Intraprostatic Gold Fiducial Markers Research Articles

The role of a radiopaque peri-rectal hydrogel spacer in aiding accurate daily image-guidance for prostate stereotactic radiotherapy.

Precise patient positioning with image guidance (IGRT) is essential for safe prostate radiotherapy. We present the first report of utilizing a CT-visible hydrogel spacer, used to decrease rectal radiation dose, as a surrogate fiducial marker to aid in daily IGRT with cone-beam CT (CBCT) in stereotactic radiotherapy (SABR) for prostate cancer. Prior to CT simulation, patients underwent placement of three intraprostatic gold fiducial markers and radiopaque hydrogel spacer per standard practice. At treatment, after initial setup, a CBCT was acquired and fused to the planning CT based on 3-dimensional matching of the spacer. A second alignment was then performed based on the fiducial markers. The six directional shifts (three linear and three rotational) were recorded, and the differences compared. 140 individual fractions across 41 consecutive patients were evaluated. Mean/median differences between hydrogel spacer-based and fiducial-based alignment in linear (vertical, longitudinal, lateral) and rotational (rotation, pitch, roll) shifts were 0.9/0.6mm, 0.8/0.5mm, and 0.6/0.4mm, and 0.38/0, 0.62/0, and 0.35/0 degrees, respectively. No difference was observed in 9.9%, 22.9%, and 22.14% of linear shifts, and 65.7%, 65%, and 66.4% rotational shifts, respectively. Significantly smaller differences were observed in the latter 70 fractions vs. the former, and results were consistent across evaluators. For precise daily IGRT with CBCT for prostate SABR, alignment using a radiopaque hydrogel spacer was highly comparable to intraprostatic fiducial markers. This represents the first report supporting an additional indication of IGRT for a CT-visible hydrogel spacer, to further enhance treatment accuracy and potentially obviate the need for the additional fiducial marker procedure.

Safety and efficacy of MRI-guided transurethral ultrasound ablation for radiorecurrent prostate cancer in the presence of gold fiducial markers.

Safety and efficacy of ultrasound prostate ablation for radiorecurrent prostate cancer (PCa) in the presence of gold fiducial markers has not been previously reported. To evaluate safety, functional, and early-stage oncological outcomes for patients with gold fiducial markers undergoing salvage magnetic resonance imaging (MRI)-guided transurethral ultrasound ablation (sTULSA) for radiorecurrent PCa. Data were acquired from an ethics-approved, single-center phase-1 study. Eight patients with 18 total gold fiducial markers inside the planned treatment volume were identified. MRI controls were performed at three and 12 months, followed by PSMA-PET-CT imaging and biopsies at 12 months. A control cohort of 13 patients who underwent sTULSA without markers were also identified for safety profile comparison. Adverse events were reported using the Clavien-Dindo classification, and questionnaires including EPIC-26, IPSS, and IIEF-5 were collected. Of 18 markers, 2 (11%) were directly responsible for poor ultrasound penetration. However, there were no local recurrences at 12 months. PSA, prostate volume, and non-perfused volume all decreased over time. At 12 months, 11/18 (61%) of fiducial markers had disappeared via sloughing. The adverse event profile was similar between both patient cohorts, and when controlled for ablation type, no statistical difference in functional outcomes between the two cohorts was observed. Patients with radiorecurrent PCa with intraprostatic gold fiducial markers can be successfully treated with TULSA. The early-stage efficacy of sTULSA for patients with intraprostatic gold markers is encouraging and the safety profile is unaffected by marker presence.

