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Evaluation of the Visibility and Artifacts of 11 Common Fiducial Markers for Image-Guided Stereotactic Body Radiation Therapy in the Abdomen

The purpose of this study was to quantitatively evaluate the visibility and artifacts of commercially available fiducial markers in order to optimize their selection for image-guided stereotactic body radiation therapy (SBRT). From six different vendors, we selected 11 fiducials commonly used in image-guided radiation therapy (IGRT); the fiducials varied in material composition (gold, platinum, carbon), shape (cylindrical, notched/linear, coiled, ball-like, step), and size measured in terms of diameter (0.28-1.0 mm) and length (3.0-20.0 mm). Each fiducial was centered in 4-mm bolus within a 13-cm-thick water-equivalent phantom. Fiducials were imaged with use of a simulation computed tomography (CT) scanner, a CT-on-rails system, and an onboard cone-beam CT system. Acquisition parameters were set according to clinical protocols. Visibility was assessed in terms of contrast and the Michelson visibility metric. Artifacts were quantified in terms of relative standard deviation and relative streak artifacts level (rSAL). Twelve radiation oncologists ranked each fiducial in terms of clinical usefulness. Contrast and artifacts increased with fiducial size. For CT imaging, maximum contrast (2722 HU) and artifacts (rSAL=2.69) occurred for the largest-diameter (0.75 mm) platinum fiducial. Minimum contrast (551 HU) and reduced artifacts (rSAL=0.65) were observed for the smallest-diameter (0.28 mm) gold fiducial. Carbon produced the least severe artifacts (rSAL = 0.29). The survey indicated that physicians preferred gold fiducials with a 0.35- to 0.43-mm diameter, 5- to 10-mm length, and a coiled or cylindrical shape that balanced contrast and artifacts. We evaluated 11 different fiducials in terms of visibility and artifacts. The results of this study may assist radiation oncologists who seek to maximize contrast, minimize artifacts, and/or balance contrast versus artifacts by fiducial selection.


Introduction
Stereotactic body radiation therapy (SBRT) involves delivering conformal high doses (≥5 Gy per fraction) of radiation over a reduced number of fractions (≤5) to body sites outside the central nervous system (1). SBRT is used for various cancer types in which ablative local doses are limited by nearby organs at risk (OARs) (2,3). SBRT has demonstrated excellent local control and overall survival results in early-stage lung cancer, and its use is growing in popularity for other cancer types including prostate, pancreatic, renal, and adrenal cancers, in addition to oligometastatic disease (4)(5)(6). To achieve the high biologically effective target dose required for SBRT, treatment planning makes use of sharp dose falloff and tight planning target volume margins to minimize normal tissue toxicity. Volumetric imaging using cone-beam CT (CBCT), CT-on-rails (CTOR), or magnetic resonance imaging (MRI) prior to treatment is thus a necessity to visualize changes in soft tissue anatomy relative to planning target volumes.
Low-contrast lesions in the liver or pancreas are not easily visualized in CBCT images.
To overcome this obstacle, high-contrast fiducials are often implanted into or nearby lowcontrast gastrointestinal (GI) tumors under endoscopic ultrasound (EUS) guidance to serve as surrogates of tumor position (7,8). During treatment setup, the fiducial markers help localize the tumor in the CBCT image. Even with CTOR, although OARs may be more easily visualized, intravenous contrast is not administered at the time of daily treatments, which may make isodense tumors impossible to visualize.
Many different types of fiducials of various shapes, sizes, and materials are available for implantation. The visualization of some fiducials can be more difficult than others due to differences in image artifacts and fiducial contrast (9,10). Optimal fiducial selection requires consideration of the tradeoff between contrast and image artifacts, as well as clinical considerations such as the probability of fiducial migration and treatment modality (e.g., photons versus protons). Fiducial contrast is dominated by the x-ray energy spectrum and linear attenuation coefficient that is a function of the fiducial composition. Photoelectric absorption is the dominant photon interaction in the diagnostic energy range (keV) responsible for image contrast and varies as the cube of the atomic number of the attenuating medium. Conversely, high atomic number materials such as metal fiducials generate streak artifacts in x-ray CT images. Image artifacts may obscure low-contrast lesions, thereby increasing uncertainty during contour delineation or reducing setup accuracy before treatment delivery. Furthermore, artifacts in CT simulation images may introduce dosimetric errors during the treatment planning stage that are particularly concerning for proton therapy (11).
Currently, only a few studies have investigated the contrast and artifacts observed with CT imaging of the fiducials available for GI radiotherapy applications. Chan et al. (12) investigated six gold markers and one polymer marker and concluded that gold markers are visible in CT, CBCT, ultrasound, and 2D kV portal imaging, but the results were strictly qualitative. Handsfield et al. (13) performed a quantitative investigation of visibility and artifacts for gold, carbon, and polymer fiducials. Only fiducials from a single vendor and a cylindrical shape were considered. Platinum fiducials were also not considered, which may be of interest for clinics that use MRI-to-CT image fusion as part of the treatment planning process. Nair et al. (14) showed that the contrast of platinum fiducials implanted in liver tissue was significantly superior to gold seeds or coils when imaged with MRI. The purpose of this study was to provide a quantitative evaluation of fiducial visibility and artifacts to optimize fiducial selection for clinical applications, primarily in isodense GI cancers near OARs.

