Inter-scanner super-resolution of 3D cine MRI using a transfer-learning network for MRgRT.

Objective. Deep-learning networks for super-resolution (SR) reconstruction enhance the spatial-resolution of 3D magnetic resonance imaging (MRI) for MR-guided radiotherapy (MRgRT). However, variations between MRI scanners and patients impact the quality of SR for real-time 3D low-resolution (LR) cine MRI. In this study, we present a personalized super-resolution (psSR) network that incorporates transfer-learning to overcome the challenges in inter-scanner SR of 3D cine MRI.Approach: Development of the proposed psSR network comprises two-stages: (1) a cohort-specific SR (csSR) network using clinical patient datasets, and (2) a psSR network using transfer-learning to target datasets. The csSR network was developed by training on breath-hold and respiratory-gated high-resolution (HR) 3D MRIs and their k-space down-sampled LR MRIs from 53 thoracoabdominal patients scanned at 1.5 T. The psSR network was developed through transfer-learning to retrain the csSR network using a single breath-hold HR MRI and a corresponding 3D cine MRI from 5 healthy volunteers scanned at 0.55 T. Image quality was evaluated using the peak-signal-noise-ratio (PSNR) and the structure-similarity-index-measure (SSIM). The clinical feasibility was assessed by liver contouring on the psSR MRI using an auto-segmentation network and quantified using the dice-similarity-coefficient (DSC).Results. Mean PSNR and SSIM values of psSR MRIs were increased by 57.2% (13.8-21.7) and 94.7% (0.38-0.74) compared to cine MRIs, with the reference 0.55 T breath-hold HR MRI. In the contour evaluation, DSC was increased by 15% (0.79-0.91). Average time consumed for transfer-learning was 90 s, psSR was 4.51 ms per volume, and auto-segmentation was 210 ms, respectively.Significance. The proposed psSR reconstruction substantially increased image and segmentation quality of cine MRI in an average of 215 ms across the scanners and patients with less than 2 min of prerequisite transfer-learning. This approach would be effective in overcoming cohort- and scanner-dependency of deep-learning for MRgRT.

Characterization of real-time cine MR imaging distortion on 0.35 T MRgRT with concentric cine imaging QA phantom.

Objective. Real-time MRgRT uses 2D-cine imaging for target tracking and motion evaluation. Rotation of gantry inducedB0off-resonance, resulting in image artifacts and imaging isocenter-shift precluding MR-guided arc therapy. Standard MRI phantoms designed for higher resolution images face challenges when low-resolution cine imaging is needed to achieve high frame rates. This work aimed to examine the spatial accuracy including geometric distortion and isocenter shift in real-time during gantry rotation on a 0.35 T MR-Linac using the concentric Cine imaging quality assurance (QA) phantom and its associated image analysis software.Approach. The Cine imaging QA phantom consists of two concentric shells of low-T1mineral oil and a central alignment structure. The phantom was scanned on three different MRI systems; 0.55 T Siemens Free.Max, 1.5 T Philips Ingenia, and 0.35 T ViewRay MRIdian MR-Linac using 2D balanced steady-state free precession (bSSFP) imaging sequence. In addition, bSSFP cine MRI with the banding artifact correction was tested on 0.35 T ViewRay MR-Linac. Images from the MR-Linac were acquired with the Linac gantry stationary and rotating from gantry 300°â†’ 0° and vice versa. Three orthogonal image planes were scanned excluding the 1.5 T Philips Ingenia, where only the axial plane was scanned. The image analysis software calculated the distortion values as well as the isocenter position for each cine frame.Main results. The geometric distortion of cine imaging on MRIs and MR-Linac at gantry stationary are within 1 mm while the substantial geometric distortion of 2 and 2.2 mm were observed on 0.35 T MR-Linac while rotating the gantry clockwise (300°â†’ 0°) and counterclockwise 0°â†’ 300° respectively. The average imaging isocenter shift was 0.1 mm for both MRIs and the static gantry and imaging isocenter shift of ≤1.5 mm was observed during the gantry rotation. The imaging isocenter shift decreased by 1 ± 0.2 mm clockwise and counterclockwise withB0compensation.Significance. The concentric Cine imaging QA phantom and its associated software effectively demonstrate the image distortion on real-time cine imaging on regular MRIs and 0.35 T MR-Linac. The results of significant geometric distortion with a rotating gantry in the MR-Linac system require further investigation to alleviate the extent of the image distortion.

