## 4 Discussion  
In this study, a novel quantitative metric obtained from SPECT V/Q images is proposed for the diagnosis of CTEPH. The metric is based on the volumetric data obtained from SPECT images that were shown to be more sensitive than planar imaging for detecting obstructed segments due to CTEPH [19]. To obtain the optimal segmentation thresholds for the ventilation and perfusion volumes of the SPECT images, a reference group was defined composed of cases without discordant defects in the pulmonary SPECT images. It is important to bear in mind that the reference group was composed of eight women and two men. Therefore, the optimal segmentation thresholds and \(V_{V\cdot P}\) reference values were more representative of a female population. This gender imbalance had a great influence on the overall classification results of the patients of the second and third group. This can be explained by the anatomical differences between female and male lungs, as the former are generally smaller [20]. Concretely, the algorithm overestimated possible defects in men because obstructed segments of the same anatomical extent in both genders tend to be greater in men and thus, the difference between ventilation and perfusion volumes was higher. Moreover, the difference needed to be much higher in women to receive a positive diagnosis. This can be observed in the results and gender distribution after applying the obtained reference values to the patients diagnosed with CTEPH or a respiratory pathology. In the case of the patients diagnosed with CTEPH, 6 of the 12 cases were classified as \"positive\" and 2 yielded a \"cannot be ruled out\" result. Regarding the gender distribution, 5 of the 8 men were correctly classified and the positive diagnosis could not be ruled out for an additional case. It is also noteworthy that only one of the patients classified as positive with certainty was a woman. Out of the three other women, for one a positive diagnosis could not be ruled out and two received a negative \begin{table}
\begin{tabular}{c c c c c} \hline \hline  & \multicolumn{2}{c}{**Patient 1**} & \multicolumn{2}{c}{**Patient 2**} \\ \hline  & **Left Lung** & **Right Lung** & **Left Lung** & **Right Lung** \\ \hline \(V_{pre}\) (cm\({}^{3}\)) & 443.04 & 335.41 & 1075.04 & 2924.69 \\ \(V_{post}\) (cm\({}^{3}\)) & 999.44 & 1488.33 & 612.37 & 1112.32 \\ \(V_{post-pre}\) (cm\({}^{3}\)) & 556.40 & 1152.93 & \(-\)43.04 & \(-\)1812.36 \\ Improvement (\%) & 12.57 & 77.46 & No improvement & No improvement \\ \hline \hline \end{tabular}
\end{table} 
Table 6: Perfusion volumes before and after treatment for CTEPH. Figure 4: Perfusion SPECT images pre-treatment (left) and post-treatment (right). The contour of the segmentation is drawn in green in the images and the color bar. (**a**) Patient 1 (right lung). (**b**) Patient 2 (left lung). diagnosis. As can be seen by this distribution, most correctly classified cases corresponded to the male patients. The same pattern can be observed when analyzing the results of the cases diagnosed with respiratory pathologies. Both men who were included in this group were correctly diagnosed with a respiratory pathology. All cases that received a negative diagnosis corresponded to female patients. Moreover, in two cases, the algorithm detected a larger ventilation volume than perfusion volume, which indicates a possible CTEPH and not a respiratory pathology. In addition to the gender imbalance of the reference group, both groups used for the validation were also not composed equally of women and men. This led to the relatively low sensitivity values, due to the aforementioned overestimation of defects in male patients. Therefore, it can be stated that the main limitation of this study was the composition of the study groups. Not only were they heterogeneous regarding the gender of the patients, but the reference group also consisted of only 10 patients, which included cases of normal lung function and concordant defects present in the SPECT images.