MR Temperature Research Articles

TU-D-210A-02: Catheter-Based Ultrasound Technology for Image-Guided Hyperthermia and Thermal Ablation

Catheter-based ultrasound applicators have been developed for delivering hyperthermia and thermal ablation for the treatment of cancer and benign diseases. This technology includes interstitial applicators for tumor ablation and hyperthermia delivery during brachytherapy, transurethral devices for conformal prostate hyperthermia and ablation, and an endocavity applicator integrated with an HDR ring applicator for intrauterine hyperthermia. The common design incorporates arrays of multiple ultrasound transducers which provide dynamic axial and angular control of hyperthermia and thermal ablation. Performance was evaluated in phantom, excised tissue, in vivo experiments in canine prostate under MR temperature monitoring, clinical hyperthermia, and 3D-biothermal simulations with patient specific anatomy. Interstitial and endocavity devices can tailor hyperthermia to large treatment volumes, with multi-sectored and multi-transducer power control useful to limit exposure to rectum and bladder. Transurethral applicators include curvilinear transducers with rotational sweeping of focused heating patterns, and multi-sectored tubular devices capable of dynamic angular control without applicator movement. Curvilinear transurethral produce target conforming coagulation zones that can cover either the whole gland or defined focal regions. Multi-sectored transurethral applicators can dynamically control the angular heating profile and target large regions of the prostate without applicator manipulation. High-power interstitial implants with directional devices can be used to effectively ablate defined target regions while avoiding sensitive tissues. MR temperature monitoring can effectively define the extent of thermal damage and provided a means for real-time control of the applicators. Preliminary investigations have also demonstrated ultrasound strain imaging can be used to monitor the ablated tissue. In summary, these catheter-based ultrasound devices allow for dynamic control of heating profiles along the length and angular expanse of the applicator during therapy delivery, are amenable to MR monitoring, and provide a minimally-invasive technique for true 3D control of hyperthermia and thermal ablation. (Support NIH R01CA122276, R01CA111981, & R41CA121740).

An MRI‐compatible system for focused ultrasound experiments in small animal models

The development of novel MRI-guided therapeutic ultrasound methods including potentiated drug delivery and targeted thermal ablation requires extensive testing in small animals such as rats and mice due to the widespread use of these species as models of disease. An MRI-compatible, computer-controlled three-axis positioning system was constructed to deliver focused ultrasound exposures precisely to a target anatomy in small animals for high-throughput preclinical drug delivery studies. Each axis was constructed from custom-made nonmagnetic linear ball stages driven by piezoelectric actuators and optical encoders. A range of motion of 5 x 5 x 2.5 cm3 was achieved, and initial bench top characterization demonstrated the ability to deliver ultrasound to the brain with a spatial accuracy of 0.3 mm. Operation of the positioning system within the bore of a clinical 3 T MR imager was feasible, and simultaneous motion and MR imaging did not result in any mutual interference. The system was evaluated in its ability to deliver precise sonications within the mouse brain, linear scanned exposures in a rat brain for blood barrier disruption, and circular scans for controlled heating under MR temperature feedback. Initial results suggest that this is a robust and precise apparatus for use in the investigation of novel ultrasound-based therapeutic strategies in small animal preclinical models.

Analysis of the spatial and temporal accuracy of heating in the prostate gland using transurethral ultrasound therapy and active MR temperature feedback