Feasibility of surface-guidance combined with CBCT for intra-fractional breath-hold motion management during Ethos RT.

PURPOSE: High-quality CBCT and AI-enhanced adaptive planning techniques allow CBCT-guided stereotactic adaptive radiotherapy (CT-STAR) to account for inter-fractional anatomic changes. Studies of intra-fractional respiratory motion management with a surface imaging solution for CT-STAR have not been fully conducted. We investigated intra-fractional motion management in breath-hold Ethos-based CT-STAR and CT-SBRT (stereotactic body non-adaptive radiotherapy) using optical surface imaging combined with onboard CBCTs. METHODS: Ten cancer patients with mobile lower lung or upper abdominal malignancies participated in an IRB-approved clinical trial (Phase I) of optical surface image-guided Ethos CT-STAR/SBRT. In the clinical trial, a pre-configured gating window (± 2 mm in AP direction) on optical surface imaging was used for manually triggering intra-fractional CBCT acquisition and treatment beam irradiation during breath-hold (seven patients for the end of exhalation and three patients for the end of inhalation). Two inter-fractional CBCTs at the ends of exhalation and inhalation in each fraction were acquired to verify the primary direction and range of the tumor/imaging-surrogate (donut-shaped fiducial) motion. Intra-fractional CBCTs were used to quantify the residual motion of the tumor/imaging-surrogate within the pre-configured breath-hold window in the AP direction. Fifty fractions of Ethos RT were delivered under surface image-guidance: Thirty-two fractions with CT-STAR (adaptive RT) and 18 fractions with CT-SBRT (non-adaptive RT). The residual motion of the tumor was quantified by determining variations in the tumor centroid position. The dosimetric impact on target coverage was calculated based on the residual motion. RESULTS: We used 46 fractions for the analysis of intra-fractional residual motion and 43 fractions for the inter-fractional motion analysis due to study constraints. Using the image registration method, 43 pairs of inter-fractional CBCTs and 100 intra-fractional CBCTs attached to dose maps were analyzed. In the motion range study (image registration) from the inter-fractional CBCTs, the primary motion (mean ± std) was 16.6 ± 9.2 mm in the SI direction (magnitude: 26.4 ± 11.3 mm) for the tumors and 15.5 ± 7.3 mm in the AP direction (magnitude: 20.4 ± 7.0 mm) for the imaging-surrogate, respectively. The residual motion of the tumor (image registration) from intra-fractional breath-hold CBCTs was 2.2 ± 2.0 mm for SI, 1.4 ± 1.4 mm for RL, and 1.3 ± 1.3 mm for AP directions (magnitude: 3.5 ± 2.1 mm). The ratio of the actual dose coverage to 99%, 90%, and 50% of the target volume decreased by 0.95 ± 0.11, 0.96 ± 0.10, 0.99 ± 0.05, respectively. The mean percentage of the target volume covered by the prescribed dose decreased by 2.8 ± 4.4%. CONCLUSION: We demonstrated the intra-fractional motion-managed treatment strategy in breath-hold Ethos CT-STAR/SBRT using optical surface imaging and CBCT. While the controlled residual tumor motion measured at 3.5 mm exceeded the predetermined setup value of 2 mm, it is important to note that this motion still fell within the clinically acceptable range defined by the PTV margin of 5 mm. Nonetheless, additional caution is needed with intra-fractional motion management in breath-hold Ethos CT-STAR/SBRT using optical surface imaging and CBCT.

Comprehensive MR imaging QA of 0.35 T MR-Linac using a multi-purpose large FOV phantom: A single-institution experience.

