Impact of MRI head placement on glioma response assessment

Abstract

Diagnosis of progressive disease or (partial) response during tumor treatment is based on manual size estimates of enhancing tumor area: an expert measures two perpendicular diameters of the enhancing tumor region in a single MRI slice with the largest enhancing area. This paper analyzes the reliability of the area measure with respect to head placement in the MRI scanner and compares it with 3D volume measures in a dataset of eight subjects (5-7 follow-up scans each) with high-grade glioma. We show that the manual area measure is highly sensitive to head position changes, with a root mean squared error of 22%, compared to volume estimates with less than 5% error. In our simulated study using the 2D manual measurements, the majority of subjects would have been incorrectly diagnosed with progressive disease without any true anatomical changes. These results highlight the urgent need for revised and more reliable response assessment criteria, for example, based on increased slice resolution, 3D volume analysis and percent change computation with respect to an average of patient specific longitudinal measurements instead of a single measurement to define progression or response.

Fig. 1

Example of measuring perpendicular diameters of the identical tumor in three different head positions (columns). The top row depicts the irregular 3D tumor shape and approximate location of the imaging slices. For each head position we show horizontal slices at the superior, middle, and inferior tumor regions (rows). Depending on the position of the head (and resulting slice position), the identical tumor appears to look different in the images, affecting location and size of the nodule with the largest diameter. Note, that RANO measurements should not include the cystic center.

Fig. 2

Methods flow chart: First the baseline MEMPRAGE gets mapped to a follow-up location and resliced to 5mm and 1mm slices. The 2D RANO measure is performed manually only on the 5mm sliced intensity image, the 3D volume analysis (automatic label update and volume computation) is performed on both the 5mm and 1mm sliced images.

Fig. 3

Axial slice showing enhancing tumor (left). The corresponding coarse label of enhancing region (middle, blue) is improved by our automated classification (right, blue).

Fig. 4

Apparent percent change (actual tumor change is 0%) of repeated measures per subject (IDs 1–8). Plots (a,c) show percent increase of contrast enhaning area (2D RANO) computed with respect to the smallest measure in each subject and (b,d) percent area decrease with respect to the largest measure (for rater 1 top row, and rater 2 middle row). Short dashed lines show the mean for each subject. Thick dashed red lines indicate the 25% increase of progressive disease (a,c,e,f), and 50% decrease of a partial response (b,d). Measurements above (or below) these thresholds are circled in red. All subjects would be “progressing” in (a) and 4 subjects in (c) (plot (c) is clipped at 150%, maximum increase in subject 5 is 203%). Plots (e,f) show apparent percent increase in 3D volume with respect to the smallest measure for thick (e) and thin (f) image slices.