Creating CT- and MRI-guided urethra planning-risk-volumes for urethra-sparing prostate stereotactic body radiotherapy

Dose-escalation in prostate cancer SBRT improves PSA nadir and negative post-treatment biopsy rates, but increases genitourinary toxicity. The definition of the urethra PRV (uPRV) is not standardized. A Foley-catheter based uPRV incorporates catheter-induced anatomic variability that is not reproduced during daily treatment without catheter, whereas anatomic uncertainty during MRI-CT registration is inherent to the MRI-based uPRV. We thus examined the urethra as delineated on CT and MRI to identify an optimal urethral PRV. The urethra was contoured on CT with catheter (uCT) and T2 MRI without catheter (uMRI) in 25 men with prostate cancer. Men received three intraprostatic gold fiducial markers for localization, and rectal spacer to reduce rectal toxicity. MRI was first registered to the CT (reg1) using automated rigid registration of fiducial markers; u_MRI in this position was labelled uMRI_1. MRI was rigidly registered to the CT again (reg2); this time manually to the posterior prostate/anterior rectal wall interface (a clinically relevant region of interest in delineating a hydrogel spacer for radiation planning without taking into account fiducial markers). The uMRI volume created from this manual MRI-CT registration was labeled uMRI_2. Urethral PRVs were created by uniform, and anterior-posterior (A-P) only, expansions in 1 mm increments around uCT. The proportion of uMRI_1, and uMRI_2 covered by each successive uPRV was measured, as was the decrement in the volume PTV-uPRV. Mean and standard deviation uCT and uMRI volumes were 1.72±0.58 and 1.01±0.51 cc, respectively. Automated MRI-CT registration (reg1) with fiducial markers resulted, on average, in 0.2 mm translational separation of each fiducial marker on MRI to its intended fiducial marker target on CT. The translation and rotation matrix differences between reg1 and reg2 (manual) were: -1.1±2.47, -2.87±6.17 and 0.08±4.68 mm; and -0.16±8.29, 0.75±3.17 and 1.42±4.01 degrees. The smallest average urethra contour that would encompass uCT and uMRI_1 was 2.34±0.75 cc; that for uCT, uMRI_1 and uMRI_2 was 2.87±1.04 cc. The likelihood of urethra coverage and mean percent PTV-uPRV for a given uPRV are shown in the table. Uniform 3 mm uPRV encompassed 88% of uCT and uMRI_1, and 83% of uCT, uMRI_1 and uMRI_2, versus 82% and 75% with A-P only uPRV. Uniform and A-P 3 mm uPRVs are created at the expense of 7% and 4% of PTV, respectively. Three-quarters of potential urethra variability on CT and MRI are included in an A-P 3 mm PRV around a catheter. Additional uniform, or A-P, uPRV expansions for urethral protection must be weighed against clinically relevant declines in PTV-uPRV.Abstract 4128; TablePRV (mm)123456% of:uCT, uMRI_1 included in uniform PRV808588919395uCT, uMRI_1 included in A-P PRV768082848687uCT, uMRI_1 and uMRI_2 included in uniform PRV717883889193uCT, uMRI_1 and uMRI_2 included in A-P PRV677275788183PTV decrease by uniform PRV457101215PTV decrease by A-P PRV344567 Open table in a new tab

Fiducial markers implantation for prostate image-guided radiotherapy: a report on the transperineal approach.

In the external beam prostate cancer radiation therapy, daily gland displacement could lead to a target missing. The use of intra-prostatic gold fiducial markers for daily prostate position verification and correction before and during treatment delivery (image-guided radiotherapy, IGRT) is widely used in the radiation therapy centers to accurately target the prostate. Usually, the fiducial markers are implanted through the rectum, with complications such as infections and rectal bleeding. We report our experience in prostate fiducial markers implantation through a transperineal approach. Between September 2011 and January 2018 at our center, 101 patients underwent gold seed fiducial marker transperineal ultrasound-guided implantation for prostate IGRT. We retrospectively reviewed their features and outcome. Twenty-two (21.8%) patients had previously been subjected to a transurethral prostate resection (TURP) for obstructive urinary symptoms because of benign prostatic hypertrophy. No antibiotic prophylaxis was used. The procedure was well tolerated. In one patient, a single episode of self-limiting urinary bleeding occurred just after it. No other complication was recorded. All the patients, at the evaluation before discharge, reported no pain or dysuria. No rectal bleeding, hematospermia, urinary obstruction or infection were reported in the next days. No markers lost or migration occurred. According to our experience, prostate fiducial markers implantation through a transperineal approach is safe and should be recommended to limit the use of antibiotic therapy and patients morbidity. A previous TURP was not related to a higher risk of loss of seeds.