Fiducial markers
Fiducial visibility and image artifacts were evaluated for 11 different fiducial markers selected from six vendors. Only fiducials suitable for implantation in the pancreas by EUS-guided placement were considered. The fiducials varied in terms of material composition (gold, platinum, carbon), shape (cylindrical, notched/linear, coiled, ball-like, step), and size measured in terms of diameter (0.28-1.0 mm) and length (3.0-20.0 mm). Carbon was considered since patients originally planned to receive proton radiation therapy (RT) may alternatively receive external photon beam RT after fiducial placement due to insurance or clinical considerations. Table 1 summarizes the relevant fiducial properties. The Gold Anchor fiducials, listed twice, have notches every 2 mm that allow the fiducials to be folded into a "ball-like" shape or placed as a "line" during implantation. The final configuration depends on tumor resistance and insertion technique.

Imaging modalities and acquisition parameters
Each of the fiducials were placed within the phantom one at a time and imaged with a 16-slice CT simulation scanner (Brilliance Big Bore, Philips Medical Systems, Best, Netherlands), a CBCT system (TrueBeam OBI, Varian Medical Systems, Palo Alto, CA, USA), and a 16-slice CTOR scanner (GE LightSpeed RT16, GE Healthcare, Waukesha, WI, USA) (15). The phantom and fiducials were centered with respect to each imaging system's isocenter using in-room lasers and phantom markings to improve the reproducibility of set-up across each CT acquisition.
Acquisition parameters were selected for each imaging modality based on institutional protocols for GI imaging, as summarized in Table 2. The CTOR exposure level may be adjusted from the default value of 84 mAs at the treatment machine, as needed. To investigate the impact of image noise on fiducial detectability a second exposure level of 250 mAs was also evaluated for the CTOR machine. The x-ray tube potential varied slightly, from 120 to 125 kV. Voxel dimensions were comparable across all imaging modalities. Slice thickness ranged from 2.0 mm for the CBCT system to 3.0 mm for the CT simulation scanner. Slice thickness is an important parameter that impacts the fiducial visibility due to volume averaging and image noise.

Fiducial visibility assessment
Fiducial visibility was evaluated in terms of contrast (∆ ) and the Michelson visibility metric ( ). Fiducial contrast was defined as: Here, ∆ represents the signal difference between the mean of image pixel values in a regionof-interest (ROI) located within the fiducial, ̅̅̅, and a nearby background ROI, ̅̅̅. The ROI, , was selected as the 10 mm 2 area within the fiducial corresponding to the region of maximum intensity. The background ROI, , was located 15 mm from the center-of-mass of the fiducial and perpendicular to the long axis of the fiducial in a 20 mm 2 region with minimal artifacts. For the CTOR machine, the contrast-to-noise ratio (CNR) was computed as CNR = ∆ / , where denotes the noise standard deviation in the background ROI, to evaluate fiducial detectability.
The purpose of the Michelson visibility metric (equation 2) was to quantify contrast in terms of the brightest region of the fiducial, independent of fiducial or ROI size.
Here, represents the maximum signal within a 30 by 30 mm 2 ROI defined about the centerof-mass of the fiducial, whereas represents the minimum value. Michelson visibility is bounded between 0 and 1 with a value of 1 corresponding to maximum visibility.

Fiducial artifact-level assessment
The presence of highly attenuating objects such as metal fiducials along x-ray paths traversing the object results in photon starvation. After image reconstruction, photon starvation manifests as streak artifacts and areas of signal void in regions adjacent to the implanted fiducial.
Here, denotes an artifact image, denotes a reference image free of fiducial induced artifacts, and ( ) is the total variation function.

