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1.  Biopsy Needle Artifact Localization in MRI-guided Robotic Transrectal Prostate Intervention 
Recently a number of robotic intervention systems for magnetic resonance image (MRI) guided needle placement in the prostate have been reported. In MRI-guided needle interventions, after a needle is inserted, the needle position is often confirmed with a volumetric MRI scan. Commonly used titanium needles are not directly visible in an MR image, but they generate a susceptibility artifact in the immediate neighborhood of the needle. This paper reports the results of a quantitative study of the relationship between the true position of titanium biopsy needle and the corresponding needle artifact position in MR images, thereby providing a better understanding of the influence of needle artifact on targeting errors. The titanium needle tip artifact extended 9 mm beyond the actual needle tip location with tendency to bend towards the scanner’s B0 magnetic field direction, and axially displaced 0.38 mm and 0.32 mm (mean) in scanner’s frequency and phase encoding direction, respectively.
doi:10.1109/TBME.2012.2192118
PMCID: PMC3675798  PMID: 22481805
Needle artifact; prostate intervention; robotic intervention; transrectal biopsy
2.  Development and Evaluation of an Actuated MRI-Compatible Robotic System for MRI-Guided Prostate Intervention 
This paper reports the design, development, and magnetic resonance imaging (MRI) compatibility evaluation of an actuated transrectal prostate robot for MRI-guided needle intervention in the prostate. The robot performs actuated needle MRI-guidance with the goals of providing (i) MRI compatibility, (ii) MRI-guided needle placement with accuracy sufficient for targeting clinically significant prostate cancer foci, (iii) reducing interventional procedure times (thus increasing patient comfort and reducing opportunity for needle targeting error due to patient motion), (iv) enabling real-time MRI monitoring of interventional procedures, and (v) reducing the opportunities for error that arise in manually actuated needle placement. The design of the robot, employing piezo-ceramic-motor actuated needle guide positioning and manual needle insertion, is reported. Results of a MRI compatibility study show no reduction of MRI signal-to-noise-ratio (SNR) with the motors disabled. Enabling the motors reduces the SNR by 80% without RF shielding, but SNR is only reduced by 40% to 60% with RF shielding. The addition of radio-frequency shielding is shown to significantly reduce image SNR degradation caused by the presence of the robotic device. An accuracy study of MRI-guided biopsy needle placements in a prostate phantom is reported. The study shows an average in-plane targeting error of 2.4 mm with a maximum error of 3.7 mm. These data indicate the system’s needle targeting accuracy is similar to that obtained with a previously reported manually actuated system, and is sufficient to reliably sample clinically significant prostate cancer foci under MRI-guidance.
doi:10.1109/TMECH.2011.2163523
PMCID: PMC3544166  PMID: 23326181
Magnetic resonance imaging; robot manipulators; image-guided intervention; prostate cancer
3.  A Study of Needle Image Artifact Localization in Confirmation Imaging of MRI-guided Robotic Prostate Biopsy 
Recently several systems for magnetic resonance image (MRI) guided needle placement in the prostate have been reported. In comparison to conventional ultrasound-guided needle placement in the prostate, these MRI-guided systems promise improved targeting accuracy for prostate intervention procedures including biopsy, fiducial marker insertion, injection and focal therapy. In MRI-guided needle interventions, after a needle is inserted, the needle position is often confirmed with a volumetric MRI scan. Commonly used titanium needles are not directly visible in an MR image, but they generate a susceptibility artifact in the immediate neighborhood of the needle. This paper reports the results of a quantitative study of the relation between the true position of titanium biopsy needle and the corresponding needle artifact position in MR images. The titanium needle artifact was found to be displaced 0.38 mm and 0.32 mm shift in scanner’s frequency and phase encoding direction, respectively. The artifact at the tip of the titanium needle was observed to bend toward the scanner’s B0 magnetic field direction.
