Ultrasound Beam Path Research Articles

High-intensity focused ultrasound beam path visualization using ultrasound imaging

In High-Intensity Focused Ultrasound (HIFU) treatment, effective localization of HIFU focus is important for developing a safe treatment plan. While Magnetic Resonance Imaging guided HIFU (MRIgHIFU) can visualize the ultrasound path during the treatment for localizing HIFU focus, it is challenging in ultrasound imaging guided HIFU (USIgHIFU). In the present study, a real-time ultrasound beam visualization technique capable of localizing HIFU focus is presented for USIgHIFU. In the proposed method, a short pulse, with the same center frequency of an imaging ultrasound transducer below the regulated acoustic intensity (i.e., Ispta < 720 mW/cm(2)), was transmitted through a HIFU transducer whereupon backscattered signals were received by the imaging transducer. To visualize the HIFU beam path, the backscattered signals underwent dynamic receive focusing and subsequent echo processing. From in vitro experiments with bovine serum albumin gel phantoms, the HIFU beam path was clearly depicted with low acoustic intensity (i.e., Ispta of 94.8 mW/cm(2)) and the HIFU focus was successfully localized before any damages were produced. This result indicates that the proposed ultrasound beam path visualization method can be used for localizing the HIFU focus in real time while minimizing unwanted tissue damage in USIgHIFU treatment.

Magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) hyperthermia for primary rectal cancer: A virtual feasibility analysis.

77 Background: MR-HIFU Hyperthermia (HT) is a non-invasive treatment modality with real-time thermometry that ensures accurate and precise heating of a target with minimal effect on adjacent tissue. This energy deposition within a tumour can produce local bioeffects resulting in thermal chemo- and radiosensitization. MR-HIFU has been shown to be safe and feasible in a companion phase I study for recurrent rectal cancer. The purpose of this study is to determine the feasibility of MR-HIFU in treating primary rectal tumours. Methods: With ethics approval, the anatomic characteristics and surrounding structures of rectal tumours diagnosed at Sunnybrook from 2014-2019 were retrospectively analyzed. Three orthogonal views of MR images were used to determine the potential ultrasound (US) beam path and organs at risk (OAR). In part 2 of the study, the gross tumour volume was delineated for 30 rectal tumours (10 low, mid &amp;high). Image datasets were imported into the Sonalleve MR-HIFU workstation for virtual treatment simulation and planning to determine tumour targetability, coverage, optimal patient set-up, and transducer positioning. Results: Of the 105 tumours analyzed, 36, 52, and 17 were low, mid, and high, respectively. The average width of the acoustic window (sciatic notch) for the US beam path was 5.8 ± 1.4cm, average tumour length was 5.24 ± 2.0cm, and average beam path (skin to tumour edge) was 7.3 ± 1.9cm. Eighty one percent of tumours were ≤ 0.3cm from an OAR. Of the 24 virtually simulated tumours to date, 6/8 lower, 6/8 mid, and 1/8 upper rectal tumours were targetable by MR-HIFU. Conclusions: This is the first virtual analysis to evaluate MR-HIFU HT targetability in primary rectal cancer. Results from this study will support MR-HIFU HT as an option to enhance the treatment of primary rectal cancer. Acknowledgments: This study has been funded by the Canadian Cancer Society. Patient &amp; tumour characteristics. [Table: see text]

Studying the Origin of Reverberation Clutter in Echocardiography: In Vitro Experiments and In Vivo Demonstrations

Clutter in echocardiography hinders the visualization of the heart and reduces the diagnostic value of the images. The detailed mechanisms that generate clutter are, however, not well understood. We present five different hypotheses for generation of clutter based on reverberation artifact with a focus on apical four-chamber view echocardiograms. We demonstrate the plausibility of our hypotheses by in vitro experiments and by comparing the results with in vivo recordings from four volunteers. The results show that clutter in echocardiography can be originated both at structures that lie in the ultrasound beam path and at those that are outside the imaging plane. We show that reverberations from echogenic structures outside the imaging plane can make clutter over the image if the ultrasound beam gets deflected out of its intended path by specular reflection at the ribs. Different clutter types in the in vivo examples show that the appearance of clutter varies, depending on the tissue from which it originates. The results of this work can be applied to improve clutter reduction techniques or to design ultrasound transducers that give higher quality cardiac images. The results can also help cardiologists have a better understanding of clutter in echocardiograms and acquire better images based on the type and the source of the clutter.

