Integration of deployable fluid lenses and reflectors with endoluminal therapeutic ultrasound applicators: Preliminary investigations of enhanced penetration depth and focal gain.

PURPOSE: Catheter-based ultrasound applicators can generate thermal ablation of tissues adjacent to body lumens, but have limited focusing and penetration capabilities due to the small profile of integrated transducers required for the applicator to traverse anatomical passages. This study investigates a design for an endoluminal or laparoscopic ultrasound applicator with deployable acoustic reflector and fluid lens components, which can be expanded after device delivery to increase the effective acoustic aperture and allow for deeper and dynamically adjustable target depths. Acoustic and biothermal theoretical studies, along with benchtop proof-of-concept measurements, were performed to investigate the proposed design. METHODS: The design schema consists of an array of tubular transducer(s) situated at the end of a catheter assembly, surrounded by an expandable water-filled conical balloon with a secondary reflective compartment that redirects acoustic energy distally through a plano-convex fluid lens. By controlling the lens fluid volume, the convex surface can be altered to adjust the focal length or collapsed for device insertion or removal. Acoustic output of the expanded applicator assembly was modeled using the rectangular radiator method and secondary sources, accounting for reflection and refraction at interfaces. Parametric studies of transducer radius (1-5 mm), height (3-25 mm), frequency (1.5-3 MHz), expanded balloon diameter (10-50 mm), lens focal length (10-100 mm), lens fluid (silicone oil, perfluorocarbon), and tissue attenuation (0-10 Np/m/MHz) on beam distributions and focal gain were performed. A proof-of-concept applicator assembly was fabricated and characterized using hydrophone-based intensity profile measurements. Biothermal simulations of endoluminal ablation in liver and pancreatic tissue were performed for target depths between 2 and 10 cm. RESULTS: Simulations indicate that focal gain and penetration depth scale with the expanded reflector-lens balloon diameter, with greater achievable performance using perfluorocarbon lens fluid. Simulations of a 50 mm balloon OD, 10 mm transducer outer diameter (OD), 1.5 MHz assembly in water resulted in maximum intensity gain of ~170 (focal dimensions: ~12 mm length × 1.4 mm width) at ~5 cm focal depth and focal gains above 100 between 24 and 84 mm depths. A smaller (10 mm balloon OD, 4 mm transducer OD, 1.5 MHz) configuration produced a maximum gain of 6 at 9 mm depth. Compared to a conventional applicator with a fixed spherically focused transducer of 12 mm diameter, focal gain was enhanced at depths beyond 20 mm for assembly configurations with balloon diameters ≥ 20 mm. Hydrophone characterizations of the experimental assembly (31 mm reflector/lens diameter, 4.75 mm transducer radius, 1.7 MHz) illustrated focusing at variable depths between 10-70 mm with a maximum gain of ~60 and demonstrated agreement with theoretical simulations. Biothermal simulations (30 s sonication, 75 °C maximum) indicate that investigated applicator assembly configurations, at 30 mm and 50 mm balloon diameters, could create localized ellipsoidal thermal lesions increasing in size from 10 to 55 mm length × 3-6 mm width in liver tissue as target depth increased from 2 to 10 cm. CONCLUSIONS: Preliminary theoretical and experimental analysis demonstrates that combining endoluminal ultrasound with an expandable acoustic reflector and fluid lens assembly can significantly enhance acoustic focal gain and penetration from inherently smaller diameter catheter-based applicators.

Endoluminal ultrasound applicators for MR-guided thermal ablation of pancreatic tumors: Preliminary design and evaluation in a porcine pancreas model.

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

Thermal therapy of pancreatic tumours using endoluminal ultrasound: Parametric and patient-specific modelling.