doi:10.1109/ICRA.2011.5980309
PMCID: PMC3299982  PMID: 22423338
4.  Design and Preliminary Accuracy Studies of an MRI-Guided Transrectal Prostate Intervention System 
This paper reports a novel system for magnetic resonance imaging (MRI) guided transrectal prostate interventions, such as needle biopsy, fiducial marker placement, and therapy delivery. The system utilizes a hybrid tracking method, comprised of passive fiducial tracking for initial registration and subsequent incremental motion measurement along the degrees of freedom using fiber-optical encoders and mechanical scales. Targeting accuracy of the system is evaluated in prostate phantom experiments. Achieved targeting accuracy and procedure times were found to compare favorably with existing systems using passive and active tracking methods. Moreover, the portable design of the system using only standard MRI image sequences and minimal custom scanner interfacing allows the system to be easily used on different MRI scanners.
PMCID: PMC3299493  PMID: 18044553
5.  An Interventional Magnetic Resonance Imaging Technique for the Molecular Characterization of Intraprostatic Dynamic Contrast Enhancement 
Molecular Imaging  2005;4(1):63-66.
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 patients with prostate cancer.
PMCID: PMC3299492  PMID: 15967127
Angiogenesis; molecular imaging; interventional MRI; prostate cancer; micro-array analysis
6.  An MRI-Compatible Robotic System With Hybrid Tracking for MRI-Guided Prostate Intervention 
This paper reports the development, evaluation, and first clinical trials of the access to the prostate tissue (APT) II system—a scanner independent system for magnetic resonance imaging (MRI)-guided transrectal prostate interventions. The system utilizes novel manipulator mechanics employing a steerable needle channel and a novel six degree-of-freedom hybrid tracking method, comprising passive fiducial tracking for initial registration and subsequent incremental motion measurements. Targeting accuracy of the system in prostate phantom experiments and two clinical human-subject procedures is shown to compare favorably with existing systems using passive and active tracking methods. The portable design of the APT II system, using only standard MRI image sequences and minimal custom scanner interfacing, allows the system to be easily used on different MRI scanners.
doi:10.1109/TBME.2011.2134096
PMCID: PMC3299494  PMID: 22009867
Image-guided intervention; MRI; prostate cancer; robot manipulators
7.  Target Motion Compensation in MRI-guided Prostate Biopsy with Static Images 
Purpose
MRI-guided prostate needle biopsy requires compensation for organ motion between target planning and needle placement.
Methods
We propose slice-to-volume registration algorithms for tracking the prostate motion. Three orthogonal intra-operative slices are acquired in the approximate center of the prostate and registered with a high-resolution target planning volume. Both rigid and deformable scenarios were implemented. MRI-guided robotic prostate biopsy cases were analyzed retrospectively.
Results
Average registration errors were 2.55mm for the rigid algorithm and 2.05mm for the deformable algorithm.
Conclusion
Slice-based tracking appears to be promising. Deformable registration does not seem warranted.
doi:10.1109/IEMBS.2010.5626497
PMCID: PMC3059728  PMID: 21096273
Biopsy; prostate; motion tracking; slice-to-volume registration
8.  MRI-Guided Robotic Prostate Biopsy: A Clinical Accuracy Validation 
Prostate cancer is a major health threat for men. For over five years, the U.S. National Cancer Institute has performed prostate biopsies with a magnetic resonance imaging (MRI)-guided robotic system.
Purpose
A retrospective evaluation methodology and analysis of the clinical accuracy of this system is reported.
Methods
Using the pre and post-needle insertion image volumes, a registration algorithm that contains a two-step rigid registration followed by a deformable refinement was developed to capture prostate dislocation during the procedure. The method was validated by using three-dimensional contour overlays of the segmented prostates and the registrations were accurate up to 2 mm.
Results
It was found that tissue deformation was less of a factor than organ displacement. Out of the 82 biopsies from 21 patients, the mean target displacement, needle placement error, and clinical biopsy error was 5.9 mm, 2.3 mm, and 4 mm, respectively.
Conclusion
The results suggest that motion compensation for organ displacement should be used to improve targeting accuracy.
PMCID: PMC2976594  PMID: 20879423
9.  Accuracy validation for MRI-guided robotic prostate biopsy 
Proceedings of SPIE  2010;7625(2010):762517-762518.