PURPOSE: Magnetic resonance-guided radiotherapy (MRgRT) is desired for the treatment of diseases in the abdominothoracic region, which has a broad imaging area and continuous motion. To ensure accurate treatment delivery, an effective image quality assurance (QA) program, with a phantom that covers the field of view (FOV) similar to a human torso, is required. However, routine image QA for a large FOV is not readily available at many MRgRT centers. In this work, we present the clinical experience of the large FOV MRgRT Insight phantom for periodic daily and monthly comprehensive magnetic resonance imaging (MRI)-QA and its feasibility compared to the existing institutional routine MRI-QA procedures in 0.35 T MRgRT. METHODS: Three phantoms; ViewRay cylindrical water phantom, Fluke 76-907 uniformity and linearity phantom, and Modus QA large FOV MRgRT Insight phantom, were imaged on the 0.35 T MR-Linac. The measurements were made in MRI mode with the true fast imaging with steady-state free precession (TRUFI) sequence. The ViewRay cylindrical water phantom was imaged in a single-position setup whereas the Fluke phantom and Insight phantom were imaged in three different orientations: axial, sagittal, and coronal. Additionally, the phased array coil QA was performed using the horizontal base plate of the Insight phantom by placing the desired coil around the base section which was compared to an in-house built Polyurethane foam phantom for reference. RESULT: The Insight phantom captured image artifacts across the entire planar field of view, up to 400 mm, in a single image acquisition, which is beyond the FOV of the conventional phantoms. The geometric distortion test showed a similar distortion of 0.45 ± 0.01  and 0.41 ± 0.01 mm near the isocenter, that is, within 300 mm lengths for Fluke and Insight phantoms, respectively, but showed higher geometric distortion of 0.8 ± 0.4 mm in the peripheral region between 300 and 400 mm of the imaging slice for the Insight phantom. The Insight phantom with multiple image quality features and its accompanying software utilized the modulation transform function (MTF) to evaluate the image spatial resolution. The average MTF values were 0.35 ± 0.01, 0.35 ± 0.01, and 0.34 ± 0.03 for axial, coronal, and sagittal images, respectively. The plane alignment and spatial accuracy of the ViewRay water phantom were measured manually. The phased array coil test for both the Insight phantom and the Polyurethane foam phantoms ensured the proper functionality of each coil element. CONCLUSION: The multifunctional large FOV Insight phantom helps in tracking MR imaging quality of the system to a larger extent compared to the routine daily and monthly QA phantoms currently used in our institute. Also, the Insight phantom is found to be more feasible for routine QA with easy setup.

System-dependent image distortion related to gantry positions of a 0.35 T MRgRT: Characterization and the corresponding correction.

PURPOSE: MR-guided radiotherapy with high accuracy treatment planning requires addressing MR imaging artifacts that originate from system imperfections. This work presents the characterization and corresponding correction of gantry-related imaging distortions including geometric distortion and isocenter shift in a 0.35 T magnetic resonance imaging (MRI)-guided radiotherapy (MRgRT) system using distortion vector fields (DVFs). METHODS: Two phantoms, the magnetic resonance imaging distortion in 3D (MRID3D ) phantom and the Fluke phantom, along with a human volunteer were imaged at different gantry angles on a 0.35 T MR-Linac. The geometric distortion and isocenter shift were characterized for both phantom images. DVFs with a field of view extended beyond the physical boundary of the MRID3D phantom were extracted from images taken at 30° gantry angle increments, with vendor-provided distortion correction turned on and off (DstOff). These extended DVFs were then applied to the relevant phantom images to correct their geometric distortions and isocenter shift at the respective gantry angles. The extended DVFs produced from the MRID3D phantom were also applied to Fluke phantom and human MR images at their respective gantry angles. The resampled images were evaluated using structural similarity index measure (SSIM) comparison with the vendor corrected images from the MRgRT system. RESULTS: Geometric distortion with "mean (± SD) distortion" of 3.2 ± 0.02, 2.9 ± 0.02, and 1.8 ± 0.01 mm and isocenter shift (±SD) of 0.49 ± 0.3, 0.05 ± 0.2, and 0.01 ± 0.03 mm were present in the DstOff MRID3D phantom images in right-left (RL), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. After resampling the originally acquired images by applying extended DVFs, the distortion was corrected to 0.18 ± 0.02, 0.09 ± 0.01, 0.15 ± 0.01 mm, and isocenter shift was corrected to 0.14 ± 0.05, -0.02 ± 0.04, and -0.07 ± 0.05 mm in RL, AP, and SI directions, respectively. The Fluke phantom average geometric distortion with "mean (± SD) distortion" of 2.7 ± 0.1 mm was corrected to 0.2 ± 0. 1 mm and the average isocenter shift (± SD) of 0.51 ± 0.2 mm, and 0.05 ± 0.03 was corrected to -0.08 ± 0.03 mm, and -0.05 ± 0.01 in RL and AP directions, respectively. SSIM (mean ± SD) of the original images to resampled images was increased from 0.49 ± 0.02 to 0.78 ± 0.01, 0.45 ± 0.02 to 0.75 ± 0.01, and 0.86 ± 0.25 to 0.98 ± 0.08 for MRID3D phantom, Fluke phantom, and human MR images, respectively, for all the gantry angles compared to the vendor corrected images. CONCLUSION: The gantry-related MR imaging distortion including geometric distortion and isocenter shift was characterized and a corresponding correction was demonstrated using extended DVFs on 0.35 T MRgRT system. The characterized gantry-related isocenter shift can be combined with geometric distortion correction to provide a technique for the correction of the full system-dependent distortion in an MRgRT system.

