Herein, we used two rat-based CXM strains of breast cancer, SSIL2Rγ−(Dll4+) and SS.BN3IL2Rγ− (Dll4−) [7,38,50], as well as eight congenic xenograft strains, CG1–CG8 (Figure 1a,b), to assess the impact of germline TME vascular heterogeneity on the signal intensity of DE-NIR imaging with systemically delivered ICG. The gene discussed is DLL4; the disease is breast cancer.