Using C-Arm X-ray images from marker insertion to confirm the gold fiducial marker identification in an MRI-only prostate radiotherapy workflow.

Prostate cancer radiotherapy workflows, solely based on magnetic resonance imaging (MRI), are now in clinical use. In these workflows, intraprostatic gold fiducial markers (GFM) show similar signal behavior as calcifications and bleeding in T2‐weighted MRI‐images. Accurate GFM identification in MRI‐only radiotherapy workflows is therefore a major challenge. C‐arm X‐ray images (CkV‐images), acquired at GFM implantation, could provide GFM position information and be used to confirm correct identification in T2‐weighted MRI‐images. This would require negligible GFM migration between implantation and MRI‐imaging. Marker migration was therefore investigated. The aim of this study was to show the feasibility of using CkV‐images to confirm GFM identification in an MRI‐only prostate radiotherapy workflow. An anterior‐posterior digitally reconstructed radiograph (DRR)‐image and a mirrored posterior‐anterior CkV‐image were acquired two weeks apart for 16 patients in an MRI‐only radiotherapy workflow. The DRR‐image originated from synthetic CT‐images (created from MRI‐images). A common image geometry was defined between the DRR‐ and CkV‐image for each patient. A rigid registration between the GFM center of mass (CoM) coordinates was performed and the distance between each of the GFM in the DRR‐ and registered CkV‐image was calculated. The same methodology was used to assess GFM migration for 31 patients in a CT‐based radiotherapy workflow. The distance calculated was considered a measure of GFM migration. A statistical test was performed to assess any difference between the cohorts. The mean absolute distance difference for the GFM CoM between the DRR‐ and CkV‐image in the MRI‐only cohort was 1.7 ± 1.4 mm. The mean GFM migration was 1.2 ± 0.7 mm. No significant difference between the measured total distances of the two cohorts could be detected (P = 0.37). This demonstrated that, a C‐Arm X‐ray image acquired from the GFM implantation procedure could be used to confirm GFM identification from MRI‐images. GFM migration was present but did not constitute a problem.

P139] Indication of accurate gold fiducial marker identification in a prostate MRI only radiotherapy workflow using C-arm X-ray imaging

Purpose Prostate cancer radiotherapy workflows solely based on magnetic resonance imaging (MRI), are now being clinically used. Intra-prostatic gold fiducial markers (GFM), appear as signal voids in MRI-images while calcifications and bleedings show similar signal behavior. Achieving accurate identification of GFM in an MRI-based workflow thereby constitute a major challenge. Several identification methods have been presented but none has reached an accuracy of 100%. C-arm X-ray images (CkV-images), acquired at GFM implantation, could provide GFM position information and be used to indicate correct identification. This would require negligible GFM migration. The aim of this study was to: 1) study the GFM migration 2) show the feasibility of using CkV-images as an indicator of accurate GFM identification. Methods Frontal digitally reconstructed radiographs (DRR)- and CkV-images were acquired two weeks apart for 31 patients in a CT-based radiotherapy workflow and for 16 patients in an MRI-based radiotherapy workflow. A common image geometry was defined between the DRR- and CkV-image for each patient. For each image, a point cloud was defined from the GFM center of mass coordinates. A rigid registration between the point clouds was performed and the distance between each of the GFM in the DRR- and registered CkV-image was calculated. The distance calculated in the CT-based patient cohort was considered a measure of GFM migration. A statistical test was performed to assess any difference between the cohorts. Results The mean GFM migration assessed in the CT-based patient cohort was 1.2 ± 0.7 mm. The mean absolute distance difference for the GFM center of mass in the MRI-based cohort was 1.7 ± 1.4 mm. No significant difference between the measured total distances of the two patient cohorts could be detected (p-value = 0.37). Conclusions A C-Arm X-ray image acquired from the GFM implantation procedure could be used as an indicator of accurate GFM identification. GFM migration was present but did not constitute a problem for the proposed method.

