MRI-guided High-intensity Focused Ultrasound Research Articles

High intensity focused ultrasound ablation of goat liver in vivo: Pathologic changes of portal vein and the “heat-sink” effect

The purpose of this study was to evaluate pathological changes of the portal vein (PV) and the effects on main branches of the hepatic PV during HIFU (high-intensity focused ultrasound) sonication when liver tissue adjacent to the main branches of hepatic PV was ablated. Normal liver tissue at 0mm, 5mm, 10mm away from the hepatic portal vein in 50 healthy goats was ablated with magnetic resonance image-guided HIFU (MRgHIFU). MRI showed a non-perfusion region at the target area but did not show any significant changes of the PV immediately after HIFU. The histological examination 1day after HIFU showed coagulative necrosis at the target area, revealed deep-dyed swelling collagen (CS) fibers and vessel wall fracture (VWF) in the PV adjacent to the target area; however, no CS or VWF was observed in the PV 1week after HIFU ablation. The energy required to ablate the foci at 0mm was 21% more than that at 10mm from the PV (p<0.05); the energy needed to ablate foci 5mm away from the PV was 10% more than that at 10mm from the PV (p<0.05). We concluded that minor injury of the hepatic portal vein may occur when ablating the adjacent liver tissue, and the acoustic energy deposition is related to the distance to the portal vein.

The effects of acoustic power and exposure time on the hyperecho in ultrasound images at 55 °C using MRI and US guided HIFU in a bovine liver specimen

Ex vivo bovine liver specimens were exposed to the MRI-guided HIFU with the focusing depth of 15 mm in the specimens and various acoustic power (50 W, 100 W, 150 W, 200 W, 250 W and 300 W). Our interest was focused on a case of 55° C in situ temperature. The temperature in situ was monitored via the T-map of MRI. The exposure time needed to reach 55° C in the focus for a acoustic power was recorded. The same procedure was repeated to new but similar bovine liver exposed to the US-guided HIFU with the same sonication parameters. The procedure was also monitored by a passive cavitation detection system. The results showed to reach 55° C in situ the exposure time decreased with the increase of acoustic power. The coagulative necrosis occurred when the acoustic power was 50 W, but no hyperecho in US images and half harmonic emission were found. The coagulative necrosis, hyperechoic US images and half harmonic emissions were observed when the acoustic power was 100 W or greater. At 55° C, since no boiling bubbles occurred, therefore we concluded that the hyperecho in US images were caused by acoustic cavitation whose occurrence is determined by the applied acoustic power. Keywords: MRI-guided HIFU, US-guided HIFU, Coagulative necrosis, hyperecho, Acoustic cavitation This work was supported by National Nature and Science Foundation of China (No. 30830040, 30970827)

Design and characterization of a laterally mounted phased-array transducer breast-specific MRgHIFU device with integrated 11-channel receiver array

This work presents the design and preliminary evaluation of a new laterally mounted phased-array MRI-guided high-intensity focused ultrasound (MRgHIFU) system with an integrated 11-channel phased-array radio frequency (RF) coil intended for breast cancer treatment. The design goals for the system included the ability to treat the majority of tumor locations, to increase the MR image's signal-to-noise ratio (SNR) throughout the treatment volume and to provide adequate comfort for the patient. In order to treat the majority of the breast volume, the device was designed such that the treated breast is suspended in a 17-cm diameter treatment cylinder. A laterally shooting 1-MHz, 256-element phased-array ultrasound transducer with flexible positioning is mounted outside the treatment cylinder. This configuration achieves a reduced water volume to minimize RF coil loading effects, to position the coils closer to the breast for increased signal sensitivity, and to reduce the MR image noise associated with using water as the coupling fluid. This design uses an 11-channel phased-array RF coil that is placed on the outer surface of the cylinder surrounding the breast. Mechanical positioning of the transducer and electronic steering of the focal spot enable placement of the ultrasound focus at arbitrary locations throughout the suspended breast. The treatment platform allows the patient to lie prone in a face-down position. The system was tested for comfort with 18 normal volunteers and SNR capabilities in one normal volunteer and for heating accuracy and stability in homogeneous phantom and inhomogeneous ex vivo porcine tissue. There was a 61% increase in mean relative SNR achieved in a homogeneous phantom using the 11-channel RF coil when compared to using only a single-loop coil around the chest wall. The repeatability of the system's energy delivery in a single location was excellent, with less than 3% variability between repeated temperature measurements at the same location. The execution of a continuously sonicated, predefined 48-point, 8-min trajectory path resulted in an ablation volume of 8.17 cm(3), with one standard deviation of 0.35 cm(3) between inhomogeneous ex vivo tissue samples. Comfort testing resulted in negligible side effects for all volunteers. The initial results suggest that this new device will potentially be suitable for MRgHIFU treatment in a wide range of breast sizes and tumor locations.