Volumetric magnetic resonance-guided high-intensity focused ultrasound ablation of uterine fibroids through abdominal scars: the impact of a scar patch on therapeutic efficacy and adverse effects

BackgroundTo retrospectively compare the treatment success, therapeutic efficacy, and adverse effects of magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) treatment for uterine fibroid patients with and without abdominal scars.MethodsSeventy-six women who underwent treatment were divided into group 1 (patients with abdominal scars, which were covered with scar patches that prevents ultrasound energy from reaching the scar tissue immediately behind the patch) and group 2 (patients without abdominal scars). Non-perfused volume (NPV) ratios immediately after treatment, and fibroid volume reduction ratios and symptom severity scores (SSS) at the 6-months follow-up were assessed. All adverse effects were recorded.ResultsThe mean NPV ratios in groups 1 and 2 were 87.0 ± 14.1% and 91.5 ± 13.3%. At the 6-months follow-up, the fibroid volume reduction ratios in groups 1 and 2 were 0.45 ± 0.27 and 0.43 ± 0.21, and the corresponding improvement in mean transformed SSS were 0.7 ± 0.39 and 0.79 ± 0.28, respectively. No serious adverse effects were reported. The minor adverse effects encountered in this study are likely related to the temperature increase in the near-field of the ultrasound beam path, which inevitably leads to skin burns, or far-field heat absorption by distant bony structures (i.e., sciatic nerve symptoms), and are typically manifested inter-procedurally and resolved shortly thereafter.ConclusionsThe findings in this study suggest that the scar patch could be used safely and efficiently in MRgHIFU treatment for the patients with uterine fibroids and abdominal scars in the ultrasound beam path.

Pediatric Sarcomas Are Targetable by MR‐Guided High Intensity Focused Ultrasound (MR‐HIFU): Anatomical Distribution and Radiological Characteristics

Despite intensive therapy, children with metastatic and recurrent sarcoma or neuroblastoma have a poor prognosis. Magnetic resonance guided high intensity focused ultrasound (MR-HIFU) is a noninvasive technique allowing the delivery of targeted ultrasound energy under MR imaging guidance. MR-HIFU may be used to ablate tumors without ionizing radiation or target chemotherapy using hyperthermia. Here, we evaluated the anatomic locations of tumors to assess the technical feasibility of MR-HIFU therapy for children with solid tumors. Patients with sarcoma or neuroblastoma with available cross-sectional imaging were studied. Tumors were classified based on the location and surrounding structures within the ultrasound beam path as (i) not targetable, (ii) completely or partially targetable with the currently available MR-HIFU system, and (iii) potentially targetable if a respiratory motion compensation technique was used. Of the 121 patients with sarcoma and 61 patients with neuroblastoma, 64% and 25% of primary tumors were targetable at diagnosis, respectively. Less than 20% of metastases at diagnosis or relapse were targetable for both sarcoma and neuroblastoma. Most targetable lesions were located in extremities or in the pelvis. Respiratory motion compensation may increase the percentage of targetable tumors by 4% for sarcomas and 10% for neuroblastoma. Many pediatric sarcomas are localized at diagnosis and are targetable by current MR-HIFU technology. Some children with neuroblastoma have bony tumors targetable by MR-HIFU at relapse, but few newly diagnosed children with neuroblastoma have tumors amenable to MR-HIFU therapy. Clinical trials of MR-HIFU should focus on patients with anatomically targetable tumors.

Phase aberration simulation study of MRgFUS breast treatments.

