Transurethral high-intensity ultrasound for treatment of stress urinary incontinence (SUI): simulation studies with patient-specific models.

BACKGROUND: Stress urinary incontinence (SUI) is prevalent in adult women, attributed to weakened endopelvic supporting tissues, and typically treated using drugs and invasive surgical procedures. The objective of this in silico study is to explore transurethral high-intensity ultrasound for delivery of precise thermal therapy to the endopelvic tissues adjacent to the mid-urethra, to induce thermal remodeling as a potential minimally invasive treatment alternative. METHODS: 3D acoustic (Rayleigh-Sommerfeld) and biothermal (Pennes bioheat) models of the ultrasound applicator and surrounding tissues were devised. Parametric studies over transducer configuration [frequency, radius-of-curvature (ROC)] and treatment settings (power, duration) were performed, and select cases on patient-specific models were used for further evaluation. Transient temperature and thermal dose distributions were calculated, and temperature and dose metrics reported. RESULTS: Configurations using a 5-MHz curvilinear transducer (3.5 × 10 mm, 28 mm ROC) with single 90 s sonication can create heated zones with 11 mm penetration (>50 °C) while sparing the inner 1.8 mm (<45 °C) radial depth of the urethral mucosa. Sequential and discrete applicator rotations can sweep out bilateral coagulation volumes (1.4 W power, 15° rotations, 600 s total time), produce large volumetric (1124 mm³ above 60 EM43 °C) and wide angular (∼50.5° per lateral sweep) coverage, with up to 15.6 mm thermal penetration and at least 1.6 mm radial urethral protection (<5 EM43 °C). CONCLUSION: Transurethral applicators with curvilinear ultrasound transducers can deliver spatially selective temperature elevations to lateral mid-urethral targets as a possible means to tighten the endopelvic fascia and adjacent tissues.

Technical note: unsupervised C-arm pose tracking with radiographic fiducial.

PURPOSE: C-arm fluoroscopy reconstruction, such as that used in prostate brachytherapy, requires that the relative poses of the individual C-arm fluoroscopy images must be known prior to reconstruction. Radiographic fiducials can provide excellent C-arm pose tracking, but they need to be segmented in the image. The authors report an automated and unsupervised method that does not require prior segmentation of the fiducial. METHODS: The authors compute the individual C-arm poses relative to a stationary radiographic fiducial of known geometry. The authors register a filtered 2D fluoroscopy image of the fiducial to its 3D model by using image intensity alone without prior segmentation. To enhance the C-arm images, the authors investigated a three-step cascade filter and a line enhancement filter. The authors tested the method on a composite fiducial containing beads, straight lines, and ellipses. Ground-truth C-arm pose was provided by a clinically proven method. RESULTS: Using 111 clinical C-arm images and +/- 10 degrees and +/- 10 mm random perturbation around the ground-truth pose, a total of 2775 cases were evaluated. The average rotation and translation errors were 0.62 degrees (STD = 0.31 degrees) and 0.72 mm (STD = 0.55 mm) for the three-step filter and 0.67 degrees (STD = 0.40 degrees) and 0.87 mm (STD = 0.27 mm) using the line enhancement filter. CONCLUSIONS: The C-arm pose tracking method was sufficiently accurate and robust on human patient data for subsequent 3D implant reconstruction.

Registration between ultrasound and fluoroscopy or CT in prostate brachytherapy.