Toward MR-guided high intensity focused ultrasound for presurgical localization: Focused ultrasound lesions in cadaveric breast tissue

To investigate magnetic resonance image-guided high intensity focused ultrasound (MR-HIFU) as a surgical guide for nonpalpable breast tumors by assessing the palpability of MR-HIFU-created lesions in ex vivo cadaveric breast tissue. MR-HIFU ablations spaced 5 mm apart were made in 18 locations using the ExAblate2000 system. Ablations formed a square perimeter in mixed adipose and fibroglandular tissue. Ablation was monitored using T1-weighted fast spin echo images. MR-acoustic radiation force impulse (MR-ARFI) was used to remotely palpate each ablation location, measuring tissue displacement before and after thermal sonications. Displacement profiles centered at each ablation spot were plotted for comparison. The cadaveric breast was manually palpated to assess stiffness of ablated lesions and dissected for gross examination. This study was repeated on three cadaveric breasts. MR-ARFI showed a collective postablation reduction in peak displacement of 54.8% ([4.41 ± 1.48] μm pre, [1.99 ± 0.82] μm post), and shear wave velocity increase of 65.5% ([10.69 ± 1.60] mm pre, [16.33 ± 3.10] mm post), suggesting tissue became stiffer after the ablation. Manual palpation and dissection of the breast showed increased palpability, a darkening of ablation perimeter, and individual ablations were visible in mixed adipose/fibroglandular tissue. The results of this preliminary study show MR-HIFU has the ability to create palpable lesions in ex vivo cadaveric breast tissue, and may potentially be used to preoperatively localize nonpalpable breast tumors.

Multifunctional Mesoporous Composite Nanocapsules for Highly Efficient MRI‐Guided High‐Intensity Focused Ultrasound Cancer Surgery

Bloodless surgical knife: Nano-biotechnology has been introduced into imaging-guided high-intensity focused ultrasound (HIFU) cancer surgery by adopting engineered multifunctional manganese-based mesoporous composite nanocapsules as the contrast agents for T(1)-weighted magnetic resonance imaging (MRI) and simultaneously as synergistic agents for MRI-guided HIFU cancer surgery.

MRIgHIFU: A tool for image‐guided therapeutics

High-intensity focused ultrasound (HIFU) provides focal delivery of mechanical energy deep into the body. This energy can be used to elevate the tissue temperature to such a degree that ablation is achieved. The elevated temperature can also be used to release drugs from temperature-sensitive carriers or activate therapeutic molecules using mechanical or thermal energy. Lower dose exposures modify the vasculature to allow large molecules to diffuse from blood in the surrounding tissue for local drug delivery. The energy delivery can be targeted and monitored using magnetic resonance imaging (MRI). The online image guidance and monitoring provides treatment delivery that is customized to each patient such that optimal, effective treatment can be achieved. This ability to localize and customize treatment delivery may further enhance the future potential of targeted drugs that are personalized for each patient. This review examines the rapid development of MRI-guided HIFU (MRIgHIFU) methods over the past few years and discuss their future potential.

