Longitudinal Correlations Between Intravoxel Incoherent Motion (IVIM) and Dynamic Contrast-Enhanced (DCE) MRI During Radiotherapy in Prostate Cancer Patients.

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-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.

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.

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.

Feasibility and accuracy of quantitative imaging on a 1.5 T MR-linear accelerator.

PURPOSE: Systems 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 METHODS: Four 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. RESULTS: Median 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. CONCLUSION: These 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.

A Self-Sorting Coronal 4D-MRI Method for Daily Image Guidance of Liver Lesions on an MR-LINAC.

PURPOSE: Novel hybrid MR-LINAC devices provide MRI's superior soft-tissue contrast in the treatment room and thus have the potential to increase accuracy of liver stereotactic body radiation therapy (SBRT). Requirements for daily position verification using 4-dimensional MRI include tumor visibility and short acquisition-reconstruction time (preferably <5 min). The proposed method provides fast acquisition-reconstruction time and the flexibility to vary T1- and T2-weighting, using standard imaging sequences for straightforward implementation on an MR-LINAC. METHODS AND MATERIALS: Images were acquired using a coronal 2-dimensional, multislice, single-shot turbo spin-echo (TSE) and turbo field-echo (TFE) sequence, which were repeated 30 times. An image-based self-sorting signal (ImS) was extracted from the data, and rigid registration of the diaphragm per slice position was performed and corrected for amplitude variation in the anteroposterior direction. Data were sorted into 10 bins according to amplitude and phase. ImS was validated in 4 healthy volunteers against a navigator signal. Positional variations within bins, missing data, and smoothness of the liver dome were compared between amplitude and phase binning in 10 volunteers. Tumor contrast and registration were investigated in 3 patients. RESULTS: Each ImS was found to be in excellent agreement with the navigator signal with a correlation coefficient of >0.95 and binning differences of <1 bin. Better liver dome smoothness per bin in case of amplitude binning compared with that in phase binning (2.0-2.6 mm vs 2.4-3.7 mm, respectively) is a tradeoff for more missing data (3.5%-17.5% vs 3.5%-4.7%, respectively). Liver lesions were visible in almost all coronal TSE and TFE images, but the lesion boundary was better defined in the TSE images. Rigid registrations could be performed on the tumor area. CONCLUSIONS: An efficient self-sorted 4-dimensional MRI method was developed and validated using standard sequences and fast reconstruction on a LINAC-integrated MRI scanner providing good tumor visibility for daily image-guided liver stereotactic body radiation therapy.