Evaluation of Focal Ablation of Magnetic Resonance Imaging Defined Prostate Cancer Using Magnetic Resonance Imaging Controlled Transurethral Ultrasound Therapy with Prostatectomy as the Reference Standard.

PURPOSE: We evaluated magnetic resonance imaging controlled transurethral ultrasound therapy as a treatment for magnetic resonance imaging defined focal prostate cancer using subsequent prostatectomy and histology as the reference standard. MATERIALS AND METHODS: Five men completed this pilot study, which was approved by the institutional review board. Prior to radical prostatectomy focal tumors identified by magnetic resonance imaging were treated by coagulating targeted subtotal 3-dimensional volumes of prostate tissue using magnetic resonance imaging controlled transurethral focused ultrasound. Treatment was performed with a 3 Tesla clinical magnetic resonance imaging unit combined with modified clinical planning software for high intensity focused ultrasound therapy. After prostatectomy whole mount histological sections parallel to the magnetic resonance imaging treatment planes were used to compare magnetic resonance imaging measurements with thermal damage at the cellular level and, thus, evaluate treatment and target accuracy. RESULTS: Three-dimensional target volumes of 4 to 20 cc and with radii up to 35 mm from the urethra were treated successfully. Mean ± SD temperature control accuracy at the target boundary was -1.6 ± 4.8C and the mean spatial targeting accuracy achieved was -1.5 ± 2.8 mm. Mean treatment accuracy with respect to histology was -0.4 ± 1.7 mm with all index tumors falling inside the histological outer limit of thermal injury. CONCLUSIONS: Magnetic resonance imaging guided transurethral ultrasound therapy is capable of generating thermal coagulation and tumor destruction in targeted 3-dimensional angular sectors out to the prostate capsule for prostate glands up to 70 cc in volume. Ultrasound parameters needed to achieve ablation at the prostate capsule were determined, providing a foundation for future studies.

MR thermometry in the human prostate gland at 3.0T for transurethral ultrasound therapy.

PURPOSE: To investigate the spatial, temporal, and temperature resolution of a segmented gradient echo echo-planar imaging (EPI) technique as applied to proton resonance frequency (PRF) shift thermometry at 3 T in the human prostate gland, and to determine appropriate sequence parameters for magnetic resonance imaging (MRI)-controlled transurethral ultrasound thermal therapy. MATERIALS AND METHODS: Eleven healthy volunteers (age range 23-58) were scanned at 3 T with a 16-channel torso coil to study the behavior of a gradient echo EPI thermometry sequence. The temperature stability and geometric distortion were assessed for 11 different parameter sets. In a further five volunteers, the prostate T2* was measured. RESULTS: For all scan parameters investigated, the temperature standard deviation within the prostate was less than 1°C, while the distortion was less than 1 mm. Temperature stability was best with higher TE values (up to 25 msec), larger voxel sizes and lower EPI factors, but this had to be balanced against requirements for good spatial and temporal resolution. Prostate T2* values ranged from 30-50 msec. CONCLUSION: A good balance between temperature stability and temporal/spatial resolution is obtained with TE = 15 msec, voxel size = 1.14 mm, and EPI factor = 9, resulting in a dynamic scan time of 7.2 seconds for the nine slices.

MR imaging-controlled transurethral ultrasound therapy for conformal treatment of prostate tissue: initial feasibility in humans.