This simulation study evaluates the effects of phase aberration in breast MR-guided focused ultrasound (MRgFUS) ablation treatments performed with a phased-array transducer positioned laterally to the breast. A quantification of these effects in terms of thermal dose delivery and the potential benefits of phase correction is demonstrated in four heterogeneous breast numerical models. To evaluate the effects of varying breast tissue properties on the quality of the focus, four female volunteers with confirmed benign fibroadenomas were imaged using 3T MRI. These images were segmented into numerical models with six tissue types, with each tissue type assigned standard acoustic properties from the literature. Simulations for a single-plane 16-point raster-scan treatment trajectory centered in a fibroadenoma in each modeled breast were performed for a breast-specific MRgFUS system. At each of the 16 points, pressure patterns both with and without applying a phase correction technique were determined with the hybrid-angular spectrum method. Corrected phase patterns were obtained using a simulation-based phase aberration correction technique to adjust each element's transmit phase to obtain maximized constructive interference at the desired focus. Thermal simulations were performed for both the corrected and uncorrected pressure patterns using a finite-difference implementation of the Pennes bioheat equation. The effect of phase correction was evaluated through comparison of thermal dose accumulation both within and outside a defined treatment volume. Treatment results using corrected and uncorrected phase aberration simulations were compared by evaluating the power required to achieve a 20 °C temperature rise at the first treatment location. The extent of the volumes that received a minimum thermal dose of 240 CEM at 43 °C inside the intended treatment volume as well as the volume in the remaining breast tissues was also evaluated in the form of a dose volume ratio (DVR), a DVR percent change between corrected and uncorrected phases, and an additional metric that measured phase spread. With phase aberration correction applied, there was an improvement in the focus for all breast anatomies as quantified by a reduction in power required (13%-102%) to reach 20 °C when compared to uncorrected simulations. Also, the DVR percent change increased by 5%-77% in seven out of eight cases, indicating an improvement to the treatment as measured by a reduction in thermal dose deposited to the nontreatment tissues. Breast compositions with a higher degree of heterogeneity along the ultrasound beam path showed greater reductions in thermal dose delivered outside of the treatment volume with correction applied than beam trajectories that propagated through more homogeneous breast compositions. An increasing linear trend was observed between the DVR percent change and the phase-spread metric (R(2) = 0.68). These results indicate that performing phase aberration correction for breast MRgFUS treatments is beneficial for the small-aperture transducer (14.4 × 9.8 cm) evaluated in this work. While all breast anatomies could benefit from phase aberration correction, greater benefits are observed in more heterogeneous anatomies.

WE‐EF‐BRA‐12: Magnetic Resonance‐ Guided High‐Intensity Focused Ultrasound for Localized Ablation of Head and Neck Tissue Structures: A Feasibility Study in An Animal Model

Purpose:High‐intensity focused ultrasound (HIFU) ablation is feasible in the head and neck [1]. This study aims to expand upon these findings to assess the feasibility of treatment planning and monitoring via magnetic resonance imaging (MRI) guidance using a clinical MR‐guided HIFU platform.Methods:Two 31 kg pigs were anaesthetized, shaved, and positioned prone on the HIFU table (Sonalleve, Philips Healthcare, Vantaa, Finland). The necks were acoustically coupled to the integrated transducer using gel pads and degassed water. MR imaging verified acoustic coupling and facilitated target selection in the thyroid and thymus. Targets were thermally ablated with 130–200 W of acoustic power over a period of 16 s at a frequency of 1.2 MHz while being monitored through real‐time, multi‐planar MR‐thermometry. Contrast‐enhanced MR imaging was used to assess treatment efficacy. Post‐treatment, animals were euthanized and sonicated tissues were harvested for histology assessment.Results:MR‐thermometry, post‐contrast‐imaging, and gross pathology demonstrated that the system was capable of causing localized thermal ablation in both the thyroid and the thymus without damaging the aerodigestive tract. In one animal, superficial bruising was observed in the ultrasound beam path. Otherwise, there were no adverse events. Analysis of the tissue histology found regions of damage consistent with acute thermal injury at the targeted locations.Conclusion:It is feasible to use a clinical MR‐guided HIFU platform for extracorporeal ablation of porcine head and neck tissues. MR guidance and thermometry are sufficient to target and monitor treatment in the thyroid region, despite the presence of the inhomogeneous aerodigestive tract. Further study is necessary to assess efficacy and survival using a tumor model, and to examine what modifications should be made to the transducer positioning system and associated patient positioning aids to adapt it for clinical head and neck targets.Reference:[1] Esnault et al. (2011). Thyroid, 21(9), 965– 973.Funding support provided by Philips Healthcare. Ari Partanen is a paid employee of Philips Healthcare.

