Recommendations for improved reproducibility of ADC derivation on behalf of the Elekta MRI-linac consortium image analysis working group.

BACKGROUND AND PURPOSE: The apparent diffusion coefficient (ADC), a potential imaging biomarker for radiotherapy response, needs to be reproducible before translation into clinical use. The aim of this study was to evaluate the multi-centre delineation- and calculation-related ADC variation and give recommendations to minimize it. MATERIALS AND METHODS: Nine centres received identical diffusion-weighted and anatomical magnetic resonance images of different cancerous tumours (adrenal gland, pelvic oligo metastasis, pancreas, and prostate). All centres delineated the gross tumour volume (GTV), clinical target volume (CTV), and viable tumour volume (VTV), and calculated ADCs using both their local calculation methods and each of the following calculation conditions: b-values 0-500 vs. 150-500 s/mm2, region-of-interest (ROI)-based vs. voxel-based calculation, and mean vs. median. ADC variation was assessed using the mean coefficient of variation across delineations (CVD) and calculation methods (CVC). Absolute ADC differences between calculation conditions were evaluated using Friedman's test. Recommendations for ADC calculation were formulated based on observations and discussions within the Elekta MRI-linac consortium image analysis working group. RESULTS: The median (range) CVD and CVC were 0.06 (0.02-0.32) and 0.17 (0.08-0.26), respectively. The ADC estimates differed 18% between b-value sets and 4% between ROI/voxel-based calculation (p-values < 0.01). No significant difference was observed between mean and median (p = 0.64). Aligning calculation conditions between centres reduced CVC to 0.04 (0.01-0.16). CVD was comparable between ROI types. CONCLUSION: Overall, calculation methods had a larger impact on ADC reproducibility compared to delineation. Based on the results, significant sources of variation were identified, which should be considered when initiating new studies, in particular multi-centre investigations.

Daily Intravoxel Incoherent Motion (IVIM) In Prostate Cancer Patients During MR-Guided Radiotherapy-A Multicenter Study.

PURPOSE: Daily quantitative MR imaging during radiotherapy of cancer patients has become feasible with MRI systems integrated with linear accelerators (MR-linacs). Quantitative images could be used for treatment response monitoring. With intravoxel incoherent motion (IVIM) MRI, it is possible to acquire perfusion information without the use of contrast agents. In this multicenter study, daily IVIM measurements were performed in prostate cancer patients to identify changes that potentially reflect response to treatment. MATERIALS AND METHODS: Forty-three patients were included, treated with 20 fractions of 3 Gy on a 1.5 T MR-linac. IVIM measurements were performed on each treatment day. The diffusion coefficient (D), perfusion fraction (f), and pseudo-diffusion coefficient (D*) were calculated based on the median signal intensities in the non-cancerous prostate and the tumor. Repeatability coefficients (RCs) were determined based on the first two treatment fractions. Separate linear mixed-effects models were constructed for the three IVIM parameters. RESULTS: In total, 726 fractions were analyzed. Pre-treatment average values, measured on the first fraction before irradiation, were 1.46 × 10-3 mm2/s, 0.086, and 28.7 × 10-3 mm2/s in the non-cancerous prostate and 1.19 × 10-3 mm2/s, 0.088, and 28.9 × 10-3 mm2/s in the tumor, for D, f, and D*, respectively. The repeatability coefficients for D, f, and D* in the non-cancerous prostate were 0.09 × 10-3 mm2/s, 0.05, and 15.3 × 10-3 mm2/s. In the tumor, these values were 0.44 × 10-3 mm2/s, 0.16, and 76.4 × 10-3 mm2/s. The mixed effects analysis showed an increase in D of the tumors over the course of treatment, while remaining stable in the non-cancerous prostate. The f and D* increased in both the non-cancerous prostate and tumor. CONCLUSIONS: It is feasible to perform daily IVIM measurements on an MR-linac system. Although the repeatability coefficients were high, changes in IVIM perfusion parameters were measured on a group level, indicating that IVIM has potential for measuring treatment response.

Integration of quantitative imaging biomarkers in clinical trials for MR-guided radiotherapy: Conceptual guidance for multicentre studies from the MR-Linac Consortium Imaging Biomarker Working Group.