PURPOSE: To evaluate the feasibility and safety of magnetic resonance (MR) imaging-controlled transurethral ultrasound therapy for prostate cancer in humans. MATERIALS AND METHODS: This pilot study was approved by the institutional review board and was performed in eight men (mean age, 60 years; range, 49-70 years) with localized prostate cancer (Gleason score≤7, prostate-specific antigen level #15 µg/L) immediately before radical prostatectomy. All patients provided written informed consent. This phase 0 feasibility and safety study is the first evaluation in humans. Transurethral ultrasound therapy was performed with the patient under spinal anesthesia by using a clinical 1.5-T MR unit. Patients then underwent radical prostatectomy, and the resected gland was sliced in the plane of treatment to compare the MR imaging measurements with the pattern of thermal damage. The overall procedure time and coagulation rate were measured. In addition, the spatial targeting accuracy was evaluated, as was the thermal history along the thermal damage boundaries in the gland. RESULTS: The average procedure time was 3 hours, with 2 or fewer hours spent in the MR unit. The treatment was well tolerated by all patients, and a temperature uncertainty of less than 2°C was observed in the treatments. The mean temperature and thermal dose measured along the boundary of thermal coagulation were 52.3°C±2.1 and 3457 (cumulative equivalent minutes at 43°C)±5580, respectively. The mean treatment rate was 0.5 mL/min, and a spatial targeting accuracy of -1.0 mm±2.6 was achieved. CONCLUSION: MR imaging-controlled transurethral ultrasound therapy is feasible, safe, and well tolerated. This technology could be an attractive approach for whole-gland or focal therapy.

Coagulation of human prostate volumes with MRI-controlled transurethral ultrasound therapy: results in gel phantoms.

PURPOSE: The feasibility and safety of magnetic resonance imaging (MRI)-controlled transurethral ultrasound therapy were demonstrated recently in a preliminary human study in which a small subvolume of prostate tissue was treated prior to radical prostatectomy. Translation of this technology to full clinical use, however, requires the capability to generate thermal coagulation in a volume up to that of the prostate gland itself. The aim of this study was to investigate the parameters required to treat a full 3D human prostate accurately with a multi-element transurethral applicator and multiplanar MR temperature control. METHODS: The approach was a combination of simulations (to select appropriate parameters) followed by experimental confirmation in tissue-mimicking phantoms. A ten-channel, MRI-compatible transurethral ultrasound therapy system was evaluated using six human prostate models (average volume: 36 cm(3)) obtained from the preliminary human feasibility study. Real-time multiplanar MR thermometry at 3 T was used to control the spatial heating pattern in up to nine planes simultaneously. Treatment strategies incorporated both single (4.6 or 8.1 MHz) and dual (4.6 and 14.4 MHz) frequencies, as well as maximum acoustic surface powers of 10 or 20 W cm(-2). RESULTS: Treatments at 4.6 MHz were capable of coagulating a volume equivalent to 97% of the prostate. Increasing power from 10 to 20 W cm(-2) reduced treatment times by approximately 50% with full treatments taking 26 ± 3 min at a coagulation rate of 1.8 ± 0.4 cm(3) min(-1). A dual-frequency 4.6∕14.4 MHz treatment strategy was shown to be the most effective configuration for achieving full human prostate treatment while maintaining good treatment accuracy for small treatment radii. The dual-frequency approach reduced overtreatment close to the prostate base and apex, confirming the simulations. CONCLUSIONS: This study reinforces the capability of MRI-controlled transurethral ultrasound therapy to treat full prostate volumes in a short treatment time with good spatial targeting accuracy and provides key parameters necessary for the next clinical trial.

Investigation of power and frequency for 3D conformal MRI-controlled transurethral ultrasound therapy with a dual frequency multi-element transducer.

Transurethral ultrasound therapy uses real-time magnetic resonance (MR) temperature feedback to enable the 3D control of thermal therapy accurately in a region within the prostate. Previous canine studies showed the feasibility of this method in vivo. The aim of this study was to reduce the procedure time, while maintaining targeting accuracy, by investigating new combinations of treatment parameters. Simulations and validation experiments in gel phantoms were used, with a collection of nine 3D realistic target prostate boundaries obtained from previous preclinical studies, where multi-slice MR images were acquired with the transurethral device in place. Acoustic power and rotation rate were varied based on temperature feedback at the prostate boundary. Maximum acoustic power and rotation rate were optimised interdependently, as a function of prostate radius and transducer operating frequency. The concept of dual frequency transducers was studied, using the fundamental frequency or the third harmonic component depending on the prostate radius. Numerical modelling enabled assessment of the effects of several acoustic parameters on treatment outcomes. The range of treatable prostate radii extended with increasing power, and tended to narrow with decreasing frequency. Reducing the frequency from 8 MHz to 4 MHz or increasing the surface acoustic power from 10 to 20 W/cm(2) led to treatment times shorter by up to 50% under appropriate conditions. A dual frequency configuration of 4/12 MHz with 20 W/cm(2) ultrasound intensity exposure can treat entire prostates up to 40 cm(3) in volume within 30 min. The interdependence between power and frequency may, however, require integrating multi-parametric functions in the controller for future optimisations.