A new MRI-guided therapy is being developed as a minimally invasive treatment for localized prostate cancer utilizing high-intensity ultrasound energy to generate a precise region of thermal coagulation within the prostate gland. The purpose of this study was to evaluate in vivo the capability to produce a spatial heating pattern in the prostate that accurately matched the shape of a target region using transurethral ultrasound heating and active MR temperature feedback. Experiments were performed in a canine model (n = 9) in a 1.5 T MR imager using a prototype device comprising a single planar transducer operated under rotational control. The spatial temperature distribution, measured every 5 s with MR thermometry, was used to adjust the acoustic power and rotation rate in order to achieve a temperature of 55 °C along the outer boundary of the target region. The results demonstrated the capability to produce accurate spatial heating patterns within the prostate gland. An average temperature of 56.2 ± 0.6 °C was measured along the outer boundary of the target region across all experiments in this study. The average spatial error between the target boundary and the 55 °C isotherm was 0.8 ± 0.7 mm (−0.2 to 3.2 mm), and the overall treatment time was ⩽20 min for all experiments. Excellent spatial agreement was observed between the temperature information acquired with MRI and the pattern of thermal damage measured on H&E-stained tissue sections. This study demonstrates the benefit of adaptive energy delivery using active MR temperature feedback, and an excellent capability to treat precise regions within the prostate gland with this technology.

The utility of pelvic coil SNR testing in the quality assurance of a clinical MRgFUS system

During MRI-guided focused ultrasound (MRgFUS) treatments of uterine fibroids using ExAblate®2000, tissue ablations are delivered by a FUS transducer while MR imaging is performed with a pelvic receiver coil. The consistency of the pelvic coil performance is crucial for reliable MR temperature measurements as well as detailed anatomic imaging in patients. Test sonications in a gel phantom combined with MR thermometry are used to test the performance of the FUS transducer prior to each treatment. As we show, however, these tests do not adequately evaluate receiver coil performance prior to clinical use. This could become a problem since the posterior part of the coil is frequently moved and can malfunction. The aim of this work is to demonstrate the utility of the signal-to-noise ratio (SNR) as a reliable indicator of pelvic coil performance. Slight modification of the vendor-provided coil support was accomplished to assure reproducible coil positioning. The SNR was measured in a gel phantom using axial acquisitions from the 3D-localizer scan. MR temperature and SNR measurements were obtained using a degraded receiver coil (with posterior element removed) and a known faulty coil, and compared to those obtained with a fully functioning coil. While the MR temperature-based tests were insensitive to change in pelvic coil performance, (degraded, p = 0.24; faulty, p = 0.28), the SNR tests were highly sensitive to coil performance, (degraded, p < 0.001; faulty, p < 0.001). Additional clinical data illustrate the utility of SNR testing of the receiver coil. These tests require minimal (or possibly no) additional scan time and have proven to be effective in our clinical practice.

Validation of fast MR thermometry at 1.5 T with gradient‐echo echo planar imaging sequences: phantom and clinical feasibility studies

The purpose of this work was to validate in phantom studies and demonstrate the clinical feasibility of MR proton resonance frequency thermometry at 1.5 T with segmented gradient-echo echo planar imaging (GRE-EPI) sequences during liver tumour radiofrequency (RF) ablation. Classical GRE acquisitions and segmented GRE-EPI acquisitions were performed at 1.5 T during simultaneous RF heating with an MR-compatible RF electrode placed in an agar gel phantom. Temperature increments were calculated and compared with four optical temperature probe measurements using Bland- Altman analysis. In a preliminary clinical feasibility study, the rapid GRE-EPI sequence (echo train length = 13) was used for MR temperature monitoring of RF ablation of liver tumours in three patient procedures. For phantom experiments, the Bland-Altman mean of differences between MR and optical probe temperature measurements was <0.4 degrees C, and the 95% limits of agreement value was <1.4 degrees C. For the in vivo studies, respiratory-triggered GRE-EPI acquisitions yielded a temperature accuracy of 1.3 +/- 0.4 degrees C (acquisition time = 0.6 s/image, spatial coverage of three slices/respiratory cycle). MR proton resonance frequency thermometry at 1.5 T yields precise and accurate measurements of temperature increment with both classical GRE and rapid GRE-EPI sequences. Rapid GRE-EPI sequences minimize intra-scan motion effects and can be used for MR thermometry during RF ablation in moving organs.

