Background and purposeThe apparent diffusion coefficient (ADC), a potential imaging biomarker for radiotherapy response, needs to be reproducible before translation into clinical use. The aim of... Show moreBackground and purposeThe 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 methodsNine 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.ResultsThe 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.ConclusionOverall, 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. Show less
Kooreman, E.S.; Pelt, V. van; Nowee, M.E.; Pos, F.; Heide, U.A. van der; Houdt, P.J. van 2022
Purpose: Intravoxel incoherent motion (IVIM) is a promising technique that can acquire perfusion information without the use of contrast agent, contrary to the more established dynamic contrast... Show morePurpose: Intravoxel incoherent motion (IVIM) is a promising technique that can acquire perfusion information without the use of contrast agent, contrary to the more established dynamic contrast-enhanced (DCE) technique. This is of interest for treatment response monitoring, where patients can be imaged on each treatment fraction. In this study, longitudinal correlations between IVIM- and DCE parameters were assessed in prostate cancer patients receiving radiation treatment.Materials and Methods: 20 prostate cancer patients were treated on a 1.5 T MR-linac with 20 x 3 or 3.1 Gy. Weekly IVIM and DCE scans were acquired. Tumors, the peripheral zone (PZ), and the transition zone (TZ) were delineated on a T2-weighted scan acquired on the first fraction. IVIM and DCE scans were registered to this scan and the delineations were propagated. Median values from these delineations were used for further analysis. The IVIM parameters D, f, D* and the product fD* were calculated. The Tofts model was used to calculate the DCE parameters Ktrans, kep and ve. Pearson correlations were calculated for the IVIM and DCE parameters on values from the first fraction for each region of interest (ROI). For longitudinal analysis, the repeated measures correlation coefficient was used to determine correlations between IVIM and DCE parameters in each ROI.Results: When averaging over patients, an increase during treatment in all IVIM and DCE parameters was observed in all ROIs, except for D in the PZ and TZ. No significant Pearson correlations were found between any pair of IVIM and DCE parameters measured on the first fraction. Significant but low longitudinal correlations were found for some combinations of IVIM and DCE parameters in the PZ and TZ, while no significant longitudinal correlations were found in the tumor. Notably in the TZ, for both f and fD*, significant longitudinal correlations with all DCE parameters were found.Conclusions: The increase in IVIM- and DCE parameters when averaging over patients indicates a measurable response to radiation treatment with both techniques. Although low, significant longitudinal correlations were found which suggests that IVIM could potentially be used as an alternative to DCE for treatment response monitoring. Show less
Kooreman, E.S.; Tanaka, M.; Beek, L.C. ter; Peters, F.P.; Marijnen, C.A.M.; Heide, U.A. van der; Houdt, P.J. van 2022
Quantitative MRI has the potential to produce imaging biomarkers for the prediction of early response to radiotherapy treatment. In this pilot study, a potential imaging biomarker, the T-1 rho... Show moreQuantitative MRI has the potential to produce imaging biomarkers for the prediction of early response to radiotherapy treatment. In this pilot study, a potential imaging biomarker, the T-1 rho relaxation time, is assessed for this purpose. A T-1 rho sequence was implemented on a 1.5 T MR-linac system, a system that combines an MRI with a linear accelerator for radiation treatment. An agar phantom with concentrations of 1-4% w/w was constructed for technical validation of the sequence. Phantom images were assessed in terms of short-term repeatability and signal-to-noise ratio. Twelve rectal cancer patients, who were treated with 5 x 5 Gy, were imaged on each treatment fraction. Individual changes in the T-1 rho values of the gross tumor volume (GTV) showed an increase for most patients, although a paired t-test comparing values in the GTV from the first to the last treatment fraction showed no statistically significant difference. The phantom measurements showed excellent short-term repeatability (0.5-1.5 ms), and phantom T-1 rho values corresponded to the literature values. T-1 rho imaging was implemented successfully on the MR-linac, with a repeatability comparable to diagnostic systems, although clinical benefit in terms of treatment response monitoring remains to be demonstrated. Show less
