Reproducibility of diffusion-weighted magnetic resonance imaging in head and neck cancer assessed on a 1.5 T MR-Linac and comparison to parallel measurements on a 3 T diagnostic scanner.

BACKGROUND AND PURPOSE: Before quantitative imaging biomarkers (QIBs) acquired with magnetic resonance imaging (MRI) can be used for interventional trials in radiotherapy (RT), technical validation of these QIBs is necessary. The aim of this study was to assess the reproducibility of apparent diffusion coefficient (ADC) values, derived from diffusion-weighted (DW) MRI, in head and neck cancer using a 1.5 T MR-Linac (MRL) by comparison to a 3 T diagnostic scanner (DS). MATERIAL AND METHODS: DW-MRIs were acquired on MRL and DS for 15 head and neck cancer patients before RT and in week 2 and rigidly registered to the planning computed tomography. Mean ADC values were calculated for submandibular (SG) and parotid (PG) glands as well as target volumes (TV, gross tumor volume and lymph nodes), which were delineated based on computed tomography. Mean absolute ADC differences as well as within-subject coefficient of variation (wCV) and intraclass correlation coefficients (ICCs) were calculated for all volumes of interest. RESULTS: A total of 23 datasets were analyzed. Mean ADC difference (DS-MRL) for SG, PG and TV resulted in 142, 254 and 93·10-6 mm2/s. wCVs/ICCs, comparing MRL and DS, were determined as 13.7 %/0.26, 24.4 %/0.23 and 16.1 %/0.73 for SG, PG and TV, respectively. CONCLUSION: ADC values, measured on the 1.5 T MRL, showed reasonable reproducibility with an ADC underestimation in contrast to the DS. This ADC shift must be validated in further experiments and considered for future translation of QIB candidates from DS to MRL for response adaptive RT.

Longitudinal monitoring of Apparent Diffusion Coefficient (ADC) in patients with prostate cancer undergoing MR-guided radiotherapy on an MR-Linac at 1.5 T: a prospective feasibility study.

BACKGROUND: Hybrid MRI linear accelerators (MR-Linac) might enable individualized online adaptation of radiotherapy using quantitative MRI sequences as diffusion-weighted imaging (DWI). The purpose of this study was to investigate the dynamics of lesion apparent diffusion coefficient (ADC) in patients with prostate cancer undergoing MR-guided radiation therapy (MRgRT) on a 1.5T MR-Linac. The ADC values at a diagnostic 3T MRI scanner were used as the reference standard. PATIENTS AND AND METHODS: In this prospective single-center study, patients with biopsy-confirmed prostate cancer who underwent both an MRI exam at a 3T scanner (MRI3T) and an exam at a 1.5T MR-Linac (MRL) at baseline and during radiotherapy were included. Lesion ADC values were measured by a radiologist and a radiation oncologist on the slice with the largest lesion. ADC values were compared before vs. during radiotherapy (during the second week) on both systems via paired t-tests. Furthermore, Pearson correlation coefficient and inter-reader agreement were computed. RESULTS: A total of nine male patients aged 67 ± 6 years [range 60 - 67 years] were included. In seven patients, the cancerous lesion was in the peripheral zone, and in two patients the lesion was in the transition zone. Inter-reader reliability regarding lesion ADC measurement was excellent with an intraclass correlation coefficient of (ICC) > 0.90 both at baseline and during radiotherapy. Thus, the results of the first reader will be reported. In both systems, there was a statistically significant elevation of lesion ADC during radiotherapy (mean MRL-ADC at baseline was 0.97 ± 0.18 × 10-3 mm2/s vs. mean MRL-ADC during radiotherapy 1.38 ± 0.3 × 10-3 mm2/s, yielding a mean lesion ADC elevation of 0.41 ± 0.20 × 10-3 mm2/s, p < 0.001). Mean MRI3T-ADC at baseline was 0.78 ± 0.165 × 10-3 mm2/s vs. mean MRI3T-ADC during radiotherapy 0.99 ± 0.175 × 10-3 mm2/s, yielding a mean lesion ADC elevation of 0.21 ± 0.96 × 10-3 mm2/s p < 0.001). The absolute ADC values from MRL were consistently significantly higher than those from MRI3T at baseline and during radiotherapy (p < = 0.001). However, there was a strong positive correlation between MRL-ADC and MRI3T-ADC at baseline (r = 0.798, p = 0.01) and during radiotherapy (r = 0.863, p = 0.003). CONCLUSIONS: Lesion ADC as measured on MRL increased significantly during radiotherapy and ADC measurements of lesions on both systems showed similar dynamics. This indicates that lesion ADC as measured on the MRL may be used as a biomarker for evaluation of treatment response. In contrast, absolute ADC values as calculated by the algorithm of the manufacturer of the MRL showed systematic deviations from values obtained on a diagnostic 3T MRI system. These preliminary findings are promising but need large-scale validation. Once validated, lesion ADC on MRL might be used for real-time assessment of tumor response in patients with prostate cancer undergoing MR-guided radiation therapy.

A comparison of emulsifiers for the formation of oil-in-water emulsions: stability of the emulsions within 9 h after production and MR signal properties.

