Value of quantitative magnetic resonance imaging T1-relaxometry in predicting contrast-enhancement in glioblastoma patients

Abstract

Summarizing the importance of the study: The repetitive usage of gadolinium-based contrast agents (GBCA) is critical for magnetic resonance imaging (MRI) evaluation of tumor burden in glioblastoma patients. It is also a crucial tool for determination of radiographical response to treatment. GBCA injection, however, comes with a 2.4% rate of adverse events including life-threatening conditions such as nephrogenic systemic fibrosis (NSF). Moreover, GBCA have been shown to be deposited in brain tissue of patients even with an intact blood-brain barrier (BBB). The present study explores quantitative T1 relaxometry as an alternative non-invasive imaging technique detection of tumor burden and determination of radiographical response. This technique exploits specific properties of brain tissue with impaired BBB. With a sensitivity and specificity as high as 86% and 80%, respectively, quantitative T1-relaxometry allows for detecting contrast-enhancing areas without the use of GBCA. This method could make it unnecessary to subject patients to the risk of adverse events associated with the use of GBCA. Nonetheless, a large-scale analysis is needed to confirm our findings.

Background: Gadolinium-based contrast agents (GBCA) are crucial for magnetic resonance imaging (MRI)-based evaluation of tumor burden in glioblastoma (GBM). Serious adverse events of GBCA, even though uncommon, and gadolinium deposition in brain tissue could be avoided by novel imaging techniques not requiring GBCA. Altered tissue composition in areas with impaired blood-brain-barrier also alters the quantified T1 relaxation time (qT1), so that qT1 analysis could replace GBCA-based MRI for the analysis of tumor burden and response.

Methods: As a part of a prospective pilot MRI-relaxometry trial, patients with newly-diagnosed GBM who relapsed under standard radiochemotherapy were selected for this study. At recurrence, subtraction of qT1 maps pre and post-GBCA application (ΔqT1 maps) was used to determine areas of contrast-enhancement. With the contrast-enhancement on ΔqT1 maps as reference, ROC analysis served to detect an optimal qT1 cut-off on qT1 maps prior to GBCA to distinguish between contrast-enhancing tissue and its surroundings.

Results: Ten patients were included. A qT1 value >2051ms predicted contrast-enhancing tumor tissue with a sensitivity of 86% and specificity of 80% (AUC, 0.92; p<0.0001). Interestingly, qT1 prolongation >2051 ms that did not overlap with contrast-enhancing area transformed into contrast-enhancement later on (n=4).

Conclusion: T1-relaxometry may be a useful technique to assess tissue properties equivalent to contrast-enhancement without the need for GBCA application. It may also provide information on sites with future tumor progression. Nonetheless, large-scale studies are needed to confirm these findings.

Keywords: BBB damage; T1-mapping; T1-relaxometry; glioblastoma; quantitative MRI.

Figure 1. ROC curve

This plot shows qT1 values [ms] at different cutoffs and quantifies their the sensitivity and specificity in discriminating the solid contrast-enhancing tumor from the surroundings. The optimal performance is reached at a qT1 value of 2051ms.

Figure 2. A patient with >90% overlap (patient 2)

The color map (A) shows areas with pre-GBCA qT1 > 2051 ms, delineated by a red line as a gradient between red and yellow. A nearly complete overlap is seen at time-point of progression between pre-GBCA qT1 (A) and the contrast-enhancing tumor on the subtraction map ΔT1, which is outlined in red (pre-GBCA qT1 – post-GBCA qT1) (B).

Figure 3. A patient with moderate overlap (patient 9)

A Quantitative map with a subtraction map qT1 at time-point TP 5) (A) and conventional MRI at TP 5 and TP 6 (B) of a 70-year-old woman with recurrent GBM. At TP 5, the quantitative map (A, on the left-hand side) shows pre-GBCA qT1 area with >2051 ms (red to yellow, green arrows) with a good overlap of the dorsal contrast-enhancing tumor seen on the subtraction map ΔT1 (A, on the right-hand side), but the second smaller contrast-enhancing tumor area (crosshair) is missing on the color map. This contrast-enhancing area without overlap (crosshair) regressed in the next conventional MRI (TP 6) (B), whereas the contrast-enhancing tumor with overlap progressed. Also, note additional area of T1-prolongation outside the contrast-enhancing tumor.

Figure 4. T1-prolongation > 2051 ms outside the solid contrast-enhancing tumor

In one patient (A; patient 5), T1-prolongation >2051 ms outside the solid contrast-enhancing tumor (red circle) partially fitted with the subtle enhancement (ΔqT1, blue). In another patient (B, C; pat 6), T1-prolongation >2051 ms outside the solid contrast-enhancing tumor at TP 2 (B) partially matched subtle enhancement (ΔqT1). At TP4 (C), this area transformed to contrast-enhancing tumor.