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In magnetic resonance guided focused ultrasound (MRgFUS) therapy sound waves are focused through the body to selectively ablate difficult to access lesions and tissues. A magnetic resonance imaging (MRI) scanner non-invasively tracks the temperature increase throughout the tissue to guide the therapy. In clinical MRI, tightly fitted hardware comprised of multichannel coil arrays are required to capture high quality images at high spatiotemporal resolution. Ablating tissue requires a clear path for acoustic energy to travel but current array materials scatter and attenuate acoustic energy. As a result coil arrays are placed outside of the transducer, clear of the beam path, compromising imaging speed, resolution, and temperature accuracy of the scan. Here we show that when coil arrays are fabricated by additive manufacturing (i.e., printing), they exhibit acoustic transparency as high as 89.5%. This allows the coils to be placed in the beam path increasing the image signal to noise ratio (SNR) five-fold in phantoms and volunteers. We also characterize printed coil materials properties over time when submerged in the water required for acoustic coupling. These arrays offer high SNR and acceleration capabilities, which can address current challenges in treating head and abdominal tumors allowing MRgFUS to give patients better outcomes.

Microbubble contrast agents are widely used in ultrasound imaging and therapy, typically with transmission center frequencies in the MHz range. Currently, an ultrasound center frequency near 250 kHz is proposed for clinical trials in which ultrasound combined with microbubble contrast agents is applied to open the blood brain barrier, since at this low frequency focusing through the human skull to a predetermined location can be performed with reduced distortion and attenuation compared to higher frequencies. However, the microbubble vibrational response has not yet been carefully evaluated at this low frequency (an order of magnitude below the resonance frequency of these contrast agents). In the past, it was assumed that encapsulated microbubble expansion is maximized near the resonance frequency and monotonically decreases with decreasing frequency. Our results indicated that microbubble expansion was enhanced for 250 kHz transmission as compared with the 1 MHz center frequency. Following 250 kHz insonation, microbubble expansion increased nonlinearly with increasing ultrasonic pressure, and was accurately predicted by either the modified Rayleigh-Plesset equation for a clean bubble or the Marmottant model of a lipid-shelled microbubble. The expansion ratio reached 30-fold with 250 kHz at a peak negative pressure of 400 kPa, as compared to a measured expansion ratio of 1.6 fold for 1 MHz transmission at a similar peak negative pressure. Further, the range of peak negative pressure yielding stable cavitation in vitro was narrow (~100 kPa) for the 250 kHz transmission frequency. Blood brain barrier opening using in vivo transcranial ultrasound in mice followed the same trend as the in vitro experiments, and the pressure range for safe and effective treatment was 75-150 kPa. For pressures above 150 kPa, inertial cavitation and hemorrhage occurred. Therefore, we conclude that (1) at this low frequency, and for the large oscillations, lipid-shelled microbubbles can be approximately modeled as clean gas microbubbles and (2) the development of safe and successful protocols for therapeutic delivery to the brain utilizing 250 kHz or a similar center frequency requires consideration of the narrow pressure window between stable and inertial cavitation.