Simulation study on the heating of the surrounding anatomy during transurethral ultrasound prostate therapy: a 3D theoretical analysis of patient safety.

PURPOSE: MRI-guided transurethral ultrasound therapy can generate highly accurate volumes of thermal coagulation conforming to 3D human prostate geometries. This work simulated, quantified, and evaluated the thermal impact of these treatments on the rectum, pelvic bone, neurovascular bundles (NVBs), and urinary sphincters because damage to these structures can lead to complications. METHODS: Twenty 3D anatomical models of prostate cancer patients were used with detailed bioacoustic simulations incorporating an active feedback algorithm which controlled a rotating, planar ultrasound transducer (17, 4 x 3 mm2 elements, 10 W(acoustic)/cm2). Heating of the adjacent surrounding anatomy was evaluated at 4.7, 9.7, and 14.2 MHz using thermal tolerances reported in literature. RESULTS: Heating of the rectum posed the most important safety concern, influenced largely by the water temperature of an endorectal cooling device (ECD); depending on anatomy, temperatures of 7-37 degrees C were required to limit potential damage to less than 10 mm3 on the outer 1 mm layer of the rectal wall. Heating of the pelvic bone could be important at 4.7 MHz. A smaller sized ECD or a higher ultrasound frequency in sectors where the bone was less than 10 mm from the prostate reduced heating in all cases below the threshold for irreversible damage. Heating of the NVB was significant in 75% of the patient models in the absence of treatment planning; this proportion was reduced to 5% by increasing treatment margins up to 4 mm. To avoid damaging the urinary sphincters, the transducer should be positioned at least 2-4 mm from the sphincters, depending on the transurethral cooling temperature. CONCLUSIONS: Simulations show that MRI-guided transurethral therapy can treat the prostate accurately, but in the absence of treatment planning, some thermal impact can be predicted on the surrounding anatomy. Treatment planning strategies have been developed, which reduce thermal injury to the surrounding anatomy.

MRI-controlled transurethral ultrasound therapy for localised prostate cancer.

Minimally invasive treatments for localised prostate cancer are being developed with the aim of achieving effective disease control with low morbidity. High-temperature thermal therapy aimed at producing irreversible thermal coagulation of the prostate gland is attractive because of the rapid onset of thermal injury, and the immediate visualisation of tissue response using medical imaging. High-intensity ultrasound therapy has been shown to be an effective means of achieving thermal coagulation of prostate tissue using minimally invasive devices inserted into the rectum, urethra, or directly into the gland itself. The focus of this review is to describe the work done in our group on the development of MRI-controlled transurethral ultrasound therapy. This technology utilises high intensity ultrasound energy delivered from a transurethral device to achieve thermal coagulation of prostate tissue. Control over the spatial pattern of thermal damage is achieved through closed-loop temperature feedback using quantitative MR thermometry during treatment. The technology, temperature feedback algorithms, and results from numerical modelling, along with experimental results obtained in animal and human studies are described. Our experience suggests that this form of treatment is technically feasible, and compatible with existing MR imaging systems. Temperature feedback control algorithms using MR thermometry can achieve spatial treatment accuracy of a few millimetres in vivo. Patient-specific simulations predict that surrounding tissues can be spared from thermal damage if appropriate measures are taken into account during treatment planning. Recent human experience has been encouraging and motivates further evaluation of this technology as a potential treatment for localised prostate cancer.