Objective Dynamic contrast enhanced (DCE)-MRI is currently not generally used for intraocular masses as lesions are small, have an inhomogeneous T-1 and the eye is prone to motion. The aim of this... Show moreObjective Dynamic contrast enhanced (DCE)-MRI is currently not generally used for intraocular masses as lesions are small, have an inhomogeneous T-1 and the eye is prone to motion. The aim of this paper is to address these eye-specific challenges, enabling accurate ocular DCE-MRI. Materials & methods DCE-MRI of 19 uveal melanoma (UM) patients was acquired using a fat-suppressed 3D spoiled gradient echo sequence with TWIST (time-resolved angiography with stochastic trajectories sequence). The analysis consisted of a two-step registration method to correct for both head and eye motion. A T-1 map was calculated to convert signal intensities to concentrations. Subsequently, the Tofts model was fitted voxel wise to obtain K-trans and v(e). Results Registration significantly improved the concentration curve quality (p < 0.001). The T-1 of melanotic lesions was significantly lower than amelanotic lesions (888 ms vs 1350 ms, p = 0.03). The average achieved B-1(+) in the lesions was 91%. The average K-trans was 0.46 min(-1) (range 0.13-1.0) and the average v(e) was 0.22 (range 0.10-0.51). Conclusion Using this eye-specific analysis, DCE of intraocular masses is possible which might aid in the diagnosis, prognosis and follow-up of UM. Show less
Background and purpose: Diffusion-weighted imaging (DWI) for treatment response monitoring is feasibleon hybrid magnetic resonance linear accelerator (MR-linac) systems. The MRI scanner of the... Show moreBackground and purpose: Diffusion-weighted imaging (DWI) for treatment response monitoring is feasibleon hybrid magnetic resonance linear accelerator (MR-linac) systems. The MRI scanner of the ElektaUnity system has an adjusted design compared to diagnostic scanners. We investigated its impact onmeasuring the DWI-derived apparent diffusion coefficient (ADC) regarding three aspects: the choice ofb-values, the spatial variation of the ADC, and scanning during radiation treatment. The aim of this studyis 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 todetermine the highest bvalue that can be measured reliably. The spatial variation of the ADC wasassessed on six Unity systems with a cylindrical phantom of 40 cm diameter. The influence of gantry rotationand irradiation was investigated by acquiring DWI images before and during treatment of 11 prostatecancer patients.Results: On the Unity system, a maximum b-value of 500 s/mm2 should be used for ADC quantification, asa trade-off between SNR and diffusion weighting. Accurate ADC values were obtained within 7 cm fromthe iso-center, while outside this region ADC values deviated more than 5%. The ADC was not influencedby the rotating linac or irradiation during treatment.Conclusion: We provide Unity system specific recommendations for measuring the ADC. This willincrease the consistency of ADC values acquired in different centers on the Unity system, enabling largecohort studies for biomarker discovery and treatment response monitoring. Show less
Background and purpose: A wide variation of MRI systems is a challenge in multicenter imaging biomarker studies as it adds variation in quantitative MRI values. The aim of this study was to design... Show moreBackground and purpose: A wide variation of MRI systems is a challenge in multicenter imaging biomarker studies as it adds variation in quantitative MRI values. The aim of this study was to design and test a quality assurance (QA) framework based on phantom measurements, for the quantitative MRI protocols of a multicenter imaging biomarker trial of locally advanced cervical cancer.Materials and methods: Fifteen institutes participated (five 1.5 T and ten 3 T scanners). Each institute optimized protocols for T2, diffusion-weighted imaging, T1, and dynamic contrast-enhanced (DCE-)MRI according to system possibilities, institutional preferences and study-specific constraints. Calibration phantoms with known values were used for validation. Benchmark protocols, similar on all systems, were used to investigate whether differences resulted from variations in institutional protocols or from system variations. Bias, repeatability (%RC), and reproducibility (%RDC) were determined. Ratios were used for T2 and T1 values.Results: The institutional protocols