Point-of care lung ultrasound in the NICU: uses and limitations of a new tool

Pulmonary imaging in the neonatal intensive care unit (NICU) relies traditionally on the conventional chest radiogram. Translating evidences from adult emergency medicine, pediatricians and neonatologists have recently started to apply lung ultrasonography to the critical infant and child with respiratory problems [1]. Because of the high impedance of a normally aerated lung, an ultrasound scan does not render an anatomical image of the organ. However, ultrasounds clearly define the pleural surface with the normal sliding movement. Pleural effusions and lung consolidations can also be reliably diagnosed with ultrasonography. However, ultrasounds penetrating the lung will also generate artifacts (i.e. structures not naturally present in the living that appear as authentic images). These imagery anomalies come from the machine acquisition of the ultrasound beam path through means with markedly different acoustic impedance in close proximity. The horizontal reverberations of the pleural line (aka the A lines - see Figure ​Figure1A)1A) and the vertical hyperecoic image departing from the pleura (aka the B lines- see Figure ​Figure1B)1B) are commonly seen artifacts. Figure 1 1A: reverberations of the pleural image (aka A-lines) in the normally aerated lung. 1B: the prevalence of vertical B-lines (in between arrows) has been linked to the interstitial syndrome in the adult and to a progressive aeration of the neonatal lung ... Real and artefactual images have been combined in disease specific ultrasound profiles. Using these profiles, adult emergency physicians have shown that lung ultrasound outperforms conventional radiology in relevant diagnoses such as pleural effusion, pneumonia or pneumothorax. Pediatricians have started to use lung ultrasound with success to their patients affected by pneumonia but also by bronchiolitis [2]. In the NICU, lung ultrasound has found its specific applications, not without controversies [3]. Transient Tachypnea of the Newborn and Respiratory Distress Syndrome have been described with ultrasound profiles that are both highly sensitive and specific [4]. A relevant limitation of chest ultrasound is that surfactant administration gives a persistent white lung image rendering any follow-up essentially unfeasible. Ultrasounds can, however, accurately describe the fluid to air transition after birth and identify those neonates who will fail to adapt to extrauterine life needing respiratory support [5]. In a series of preterm neonates with moderate respiratory distress, recent work by our group shows that chest ultrasound is significantly more accurate than conventional radiograph in predicting the failure of non invasive ventilation [6]. Lung ultrasound is a very promising clinical tool in the NICU whose potential applications are well worth future multicenter trials.

Imaging Artifacts During Transesophageal Echocardiography

Imaging Artifacts During Transesophageal Echocardiography

Technical Eligibility for Treatment of Magnetic Resonance-guided Focused Ultrasound Surgery

This study was designed to evaluate the technical eligibility for magnetic resonance-guided focused ultrasound surgery (MRgFUS) treatment of women with symptomatic fibroids. Technical eligibility for MRgFUS treatment without mitigation techniques was evaluated retrospectively in 783 premenopausal women (median age, 44.2 years) with symptomatic fibroids who applied for uterine artery embolization (UAE) at our institution from 2001 to 2012. Technical eligibility for MRgFUS was defined as primary study endpoint. Technical ineligibility was assessed on the basis of MRI criteria, such as bowel interposition/foreign material in the ultrasound beam path, more than five fibroids, distance from fibroid to sacral bone surface, fibroid size/shape, severe concomitant adenomyosis or extensive cutaneous scars in accordance to the US Food and Drug Administration approvals. Secondary study endpoint was defined as evaluation of the most frequent exclusion criteria and differences in technical eligibility for MRgFUS and UAE. On the basis of MRI, 38.9% of women who applied for UAE were found to be technically eligible for MRgFUS treatment without mitigation techniques. Most frequent reason for ineligibility was bowel interposition in the ultrasound beam path (60.4%). Differences in technical eligibility for MRgFUS (38.9%) and UAE (99.2%) were significant (P < 0.001). MRgFUS treatment is technically possible in up to 40% of women with symptomatic fibroids. The most frequent exclusion criterion is the presence of bowel in the ultrasound beam path.

