## Materials and Methods
### Spatial Correlation  
The spatial correlation between labeled microdamage in paired BSE and \(\upmu\)CT images (i.e., from the same sample) was determined using a probability-based method [38,39]. All calculations and comparisons were performed within image pairs. For each sample, there were four imaging modalities: baseline \(\upmu\)CT parameters, enhanced \(\upmu\)CT parameters, enhanced \(\upmu\)CT parameters, enhanced \(\upmu\)CT parameters with deblurring, and BSE imaging. The probability of observing labeled microdamage in a \(\upmu\)CT image within some radius of labeled microdamage in a BSE image was determined for all labeled voxels. Additionally, the probability of observing labeled microdamage in a BSE image within some radius of labeled microdamage in a \(\upmu\)CT image was determined. Probabilities were calculated at radii of 0, 10, 20, 30, 40, 50, and 60 \(\upmu\)m from labeled pixels, chosen based on the trabecular thickness and the \(\upmu\)CT spatial resolution. To demonstrate, Figure 2 shows the label fields used for the probability of spatial correlation calculations at a 30 \(\upmu\)m radius between a BSE and enhanced \(\upmu\)CT image. To model varying radii considered as correlated, \(BaSO_{4}\) labeled pixels in one image (i.e., the BSE image in Figure 2a, the enhanced \(\upmu\)CT image in Figure 2b) was \"inflated\" using convolution with circular kernels with radii of 10-60 \(\upmu\)m. The probability of observing spatially close pixels was calculated as the relative number of intersecting \(BaSO_{4}\)-labeled pixels in paired images. As the inflation radius increases, more pixels in the inflated image are labeled as \(BaSO_{4}\), thus increasing the likelihood that a \(BaSO_{4}\)-labeled pixel in the non-inflated image will intersect. The probability is calculated twice for each pair to ensure mutual correlation. Figure 2a shows the label fields used to calculate the probability that \(BaSO_{4}\)-labeled pixels in an enhanced \(\upmu\)CT image fall within 30 \(\upmu\)m of \(BaSO_{4}\)-labeled pixels in a BSE image. Figure 2b shows the label fields used to calculate the probability for the opposite direction, namely that \(BaSO_{4}\)-labeled pixels in a BSE image fall within 30 \(\upmu\)m of \(BaSO_{4}\)-labeled pixels in an enhanced \(\upmu\)CT image.  
Figure 1: Stain segmentation procedure on an enhanced \(\upmu\)CT image. (**a**) unlabeled enhanced \(\upmu\)CT image with background removed; (**b**) bone label field (blue) less than 50 \(\upmu\)m of the outer edge of the cortical shell (light green); (**c**) labeled \(BaSO_{4}\) (light blue) used for damage volume fraction calculations and showing excluded \(BaSO_{4}\) contrast (green).  
Figure 2: Label fields used to calculate spatial correlation probability of \(BaSO_{4}\)-labeled pixels between BSE and enhanced \(\upmu\)CT images at an inflation radius of 30 \(\upmu\)m. (**a**) the probability of \(BaSO_{4}\)-labeled pixels in an enhanced \(\upmu\)CT image (blue) being within 30 \(\upmu\)m of \(BaSO_{4}\)-labeled pixels in an inflated BSE image (white). The probability of spatial correlation is calculated as the ratio of red to blue pixels. (**b**) the probability of \(BaSO_{4}\)-labeled pixels in a BSE image (white) being within 30 \(\upmu\)m of \(BaSO_{4}\)-labeled pixels in an inflated enhanced \(\upmu\)CT image (blue). Red areas represent overlapping \(BaSO_{4}\)-labeled pixels in both images. The probability of spatial correlation is calculated as the ratio of red to white pixels.  
Damage area fraction (DAF) was defined as the ratio of intersecting bone and _BaSO4_ pixels to bone pixels, described in Equation (1):  
\[DAF=\frac{\#\big{(}p_{BaSO4}\cap\ p_{bone}\big{)}}{\#p_{bone}} \tag{1}\]  
where \(p_{BaSO4}\) is the set of all _BaSO4_-labeled pixels and \(p_{bone}\) is the set of all bone-labeled pixels. DAF was calculated for every modality after each convolution for inflation.