MRI is increasingly incorporated into radiotherapy workflow. Recently, a MRI-guided radiotherapy system (ViewRay) has become commercially available. This system has a 0.35 Tesla magnet and 3 Cobalt 60 radiation sources. We hypothesize that such a system will enable practical adaptive radiotherapy wherein the therapy plan is adapted during the course of therapy based on tumor response assessed by diffusion MRI. In this work, we demonstrate for the first time the preliminary feasibility of a longitudinal diffusion MRI strategy using ViewRay for assessing patient response to radiotherapy.

We implemented a spin echo (SE)-based diffusion sequence on the ViewRay 0.35 Tesla MRI system (18 mT/m maximum gradient and 200 mT/m/ms max slew rate) using a single-shot echo planar imaging (EPI) readout. The diffusion encoding gradients were symmetrically played on both sides of the refocusing radiofrequency (RF) pulse of the spin echo. The sequence was tested in a diffusion phantom and subsequently used for in vivo studies.

Six patients (3 head and neck cancer, 3 sarcoma) who underwent fractionated radiotherapy were enrolled in this study. The pulse sequence parameters included: flip angle=90°, echo time (TE) = 160ms, repetition time (TR) = 2600ms, slice thickness=6 mm, EPI factor=128, field of view (FOV) = 350 mm × 350 mm, b-values = 0, 100, 200, 300, 400, 500 s/mm², 5 averages and total scan time of 70 seconds for all 10 slices. The same pulse sequence was used to acquire longitudinal diffusion data (every 2-5 days) on the 6 patients throughout the entire course of radiotherapy (ranging from 8-35 fractions). Regions of interest (ROIs) were drawn in the tumor on the diffusion images based on the GTV contours from each patient’s standard clinical simulation. To evaluate the reproducibility and reliability of our ADC measurements, a separate reference ROI was drawn in the brain stem for the three head and neck cancer patients. The ADC values for these reference ROIs were not expected to change over the course of the treatment and were used to assess the reproducibility of our ADC measurements.

In diffusion phantom studies, the ADC values measured on the ViewRay 0.35T system matched well with reference ADC values acquired on 3T with <5% error for a range of ground truth diffusion coefficients of 0.4 - 1.1 ×10^-3 mm²/s.

All the patients in this study completed the longitudinal diffusion MRI with no complications. Each patient underwent 4 - 7 diffusion MRI scans depending on their treatment length. Figure 1 shows ADC maps from a 45 y.o H&N cancer patient acquired at 7 time points during the course of treatment. The patient had squamous cell carcinoma (SCC) of the left maxillary sinus. The brainstem ADC values remained stable throughout the treatment and the mean brainstem ADC was between 0.47 ×10^-3 mm²/s and 0.57 ×10^-3 mm²/s for all 7 times points, which confirms the reproducibility of our ADC measurements. The mean ADC for the tumor, however, increased from 1.3 ×10^-3 mm²/s at the 4th fraction to 1.6 ×10^-3 mm²/s at the 31st fraction. In another head and neck cancer patient shown in Fig. 2, the brainstem ADC values also remained relatively stable throughout the treatment (between 0.49 ×10^-3 mm²/s to 0.56 ×10^-3 mm²/s); however, the tumor ADC value substantially decreased from 1.5 ×10^-3 mm²/s at the 2nd fraction of the treatment to 1.0 ×10^-3 mm²/s at the 29th fraction (33% reduction).

We hypothesize that for large tumors, our ADC maps may be used to assess localized treatment response for tumor subregions. Figure 3 shows a sarcoma patient with a 32 x 22 x 14 cm³ tumor. The simulation CT image (Fig. 3a) did not differentiate well between tumor and surrounding normal tissue. The diffusion-weighted image (Fig. 3b, b=500) clearly shows the hyper-intense tumor that matched well with the patient’s gross tumor volume (GTV) contour, which was drawn by a clinical radiation oncologist based on the simulation CT. In the corresponding ADC map (Fig. 3c); there was considerable heterogeneity within the tumor. The ADC values within the right lateral region of the tumor had much higher ADC values than other regions.

We demonstrated that longitudinal diffusion MRI on a weekly basis or more often is feasible at 0.35 Tesla using the ViewRay system. Our longitudinal diffusion data show different temporal variations in ADC values during the course of treatment. Larger patient cohort studies are warranted to correlate our longitudinal diffusion imaging to patient outcome and tumor control. Such an approach may overcome many of the scientific and practical challenges of diffusion MRI-based adaptive radiotherapy.