Persistent homology index as a robust quantitative measure of immunohistochemical scoring

Immunohistochemical data (IHC) plays an important role in clinical practice, and is typically gathered in a semi-quantitative fashion that relies on some degree of visual scoring. However, visual scoring by a pathologist is inherently subjective and manifests both intra-observer and inter-observer variability. In this study, we introduce a novel computer-aided quantification methodology for immunohistochemical scoring that uses the algebraic concept of persistent homology. Using 8 bit grayscale image data derived from 90 specimens of invasive ductal carcinoma of the breast, stained for the replicative marker Ki-67, we computed homology classes. These were then compared to nuclear grades and the Ki-67 labeling indices obtained by visual scoring. Three metrics for IHC staining were newly defined: Persistent Homology Index (PHI), center coordinates of positive and negative groups, and the sum of squares within groups (WSS). This study demonstrates that PHI, a novel index for immunohistochemical labeling using persistent homology, can produce highly similar data to that generated by a pathologist using visual evaluation. The potential benefits associated with our novel technology include both improved quantification and reproducibility. Since our method reflects cellularity and nuclear atypia, it carries a greater quantity of biologic data compared to conventional evaluation using Ki-67

Accurate delineation of mucosal lesions in treatment planning computed tomography using iodine paste markers for oral mucosal melanoma

We introduce the utility of iodine paste markers using endodontic materials for the accurate contouring of mucosal lesions of oral mucosal melanoma (OMM), which are difficult to delineate on imaging during the planning of carbon-ion radiation therapy (CIRT). The patient had a primary OMM located in the palatal mucosa without palatal or maxillary bone invasion. A dental root canal filling material, which is a calcium hydroxide/iodoform non-hardenable paste, was used as a marker. We first performed treatment planning computed tomography (CT) without an iodine paste marker for mucosal lesions. Subsequently, we placed an iodine paste marker on the palatal mucosal lesion to accurately delineate the mucosal lesions of the palate. Finally, we took reference CT with an iodine paste marker. CT without the marker was fused to the reference CT with markers during treatment planning, and the gross tumor volume (GTV) was contoured. Thereafter, CIRT was delivered without markers. During CIRT, expected acute mucositis was observed in the area of the planning target volume (PTV), including melanosis, in accordance with the dose distribution. The use of iodine paste markers for localized mucosal lesions, which are difficult to delineate on CT and MRI, may be useful for contouring GTVs on treatment planning CT accurately