Basal Ganglia Iron Content Increases with Glioma Severity Using Quantitative Susceptibility Mapping: A Potential Biomarker of Tumor Severity

Abstract

Background and Purpose: Gliomas have been found to alter iron metabolism and transport in ways that result in an expansion of their intracellular iron compartments to support aggressive tumor growth. This study used deep neural network trained quantitative susceptibility mapping to assess basal ganglia iron concentrations in glioma patients. Materials and Methods: Ninety-two patients with brain lesions were initially enrolled in this study and fifty-nine met the inclusion criteria. Susceptibility-weighted images were collected at 3.0 T and used to construct quantitative susceptibility maps via a deep neural network-based method. The regions of interest were manually drawn within basal ganglia structures and the mean voxel intensities were extracted and averaged across multiple slices. One-way ANCOVA tests were conducted to compare the susceptibility values of groups of patients based on tumor grade while controlling for age, sex, and tumor type. Results: The mean basal ganglia susceptibility for patients with grade IV tumors was higher than that for patients with grade II tumors (p = 0.00153) and was also higher for patients with grade III tumors compared to patients with grade II tumors (p = 0.020), after controlling for age, sex, and tumor type. Patient age influenced susceptibility values (p = 0.00356), while sex (p = 0.69) and tumor type (p = 0.11) did not. Conclusions: The basal ganglia iron content increased with glioma severity. Basal ganglia iron levels may thus be a useful biomarker in glioma prognosis and treatment, especially with regard to iron-based cancer therapies.

Analysing the role of SERPINE1 network in the pathogenesis of human glioblastoma

“…Further vasculogenesis through involvement of myeloid cells disrupts the normal physiological barrier, causing blood vessel leakiness and potential collateral pathophysiology. [3] Targeting of SERPINE1 is likely to impact several such collateral pathophysiology associated with severity of GBM.…”

“…Further vasculogenesis through involvement of myeloid cells disrupts the normal physiological barrier, causing blood vessel leakiness and potential collateral pathophysiology. [3] Targeting of SERPINE1 is likely to impact several such collateral pathophysiology associated with severity of GBM. Tumorigenesis and its evasion can also be influenced by cellular energetics [5] and targeting of SERPINE1 can interfere with cellular energetics of GBM and improve therapeutic efficacy.…”

“…[1][2][3] Contributing to the hostile nature of this tumour are finger-like projections that heterogeneously extend into surrounding brain areas which make this tumour a challenge to treat on account of its poor localization and difficult anatomical access. [1][2][3] The poor localisation of GBM further contributes to the difficulties in performing post-surgical resection and hence its higher incidence of recurrence. GBM exhibits considerable intra and inter-tumour heterogeneity, with as much as 50% of recurrent tumour samples showing diverse genetic mutations from the primary tumour.…”

“…Glioblastoma multiforme (GBM) is an aggressive type IV cancer [1,2] with median survival duration of 15-23 months and less than 6% 5-year survival rate. [2,3] The tumour arises from astrocytes but significantly affects the glial cells surrounding neurons. [1][2][3] Contributing to the hostile nature of this tumour are finger-like projections that heterogeneously extend into surrounding brain areas which make this tumour a challenge to treat on account of its poor localization and difficult anatomical access.…”

Imaging in translational cancer research

“…Quantitative susceptibility mapping, the quantitative extension of SWI, has been proposed to provide local magnetic susceptibility values and evaluate their spatial distribution 87 , 88 . This method has been investigated as a potential biomarker of tumor severity in glioma, in which basal ganglia iron content increases with glioma severity 89 . Further studies are needed to assess its utility in oncological research and clinical imaging.…”