Synthesis, Characterizations, and 9.4 Tesla T2 MR Images of Polyacrylic Acid-Coated Terbium(III) and Holmium(III) Oxide Nanoparticles.

Polyacrylic acid (PAA)-coated lanthanide oxide (Ln2O3) nanoparticles (NPs) (Ln = Tb and Ho) with high colloidal stability and good biocompatibility were synthesized, characterized, and investigated as a new class of negative (T2) magnetic resonance imaging (MRI) contrast agents at high MR fields. Their r2 values were appreciable at a 3.0 T MR field and higher at a 9.4 T MR field, whereas their r1 values were negligible at all MR fields, indicating their exclusive induction of T2 relaxations with negligible induction of T1 relaxations. Their effectiveness as T2 MRI contrast agents at high MR fields was confirmed from strong negative contrast enhancements in in vivo T2 MR images at a 9.4 T MR field after intravenous administration into mice tails.

Chitosan Oligosaccharide Lactate-Coated Ultrasmall Gadolinium Oxide Nanoparticles: Synthesis, In Vitro Cytotoxicity, and Relaxometric Properties.

In this study, hydrophilic and biocompatible chitosan oligosaccharide lactate (COL)-coated ultra-small gadolinium oxide nanoparticles (NPs) were synthesized through a one-pot polyol method and characterized by various experimental techniques. The In Vitro cellular cytotoxicity assay indicated that the COL-coated gadolinium oxide NPs were non-toxic up to 500 µM Gd. In addition, their water proton spin relaxivities (i.e., r1 and r2) were estimated to be 13.0 and 27.0 s-1mM-1, respectively, which are higher than those of commercial magnetic resonance imaging (MRI) contrast agents. The application potential of the solution sample as a T1 MRI contrast agent was demonstrated In Vitro by measuring map images in which dose-dependent contrast enhancements were observed.

Hydrophilic Biocompatible Poly(Acrylic Acid-co-Maleic Acid) Polymer as a Surface-Coating Ligand of Ultrasmall Gd2O3 Nanoparticles to Obtain a High r1 Value and T1 MR Images.

The water proton spin relaxivity, colloidal stability, and biocompatibility of nanoparticle-based magnetic resonance imaging (MRI) contrast agents depend on the surface-coating ligands. Here, poly(acrylic acid-co-maleic acid) (PAAMA) (Mw = ~3000 amu) is explored as a surface-coating ligand of ultrasmall gadolinium oxide (Gd2O3) nanoparticles. Owing to the numerous carboxylic groups in PAAMA, which allow its strong conjugation with the nanoparticle surfaces and the attraction of abundant water molecules to the nanoparticles, the synthesized PAAMA-coated ultrasmall Gd2O3 nanoparticles (davg = 1.8 nm and aavg = 9.0 nm) exhibit excellent colloidal stability, extremely low cellular toxicity, and a high longitudinal water proton spin relaxivity (r1) of 40.6 s-1mM-1 (r2/r1 = 1.56, where r2 = transverse water proton spin relaxivity), which is approximately 10 times higher than those of commercial molecular contrast agents. The effectiveness of PAAMA-coated ultrasmall Gd2O3 nanoparticles as a T1 MRI contrast agent is confirmed by the high positive contrast enhancements of the in vivo T1 MR images at the 3.0 T MR field.

