Age-associated gadolinium leakage into ocular structures in patients with acute traumatic brain injury

Abstract

Background: Gadolinium Leakage into Ocular Structures (GLOS) is common following acute cerebrovascular events. The objective of this study was to investigate the occurrence of GLOS in an acute traumatic brain injury (TBI) cohort without acute cerebrovascular injury and to explore associated factors.

Methods: Enrolled acute TBI patients had a baseline MRI ≤48 h of injury (TP1) and follow-up MRI ≤72 h after baseline (TP2). Vitreous chamber enhancement and signal intensity ratios (SIRs) were calculated using pre- and post-contrast Fluid Attenuated Inversion Recovery (FLAIR). White matter hyperintensities (WMHs) were assessed using the Fazekas scale.

Results: Of the 128 TBI patients included, median age was 47 years, 70% male, and 66% presented with Glasgow Coma Scale of 15. No GLOS was detected at TP1 but was present in 23% of patients at TP2. GLOS+ patients were older (68 years [56-76] vs 39 years [27-53], p < 0.001), more likely to report falls as injury mechanism (62% vs 36%, p = 0.006), report history of hypertension (41% vs 19%, p = 0.025), and had a higher burden of WMHs (59% vs 14% with a total Fazekas ≥2, p < 0.001). Quantitative SIRs confirmed qualitative assessments: GLOS+ patients had higher SIRs at TP2 (0.43 vs 0.22, p < 0.001). Age (OR 3.28, 95%CI [1.88-5.71], p < 0.001) and prior TBI history (OR 4.99, 95%CI [1.46-17.06], p = 0.010) were independent predictors of GLOS. When age was removed, total Fazekas score (OR 2.53, 95%CI [1.60-4.00], p < 0.001) was an independent predictor of GLOS.

Conclusions: GLOS is primarily associated with age and may serve as another imaging marker of chronic vascular disease.

Keywords: Blood-ocular barrier disruption; Cerebral small vessel disease; Gadolinium leakage into ocular structures; MRI; Traumatic brain injury.

Figure 1.. Flowchart of patient selection.

Abbreviations: FLAIR: Fluid Attenuated Inversion Recovery; THINC: Traumatic Head Injury Neuroimaging Classification; TP1: Timepoint 1; TP2: Timepoint 2

Figure 2.. GLOS categorization.

This figure illustrates examples of a GLOS− patient and GLOS + patients (asymmetric or symmetric) on FLAIR MRI. No GLOS was noted at TP1, so GLOS categorization was determined using TP2 FLAIR. Abbreviations: GLOS: Gadolinium Leakage into Ocular Structures; TP1: Timepoint 1 (≤48 hours of injury); TP2: Timepoint 2 (≤72 hours of TP1); FLAIR: Fluid Attenuated Inversion Recovery.

Figure 3.. Quantitative Analysis of GLOS.

(A) Distribution of SIRs for pre- and post-contrast MRIs at both timepoints between those categorized as GLOS+ vs GLOS−. (B) Scatterplot displaying the pre-contrast SIRs at TP1 and TP2 amongst GLOS+ and GLOS− patients. (C) Distribution of the ratio of the pre-contrast SIR TP2/TP1 amongst GLOS+ and GLOS− patients.^{^}Note: One patient is not illustrated as their ratio is a clear outlier (>6). Note for all panels: Each distribution consists of 2 SIRs per patient (one for each eye). GLOS categorization was determining using the TP2 FLAIR. Note for B & C: Only the pre-contrast SIRs are displayed; similar trends appear for post-contrast SIRs. Abbreviations: FLAIR: Fluid Attenuated Inversion Recovery; GLOS: Gadolinium Leakage into Ocular Structures; SIR=Signal Intensity Ratio; TP1: Timepoint 1 (≤48 hours of injury); TP2: Timepoint 2 (≤72 hours of TP1); *: p<0.001; ns: not significant (p≥0.05)