MR temperature monitoring applying the proton resonance frequency method in liver and kidney at 0.2 and 1.5 T: segment-specific attainable precision and breathing influence

The objective of this study was to evaluate breathing influence on precision in temperature determination by using the proton resonance frequency (PRF) shift method depending on the location in abdominal organs at 0.2 and 1.5 T. Phase images were acquired with gradient echo sequences in a total of 12 volunteers at 1.5 and 0.2 T. Different examination protocols were performed (each 8 measurements with (1) in-/expiration, (2) free breathing, (3) under breathhold, (4) with breathing belt triggering, and (5) with navigator triggering (integrated in MR signal acquisition). Regions of interest were placed on liver and kidneys, and the resulting phase differences between the measurements were transformed into corresponding temperature differences. Precision significantly varied depending on the liver segment or location in the kidney. Gating techniques were found better than breathhold techniques and clearly better than non-gated examinations. The most precise approach reached a standard deviation of 2.0 degrees C under continuous breathing when navigator gating was used at 1.5 T. PRF temperature measurement is feasible even for moving organs in the abdomen at 0.2 and 1.5 T. The location of the target region and the required precision of the measurements should direct the choice of examination mode.

WE-C-351-01: Characterization of Gold Nanoshells for Thermal Therapy Using MRI

Purpose: To investigate the development of light activated gold nanoshells as mediators for highly conformal photothermal therapy of soft‐tissue tumors with an emphasis on illustrating how results from MR‐guidance in phantoms, in vivo small and large animals have helped demonstrate feasibility and shape the therapeutic approach. Method and Materials: Experiments were performed on a 1.5T MRI.Temperature was measured in real‐time using MR thermography based on the proton resonance frequency shift. Nanoshell phantoms were employed to evaluate effects of concentration and size on distribution of heat when activated by an 808‐nm laser and quantitatively correlated to a 3D finite element model. Passive (enhanced permeability and retention) and active (EGFR receptor) targeting was studied in tumor xenografts. Feasibility of interstitial therapy delivery was investigated in a large animalmodel of braincancer using a canine sarcomamodel.Results: Numerical modeling of heating of gold‐silica nanoshells in phantom correlated excellently with observed MR measured heating patterns. SEM results indicate that passive accumulation of nanoshells (∼140 nm) results in large concentrations near tumor microvasculature (corroborated by MR heating and dynamic enhancement patterns) and this results in statistically significant increase in temperature (21±4°C) over controls after 3 minutes at 4 W/cm2 in a PC3 xenograph. Intravenous injection of these nanoshells into a dog model of cancer resulted in selective heating of the target tumor observable on MRI. EGFR receptor targeting allowed increased uptake of smaller nanoshells (<30 nm) versus non‐targeted nanoshells. Addition of iron‐oxide cores facilitated MR imaging of nanoshells in addition to heating. Conclusion:Gold nanoshells effect a more conformal thermal therapy delivery, as confirmed in a large animalmodel of braincancer. MR temperature imaging and guidance is an invaluable tool in the investigation and development of this emerging thermal therapy technique as it moves from Petri dish to patient.

Transurethral ultrasound applicators with dynamic multi‐sector control for prostate thermal therapy: In vivo evaluation under MR guidance

