Juan Plata

Applicators for magnetic resonance-guided ultrasonic ablation of benign prostatic hyperplasia.

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.

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

PURPOSE Feasibility of targeted and volumetric hyperthermia (40-45 °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. METHODS The 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). RESULTS Acoustic intensities considered during simulation were limited to ensure mild hyperthermia (Tmax < 45 °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 > 41 °C) were estimated. Numerical simulations indicated that T > 41 °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. CONCLUSIONS The ExAblate 2100, designed specifically for thermal ablation, can be controlled for delivering continuous hyperthermia in prostate while working within operational constraints.

Toward Volumetric MR Thermometry With the MASTER Sequence

MR temperature monitoring is an indispensable tool for high intensity focused ultrasound. In this paper, a new technique known as MASTER (multiple adjacent slice thermometry with excitation refocusing) is presented which improves the speed and accuracy of multiple-slice MR thermometry. Defocusing the magnetization after exciting a slice allows for multiple slices to be excited concurrently and stored in k-space. The magnetization from each excitation is then refocused and read in sequence. This approach increases TE for each slice, greatly improving temperature SNR as compared to conventional slice interleaving. Gradient sequence design optimization is required to minimize diffusion losses while maintaining high sequence efficiency. Flexibility in selecting position, update rate, accuracy, and voxel size for each slice independently allows for freedom in design to fit different application needs. Results are shown in phantom and in vivo validating the feasibility of the sequence, and comparing it to interleaved GRE. Sample design curves are presented that contrast the MASTER design space with that of interleaved GRE thermometry.

Autonomous Real-Time Interventional Scan Plane Control With a 3-D Shape-Sensing Needle

This study demonstrates real-time scan plane control dependent on three-dimensional needle bending, as measured from magnetic resonance imaging (MRI)-compatible optical strain sensors. A biopsy needle with embedded fiber Bragg grating (FBG) sensors to measure surface strains is used to estimate its full 3-D shape and control the imaging plane of an MR scanner in real-time, based on the needles estimated profile. The needle and scanner coordinate frames are registered to each other via miniature radio-frequency (RF) tracking coils, and the scan planes autonomously track the needle as it is deflected, keeping its tip in view. A 3-D needle annotation is superimposed over MR-images presented in a 3-D environment with the scanners frame of reference. Scan planes calculated based on the FBG sensors successfully follow the tip of the needle. Experiments using the FBG sensors and RF coils to track the needle shape and location in real-time had an average root mean square error of 4.2 mm when comparing the estimated shape to the needle profile as seen in high resolution MR images. This positional variance is less than the image artifact caused by the needle in high resolution SPGR (spoiled gradient recalled) images. Optical fiber strain sensors can estimate a needles profile in real-time and be used for MRI scan plane control to potentially enable faster and more accurate physician response.

MR guided thermal therapy of pancreatic tumors with endoluminal, intraluminal and interstitial catheter-based ultrasound devices: Preliminary theoretical and experimental investigations.

Image-guided thermal interventions have been proposed for potential palliative and curative treatments of pancreatic tumors. Catheter-based ultrasound devices offer the potential for temporal and 3D spatial control of the energy deposition profile. The objective of this study was to apply theoretical and experimental techniques to investigate the feasibility of endogastric, intraluminal and transgastric catheter-based ultrasound for MR guided thermal therapy of pancreatic tumors. The transgastric approach involves insertion of a catheter-based ultrasound applicator (array of 1.5 mm OD x 10 mm transducers, 360° or sectored 180°, ~7 MHz frequency, 13-14G cooling catheter) directly into the pancreas, either endoscopically or via image-guided percutaneous placement. An intraluminal applicator, of a more flexible but similar construct, was considered for endoscopic insertion directly into the pancreatic or biliary duct. An endoluminal approach was devised based on an ultrasound transducer assembly (tubular, planar, curvilinear) enclosed in a cooling balloon which is endoscopically positioned within the stomach or duodenum, adjacent to pancreatic targets from within the GI tract. A 3D acoustic bio-thermal model was implemented to calculate acoustic energy distributions and used a FEM solver to determine the transient temperature and thermal dose profiles in tissue during heating. These models were used to determine transducer parameters and delivery strategies and to study the feasibility of ablating 1-3 cm diameter tumors located 2-10 mm deep in the pancreas, while thermally sparing the stomach wall. Heterogeneous acoustic and thermal properties were incorporated, including approximations for tumor desmoplasia and dynamic changes during heating. A series of anatomic models based on imaging scans of representative patients were used to investigate the three approaches. Proof of concept (POC) endogastric and transgastric applicators were fabricated and experimentally evaluated in tissue mimicking phantoms, ex vivo tissue and in vivo canine model under multi-slice MR thermometry. RF micro-coils were evaluated to enable active catheter-tracking and prescription of thermometry slice positions. Interstitial and intraluminal ultrasound applicators could be used to ablate (t43>240min) tumors measuring 2.3-3.4 cm in diameter when powered with 20-30 W/cm2 at 7 MHz for 5-10 min. Endoluminal applicators with planar and curvilinear transducers operating at 3-4 MHz could be used to treat tumors up to 20-25 mm deep from the stomach wall within 5 min. POC devices were fabricated and successfully integrated into the MRI environment with catheter tracking, real-time thermometry and closed-loop feedback control.

