Dynamic Changes in Microvascular Density Can Predict Viable and Non-Viable Areas in High-Risk Neuroblastoma

Simple Summary Neuroblastoma (NB) is the most common extracranial tumor in children. Despite the development of new therapeutic options, high-risk patients still have poor long-term survival. Distinguishing viable malignant tissue from necrotic areas and surrounding healthy tissue is pivotal during surgery. Variations in the tumor vascular architecture could guide surgeons to remove only viable tumor regions, achieving a safer and more efficient resection. In this paper, using histopathology scanned slides, we first examined variations in the vasculature density of different tumor regions, showing that viable and necrotic areas are associated with a distinct vascular signature. Then, we scanned an excised human NB specimen using a custom-made high-definition preclinical imaging device based on photoacoustic imaging, which is ideal for imaging vasculature, showing that the acquired images can differentiate macroscopic regions within the tumor. Despite aggressive treatments, the prognosis of high-risk NB remains poor. Surgical oncology needs innovative intraoperative devices to help surgeons discriminate malignant tissue from necrotic and surrounding healthy tissues. Changes within the tumor vasculature could be used intraoperatively as a diagnostic tool to guide surgical resection. Here, we retrospectively analyzed the mean vascular density (MVD) of different NB subtypes at diagnosis and after induction chemotherapy using scanned histological samples. One patient was prospectively enrolled, and an ex vivo photoacoustic imaging (PAI) scan was performed on two representative sections to assess its capacity to discriminate different tumor regions. We found that post-chemotherapy, viable areas of differentiating NBs and ganglioneuroblastomas are associated with higher MVD compared to poorly differentiated NBs. Early necrotic regions showed higher MVD than late necrotic and viable regions. Finally, calcified areas showed significantly lower MVD than any other histological component. The acquired PAI images showed a good high-resolution ex vivo 3D delineation of NB margins. Overall, these results suggest that a high-definition preclinical imaging device such as PAI could potentially be exploited to guide surgical resection by identifying different vasculature signatures.