The purpose of this study was to explore the feasibility and performance of a multi-sectored tubular array transurethral ultrasound applicator for prostate thermal therapy, with potential to provide dynamic angular and length control of heating under MR guidance without mechanical movement of the applicator. Test configurations were fabricated, incorporating a linear array of two multi-sectored tubular transducers (7.8-8.4 MHz, 3 mm OD, 6 mm length), with three 120 degrees independent active sectors per tube. A flexible delivery catheter facilitated water cooling (100 ml min(-1)) within an expandable urethral balloon (35 mm long x 10 mm diameter). An integrated positioning hub allows for rotating and translating the transducer assembly within the urethral balloon for final targeting prior to therapy delivery. Rotational beam plots indicate approximately 90 degrees-100 degrees acoustic output patterns from each 120 degrees transducer sector, negligible coupling between sectors, and acoustic efficiencies between 41% and 53%. Experiments were performed within in vivo canine prostate (n = 3), with real-time MR temperature monitoring in either the axial or coronal planes to facilitate control of the heating profiles and provide thermal dosimetry for performance assessment. Gross inspection of serial sections of treated prostate, exposed to TTC (triphenyl tetrazolium chloride) tissue viability stain, allowed for direct assessment of the extent of thermal coagulation. These devices created large contiguous thermal lesions (defined by 52 degrees C maximum temperature, t43 = 240 min thermal dose contours, and TTC tissue sections) that extended radially from the applicator toward the border of the prostate (approximately15 mm) during a short power application (approximately 8-16 W per active sector, 8-15 min), with approximately 200 degrees or 360 degrees sector coagulation demonstrated depending upon the activation scheme. Analysis of transient temperature profiles indicated progression of lethal temperature and thermal dose contours initially centered on each sector that coalesced within approximately 5 min to produce uniform and contiguous zones of thermal destruction between sectors, with smooth outer boundaries and continued radial propagation in time. The dimension of the coagulation zone along the applicator was well-defined by positioning and active array length. Although not as precise as rotating planar and curvilinear devices currently under development for MR-guided procedures, advantages of these multi-sectored transurethral applicators include a flexible delivery catheter and that mechanical manipulation of the device using rotational motors is not required during therapy. This multi-sectored tubular array transurethral ultrasound technology has demonstrated potential for relatively fast and reasonably conformal targeting of prostate volumes suitable for the minimally invasive treatment of BPH and cancer under MR guidance, with further development warranted.

MRI‐compatible transurethral ultrasound system for the treatment of localized prostate cancer using rotational control

Magnetic resonance imaging (MRI)-guided transurethral ultrasound therapy is a potential minimally invasive treatment for localized prostate cancer offering precise targeting of tissue within the gland, short treatment times, and the capability to quantify the spatial heating pattern delivered during therapy. A significant challenge in MRI-guided ultrasound therapy is the design and construction of MRI-compatible equipment capable of operation in a closed-bore MR imager. We describe a prototype system developed for MRI-guided transurethral ultrasound therapy and characterize the performance of the different components including the heating applicator design, rotational motor, and radio frequency electronics. The ultrasound heating applicator described in this study incorporates a planar transducer and is capable of producing high intensity ultrasound energy in a localized region of tissue. Results demonstrated that the heating applicator exhibits excellent MRI-compatibility, enabling precise MR temperature measurements to be acquired as close as 6 mm from the device. Simultaneous imaging and rotational motion was also possible during treatment using a motor based on piezoelectric actuators. Heating experiments performed in both phantoms and in a canine model with the prototype system verified the capability to perform simultaneous MR imaging and therapy delivery with this system. Real-time control over therapy using MR temperature measurements acquired during heating can be implemented to achieve precise patterns of thermal damage within the prostate gland. The technical feasibility of using the system developed in this study for MRI-guided transurethral ultrasound therapy in a closed-bore MR imager has been demonstrated.

Real time monitoring of radiofrequency ablation based on MR thermometry and thermal dose in the pig liver in vivo

To evaluate the feasibility and accuracy of MR thermometry based on the thermal dose (TD) concept for monitoring radiofrequency (RF) ablations, 13 RF ablations in pig livers were performed under continuous MR thermometry at 1.5 T with a filtered clinical RF device. Respiratory gated fast gradient echo images were acquired simultaneously to RF deposition for providing MR temperature maps with the proton resonant frequency technique. Residual motion, signal to noise ratio (SNR) and standard deviation (SD) of MR temperature images were quantitatively analyzed to detect and reject artifacted images in the time series. SD of temperature measurement remained under 2 degrees C. Macroscopic analysis of liver ablations showed a white zone (Wz) surrounded by a red zone (Rz). A detailed histological analysis confirmed the ongoing nature of the coagulation necrosis in both Wz and Rz. Average differences (+/-SD) between macroscopic size measurements of Wz and Rz and TD predictions of ablation zones were 4.1 (+/-1.93) mm and -0.71 (+/-2.47) mm, respectively. Correlation values between TD and Wz and TD and Rz were 0.97 and 0.99, respectively. MR thermometry monitoring based on TD is an accurate method to delineate the size of the ablation zone during the RF procedure and provides a clinical endpoint.

