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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