4.3 Amyloid PET normalisation
4.3.1.4 Data analysis
SUVR values were calculated for all segmented regions using a 10% trimmed mean value. Left and right regions were combined for the purposes of analysis in order to compare the results with that of Vandenberghe et al. [2010a]. The SD across subjects in a group was also calculated. The [18F]flutemetamol WM analysis was carried out using cerebellar GM
normalisation. The SWM and cerebellar white matter (CWM) were evaluated through SUVR analysis and also by linear regression.
Both SUVR and linear regression analysis were performed for the [11C]PIB \
[18F]flutemetamol comparison. The MCI group was sub-divided into amyloid-positive
(n = 9) and amyloid-negative (n = 11) groups. The division was carried out using the SUVR threshold as described in section 4.1.2.2 (page 93). All images were normalised and analysed using MATLAB R2010b (Mathworks, Natick, M.A., USA). Statistical analysis was performed in MATLAB and G*Power. Where the MDD was calculated, a power of 90% and p< 0.01 was assumed. The linear regression analysis was performed between the [11C]PIB
and[18F]flutemetamol SUVR for all 40 subjects, for each of the three reference regions under evaluation. The assessed regions were the cerebellar GM, SWM and brain stem.
In the tracer comparison, the differences in CWM and SWM were reported in terms of a cerebellar WM to sub-cortical WM ratio (WMR), defined as:
WMR= cerebellar WM
sub-cortical WM (4.1)
The WMR was calculated using the non-normalised images of each subject, with and without PVC, for both tracers. The mean WMR and SD across subjects within a group was calculated. The results of the linear regression were reported in terms of the slope of the line (m), corre- lation coefficient (r ) and the normalised standard error of the estimate (NSEE) was calculated
4.3. Amyloid PET normalisation 109 using the sum of square errors normalised to the mean of the data. TheN SE E is defined as:
N SE E = 1 x q PN i=1(yi− ˆyi)2 N − 2 (4.2)
whereyi is the[11C]PIB value, ˆyi is the predicted value,N is the number of points (N= 40)
andx is the mean of the[18F]flutemetamol values.
4.3.2 Results
4.3.2.1 [18F]flutemetamol white matter analysis
SUVR analysis was performed on the WM regions of the SWM and CWM. As previously described in section 4.1.1.1 (page 89), the HC group was originally sub-divided into elderly and young subjects. Wilcoxon rank-sum tests were performed between the eHC and yHC groups to establish if there was any WM differences within the control group. Tests were performed between the groups for both the SWM and CWM. No significant difference at the p< 0.05 threshold was found for either region (SWM: MDD =0.11; CWM: MDD =0.07). As a result, the controls were considered as a single group for the WM analysis.
Trimmed mean SUVR values were calculated in both WM regions for the AD and HC groups. These values can be seen in table 4.9. The CWM values were consistent across the groups before and after correction. Wilcoxon signed-rank tests were highly significant (p < 0.001) between the regions without PVC. SWM exhibited higher SUVR values than CWM in the AD subjects. This pattern was reversed in control subjects.
When RBV correction was applied, both subject groups had a higher CWM than SWM SUVR. No significant (p> 0.05) difference was found between the AD and HC group, for either region, after PVC. However, Wilcoxon signed-rank tests between the regions of both subject groups exhibited highly significant differences (p< 0.001).
Uncorrected RBV Cerebellar WM AD 1.96 ± 0.16 2.30 ± 0.30 HC 1.98 ± 0.13 2.35 ± 0.23 Sub-cortical WM AD 2.17 ± 0.22 2.01 ± 0.32 HC 1.78 ± 0.09 2.01 ± 0.22
Table 4.9: White matter SUVR values[mean ± SD] in AD and control groups, with and without RBV PV-correction.
In addition to an SUVR analysis of the WM regions, a linear regression analysis was per- formed for RBV-corrected and the uncorrected data. The results can be seen in figure 4.6.
4.3. Amyloid PET normalisation 110 A much stronger relationship between SWM and CWM was observed after RBV correction. The correlation coefficient increased from 0.51 to 0.82 for the HC group and from 0.37 to 0.89 for the AD group. The changes in correlation coefficient were compared using the ¯Z2∗ test for differences between dependent correlations proposed by Steiger[1980]. The increases in correlation coefficient after PVC were highly significant (p< 0.001) for both groups. Be- fore PVC, the HC and AD groups appear distinct. After RBV correction, this distinction disappears, and suggests that disease has no influence on the true signal in WM. The higher SWM values in the AD group are due to PVEs as they are not observed in the PV-corrected data.
4.3.2.2 [11C]PIB and [18F]flutemetamol comparison
All cortical GM regions exhibited strong agreement during linear regression analysis between [11C]PIB and [18F]flutemetamol SUVR values. Figure 4.7 shows the linear regression analysis
of the composite cortical region, for each reference region, with and without PVC. The agreement was observed for each of the three reference regions, irrespective of whether PVC had been applied. In WM regions, the weak agreement between the two tracers was further reduced after PVC (see figure A.1, page 167). The results of the linear regression analysis are shown in table 4.10. The RBV-corrected and uncorrected SUVR images of both tracers from an AD subject are shown in figure 4.8.
In terms of reference regions, the brain stem produced the lowestN SE E values (table 4.11) after PVC, suggesting that of the three regions, brain stem normalisation resulted in the strongest agreement between the tracers. Assessing the slopes of the lines, both cerebellar GM and brain stem normalisation were consistent before and after RBV correction. SWM normalisation exhibited greater changes in slope when comparing the uncorrected with the RBV-corrected data.
Further F-tests were performed on theN SE E values. The N SE E2values were evaluated for each pair of reference regions (cerebellar GM vs. SWM, cerebellar GM vs. brain stem and SWM vs. brain stem), with and without PVC. For the uncorrected data, comparison of the cerebellar WM to both the brain stem (F(1,39) = 6.61) and SWM (F(1,39) = 12.96) achieved significance at the p< 0.05 threshold. Given the lower N SEE values of the brain stem and SWM, this suggests that these reference regions result in stronger agreement between the two tracers. The comparison of brain stem to SWM did not reach significance. When assessing the RBV-corrected data, only the comparison between cerebellar GM and the brain stem reached significance (F(1,39)= 5.76). This suggests that PVC makes the three reference regions become more similar to each other, at least in terms of their spread about the regression line. The
4.3. Amyloid PET normalisation 111 ‘dissimilarity’ in the PV-uncorrected reference regions may therefore be logically attributed to PVEs.