Size, anisotropy and doping effects on the coercive field of ferromagnetic nanoparticles

The influence of size, anisotropy and doping effects on the hysteresis loop of ferromagneticnanoparticles is studied, based on the modified Heisenberg model. A Green’s function techniquein real space allows the calculation of the dependence of the magnetization on the temperature,magnetic field, anisotropy, defects and particle size. It is demonstrated that the coercive fieldHc is verysensitive to the surface single-ion anisotropy, and to the exchange interaction constant on the surfaceJs and in thedefect shells Jd. With respect to the strong surface single-site anisotropyDs, we observe atsmall particle size, N = 4 shells, a maximum in the size dependence of the coercive field, whereas forthe small surface anisotropy there is no maximum. Taking into account thatJ can be different in the defect shells compared to the case withoutdefects, we have obtained for the first time that the coercive fieldHc, the permanentmagnetization Mr and theCurie temperature TC can increase or decrease for different kinds of doping ions. The dependence on the particlesize is discussed, too. The results are in accordance with the experimental data.

TU‐C‐M100F‐03: MRI‐Controlled Transurethral Ultrasound Therapy for Prostate Cancer

Purpose: To develop and test a transurethral ultrasound therapy system which uses quantitative real‐time MRI temperature feedback to control the shape of the coagulated region within the prostate while sparing surrounding structures from thermal damage. Method and Materials: An MRI‐compatible transurethral heating applicator comprised of planar ultrasound transducers that produce a directional heating pattern has been constructed. This device is rotated within a 1.5T MR imager to distribute energy to targeted regions of the prostate by an MRI‐compatible motor, concurrent with imaging. The region of the prostate to be treated is selected based on MR imaging information. Subsequent heating is controlled by MRI temperature images acquired every 5s and a complete prostate volume can be coagulated with a single rotation in about 20m. In‐vivo experiments have been performed in a canine model and the spatial accuracy of the coagulation patterns has been assessed using contrast‐enhanced MR images and a novel, quantitative whole‐mount histology technique with image registration to the MR temperature maps. Results: Sufficient spatial resolution and temperature accuracy can be obtained at 1.5T to provide accurate feedback control of the coagulation pattern within ±1.5mm of the targeted heating radius. Histological analysis indicates that, under these treatment conditions, the margin between completely coagulated tissue and apparently undamaged tissue is ⩽3mm in this acute assay. These histological boundaries, when registered carefully with the quantitative MRI temperature histories, provide a good estimate of the temperature threshold (54.6±1.7°C) for complete coagulation. The contrast‐enhanced MR images clearly show the coagulated region but register less accurately with the histological boundaries. Conclusion: Successful control of transurethral ultrasound therapy using quantitative, real‐time MRI temperature images has been demonstrated in vivo. This technology offers good potential for an effective treatment for localized prostate cancer with reduction in morbidity.

Conformal thermal therapy using planar ultrasound transducers and adaptive closed-loop MR temperature control: demonstration in gel phantoms and ex vivo tissues