We report a quantitative evaluation of the clinical accuracy of a MRI-guided robotic prostate biopsy system that has been in use for over five years at the U.S. National Cancer Institute. A two-step rigid volume registration using mutual information between the pre and post needle insertion images was performed. Contour overlays of the prostate before and after registration were used to validate the registration. A total of 20 biopsies from 5 patients were evaluated. The maximum registration error was 2 mm. The mean biopsy target displacement, needle placement error, and biopsy error was 5.4 mm, 2.2 mm, and 5.1 mm respectively. The results show that the pre-planned biopsy target did dislocate during the procedure and therefore causing biopsy errors.
doi:10.1117/12.844251
PMCID: PMC2995279  PMID: 21132060
Accuracy validation; image guided prostate biopsy; rigid volume registration; MRI
10.  Initial clinical experience with real-time transrectal ultrasonography-magnetic resonance imaging fusion-guided prostate biopsy 
BJU international  2007;101(7):841-845.
OBJECTIVE
To evaluate the feasibility and utility of registration and fusion of real-time transrectal ultrasonography (TRUS) and previously acquired magnetic resonance imaging (MRI) to guide prostate biopsies.
PATIENTS AND METHODS
Two National Cancer Institute trials allowed MRI-guided (with or with no US fusion) prostate biopsies during placement of fiducial markers. Fiducial markers were used to guide patient set-up for daily external beam radiation therapy. The eligible patients had biopsy-confirmed prostate cancer that was visible on MRI. A high-field (3T) MRI was performed with an endorectal coil in place. After moving to an US suite, the patient then underwent TRUS to visualize the prostate. The US transducer was equipped with a commercial needle guide and custom modified with two embedded miniature orthogonal five-degrees of freedom sensors to enable spatial tracking and registration with MR images in six degrees of freedom. The MRI sequence of choice was registered manually to the US using custom software for real-time navigation and feedback. The interface displayed the actual and projected needle pathways superimposed upon the real-time US blended with the prior MR images, with position data updating in real time at 10 frames per second. The registered MRI information blended to the real-time US was available to the physician who performed targeted biopsies of highly suspicious areas.
RESULTS
Five patients underwent limited focal biopsy and fiducial marker placement with real-time TRUS-MRI fusion. The Gleason scores at the time of enrolment on study were 8, 7, 9, 9, and 6. Of the 11 targeted biopsies, eight showed prostate cancer. Positive biopsies were found in all patients. The entire TRUS procedure, with fusion, took ≈10 min.
CONCLUSION
The fusion of real-time TRUS and prior MR images of the prostate is feasible and enables MRI-guided interventions (like prostate biopsy) outside of the MRI suite. The technique allows for navigation within dynamic contrast-enhanced maps, or T2-weighted or MR spectroscopy images. This technique is a rapid way to facilitate MRI-guided prostate therapies such as external beam radiation therapy, brachytherapy, cryoablation, high-intensity focused ultrasound ablation, or direct injection of agents, without the cost, throughput, or equipment compatibility issues that might arise with MRI-guided interventions inside the MRI suite.
doi:10.1111/j.1464-410X.2007.07348.x
PMCID: PMC2621260  PMID: 18070196
magnetic resonance; ultrasound; prostate cancer; imaging; transrectal
11.  Closed-Loop Control in Fused MR-TRUS Image-Guided Prostate Biopsy 
Multi-modality fusion imaging for targeted prostate biopsy is difficult because of prostate motion during the biopsy procedure. A closed-loop control mechanism is proposed to improve the efficacy and safety of the biopsy procedure, which uses real-time ultrasound and spatial tracking as feedback to adjust the registration between a preoperative 3D image (e.g. MRI) and real-time ultrasound images. The spatial tracking data is used to initialize the image-based registration between intraoperative ultrasound images and a preoperative ultrasound volume. The preoperative ultrasound volume is obtained using a 2D sweep and manually registered to the MRI dataset before the biopsy procedure. The accuracy of the system is 2.3±0.9 mm in phantom studies. The results of twelve patient studies show that prostate motion can be effectively compensated using closed-loop control.