PurposeEndoluminal ultrasound may serve as a minimally invasive option for delivering thermal ablation to pancreatic tumors adjacent to the stomach or duodenum. The objective of this study was to explore the basic feasibility of this treatment strategy through the design, characterization, and evaluation of proof-of-concept endoluminal ultrasound applicators capable of placement in the gastrointestinal (GI) lumen for volumetric pancreas ablation under MR guidance.MethodsTwo variants of the endoluminal applicator, each containing a distinct array of two independently powered transducers (10 × 10 mm 3.2 MHz planar; or 8 × 10 × 20 mm radius of curvature 3.3 MHz curvilinear geometries) at the distal end of a meter long flexible catheter assembly, were designed and fabricated. Transducers and circulatory water flow for acoustic coupling and luminal cooling were contained by a low-profile polyester balloon covering the transducer assembly fixture. Each applicator incorporated miniature spiral MR coils and mechanical features (guiding tips and hinges) to facilitate tracking and insertion through the GI tract under MRI guidance. Acoustic characterization of each device was performed using radiation force balance and hydrophone measurements. Device delivery into the upper GI tract, adjacent to the pancreas, and heating characteristics for treatment of pancreatic tissue were evaluated in MR-guided ex vivo and in vivo porcine experiments. MR guidance was utilized for anatomical target identification, tracking/positioning of the applicator, and MR temperature imaging (MRTI) for PRF-based multislice thermometry, implemented in the real-time RTHawk software environment.ResultsForce balance and hydrophone measurements indicated efficiencies of 48.8% and 47.8% and -3 dB intensity beam-widths of 3.2 and 1.2 mm for the planar and curvilinear transducers, respectively. Ex vivo studies on whole-porcine carcasses revealed capabilities of producing ablative temperature rise (ΔT > 15 °C) contours in pancreatic tissue 4-40 mm long and 4-28 mm wide for the planar transducer applicator (1-13 min sonication duration, ∼4 W/cm(2) applied acoustic intensity). Curvilinear transducers produced more selective heating, with a narrower ΔT > 15 °C contour length and width of up to 1-24 mm and 2-7 mm, respectively (1-7 min sonication duration, ∼4 W/cm(2) applied acoustic intensity). Active tracking of the miniature spiral coils was achieved using a Hadamard encoding tracking sequence, enabling real-time determination of each coil's coordinates and automated prescription of imaging planes for thermometry. In vivo MRTI-guided heating trials in three pigs demonstrated capability of ∼20 °C temperature elevation in pancreatic tissue at 2 cm depths from the applicator, with 5-7 W/cm(2) applied intensity and 6-16 min sonication duration. Dimensions of thermal lesions in the pancreas ranged from 12 to 28 mm, 3 to 10 mm, and 5 to 10 mm in length, width, and depth, respectively, as verified through histological analysis of tissue sections. Multiple-baseline reconstruction and respiratory-gated acquisition were demonstrated to be effective strategies in suppressing motion artifacts for clear evolution of temperature profiles during MRTI in the in vivo studies.ConclusionsThis study demonstrates the technical feasibility of generating volumetric ablation in pancreatic tissue using endoluminal ultrasound applicators positioned in the stomach lumen. MR guidance facilitates target identification, device tracking/positioning, and treatment monitoring through real-time multislice PRF-based thermometry.

PurposeEvaluate whether a decrease in apparent diffusion coefficient (ADC), associated with loss of tissue viability (LOTV), can be observed during the course of thermal ablation of the prostate.MethodsThermal ablation was performed in a healthy in vivo canine prostate model (N = 2, ages: 5 yr healthy, mixed breed, weights: 13-14 kg) using a transurethral high-intensity ultrasound catheter and was monitored using a strategy that interleaves diffusion weighted images and gradient-echo images. The two sequences were used to measure ADC and changes in temperature during the treatment. Changes in temperature were used to compute expected changes in ADC. The difference between expected and measured ADC, ADCDIFF, was analyzed in regions ranging from moderate hyperthermia to heat fixation. A receiver operator characteristic (ROC) curve analysis was used to select a threshold of detection of LOTV. Time of threshold activation, tLOTV, was compared with time to reach CEM43 = 240, tDOSE.ResultsThe observed relationship between temperature and ADC in vivo (2.2%/ °C, 1.94%-2.47%/ °C 95% confidence interval) was not significantly different than the previously reported value of 2.4%/ °C in phantom. ADCDIFF changes after correction for temperature showed a mean decrease of 25% in ADC 60 min post-treatment in regions where sufficient thermal dose (CEM43 > 240) was achieved. Following our ROC analysis, a threshold of 2.25% decrease in ADCDIFF for three consecutive time points was chosen as an indicator of LOTV. The ADCDIFF was found to decrease quickly (1-2 min) after reaching CEM43 = 240 in regions associated with heat fixation and more slowly (10-20 min) in regions that received slower heating.ConclusionsSimultaneous monitoring of ADC and temperature during treatment might allow for a more complete tissue viability assessment of ablative thermal treatments in the prostate. ADCDIFF decreases during the course of treatment may be interpreted as loss of tissue viability.

ObjectivesThe aims of this study were to evaluate in a canine model applicators designed for ablation of human benign prostatic hyperplasia (BPH) in vivo under magnetic resonance imaging (MRI) guidance, including magnetic resonance thermal imaging (MRTI), determine the ability of MRI techniques to visualize ablative changes in prostate, and evaluate the acute and longer term histologic appearances of prostate tissue ablated during these studies.Materials and methodsAn MRI-compatible transurethral device incorporating a tubular transducer array with dual 120° sectors was used to ablate canine prostate tissue in vivo, in zones similar to regions of human BPH (enlarged transition zones). Magnetic resonance thermal imaging was used for monitoring of ablation in a 3-T environment, and postablation MRIs were performed to determine the visibility of ablated regions. Three canine prostates were ablated in acute studies, and 2 animals were rescanned before killing at 31 days postablation. Acute and chronic appearances of ablated prostate tissue were evaluated histologically and were correlated with the MRTI and postablation MRI scans.ResultsIt was possible to ablate regions similar in size to enlarged transition zone in human BPH in 6 to 18 minutes. Regions of acute ablation showed a central "heat-fixed" region surrounded by a region of more obvious necrosis with complete disruption of tissue architecture. After 31 days, ablated regions demonstrated complete apparent resorption of ablated tissue with formation of cystic regions containing fluid. The inherent cooling of the urethra using the technique resulted in complete urethral preservation in all cases.ConclusionsProstatic ablation of zones of size and shape corresponding to human BPH is possible using appropriate transurethral applicators using MRTI, and ablated tissue may be depicted clearly in contrast-enhanced magnetic resonance images. The ability accurately to monitor prostate tissue heating, the apparent resorption of ablated regions over 1 month, and the inherent urethral preservation suggest that the magnetic resonance-guided techniques described are highly promising for the in vivo ablation of symptomatic human BPH.