PURPOSE: The aim of this study is to investigate endoluminal ultrasound applicator configurations for volumetric thermal ablation and hyperthermia of pancreatic tumours using 3D acoustic and biothermal finite element models. MATERIALS AND METHODS: Parametric studies compared endoluminal heating performance for varying applicator transducer configurations (planar, curvilinear-focused, or radial-diverging), frequencies (1-5 MHz), and anatomical conditions. Patient-specific pancreatic head and body tumour models were used to evaluate feasibility of generating hyperthermia and thermal ablation using an applicator positioned in the duodenal or stomach lumen. Temperature and thermal dose were calculated to define ablation (> 240 EM(43 °C)) and moderate hyperthermia (40-45 °C) boundaries, and to assess sparing of sensitive tissues. Proportional-integral control was incorporated to regulate maximum temperature to 70-80 °C for ablation and 45 °C for hyperthermia in target regions. RESULTS: Parametric studies indicated that 1-3 MHz planar transducers are the most suitable for volumetric ablation, producing 5-8 cm(3) lesion volumes for a stationary 5-min sonication. Curvilinear-focused geometries produce more localised ablation to 20-45 mm depth from the GI tract and enhance thermal sparing (T(max) < 42 °C) of the luminal wall. Patient anatomy simulations show feasibility in ablating 60.1-92.9% of head/body tumour volumes (4.3-37.2 cm(3)) with dose < 15 EM(43 °C) in the luminal wall for 18-48 min treatment durations, using 1-3 applicator placements in GI lumen. For hyperthermia, planar and radial-diverging transducers could maintain up to 8 cm(3) and 15 cm(3) of tissue, respectively, between 40-45 °C for a single applicator placement. CONCLUSIONS: Modelling studies indicate the feasibility of endoluminal ultrasound for volumetric thermal ablation or hyperthermia treatment of pancreatic tumour tissue.

Development of an endoluminal high-intensity ultrasound applicator for image-guided thermal therapy of pancreatic tumors.

An ultrasound applicator for endoluminal thermal therapy of pancreatic tumors has been introduced and evaluated through acoustic/biothermal simulations and ex vivo experimental investigations. Endoluminal therapeutic ultrasound constitutes a minimally invinvasive conformal therapy and is compatible with ultrasound or MR-based image guidance. The applicator would be placed in the stomach or duodenal lumen, and sonication would be performed through the luminal wall into the tumor, with concurrent water cooling of the wall tissue to prevent its thermal injury. A finite-element (FEM) 3D acoustic and biothermal model was implemented for theoretical analysis of the approach. Parametric studies over transducer geometries and frequencies revealed that operating frequencies within 1-3 MHz maximize penetration depth and lesion volume while sparing damage to the luminal wall. Patient-specific FEM models of pancreatic head tumors were generated and used to assess the feasibility of performing endoluminal ultrasound thermal ablation and hyperthermia of pancreatic tumors. Results indicated over 80% of the volume of small tumors (~2 cm diameter) within 35 mm of the duodenum could be safely ablated in under 30 minutes or elevated to hyperthermic temperatures at steady-state. Approximately 60% of a large tumor (~5 cm diameter) model could be safely ablated by considering multiple positions of the applicator along the length of the duodenum to increase coverage. Prototype applicators containing two 3.2 MHz planar transducers were fabricated and evaluated in ex vivo porcine carcass heating experiments under MR temperature imaging (MRTI) guidance. The applicator was positioned in the stomach adjacent to the pancreas, and sonications were performed for 10 min at 5 W/cm2 applied intensity. MRTI indicated over 40°C temperature rise in pancreatic tissue with heating penetration extending 3 cm from the luminal wall.

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

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

Model-based iterative reconstruction compared to adaptive statistical iterative reconstruction and filtered back-projection in CT of the kidneys and the adjacent retroperitoneum.

RATIONALE AND OBJECTIVES: To prospectively evaluate the perceived image quality of model-based iterative reconstruction (MBIR) compared to adaptive statistical iterative reconstruction (ASIR) and filtered back-projection (FBP) in computed tomography (CT) of the kidneys and retroperitoneum. MATERIALS AND METHODS: With investigational review board and Health Insurance Portability and Accountability Act compliance, 17 adults underwent 31 contrast-enhanced CT acquisitions at constant tube potential and current (range 30-300 mA). Each was reconstructed with MBIR, ASIR (50%), and FBP. Four reviewers scored each reconstruction's perceived image quality overall and the perceived image quality of seven imaging features that were selected by the authors as being relevant to imaging in the region and pertinent to the evaluation of high-quality diagnostic CT. RESULTS: MBIR perceived image quality scored superior to ASIR and FBP both overall (P < .001) and for observations of the retroperitoneal fascia (99.2%), corticomedullary differentiation (94.4%), renal hilar structures (96.8%), focal renal lesions (92.5%), and mitigation of streak artifact (100.0%; all, P < .001). MBIR achieved diagnostic overall perceived image quality with approximately half the radiation dose required by ASIR and FBP. The noise curve of MBIR was significantly lower and flatter (P < .001). CONCLUSIONS: Compared to ASIR and FBP, MBIR provides superior perceived image quality, both overall and for several specific imaging features, across a broad range of tube current levels, and requires approximately half the radiation dose to achieve diagnostic overall perceived image quality. Accordingly, MBIR should enable CT scanning with improved perceived image quality and/or reduced radiation exposure.

Focal ablation of prostate cancer: four roles for magnetic resonance imaging guidance.

