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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