The prognostic importance of traumatic axonal injury on early MRI: the Trondheim TAI-MRI grading and quantitative models.

OBJECTIVES: We analysed magnetic resonance imaging (MRI) findings after traumatic brain injury (TBI) aiming to improve the grading of traumatic axonal injury (TAI) to better reflect the outcome. METHODS: Four-hundred sixty-three patients (8-70 years) with mild (n = 158), moderate (n = 129), or severe (n = 176) TBI and early MRI were prospectively included. TAI presence, numbers, and volumes at predefined locations were registered on fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging, and presence and numbers on T2*GRE/SWI. Presence and volumes of contusions were registered on FLAIR. We assessed the outcome with the Glasgow Outcome Scale Extended. Multivariable logistic and elastic-net regression analyses were performed. RESULTS: The presence of TAI differed between mild (6%), moderate (70%), and severe TBI (95%). In severe TBI, bilateral TAI in mesencephalon or thalami and bilateral TAI in pons predicted worse outcomes and were defined as the worst grades (4 and 5, respectively) in the Trondheim TAI-MRI grading. The Trondheim TAI-MRI grading performed better than the standard TAI grading in severe TBI (pseudo-R2 0.19 vs. 0.16). In moderate-severe TBI, quantitative models including both FLAIR volume of TAI and contusions performed best (pseudo-R2 0.19-0.21). In patients with mild TBI or Glasgow Coma Scale (GCS) score 13, models with the volume of contusions performed best (pseudo-R2 0.25-0.26). CONCLUSIONS: We propose the Trondheim TAI-MRI grading (grades 1-5) with bilateral TAI in mesencephalon or thalami, and bilateral TAI in pons as the worst grades. The predictive value was highest for the quantitative models including FLAIR volume of TAI and contusions (GCS score <13) or FLAIR volume of contusions (GCS score ≥ 13), which emphasise artificial intelligence as a potentially important future tool. CLINICAL RELEVANCE STATEMENT: The Trondheim TAI-MRI grading reflects patient outcomes better in severe TBI than today's standard TAI grading and can be implemented after external validation. The prognostic importance of volumetric models is promising for future use of artificial intelligence technologies. KEY POINTS: Traumatic axonal injury (TAI) is an important injury type in all TBI severities. Studies demonstrating which MRI findings that can serve as future biomarkers are highly warranted. This study proposes the most optimal MRI models for predicting patient outcome at 6 months after TBI; one updated pragmatic model and a volumetric model. The Trondheim TAI-MRI grading, in severe TBI, reflects patient outcome better than today's standard grading of TAI and the prognostic importance of volumetric models in all severities of TBI is promising for future use of AI.

Lesion Frequency Distribution Maps of Traumatic Axonal Injury on Early Magnetic Resonance Imaging After Moderate and Severe Traumatic Brain Injury and Associations to 12 Months Outcome.

Traumatic axonal injury (TAI) is a common finding on magnetic resonance imaging (MRI) in patients with moderate-severe traumatic brain injury (TBI), and the burden of TAI is associated with outcome in this patient group. Lesion mapping offers a way to combine imaging findings from numerous individual patients into common lesion maps where the findings from a whole patient cohort can be assessed. The aim of this study was to evaluate the spatial distribution of TAI lesions on different MRI sequences and its associations to outcome with use of lesion mapping. Included prospectively were 269 patients (8-70 years) with moderate or severe TBI and MRI within six weeks after injury. The TAI lesions were evaluated and manually segmented on fluid-attenuated inversed recovery (FLAIR), diffusion weighted imaging (DWI), and either T2* gradient echo (T2*GRE) or susceptibility weighted imaging (SWI). The segmentations were registered to the Montreal Neurological Institute space and combined to lesion frequency distribution maps. Outcome was assessed with Glasgow Outcome Scale Extended (GOSE) score at 12 months. The frequency and distribution of TAI was assessed qualitatively by visual reading. Univariable associations to outcome were assessed qualitatively by visual reading and also quantitatively with use of voxel-based lesion-symptom mapping (VLSM). The highest frequency of TAI was found in the posterior half of corpus callosum. The frequency of TAI was higher in the frontal and temporal lobes than in the parietal and occipital lobes, and in the upper parts of the brainstem than in the lower. At the group level, all voxels in mesencephalon had TAI on FLAIR. The patients with poorest outcome (GOSE scores ≤4) had higher frequencies of TAI. On VLSM, poor outcome was associated with TAI lesions bilaterally in the splenium, the right side of tectum, tegmental mesencephalon, and pons. In conclusion, we found higher frequency of TAI in posterior corpus callosum, and TAI in splenium, mesencephalon, and pons were associated with poor outcome. If lesion frequency distribution maps containing outcome information based on imaging findings from numerous patients in the future can be compared with the imaging findings from individual patients, it would offer a new tool in the clinical workup and outcome prediction of the patient with TBI.

Traumatic axonal injury on clinical MRI: association with the Glasgow Coma Scale score at scene of injury or at admission and prolonged posttraumatic amnesia.

OBJECTIVE: The aim in this study was to investigate if MRI findings of traumatic axonal injury (TAI) after traumatic brain injury (TBI) are related to the admission Glasgow Coma Scale (GCS) score and prolonged duration of posttraumatic amnesia (PTA). METHODS: A total of 490 patients with mild to severe TBI underwent brain MRI within 6 weeks of injury (mild TBI: median 2 days; moderate to severe TBI: median 8 days). The location of TAI lesions and measures of total TAI lesion burden (number and volume of lesions on FLAIR and diffusion-weighted imaging and number of lesions on T2*-weighted gradient echo or susceptibility-weighted imaging) were quantified in a blinded manner for clinical information. The volume of contusions on FLAIR was likewise recorded. Associations between GCS score and the location and burden of TAI lesions were examined with multiple linear regression, adjusted for age, Marshall CT score (which includes compression of basal cisterns, midline shift, and mass lesions), and alcohol intoxication. The predictive value of TAI lesion location and burden for duration of PTA > 28 days was analyzed with multiple logistic regression, adjusted for age and Marshall CT score. Complete-case analyses of patients with TAI were used for the regression analyses of GCS scores (n = 268) and PTA (n = 252). RESULTS: TAI lesions were observed in 58% of patients: in 7% of mild, 69% of moderate, and 93% of severe TBI cases. The TAI lesion location associated with the lowest GCS scores were bilateral lesions in the brainstem (mean difference in GCS score -2.5), followed by lesions bilaterally in the thalamus, unilaterally in the brainstem, and lesions in the splenium. The volume of TAI on FLAIR was the measure of total lesion burden most strongly associated with the GCS score. Bilateral TAI lesions in the thalamus had the largest predictive value for PTA > 28 days (OR 16.2, 95% CI 3.9-87.4). Of the measures of total TAI lesion burden, the FLAIR volume of TAI predicted PTA > 28 days the best. CONCLUSIONS: Bilateral TAI lesions in the brainstem and thalamus, as well as the total volume of TAI lesions on FLAIR, had the strongest association with the GCS score and prolonged PTA. The current study proposes a first step toward a modified classification of TAI, with grades ranked according to their relation to these two measures of clinical TBI severity.