PURPOSE: In prostate brachytherapy, transrectal ultrasound (TRUS) is used to visualize the anatomy, while implanted seeds can be visualized by fluoroscopy. Intraoperative dosimetry optimization is possible using a combination of TRUS and fluoroscopy, but requires localization of the fluoroscopy-derived seed cloud, relative to the anatomy as seen on TRUS. The authors propose to develop a method of registration of TRUS images and the implants reconstructed from fluoroscopy. METHODS: A phantom was implanted with 48 seeds then imaged with TRUS and CT. Seeds were reconstructed from CT yielding a cloud of seeds. Fiducial-based ground-truth registration was established between the TRUS and CT. TRUS images are filtered, compounded, and registered to the reconstructed implants by using an intensity-based metric. The authors evaluated a volume-to-volume and point-to-volume registration scheme. In total, seven TRUS filtering techniques and three image similarity metrics were analyzed. The method was also tested on human subject data captured from a brachytherapy procedure. RESULTS: For volume-to-volume registration, noise reduction filter and normalized correlation metrics yielded the best result: An average of 0.54 +/- 0.11 mm seed localization error relative to ground truth. For point-to-volume registration, noise reduction combined with beam profile filter and mean squares metrics yielded the best result: An average of 0.38 +/- 0.19 mm seed localization error relative to the ground truth. In human patient data, C-arm fluoroscopy images showed 81 radioactive seeds implanted inside the prostate. A qualitative analysis showed clinically correct agreement between the seeds visible in TRUS and reconstructed from intraoperative fluoroscopy imaging. The measured registration error compared to the manually selected seed locations by the clinician was 2.86 +/- 1.26 mm. CONCLUSIONS: Fully automated registration between TRUS and the reconstructed seeds performed well in ground-truth phantom experiments and qualitative observation showed adequate performance on early clinical patient data.

INTENSITY-BASED REGISTRATION OF PROSTATE BRACHYTHERAPY IMPLANTS AND ULTRASOUND.

PURPOSE: In prostate brachytherapy, determining the 3D location of the seeds relative to surrounding structures is necessary for calculating dosimetry. Ultrasound imaging provides the ability to visualize soft tissues, and implanted seeds can be reconstructed from C-arm fluoroscopy. Registration between these two complementary modalities would allow us to make immediate provisions for dosimetric deviation from the optimal implant plan. METHODS: We propose intensity-based registration between ultrasound and a reconstructed model of seeds from fluoroscopy. The ultrasound images are pre-processed with recursive thresholding and phase congruency. Then a 3D ultrasound volume is reconstructed and registered to the implant model using mutual information. RESULTS: A standard training phantom was implanted with 49 seeds. Average registration error between corresponding seeds relative to the ground truth is 0.09 mm. The effect of false positives in ultrasound was investigated by masking seeds from the fluoroscopy reconstructed model. The registration error remained below 0.5 mm at a rate of 30% false positives. CONCLUSION: Our method promises to be clinically adequate, where requirements for registration is 1.5 mm.

An automatic seed finder for brachytherapy CT postplans based on the Hough transform.

PURPOSE: The purpose of the work is to describe a new algorithm for the automatic detection of implanted radioactive seeds within the prostate. The algorithm is based on the traditional Hough transform. A method of quality assurance is described as well as a quantitative phantom study to determine the accuracy of the algorithm. METHODS AND MATERIALS: An algorithm is described which is based on the Hough transform. The Hough transform is a well known transform traditionally used to automatically segment lines and other well defined geometric objects from images. The traditional Hough transform is extended to three-dimensions and applied to CT images of seed implanted prostate glands. A method based on digitally reconstructed radiographs is described to quality assure the determined three-dimensional positions of the detected seeds. Two phantom studies utilizing eight seeds and nine seeds are described. All eight seeds form a contiguous a square while the nine seed phantom describes seeds which are placed side-by-side in groups of two and three. The algorithm is applied to the CT scans of both phantoms and the seed positions determined. RESULTS: The algorithm has been commercially developed and used to perform postsurgical dosimetric assessment on approximately 1000 patients. Using the described quality assurance tool it was determined that the algorithm accurately determined the seed positions in all 1000 patients. The algorithm was also applied to the eight seed phantom. The algorithm successfully found all eight seeds as well as their seed coordinates. The average radial error was determined to be 0.9 mm. For the nine seed phantom, the algorithm correctly identified all nine seeds, with an average radial error of 3 mm. CONCLUSIONS: The described algorithm is a robust, accurate, automatic, three-dimensional application for CT based seed determination.

Transurethral ultrasound applicators with directional heating patterns for prostate thermal therapy: in vivo evaluation using magnetic resonance thermometry.