Breast-tissue composition and other risk factors for breast cancer in young women: a cross-sectional study.

BACKGROUND: Mammographic density is a heritable quantitative trait and is a strong risk factor for breast cancer in middle-aged and older women. However, little is known about the development of mammographic density in early life. We used MRI to measure the water content of the breast, which provides a measurement of the fibro-glandular content of breast tissue with similar accuracy to mammography, but without the attendant exposure to radiation. METHODS: Between December, 2003, and December, 2007, we recruited 400 young women, aged 15-30 years, and their mothers. We used MRI scans to measure daughters' breast water and fat, and on the same day obtained blood for hormone assays in the follicular phase of the menstrual cycle for each young woman. Mothers underwent mammography (n=356), and a random sample (n=100) also consented to have a breast MRI scan. FINDINGS: In mothers, per cent water-as measured by MRI-was strongly correlated with per cent mammographic density (r=0.85). Per cent water in daughters (median 44.8%) was significantly higher than in mothers (median 27.8%; p<0.0001), and was independently inversely associated with both their age (p=0.04) and weight (p<0.0001), and positively associated with their height (p<0.0001) and their mothers' per cent mammographic density (p<0.0001). Serum growth hormone concentrations, adjusted for covariates, were positively associated with per cent breast water (p=0.001) in a subgroup of young women (n=280) who had not used oral contraceptives within 6 months. INTERPRETATION: Per cent breast water was greatest during the ages when women are most susceptible to breast carcinogens, and was associated with weight, height, and mother's breast-tissue characteristics, and with serum concentrations of growth hormone: a breast mitogen that also mediates postnatal somatic growth. Mammographic density in middle age might partly be the result of genetic factors that affect growth and development in early life. FUNDING: Canadian Breast Cancer Research Alliance.

In vivo MR elastography of the prostate gland using a transurethral actuator.

Conventional approaches for MR elastography (MRE) using surface drivers have difficulty achieving sufficient shear wave propagation in the prostate gland due to attenuation. In this study we evaluate the feasibility of generating shear wave propagation in the prostate gland using a transurethral device. A novel transurethral actuator design is proposed, and the performance of this device was evaluated in gelatin phantoms and in a canine prostate gland. All MRI was performed on a 1.5T MR imager using a conventional gradient-echo MRE sequence. A piezoceramic actuator was used to vibrate the transurethral device along its length. Shear wave propagation was measured transverse and parallel to the rod at frequencies between 100 and 250 Hz in phantoms and in the prostate gland. The shear wave propagation was cylindrical, and uniform along the entire length of the rod in the gel experiments. The feasibility of transurethral MRE was demonstrated in vivo in a canine model, and shear wave propagation was observed in the prostate gland as well as along the rod. These experiments demonstrate the technical feasibility of transurethral MRE in vivo. Further development of this technique is warranted.

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 degrees 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 degrees 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 degrees C isotherm was 0.8 +/- 0.7 mm (-0.2 to 3.2 mm), and the overall treatment time was < or =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.

Quantitative analysis of 3-D conformal MRI-guided transurethral ultrasound therapy of the prostate: theoretical simulations.