IntroductionThere is currently a great deal of interest in the possible use of focal therapies for prostate cancer, since such treatments offer the prospect for control or cure of the primary disease with minimal side effects. Many forms of thermal therapy have been proposed for focal ablation of prostate cancer, including laser, high intensity ultrasound and cryotherapy. This review will demonstrate the important roles that magnetic resonance imaging (MRI) guidance can offer to such focal ablation, focusing on the use of high intensity ultrasonic applicators as an example of one promising technique.Materials and methodsTransurethral and interstitial high intensity ultrasonic applicators, designed specifically for ablation of prostate tissue were tested extensively in vivo in a canine model. The roles of MRI in positioning the devices, monitoring prostate ablation, and depicting ablated tissue were assessed using appropriate MRI sequences.ResultsMRI guidance provides a very effective tool for the positioning of ablative devices in the prostate, and thermal monitoring successfully predicted ablation of prostate tissue when a threshold of 52 ºC was achieved. Contrast enhanced MRI accurately depicted the distribution of ablated prostate tissue, which is resorbed at 30 days.ConclusionsGuidance of thermal therapies for focal ablation of prostate cancer will likely prove critically dependent on MRI functioning in four separate roles. Our studies indicate that in three roles: device positioning; thermal monitoring of prostate ablation; and depiction of ablated prostate tissue, MR techniques are highly accurate and likely to be of great benefit in focal prostate cancer ablation. A fourth critical role, identification of cancer within the gland for targeting of thermal therapy, is more problematic at present, but will likely become practical with further technological advances.

Background Moderate-to-severe acute pain is prevalent in many healthcare settings and associated with adverse outcomes. Peripheral nerve blockade using traditional needle-based and local anesthetic-based techniques improves pain outcomes for some patient populations but has shortcomings limiting use. These limitations include its invasiveness, potential for local anesthetic systemic toxicity, risk of infection with an indwelling catheter, and relatively short duration of blockade compared with the period of pain after major injuries. Focused ultrasound is capable of inhibiting the peripheral nervous system and has potential as a pain management tool. However, investigations of its effect on peripheral nerve nociceptive fibers in animal models of acute pain are lacking. In an in vivo acute pain model, we investigated focused ultrasound's effects on behavior and peripheral nerve structure. Methods Focused ultrasound was applied directly to the sciatic nerve of rats just prior to a hindpaw incision; three control groups (focused ultrasound sham only, hindpaw incision only, focused ultrasound sham+hindpaw incision) were also included. For all four groups (intervention and controls), behavioral testing (thermal and mechanical hyperalgesia, hindpaw extension and flexion) took place for 4 weeks. Structural changes to peripheral nerves of non-focused ultrasound controls and after focused ultrasound application were assessed on days 0 and 14 using light microscopy and transmission electron microscopy. Results Compared with controls, after focused ultrasound application, animals had (1) increased mechanical nociceptive thresholds for 2 weeks; (2) sustained increase in thermal nociceptive thresholds for =4 weeks; (3) a decrease in hindpaw motor response for 0.5 weeks; and (4) a decrease in hindpaw plantar sensation for 2 weeks. At 14 days after focused ultrasound application, alterations to myelin sheaths and nerve fiber ultrastructure were observed both by light and electron microscopy. Discussion Focused ultrasound, using a distinct parameter set, reversibly inhibits A-delta peripheral nerve nociceptive, motor, and non-nociceptive sensory fiber-mediated behaviors, has a prolonged effect on C nociceptive fiber-mediated behavior, and alters nerve structure. Focused ultrasound may have potential as a peripheral nerve blockade technique for acute pain management. However, further investigation is required to determine C fiber inhibition duration and the significance of nerve structural changes. [ABSTRACT FROM AUTHOR]