × 4.0 cm(2), ∼1000 channels) using the rectangular radiator method. Array beamforming strategies were investigated to deliver protracted, continuous-wave hyperthermia to focal prostate cancer targets identified from representative patient cases. Constraints on power densities, sonication durations and switching speeds imposed by ExAblate hardware and software were incorporated in the models. Preliminary experiments included beamformed sonications in tissue mimicking phantoms under MR temperature monitoring at 3 T (GE Discovery MR750W).nnnRESULTSnAcoustic intensities considered during simulation were limited to ensure mild hyperthermia (Tmax < 45u2009°C) and fail-safe operation of the ExAblate array (spatial and time averaged acoustic intensity ISATA < 3.4 W/cm(2)). Tissue volumes with therapeutic temperature levels (T > 41u2009°C) were estimated. Numerical simulations indicated that T > 41u2009°C was calculated in 13-23 cm(3) volumes for sonications with planar or diverging beam patterns at 0.9-1.2 W/cm(2), in 4.5-5.8 cm(3) volumes for simultaneous multipoint focus beam patterns at ∼0.7 W/cm(2), and in ∼6.0 cm(3) for curvilinear (cylindrical) beam patterns at 0.75 W/cm(2). Focused heating patterns may be practical for treating focal disease in a single posterior quadrant of the prostate and diffused heating patterns may be useful for heating quadrants, hemigland volumes or even bilateral targets. Treatable volumes may be limited by pubic bone heating. Therapeutic temperatures were estimated for a range of physiological parameters, sonication duty cycles and rectal cooling. Hyperthermia specific phasing patterns were implemented on the ExAblate prostate array and continuous-wave sonications (∼0.88 W/cm(2), 15 min) were performed in tissue-mimicking material with real-time MR-based temperature imaging (PRFS imaging at 3.0 T). Shapes of heating patterns observed during experiments were consistent with simulations.nnnCONCLUSIONSnThe ExAblate 2100, designed specifically for thermal ablation, can be controlled for delivering continuous hyperthermia in prostate while working within operational constraints.

Approaches for modelling interstitial ultrasound ablation of tumours within or adjacent to bone: Theoretical and experimental evaluations

Abstract Purpose: The objectives of this study were to develop numerical models of interstitial ultrasound ablation of tumours within or adjacent to bone, to evaluate model performance through theoretical analysis, and to validate the models and approximations used through comparison to experiments. Methods: 3D transient biothermal and acoustic finite element models were developed, employing four approximations of 7-MHz ultrasound propagation at bone/soft tissue interfaces. The various approximations considered or excluded reflection, refraction, angle-dependence of transmission coefficients, shear mode conversion, and volumetric heat deposition. Simulations were performed for parametric and comparative studies. Experiments within ex vivo tissues and phantoms were performed to validate the models by comparison to simulations. Temperature measurements were conducted using needle thermocouples or magnetic resonance temperature imaging (MRTI). Finite element models representing heterogeneous tissue geometries were created based on segmented MR images. Results: High ultrasound absorption at bone/soft tissue interfaces increased the volumes of target tissue that could be ablated. Models using simplified approximations produced temperature profiles closely matching both more comprehensive models and experimental results, with good agreement between 3D calculations and MRTI. The correlation coefficients between simulated and measured temperature profiles in phantoms ranged from 0.852 to 0.967 (p-valueu2009<u20090.01) for the four models. Conclusions: Models using approximations of interstitial ultrasound energy deposition around bone/soft tissue interfaces produced temperature distributions in close agreement with comprehensive simulations and experimental measurements. These models may be applied to accurately predict temperatures produced by interstitial ultrasound ablation of tumours near and within bone, with applications toward treatment planning.