PURPOSE: The capability of MRI-guided transurethral ultrasound therapy to produce continuous regions of thermal coagulation that conform to human prostate geometries was evaluated using 3-D anatomical models of prostate cancer patients. METHODS: Numerical simulations incorporating acoustic and biothermal modeling and a novel temperature control feedback algorithm were used to evaluate treatment accuracy of a rotating dual-frequency multi-element transducer. Treatments were simulated on twenty anatomical models obtained from the manual segmentation of the prostate and surrounding structures on MR images of prostate cancer patients obtained prior to radical prostatectomy. RESULTS: Regions of thermal coagulation could be accurately shaped to predefined volumes within 1 mm across the vast majority of the prostates. Over- and under-treated volumes remained smaller than 4% of the corresponding prostate volumes which ranged from 14 to 60 cc. Treatment times were typically 30 min and remained below 60 min even for large 60 cc prostates. Heating of the rectal wall remained below 30 min(43 degrees C) in half of the patient models with only minor, superficial heating in the other cases. The simulated feedback control algorithm adjusted the ultrasound transducer parameters such that high treatment accuracy was maintained despite variable blood perfusion, changing tissue ultrasound attenuation, and practical temperature measurement noise and sampling rate. CONCLUSIONS: Numerical simulations predict that MRI-guided transurethral ultrasound therapy is capable of producing highly accurate volumes of thermal coagulation that conform to human prostate glands.

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.

Corpus callosum anatomy in right-handed homosexual and heterosexual men.

The results of several studies have shown that homosexual men have an increased prevalence of non-right-handedness and atypical patterns of hemispheric functional asymmetry. Non-right-handedness in men has been associated with increased size of the corpus callosum (CC), particularly of the isthmus, which is the posterior region of the callosal body connecting parietotemporal cortical regions. We hypothesized that isthmal area would be greater in homosexual men, even among right handers. Twelve homosexual and ten heterosexual healthy young men, all consistently right-handed, underwent a research-designed magnetic resonance imaging scan. We found that the isthmal area was larger in the homosexual group, adding to the body of findings of structural brain differences between homosexual and heterosexual men. This result suggests that right-handed homosexual men have less marked functional asymmetry compared to right-handed heterosexual men. The results also indicate that callosal anatomy and laterality for motoric functions are dissociated in homosexual men. A logistic regression analysis to predict sexual orientation category correctly classified 21 of the 22 men (96% correct classification) based on area of the callosal isthmus, a left-hand performance measure, water level test score, and a measure of abstraction ability. Our findings indicate that neuroanatomical structure and cognition are associated with sexual orientation in men and support the hypothesis of a neurobiological basis in the origin of sexual orientation.

Analysis of factors important for transurethral ultrasound prostate heating using MR temperature feedback.

The feasibility of using MR thermometry for temperature feedback to control a transurethral ultrasound heating applicator with planar transducers was investigated. The sensitivity of a temperature-based feedback algorithm to spatial (control point area, slice thickness, angular alignment) and non-spatial (imaging time, temperature uncertainty) parameters was evaluated through numerical simulations. The angular alignment of the control point with the ultrasound beam was an important parameter affecting the average spatial error in heat delivery. The other spatial parameters were less influential, thus providing an opportunity to reduce spatial resolution for increased SNR in the MR imaging. The update time was the most important non-spatial parameter determining the performance of the control algorithm. Combined non-spatial and spatial parameters achieved acceptable performance with a voxel size of 3 mm x 3 mm, a 10 mm slice thickness and a 5 s update time. Temperature uncertainty of up to 2 degrees C had little effect on the performance of the control algorithm but did reduce the average error slightly due to a systematic, noise-induced overestimation of the boundary temperature. These simulations imply that MR thermometry performed on clinical 1.5 T imaging systems is of sufficient quality for use as thermal feedback for conformal prostate thermal therapy with transurethral ultrasound heating applicators incorporating planar transducers.

Influence of geometric and material properties on artifacts generated by interventional MRI devices: Relevance to PRF-shift thermometry.

