Elsevier

Neuroscience Letters

Volume 617, 23 March 2016, Pages 207-212
Neuroscience Letters

Research paper
Microbleeds may expand acutely after traumatic brain injury

https://doi.org/10.1016/j.neulet.2016.02.028Get rights and content

Highlights

  • A certain portion of the traumatic microbleeds changed within a week after the injury.

  • This change occurred in forms of microbleed expansion and confluence.

  • Due to this, both the overall microbleed count and volume was altered.

  • Imaging timing may be relevant for optimizing the prognostic utility of this biomarker.

Abstract

Background and purpose

Susceptibility weighted imaging (SWI) is a very sensitive tool for the detection of microbleeds in traumatic brain injury (TBI). The number and extent of such traumatic microbleeds (TMBs) have been shown to correlate with the severity of the injury and the clinical outcome. However, the acute dynamics of TMBs have not been revealed so far. Since TBI is known to constitute dynamic pathological processes, we hypothesized that TMBs are not constant in their appearance, but may progress acutely after injury.

Materials and methods

We present here five closed moderate/severe (Glasgow coma scale  13) TBI patients who underwent SWI very early (average = 23.4 h), and once again a week (average = 185.8 h) after the injury. The TMBs were mapped at both time points by a conventional radiological approach and their numbers and volumes were measured with manual tracing tools by two observers. TMB counts and extents were compared between time points.

Results

TMBs were detected in four patients, three of them displaying an apparent TMB change. In these patients, TMB confluence and apparent growth were detected in the corpus callosum, coronal radiation or subcortical white matter, while unchanged TMBs were also present. These changes caused a decrease in the TMB count associated with an increase in the overall TMB volume over time.

Conclusion

We have found a compelling evidence that diffuse axonal injury-related microbleed development is not limited strictly to the moment of injury: the TMBs might expand in the acute phase of TBI. The timing of SWI acquisition may be relevant for optimizing the prognostic utility of this imaging biomarker.

Introduction

Traumatic brain injury (TBI) constitutes a public health problem worldwide [5]. Diffuse axonal injury (DAI) is a substantial pathological component of brain injury, and is highly related to the patient outcome [16]. However, in consequence of its microscopic range, it is basically “invisible” to standard TBI imaging protocols.

Interest in the application of susceptibility weighted imaging (SWI) [21] in TBI has recently been increasing rapidly, since it has been shown to be a very sensitive imaging method for the detection of the possible hemorrhagic components of DAI, traumatic microbleeds (TMBs) [28]. SWI is a fully velocity-compensated, high-resolution 3D gradient echo sequence that uses magnitude and filtered-phase information, both separately and in combination, and is therefore able to create a strong contrast for the susceptibility effects of microbleeds [21]. Other imaging methods, such as CT, T2- and T2*-weighted MRI or FLAIR are also able to depict punctual DAI-related lesions, though less reliably so than SWI [3], [7], [10], [30]. SWI allows patients with a DAI to be dichotomized as hemorrhagic or nonhemorrhagic, and this has been proposed to be of clinical relevance [9], [31]. Moreover, the number, localization, type and volume of TMBs have been linked to the severity of injury and the clinical outcome [1], [2], [8], [10], [14], [18], [30], [33].

Other advanced MRI methods, and primarily diffusion tensor imaging, are also sensitive in the detection of axonal injury, but to date these results have been based on group analyses, generally with the use of post-processing computation and statistics [13].

In contrast, SWI might be easily applied at an individual level too. A conventional morphological assessment might define TMB number, extent and anatomical distribution per patient.

However, no consensus has yet been reached as concerns the optimal clinical use of SWI (or T2*GRE) in TBI. Whereas studies largely agree that TMBs are related to the injury severity or outcome, they differ from the aspects of the investigated population size, the injury severity, the image acquisition method, the outcome assessment method, the TMB detection and even the definition of TMB, features that may explain their heterogeneous results.