showed a range in bias of 0.88-0.98 for T2 (median %RC = 1%; % RDC = 12%), -0.007 to 0.029 x 10(-3) mm(2)/s for the apparent diffusion coefficient (median %RC = 3%; % RDC = 18%), and 0.39-1.29 for T1 (median %RC = 1%; %RDC = 33%). For DCE a nonlinear vendor-specific relation was observed between measured and true concentrations with magnitude data, whereas the relation was linear when phase data was used.Conclusion: We designed a QA framework for quantitative MRI protocols and demonstrated for a multi-center trial for cervical cancer that measurement of consistent T2 and apparent diffusion coefficient values is feasible despite protocol differences. For DCE-MRI and T1 mapping with the variable flip angle method, this was more challenging. (C) 2020 The Authors. Published by Elsevier B.V. Show less
Heide, U.A. van der; Frantzen-Steneker, M.; Astreinidou, E.; Nowee, M.E.; Houdt, P.J. van 2019
MRI is increasingly used in radiation oncology to facilitate tumor and organ-at-risk delineation and image guidance. In this review, we address issues of MRI that are relevant for radiation... Show moreMRI is increasingly used in radiation oncology to facilitate tumor and organ-at-risk delineation and image guidance. In this review, we address issues of MRI that are relevant for radiation oncologists when interpreting MR images offered for radiotherapy. Whether MRI is used in combination with CT or in an MRI-only workflow, it is generally necessary to ensure that MR images are acquired in treatment position, using the positioning and fixation devices that are commonly applied in radiotherapy. For target delineation, often a series of separate image sets are used with distinct image contrasts, acquired within a single exam. MR images can suffer from image distortions. While this can be avoided with dedicated scan protocols, in a diagnostic setting geometrical fidelity is less relevant and is therefore less accounted for. Since geometrical fidelity is of utmost importance in radiation oncology, it requires dedicated scan protocols. The strong magnetic field of an MRI scanner and the use of radiofrequency radiation can cause safety hazards if not properly addressed. Safety screening is crucial for every patient and every operator prior to entering the MRI room. (C) 2019 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology. Show less
PurposeSystems for magnetic resonance (MR-) guided radiotherapy enable daily MR imaging of cancer patients during treatment, which is of interest for treatment response monitoring and biomarker... Show morePurposeSystems for magnetic resonance (MR-) guided radiotherapy enable daily MR imaging of cancer patients during treatment, which is of interest for treatment response monitoring and biomarker discovery using quantitative MRI (qMRI). Here, the performance of a 1.5 T MR-linac regarding qMRI was assessed on phantoms. Additionally, we show the feasibility of qMRI in a prostate cancer patient on this system for the first time.Materials and methodsFour 1.5 T MR-linac systems from four institutes were included in this study. T1 and T2 relaxation times, and apparent diffusion coefficient (ADC) maps, as well as dynamic contrast enhanced (DCE) images were acquired. Bland–Altman statistics were used, and accuracy, repeatability, and reproducibility were determined.ResultsMedian accuracy for T1 ranged over the four systems from 2.7 to 14.3%, for T2 from 10.4 to 14.1%, and for ADC from 1.9 to 2.7%. For DCE images, the accuracy ranged from 12.8 to 35.8% for a gadolinium concentration of 0.5 mM and deteriorated for higher concentrations. Median short-term repeatability for T1 ranged from 0.6 to 5.1%, for T2 from 0.4 to 1.2%, and for ADC from 1.3 to 2.2%. DCE acquisitions showed a coefficient of variation of 0.1–0.6% in the signal intensity. Long-term repeatability was 1.8% for T1, 1.4% for T2, 1.7% for ADC, and 17.9% for DCE. Reproducibility was 11.2% for T1, 2.9% for T2, 2.2% for ADC, and 18.4% for DCE.ConclusionThese results indicate that qMRI on the Unity MR-linac is feasible, accurate, and repeatable which is promising for treatment response monitoring and treatment plan adaptation based on daily qMRI. Show less
Klawer, E.M.E.; Houdt, P.J. van; Pos, F.J.; Heijmink, S.W.T.P.J.; Osch, M.J.P. van; Heide, U.A. van der 2018
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,... Show moreBackground 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 2018. Show less
Fernandes, C.D.; Ghobadi, G.; Poel, H.G. van der; Jong, J. de; Heijmink, S.W.T.P.J.; Schoots, I.; ... ; Heide, U.A. van der 2018
