Abstract
Magnetic resonance imaging (MRI) is frequently used for preclinical treatment monitoring in glioblastoma (GB). Discriminating between tumors and tumor-associated changes is challenging on in vivo MRI. In this study, we compared in vivo MRI scans with ex vivo MRI and histology to estimate more precisely the abnormal mass on in vivo MRI. Epileptic seizures are a common symptom in GB. Therefore, we used a recently developed GB-associated epilepsy model from our group with the aim of further characterizing the model and making it useful for dedicated epilepsy research. Ten days after GB inoculation in rat entorhinal cortices, in vivo MRI (T2w and mean diffusivity (MD)), ex vivo MRI (T2w) and histology were performed, and tumor volumes were determined on the different modalities. The estimated abnormal mass on ex vivo T2w images was significantly smaller compared to in vivo T2w images, but was more comparable to histological tumor volumes, and might be used to estimate end-stage tumor volumes. In vivo MD images displayed tumors as an outer rim of hyperintense signal with a core of hypointense signal, probably reflecting peritumoral edema and tumor mass, respectively, and might be used in the future to distinguish the tumor mass from peritumoral edema—associated with reactive astrocytes and activated microglia, as indicated by an increased expression of immunohistochemical markers—in preclinical models. In conclusion, this study shows that combining imaging techniques using different structural scales can improve our understanding of the pathophysiology in GB.
Highlights
Glial tumors or gliomas represent 80% of all malignant brain tumors [1,2]
The present study shows that the estimated abnormal mass on in vivo T2w images was approximately four times larger in volume compared to histological tumor volumes
As vimentin expression is an early event in normal glial differentiation, while glial fibrillary acidic protein (GFAP) only appears in later stages, this indicates that the majority of tumor cells in these GB tumors were neoplastic astrocytes in a dedifferentiated state [36]
Summary
Glial tumors or gliomas represent 80% of all malignant brain tumors [1,2]. Grade IV gliomas, called glioblastoma (GB), represent the most common and aggressive form of malignant primary brain tumors in adults, with an average age-adjusted incidence of3.2 cases per 100,000 people [3]. Glial tumors or gliomas represent 80% of all malignant brain tumors [1,2]. Grade IV gliomas, called glioblastoma (GB), represent the most common and aggressive form of malignant primary brain tumors in adults, with an average age-adjusted incidence of. 3.2 cases per 100,000 people [3]. The current standard of care for newly diagnosed GB patients consists of maximum safe surgical resection, followed by radiation therapy, with concomitant and adjuvant chemotherapy with temozolomide [5]. The prognosis for GB patients remains poor with a median survival of 15–17 months and a 5-year survival rate of 5% [6,7]. Relapse occurs in the cavity margin in 85% of all cases and, GB remains an essentially incurable disease [8,9]
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