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

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

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

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

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

Intravaginal gel for staging of female pelvic cancers--preliminary report of safety, distention, and gel-mucosal contrast during magnetic resonance examination.

To more fully outline cervical and vaginal contours and distend the vagina, we have filled the vagina with sterile water-based gel before the magnetic resonance (MR) examination. The technique is similar to that used for defecating MR proctography and other MR examinations, but has not been well described for MR imaging of female pelvic cancer. We present our preliminary clinical experience, including a review of safety imaging characteristics and maintenance of the distention during the examination.

Evaluation of dynamic contrast-enhanced MRI in detecting renal scarring in a rat injury model.

PURPOSE: To create a reliable rat model with small renal cortical scars and evaluate the accuracy and sensitivity of dynamic contrast-enhanced MRI in detecting the kinds of lesions that are associated with reflux nephropathy. MATERIALS AND METHODS: In 16 rats, three unilateral renal cortical lesions were created using either electrocautery or pure alcohol with the contralateral kidney serving as control. MRI on a 1.5 Tesla GE Signa was performed 10-14 days after surgery. After bolus injection of 0.2 mM/Kg Gd-DTPA, sequential MRI acquisitions were performed using a 4-inch quadrature birdcage coil. Renal and scar volumes and pathology were compared after scanning and killing. RESULTS: Of the 48 points of injury, 40 (83%) in the 16 rats were detected grossly. Under microscopy, 36 injuries (75%) were detected on mid-kidney cross-sections. The average lesion was 4.2 mm(3) corresponding to 0.5% of the kidney volume. Using pathological findings as the gold standard, the sensitivity and specificity of scar detection using MRI was 69% and 93%, respectively. CONCLUSION: A rat model was created to demonstrate the sensitivity of dynamic contrast-enhanced MRI for detecting renal scars. Alcohol and electrocautery created reliable renal scars that were confirmed pathologically. MRI detected these lesions that averaged 4.2 mm(3) (0.5% total renal volume) with sensitivity and specificity of 69% and 93%, respectively.

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.

Monitoring prostate thermal therapy with diffusion-weighted MRI.

For MR-guided minimally invasive therapies, it is important to have a repeatable and reliable tissue viability evaluation method. The use of diffusion-weighted MRI (DWI) to evaluate tissue damage was assessed in 19 canine prostates with cryoablation or high-intensity ultrasound (HIU) ablation. The apparent diffusion coefficient (ADC) trace value was measured in the treated tissue immediately upon the procedure and on the posttreatment follow-up. For the acute lesions, the ADC value decreased to (1.05+/-0.25)x10(-3) mm2/s, as compared to (1.64+/-0.24)x10(-3) mm2/s before the treatment. There was no statistical difference between previously frozen or previously ultrasound-heated lesions in terms of the 36% ADC reduction (P=0.66). The ADC decrease occurred early during the course of the treatment, which appears to complicate DWI-based thermometry. Over time, the ADC value increased as the tissue recovered and regenerated. This study shows that DWI could be a promising method to monitor prostate thermal therapies and to provide insight on tissue damage and tissue remodeling after injury.

Catheter-based ultrasound devices and MR thermal monitoring for conformal prostate thermal therapy.

Catheter-based ultrasound applicators have been developed for delivering hyperthermia or high-temperature thermal ablation of cancer and benign disease of the prostate. These devices allow for control of heating along the length and angular expanse during therapy delivery. Four types of transurethral applicators were devised for thermal treatment of prostate combined with MR thermal monitoring: sectored tubular transducer devices with directional heating patterns and rotation; planar and curvilinear devices with narrow heating patterns and rotation; and multi-sectored tubular devices capable of dynamic angular control without applicator movement. Interstitial devices (2.4 mm OD) have been developed for percutaneous implantation with directional or dynamic angular control. In vivo experiments in canine prostate under MR temperature imaging were used to evaluate these devices and develop treatment delivery strategies. MR thermal imaging was used to monitor temperature and thermal dose in multiple slices through the target volume. Multi-sectored transurethral applicators can dynamically control the angular heating profile and target large regions of the gland in short treatment times without applicator manipulation. The sectored tubular, planar, and curvilinear transurethral devices produce directional coagulation zones, extending 15-20 mm radial distance to the outer prostate capsule. Sequential rotation under motor control and modulated dwell time can be used to tightly conform thermal ablation to selected regions. Interstitial implants with directional devices can be used to effectively ablate targeted regions of the gland while protecting the rectum. The MR derived 52 degrees C and lethal thermal dose contours (t43=240 min) effectively defined the extent of thermal damage and provided a means for real-time control of the applicators. Catheter-based ultrasound devices, combined with MR thermal monitoring, can produce relatively fast (5-40 min) and precise thermal ablation of prostate.