PURPOSE: Magnetic resonance imaging (MRI) is capable of providing valuable real-time feedback during medical procedures, partly due to the excellent soft-tissue contrast available. Several technical hurdles still exist to seamless integration of medical devices with MRI due to incompatibility of most conventional devices with this imaging modality. In this study, the effect of local perturbations in the magnetic field caused by the magnetization of medical devices was examined using finite element analysis modeling. As an example, the influence of the geometric and material characteristics of a transurethral high-intensity ultrasound applicator on temperature measurements using proton resonance frequency (PRF)-shift thermometry was investigated. METHODS: The effect of local perturbations in the magnetic field, caused by the magnetization of medical device components, was examined using finite element analysis modeling. The thermometry artifact generated by a transurethral ultrasound applicator was simulated, and these results were validated against analytic models and scans of an applicator in a phantom. Several parameters were then varied to identify which most strongly impacted the level of simulated thermometry artifact, which varies as the applicator moves over the course of an ablative high-intensity ultrasound treatment. RESULTS: Key design parameters identified as having a strong influence on the magnitude of thermometry artifact included the susceptibility of materials and their volume. The location of components was also important, particularly when positioned to maximize symmetry of the device. Finally, the location of component edges and the inclination of the device relative to the magnetic field were also found to be important factors. CONCLUSIONS: Previous design strategies to minimize thermometry artifact were validated, and novel design strategies were identified that substantially reduce PRF-shift thermometry artifacts for a variety of device orientations. These new strategies are being incorporated into the next generation of applicators. The general strategy described in this study can be applied to the design of other interventional devices intended for use with MRI.

Method for MRI-guided conformal thermal therapy of prostate with planar transurethral ultrasound heating applicators.

A method for conformal prostate thermal therapy using transurethral ultrasound heating applicators incorporating planar transducers is described. The capability to shape heating patterns to the geometry of the prostate gland from a single element in a multi-element heating applicator was evaluated using Bioheat transfer modelling. Eleven prostate geometries were obtained from patients who underwent MR imaging of the prostate gland prior to radical prostatectomy. Results indicate that ultrasound heating applicators incorporating multi-frequency planar transducers (4 x 20 mm, f = 4.7 MHz, 9.7 MHz) are capable of shaping thermal damage patterns to the geometry of individual prostates. A temperature feedback control algorithm has been developed to control the frequency, rotation rate and applied power level from transurethral heating applicators based on measurements of the boundary temperature during heating. The discrepancy between the thermal damage boundary and the target boundary was less than 5 mm, and the transition distance between coagulation and normal tissue was less than 1 cm. Treatment times for large prostate volumes were less than 50 min, and perfusion did not have significant impact on the control algorithm. Rectal cooling will play an important role in reducing undesired heating near the rectal wall. Experimental validation of the simulations in a tissue-mimicking gel phantom demonstrated good agreement between the predicted and generated patterns of thermal damage.

Multi-modality tissue-mimicking phantom for thermal therapy.

A tissue-mimicking phantom material has been developed for use with thermal therapy devices and techniques. This material has magnetic resonance properties (primarily T2) which change drastically upon thermal coagulation, enabling its use for device characterization and treatment verification using simple T2-weighted imaging techniques. The coagulation temperature of the phantom can be changed from 50-60 degrees C by adjusting the pH from 4.3 to 4.7. The energy absorption properties can be adjusted to match the acoustical and optical properties of tissues. T2 relaxation measurements are provided as a function of temperature, along with T2-weighted MR images to illustrate the visualization of heating patterns. A complete recipe for fabricating phantoms is provided.

Utility of simultaneous brain, CSF and hyperintensity quantification in dementia.

Improved methods of quantifying MRI are needed to study brain-behavior relationships in dementia. Rating scales are variable; lesion-tracing approaches can be subjective and ignore atrophy; segmentation of MRI hyperintensities is complicated by partial volume effects; and hyperintense lesions in different anatomical areas may have different effects. The goal of this study was to extend existing segmentation approaches to include hyperintensities and to demonstrate the utility of simultaneously assessing atrophy and lesion compartments in dementia. A semi-automated method was applied to quantify brain and cerebrospinal fluid (CSF) compartments and to subclassify hyperintensities into periventricular, deep white matter, thalamic and basal ganglia compartments. Twenty MR scans from participants in an ongoing dementia study were used to generate intra- and inter-rater reliability estimates. High intra- and inter-class correlation coefficients (0.83-0.99) were obtained for all measures and the semi-automated measurements were highly correlated with traced volumes. Brain, CSF and specific lesion volumes were significantly correlated with neuropsychological functions. In models using only total hyperintensity volumes, the effects of lesion compartments (such as thalamic) were masked. Simultaneous quantification of atrophy and anatomically distinct hyperintensities is important for understanding cognitive impairments in dementia.

