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Table 2 MRI imaging biomarkers for assessment of the immune and tumor environment of glioblastoma

From: Imaging-guided precision medicine in glioblastoma patients treated with immune checkpoint modulators: research trend and future directions in the field of imaging biomarkers and artificial intelligence

Hallmark Threshold Advantages Limitations
Cellular proliferation MRS: ↑Chomax, ↑Chomean, ↓NAA, ↓Cr, ↑mI, ↓NAA/Cr, ↑Cho/Cr, ↑Cho/NAA ratio MRI: ↓ADC Specificity Tumor heterogeneity Low sensitivity (mM) No specific patterns Acquisition time (MRS) Peripheral lesions (MRS: pitfalls with bone and skin) No absolute reference value (ADC)
Membrane proliferation MRS: ↑Chomax, ↑Chomean, ↑Cho/Cr, ↑Cho/NAA ratio   Low sensitivity (mM)
Structural complexity ↑Diffusion kurtosis imaging ↓ Fractional anisotropy (brain fibers) Specificity Sensitivity Availability Still experimental
Aminoacid metabolism
Glucose metabolism MRS: ↑free lipids Pitfalls: lymphoma, lactates (TE = 35 ms)
Angiogenesis ↑Ktrans on DCE-MR (permeability) ↓BOLD fMRI signal Level of evidence Software Steroids Non specific
Perfusion DSC MRI: ↑CBV↑CBF↑rCBV > 4 ↑Relative CBV on DCE-MR Robust software Normalization is required Operator dependent Nonspecific of gliomas
Invasiveness ↑FLAIR ↓ADC (except in the edema) ↓FA (experimental) Sensitivity Non-standardized Operator dependent Normalization is required
Hypoxia MRS: lactate > 0 (no lactate accumulation in healthy tissue) ↓19F-MRI Specificity Non-standardized
Necrosis ↓DWI ↓ADC MRS: lipids > 0 (TE = 35 ms), no lipid accumulation in healthy tissue, Lactate > 0 Specificity Non-standardized
Edema ↑ADC ↑T2FLAIR Sensitivity Specificity
Infiltration of cytotoxic T cells
Anergy of T cells
Activated microglia
  1. Note: [6]. MRS magnetic resonance spectroscopy, Chomax maximum concentration of choline-containing compounds, Chomean mean concentration of choline-containing compounds, Cr creatinine, mI myoinositol, NAA N-acetyl-aspartate, BBB blood-brain barrier, CBV cerebral blood volume, CBF cerebral blood flow, rCBV related CBV, FLAIR fluid-attenuated inversion recovery, ADC apparent diffusion coefficient, FA fractional anisotropy. BOLD blood oxygenation level dependent, fMRI functional magnetic resonance imaging, TE EchoTime (ms), ↓ decrease, ↑ increase