Feasibility of real-time magnetic resonance imaging for catheter guidance in electrophysiology studies.

BACKGROUND: Compared with fluoroscopy, the current imaging standard of care for guidance of electrophysiology procedures, magnetic resonance imaging (MRI) provides improved soft-tissue resolution and eliminates radiation exposure. However, because of inherent magnetic forces and electromagnetic interference, the MRI environment poses challenges for electrophysiology procedures. In this study, we sought to test the feasibility of performing electrophysiology studies with real-time MRI guidance. METHODS AND RESULTS: An MRI-compatible electrophysiology system was developed. Catheters were targeted to the right atrium, His bundle, and right ventricle of 10 mongrel dogs (23 to 32 kg) via a 1.5-T MRI system using rapidly acquired fast gradient-echo images (approximately 5 frames per second). Catheters were successfully positioned at the right atrial, His bundle, and right ventricular target sites of all animals. Comprehensive electrophysiology studies with recording of intracardiac electrograms and atrial and ventricular pacing were performed. Postprocedural pathological evaluation revealed no evidence of thermal injury to the myocardium. After proof of safety in animal studies, limited real-time MRI-guided catheter mapping studies were performed in 2 patients. Adequate target catheter localization was confirmed via recording of intracardiac electrograms in both patients. CONCLUSIONS: To the best of our knowledge, this is the first study to report the feasibility of real-time MRI-guided electrophysiology procedures. This technique may eliminate patient and staff radiation exposure and improve real-time soft tissue resolution for procedural guidance.

Inverse treatment planning based on MRI for HDR prostate brachytherapy.

PURPOSE: To develop and optimize a technique for inverse treatment planning based solely on magnetic resonance imaging (MRI) during high-dose-rate brachytherapy for prostate cancer. METHODS AND MATERIALS: Phantom studies were performed to verify the spatial integrity of treatment planning based on MRI. Data were evaluated from 10 patients with clinically localized prostate cancer who had undergone two high-dose-rate prostate brachytherapy boosts under MRI guidance before and after pelvic radiotherapy. Treatment planning MRI scans were systematically evaluated to derive a class solution for inverse planning constraints that would reproducibly result in acceptable target and normal tissue dosimetry. RESULTS: We verified the spatial integrity of MRI for treatment planning. MRI anatomic evaluation revealed no significant displacement of the prostate in the left lateral decubitus position, a mean distance of 14.47 mm from the prostatic apex to the penile bulb, and clear demarcation of the neurovascular bundles on postcontrast imaging. Derivation of a class solution for inverse planning constraints resulted in a mean target volume receiving 100% of the prescribed dose of 95.69%, while maintaining a rectal volume receiving 75% of the prescribed dose of <5% (mean 1.36%) and urethral volume receiving 125% of the prescribed dose of <2% (mean 0.54%). CONCLUSION: Systematic evaluation of image spatial integrity, delineation uncertainty, and inverse planning constraints in our procedure reduced uncertainty in planning and treatment.

Design of a novel MRI compatible manipulator for image guided prostate interventions.

This paper reports a novel remotely actuated manipulator for access to prostate tissue under magnetic resonance imaging guidance (APT-MRI) device, designed for use in a standard high-field MRI scanner. The device provides three-dimensional MRI guided needle placement with millimeter accuracy under physician control. Procedures enabled by this device include MRI guided needle biopsy, fiducial marker placements, and therapy delivery. Its compact size allows for use in both standard cylindrical and open configuration MRI scanners. Preliminary in vivo canine experiments and first clinical trials are reported.

MRI-guided HDR prostate brachytherapy in standard 1.5T scanner.

PURPOSE: Magnetic resonance imaging (MRI) provides superior visualization of the prostate and surrounding anatomy, making it the modality of choice for imaging the prostate gland. This pilot study was performed to determine the feasibility and dosimetric quality achieved when placing high-dose-rate prostate brachytherapy catheters under MRI guidance in a standard "closed-bore" 1.5T scanner. METHODS AND MATERIALS: Patients with intermediate-risk and high-risk localized prostate cancer received MRI-guided high-dose-rate brachytherapy boosts before and after a course of external beam radiotherapy. Using a custom visualization and targeting program, the brachytherapy catheters were placed and adjusted under MRI guidance until satisfactory implant geometry was achieved. Inverse treatment planning was performed using high-resolution T(2)-weighted MRI. RESULTS: Ten brachytherapy procedures were performed on 5 patients. The median percentage of volume receiving 100% of prescribed minimal peripheral dose (V(100)) achieved was 94% (mean, 92%; 95% confidence interval, 89-95%). The urethral V(125) ranged from 0% to 18% (median, 5%), and the rectal V(75) ranged from 0% to 3.1% (median, 0.3%). In all cases, lesions highly suspicious for malignancy could be visualized on the procedural MRI, and extracapsular disease was identified in 2 patients. CONCLUSION: High-dose-rate prostate brachytherapy in a standard 1.5T MRI scanner is feasible and achieves favorable dosimetry within a reasonable period with high-quality image guidance. Although the procedure was well tolerated in the acute setting, additional follow-up is required to determine the long-term safety and efficacy of this approach.

