*2.7. The Volume of Distribution in Tissue (VT)*

Based on the AICc results, only the *VT* results from the rev2TCM were considered.

The volume of distribution in tissue (*VT*) from the VOIs in the infected (right hind limb) and the control (left hind limb) positions are compared in Figure 10. Generally, the *VT* results for bone infections (osteomyelitis) were close to the identity line, i.e., similar uptake in infection and control tissue. For the soft tissue infections, most points were above the identity line, indicating higher uptake in the infected soft tissues than in the corresponding control tissues, although this result was less clear when the corrected input function was used.

**Figure 10.** Volume of distribution in infected versus control tissues. Data are the *VT* from Equation (6) in infection VOIs and control VOIs. Blue squares are bone VOIs, and red circles are soft tissue VOIs. **Left**: *VT* from fit with the uncorrected input function. **Right**: *VT* from fit with the corrected input function. Positions on the line correspond to equal values for the infection and control positions. The underlying data of the plots can be found in Supplementary Table S4. See Discussion for a comparison of the scales.

Based on the modelling results from uncorrected input function, the *VT* differences between infection VOIs and control VOIs were statistically significant in the soft tissue infections (*p* < 0.0001), but not in the bone infections (*p* = 0.83). More precisely, for soft tissue VOI pairs (*n* = 14), the mean difference <sup>Δ</sup>*VT* = *VT,*infection <sup>−</sup> *VT,*control was 0.18 mL/cm3, with 95% limits of agreement (LOA) from 0.12 to 0.25 mL/cm3. For bone VOI pairs (*n* = 10), the mean difference was 0.005 mL/cm3, with 95% LOA from <sup>−</sup>0.050 to +0.062 mL/cm3. No signs of non-normal distributions were found (*p* > 0.1 for both soft tissue and bone infections).