MRI-guided transurethral ultrasound therapy offers a minimally invasive approach for the treatment of localized prostate cancer. Integrating a multi-element planar transducer with active MR temperature feedback can enable three-dimensional conformal thermal therapy of a target region within the prostate gland while sparing surrounding normal tissues. Continuous measurement of the temperature distribution in tissue enables dynamic compensation for unknown changes in blood flow and tissue properties during treatment. The main goal of this study was to evaluate the feasibility of using active temperature feedback on a clinical 1.5 T MR imager for conformal thermal therapy. MR thermometry was performed during heating in both gel phantoms and excised tissue with a transurethral heating applicator, and the rotation rate and power were varied based on the thermal measurements. The capability to produce a region of thermal damage that matched a target boundary was evaluated. The influence of a cooling gradient (to simulate cooling of the rectum or urethra) on the desired pattern of thermal damage was also investigated in gel phantoms. Results showed high correlation between the desired target boundary and the 55 °C isotherm generated during heating with an average distance error of 0.9 mm ± 0.4 mm (n = 6) in turkey breasts, 1.4 mm ± 0.6 mm (n = 4) in gel phantoms without rectal cooling and 1.4 mm ± 0.6 mm (n = 3) in gel phantoms with rectal cooling. The results were obtained using a temporal update rate of 5 s, a spatial resolution of 3 × 3 × 10 mm for the control point, and a temperature uncertainty of approximately 1 °C. The performance of the control algorithm under these conditions was comparable to that of simulations conducted previously by our group. Overall, the feasibility of generating targeted regions of thermal damage with a transurethral heating applicator and active MR temperature feedback has been demonstrated experimentally. This method of treatment appears capable of accounting for unpredictable and varying tissue properties during the treatment.

MR-Thermometrie bei 1,5 Tesla zur thermischen Ablation mittels laserinduzierter Thermotherapie

Evaluation of thermometry with fast MR sequences for laser-induced interstitial laser therapy (LITT) and verification of the thermometric results with a fiber-optic thermometer. In vitro experiments were conducted using an agarose gel mixture and pig liver lobes. MR-guided LITT was performed using a laser power between 3 and 15 watts. Thermometry was performed using longitudinal relaxation time T1 and proton resonance frequency shift (PRF) methods under acquisition of amplitude and phase shift images. PRF was measured with a fast spoiled GRE sequence. Four different sequences were used for T1 thermometry: gradient echo (GE), TrueFISP (TRUFI), Saturation Recovery Turbo-FLASH (SRTF) and Inversion Recovery Turbo-FLASH (IRTF) sequences. The temperature was controlled using a fiber-optic Luxtron device and correlated with the MR temperature. The range of applied and monitored temperatures exceeded 80 degrees Celsius. The temperature dependence showed a good linear relationship up to 60 degrees Celsius. Calibration experiments for the T1 method delivered coefficients of determination from 0.977 to 0.997 for agarose and from 0.958 to 0.995 for the pig liver samples. The IRTF sequence had the highest temperature sensitivity (agarose 0.99, liver 1.19). During LITT the TRUE-FISP sequence exhibited a strong nonlinear relationship. R (2) of this sequence was 0.809 in the agarose experiments. The average temperature errors when heated up to 80 degrees Celsius were 3.86-11.38 degrees Celsius for Agarose gel and 5.7-12.16 degrees Celsius for the liver tissue. SRTF and IRTF sequences exhibited the most linear relationship with temperature but were more dependent on tissue differences. The accuracy of the temperature measurement is sufficient for controlling the coagulation area of the LITT. PRF is the method of choice since it shows the best linear correlation with fiber-optic temperature. If only T1 sequences are concerned, the FLASH sequence is preferred. It is the most robust, though not the most accurate, T1 sequence.

ＭＲガイド下マイクロ波子宮内膜凝固治療のための電極とナビゲーションシステム

To accomplish MR-guided microwave endometrial ablation, a sounding applicator type MR-compatible microwave electrode has been constructed. The visibility of the electrode in MR images was appropriate and temperature changes during microwave ablation were clearly shown with MR temperature maps. Optical and electromagnetic tracking systems for this electrode have also been developed. Both of them were able to control MR image planes with its curved electrode tip, successfully. With the optical tracking system, however, the configuration needs to be changed depending on the direction of the electrode because of the visibility of diodes. Meanwhile, electromagnetic tracking system could be used in any directions of the electrode without taking care of the line of sights and was found to be quite useful for such curved surgical instruments.