A catheter-based transurethral ultrasound applicator with angularly directional heating patterns has been designed for prostate thermal therapy and evaluated in canine prostate in vivo using MRI to monitor and assess performance. The ultrasound transducer array (3.5 mm diameter tubular transducers, 180 degrees active sectors, approximately 7.5 MHz) was integrated to a flexible delivery catheter (4 mm OD), and encapsulated within an expandable balloon (35 mm x 10 mm OD, 80 ml min(-1) ambient water) for coupling and cooling of the prostatic urethra. These devices were used to thermally coagulate targeted portions of the canine prostate (n = 2) while using MR thermal imaging (MRTI) to monitor the therapy. MRI was also used for target definition, positioning of the applicator, and evaluation of target viability post-therapy. MRTI was based upon the complex phase-difference mapping technique using an interleaved gradient echo-planar imaging sequence with lipid suppression. MRTI derived temperature distributions, thermal dose exposures, T1-contrast enhanced MR images, and histology of sectioned prostates were used to define destroyed tissue zones and characterize the three-dimensional heating patterns. The ultrasound applicators produced approximately 180 degrees directed zones of thermal coagulation within targeted tissue which extended 15-20 mm radially to the outer boundary of the prostate within 15 min. Transducer activation lengths of 17 mm and 24 mm produced contiguous zones of coagulation extending axially approximately 18 mm and approximately 25 mm from base to apex, respectively. Peak temperatures around 90 degrees C were measured, with approximately 50 degrees C-52 degrees C corresponding to outer boundary t43 = 240 min at approximately 15 min treatment time. These devices are MRI compatible, and when coupled with multiplanar MRTI provide a means for selectively controlling the length and sector angle of therapeutic thermal treatment in the prostate.

Evaluation of multielement catheter-cooled interstitial ultrasound applicators for high-temperature thermal therapy.

Catheter-cooled (CC) interstitial ultrasound applicators were evaluated for their use in high-temperature coagulative thermal therapy of tissue. Studies in ex vivo beef muscle were conducted to determine the influences of applied electrical power levels (5-20 W per element), catheter flow rate (20-60 ml min(-1)), circulating water temperature (7-40 degrees C), and frequency (7-9 MHz) on temperature distribution and thermal lesion geometry. The feasibility of using multiple interstitial applicators to thermally coagulate a predetermined volume of tissue was also investigated. Results of these studies revealed that the directional shape of the thermal lesions is maintained with increasing time and power. Radial depths of the thermal lesions ranged from 10.7 +/- 0.7 mm after heating for 4 min with an applied power level of 5 W, to 16.2 +/- 1.4 mm with 20 W. The axial length of the thermal lesions is controlled tightly by the number of active transducers. A catheter flow rate of 20 to 40 ml min(-1) (52.2 +/- 5.5 kPa at 40 ml min(-1)) with 22 degrees C water was determined to provide sufficient cooling of the transducers for power levels used in this study. In vivo temperatures measured in the center of a 3-cm-diam peripheral implant of four applicators in pig thigh muscle reached 89.3 degrees C after 4 min of heating, with boundaries of coagulation clearly defined by applicator position and directivity. Conformability of heating in a clinically relevant model was demonstrated by inserting two directional CC applicators with a 2 cm separation within an in vivo canine prostate, and generating a thermal lesion measuring 3.8 cm x 2.2 cm in cross section while directing energy away from, and protecting the rectum. Maximum measured temperatures at midgland exceeded 90 degrees C within 20 min of heating. The results of this study demonstrate the utility of single or multiple CC applicators for conformal thermal coagulation and high temperature thermal therapy, with potential for clinical applications in sites such as prostate, liver, breast, or uterus.

Combination of transurethral and interstitial ultrasound applicators for high-temperature prostate thermal therapy.