OBJECTIVE: To provide a basis for the selection of suitable emulsifiers in oil-in-water emulsions used as tissue analogs for MRI experiments. Three different emulsifiers were investigated with regard to their ability to stabilize tissue-like oil-in-water emulsions. Furthermore, MR signal properties of the emulsifiers themselves and influences on relaxation times and ADC values of the aqueous phase were investigated. MATERIALS AND METHODS: Polysorbate 60, sodium dodecyl sulfate (SDS) and soy lecithin were used as emulsifiers. MR characteristics of emulsifiers were assessed in aqueous solutions and their function as a stabilizer was examined in oil-in-water emulsions of varying fat content (10, 20, 30, 40, 50%). Stability and homogeneity of the oil-in-water emulsions were evaluated with a delay of 3 h and 9 h after preparation using T1 mapping and visual control. Signal properties of the emulsifiers were investigated by 1H-MRS in aqueous emulsifier solutions. Relaxometry and diffusion weighted MRI (DWI) were performed to investigate the effect of various emulsifier concentrations on relaxation times (T1 and T2) and ADC values of aqueous solutions. RESULTS: Emulsions stabilized by polysorbate 60 or soy lecithin were stable and homogeneous across all tested fat fractions. In contrast, emulsions with SDS showed a significantly lower stability and homogeneity. Recorded T1 maps revealed marked creaming of oil droplets in almost all of the emulsions with SDS. The spectral analysis showed several additional signals for polysorbate and SDS. However, lecithin remained invisible in 1H-MRS. Relaxometry and DWI revealed different influences of the emulsifiers on water: Polysorbate and SDS showed only minor effects on relaxation times and ADC values of aqueous solutions, whereas lecithin showed a strong decrease in both relaxation times (r1,lecithin = 0.11 wt.%-1 s-1, r2,lecithin = 0.57 wt.%-1 s-1) and ADC value (Δ(ADC)lecithin = - 0.18 × 10-3 mm2/s⋅wt.%) with increasing concentration. CONCLUSION: Lecithin is suggested as the preferred emulsifier of oil-in-water emulsions in MRI as it shows a high stabilizing ability and remains invisible in MRI experiments. In addition, lecithin is suitable as an alternative means of adjusting relaxation times and ADC values of water.

Prospective Image Quality and Lesion Assessment in the Setting of MR-Guided Radiation Therapy of Prostate Cancer on an MR-Linac at 1.5 T: A Comparison to a Standard 3 T MRI.

The objective of this study is to conduct a qualitative and a quantitative image quality and lesion evaluation in patients undergoing MR-guided radiation therapy (MRgRT) for prostate cancer on a hybrid magnetic resonance imaging and linear accelerator system (MR-Linac or MRL) at 1.5 Tesla. This prospective study was approved by the institutional review board. A total of 13 consecutive patients with biopsy-confirmed prostate cancer and an indication for MRgRT were included. Prior to radiation therapy, each patient underwent an MR-examination on an MRL and on a standard MRI scanner at 3 Tesla (MRI3T). Three readers (two radiologists and a radiation oncologist) conducted an independent qualitative and quantitative analysis of T2-weighted (T2w) and diffusion-weighted images (DWI). Qualitative outcome measures were as follows: zonal anatomy, capsule demarcation, resolution, visibility of the seminal vesicles, geometric distortion, artifacts, overall image quality, lesion conspicuity, and diagnostic confidence. All ratings were performed on an ordinal 4-point Likert scale. Lesion conspicuity and diagnostic confidence were firstly analyzed only on MRL. Afterwards, these outcome parameters were analyzed in consensus with the MRI3T. Quantitative outcome measures were as follows: anteroposterior and right left diameter of the prostate, lesion size, PI-RADS score (Prostate Imaging-Reporting and Data System) and apparent diffusion coefficient (ADC) of the lesions. Intergroup comparisons were computed using the Wilcoxon-sign rank test and t tests. A post-hoc regression analysis was computed for lesion evaluation. Finally, inter-/intra-reader agreement was analyzed using the Fleiss kappa and intraclass correlation coefficient. For T2w images, the MRL showed good results across all quality criteria (median 3 and 4). Furthermore, there were no significant differences between MRL and MRI3T regarding capsule demarcation or geometric distortion. For the DWI, the MRL performed significantly less than MRI3T across most image quality criteria with a median ranging between 2 and 3. However, there were no significant differences between MRL and MRI3T regarding geometric distortion. In terms of lesion conspicuity and diagnostic confidence, inter-reader agreement was fair for MRL alone (Kappa = 0.42) and good for MRL in consensus with MRI3T (Kappa = 0.708). Thus, lesion conspicuity and diagnostic confidence could be significantly improved when reading MRL images in consensus with MRI3T (Odds ratio: 9- to 11-fold for the T2w images and 5- to 8-fold for the DWI) (p < 0.001). For measures of lesion size, anterior-posterior and right-left prostate diameter, inter-reader and intersequence agreement were excellent (ICC > 0.90) and there were no significant differences between MRL and MRI3T among all three readers. In terms of Prostate Imaging Reporting and Data System (PIRADS) scoring, no significant differences were observed between MRL and MRI3T. Finally, there was a significant positive linear relationship between lesion ADC measurements (r = 0.76, p < 0.01) between the ADC values measured on both systems. In conclusion, image quality for T2w was comparable and diagnostic even without administration of spasmolytic- or contrast agents, while DWI images did not reach diagnostic level and need to be optimized for further exploitation in the setting of MRgRT. Diagnostic confidence and lesion conspicuity were significantly improved by reading MRL in consensus with MRI3T which would be advisable for a safe planning and treatment workflow. Finally, ADC measurements of lesions on both systems were comparable indicating that, lesion ADC as measured on the MRL could be used as a biomarker for evaluation of treatment response, similar to examinations using MRI3T.