Magnetic resonance-guided focused ultrasound surgery (MRgFUS). Four ablation treatments of a single canine hepatocellular adenoma

Background. Canine hepatocellular adenomas are benign, well-differentiated, primary hepatic tumors. Surgical resection is technically demanding and is considered a major procedure with relatively high morbidity rates. Magnetic resonance-guided focused ultrasound surgery (MRgFUS) uses focused ultrasonic energy to non-invasively create a heat-coagulated lesion deep within the body. This effect can be achieved in a controlled, accurate manner. The aim of this study was to evaluate the safety, accuracy and efficacy of non-invasive focal ablation of tissue volumes of a canine benign liver tumour by consecutive MRgFUS sonications. Materials and methods. Four MRgFUS procedures were performed in a 10-year-old, male, mixed large breed dog (45 kg) under general anaesthesia. The exact location and volume of the ablated areas were planned on the MR images. Real-time MR imaging and temperature mapping enabled the immediate evaluation of the effect of each sonication. Different areas were chosen within the tumour. These volumes of tumoral tissue were ablated by multiple sonications. To allow accurate targeting and quality imaging, sonications were performed during 20–30s of apnoea. Between the sonications the dog was normally ventilated. The dog was operated 21 days after the fourth ablative procedure. The tumour was resected and histopathologically examined. Results. The MRgFUS created necrosis with contiguous areas of complete tissue destruction within the liver tumour, in full accordance with the planning. A focal thermal injury to the cartilage of the right lower ribs was noted after the fourth treatment. This lesion became infected and was treated surgically. Ten months after the last treatment the dog is well and healthy. Conclusions. Focused ultrasound ablation of liver tumoral tissue with MR guidance under general anaesthesia and controlled apnoea is a safe and accurate treatment modality. Its main advantage is that it is a completely non-invasive image-guided treatment. The ablation of significant volumes of a highly vascular liver tumoral tissue was achieved. Such tissue can be ablated in a very accurate manner, exactly according to the pretreatment planning on the MR images. The MR imaging characteristics, including real-time temperature mapping, enable real-time control of every step of the ablation process. Mechanical ventilation with intermittent apnoea periods overcomes the problem of the respiratory movements of the liver. Care must be taken to avoid the passage of the ultrasound beam through energy-absorbing calcified tissue.

Real‐time monitoring of radiofrequency ablation of rabbit liver by respiratory‐gated quantitative temperature MRI

To evaluate the feasibility and precision of magnetic resonance imaging (MRI) thermometry for monitoring radiofrequency (RF) liver ablation in vivo and predicting the size of the ablation zone. At 1.5T, respiratory-triggered real-time MR temperature mapping (the proton resonance frequency (PRF) method) was used to monitor RF ablation in rabbit liver (N = 6) under free breathing. The size of the ablation zones, as assessed by histological analyses, was compared with that predicted from MR thermal dose (TD) maps or derived from conventional T1-weighted (T1w), T2-weighted (T2w), and T1w gadolinium (Gd)-enhanced (T1w-Gd) images acquired immediately after the ablation, and on days 4 and 8 postprocedure. MR temperature uncertainty remained under 1-2 degrees C even during RF deposition. The TD maps were shown to be more predictive and precise than the other MR images, with an average predictive precision for the final ablation zone size of about 1 mm as compared to the histologically proven lesion on day 8. Quantitative temperature MRI during RF ablation is feasible and offered a precise indication of the ablation zone size in this preclinical study based on the lethal dose threshold.

Multisectored interstitial ultrasound applicators for dynamic angular control of thermal therapy