Quantitative imaging biomarkers (QIBs) derived from MRI techniques have the potential to be used for the personalised treatment of cancer patients. However, large-scale data are missing to validate their added value in clinical practice. Integrated MRI-guided radiotherapy (MRIgRT) systems, such as hybrid MRI-linear accelerators, have the unique advantage that MR images can be acquired during every treatment session. This means that high-frequency imaging of QIBs becomes feasible with reduced patient burden, logistical challenges, and costs compared to extra scan sessions. A wealth of valuable data will be collected before and during treatment, creating new opportunities to advance QIB research at large. The aim of this paper is to present a roadmap towards the clinical use of QIBs on MRIgRT systems. The most important need is to gather and understand how the QIBs collected during MRIgRT correlate with clinical outcomes. As the integrated MRI scanner differs from traditional MRI scanners, technical validation is an important aspect of this roadmap. We propose to integrate technical validation with clinical trials by the addition of a quality assurance procedure at the start of a trial, the acquisition of in vivo test-retest data to assess the repeatability, as well as a comparison between QIBs from MRIgRT systems and diagnostic MRI systems to assess the reproducibility. These data can be collected with limited extra time for the patient. With integration of technical validation in clinical trials, the results of these trials derived on MRIgRT systems will also be applicable for measurements on other MRI systems.

ADC measurements on the Unity MR-linac - A recommendation on behalf of the Elekta Unity MR-linac consortium.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) for treatment response monitoring is feasible on hybrid magnetic resonance linear accelerator (MR-linac) systems. The MRI scanner of the Elekta Unity system has an adjusted design compared to diagnostic scanners. We investigated its impact on measuring the DWI-derived apparent diffusion coefficient (ADC) regarding three aspects: the choice of b-values, the spatial variation of the ADC, and scanning during radiation treatment. The aim of this study is to give recommendations for accurate ADC measurements on Unity systems. MATERIALS AND METHODS: Signal-to-noise ratio (SNR) measurements with increasing b-values were done to determine the highest bvalue that can be measured reliably. The spatial variation of the ADC was assessed on six Unity systems with a cylindrical phantom of 40 cm diameter. The influence of gantry rotation and irradiation was investigated by acquiring DWI images before and during treatment of 11 prostate cancer patients. RESULTS: On the Unity system, a maximum b-value of 500 s/mm2 should be used for ADC quantification, as a trade-off between SNR and diffusion weighting. Accurate ADC values were obtained within 7 cm from the iso-center, while outside this region ADC values deviated more than 5%. The ADC was not influenced by the rotating linac or irradiation during treatment. CONCLUSION: We provide Unity system specific recommendations for measuring the ADC. This will increase the consistency of ADC values acquired in different centers on the Unity system, enabling large cohort studies for biomarker discovery and treatment response monitoring.

Applicator visualization using ultrashort echo time MRI for high-dose-rate endorectal brachytherapy.

PURPOSE: The individual channels in an endorectal applicator for high-dose-rate endorectal brachytherapy are not visible on standard MRI sequences. The aim of this study was to test whether an ultrashort echo time (UTE) MRI sequence could be used to visualize the individual channels to enable MR-only treatment planning for rectal cancer. METHODS AND MATERIALS: We used a radial three-dimensional (3D) UTE pulse sequence and acquired images of phantoms and two patients with rectal cancer. We rigidly registered a UTE image and CT scan of an applicator phantom, based on the outline of the applicator. One observer compared channel positions on the UTE image and CT scan in five slices spaced 25 mm apart. To quantify geometric distortions, we scanned a commercial 3D geometric quality assurance phantom and calculated the difference between detected marker positions on the UTE image and corresponding marker positions on two 3D T1-weighted images with opposing readout directions. RESULTS: On the UTE images, there is sufficient contrast to discern the individual channels. The difference in channel positions on the UTE image compared with the CT was on average -0.1 ± 0.1 mm (left-right) and 0.1 ± 0.3 mm (anteroposterior). After rigid registration to the 3D T1-weighted sequences, the residual 95th percentile of the geometric distortion inside a 550-mm-diameter sphere was 1.0 mm (left-right), 0.9 mm (anteroposterior), and 0.9 mm (craniocaudal). CONCLUSIONS: With a UTE sequence, the endorectal applicator and individual channels can be adequately visualized in both phantom and patients. The geometrical fidelity is within an acceptable range.