New Class of Efficient T2 Magnetic Resonance Imaging Contrast Agent: Carbon-Coated Paramagnetic Dysprosium Oxide Nanoparticles.

Nanoparticles are considered potential candidates for a new class of magnetic resonance imaging (MRI) contrast agents. Negative MRI contrast agents require high magnetic moments. However, if nanoparticles can exclusively induce transverse water proton spin relaxation with negligible induction of longitudinal water proton spin relaxation, they may provide negative contrast MR images despite having low magnetic moments, thus acting as an efficient T2 MRI contrast agent. In this study, carbon-coated paramagnetic dysprosium oxide (DYO@C) nanoparticles (core = DYO = DyxOy; shell = carbon) were synthesized to explore their potential as an efficient T2 MRI contrast agent at 3.0 T MR field. Since the core DYO nanoparticles have an appreciable (but not high) magnetic moment that arises from fast 4f-electrons of Dy(III) (6H15/2), the DYO@C nanoparticles exhibited an appreciable transverse water proton spin relaxivity (r2) with a negligible longitudinal water proton spin relaxivity (r1). Consequently, they acted as a very efficient T2 MRI contrast agent, as proven from negative contrast enhancements seen in the in vivo T2 MR images.

D-Glucuronic Acid-Coated Ultrasmall Bi2O3 Nanoparticles for CT Imaging.

Ultrasmall Bi2O3 nanoparticles (davg = 1.5 nm) coated with biocompatible and hydrophilic D-glucuronic acid were prepared for the first time through a simple one-step polyol process and their potential as CT contrast agents were investigated by measuring their X-ray attenuation properties. Their observed X-ray attenuation power was stronger than that of a commercial iodine CT contrast agent at the same atomic concentration, as consistent with the magnitudes of atomic X-ray attenuation coefficients (i.e., Bi > I), and much stronger at the same number density. The results indicate that the nanoparticle sample is a potential CT contrast agent.

In Vivo Positive Magnetic Resonance Imaging Applications of Poly(methyl vinyl ether-alt-maleic acid)-coated Ultra-small Paramagnetic Gadolinium Oxide Nanoparticles.

The study of ultra-small paramagnetic gadolinium oxide (Gd2O3) nanoparticles (NPs) as in vivo positive (T1) magnetic resonance imaging (MRI) contrast agents is one of the most attractive fields in nanomedicine. The performance of the Gd2O3 NP imaging agents depends on the surface-coating materials. In this study, poly(methyl vinyl ether-alt-maleic acid) (PMVEMA) was used as a surface-coating polymer. The PMVEMA-coated paramagnetic ultra-small Gd2O3 NPs with an average particle diameter of 1.9 nm were synthesized using the one-pot polyol method. They exhibited excellent colloidal stability in water and good biocompatibility. They also showed a very high longitudinal water proton spin relaxivity (r1) value of 36.2 s-1mM-1 (r2/r1 = 2.0; r2 = transverse water proton spin relaxivity) under a 3.0 tesla MR field which is approximately 10 times higher than the r1 values of commercial molecular contrast agents. High positive contrast enhancements were observed in in vivo T1 MR images after intravenous administration of the NP solution sample, demonstrating its potential as a T1 MRI contrast agent.

In vivo neutron capture therapy of cancer using ultrasmall gadolinium oxide nanoparticles with cancer-targeting ability.

