## 4 Discussion
To improve the preliminary results presented in this study, the algorithm should be applied separately to women and men. Thus, the segmentation thresholds and reference values for the classification would be gender specific and it can be assumed that the results improve. Another limitation, related to the selected study group, was the exclusion of cases with extensively accumulated radiotracer in the SPECT images. However, less extensive accumulations were still present in some studies and would affect the algorithm. Therefore, an image preprocessing algorithm should be implemented to be able to include these cases and improve the overall performance of the algorithm. Moreover, in this study, only two cases were available for the comparison of the perfusion volumes before and after the treatment. In addition, similar to the previous cases, the segmentation thresholds need to be revaluated. Moreover, volumetric measurements were only partially useful when evaluating treatment response, as it offers no spatial information. While a general improvement could be determined when the perfusion volume increases, the same could not be said when the difference is low. In that case, the obstructed segment could have been resolved by the treatment, but a new one may have appeared. Therefore, no conclusion can be drawn, and the metric needs to be tested with a larger study population. Regarding the metric and results of the present work, it needs to be noted that quantitative volumetric data of both ventilation and perfusion scans were not evaluated in any of the referenced studies [10; 11; 12; 13; 14; 15; 16; 17]. The main image analysis method is a qualitative assessment of the perfusion SPECT and segmental or subsegmental defects, as defined in the clinical guidelines of the EANM [3]. For example, [PERSON] et al. [10] determined a positive or negative diagnosis for CTEPH based on visual interpretation of perfusion SPECT images. [PERSON] et al. [15] also classified the images visually as positive or negative for PE, as the clinical guidelines do not differentiate between acute PE and CTEPH. In [PERSON] et al. [11], the defects in the perfusion SPECT scan are graded on a four-point scale and only planar V/Q scanning is used for quantitative measurements. On the other hand, [PERSON] et al. [17] studied the correlation between the perfusion volume and clinical parameters, but did not include the ventilation information nor conduct a classification procedure based on SPECT images. However, they showed that the perfusion volume is capable of identifying patients with mean PAP greater than 50 mmHg, which is a biomarker of PH (sensitivity, 80%; specificity, 64%). Lastly, the implemented image segmentation algorithm requires further optimization. Thus, preprocessing should be added to remove possible tracer accumulations on the images. Moreover, alternative automatic segmentation algorithms like active contours could improve the detection of the perfused tissue. Computed tomography scans and its anatomical reference are also a useful tool for the quantitative analysis in CTEPH, as proposed in [17]. However, these were not available for the study group.