Feasibility of MRI-guided high intensity focused ultrasound treatment for adenomyosis

PurposeTo test the feasibility of MRI-guided high intensity focused ultrasound ablation for adenomyosis. Materials and methodsPatients with symptomatic adenomyosis were treated with MRI-guided high intensity focused ultrasound (MRIgHIFU). Under conscious sedation, MRIgHIFU was performed by a clinical MRI-compatible focused ultrasound tumour therapeutic system (JM15100, Haifu® Technology Co. Ltd., Chongqing, China) which is combined with a 1.5T MRI system (Magnetom Symphony, Siemens Healthcare, Erlangen, Germany). MRI was used to calculate the volume of the uterus and lesion. Non-perfused volume of the targeted lesions was evaluated immediately after MRIgHIFU. Patient symptoms were assessed using symptom severity score (SSS) and uterine fibroids symptoms and quality of life questionnaire (UFS-QOL). ResultsTen patients with mean age of 40.3±4 years with an average lesion size of 56.9±12.7mm in diameter were treated. Non-perfused volume and the percentage of non-perfused volume obtained from contrast-enhanced T1 Magnetic resonance images immediately post-treatment were 66.6±49.4cm3 and 62.5±21.6%, respectively. The mean SSS and UFS-QOL showed significant improvements of 25%, 16% and 25% at 3, 6 and 12 months follow up, respectively, to pre-treatment scores. No serious complications were observed. ConclusionBased on the results from this study, MRIgHIFU treatment appears to be a safe and feasible modality to ablate adenomyosis lesion and alleviate its symptoms.

Rapid motion correction in MR‐guided high‐intensity focused ultrasound heating using real‐time ultrasound echo information

The objective of this study was to evaluate the feasibility of integrating real-time ultrasound echo guidance in MR-guided high-intensity focused ultrasound (HIFU) heating of mobile targets in order to reduce latency between displacement analysis and HIFU treatment. Experiments on a moving phantom were carried out with MRI-guided HIFU during continuous one-dimensional ultrasound echo detection using separate HIFU and ultrasound imaging transducers. Excellent correspondence was found between MR- and ultrasound-detected displacements. Real-time ultrasound echo-based target tracking during MR-guided HIFU heating is shown with the dimensions of the heated area similar to those obtained for a static target. This work demonstrates that the combination of the two modalities opens up perspectives for motion correction in MRI-guided HIFU with negligible latency.

Temperature measurement error reduction for MRI-guided HIFU treatment

Purpose: We present a method to remove the temperature measurement errors due to the movement of the ultrasound applicator during MRI-guided high-intensity focused ultrasound (MRgHIFU) treatment.Methods: MR thermometry, based on proton resonance frequency (PRF) shift, can provide high accuracy and temporal resolution of MR temperature imaging for tumour treatment by MRgHIFU. However, the challenge is that the movement of the ultrasound applicator causes temperature measurement errors due to the magnetic susceptibility of the applicator. In a clinical environment the applicator has to be moved to cover the whole tumour volume, even in the case of a phased array ultrasound applicator. With conventional PRF shift-based phase mapping method, a reference image must be repetitively acquired as the ultrasound applicator is repositioned and tissue cooling down time must be inserted before a new reference scan. Therefore, the treatment workflow becomes complex and time consuming. In this paper we propose a method to reduce temperature measurement error by compensating the ultrasound applicator susceptibility through a pre-measured or calculated magnetic field distribution of the applicator.Results: The large temperature measurement error shown around the ultrasound focal region can be significantly reduced by compensating the ultrasound applicator-induced delta magnetic field. Accurate temperature maps can be obtained when the ultrasound applicator is repositioned without repetitively acquiring new reference images.Conclusions: The reference image can be repetitively used for the temperature imaging when the ultrasound applicator is repositioned. Therefore, the treatment workflow is simplified resulting in a reduction in total treatment time.

Image-guided, noninvasive, spatiotemporal control of gene expression

Spatiotemporal control of transgene expression is of paramount importance in gene therapy. Here, we demonstrate the use of magnetic resonance temperature imaging (MRI)-guided, high-intensity focused ultrasound (HIFU) in combination with a heat-inducible promoter [heat shock protein 70 (HSP70)] for the in vivo spatiotemporal control of transgene activation. Local gene activation induced by moderate hyperthermia in a transgenic mouse expressing luciferase under the control of the HSP70 promoter showed a high similarity between the local temperature distribution in vivo and the region emitting light. Modulation of gene expression is possible by changing temperature, duration, and location of regional heating. Mild heating protocols (2 min at 43 degrees C) causing no tissue damage were sufficient for significant gene activation. The HSP70 promoter was shown to be induced by the local temperature increase and not by the mechanical effects of ultrasound. Therefore, the combination of MRI-guided HIFU heating and transgenes under control of heat-inducible HSP promoter provides a direct, noninvasive, spatial control of gene expression via local hyperthermia.