The purpose of this study was to determine the feasibility of using a transurethral ultrasound applicator in combination with implantable ultrasound applicators for inducing thermal coagulation and necrosis of localized cancer lesions or benign disease within the prostate gland. The potential to treat target zones in the anterior and lateral portions of the prostate with the angularly directive transurethral applicator, while simultaneously treating regions of extracapsular extension and zones in the posterior prostate with the directive implantable applicators in combination with a rectal cooling bolus, is evaluated. Biothermal computer simulations, acoustic characterizations, and in vivo thermal dosimetry experiments with canine prostates were used to evaluate the performance of each applicator type and combinations thereof. Simulations have demonstrated that transurethral applicators with 180-270 degrees acoustic active zones can direct therapeutic heating patterns to the anterior and lateral prostate, implantable needles can isolate heating to the posterior gland while avoiding rectal tissue, and that the combination of applicators can be used to produce conformal heating to the whole gland. Single implantable applicators (1.8 mm OD x 10 mm long, approximately 180 degrees active sector, approximately 7 MHz, direct-coupled type) produced directional thermal lesions within in vivo prostate, with temperatures >50 degrees C extending more than 10 mm radially after 10-15 min. Combination of interstitial applicators (1-2) and a transurethral applicator (3-2.5 mm OD x 6 mm long, approximately 180 degrees active sector, 6.8 MHz, 6 mm OD delivery catheter) produced conforming temperature distributions (48-85 degrees C) and zones of acute thermal damage within 15 min. The preliminary results of this investigation demonstrate that implantable directional ultrasound applicators, in combination with a transurethral ultrasound applicator, have the potential to provide thermal coagulation and necrosis of small or large regions within the prostate gland, while sparing thermally sensitive rectal tissue.

Ultrasound field calculation in a water-soft tissue medium.

An efficient numerical approximation for ultrasound field calculation in a two or three layer water-soft tissue medium is presented. It is extended from a method developed previously in a homogeneous medium. The emphasis of this study is to examine the conditions that are required for this approximation. Criteria are given for achieving an appropriate accuracy, which is verified by comparing it with the Rayleigh integral.

Ultrasound image fusion for external beam radiotherapy for prostate cancer.

PURPOSE: To determine whether real-time ultrasound imaging and targeting system for the treatment of prostate cancer was feasible. The initial phase of this project included a study to develop and determine (a) software for the fusion of ultrasound images to standard x-rays obtained during simulation, and (b) the potential reduction in field size with real-time imaging. METHODS AND MATERIALS: During 13 patient simulations a transrectal ultrasound image was obtained. Orthogonal x-ray films were acquired with the rectal probe in place. Both the x-ray and ultrasound images were digitized and a fusion image was created of the prostate position in relation to the probe, bladder, and rectum. The two-dimensional area of the rectum, bladder, and prostate was determined in the lateral projection. Potential conformal blocks were designed for the lateral portals in a four-field treatment technique. RESULTS: The transrectal ultrasound probe enabled real-time prostate imaging. The lateral field size can be reduced to 6.08 x 5.68 cm2 +/- 0.62 x 0.48 cm2 from the standard 8 x 8 cm2 field. The posterior rectal wall was physically displaced out of the lateral field. The area of the rectum included in the lateral field is 1.75 cm2 +/- 0.85 cm2. CONCLUSION: The prostate position can be determined with certainty on a regular basis with transrectal ultrasonography. The amount of normal tissue in the high dose volume can be reduced. This approach may reduce acute and chronic morbidity and allow further dose escalation.

Design of an ultrasonic therapy system for breast cancer treatment.

This paper describes the design of a novel ultrasonic therapy system dedicated to the breast cancer treatment and the theoretical investigation of the heating characteristics of the system. The applicator is a cylinder comprised of a stack of rings. Each ring has up to 48 transducers mounted on the inside of the ring and directed towards the centre. The transducers operate in one of two frequency bands (1.8-2.8 MHz and 4.3-40.8 MHz), arranged alternately in each ring. During treatment the patient is positioned in prone position, with the breast immersed in water and surrounded by this array. This design was modelled and optimized by 3-D simulations for a variety of treatment conditions. The simulated results demonstrate that the system has an excellent capability to achieve and maintain a temperature distribution (41.5-44 degrees C) in a quadrant to a whole breast. Initial experiments using a single ring of transducers has been performed to verify the power deposition calculation.

Stereotactic uses beyond core biopsy: model development for minimally invasive treatment of breast cancer through interstitial laser hyperthermia.