Evaluation of gold fiducial marker manual localisation for magnetic resonance-only prostate radiotherapy

BackgroundThe use of intraprostatic gold fiducial markers (FMs) ensures highly accurate and precise image-guided radiation therapy for patients diagnosed with prostate cancer thanks to the ease of localising FMs on photon-based imaging, like Computed Tomography (CT) images. Recently, Magnetic Resonance (MR)-only radiotherapy has been proposed to simplify the workflow and reduce possible systematic uncertainties. A critical, determining factor in the accuracy of such an MR-only simulation will be accurate FM localisation using solely MR images.PurposeThe aim of this study is to evaluate the performances of manual MR-based FM localisation within a clinical environment.MethodsWe designed a study in which 5 clinically involved radiation therapy technicians (RTTs) independently localised the gold FMs implanted in 16 prostate cancer patients in two scenarios: employing a single MR sequence or a combination of sequences. Inter-observer precision and accuracy were assessed for the two scenarios for localisation in terms of 95% limit of agreement on single FMs (LoA)/ centre of mass (LoA CM) and inter-marker distances (IDs), respectively.ResultsThe number of precisely located FMs (LoA <2 mm) increased from 38/48 to 45/48 FMs when localisation was performed using multiple sequences instead of single one. When performing localisation on multiple sequences, imprecise localisation of the FMs (3/48 FMs) occurred for 1/3 implanted FMs in three different patients. In terms of precision, we obtained LoA CM within 0.25 mm in all directions over the precisely located FMs. In terms of accuracy, IDs difference of manual MR-based localisation versus CT-based localisation was on average (±1 STD) 0.6 ±0.6 mm.ConclusionsFor both the investigated scenarios, the results indicate that when FM classification was correct, the precision and accuracy are high and comparable to CT-based FM localisation. We found that use of multiple sequences led to better localisation performances compared with the use of single sequence. However, we observed that, due to the presence of calcification and motion, the risk of mislocated patient positioning is still too high to allow the sole use of manual FM localisation. Finally, strategies to possibly overcome the current challenges were proposed.

Evaluation of an automatic MR-based gold fiducial marker localisation method for MR-only prostate radiotherapy

An MR-only radiotherapy planning (RTP) workflow would reduce the cost, radiation exposure and uncertainties introduced by CT-MRI registrations. In the case of prostate treatment, one of the remaining challenges currently holding back the implementation of an RTP workflow is the MR-based localisation of intraprostatic gold fiducial markers (FMs), which is crucial for accurate patient positioning.Currently, MR-based FM localisation is clinically performed manually. This is sub-optimal, as manual interaction increases the workload. Attempts to perform automatic FM detection often rely on being able to detect signal voids induced by the FMs in magnitude images. However, signal voids may not always be sufficiently specific, hampering accurate and robust automatic FM localisation.Here, we present an approach that aims at automatic MR-based FM localisation. This method is based on template matching using a library of simulated complex-valued templates, and exploiting the behaviour of the complex MR signal in the vicinity of the FM. Clinical evaluation was performed on seventeen prostate cancer patients undergoing external beam radiotherapy treatment. Automatic MR-based FM localisation was compared to manual MR-based and semi-automatic CT-based localisation (the current gold standard) in terms of detection rate and the spatial accuracy and precision of localisation. The proposed method correctly detected all three FMs in 15/17 patients. The spatial accuracy (mean) and precision (STD) were 0.9 mm and 0.5 mm respectively, which is below the voxel size of mm3 and comparable to MR-based manual localisation. FM localisation failed (3/51 FMs) in the presence of bleeding or calcifications in the direct vicinity of the FM.The method was found to be spatially accurate and precise, which is essential for clinical use. To overcome any missed detection, we envision the use of the proposed method along with verification by an observer. This will result in a semi-automatic workflow facilitating the introduction of an MR-only workflow.

