Radiogenomics of medulloblastoma: imaging surrogates of molecular biology

Abstract

Medulloblastoma is a heterogeneous disease comprising four molecular subgroups-wingless (WNT), sonic hedge hog (SHH), group 3, and group 4, with distinct developmental origins, unique transcriptional profiles, diverse phenotypes, and varying clinical outcomes. Magnetic resonance imaging (MRI) is the preferred first-line imaging modality in the diagnosis and staging of suspected brain tumors including medulloblastoma. It is being increasingly recognized that imaging features reflect underlying disease biology that can serve as independent predictive and prognostic biomarkers. Radiogenomics is an emerging field of research that aims to define relationships between non-invasive imaging features (radio-phenotypes) and genomic data/molecular markers (molecular phenotypes). Recent studies have reported encouraging data regarding imaging genomics of medulloblastoma with certain MRI features correlating with specific molecular subgroups. These include lateralized cerebellar location for SHH-subgroup; cerebellopontine angle location for WNT-subgroup; and inferior location with dilation of superior recess of the IVth ventricle for group 4 tumors. Minimal enhancement of primary tumor and ependymal metastases (infundibular/suprasellar) with mismatching pattern is a specific feature of group 4 medulloblastoma. A 5-metabolite signature profile on magnetic resonance spectroscopy reliably differentiates SHH-subgroup from non-WNT/non-SHH medulloblastoma. SHH-specific binary nomogram (location on horizontal and vertical axis, relationship with dorsal brainstem, pattern of contrast-enhancement, and peri-tumoral edema as discriminating imaging features) is associated with excellent predictive accuracy, followed by group 4-specific nomogram, with suboptimal accuracy of WNT and group 3-specific nomograms. The advent of deep machine-learning techniques and convoluted artificial neural networks should provide unique opportunities to further improve the accuracy of such radiogenomic correlation and prediction.

Importance of magnetic resonance imaging for diagnostics and complex treatment in patients with Leptomeningial Disease- Six clinical cases with a literature overview

“…The special in this case is the lack of contrast enhancement ("mismatching" pattern) of the leptomeningeal metastases on the MRI. Similar examples have been found in the literature, where it is demonstrated, that the absorption of the contrast depends on the genetic type and the histological variant of the meduloblastoma cells [28,30,31]. This fact increases the significance of the MRI, not only for the diagnosis and staging of meduloblastoma, but also for the preliminary determination of the prognosis, closely related to the complex treatment.…”

“…Mеduloblastoma (MB) is a malignant embryonal tumour, a subtype of primitive neuroectodermal brain tumors (PNET), predominantly growing infratentorially in the cerebellum [21]. MB is a heterogeneous disease comprising four molecular subgroups -wingless (WNT), sonic hedge hog (SHH), group 3, and group 4, with distinct developmental origins, unique transcriptional profiles, diverse phenotypes and varying clinical outcomes [24,25,28,29]. Some MR images of LMD in medulloblastoma appear to be characteristic, perhaps even specific to certain molecular subgroups [30].…”

Extra-axial desmoplastic medulloblastoma in adult cerebellopontine angle: Case report and noninvasive molecular subgrouping utilizing magnetic resonance imaging-based radiomics nomogram

“…Moreover, in the era of molecular genetics, radiogenomics have provided sufficient data to define certain molecular subtypes noninvasively, although it is quite clear that no single imaging feature is pathognomonic of any particular subgroup, certain imaging characteristics are much more prevalent in one subgroup compared to others and may even be highly specific for an individual molecular subgroup. [ 14 ]…”

Prognostic Impact of Semantic MRI Features on Survival Outcomes in Medulloblastoma: Does It Reflect or Transcend Radiogenomic Correlation?

“…In adult diffuse gliomas, contrast-enhancement has been an imaging surrogate for histologic grading, with higher grade gliomas showing signi cantly more enhancement, suggesting blood-brain barrier disruption, increased neovascularization, and transendothelial diffusion [22]. Previous studies have shown differential pattern of contrast-uptake within individual subgroups of medulloblastoma; WNT-pathway tumors are associated with bright homogenous enhancement while Group 4 medulloblastomas have large non-enhancing areas or faint/patchy contrast-uptake [12,15]. We found contrast-uptake in ≤80% of tumor volume to be associated with worse outcomes for the entire cohort and within Group 3 medulloblastoma.…”

“…Similar prediction accuracy was later reported using radiomics-based approaches with support machine vector classi er [13] and random forest model [14] to identify molecular subgroups. Several other studies have used semantic, radiomic, or spectroscopic features to predict molecular subgroups with acceptable accuracy [15,16], but none of them have attempted to correlate speci c imaging features with survival in medulloblastoma. In the present study, we report the prognostic impact of semantic MRI features on recurrence and survival in our institutional cohort of medulloblastoma across molecular subgroups as well as within individual molecular subgroups.…”