Bone Remodeling after MR Imaging–guided High-Intensity Focused Ultrasound Ablation: Evaluation with MR Imaging, CT, Na18F-PET, and Histopathologic Examination in a Swine Model

PURPOSEnTo serially monitor bone remodeling in the swine femur after magnetic resonance (MR) imaging-guided high-intensity focused ultrasound (HIFU) ablation with MR imaging, computed tomography (CT), sodium fluorine 18 (Na(18)F)-positron emission tomography (PET), and histopathologic examination, as a function of sonication energy.nnnMATERIALS AND METHODSnExperimental procedures received approval from the local institutional animal care and use committee. MR imaging-guided HIFU was used to create distal and proximal ablations in the right femurs of eight pigs. The energy used at the distal target was higher (mean, 419 J; range, 390-440 J) than that used at the proximal target (mean, 324 J; range, 300-360 J). Imaging was performed before and after ablation with 3.0-T MR imaging and 64-section CT. Animals were reevaluated at 3 and 6 weeks with MR imaging (n = 8), CT (n = 8), Na(18)F-PET (n = 4), and histopathologic examination (n = 4). Three-dimensional ablation lengths were measured on contrast material-enhanced MR images, and bone remodeling in the cortex was measured on CT images.nnnRESULTSnAblation sizes at MR imaging 3 and 6 weeks after MR imaging-guided HIFU ablation were similar between proximal (low-energy) and distal (high-energy) lesions (average, 8.7 × 21.9 × 16.4 mm). However, distal ablation lesions (n = 8) demonstrated evidence of subperiosteal new bone formation at CT, with a subtle focus of new ossification at 3 weeks and a larger focus of ossification at 6 weeks. New bone formation was associated with increased uptake at Na(18)F-PET in three of four animals; this was confirmed at histopathologic examination in four of four animals.nnnCONCLUSIONnMR imaging-guided HIFU ablation of bone may result in progressive remodeling, with both subcortical necrosis and subperiosteal new bone formation. This may be related to the use of high energies. MR imaging, CT, and PET are suitable noninvasive techniques to monitor bone remodeling after MR imaging-guided HIFU ablation.

MRI-guided high-intensity focused ultrasound ablation of bone: Evaluation of acute findings with MR and CT imaging in a swine model

To evaluate hyperacute (<1 hour) changes on magnetic resonance (MR) and computed tomography (CT) imaging following MR‐guided high‐intensity focused ultrasound (MRgHIFU) in a swine bone model as a function of sonication number and energy.

Quantifying temperature-dependent T1 changes in cortical bone using ultrashort echo-time MRI.

To demonstrate the feasibility of using ultrashort echo‐time MRI to quantify T1 changes in cortical bone due to heating.

T2-based temperature monitoring in abdominal fat during MR-guided focused ultrasound treatment of patients with uterine fibroids.

BackgroundNear-field heating is a potential problem in focused ultrasound treatments, as it can result in thermal injury to skin, subcutaneous fat, and other tissues. Our goals were to determine if T2-based temperature mapping could be used reliably to measure near-field heating in adipose tissue and whether it is practical to perform such mapping during focused ultrasound treatments.MethodsWe investigated the dependence of T2 on temperature in ex vivo adipose tissue at 3T using a double-echo fast spin echo (FSE) sequence. We implemented and evaluated the T2-based temperature mapping technique in the adipose tissue of two healthy volunteers. Finally, we applied the technique during magnetic resonance-guided focused ultrasound (MRgFUS) treatments to measure near-field heating in eight patients with uterine fibroids.ResultsCalibration experiments in porcine adipose tissue determined a temperature coefficient of 6.16xa0ms/°C during heating and 5.37xa0ms/°C during cooling. The volunteer experiments demonstrated a strong correlation between the skin temperature and T2-based temperature measurements in the fat layer. During the treatments of patients with uterine fibroids, we observed a measurable change in the T2 of fat tissue within the path of the ultrasound beam and a temperature increase of up to 15xa0°C with sustained heating of more than 10xa0°C.ConclusionsOur results demonstrate the feasibility and importance of monitoring near-field heating in fatty tissues. The implementation of near-field monitoring between sonications can shorten treatments by reducing the cooling time. It can help improve safety by avoiding excessive heating in the near field.