The effect of anterior proton beams in the setting of a prostate-rectum spacer.

Studies suggest that anterior beams with in vivo range verification would improve rectal dosimetry in proton therapy for prostate cancer. We investigated whether prostate-rectum spacers would enhance or diminish the benefits of anterior proton beams in these treatments. Twenty milliliters of hydrogel was injected between the prostate and rectum of a cadaver using a transperineal approach. Computed tomography (CT) and magnetic resonance (MR) images were used to generate 7 uniform scanning (US) and 7 single-field uniform dose pencil-beam scanning (PBS) plans with different beam arrangements. Pearson correlations were calculated between rectal, bladder, and femoral head dosimetric outcomes and beam arrangement anterior scores, which characterize the degree to which dose is delivered anteriorly. The overall quality of each plan was compared using a virtual dose-escalation study. For US plans, rectal mean dose was inversely correlated with anterior score, but for PBS plans there was no association between rectal mean dose and anterior score. For both US and PBS plans, full bladder and empty bladder mean doses were correlated with anterior scores. For both US and PBS plans, femoral head mean doses were inversely correlated with anterior score. For US plans and a full bladder, 4 beam arrangements that included an anterior beam tied for the highest maximum prescription dose (MPD). For US plans and an empty bladder, the arrangement with 1 anterior and 2 anterior oblique beams achieved the highest MPD in the virtual dose-escalation study. The dose-escalation study did not differentiate beam arrangements for PBS. All arrangements in the dose-escalation study were limited by bladder constraints except for the arrangement with 2 posterior oblique beams. The benefits of anterior proton beams in the setting of prostate-rectum spacers appear to be proton modality dependent and may not extend to PBS.

Effects of prostate-rectum separation on rectal dose from external beam radiotherapy.

PURPOSE: In radiotherapy for prostate cancer, the rectum is the major dose-limiting structure. Physically separating the rectum from the prostate (e.g., by injecting a spacer) can reduce the rectal radiation dose. Despite pilot clinical studies, no careful analysis has been done of the risks, benefits, and dosimetric effects of this practice. METHODS AND MATERIALS: Using cadaveric specimens, 20 mL of a hydrogel was injected between the prostate and rectum using a transperineal approach. Imaging was performed before and after spacer placement, and the cadavers were subsequently dissected. Ten intensity-modulated radiotherapy plans were generated (five before and five after separation), allowing for characterization of the rectal dose reduction. To quantify the amount of prostate-rectum separation needed for effective rectal dose reduction, simulations were performed using nine clinically generated intensity-modulated radiotherapy plans. RESULTS: In the cadaveric studies, an average of 12.5 mm of prostate-rectum separation was generated with the 20-mL hydrogel injections (the seminal vesicles were also separated from the rectum). The average rectal volume receiving 70 Gy decreased from 19.9% to 4.5% (p < .05). In the simulation studies, a prostate-rectum separation of 10 mm was sufficient to reduce the mean rectal volume receiving 70 Gy by 83.1% (p <.05). No additional reduction in the average rectal volume receiving 70 Gy was noted after 15 mm of separation. In addition, spacer placement allowed for increased planning target volume margins without exceeding the rectal dose tolerance. CONCLUSION: Prostate-rectum spacers can allow for reduced rectal toxicity rates, treatment intensification, and/or reduced dependence on complex planning and treatment delivery techniques.

A preliminary analysis and model of prostate injection distributions.