Fiduciels intraprostatiques dans le cadre de la radiothérapie stéréotaxique du cancer de la prostate

PurposeImage-guided radiotherapy for prostate cancer is widely used in radiotherapy departments. Intraprostatic gold fiducial markers are used to visualize prostate position and motion before and during treatment. The aim of this report is to describe our experience of implanting intraprostatic fiducial markers under local anesthesia before hypofractionated stereotactic radiotherapy for prostate cancer and to assess its tolerance and reproducibility. Patients and methodsOver a 6 and a half year period, 226 patients with prostate cancer received a stereotactic radiotherapy using the CyberKnife® system (Accuray) in our institution. Eighteen patients were treated for recurrence after prostatectomy; these patients were excluded from the study. Among the 208 remaining patients, 94 patients (45.2%) received stereotactic radiotherapy as a boost after external beam radiotherapy (three fractions of 6Gy); 36 patients (17.3%) were had a re-irradiation (six fractions of 6Gy) and 78 patients (37.5%) had a exclusive stereotactic radiotherapy (68 patients received five fractions of 7.25Gy and 11 patients five fractions of 6.25Gy). Four markers were implanted in all patients using transrectal ultrasound; the procedure was performed under local anesthesia, using transperineal access. The four fiducial markers were implanted in two strands with two fiducial each one, 1cm apart. In order to follow the recommendations of the image-guided radiotherapy system, the two strands of the two markers were located on the same plane in the middle of the prostate, at least 2cm apart from the midline. After insertion, correct positioning of fiducials markers was verified by X-ray. Dosimetry scanning was performed after the implantation procedure; prostate position tracking was possible before and during treatment through the kilovoltage incorporated system of the robotic accelerator. Clinical data, X-ray verification and dosimetry scanner have been retrospectively reviewed for all patients. ResultsThe tolerance to procedure was excellent; only four patients (1.8%) described pain related to implant. No urinary side effects were reported. Median time from fiducial implantation to dosimetry scanner was 16 days (4–113 days). Four fiducials were found within the prostate at dosimetry scanner in 181 patients and three in 27 remaining patients. All intraprostatic fiducials were used to track the prostate gland before and during treatment. ConclusionsIntraprostatic fiducial markers implantation is a safe and reproducible procedure that allows us to have reliable prostate information before and during stereotactic radiotherapy.

MRI-alone radiation therapy planning for prostate cancer: Automatic fiducial marker detection.

The feasibility of radiation therapy treatment planning using substitute computed tomography (sCT) generated from magnetic resonance images (MRIs) has been demonstrated by a number of research groups. One challenge with an MRI-alone workflow is the accurate identification of intraprostatic gold fiducial markers, which are frequently used for prostate localization prior to each dose delivery fraction. This paper investigates a template-matching approach for the detection of these seeds in MRI. Two different gradient echo T1 and T2* weighted MRI sequences were acquired from fifteen prostate cancer patients and evaluated for seed detection. For training, seed templates from manual contours were selected in a spectral clustering manifold learning framework. This aids in clustering "similar" gold fiducial markers together. The marker with the minimum distance to a cluster centroid was selected as the representative template of that cluster during training. During testing, Gaussian mixture modeling followed by a Markovian model was used in automatic detection of the probable candidates. The probable candidates were rigidly registered to the templates identified from spectral clustering, and a similarity metric is computed for ranking and detection. A fiducial detection accuracy of 95% was obtained compared to manual observations. Expert radiation therapist observers were able to correctly identify all three implanted seeds on 11 of the 15 scans (the proposed method correctly identified all seeds on 10 of the 15). An novel automatic framework for gold fiducial marker detection in MRI is proposed and evaluated with detection accuracies comparable to manual detection. When radiation therapists are unable to determine the seed location in MRI, they refer back to the planning CT (only available in the existing clinical framework); similarly, an automatic quality control is built into the automatic software to ensure that all gold seeds are either correctly detected or a warning is raised for further manual intervention.

