Fig. 4

Multimodality imaging and histopathology after injection of ¹⁶⁶Ho microspheres in patient number 3. a Unenhanced computed tomography (CT); microspheres are visible as hyperdense area on the left side of the tongue (arrow). b Single-photon computed tomography/CT; the location of the microspheres dose distribution is observed as a large hotspot. c Magnetic resonance imaging; with dose reconstruction derived and overlaid on this image, obtained with a T2* multi-gradient echo weighted sequence acquiring 16 echoes (TR/TE1/ΔTE: 1000 ms/1.33 ms/1.15 ms; flip angle 70°), the black centre has ¹⁶⁶Ho microsphere concentration > 10 mg/ml, resulting in a rapid signal loss restricting the nonlinear least squares (exponential) fit to compute a T2* value and thus a dose value. d Histopathology. The haematoxylin and eosin staining shows a moderately differentiated and partly invasive growing oral squamous cell carcinoma with clusters of ¹⁶⁶Ho microspheres. The black arrow indicates purple spherical structures that are sliced microspheres. The white arrow indicates white spherical structures that are partly or totally removed microspheres by slicing the tissue in 4-μm slices. In the direct environment of the microspheres, a necrotic tissue is seen, while the periphery is unaffected by radiation. Infiltration of lymphocytes is most likely radiation unrelated and often seen in oral squamous cell carcinoma [18]