Dynamic angular control of thermal ablation and hyperthermia therapy with current interstitial heating technology is limited in capability, and often relies upon nonadjustable angular power deposition patterns and/or mechanical manipulation of the heating device. The objective of this study was to investigate the potential of multisectored tubular interstitial ultrasound devices to provide control of the angular heating distribution without device manipulation. Multisectored tubular transducers with independent sector power control were incorporated into modified versions of internally cooled (1.9 mm OD) and catheter-cooled (2.4 mm OD) interstitial ultrasound applicators in this work. The heating capabilities of these multisectored devices were evaluated by measurements of acoustic output properties, measurements of thermal lesions produced in ex vivo tissue samples, biothermal simulations of thermal ablation and hyperthermia treatments, and MR temperature imaging of ex vivo and in vivo experiments. Acoustic beam measurements of each applicator type displayed a 35 degrees -40 degrees acoustic dead zone between each independent sector, with negligible mechanical or electrical coupling. Thermal lesions produced in ex vivo liver tissue with one, two, or three sectors activated ranged from 13-18 mm in radius with contiguous zones of coagulation between active sectors. The simulations demonstrated the degree of angular control possible by using variable power levels applied to each sector, variable duration of applied constant power to individual sectors, respectively, or a multipoint temperature controller to vary the power applied to each sector. Despite the acoustic dead zone between sectors, the simulations also showed that the variance from the maximum lesion radius with three elements activated is within 4%-13% for tissue perfusions from 1-10 kg m(-3) s(-1). Simulations of hyperthermia with maximum tissue temperatures of 45 degrees C and 48 degrees C displayed radial penetration up to 2 cm of the 40 degrees C steady-state contour. Thermal characterizations of trisectored applicators in ex vivo and in vivo muscle, using real-time MR thermal imaging, reinforced angular controllability and negligible radial variance of the heating pattern from the applicators, demonstrated effective heating penetration, and displayed MR compatibility. The multisectored interstitial ultrasound applicators developed in this study demonstrated a significant degree of dynamic angular control of a heating pattern without device manipulation, while maintaining heat penetration consistent with previously reported results from other interstitial ultrasound applicators.

An Easy-to-Use Microwave Hyperthermia System Combined with Spatially Resolved MR Temperature Maps: Phantom and Animal Studies

Hyperthermia has been used in multimodal cancer treatments, and in randomized, controlled studies, hyperthermia is an effective cancer therapy. For clinical accuracy and safety, however, temperature monitoring during treatment is essential. We aimed to develop a convenient microwave hyperthermia system combined with spatially resolved real-time temperature monitoring to improve its efficacy and safety. Using an MR-compatible irradiation-type microwave applicator, agar phantoms, thigh muscles of rabbit, and subcutaneous VX2 tumors of rabbit were heated in combination with noninvasive MR temperature maps. For MR temperature calculation, a proton resonance frequency method was used. After determination of temperature coefficients and evaluation of the precision in MR thermometry, distribution of microwave heating over time was examined for each substance. The temperature coefficients of phantoms, rabbit muscles, and VX2 tumors were -0.00977, -0.00976, and -0.01027 ppm/ degrees C, respectively. The 95% limits of agreement of MR and fluoroptic thermometry in the three subjects were +0.318/-0.339 degrees C, +0.693/-0.661 degrees C, and +0.564/-0.526 degrees C, respectively. Concerning VX2 tumor, the average tumor temperature was 42.60 +/- 0.14 degrees C and the surface of skin was 43.27 +/- 0.45 degrees C in the 60-min experimental period. With this easy-to-use microwave hyperthermia system, effective hyperthermia was accomplished in phantoms and living animals in combination with MR temperature maps.

Comparing small molecules and polymer for future organic spin-valves

We report spin polarized injection and transport in organic spin-valves made from both organic small molecules and polymers. The devices with the structure La 0.67Sr 0.33MnO 3 (LSMO)/organic spacer/Co showed inverse magnetoresistance and low temperature operation with the vacuum evaporated π-conjugated small molecule 8-hydroxyquinoline aluminium (Alq 3) while normal MR and high temperature operation was observed in devices with the π-conjugated polymer poly(3-hexylthiophene). Due to the proximate values of the work functions of LSMO and Co with the highest occupied molecular orbital (HOMO) energy of the polymers, spin polarized carrier injection is much more efficient in the polymeric spin-valves compared to the organic spin-valves with Alq 3 where carrier injection is hindered due to greater barrier height. Efficient spin transport is also observed in polymeric spin-valves and can be attributed to longer conjugation in the polymeric chains compared to the small molecules.