PURPOSE: Understanding the internal dynamics of prostate injections, particularly injection pattern distribution is a key step to developing new therapies for prostate disease that may be best served with a direct injection approach. Due to excellent properties involving liquid contrast agents, MRI can be used for targeting and monitoring of injections into organs and tissues. MATERIALS AND METHODS: Eleven intraprostatic injections were performed in vivo with canines using a custom transrectal guiding and imaging system for use in a standard 1.5 T MR scanner. In addition, 25 injections were performed on excised cadaveric human prostates, using a MedRad Spectris injector system. MRI was used to guide the injections and monitor intraparenchymal injection distribution. RESULTS: T1 and T2-weighted MR images were correlated with histology to produce three-dimensional data sets that can be used to analyze trends in injection patterns. This analysis was used to develop strategies for injection prediction such as gadolinium pre-injections and diffusion-weighted imaging guidance. In addition, a rough model of prostate injections is described, and a preliminary injection guide is developed that takes into account the individual clinician's goals for therapy. CONCLUSIONS: MR visualization of injected therapeutic agents allows for prediction and monitoring of drug distributions, possibly improving efficacy and reducing side effects. Injection analysis and modeling may be used to assist in optimizing clinical treatments that require or would benefit from focal parenchymal injections into the prostate.

Transrectal prostate biopsy and fiducial marker placement in a standard 1.5T magnetic resonance imaging scanner.

PURPOSE: We investigated the accuracy and feasibility of a system that provides transrectal needle access to the prostate concurrent with 1.5 Tesla MRI which previously has not been possible. MATERIALS AND METHODS: In 5 patients with previously diagnosed prostate cancer, MRI guided intraprostatic placement of gold fiducial markers (4 procedures) and/or prostate biopsy (3 procedures) was performed using local anesthesia. RESULTS: Mean procedure duration was 76 minutes and all patients tolerated the intervention well. Procedure related adverse events included self-limited hematuria and hematochezia following 3 of 8 procedures (all resolved in less than 1 week). Mean needle placement accuracy was 1.9 mm for the fiducial marker placement studies and 1.8 mm for the biopsy procedures. Mean fiducial marker placement accuracy was 4.8 mm and the mean fiducial marker placement accuracy transverse to the needle direction was 2.6 mm. All patients who underwent the procedure were able to complete their course of radiotherapy without delay or complication. CONCLUSIONS: While studies of clinical usefulness are warranted, transrectal 1.5 T MRI guided prostate biopsy and fiducial marker placement is feasible using this system, providing new opportunities for image guided diagnostic and therapeutic prostate interventions.

Early observed transient prostate-specific antigen elevations on a pilot study of external beam radiation therapy and fractionated MRI guided high dose rate brachytherapy boost.

PURPOSE: To report early observation of transient PSA elevations on this pilot study of external beam radiation therapy and magnetic resonance imaging (MRI) guided high dose rate (HDR) brachytherapy boost. MATERIALS AND METHODS: Eleven patients with intermediate-risk and high-risk localized prostate cancer received MRI guided HDR brachytherapy (10.5 Gy each fraction) before and after a course of external beam radiotherapy (46 Gy). Two patients continued on hormones during follow-up and were censored for this analysis. Four patients discontinued hormone therapy after RT. Five patients did not receive hormones. PSA bounce is defined as a rise in PSA values with a subsequent fall below the nadir value or to below 20% of the maximum PSA level. Six previously published definitions of biochemical failure to distinguish true failure from were tested: definition 1, rise >0.2 ng/mL; definition 2, rise >0.4 ng/mL; definition 3, rise >35% of previous value; definition 4, ASTRO defined guidelines, definition 5 nadir + 2 ng/ml, and definition 6, nadir + 3 ng/ml. RESULTS: Median follow-up was 24 months (range 18-36 mo). During follow-up, the incidence of transient PSA elevation was: 55% for definition 1, 44% for definition 2, 55% for definition 3, 33% for definition 4, 11% for definition 5, and 11% for definition 6. CONCLUSION: We observed a substantial incidence of transient elevations in PSA following combined external beam radiation and HDR brachytherapy for prostate cancer. Such elevations seem to be self-limited and should not trigger initiation of salvage therapies. No definition of failure was completely predictive.

Intra- and inter-radiation therapist reproducibility of daily isocenter verification using prostatic fiducial markers.

BACKGROUND: We sought to determine the intra- and inter-radiation therapist reproducibility of a previously established matching technique for daily verification and correction of isocenter position relative to intraprostatic fiducial markers (FM). MATERIALS AND METHODS: With the patient in the treatment position, anterior-posterior and left lateral electronic images are acquired on an amorphous silicon flat panel electronic portal imaging device. After each portal image is acquired, the therapist manually translates and aligns the fiducial markers in the image to the marker contours on the digitally reconstructed radiograph. The distances between the planned and actual isocenter location is displayed. In order to determine the reproducibility of this technique, four therapists repeated and recorded this operation two separate times on 20 previously acquired portal image datasets from two patients. The data were analyzed to obtain the mean variability in the distances measured between and within observers. RESULTS: The mean and median intra-observer variability ranged from 0.4 to 0.7 mm and 0.3 to 0.6 mm respectively with a standard deviation of 0.4 to 1.0 mm. Inter-observer results were similar with a mean variability of 0.9 mm, a median of 0.6 mm, and a standard deviation of 0.7 mm. When using a 5 mm threshold, only 0.5% of treatments will undergo a table shift due to intra or inter-observer error, increasing to an error rate of 2.4% if this threshold were reduced to 3 mm. CONCLUSION: We have found high reproducibility with a previously established method for daily verification and correction of isocenter position relative to prostatic fiducial markers using electronic portal imaging.

