Quantitative analysis using intraoperative contrast-enhanced ultrasound in adult-type diffuse gliomas with isocitrate dehydrogenase mutations: association between hemodynamics and molecular features

Abstract

Purpose: The relationship between contrast-enhanced ultrasound (CEUS) hemodynamics and the molecular biomarkers of adult-type diffuse gliomas, particularly isocitrate dehydrogenase (IDH), remains unclear. This study was conducted to provide a comprehensive description of the vascularization of adult-type diffuse gliomas using quantitative indicators. Additionally, it was designed to identify any variables with the potential to intraoperatively predict IDH mutation status.

Methods: This prospective study enrolled patients with adult-type diffuse gliomas between November 2021 and September 2022. Intraoperative CEUS was performed, and CEUS videos were recorded for 90-second periods. Hemodynamic parameters, including the peak enhancement (PE) difference, were calculated based on the time-intensity curve of the region of interest. A differential analysis was performed on the CEUS parameters with respect to molecular biomarkers and grades. Receiver operating characteristic curves for various parameters were analyzed to evaluate the ability of those parameters to predict IDH mutation status.

Results: Sixty patients with adult-type diffuse gliomas were evaluated. All hemodynamic parameters, apart from rising time, demonstrated significant differences between IDH-mutant and IDH-wildtype adult-type diffuse gliomas. The PE difference emerged as the optimal indicator for differentiating between IDH-wildtype and IDH-mutant gliomas, with an area under the curve of 0.958 (95% confidence interval, 0.406 to 0.785). Additionally, the hemodynamic parameters revealed significant differences across both grades and types of adult-type diffuse gliomas.

Conclusion: Hemodynamic parameters can be used intraoperatively to effectively distinguish between IDHwildtype and IDH-mutant adult-type diffuse gliomas. Additionally, quantitative CEUS equips neurosurgeons with dynamic perfusion information for various types and grades of adult-type diffuse gliomas.

Keywords: Adult-type diffuse gliomas; Hemodynamics; Isocitrate dehydrogenase; Ultrasonography, contrast agent.

Fig. 1.. Quantitative hemodynamic analysis and parameter definition.

A, B. The schematic illustrates the process of establishing regions of interest (ROIs) in contrast-enhanced ultrasonography. (1) An ROI was selected within the parenchyma of the glioma lesion. (2) Another ROI was chosen in the brain tissue at an equivalent depth, avoiding large blood vessels. (1) A third ROI was determined that included the entire glioma lesion at PE. ROIs were delineated based on the lesions identified in the grayscale image (left), and the same ROI outline is displayed in the contrast-enhanced ultrasound image (right). C, D. The red and blue curves represent the average intensity over time for ROI (1) and ROI (2), respectively, forming the time-intensity curve (TIC) and allowing for calculations of hemodynamic parameters through the TIC. t_p is defined as the time corresponding to the peak, t₀ as the onset of enhancement, and t₁ as the end of enhancement. ROI (3) includes the entire glioma lesion at its peak, and enhancement dispersion (ED) represents the difference between the maximum and minimum intensity within the ROI. PE, peak enhancement; RBF, regional blood flow; RS, rising slope; RT, rising time; S, area under curve.

Fig. 2.. Violin plots of hemodynamic parameters according to grade, type, and IDH mutation status.

Differential analysis of quantitative parameters is shown: (A) PE difference, (B) S difference, (C) RT, (D) RBF difference, (E) RS, and (F) ED, in relation to IDH mutation status, glioma types, and grades in supratentorial adult-type diffuse gliomas using contrast-enhanced ultrasound. ED, enhancement dispersion; GBM, glioblastoma; HGG, high-grade glioma; IDH, isocitrate dehydrogenase; LGG, low-grade glioma; PE, peak enhancement; RBF, regional blood flow; RS, rising slope; RT, rising time; S, area under curve. *P<0.05 were considered to indicate statistical significance.

Fig. 3.. Peak enhancement difference in isocitrate dehydrogenase (IDH)-wildtype adult-type diffuse gliomas.

A 53-year-old woman was diagnosed with a high-grade glioma in the left lateral ventricle based on preoperative magnetic resonance imaging (MRI). A. Postoperative immunohistochemical analysis confirmed the diagnosis as a glioblastoma, IDH-wildtype (IDH1, ×200). B, C. Contrast-enhanced MRI and grayscale ultrasound reveals that the lesion was in the left lateral ventricle (The yellow circle represents the approximate extent of the lesion). D. Basline enhancement at the beginning of recording contrast-enhanced ultrasound video (time=0 s). E, F. The peak enhancement (PE) of the tumor and of the brain tissue at the same depth, respectively. The enhancement of the tumor parenchyma at PE was significantly stronger than that of the brain tissue. G. The regions of interest (ROIs) were delineated in the tumor parenchyma (red circle) and brain tissue (blue circle) at the same depth to generate the time-intensity curve. H. The color of the curve corresponded to the color of the ROI in G. The PE on the time-intensity curve was distinct between the glioma parenchyma and the brain tissue, with a PE difference of 13.99.

Fig. 4.. Peak enhancement difference in isocitrate dehydrogenase (IDH)-mutant adult-type diffuse gliomas.

A 55-year-old woman was diagnosed with a high-grade glioma in the right frontal lobe based on preoperative magnetic resonance imaging (MRI). A. Postoperative immunohistochemical analysis confirmed the diagnosis as an astrocytoma, IDH-mutant (IDH1, ×200). B, C. Contrast-enhanced MRI and grayscale ultrasound reveals that the lesion was in the right frontal lobe (The yellow circle represents the approximate extent of the lesion). D. Basline enhancement at the beginning of recording contrast-enhanced ultrasound video (time=0 s). E, F. The peak enhancement (PE) of the tumor and of the brain tissue at the same depth, respectively. The enhancement of the tumor parenchyma at its peak was close to that of the brain tissue. G. The regions of interest (ROIs) were delineated in the tumor parenchyma (red circle) and the brain tissue (blue circle) at the same depth to generate a time-intensity curve. H. The color of the curve corresponded to the color of the ROI in G. The PE on the time-intensity curve was slightly higher in the brain tissue than in the glioma parenchyma, with a PE difference of -0.89.