## 3 Results and Discussion
### Histological Image Evaluation of Intratumor Sarcoma-45 Heterogeneity  
Morphological features observed in sarcoma-45 are summarized in Table 6. In the control group, tumor core tissue mainly contained eosinophilic cells, numerous apoptotic bodies and necrotic foci (<20% of the section area), while connective tissue fibers were rare (Figure 6a). In contrast, the tumor core was composed of broad bands of connective tissue fibers in nearly 70% of the section area, large cells with hypochromic nuclei, eosinophilic nonnucleated cells and necrotic foci (<20%) after IMH (Figure 6b). On the tumor periphery, tissue consisted of large cells with hypochromic nuclei, occasionally observed mitotic figures, large masses of eosinophilic nonnucleated cells and minimal ongoing necrosis (<10%) following no treatment (Figure 6c). However, in response to IMH, there were extensive masses of necrosis (<50%) infiltrated with eosinophil nonnucleated cells and commonly observed connective tissue fibers (Figure 6d). As shown in Figure 6e,f, the  
Figure 5: Wavelet transform scalogram of sarcoma-45 blood flow signals in control (**a**) and IMH (**b**) groups. Color bars represent the magnitude of continuous wavelet transform coefficients. \begin{table}
\begin{tabular}{c c c c} \hline
**Group** & **Treatment** & **Mean Blood Flow Velocity, cm/s** & **Resistive Index** \\ \hline
1 & Control (no treatment) & 9.87 \(\pm\) 0.18 & 0.51 \(\pm\) 0.03 \\
2 & IMH & 7.78 \(\pm\) 0.17 * & 0.78 \(\pm\) 0.01 * \\ \hline \end{tabular}
\end{table} 
Table 5: Sarcoma-45 blood flow characteristics, M \(\pm\) m.  
cells also had a 42% lower Ki-67 protein expression in the periphery of the tumor after IMH (53.5 \(\pm\) 0.1 a.u.) than no-treatment (92.4 \(\pm\) 0.2 a.u. ), \(p\) < 0.05. Histological findings in the capsule of untreated tumors (Figure 6g) were similar to those on the periphery. The IMH group presented abundant connective tissue fibers observed alone and surrounding necrotic foci (Figure 6h). These results demonstrate more extensive tumor necrosis, reduced cell proliferation and more pronounced connective tissue replacement in animals subjected to IMH compared to the control group. With regard to spatial heterogeneity, connective tissue fibers are oriented more uniformly in the normal tissue and treatment-induced fibrosis than in the tumor stroma [75]. Figure 6: Histological findings observed in sarcoma-45. H&E, \(\times\)400. Control group ((a)—tumor core; (c)—tumor periphery; (e)–Ki-67 expression in tumor periphery; (g)—tumor capsule) and IMH group ((b)—tumor core; (d)—tumor periphery; (f)–Ki-67 expression in tumor periphery; (h)—tumor capsule): short arrows—nucleated cells; long arrows—nonnucleated cells and karyorrhexis, arrowhead—mitotic figure; dotted arrows—apoptotic bodies; asterisks—nercrotic foci; triangles—connective tissue replacement. These findings are supported by prior work in which radiation-induced fibrosis had higher stiffness than soft-tissue sarcoma [76]. In addition, an earlier study reported a two-fold increase in collagen expression and enhanced connective tissue replacement in animals exposed to a 27 MHz electromagnetic field [77]. Several clinical trials have demonstrated that connective tissue replacement in sarcomas in response to neoadjuvant treatment is associated with a more favorable prognosis [78]. As shown in Table 7, IMH treatment reduced image heterogeneity in the tumor core, periphery and capsule, on average, by 21% in comparison with the control group. Furthermore, there was a 25% decrease in heterogeneity of Ki-67 protein distribution measured by higher values of [PERSON]'s index in immunohistochemistry images (\(p<0.05\)). Consistent with MRI findings (Table 3) and US elastography (Table 4), [PERSON]'s index of core and periphery images after IMH did not significantly differ. Ki-67 is a cell proliferation marker that exhibits a distinct nuclear localization with maximal levels in mitosis and minimal levels in the late G\({}_{1}\) phase of the cell cycle.