Paradoxical loss of excitation with high intensity pulses during electric field stimulation of single cardiac cells.

Transmembrane potential responses of single cardiac cells stimulated at rest were studied with uniform rectangular field pulses having durations of 0.5-10 ms. Cells were enzymatically isolated from guinea pig ventricles, stained with voltage sensitive dye di-8-ANEPPS, and stimulated along their long axes. Fluorescence signals were recorded with spatial resolution of 17 microm for up to 11 sites along the cell. With 5 and 10 ms pulses, all cells (n = 10) fired an action potential over a broad range of field amplitudes (approximately 3-65 V/cm). With 0.5 and 1 ms pulses, all cells (n = 7) fired an action potential for field amplitudes ranging from the threshold value (approximately 4-8 V/cm) to 50-60 V/cm. However, when the field amplitude was further increased, five of seven cells failed to fire an action potential. We postulated that this paradoxical loss of excitation for higher amplitude field pulses is the result of nonuniform polarization of the cell membrane under conditions of electric field stimulation, and a counterbalancing interplay between sodium current and inwardly rectifying potassium current with increasing field strength. This hypothesis was verified using computer simulations of a field-stimulated guinea pig ventricular cell. In conclusion, we show that for stimulation with short-duration pulses, cells can be excited for fields ranging between a low amplitude excitation threshold and a high amplitude threshold above which the excitation is suppressed. These results can have implications for the mechanistic understanding of defibrillation outcome, especially in the setting of diseased myocardium.

An interventional magnetic resonance imaging technique for the molecular characterization of intraprostatic dynamic contrast enhancement.

The biological characterization of an individual patient's tumor by noninvasive imaging will have an important role in cancer care and clinical research if the molecular processes that underlie the image data are known. Spatial heterogeneity in the dynamics of magnetic resonance imaging contrast enhancement (DCE-MRI) is hypothesized to reflect variations in tumor angiogenesis. Here we demonstrate the feasibility of precisely colocalizing DCE-MRI data with the genomic and proteomic profiles of underlying biopsy tissue using a novel MRI-guided biopsy technique in a patients with prostate cancer.

Intravascular extended sensitivity (IVES) MRI antennas.

The design and application of an intravascular extended sensitivity (IVES) MRI antenna is described. The device is a loopless antenna design that incorporates both an insulating, dielectric coating and a winding of the antenna whip into a helical shape. Because this antenna produces a broad region of high SNR and also allows for imaging near the tip of the device, it is useful for imaging long, luminal structures. To elucidate the design and function of this device, the effects of both insulation and antenna winding were characterized by theoretical and experimental studies. Insulation broadens the longitudinal region over which images can be collected (i.e., along the lumen of a vessel) by increasing the resonant pole length. Antenna winding, conversely, allows for imaging closer to the tip of the antenna by decreasing the resonant pole length. Over a longitudinal region of 20 cm, the IVES imaging antenna described here produces a system SNR of approximately 40,000/r (mL(-1)Hz(1/2)), where r is the radial distance from the antenna axis in centimeters. As opposed to microcoil antenna designs, these antennas do not require exact positioning and allow for imaging over broad tissue regions. While focusing on the design of the IVES antenna, this work also serves to enhance our overall understanding of the properties and behavior of the loopless antenna design.

RF safety of wires in interventional MRI: using a safety index.