Referenceless MR thermometry for monitoring thermal ablation in the prostate.

Referenceless proton resonance frequency (PRF) shift thermometry provides a means to measure temperature changes during minimally invasive thermotherapy that is inherently robust to motion and tissue displacement. However, if the referenceless method is used to determine temperature changes during prostate ablation, phase gaps between water and fat in image regions used to determine the background phase can confound the phase estimation. We demonstrate an extension to referenceless thermometry which eliminates this problem by allowing background phase estimation in the presence of phase discontinuities between aqueous and fatty tissue. In this method, images are acquired with a multiecho sequence and binary water and fat maps are generated from a Dixon reconstruction. For the background phase estimation, water and fat regions are treated separately and the phase offset between the two tissue types is determined. The method is demonstrated feasibile in phantoms and during in vivo thermal ablation of canine prostate.

Split-bolus MDCT urography with synchronous nephrographic and excretory phase enhancement.

OBJECTIVE: Our purpose was to evaluate the utility of CT urography performed using a split contrast bolus that yields synchronous nephrographic and excretory phase enhancement. MATERIALS AND METHODS: Five hundred consecutive patients referred for evaluation of possible urinary tract abnormalities (327 for painless hematuria) underwent CT urography with unenhanced scanning of the abdomen and pelvis and scanning during concurrent nephrographic and excretory phase enhancement produced by administration of a split contrast bolus. The enhanced abdomen scan was obtained with abdominal compression; the enhanced pelvis scan was obtained after release of compression. Findings from axial sections and coronal maximum intensity projections were correlated with clinical follow-up and, as available, with laboratory and other imaging studies including cystoscopy, ureteroscopy, urine cytology, surgery, and pathology. Follow-up management for each patient was determined by the clinical judgment of the referring physician. RESULTS: CT urography identified 100% of pathologically confirmed renal cell carcinomas (n = 10) and uroepithelial malignancies involving the renal collecting system or ureter (n = 8). An additional nine renal masses were identified for which no pathologic proof has yet been obtained, including eight subcentimeter solid renal masses and one multiloculated lesion. Fourteen of 19 confirmed cases of uroepithelial neoplasm involving the bladder were identified. CT urography yielded one false-positive for bladder tumor, two false-positives for ureteral tumor, and one patient with a bladder mass who refused further evaluation. CT urography yielded sensitivity and specificity of 100% and 99% and 74% and 99% and positive predictive value and negative predictive value of 80% and 100% and 93% and 99% for the renal collecting system and ureter and bladder, respectively. CT urography was ineffective in identifying 11 cases of noninfectious cystitis. CT urography also depicted numerous other congenital and acquired abnormalities of the urinary tract. CONCLUSION: Split-bolus MDCT urography detected all proven cases of tumors of the upper urinary tract, yielding high sensitivity and specificity. The split-bolus technique has the potential to reduce both radiation dose and the number of images generated by MDCT urography.

Determination of 3-dimensional zonal renal volumes using contrast-enhanced computed tomography.

OBJECTIVE: To determine the accuracy with which total and cortical renal volumes may be measured in vivo with contrast-enhanced computed tomography (CT) in an animal model. METHODS: Seven female Yorkshire pigs were scanned in vivo using both a 64-channel multidetector row computed tomography (MDCT) scanner (Siemens Medical Solutions, Erlangen, Germany) and a C-arm CT scanner (Siemens AXIOM). Kidneys were scanned in corticomedullary and nephrographic phases after contrast injection. Three-dimensional volumetric analysis of CT data was performed to determine renal cortical and overall renal volumes, and renal lengths. We measured renal weights, water displacement volumes, and overall and cortical renal volumes of resected kidneys. RESULTS: Overall and cortical renal volumes by CT showed excellent correlation (R2 values varying from 0.77 to 0.92) with anatomic measurements of renal volume. There was poor correlation of anatomic renal volumes with renal lengths by CT. CONCLUSIONS: Three-dimensional analysis of contrast-enhanced CT provides accurate measurement of overall and cortical renal volumes in vivo.

Magnetic resonance-guided high-intensity ultrasound ablation of the prostate.

