Epidemiology:
In total, datasets from 344 patients with thoracolumbar spinal fractures were analyzed (mean age 68 years (range 23 – 92), 130 male, 214 female). 323 patients had native CT scans and qCT. Five patients had all modalities available (native CT, qCT and contrast CT) and 16 had only qCT and contrast CT. Twenty-one patients (12 male, 9 female) received a contrast CT scan.
CT scanner model:
A subgroup of 164 patients (CT One: 106, CT Prime: 58) was analyzed to assess the impact of the scanner device on HU values. No significant differences were found in the analyses to determine the comparability of HU determinations between CT scanner models (F(1, 162)=0.972, p=0.326) and observers (F(3, 486)=1.467, p=0.223).
In the subgroup of stratified 164 patients the qCT values were similarly unaffected by the CT scanner model. The univariate ANOVA showed no significance (p=0.761). Imaging obtained with either scanner (CT One: n=211, CT Prime: n=133) was therefore deemed suitable for inclusion in the further analyses.
Slice thickness:
In total data from 344 patients were analyzed to determine the effect of slice thickness on HU and qCT values. The analyzed dataset contained 14 CT scans with a slice thickness of 2mm (without CM), 317 with a slice thickness of 3mm (without CM=311, with CM=8) and 13 with a slice thickness of 5mm (all with CM). The presence or absence of CM was used as the covariate.
For the HU values, the rmANOVA showed no significance for slice thickness (F(2, 340)=0.004, p=0.996). The second main effect (observer) showed non-significance (F(3, 1020)=1.225, p=0.299). The covariate also showed no significant effect (F(1, 340)=3.336, p=0.069). For the qCT values, no significance was found, neither for slice thickness (F(2, 340)=0.058, p=0.943) nor for the covariate (F(1, 340)=, p=0.361).
In conclusion, no significant effects of slice thicknesses on HU values or qCT values could be determined. As a result, datasets of varying slice thicknesses were included in the further analyses.
HU values from native CT scans:
Results based on native and contrast CT scans will be presented separately. Firstly, determinations from native scans will be considered.
The lowest and highest absolute measured HU values without CM of the four observers were very close to one other. The smallest measured HU values differed by 10 units between the four observers, between -14 and -24 HU. The highest measured values were also very close to each other and varied between 250 and 267 HU. A detailed overview is given in Table 1.
Inter-rater reliability of HU measurements from native CT scans:
The inter-rater reliability for HU measurements from native CT scans was very high (ICC(3, 1)=0.932, CI95: 0.919 – 0.943, p<0.001). The inter-item correlation matrix is shown in Table 2.
Linear regression (native CT scans):
To predict qCT values from HU (native Scans) a linear regression for each observer was performed. A detailed overview is given in Table 3. Very high correlation between qCT and HU values was found for each observer. By averaging the constants and factors of the observers, a general equation for the prediction of qCT values from HU in the absence of CM was generated:
qCT=0.8·HUnative+5.
The measured density attenuation in HU for native CT scans across the four observers with linear regressions and their CI95 are shown in Figure 1(a).
Predicting qCT from HU derived from native CT scans:
Based on the linear regression model and the predicted qCT values obtained using the general equation above, the bivariate correlation showed significant correlation (p<0.001) between the measured and predicted qCT values for each observer (Table 4). High correlation between measured and predicted qCT values was found. The mean r was 0.91±0.03. The mean predicted qCT values were between 81±30 and 84±33, depending on the observer.
ROC analysis (native CT scans):
In our cohort of 328 patients, 171 (52%) were assigned a diagnosis of osteoporosis (i.e., qCT<80). For each observer, statistical significance could be shown regarding prediction of osteoporosis (p<0.001). The area under the curve (AUC) ranged from 0.94 to 0.98 among raters. The ROC curves for each rater are shown in Figure 2(a). All four ROC curves, based on HU measurements from native scans to predict qCT-confirmed osteoporosis, lay close together. The best positive predictive value (PPV) was obtained using 93 HU as the cut-off value. The maximum sensitivity and specificity of 0.91 and 0.93, respectively, were found with a cut-off value of 93 HU. The sensitivity and specificity for each observer are provided in Table 5. One observer reached a PPV of 93%, representing very high concordance. The PPV of the other observers reached agreement levels between 65 and 69%. The NPVs were quite similar between the observers and were between 90 and 100%.
HU values from contrast CT scans:
For the assessment of HU derived from contrast CT scans, integer matched pairs could be found for the 16 cases for which native CT scans where not available. The qCT values matched identically except for two patients. In one matched pair the qCT value was 1 value less and in the other the qCT value was 2 higher. The minima (qCT=17), maxima (qCT=121), mean (qCT=72) and standard deviation (qCT=26) were identical in both groups (contrast enhanced and native scans).
The smallest measured HU values were even closer between the four observers than seen for native scans and differed just by 6 units (from 55 to 61 HU), as shown in Table 1. In contrast, the maxima differed between the observers by 48 units, from 179 to 227. Nevertheless, the mean values were again very close.
Inter-rater reliability of HU measurements from contrast CT scans:
For HU measurements from CT scans with CM, the ICC(3,1) was 0.889 (CI95: 0.801 – 0.948, p<0.001), demonstrating very good inter-rater reliability. The inter-item correlation matrix for the HU values from scans with CM is shown in Table 2.
Linear regression (contrast CT scans):
In patients with contrast CT scans, qCT values between 17 and 121 with a mean of 72±26 were measured. Twelve of 21 patients (57%) had qCT values below 80, consistent with osteoporosis. The measured density attenuation in HU for contrast CT scans across the four observers with linear regression is shown in Figure 1(b). The correlation between qCT and HU for contrast scans showed, as for the native scans, very good predictability. Averaging the constants and factors of the observers (Table 3) allowed the formulation of a general equation for the prediction of qCT values based on HU in the presence of CM:
qCT=0.6·HUcontrast enhanced-4.
Predicting qCT with HU from contrast CT scans:
For the predicted qCT values using the generalized equation for HU values in the presence of CM, the bivariate correlation showed significant correlation (p<0.001) between the measured and predicted qCT values for each observer (Table 4). High correlation between measured and predicted qCT values was shown. The mean r was 0.86±0.04. The mean predicted qCT values were between 68±22 and 71±24, depending on the observer.
ROC analysis (contrast CT scans):
Classification showed that in this cohort of 21 patients, there were 12 (57%) with osteoporosis (qCT<80). The ROC-analysis showed significance for each observer (p<0.001). The AUCs were slightly smaller, compared to the AUCs for the cut-off values without CM. Nevertheless, the AUCs were high, ranging from 0.84 to 0.91 (Figure 2(b)). All ROC curves lay quite close together. The maximum sensitivity and specificity calculated using HU in the presence of CM were 0.83 and 0.89 with cut-off of values of 122 or 125 HU, respectively, depending on the observer. The sensitivity and specificity results for each observer are provided in Table 5. The PPV and NPV were quite similar between observers. The highest PPV (91%) was seen for two observers and this PPV was obtained with cut-off values of 122 and 125 HU. The NPVs were slightly lower (80%), again using 122 and 125 HU as the cut-offs.