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Purpose: X-ray based position verification of the target volume in image-guided radiation therapy (IGRT) of patients with pancreatic ductal adenocarcinoma (PDAC) is currently performed on rigid fiducial markers that are implanted under endoscopic ultrasonography. A new biodegradable liquid fiducial marker has recently been introduced. To assess its potential use for magnetic resonance imaging (MRI) guided radiotherapy of PDAC, the MRI visibility and artefacts of this marker were quantified and compared against rigid gold markers. Material and Methods: Different spherical volumes (10 µL, 25 µL, 50 µL and 100 µL) of BioXmark® (Nanovi Radiotherapy A/S) as well as four differently oriented Gold Anchor™ (Naslund Medical AB; Ø 0.28 mm, 1 cm and 2 cm length) and three VisiCoil™ (IBA Dosimetry; Ø 0.35 mm, 5 mm and 10 mm length) were implanted in a spherical gel phantom mimicking the proton spin relaxation properties of healthy pancreatic tissue at 3 Tesla. MR relaxometry was performed to quantify the size and magnitude of the decrease in T¬2* relaxation time and relative proton density ρ(H) as a measure of visibility, and to quantify the size and magnitude of the increase in magnetic field inhomogeneity ΔB_0 as a measure of signal artefacts. The phantom was scanned in a 3.0 T Philips Ingenuity TF PET/MR scanner with an 8-channel head coil. For T2*- and ΔB_0-mapping a spoiled 3D multi-echo gradient echo sequence (GRE) was performed. ρ(H)-mapping was based on the signal intensity at TE = 0 ms relative to ultrapure water extrapolated from the T2-decay curve deduced from a spin echo sequence with different echo times. The signal was corrected for its T1 decay and B1- field inhomogeneity, for which an inversion-recovery spin echo sequence with multiple inversion times and a gradient echo sequence with different repetition times was utilized respectively. Results: The rigid markers showed a direct linear relationship between size of visibility and artefact. BioXmark® showed a tendency towards larger size of visibility at smaller artefacts. BioXmark® markers up to 100 µL created volumes of visibility comparable to the size of visibility of VisiCoil™ and Gold Anchor™ markers. The magnitude of visibility was the highest for BioXmark® from 25µL – 100µL showing no correlation with the magnitude of artefact. The rigid markers show a non-linear correlation between magnitude of visibility and artefact where Gold Anchor™ induce the strongest artefacts. Conclusion: BioXmark® causes signal voids on MRI due to its low proton density without strongly affecting the magnetic field in the surrounding tissue. The latter was found to be the main effect leading to the visibility of the rigid markers especially in GRE sequences. Hence, especially when a low level of image distortion is required, MRI characteristics of the BioXmark® surpass those of rigid gold markers currently being used for IGRT of PDAC.

Introduction: Image-guided radiotherapy (IGRT) of pancreatic ductal adenocarcinoma (PDAC) based on implanted fiducial markers and daily orthogonal kV X-ray imaging or cone-beam computed tomography (CBCT) has been shown to significantly reduce the setup error as compared to bony alignment1. In state-of-the-art IGRT solid gold markers are implanted into the pancreas using endoscopic ultrasonography (EUS), a procedure that is well established and generally well tolerated. However, solid gold markers not only deteriorate image quality in both CT and MRI, but additionally cause significant dose alterations in particle therapy, showing local dose perturbations up to 80% of the prescribed dose. Recently, a new biodegradable liquid marker has been developed, which forms a semisolid gel after injection into soft tissue. This marker may particularly benefit patients with PDAC who are scheduled for particle therapy, because it can be implanted using very thin (≤25 G) needles, its low Z-elemental (non-ferrous and non-magnetic) composition causes minimal proton dose perturbation in soft tissues, its size and visibility on X-ray images, CT and CBCT can be adjusted by controlling the injected volume and compound composition, and its soft-surface adhesiveness may decrease migration behaviour relative to solid markers. So far, the characteristics of the liquid marker on magnetic resonance imaging (MRI) have not been investigated. It is the aim of the present work to provide a quantitative, pulse sequence-independent assessment of the visibility and artefacts of the new liquid fiducial marker on MRI and compare them against those of two gold markers commonly applied in IGRT of PDAC. Methods: To quantify the propensity of the different markers to generate signal voids and signal shifts on MRI, a spherical gel phantom mimicking the relaxation properties of healthy pancreatic tissue at 3 Tesla was constructed. Different volumes (10 µL, 25 µL, 50 µL and 100 µL) of the liquid marker (BioXmark®, Nanovi Radiotherapy A/S) were casted into the gel as well as four Gold Anchor™ (Naslund Medical AB; 0.28 mm diameter, 10 mm and 20 mm length) and three VisiCoil™ (IBA Dosimetry; 0.35 mm diameter, 5 mm and 10 mm length) markers, implanted in different orientations. MR relaxometry was performed to quantify the size and magnitude of the decrease in the effective transversal relaxation time T2* and water proton density ρ(H) relative to pure water as a measure of potential visibility, and to quantify the size and magnitude of the increase in magnetic field inhomogeneity ΔB0 as a measure of potential signal artefacts. The phantom was scanned with a 3.0 T Philips Ingenuity TF PET/MR scanner using an 8-channel head coil. Results: The solid fiducial markers showed a direct linear relationship between the potentially visible size and artefact size. The liquid fiducial marker showed a tendency towards a potentially visible size at smaller artefacts. Liquid markers from 25-100 μL generated visible volumes comparable to the visible size of the solid markers. The visible magnitude was the largest for the liquid fiducial marker with volumes of 25μL – 100μL showing no correlation with the magnitude of artefact. The solid markers showed a strong non-linear correlation between magnitude of visibility and artefact. The gold-iron alloy marker induced the strongest artefacts. Discussion: The liquid fiducial marker causes signal voids on MRI due to its absence of water hydrogen atoms without strongly affecting the magnetic field in the surrounding tissue. The alteration of the static magnetic field was found to be the main effect leading to the visibility of the solid fiducial markers. Conclusion: BioXmark® has beneficial MRI properties regarding the trade-off between potential visibility and artefacts compared to the tested solid gold markers that are currently being used for IGRT of PDAC. Contrary to the solid markers, an increase in visibility of BioXmark® was not directly coupled to an increase in artefact. Due to the proton density effect, BioXmark® behaves comparably in all pulse sequences if acquired at similar resolution.