Multifrequency ultrasound transducers for conformal interstitial thermal therapy.

Control over the pattern of thermal damage generated by interstitial ultrasound heating applicators can be enhanced by changing the ultrasound frequency during heating. The ability to change transmission frequency from a single transducer through the use of high impedance front layers was investigated in this study. The transmission spectrum of multifrequency transducers was calculated using the KLM equivalent circuit model and verified with experimental measurements on prototype transducers. The addition of a quarter-wavelength thick PZT (unpoled) front layer enabled the transmission of ultrasound at two discrete frequencies, 4.7 and 9.7 MHz, from a transducer with an original resonant frequency of 8.4 MHz. Three frequency transmission at 3.3, 8.4, and 10.8 MHz was possible for a transducer with a half-wavelength thick front layer. Calculations of the predicted thermal lesion size at each transmission frequency indicated that the depth of thermal lesion could be varied by a factor of 1.6 for the quarter-wavelength front layer. Heating experiments performed in excised liver tissue with a dual-frequency applicator confirmed this ability to control the shape of thermal lesions during heating to generate a desired geometry. Practical interstitial designs that enable the generation of shaped thermal lesions are feasible.

3D conformal MRI-controlled transurethral ultrasound prostate therapy: validation of numerical simulations and demonstration in tissue-mimicking gel phantoms.

MRI-controlled transurethral ultrasound therapy uses a linear array of transducer elements and active temperature feedback to create volumes of thermal coagulation shaped to predefined prostate geometries in 3D. The specific aims of this work were to demonstrate the accuracy and repeatability of producing large volumes of thermal coagulation (>10 cc) that conform to 3D human prostate shapes in a tissue-mimicking gel phantom, and to evaluate quantitatively the accuracy with which numerical simulations predict these 3D heating volumes under carefully controlled conditions. Eleven conformal 3D experiments were performed in a tissue-mimicking phantom within a 1.5T MR imager to obtain non-invasive temperature measurements during heating. Temperature feedback was used to control the rotation rate and ultrasound power of transurethral devices with up to five 3.5 × 5 mm active transducer elements. Heating patterns shaped to human prostate geometries were generated using devices operating at 4.7 or 8.0 MHz with surface acoustic intensities of up to 10 W cm(-2). Simulations were informed by transducer surface velocity measurements acquired with a scanning laser vibrometer enabling improved calculations of the acoustic pressure distribution in a gel phantom. Temperature dynamics were determined according to a FDTD solution to Pennes' BHTE. The 3D heating patterns produced in vitro were shaped very accurately to the prostate target volumes, within the spatial resolution of the MRI thermometry images. The volume of the treatment difference falling outside ± 1 mm of the target boundary was, on average, 0.21 cc or 1.5% of the prostate volume. The numerical simulations predicted the extent and shape of the coagulation boundary produced in gel to within (mean ± stdev [min, max]): 0.5 ± 0.4 [-1.0, 2.1] and -0.05 ± 0.4 [-1.2, 1.4] mm for the treatments at 4.7 and 8.0 MHz, respectively. The temperatures across all MRI thermometry images were predicted within -0.3 ± 1.6 °C and 0.1 ± 0.6 °C, inside and outside the prostate respectively, and the treatment time to within 6.8 min. The simulations also showed excellent agreement in regions of sharp temperature gradients near the transurethral and endorectal cooling devices. Conformal 3D volumes of thermal coagulation can be precisely matched to prostate shapes with transurethral ultrasound devices and active MRI temperature feedback. The accuracy of numerical simulations for MRI-controlled transurethral ultrasound prostate therapy was validated experimentally, reinforcing their utility as an effective treatment planning tool.