Acoustic Radiation Contrast in MR Images for Breast Cancer Diagnostics - Initial Phantom Study

Acoustic radiation contrast in magnetic resonance images is an approach to visualize the changes in ultrasonic loss and viscoelastic changes of the sample with the resolution of a magnetic resonance imaging (MRI) system. By irradiating ultrasound (US) into a tissue-mimicking sample, a displacement along the US beam path caused by the acoustic radiation force is obtained. This displacement varies with the US intensity, the duration of irradiation, the US attenuation and the viscoelastic properties of the sample. US pulses of 2.5 MHz with a duration of 20 ms and an intensity of <17 W/cm 2 are used. An MRI sequence was programmed to produce images in which the magnitude of the displacement is visualized by gray value changes. In addition, a finite element simulation of the measurements was performed to demonstrate the feasibility of the method. Through examination of the measurements and the simulations, information about viscoelastic changes was achieved. In this work, measurements on different breast phantoms are presented. (E-mail: marcus.radicke@gmx.de)

Effects of ribs in high intensity focused ultrasound beam path on formation of coagulated necrosis in cattle liver in vitro

Objective To investigate the effects of ribs in high intensity focused ultrasound (HIFU)beam path on formation of coagulative necrosis in cattle liver in vitro in the same acoustic power. Methods The HIFU ablation was carried out in the manner of a single dot in the liver in vitro. The liver was ablated by HIFU in free field,then the ribs were placed between the focal plane and transducer,directing the beam axis through the intercostals space, lied at the rib edge and on the centre of middle rib. For each of these axial arrangements,the plane of the front surface of ribs was placed 3 cm,6 cm or 9 cm in front of the focus. After HIFU exposure,the tissue necrosis rate(TNR),the maximum length,width,depth and position of the coagulated necrosis in the liver were measured. Results ①The TNR was 100% in the free field. When the ribs were placed 3 cm in front of the focal plane,directing the beam axis through the intercostals space, the TNR was 100%. When directing the beam axis lied at the rib edge and on the centre of middle rib,the TNR decreased sharply. When the ribs were placed 6cm and 9cm in front of the focal plane, the TNR was more than 50%. ②When the ribs were placed in HIFU beam path, the volume of necrosis decreased compared with those in free field. The relationship between the ribs and beam axis, the location of ribs placed away from the focal plane different,the volume,length,width and position of the coagulated necrosis different. ③ When the ribs were close to the focal plane,unacceptable damage could been observed on the surface of ribs.When the ribs were far away from the focal plane, the ribs were safe. Conclusions The volume of necrosis decrease when the ribs are placed in HIFU beam path. The relative location of ribs and HIFU beam axis, the location of ribs away from the focal plane are relative with the volume of the coagulated necrosis. When directing the beam axis through the intercostals space, the volume of necrosis is large, and the shape of coagulated necrosis is regulated. When the ribs are closed with the focal plane,ribs are damaged probably. Key words: Ultrasound,high intensity focused; Ribs; Coagulated necrosis; Rib-like barrier

High-intensity focused ultrasound ablation in hepatic and pancreatic cancer: complications

To evaluate the complications of high-intensity focused ultrasound (HIFU) in patients with hepatic and pancreatic cancer. From January 2006 to December 2008, 133 sessions of HIFU treatment were performed in 114 consecutive patients with primary hepatic tumor (n = 57), hepatic metastasis (n = 22), and pancreatic cancer (n = 35) under general anesthesia. The extracorporeal, ultrasound-guided Model-JC system (HAIFU, Chongqing, China) was used. Artificial pleural effusion was created to obtain an adequate sonographic window for ablating hepatic dome masses in 53 patients. We reviewed medical records and imaging findings before, during, and after HIFU. All patients had skin redness, edema, and pain in the treatment regions. All hepatic tumor patients had necrosis of the ribs along the main ultrasound beam path that did not require further treatment. Major complications included biliary obstruction, symptomatic pleural effusion, pneumothorax and fistula formation between an abdominal wall abscess and the ablated hepatic tumor. In 35 pancreatic cancer patients, major complications included third-degree burns and fistula formation between the tumor and duodenum. Delayed complications in hepatic tumor patients included a diaphragmatic rupture and rib fractures along the ultrasound pathway. The complications of HIFU develop mainly around the targeted lesions or along the ultrasound beam pathway. It is essential to have awareness of the possible complications related to HIFU and its imaging features for to avoiding serious complications.