Clinical workflow for treating patients with a metallic hip prosthesis using magnetic resonance imaging-guided radiotherapy.

BACKGROUND & PURPOSE: Metallic prostheses distort the magnetic field during magnetic resonance imaging (MRI), leading to geometric distortions and signal loss. The purpose of this work was to develop a method to determine eligibility for MRI-guided radiotherapy (MRIgRT) on a per patient basis by estimating the magnitude of geometric distortions inside the clinical target volume (CTV). MATERIALS & METHODS: Three patients with prostate cancer and hip prosthesis, treated using MRIgRT, were included. Eligibility for MRIgRT was based on computed tomography and associated CTV delineations, together with a field-distortion (B0) map and anatomical images acquired during MR simulation. To verify the method, B0 maps made during MR simulation and each MRIgRT treatment fraction were compared. RESULTS: Estimates made during MR simulation of the magnitude of distortions inside the CTV were 0.43 mm, 0.19 mm and 2.79 mm compared to the average over all treatment fractions of 1.40 mm, 0.32 mm and 1.81 mm, per patient respectively. CONCLUSIONS: B0 map acquisitions prior to treatment can be used to estimate the magnitude of distortions during MRIgRT to guide the decision on eligibility for MRIgRT of prostate cancer patients with metallic hip implants.

Correcting geometric image distortions in slice-based 4D-MRI on the MR-linac.

PURPOSE: The importance of four-dimensional-magnetic resonance imaging (4D-MRI) is increasing in guiding online plan adaptation in thoracic and abdominal radiotherapy. Many 4D-MRI sequences are based on multislice two-dimensional (2D) acquisitions which provide contrast flexibility. Intrinsic to MRI, however, are machine- and subject-related geometric image distortions. Full correction of slice-based 4D-MRIs acquired on the Unity MR-linac (Elekta AB, Stockholm, Sweden) is challenging, since through-plane corrections are currently not available for 2D sequences. In this study, we implement a full three-dimensional 3D correction and quantify the geometric and dosimetric effects of machine-related (residual) geometric image distortions. METHODS: A commercial three-dimensional (3D) geometric QA phantom (Philips, Best, the Netherlands) was used to quantify the effect of gradient nonlinearity (GNL) and static-field inhomogeneity (B0I) on geometric accuracy. Additionally, the effectiveness of 2D (in-plane, machine-generic), 3D (machine-generic), and in-house developed 3D + (machine-specific) corrections was investigated. Corrections were based on deformable vector fields derived from spherical harmonics coefficients. Three patients with oligometastases in the liver were scanned with axial 4D-MRIs on our MR-linac (total: 10 imaging sessions). For each patient, a step-and-shoot IMRT plan (3 × 20 Gy) was created based on the simulation mid-position (midP)-CT. The 4D-MRIs were then warped into a daily midP-MRI and geometrically corrected. Next, the treatment plan was adapted according to the position offset of the tumor between midP-CT and the 3D-corrected midP-MRIs. The midP-CT was also deformably registered to the daily midP-MRIs (different corrections applied) to quantify the dosimetric effects of (residual) geometric image distortions. RESULTS: Using phantom data, median GNL distortions were 0.58 mm (no correction), 0.42-0.48 mm (2D), 0.34 mm (3D), and 0.34 mm (3D + ), measured over a diameter of spherical volume (DSV) of 200 mm. Median B0I distortions were 0.09 mm for the same DSV. For DSVs up to 500 mm, through-plane corrections are necessary to keep the median residual GNL distortion below 1 mm. 3D and 3D + corrections agreed within 0.15 mm. 2D-corrected images featured uncorrected through-plane distortions of up to 21.11 mm at a distance of 20-25 cm from the machine's isocenter. Based on the 4D-MRI patient scans, the average external body contour distortions were 3.1 mm (uncorrected) and 1.2 mm (2D-corrected), with maximum local distortions of 9.5 mm in the uncorrected images. No (residual) distortions were visible for the metastases, which were all located within 10 cm of the machine's isocenter. The interquartile range (IQR) of dose differences between planned and daily dose caused by variable patient setup, patient anatomy, and online plan adaptation was 1.37 Gy/Fx for the PTV D95%. When comparing dose on 3D-corrected with uncorrected (2D-corrected) images, the IQR was 0.61 (0.31) Gy/Fx. CONCLUSIONS: GNL is the main machine-related source of image distortions on the Unity MR-linac. For slice-based 4D-MRI, a full 3D correction can be applied after respiratory sorting to maximize spatial fidelity. The machine-specific 3D + correction did not substantially reduce residual geometric distortions compared to the machine-generic 3D correction for our MR-linac. In our patients, dosimetric variations in the target not related to geometric distortions were larger than those caused by geometric distortions.

