Simultaneous quantification of perfusion, permeability, and leakage effects in brain gliomas using dynamic spin-and-gradient-echo echoplanar imaging MRI

Abstract

Objective To determine the feasibility and biologic correlations of dynamic susceptibility contrast (DSC), dynamic contrast enhanced (DCE), and quantitative maps derived from contrast leakage effects obtained simultaneously in gliomas using dynamic spin-and-gradient-echo echoplanar imaging (dynamic SAGE-EPI) during a single contrast injection. Materials and methods Thirty-eight patients with enhancing brain gliomas were prospectively imaged with dynamic SAGE-EPI, which was processed to compute traditional DSC metrics (normalized relative cerebral blood flow [nrCBV], percentage of signal recovery [PSR]), DCE metrics (volume transfer constant [Ktrans], extravascular compartment [ve]), and leakage effect metrics: ΔR2,ss* (reflecting T2*-leakage effects), ΔR1,ss (reflecting T1-leakage effects), and the transverse relaxivity at tracer equilibrium (TRATE, reflecting the balance between ΔR2,ss* and ΔR1,ss). These metrics were compared between patient subgroups (treatment-naïve [TN] vs recurrent [R]) and biological features (IDH status, Ki67 expression). Results In IDH wild-type gliomas (IDHwt—i.e., glioblastomas), previous exposure to treatment determined lower TRATE (p = 0.002), as well as higher PSR (p = 0.006), Ktrans (p = 0.17), ΔR1,ss (p = 0.035), ve (p = 0.006), and ADC (p = 0.016). In IDH-mutant gliomas (IDHm), previous treatment determined higher Ktrans and ΔR1,ss (p = 0.026). In TN-gliomas, dynamic SAGE-EPI metrics tended to be influenced by IDH status (p ranging 0.09–0.14). TRATE values above 142 mM−1s−1 were exclusively seen in TN-IDHwt, and, in TN-gliomas, this cutoff had 89% sensitivity and 80% specificity as a predictor of Ki67 > 10%. Conclusions Dynamic SAGE-EPI enables simultaneous quantification of brain tumor perfusion and permeability, as well as mapping of novel metrics related to cytoarchitecture (TRATE) and blood–brain barrier disruption (ΔR1,ss), with a single contrast injection. Clinical relevance statement Simultaneous DSC and DCE analysis with dynamic SAGE-EPI reduces scanning time and contrast dose, respectively alleviating concerns about imaging protocol length and gadolinium adverse effects and accumulation, while providing novel leakage effect metrics reflecting blood–brain barrier disruption and tumor tissue cytoarchitecture. Key Points • Traditionally, perfusion and permeability imaging for brain tumors requires two separate contrast injections and acquisitions. • Dynamic spin-and-gradient-echo echoplanar imaging enables simultaneous perfusion and permeability imaging. • Dynamic spin-and-gradient-echo echoplanar imaging provides new image contrasts reflecting blood–brain barrier disruption and cytoarchitecture characteristics. Graphical Abstract

Structural and practical identifiability of contrast transport models for DCE-MRI

“…As we have shown that practical identifiability improves with increasing SNR, we emphasize the need for image acquisition standards to increase the quality of imaging data and therefore reliability of parameter estimations such as the standards proposed by the Quantitative Imaging Biomarkers Alliance (QIBA) [ 75 ]. As DCE-MRI acquisition protocols and quantification methods continue to rapidly develop [ 76 ], it is important to ensure rigor in model fitting and analysis.…”

Standardized brain tumor imaging protocols for clinical trials: current recommendations and tips for integration

“…The comparison of post-bolus to pre-bolus DSC signal intensity, as measured with the percentage of signal recovery (PSR), is thought to be influenced by tissue microstructure, and therefore useful for differential diagnosis ( 65 , 79 ). Post-bolus signal intensity is influenced by the balance between T 2 * and T 1 leakage effects, which has been suggested to reflect tissue cytoarchitecture ( 77 , 80 , 81 ). PSR utility has been demonstrated in the diagnostic phase rather than in treatment response monitoring so far, thus its evaluation may not be directly relevant for clinical trials at the moment.…”

“…DCE maps reflect the contrast leakage characteristics. In this case, DCE metrics were obtained simultaneously with DSC, using a dynamic spin-and-gradient-echo perfusion sequence as described in ( 81 ). Finally, sodium images were obtained at the end of the protocol and sodium signal voxel-wise was normalized to the eye sodium signal.…”

Model discovery approach enables noninvasive measurement of intra-tumoral fluid transport in dynamic MRI

“… 24–27 While there do exist MRI sequences which directly measure interstitial fluid velocity, they struggle with separating vascular flow from interstitial flow and require additional imaging sequences to be applied, significantly increasing the time a patient spends in the scanner. 28,29 Given that DCE-MRI is becoming a standard clinical practice and novel methods for its acquisition are being actively developed, 30 there is growing opportunity to utilize it for studying interstitial flow, without the need for requiring more time in the scanner.…”