1436: The Study of Effects of Ribs in High Intensity Focused Ultrasound Beam Path on Biological Focal Region and Acoustic Field

1436: The Study of Effects of Ribs in High Intensity Focused Ultrasound Beam Path on Biological Focal Region and Acoustic Field

Analysis of Ultrasound Propagation in High-Temperature Nuclear Reactor Feedwater to Investigate a Clamp-on Ultrasonic Pulse Doppler Flowmeter

The flow rate of nuclear reactor feedwater is an important factor in the operation of a nuclear power reactor. Venturi nozzles are widely used to measure the flow rate. Other types of flowmeters have been proposed to improve measurement accuracy and permit the flow rate and reactor power to be increased. The ultrasonic pulse Doppler system is expected to be a candidate method because it can measure the flow profile across the pipe cross section, which changes with time. For accurate estimation of the flow velocity, the incidence angle of ultrasound entering the fluid should be estimatedusing Snell's law. However, evaluation of the ultrasound propagation is not straightforward, especially for a high-temperature pipe with a clamp-on ultrasonic Doppler flowmeter. The ultrasound beam path may differ from what is expected fromSnell's law due to the temperature gradient in the wedge and variation in the acoustic impedance between interfaces. Recently, simulation code for ultrasound propagation has come into use in the nuclear field for nondestructive testing. This article analyzes and discusses ultrasound propagation, using 3D-FEM simulation code plus the Kirchhoff method, as it relates to flow profile measurement in nuclear reactor feed-water with the ultrasonic pulse Doppler system.

Analysis of Ultrasound Propagation in High-Temperature Nuclear Reactor Feedwater to Investigate a Clamp-on Ultrasonic Pulse Doppler Flowmeter

The flow rate of nuclear reactor feedwater is an important factor in the operation of a nuclear power reactor. Venturi nozzles are widely used to measure the flow rate. Other types of flowmeters have been proposed to improve measurement accuracy and permit the flow rate and reactor power to be increased. The ultrasonic pulse Doppler system is expected to be a candidate method because it can measure the flow profile across the pipe cross section, which changes with time. For accurate estimation of the flow velocity, the incidence angle of ultrasound entering the fluid should be estimatedusing Snell's law. However, evaluation of the ultrasound propagation is not straightforward, especially for a high-temperature pipe with a clamp-on ultrasonic Doppler flowmeter. The ultrasound beam path may differ from what is expected fromSnell's law due to the temperature gradient in the wedge and variation in the acoustic impedance between interfaces. Recently, simulation code for ultrasound propagation has come into use in the nuclear field for nondestructive testing. This article analyzes and discusses ultrasound propagation, using 3D-FEM simulation code plus the Kirchhoff method, as it relates to flow profile measurement in nuclear reactor feed-water with the ultrasonic pulse Doppler system.

E204 超音波パルスドップラー式流速分布計測法を利用した管路内流速分布及び流量計測実験(OS-10 混相流動(2),一般講演,地球温暖化防止と動力エネルギー技術)

In order to improve thermal efficiency and optimize plant operation at electric power plants, ultrasonic pulse Doppler method is being developed to attain the high accuracy in flow rate measurements. Ultrasound waves are emitted into fluid from ultrasonic transducer mounted on the outer surface of a pipe. Waves are bounced back at the surface of ultrasound reflectors flowing in fluid. By detecting Doppler shift frequency of those waves, velocity profiles along the ultrasound beam path can be obtained. Integration of those instantaneous velocity profiles gives us the flow rate in a pipe. In this report, the series of velocity profile measurements are summarized with field tests at an actual power plant for the downstream of an elbow with micro bubbles generated for ultrasonic reflectors.

Features Influencing Patient Selection for Fibroid Treatment with Magnetic Resonance–guided Focused Ultrasound

Of 333 women inquiring about minimally invasive image-guided treatments for fibroids, 209 (63%) were clinically eligible for magnetic resonance-guided focused ultrasound (MRgFUS) according to criteria specified by the Food and Drug Administration and our institution's institutional review board. One hundred three clinically eligible patients had pelvic MR imaging, and 26 (25%) were anatomically eligible for MRgFUS. A substantial proportion were anatomically ineligible for more than one reason, including too much fibroid volume (19%), presence of bowel in the ultrasound beam path (13%), and significant adenomyosis (12%). Overall, 14% of women inquiring about minimally invasive image-guided treatments for fibroids were eligible for MRgFUS, a percentage that increased when additional institutional review board restrictions were lifted.