Quantitative 3T multiparametric MRI of benign and malignant prostatic tissue in patients with and without local recurrent prostate cancer after external-beam radiation therapy.

BACKGROUND: Post-radiotherapy locally recurrent prostate cancer (PCa) patients are candidates for focal salvage treatment. Multiparametric MRI (mp-MRI) is attractive for tumor localization. However, radiotherapy-induced tissue changes complicate image interpretation. To develop focal salvage strategies, accurate tumor localization and distinction from benign tissue is necessary. PURPOSE: To quantitatively characterize radio-recurrent tumor and benign radiation-induced changes using mp-MRI, and investigate which sequences optimize the distinction between tumor and benign surroundings. STUDY TYPE: Prospective case-control. SUBJECTS: Thirty-three patients with biochemical failure after external-beam radiotherapy (cases), 35 patients without post-radiotherapy recurrent disease (controls), and 13 patients with primary PCa (untreated). FIELD STRENGTH/SEQUENCES: 3T; quantitative mp-MRI: T2 -mapping, ADC, and Ktrans and kep maps. ASSESSMENT: Quantitative image-analysis of prostatic regions, within and between cases, controls, and untreated patients. STATISTICAL TESTS: Within-groups: nonparametric Friedman analysis of variance with post-hoc Wilcoxon signed-rank tests; between-groups: Mann-Whitney tests. All with Bonferroni corrections. Generalized linear mixed modeling to ascertain the contribution of each map and location to tumor likelihood. RESULTS: Benign imaging values were comparable between cases and controls (P = 0.15 for ADC in the central gland up to 0.91 for kep in the peripheral zone), both with similarly high peri-urethral Ktrans and kep values (min-1 ) (median [range]: Ktrans = 0.22 [0.14-0.43] and 0.22 [0.14-0.36], P = 0.60, kep = 0.43 [0.24-0.57] and 0.48 [0.32-0.67], P = 0.05). After radiotherapy, benign central gland values were significantly decreased for all maps (P ≤ 0.001) as well as T2 , Ktrans , and kep of benign peripheral zone (all with P ≤ 0.002). All imaging maps distinguished recurrent tumor from benign peripheral zone, but only ADC, Ktrans , and kep were able to distinguish it from benign central gland. Recurrent tumor and peri-urethral Ktrans values were not significantly different (P = 0.81), but kep values were (P < 0.001). Combining all quantitative maps and voxel location resulted in an optimal distinction between tumor and benign voxels. DATA CONCLUSION: Mp-MRI can distinguish recurrent tumor from benign tissue. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:269-278.

Numerical study of the F model with domain-wall boundaries.

We perform a numerical study of the F model with domain-wall boundary conditions. Various exact results are known for this particular case of the six-vertex model, including closed expressions for the partition function for any system size as well as its asymptotics and leading finite-size corrections. To complement this picture we use a full lattice multicluster algorithm to study equilibrium properties of this model for systems of moderate size, up to L=512. We compare the energy to its exactly known large-L asymptotics. We investigate the model's infinite-order phase transition by means of finite-size scaling for an observable derived from the staggered polarization in order to test the method put forward in our recent joint work with Duine and Barkema. In addition we analyze local properties of the model. Our data are perfectly consistent with analytical expressions for the arctic curves. We investigate the structure inside the temperate region of the lattice, confirming the oscillations in vertex densities that were first observed by Syljuåsen and Zvonarev and recently studied by Lyberg et al. We point out "(anti)ferroelectric" oscillations close to the corresponding frozen regions as well as "higher-order" oscillations forming an intricate pattern with saddle-point-like features.