Another important factor might be the interval between injury and imaging. This has varied widely across and within the published studies (from days to years [10], [30]). If microbleeds are not static, but change (in number, extent, etc.) over time, the timing of imaging should be a crucial aspect as concerns the drawing of correct relations with the clinical features. We are aware of only two studies that have longitudinally investigated microbleeds in TBI; they concentrated on the long-term (several months to years) microbleed changes and revealed a slight attenuation in the microbleed visibility, probably due to hemosiderin absorption [20]. However, since acute TBI constitutes dynamic pathological processes, a microbleed status change in the acute phase is also highly possible.

We hypothesized that the microbleed parameters might change in the acute phase of TBI and we present here a follow-up SWI investigation of five TBI patients within the acute period.

Section snippets

Subjects and methods

Adults with a severe or moderate closed TBI (Glasgow Coma Scale, GCS < 14), but lacking major intracranial bleeding on the acute CT scans, were recruited prospectively from the trauma center at the University of Pécs in 2015. Exclusion criteria included an age above 50 years, a previously documented TBI, any known neurological or psychiatric disease, uncontrolled hypertension, diabetes, a history of smoking, a history of anticoagulant therapy, any contraindication of acute MRI, or a refusal to

Results

TMBs were found in 4 of the 5 patients (patients 1–4). Obvious TMB growth and/or confluence between the two imaging time-points were observed in three patients (patients 1–3, see Fig. 1). These were found in the splenium of the corpus callosum, the coronal radiation, or the subcortical white matter. Novel TMB formation (the appearance of a TMB at a previously unaffected site) or the disappearance of a TMB was not detected between the imaging time points. TMBs without any apparent change were

Discussion

The findings reported here demonstrate that the SWI TMB appearance may change in the acute phase after injury. The TMBs did not appear or disappear over time, but a proportion of the initially existing ones underwent an apparent expansion. This was manifested in considerable changes in both the overall TMB count and volume. CT, T1 and T2 MRI failed to detect this expansion. Although it is yet not possible to estimate the rate of occurrence of the TMB expansion in TBI because of the small sample

Conclusion

In conclusion, this study has shown that the development of microbleeds is not limited to the moment of injury, but a proportion of them may undergo an apparent expansion in the subsequent days. This affects both the overall microbleed count and volume. Scan timing may therefore be a crucial factor when the severity or outcome of DAI is assessed on the basis of SWI-detected TMB parameters.

Acknowledgments

This study was funded by Hungarian Brain Research Program Grant No. KTIA_13_NAP-A-II/8, Grant No. KTIA_13_NAP-A-II/9, SROP-4.2.2.A-11/1/KONV-2012-0017 and Hungarian Scientific Research Fund Grant No. OTKA/109132.

The present scientific contribution is dedicated to the 650th anniversary of the foundation of the University of Pécs.

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      Cerebral microhaemorrhages are a common finding in the acute to subacute stages of TBI (Perel et al., 2009; Wu et al., 2010; Liu et al., 2016) and their presence has been linked to injury severity and clinical outcome (Huang et al., 2015b). While some studies have found the number, location, type and volume of cerebral microhaemorrhages to correlate with injury severity and clinical outcome, others have not (Toth et al., 2016; Lawrence et al., 2017). Keeping in mind that an optimal timeframe for image acquisition has not yet been established, the discrepancy in reported findings may be explained by differences in time elapsed between injury and when imaging was conducted, which ranges from days to years (Lawrence et al., 2017).

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      Concerning TMBs, this is very unlikely. Though TMBs were shown to possibly change (expand) in the very acute phase after the injury [54], in the chronic phase, apart from a possible slight attenuation, they were mostly shown to be constant in their appearance even through years [55–57]. Regarding NHLs, we are not aware of long-term studies investigating lesion progression or cessation, we cannot exclude that some lesions disappeared till the imaging time point.

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