Gadolinium neutron capture therapy (GdNCT) is considered as a new promising cancer therapeutic technique. Nevertheless, limited GdNCT applications have been reported so far. In this study, surface-modified ultrasmall gadolinium oxide nanoparticles (UGNPs) with cancer-targeting ability (d avg = 1.8 nm) were for the first time applied to the in vivo GdNCT of cancer using nude model mice with cancer, primarily because each nanoparticle can deliver hundreds of Gd to the cancer site. For applications, the UGNPs were grafted with polyacrylic acid (PAA) for biocompatibility and colloidal stability, which was then conjugated with cancer-targeting arginylglycylaspartic acid (RGD) (shortly, RGD-PAA-UGNPs). The solution sample was intravenously administered into the tails of nude model mice with cancer. At the time of the maximum accumulation of the RGD-PAA-UGNPs at the cancer site, which was monitored using magnetic resonance imaging, the thermal neutron beam was locally irradiated onto the cancer site and the cancer growth was monitored for 25 days. The cancer growth suppression was observed due to the GdNCT effects of the RGD-PAA-UGNPs, indicating that the surface-modified UGNPs with cancer-targeting ability are potential materials applicable to the in vivo GdNCT of cancer.

Relaxometric, Optical and Cell Viability Properties of D-Glucuronic Acid Coated Cr2O3 Nanoparticles.

D-glucuronic acid-coated ultrasmall chromium oxide (Cr2O3) nanoparticles were synthesized by a one-pot polyol method and their relaxometric and optical properties were investigated. The as-synthesized D-glucuronic acid-coated nanoparticles were amorphous owing to ultrasmall particle diameters (davg = 2.0 nm), whereas orthorhombic Cr2O3 nanoparticles with two size groups (davg = 3.6 and 5.7 nm) were observed after thermogravimetric analysis (900 °C) as a result of particle growth. The nanoparticles exhibited size-dependent UV-visible absorption maxima at 238, 274, and 372 nm with increasing particle diameter, corresponding to band gaps of 5.13, 4.45, and 3.28 eV, respectively. D-glucuronic acid-coated ultrasmall Cr2O3 nanoparticles revealed low water proton relaxivities of r1 = 0.05 s-1mM-1 and r2 = 0.20 s-1mM-1, consistent with the antiferromagnetic property of Cr2O3. They showed good biocompatibility up to 500 µM of Cr.

Stable and non-toxic ultrasmall gadolinium oxide nanoparticle colloids (coating material = polyacrylic acid) as high-performance T 1 magnetic resonance imaging contrast agents.

For use as positive (T 1) magnetic resonance imaging contrast agents (MRI-CAs), gadolinium oxide (Gd2O3) nanoparticle colloids (i.e. nanoparticles coated with hydrophilic ligands) should be stable, non-toxic, and ultrasmall in particle diameter for renal excretion. In addition, they should have a high longitudinal water proton relaxivity (r 1) and r 2/r 1 ratio that is close to one (r 2 = transverse water proton relaxivity) for high-performance. In this study, we report ultrasmall Gd2O3 nanoparticle colloids [coating material = polyacrylic acid, M w = ∼5100 Da] satisfying these conditions. The particle diameter was monodisperse with an average value of 2.0 ± 0.1 nm. The colloidal suspension exhibited a high r 1 value of 31.0 ± 0.1 s-1 mM-1 and r 2/r 1 ratio of 1.2, where r 1 was ∼8 times higher than that of commercial Gd-chelates: the cooperative induction model was proposed to explain this. The effectiveness of the colloidal suspension as a high-performance T 1 MRI-CA was confirmed by taking in vivo T 1 MR images in a mouse after intravenous administration. Highly positive contrast enhancements were observed in various organs of the mouse such as the liver, kidneys, and bladder. The colloidal suspension was then excreted through the bladder.

Antileishmanial diterpenoid alkaloids from Aconitum spicatum (Bruhl) Stapf.

The crude extracts of tubers of Aconitum spicatum (Bruhl) Stapf were investigated for in vitro antileishmanial activity against Leishmania major. The dichloromethane extract at pH 2.5 showed antileishmanial activity with IC50 value of 27.10 ± 0.0 µg/mL. Chromatographic purification of the dichloromethane extract led to isolation of three C-19 norditerpenoid alkaloids indaconitine (1), chasmaconitine (2) and ludaconitine (3). Compounds 3 and 2 showed antileishmanial activity with IC50 = 36.10 ± 3.4 and 56.30 ± 2.1 µg/mL, respectively. Compound 1 was less effective (IC50 > 100 µg/mL). The cytotoxicity of compounds 1, 2 and 3 studied against MCF7, HeLa and PC3 cancer cell lines and 3T3 normal fibroblast cell line did not show cytotoxicity at 30 µM.