Spatio-Temporal Control of Gene Expression and Cancer Treatment Using Magnetic Resonance Imaging–Guided Focused Ultrasound

Local temperature elevation may be used for tumor ablation, gene expression, drug activation, and gene and/or drug delivery. High-intensity focused ultrasound (HIFU) is the only clinically viable technology that can be used to achieve a local temperature increase deep inside the human body in a noninvasive way. Magnetic resonance imaging (MRI) guidance of the procedure allows in situ target definition and identification of nearby healthy tissue to be spared. In addition, MRI can be used to provide continuous temperature mapping during HIFU for spatial and temporal control of the heating procedure and prediction of the final lesion based on the received thermal dose. The primary purpose of the development of MRI-guided HIFU was to achieve safe noninvasive tissue ablation. The technique has been tested extensively in preclinical studies and is now accepted in the clinic for ablation of uterine fibroids. MRI-guided HIFU for ablation shows conceptual similarities with radiation therapy. However, thermal damage generally shows threshold-like behavior, with necrosis above the critical thermal dose and full recovery below. MRI-guided HIFU is being clinically evaluated in the cancer field. The technology also shows great promise for a variety of advanced therapeutic methods, such as gene therapy. MR-guided HIFU, together with the use of a temperature-sensitive promoter, provides local, physical, and spatio-temporal control of transgene expression. Specially designed contrast agents, together with the combined use of MRI and ultrasound, may be used for local gene and drug delivery.

MAGNETIC RESONANCE IMAGING-GUIDED, HIGH-INTENSITY FOCUSED ULTRASOUND FOR BRAIN TUMOR THERAPY

Magnetic resonance imaging-guided high-intensity focused ultrasound (MRIgFUS) is a novel technique that may have the potential for precise image-guided thermocoagulation of intracranial lesions. The system delivers small volumetric sonications from an ultrasound phased array transmitter that focuses energy selectively to destroy the target with verification by magnetic resonance imaging-generated thermal maps. A Phase I clinical study was initiated to treat patients with recurrent glioma with MRIgFUS. To date, three patients with histologically verified recurrent glioblastoma multiforme have been treated with MRIgFUS. All patients underwent craniectomy 7 to 10 days before therapy to create a bony window for the ultrasound treatment. Sonications were applied to induce thermocoagulation of the enhancing tumor mass. Long-term radiological follow-up and post-treatment tissue specimens were available for all patients. MRIgFUS treatment resulted in immediate changes in contrast-enhanced T1-, T2-, and diffusion-weighted magnetic resonance imaging scans in the treated regions with subsequent histological evidence of thermocoagulation. In one patient, heating of brain tissue in the sonication path resulted in a secondary focus outside the target causing neurological deficit. New software modifications were developed to address this problem. In this first clinical report, MRIgFUS was demonstrated to be a potentially effective means of destroying tumor tissue by thermocoagulation, although with an associated morbidity and the inherent invasive nature of the procedure requiring creation of a bone window. A modified technology to allow MRIgFUS treatment through a closed cranium is being developed.

Significant clinical improvement following non-invasive transcutaneous thermal ablation of uterine fibroids by magnetic-resonance-imaging-guided high-focus ultrasound

Objective: Surgery is the treatment of choice for symptomatic uterine fibroids. However, surgical procedures can be associated with significant morbidity and mortality as well as variable length of hospitalization and time of reconvalescence. High intensity focused ultrasound (HIFUS) can induce coagulation necrosis in the targeted tissue without significant thermal alteration in adjacent tissue. Magnetic resonance imaging (MRI) can provide real-time thermal imaging mapping of the treated area and guide the ultrasound waves to the desired area of treatment. The aim of the present study was to determine the safety, feasibility and clinical efficacy of non-invasive, transcutaneous thermal ablation of uterine fibroids by MRI-guided HIFUS (InsSightec, Haifa, Israel).