4.4 Comparison of Multiple Extravasation Correction Methods in Patient Data
4.5.1 Conformity between First and Second Bolus
In order to characterize the curve shapes of time series acquired during the first and second dose, the summary parameters rPH and rPSR (section 3.1.1) were compared in CET. A weakly significant difference was found for rPSR, which is an indicator for extravasation effects. Figure 4.12-B shows that rPSR values of the first and the second bolus are higher and lower than one, respectively. With respect to the evolution of rPSR, this indicates a signal overshoot (T1 effects) for the first bolus acquisition. For rPH, being proportional to CBV, values were comparable between both acquisitions (Figure 4.12-A).
Figure 4.12: Boxplots of rPH (A) and rPSR (B) in VOICET for the first and second bolus (n = 8).
A significant difference was only found for rPSR (p < 0.05, Wilcoxon signed rank test). The bold line indicates the median, the box covers the range between the 25th and 75th quantile, and the whiskers reach from minimum to maximum.
With regard to CBV, the use of a pre-bolus reduced the variance across patients. In nearly all VOIs and patients, the absolute CBV values were higher for data acquired with PB (CBV2nd). The post-processing reduced, but did not eliminate this difference between CBVs of both boli. Therefore, after leakage correction the CBV values calculated from the first bolus (CBV1st) were still smaller than the CBV values calculated from the second bolus (CBV2nd). VOI- and voxel-wise correlations between CBV values, obtained using
Evaluation of Post-Processing Methods Using Two Boli
the first and the second bolus, were improved after post-processing (rCET,before ≤ 0.5, rCET,after ≥ 0.6), except for method IV.
Similar to absolute CBV, nCBV1st (without PB) was smaller than nCBV2nd (with PB).
The post-processing methods reduced the variance of nCBV within the tumor regions as well as between patients compared to the corresponding uncorrected nCBV values.
Applied to data without PB, post-processing predominantly increased nCBV values.
Uncorrected nCBV maps calculated from the first bolus acquisition demonstrated many zeros (clipped negative values). The leakage correction eliminated or at least reduced the amount of those zero values (Figure 4.13). Following, in VOICET the averaged nCBV values of all patients (n = 8) and methods increased by about 52 % from 2.1 ± 1.2 % (without correction) to 3.2 ± 0.7 % (with post-processing correction). For acquisitions with PB, nearly all correction methods reduced nCBV values. Averaged over all correction methods of the same patients, nCBVCET was 6.0 ± 0.8 % before and 5.3 ± 1.0 % (-12 %) after leakage correction.
Figure 4.13 shows one example of voxel-wise correlations between nCBVCET of the first and second bolus for three correction methods and the corresponding uncorrected data.
The correlation coefficient r increased after post-processing correction from 0.67 to 0.98 (A), 0.46 to 0.92 (B) and 0.49 to 0.71 (C). In most comparisons of nCBV1st and nCBV2nd, voxel values correlated significantly with each other (p < 0.001). The worst correlations were encountered for method IV. The strongest correlations combined with the highest accordance between nCBV values obtained from both boli (RPC < 2.8 %) were found for method I (Figure 4.15-B).
Figure 4.13: Effect of post-processing leakage correction for one representative patient.
Voxel-wise correlations of nCBV values (normalized to healthy WM) in contrast enhancing tissue (CET) between 1st and 2nd bolus before (blue) and after leakage correction (red) with different methods: (A) method I, (B) method III (sSVD, ATC), (C) method III (TiSVD, ATC).
Figure 4.14 represents a single slice of one exemplary patient for all acquisitions and all post-processing methods. On the one hand, the described discrepancies can be observed
between methods and acquisition modes. On the other hand, also the homogenizing effects of the second bolus and the first pass integration range are visually perceptible.
Figure 4.14: One slice of an exemplary patient with glioblastoma. The rows present complete overviews of all investigated leakage correction methods. Upper two rows: full time course integration range for the first and second bolus acquisitions. Bottom two rows: first pass only integration range for the first and second bolus acquisitions. nCBVunc 2 is only shown for sSVD calculation (other three maps were visually similar). w/o ATC = without arrival time correction. Colorbar shows nCBV values in %.
For DSC acquisitions with PB, the integration range was shown to have a high impact on absolute CBV (chapter 4.4.4). Without an initial pre-dose (CBV1st) the differences were much higher. Generally, absolute CBVfp values were again larger than CBVfull values, irrespective of whether they were uncorrected or corrected for leakage. In healthy tissue, the integration range affected SVD-based techniques to a lesser extent.
In CET, if uncorrected for leakage, estimated CBVs integrated over the full time course were smaller for both boli. Exceptions were values of CBVunc 2 that were based on TiSVD.
Here, CBV1st increased and CBV2nd decreased using first pass integration. Although differences between both boli diminished for all uncorrected CBVs using first pass integration, TiSVD-based methods showed the smallest absolute deviations.
Furthermore, the correlation coefficient between CBVunc 1 values of the first and second bolus increased from rfull = 0.34 (full integration) to rfp = 0.86 (first pass integration). The correlation coefficient between CBVunc 2 values of the first and second bolus also slightly increased with first pass integration, but remained below 0.1.
Evaluation of Post-Processing Methods Using Two Boli
Figure 4.15: Boxplots of differences between extravasation corrected CBV values of 1st (CBV1st) and 2nd bolus (CBV2nd) for two integration intervals in VOICET. (A) Differences of absolute CBVs and (B) normalized CBVs for first pass integration (blue) and full time course integration (green). The boxes contain all values between the first and third quartile, the line inside marks the median, the whiskers reach from minimum to maximum and circles are outliers. The gray diamonds indicate individual patient averages (n = 8) and the horizontal dashed gray lines indicate zero difference.
Combining leakage correction and first pass integration usually improved the accordance between absolute CBV values obtained from both boli (Figure 4.15-A). Only methods I and III (sSVD, ATC) resulted in increased median differences if integration was restricted to the first pass. CBV1st and CBV2nd agreed best with method IV using the first pass integration. Here, besides the similarity of absolute values also the correlation increased compared to that obtained with full integration (rfull = 0.14 to rfp = 0.72).
The first pass integration also homogenized nCBV values, especially nCBV1st, among all correction methods. Figure 4.14 illustrates this for one exemplary slice of one patient. For all correction methods, the differences between first and second dose nCBVCET values were clearly reduced (Figure 4.15-B). Normalized CBVmethod I values showed nearly no difference between both integration ranges. Overall, using the first pass integration, nCBV maps seemed to be less noisy, especially for data acquired with the smaller first CA dose (Figure 4.16).
Figure 4.16: One slice of an exemplary patient with glioblastoma showing the influence of the integration intervals (full time course versus first pass only) on normalized CBV. First row: nCBVunc 1 and nCBVmethod IV for the first bolus. Second row: nCBVunc 1 and nCBVmethod IV
for the second bolus.