Survey of fiducial image quality
Five faculty radiation oncologists and seven radiation oncology residents or fellows each rated the 11 different fiducial markers in terms of clinical usefulness. Participants were instructed to consider both the fiducial visibility and artifact level as seen on CT simulator and CBCT images of each marker placed in the water equivalent phantom. Each radiation oncologist was asked to rank each image (22 total) on a scale of 1 to 5 as follows: 1 = not useful at all for clinical practice, 3 = acceptable/sufficient for clinical practice, and 5 = ideal for clinical use. The differences between mean faculty and resident rankings were assessed by a right-tailed paired Wilcoxon signed-ranked test. Statistical significance was defined at the p-value < 0.05 threshold.
The Pearson correlation coefficient was also reported. The maximum contrast value was observed for the 0.75-mm-diameter coiled platinum fiducial (Visicoil 5 mm) for each of the imaging systems. Figure 2 shows that the fiducial contrast and image artifact level increase as the diameter of the fiducial (Table 1) increases, as expected, except for the low atomic number carbon fiducial. The minimum contrast value was observed for the 0.28-mm-diameter linear-shaped gold fiducials. The contrast of the Gold Anchor fiducials was improved when the fiducial was deployed in the ball-like configuration.

Fiducial visibility and artifacts
Likewise, a higher level of artifacts may be observed for the ball-like configuration.
Qualitatively, fewer streak artifacts were present for the carbon and linear gold fiducials.  Table 1. Table 3   The contrast-to-noise ratio is plotted for imaging performed with CT-on-rails at 84 mAs and 250 mAs for 11 different fiducial configurations. The error bars plotted for the Beacon FNF fiducial represent ±1 standard deviation uncertainty estimated from a series of 10 independent measurements and phantom set-ups. Abbreviations for the fiducial labels shown in the legend are defined in Table 1. Abbreviations: rSAL = relative streak artifacts level, rStdDev = relative standard deviation. Fiducial abbreviations are defined in Figure 1. Table 4 presents the results from the physician survey of fiducial image quality. The Beacon FNF and Visicoil 10-mm gold markers were the two highest-ranked fiducials for both CT and CBCT imaging (mean ranking, 4.1 and 4.2, respectively). The Gold Anchor 20-mm fiducial marker (linear configuration, mean ranking, 2.1) was ranked the lowest for CT imaging, and the Best Medical fiducial (mean ranking, 2.4) was ranked the lowest for CBCT. Physicians preferred the Gold Anchor fiducials in the ball-like configuration versus the linear configuration. No significant difference was observed between faculty and resident rankings (p-value = 0.36). The correlation between mean faculty and resident rankings was 0.76.   (Table 3) which showed these fiducials demonstrated the lowest image contrast (∆HU).

Survey of fiducial image quality
In addition to image quality, certain practical aspects must be considered during the fiducial selection process. Fiducial selection must include a discussion of the placement-related technical challenges, complications, and migration probability unique to each fiducial type.
The size and shape of the fiducial marker typically dictate the type of needle to be used. image acquisition parameters were selected based on current clinical protocols. The impact of tube potential and exposure time on contrast-to-noise were described previously by Hansfield et al (13). In addition to tube parameters, the impacts of image reconstruction parameters, including pixel size, algorithm, and metal artifact correction, could be investigated as follow-up work.
Brook et al. (18) demonstrated that metal artifact reduction software may improve tumor visibility near gold fiducial markers. However, Brook et al. focused on spectral CT, which is not readily available for RT simulation. Fourth, only a single fiducial orientation was investigated.
All fiducials were positioned orthogonal (90°) to the longitudinal axis of the couch in order to maximize image contrast. To demonstrate the impact of fiducial orientation, the 5-mm platinum fiducial was imaged at different angular orientations corresponding to 0°, 45°, and 90° relative to the long axis of the treatment couch. Figure 4 shows that the Michelson contrast and rSAL increased as the fiducial rotated from parallel (0°) to perpendicular (90°) to the imaging volume's slice dimension and long axis of the treatment couch. The increase is expected as a greater portion of the fiducial is contained within an individual image slice compared with the parallel orientation, which increases photon absorption.

Conclusion
We evaluated 11 commonly used fiducials for image-guided SBRT in terms of visibility and artifacts under imaging performed with a CT simulator, CTOR, and on-board CBCT. The results will provide useful information when selecting a fiducial type with a preference towards high fiducial contrast, low image artifacts, or a balanced tradeoff between contrast and artifacts. A survey of radiation oncologists indicated that fiducials balancing image contrast and artifacts are preferred.