Elsevier

Cortex

Volume 48, Issue 2, February 2012, Pages 156-165
Cortex

Special issue: Review
Traumatic brain injury and the frontal lobes: What can we gain with diffusion tensor imaging?

https://doi.org/10.1016/j.cortex.2011.06.020Get rights and content

Abstract

Traumatic brain injury (TBI) is a leading cause of death in the young population and long-term disability in relation to pervasive cognitive–behavioural disturbances that follow frontal lobe damage. To date, emphasis has been placed primarily on the clinical correlates of frontal cortex damage, whilst identification of the contribution of subjacent white matter lesion is less clear. Our poor understanding of white matter pathology in TBI is primarily due to the low sensitivity of conventional neuroimaging to identify pathological changes in less severe traumatic injury and the lack of methods to localise white matter pathology onto individual frontal lobe connections. In this paper we focus on the potential contribution of diffusion tensor imaging (DTI) to TBI. Our review of the current literature supports the conclusion that DTI is particularly sensitive to changes in the microstructure of frontal white matter, thus providing a valuable biomarker of the severity of traumatic injury and prognostic indicator of recovery of function. Furthermore we propose an atlas approach to TBI to map white matter lesions onto individual tracts. In the cases presented here we showed a direct correspondence between the clinical manifestations of the patients and the damage to specific white matter tracts. We are confident that in the near future the application of DTI to TBI will improve our understanding of the complex and heterogeneous clinical symptomatology which follows a TBI, especially mild and moderate head injury, which still represents 70–80% of all clinical population.

Introduction

Traumatic brain injury (TBI) is reported at all ages and is a leading cause of disability among citizens younger than 45 years of age, affecting about 235 cases per 100,000 individuals each year in most Western societies (Tagliaferri et al., 2006). In 1990, estimates of worldwide TBI requiring medical care or resulting in death were reported at 9,500,000 persons (Thurman et al., 2007), attributed to enormous public health costs and burdens. Despite its frequency, pathophysiological mechanisms of TBI remain poorly understood (Zappalà, 2008, Jennett, 1978, Gualtieri, 1995).

TBI produces rapid deformation of the brain, resulting in a cascade of specific pathological events. The resulting changes in the anatomy and neurophysiology of the brain can disrupt multiple cerebral networks affecting cognitive, autonomic and emotional functions, as well as other aspects of behaviour (Eslinger et al., 2007). Damage to brain connections, involving widely distributed brain networks, is a crucial factor in the development of cognitive impairment (Mesulam, 1998). Diffuse axonal injury, more recently referred to as traumatic axonal injury, occurs in most TBI after motor vehicle collisions and falls, in which deceleration and rotational forces cause a shearing of the brain’s white matter, especially within the frontal lobes (Marquez de La Plata et al., 2011). After a TBI, the integrity of white matter is correlated with the severity of the injury, as well as the outcome. Kraus et al. (2007) documented that reduction in the integrity of various white matter structures was associated with poorer performance on measures of attention, memory and executive functions. TBI produces a complex pattern of diffuse axonal injury at variable locations across individuals, rendering it difficult to localise white matter disruption (Kinnunen et al., 2011). Although, white matter disruption is an important determinant of cognitive impairment after TBI, conventional neuroimaging underestimates its extent.

Diffusion tensor imaging (DTI) is a novel neuroimaging method for studying in vivo the anatomy and integrity of white matter tracts in the human brain (Lawes et al., 2008, Beaulieu, 2009, Thiebaut de Schotten et al., 2011). Recent studies suggest that DTI may provide more sensitive measurements of discrete axonal injury in TBI compared to other neuroimaging methods not only in the acute phase but also after the traumatic injury in the chronic stage (Thomas et al., 2009, Thomas et al., 2011, Rimrodt et al., 2010, Charlton et al., 2010, Arfanakis et al., 2002, Assaf and Pasternak, 2008). Anatomical information derived from DTI atlases can also be used to assess the extension of the white matter damage in TBI. In this article we focus on the impact of physical and neuropathological causes of TBI on white matter damage and describe three single cases representatives of the typical clinical profiles observed following TBI. We then use a recently published white matter atlas of human brain connections derived from DTI tractography to identify the extension of the injury to underlying white matter tracts (Catani and Thiebaut de Schotten, 2012). Finally, we briefly review the preliminary results reported in studies employing DTI to measure axonal injury in TBI.

Section snippets

Physical and neuropathological causes of TBI

Traumatic injury mechanisms encompass a cascade of events, that produce widespread, multifocal, diffuse damage that varies according to the severity of the impact. Three mechanisms have been described.

A combination of physical and mechanical forces following a coup-contrecoup blow causes lacerations mostly in the frontal, temporo-polar and occipital areas due to the brain impacting against the base of the skull. The resulting damage is greater for closed TBI where the skull is not fractured and

Clinical profiles following TBI

Clinical profiles of TBI are highly variable and present themselves along a spectrum of severity that depends on the intensity and site of the injury. In mild and moderate TBI, the traumatic forces are more frequently localised to the orbitofrontal and temporal polar zones including the amygdala and anterior hippocampus. These regions are interconnected via the uncinate fasciculus, a bilateral tract involved in memory, inhibition and emotion processing. The clinical manifestations associated

An atlas approach to TBI

In the last 10 years the advent of DTI has permitted to create normalised average maps of the major white matter connections. These atlases allow to identify affected tracts in patients with lesions extending into the deep white matter. In this section we describe three single cases of TBI representative of each clinical syndrome described above. To identify frontal white matter damage induced by TBI, the T1 or T2 structural images of these three subjects with TBI were normalized in the MNI with

DTI in TBI

Based on the aforementioned cases, as well as available clinical literature, it is clear that imaging of the damage resulting from TBI remains limited. Thus patients with diffuse cerebral damage, secondary to TBI, often chronically exhibit cognitive and behavioural disorders, although CT and conventional MRI scans can be frequently normal or show lesions poorly related to the nature and severity of cognitive post-traumatic disturbances (Fig. 4) (Sugiyama et al., 2007).

DTI is a less conventional

Discussion

TBI, although the most frequent of all neurological illnesses in the Western societies, still has not gained relevance in the “eyes” of most neurologists because its consequences are not commonly defined within traditional “organic” templates and definitions of structure–function correlations associated with focal cortical lesions. The field of neurology is generally more attracted by deficits and syndromes, whose main basis remains “physical and objective”, or at least easily documentable with

Acknowledgements

We would like to thank the NATBRAINLAB (http://www. natbrainlab.com) for helpful discussion. This work was supported by the Agence Nationale de Recherche (ANR) [project CAFORPFC, number ANR-09-RPDOC-004-01 and project HM-TC, number ANR-09-EMER-006] and by a Dean’s Feasibility grant from the Penn State College of Medicine. Many thanks to Mimmo Tomaselli, MD who helped during elaboration and post-processing of MRI images and Lauren Sakuma who edited the paper for English.

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