OBJECTIVES: This paper describes our work in developing techniques and devices for magnetic resonance (MR)-guided high-intensity ultrasound ablation of the prostate and includes review of relevant literature. METHODS: Catheter-based high-intensity ultrasound applicators, in interstitial and transurethral configurations, were developed to be used under MR guidance. Magnetic resonance thermometry and the relevant characteristics and artifacts were evaluated during in vivo thermal ablation of the prostate in 10 animals. Contrast-enhanced MR imaging (MRI) and diffusion-weighted MRI were used to assess tissue damage and compared with histology. RESULTS: During evaluation of these applicators, MR thermometry was used to monitor the temperature distributions in the prostate in real time. Magnetic resonance-derived maximum temperature thresholds of 52 degrees C and thermal dose thresholds of 240 minutes were used to control the extent of treatment and qualitatively correlated well with posttreatment imaging studies and histology. The directional transurethral devices are selective in their ability to target well-defined regions of the prostate gland and can be rotated in discrete steps to conform treatment to prescribed boundaries. The curvilinear applicator is the most precise of these directional techniques. Multisectored transurethral applicators, with dynamic angular control of heating and no rotation requirements, offer a fast and less complex means of treatment with less selective contouring. CONCLUSIONS: The catheter-based ultrasound devices can produce spatially selective regions of thermal destruction in prostate. The MR thermal imaging and thermal dose maps, obtained in multiple slices through the target volume, are useful for controlling therapy delivery (rotation, power levels, duration). Contrast-enhanced T1-weighted MRI and diffusion-weighted imaging are useful tools for assessing treatment.

Measurement of renal extraction fraction with contrast-enhanced CT.

Study was approved by the institutional review board, and informed patient consent was waived. A method for minimization of sources of variability in measuring single-kidney extraction fraction (EF) was determined retrospectively with contrast material-enhanced computed tomography (CT). Ten adults underwent CT of the kidneys; precontrast scans were obtained, followed by postcontrast scanning 2 minutes after contrast material injection. Single-kidney EF was then calculated for each patient with the formula EF = (CT(A) - CT(V))/(CT(A) - CT(PRE)), where CT(A) and CT(V) are the postcontrast CT values (in Hounsfield units) of the systemic blood and renal venous blood, respectively, and CT(PRE) is the precontrast CT value of the blood. Both conventional two-dimensional and volumetric three-dimensional regions of interest were used for determining mean CT values of the blood. By using the volumetric regions of interest, left and right renal EF values averaged 17.3% and 18.0%, respectively, for two observers, compared with the accepted value of 15%-20%. This latter technique also minimized right-left kidney and interobserver variability in the measurement of EF.

Curvilinear transurethral ultrasound applicator for selective prostate thermal therapy.

Thermal therapy offers a minimally invasive option for treating benign prostatic hyperplasia (BPH) and localized prostate cancer. In this study we investigated a transurethral ultrasound applicator design utilizing curvilinear, or slightly focused, transducers to heat prostatic tissue rapidly and controllably. The applicator was constructed with two independently powered transducer segments operating at 6.5 MHz and measuring 3.5 mm x 10 mm with a 15 mm radius of curvature across the short axis. The curvilinear applicator was characterized by acoustic efficiency measurements, acoustic beam plots, biothermal simulations of human prostate, ex vivo heating trials in bovine liver, and in vivo heating trials in canine prostate (n=3). Each transducer segment was found to emit a narrow acoustic beam (max width <3 mm), which extended the length of the transducer, with deeper penetration than previously developed planar or sectored tubular transurethral ultrasound applicators. Acoustic and biothermal simulations of human prostate demonstrated three treatment schemes for the curvilinear applicator: single shot (10 W, 60 s) schemes to generate narrow ablation zones (13 x 4 mm, 52 degrees C at the lesion boundary), incremental rotation (10 W, 10 degrees/45 s) to generate larger sector-shaped ablation zones (16 mm x 180 degrees sector), and rotation with variable sonication times (10 W, 10 degrees/15-90 s) to conform the ablation zone to a predefined boundary (9-17 mm x 180 degrees sector, 13 min total treatment time). During in vivo canine prostate experiments, guided by MR temperature imaging, single shot sonications (6 W/transducer, 2-3 min) with the curvilinear applicator ablated 20 degree sections of tissue to the prostate boundary (9-15 mm). Multiple adjacent sonications ("sweeping") ablated large sections of the prostate (180 degrees) by using the MR temperature imaging to adjust the power (4-6.4 W/transducer) and sonication time (30-180 s) at each 10 degrees rotation such that the periphery of the prostate reached 52 degrees C before the next rotation. The conclusion of this study was that the curvilinear applicator produces a narrow and penetrating ultrasound beam that, when combined with image guidance, can provide a precise technique for ablating target regions with a contoured outer boundary, such as the prostate capsule, by rotating in small steps while dynamically adjusting the net applied electrical power and sonication time at each position.