With the rapid growth of interventional MRI, radiofrequency (RF) heating at the tips of guidewires, catheters, and other wire-shaped devices has become an important safety issue. Previous studies have identified some of the variables that affect the relative magnitude of this heating but none could predict the absolute amount of heating to formulate safety margins. This study presents the first theoretical model of wire tip heating that can accurately predict its absolute value, assuming a straight wire, a homogeneous RF coil, and a wire that does not extend out of the tissue. The local specific absorption rate (SAR) amplification from induced currents on insulated and bare wires was calculated using the method of moments. This SAR gain was combined with a semianalytic solution to the bioheat transfer equation to generate a safety index. The safety index ( degrees C/(W/kg)) is a measure of the in vivo temperature change that can occur with the wire in place, normalized to the SAR of the pulse sequence. This index can be used to set limits on the spatial peak SAR of pulse sequences that are used with the interventional wire. For the case of a straight resonant wire in a tissue with very low perfusion, only about 100 mW/kg/ degrees C spatial peak SAR may be used at 1.5 T. But for < or =10-cm wires with an insulation thickness > or =30% of the wire radius that are placed in well-perfused tissues, normal operating conditions of 4 W/kg spatial peak SAR are possible at 1.5 T. Further model development to include the influence of inhomogeneous RF, curved wires, and wires that extend out of the sample are required to generate safety indices that are applicable to common clinical situations. We propose a simple way to ensure safety when using an interventional wire: set a limit on the SAR of allowable pulse sequences that is a factor of a safety index below the tolerable temperature increase.

RF heating due to conductive wires during MRI depends on the phase distribution of the transmit field.

In many studies concerning wire heating during MR imaging, a "resonant wire length" that maximizes RF heating is determined. This may lead to the nonintuitive conclusion that adding more wire, so as to avoid this resonant length, will actually improve heating safety. Through a theoretical analysis using the method of moments, we show that this behavior depends on the phase distribution of the RF transmit field. If the RF transmit field has linear phase, with slope equal to the real part of the wavenumber in the tissue, long wires always heat more than short wires. In order to characterize the intrinsic safety of a device without reference to a specific body coil design, this maximum-tip heating phase distribution must be considered. Finally, adjusting the phase distribution of the electric field generated by an RF transmit coil may lead to an "implant-friendly" coil design.

Multifunctional interventional devices for MRI: a combined electrophysiology/MRI catheter.

The design and application of a two-wire electrophysiology (EP) catheter that simultaneously records the intracardiac electrogram and receives the MR signal for active catheter tracking is described. The catheter acts as a long loop receiver, allowing for visualization of the entire catheter length while simultaneously behaving as a traditional two-wire EP catheter, allowing for intracardiac electrogram recording and ablation. The application of the device is demonstrated by simultaneously tracking the catheter and recording the intracardiac electrogram in canine models using 7 and 10 frame/sec real-time imaging sequences. Using solely MR imaging, the entire catheter was visualized and guided from the jugular vein into the cardiac chambers, where the intracardiac electrogram was recorded. By combining several functions in a single, simple structure, the excellent tissue contrast and functional imaging capabilities of MR can be used to improve the efficacy of EP interventions. This catheter will facilitate MR-guided interventions and demonstrates the design of multifunctional interventional devices for use in MRI.

System for MR image-guided prostate interventions: canine study.

The purpose of this study was to demonstrate the use of a transrectal system that enables precise magnetic resonance (MR) image guidance and monitoring of prostate interventions. The system used a closed-bore 1.5-T MR imaging unit and enables one to take advantage of the higher signal-to-noise ratio achieved with traditional magnet designs, which is crucial for accurate targeting and monitoring of prostate interventions. In the first of the four canine studies, reliable needle placement, with all needles placed within 2 mm of the desired target site, was achieved. In two other studies, MR imaging was used to monitor distribution of injected contrast agent solution (gadopentetate dimeglumine mixed with trypan blue dye) in and around the prostate, thereby confirming that solution had been delivered to the desired tissue and also detecting faulty injections. In the final study, accurate placement and MR imaging of brachytherapy seeds in the prostate were demonstrated. The described system provides a flexible platform for a variety of minimally invasive MR image-guided therapeutic and diagnostic prostate interventions.

System for prostate brachytherapy and biopsy in a standard 1.5 T MRI scanner.

A technique for transperineal high-dose-rate (HDR) prostate brachytherapy and needle biopsy in a standard 1.5 T MRI scanner is demonstrated. In each of eight procedures (in four patients with intermediate to high risk localized prostate cancer), four MRI-guided transperineal prostate biopsies were obtained followed by placement of 14-15 hollow transperineal catheters for HDR brachytherapy. Mean needle-placement accuracy was 2.1 mm, 95% of needle-placement errors were less than 4.0 mm, and the maximum needle-placement error was 4.4 mm. In addition to guiding the placement of biopsy needles and brachytherapy catheters, MR images were also used for brachytherapy treatment planning and optimization. Because 1.5 T MR images are directly acquired during the interventional procedure, dependence on deformable registration is reduced and online image quality is maximized.