Intra-prostatic Fiducial Markers and Concurrent Androgen Deprivation

To document the case of a man with adenocarcinoma of the prostate treated with external beam radiotherapy and concurrent androgen deprivation. The man, who received 79.8 Gy in 42 fractions of radiotherapy over 8.5 weeks using three intra-prostatic gold fiducial markers for on-line set-up correction, started an anti-androgen 2.5 weeks before radiotherapy, on the day of his planning computed tomography, and a gonadotropin-releasing hormone agonist on his first day of radiotherapy. In the sixth week of radiotherapy, the distance between the fiducial markers had diminished: superior to posterior-mid (from 19 to 11 mm), posterior-mid to inferior (from 19 to 15 mm), and superior to inferior (from 31 to 22 mm), so the patient was rescanned. Between the two planning computed tomographies, the prostate volume had decreased from 44.3 to 28.3 cm3 (-36%). Had the planned radiotherapy been delivered to the anatomy of the rescan, the dose to the rectal wall would have exceeded the planned dose-volume histogram constraints. However, with the patient set up to the fiducial markers, the dose-volume histogram constraints for the rectal wall and bladder wall were met throughout the course of radiotherapy. Involution of the prostate owing to concurrent androgen deprivation may cause in-migration of implanted fiducial markers and excessive dose to the rectal wall. With concurrent androgen deprivation, daily on-line set-up correction to fiducial markers can aid in safe dose escalation.

Prostate position relative to pelvic bony anatomy based on intraprostatic gold markers and electronic portal imaging

To describe the relative positions and motions of the prostate, pelvic bony anatomy, and intraprostatic gold fiducial markers during daily electronic portal localization of the prostate. Twenty prostate cancer patients were treated supine with definitive external radiotherapy according to an on-line target localization protocol using three or four intraprostatic gold fiducial markers and an electronic portal imaging device. Daily pretherapy and through-treatment electronic portal images (EPIs) were obtained for each of four treatment fields. The patients' pelvic bony anatomy, intraprostatic gold markers, and a best visual match to the target (i.e., prostate) were identified on simulation digitally reconstructed radiographs and during daily treatment setup and delivery. These data provided quantitative inter- and intrafractional analysis of prostate motion, its position relative to the bony anatomy, and the individual intraprostatic fiducial markers. Treatment planning margins, with and without on-line localization, were subsequently compared. A total of 22,266 data points were obtained from daily pretherapy and through-treatment EPIs. The pretherapy three-dimensional (3D) average displacement of the fiducial markers, as a surrogate for the prostate, was 5.6 mm, which improved to 2.8 mm after use of the localization protocol. The bony anatomy 3D average displacement was 4.4 mm both before and after localization to the prostate (p = 0.46). Along the superior-inferior (SI), anterior-posterior (AP), and right-left (RL) axes, the average prostate displacement improved from 2.5, 3.7, and 1.9 mm, respectively, before localization to 1.4, 1.6, and 1.1 mm after (all p < 0.001). The pretherapy to through-treatment position of the bony landmarks worsened from 1.7 to 2.5 mm (p < 0.001) in the SI axis, remained statistically unchanged at 2.8 mm (p = 0.39) in the AP axis, and improved from 2.0 to 1.2 mm in the RL axis (p < 0.001). There was no significant intrafractional displacement of prostate position or bony anatomic landmarks. An intermarker distance was identified for all fiducial markers, and 96 were followed daily. Seventy-nine percent had a standard deviation of <1 mm, and 96% were <1.5 mm. Margins were 5.1, 7.3, and 5.0 mm in the SI, AP, and RL axes, respectively, before localization and 2.7, 2.9, and 2.8 mm after localization. Significant interfractional motion exists for patients' prostate and pelvic bony anatomy. However, these move independently, so the pelvic bony anatomy should not be used as a surrogate for prostate motion. Fiducial markers are stable within the prostate and allow significant margin reduction when used for on-line localization of the prostate.

Position of the prostate relative to pelvic bony anatomy based on intraprostatic gold fiducial markers and electronic portal imaging

To describe the relative positions and motions of the prostate, pelvic bony anatomy, and intraprostatic gold fiducial markers based on daily on-line localization of the prostate during external beam radiotherapy (EBRT).

Position of the prostate relative to pelvic bony anatomy based on intraprostatic gold fiducial markers and electronic portal imaging

To describe the relative positions and motions of the prostate, pelvic bony anatomy, and intraprostatic gold fiducial markers based on daily on-line localization of the prostate during external beam radiotherapy (EBRT).