A feasibility study on monitoring the evolution of apparent diffusion coefficient decrease during thermal ablation.

PURPOSE Evaluate 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. METHODS Thermal 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. RESULTS The 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. CONCLUSIONS Simultaneous 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.

Targeted hyperthermia in prostate with an MR-guided endorectal ultrasound phased array: patient specific modeling and preliminary experiments

Feasibility of hyperthermia delivery to the prostate with a commercially available MR-guided endorectal ultrasound (ERUS) phased array ablation system (ExAblate 2100, Insightec, LTD) was assessed through computer simulations and ex vivo experiments. The simulations included a 3D FEM-based biothermal model, and acoustic field calculations for the ExAblate phased array (2.3 MHz, 2.3x4.0 cm2) using the rectangular radiator method. Array beamforming strategies were investigated to deliver 30-min hyperthermia (<41 °C) to focal regions of prostate cancer, identified from MR images in representative patient cases. Constraints on power densities, sonication durations and switching speeds imposed by ExAblate hardware and software were incorporated in the models. T<41 °C was calculated in 14-19 cm3 for sonications with planar or diverging beam patterns at 0.9-1.2 W/cm2, and in 3-10 cm3 for curvilinear (cylindrical) or multifocus beam patterns at 1.5-3.3 W/cm2, potentially useful for treating focal disease in a single posterior quadrant. Preliminary experiments included beamformed sonications in tissue mimicking phantom material under MRI-based temperature monitoring at 3T (GRE TE=7.0 ms, TR=15 ms, BW=10.5 kHz, FOV=15 cm, matrix 128x128, FA=40°). MR-temperature rises of 2-6 °C were induced in a phantom with the ExAblate array, consistent with calculated values and lower power settings (~0.86 W/cm2, 3 min.). Conformable hyperthermia may be delivered by tailoring power deposition along the array length and angular expanse. MRgERUS HIFU systems can be controlled for continuous hyperthermia in prostate to augment radiotherapy and drug delivery. [FUS Foundation, NIH R01 122276, 111981].

Catheter-based and endoluminal ultrasound applicators for magnetic resonance image-guided thermal therapy of pancreatic cancer: Preliminary investigations

Ultrasound devices are being investigated for endoluminal and intraductal access for targeted thermal ablation or hyperthermia of pancreas under MR guidance and temperature monitoring. Simulations using patient-specific 3D models were developed for applicator design and development of treatment delivery strategies. MR-compatible devices were constructed for endoluminal (3-5 MHz planar or lightly focused rectangular elements, 12-mm OD assembly, expandable balloon), transgastric interstitial and intraductal (6-8 MHz multi-sectored tubular elements, 2-mm catheter) deployment. Micro-coils were integrated for active MR tracking of position and alignment. The proof-of-concept devices were tested in phantoms, ex vivo tissues, cadaveric porcine models, and in vivo animal models under 3T MR temperature imaging (MRTI). Results indicate endoluminal devices could ablate 2-2.5 cm depth from gastric wall for tumors of the pancreatic head, and multi-sectored tubular intraductal and interstitial applicators could ablate ...

Experimental investigations of an endoluminal ultrasound applicator for MR-guided thermal therapy of pancreatic cancer

An MR-guided endoluminal ultrasound applicator has been proposed for palliative and potential curative thermal therapy of pancreatic tumors. Minimally invasive ablation or hyperthermia treatment of pancreatic tumor tissue would be performed with the applicator positioned in the gastrointestinal (GI) lumen, and sparing of the luminal tissue would be achieved with a water-cooled balloon surrounding the ultrasound transducers. This approach offers the capability of conformal volumetric therapy for fast treatment times, with control over the 3D spatial deposition of energy. Prototype endoluminal ultrasound applicators have been fabricated using 3D printed fixtures that seat two 3.2 or 5.6 MHz planar or curvilinear transducers and contain channels for wiring and water flow. Spiral surface coils have been integrated onto the applicator body to allow for device localization and tracking for therapies performed under MR guidance. Heating experiments with a tissue-mimicking phantom in a 3T MR scanner were performe...

Model-based feasibility assessment and evaluation of prostate hyperthermia with a commercial MRI-guided endorectal high intensity focused ultrasound ablation array

Numerical simulations were conducted to devise methods for targeted and protracted hyperthermia (40–46 °C, 30–60 min) to the prostate with a commercial MR-guided endorectal ultrasound phased array (2.3 MHz, ExAblate, InSightec). The intention is to fast-track clinical implementation of this FDA approved ablation system for delivering targeted hyperthermia in conjunction with radiation or chemotherapy. Conformable hyperthermia to focal tumors in posterior and hemi-gland prostate was simulated through 3D patient-specific biothermal models and beamformed acoustic patterns that incorporated the specific constraints imposed on the ExAblate array: irregular element spacing, switching speeds, operating power and short pulse duration. Simulations indicated that diverging and iso-phase sonications could treat (T > 41 °C, max < 46 °C) 13–23 cm3 with ~1.1 W/cm2, multi-focused patterns could treat 4.0 cm3 with 3.4 W/cm2, and curvilinear patterns could treat 6.5 cm3 with 0.8 W/cm2 while avoiding rectum, urethra, pubic...