Microbubble Contrast Agent with Focused Ultrasound to Create Brain Lesions at Low Power Levels: MR Imaging and Histologic Study in Rabbits

To evaluate magnetic resonance (MR) imaging-based thermometry for predicting the onset and spatial extent of lesions produced by focused ultrasound combined with a microbubble contrast agent (Optison; GE Healthcare, Milwaukee, Wis) and to compare the resulting induced temperature increase and threshold for damage with those in studies performed without the agent. The experiments were approved by the animal care committee. Fifty-three locations in the brains of 15 rabbits were sonicated with various exposure parameters by using a 1.5-MHz focused ultrasound transducer. MR imaging was used to map the temperature rise and, along with light microscopy, to examine the lesions. Diameters of isotherms created from thermometry were compared with the resulting lesions by using Bland-Altman analysis and linear regression. The minimum acoustic power necessary for lesion creation was determined, and the apparent temperature threshold for damage was calculated with probit analysis. These thresholds were compared with prior work performed without the contrast agent. The heating induced with the microbubbles was compared with that in sonications performed without them by using a t test. The MR imaging-mapped temperature distributions matched the shape of the lesions. The diameters of isotherms correlated well with diameters measured at contrast material-enhanced MR imaging (mean difference between measurements, 0.0 mm +/- 0.5; R = 0.93). The temperature increase with microbubbles was statistically larger (P < .01) than for sonications performed without microbubbles. In some locations (mostly continuous wave exposures), damage was observed along the ultrasound beam path. The time-averaged acoustic power damage threshold was reduced by 91% for 10-second exposures when compared with earlier studies performed without microbubbles. The probability of producing lesions was 50% at a temperature increase of 5.9 degrees C, 5.5 degrees C lower than was observed earlier without the agent. MR imaging-based temperature measurements appeared to correlate with focused ultrasound-induced lesions in the brain when microbubbles were present, even though the temperature appeared to be below the threshold for thermal damage.

Thermal contribution of compact bone to intervening tissue-like media exposed to planar ultrasound

The presence of bone in the ultrasound beam path raises concerns, both in diagnostic and therapeutic applications, because significant temperature elevations may be induced at nearby soft tissue–bone interfaces due the facts that ultrasound is (i) highly absorbed in bone and (ii) reflected at soft tissue–bone interfaces in various degrees depending on angle of incidence. Consequently, in ultrasonic thermal therapy, the presence of bone in the ultrasound beam path is considered a major disadvantage and it is usually avoided. However, based on clinical experience and previous theoretical studies, we hypothesized that the presence of bone in superficial unfocused ultrasound hyperthermia can actually be exploited to induce more uniform and enhanced (with respect to the no-bone situation) temperature distributions in superficial target volumes. In particular, we hypothesize that the presence of underlying bone in superficial target volume enhances temperature elevation not only by additional direct power deposition from acoustic reflection, but also from thermal diffusion from the underlying bone. Here we report laboratory results that corroborate previous computational studies and strengthen the above-stated hypothesis. Three different temperature measurement techniques, namely, thermometric (using fibre-optic temperature probes), thermographic (using an infrared camera) and magnetic resonance imaging (using proton resonance frequency shifts), were used in high-power short-exposure, and in low-power extended-exposure, experiments using a 19 mm diameter planar transducer operating at 1.0 and 3.3 MHz (frequencies of clinical relevance). The measurements were performed on three technique-specific phantoms (with and without bone inclusions) and experimental set-ups that resembled possible superficial ultrasound hyperthermia clinical situations. Results from all three techniques were in general agreement and clearly showed that significantly higher heating rates (greater than fourfold) were induced in soft tissue-like phantom materials adjacent (within ∼5 mm) to a bovine bone as compared to similar experiments without bone inclusions. For low-power long-exposure experiments, where thermal conduction effects are significant, the thermal impact of bone reached at distances >10 mm from the bone surface (upstream of the bone). Therefore, we hypothesize that underlying bone exposed to planar ultrasound hyperthermia creates a high-temperature thermal boundary at depth that compensates for beam attenuation, thus producing more uniform temperature distribution in the intervening tissue layers. With appropriate technology, this finding may lead to improved thermal doses in superficial treatment sites such as the chest wall and the head/neck.