Light of a Nd:YAG laser presented through a fiberoptic cable to a diffusing tip can be adapted to mammographic stereotactic instruments now used for core biopsy in the hyperthermic endoablation of breast cancer. This approach to cancer destruction extends breast preservation to the point of no observable surface skin change. The initial analysis characterizes the effects of laser endohyperthermia in a physical model as well as in tissue, both ex vivo and in vivo, to create a reliable technique that will lead to human trials. A fiberoptic cable with a diffusing quartz tip placed deep within soft tissue can pass light of a neodymium laser and consequent thermal energy for the destruction of surrounding soft tissues. Because breast cancer occurs with greatest frequency in the involuted breasts of women more than 50 years of age and because this tissue is predominantly fibro-fatty in nature, our work has concentrated on model development and the determination of heat distribution and destruction of fat and fibro-fatty tissue. Following the development of a physical model, time-temperature courses were found to be similar in ex vivo human breast tissue and subcutaneous porcine fat. This led to in vivo porcine studies that confirmed similar time-temperature courses. For tissues brought to a range of 60 degrees C to 80 degrees C and sustained for the better part of 20 minutes, gross and histological analyses reveal complete destruction over a 1 1/2 cm radial region around the laser tip. This approach offers great promise for the treatment of stereotactically biopsied small T1 breast carcinomas.

Performance of a multi-sector ultrasound hyperthermia applicator and control system: in vivo studies.

A multi-element ultrasound hyperthermia system (Labthermics Technologies, Inc., Sonotherm 1000) was utilized to deliver energy to two relatively well-defined regions (3.8 X 3.8 cm) on the lateral aspect of the right rear leg of 22 dogs in 1, 2 and 3 weekly treatments to a target temperature of 42-43 degrees C, at a depth of 1 cm. The total treatment time was 30 min. One area heated on each dog was adjacent to the proximal femur and the other was 2-3 cm away from the distal aspect of the same bone. The system performed in an acceptably controlled manner and was able to deliver energy to a well-defined site. The mean temperature achieved, and rate of temperature rise in the heated regions, was independent of the region being treated. Little difference (0.12 degrees C) was noted between the mean temperatures of the heated regions, and the temperature bounds (42-43 degrees C) were exceeded by a small amount and for a relatively short period of time (out of range RMSE = 0.6 degrees C). Unheated regions showed much lower mean temperatures than did heated regions located 3.8 cm away, indicating that the energy was delivered in a well-defined manner. Superficial thermal injuries occurred in three of 22 dogs in the area heated 2-3 cm away from bone, and 11 of 22 dogs exhibited injuries in the tissue heated immediately adjacent to the femur.

A multi-element ultrasonic hyperthermia applicator with independent element control.

Acoustic field patterns from a planar multi-element ultrasonic applicator were determined experimentally and compared with theory. Measurements were obtained from square arrays of 4 and 16 elements. The acoustic fields produced by various configurations of individual square elements (3.6 cm X 3.6 cm) driven at 1 MHz were measured in water. Transverse and axial scans paths were used to characterize the acoustic beam for different aperture sizes and individual element excitations. Unequal power excitation of adjacent elements produced multiple peaked acoustic intensity patterns. While a simple theoretical model was not able to account for all the experimentally determined transverse and axial field patterns, a model including mechanical damping improved the agreement between theory and experiment. However, less ripple in the axial pattern was measured than predicted by either theoretical model. The ability of the applicator to generate acoustic field patterns suitable for local tissue heating was demonstrated by an experimental study in dog thigh muscle.

Technetium 99m pertechnetate measurement of renal blood flow distribution.

The accuracy of measuring anatomical blood flow using the rising slopes of first-pass time-activity curves were studied in six isolated dog kidneys. In each case, the canine kidney was placed on an open-circuit in vitro perfusion apparatus, which included an in-line flow meter and an in-line variable resistance for adjusting the flow rate. Time-activity curves from images acquired at 2-second intervals were generated for each kidney following injection of 4 mCi of 99mTc pertechnetate into the perfusate solution for each flow rate condition studied. The flow rate was calculated from the average slope of the ascending segment, initial rise to peak, of the time-activity curves. Excellent agreement was found between the radioactive tracer and established flow meter measurements (r = 0.995). With the availability of mobile gamma camera/computer systems, this technique could easily be utilized in evaluating perfusion function of transplant kidneys prior to surgery. Also, this technique can be useful in monitoring the renal anatomical distribution of blood flow in postsurgical patients.