PMCID: PMC2567020  PMID: 18051052
motion compensation; prostate biopsy; image registration
12.  Intrarectal Amifostine During External Beam Radiation Therapy for Prostate Cancer Produces Significant Improvements in Quality of Life Measured by EPIC Score 
Purpose
To test whether intrarectal Amifostine limits symptoms of radiation proctitis as measured by the RTOG GI toxicity score and the expanded prostate cancer index composite (EPIC) score.
Methods and Materials
Patients with localized prostate cancer recieved Amifostine as a rectal suspension 30–45 min before daily 3D-conformal radiation treatments (3D-CRT). The first 18 patients received 1gm of Amifostine and the next 12 patients received 2gm. Toxicity was assessed at baseline, during treatment, and at follow-up visits using RTOG grading and the EPIC Quality of Life (QoL) 50 item questionnaire. The “Bowel Function” subset of the bowel domain (EPIC-BF), which targets symptom severity, and “Bowel Bother” subset of the bowel domain (EPIC-BB), which assesses quality of life, were evaluated and compared to the RTOG GI toxicity score.
Results
Median follow-up was 30 months (range 18–36). Overall, the EPIC-BF and EPIC-BB scores both track closely with the RTOG GI toxicity score. Seven weeks after the start of radiation therapy, the incidence of RTOG Grade 2 toxicity was 33% in the 1gm group (6/18) compared with 0% (0/12) in the 2gm group and trended towards statistical significance (p=0.06). A significant difference between Amifostine groups was observed using the EPIC-BF score at 7 weeks (p=0.04). A difference in EPIC-BB score between dose groups was evident at 7 weeks (p=0.07) and was significant at 12 months (p=0.04).
Conclusions
Higher doses of Amifostine produce significant improvements in acute and late bowel QoL (up to one year following therapy) as measured by the EPIC score.
doi:10.1016/j.ijrobp.2007.05.057
PMCID: PMC2267374  PMID: 17855015
Amifostine; Prostate; Radiation-induced Proctitis; EPIC; Quality of Life
13.  Simultaneous integrated boost of biopsy proven, MRI defined dominant intra-prostatic lesions to 95 Gray with IMRT: early results of a phase I NCI study 
Background
To assess the feasibility and early toxicity of selective, IMRT-based dose escalation (simultaneous integrated boost) to biopsy proven dominant intra-prostatic lesions visible on MRI.
Methods
Patients with localized prostate cancer and an abnormality within the prostate on endorectal coil MRI were eligible. All patients underwent a MRI-guided transrectal biopsy at the location of the MRI abnormality. Gold fiducial markers were also placed. Several days later patients underwent another MRI scan for fusion with the treatment planning CT scan. This fused MRI scan was used to delineate the region of the biopsy proven intra-prostatic lesion. A 3 mm expansion was performed on the intra-prostatic lesions, defined as a separate volume within the prostate. The lesion + 3 mm and the remainder of the prostate + 7 mm received 94.5/75.6 Gray (Gy) respectively in 42 fractions. Daily seed position was verified to be within 3 mm.
Results
Three patients were treated. Follow-up was 18, 6, and 3 months respectively. Two patients had a single intra-prostatic lesion. One patient had 2 intra-prostatic lesions. All four intra-prostatic lesions, with margin, were successfully targeted and treated to 94.5 Gy. Two patients experienced acute RTOG grade 2 genitourinary (GU) toxicity. One had grade 1 gastrointestinal (GI) toxicity. All symptoms completely resolved by 3 months. One patient had no acute toxicity.
Conclusion
These early results demonstrate the feasibility of using IMRT for simultaneous integrated boost to biopsy proven dominant intra-prostatic lesions visible on MRI. The treatment was well tolerated.
doi:10.1186/1748-717X-2-36
PMCID: PMC2075521  PMID: 17877821
14.  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.
doi:10.1186/1748-717X-1-28
PMCID: PMC1564026  PMID: 16914054
15.  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.
doi:10.1186/1748-717X-1-2
PMCID: PMC1436003  PMID: 16722575

Results 1-15 (15)