The Shrinking Brain: Cerebral Atrophy Following Traumatic Brain Injury

Abstract

Cerebral atrophy in response to traumatic brain injury is a well-documented phenomenon in both primary investigations and review articles. Recent atrophy studies focus on exploring the region-specific patterns of cerebral atrophy; yet, there is no study that analyzes and synthesizes the emerging atrophy patterns in a single comprehensive review. Here we attempt to fill this gap in our current knowledge by integrating the current literature into a cohesive theory of preferential brain tissue loss and by identifying common risk factors for accelerated atrophy progression. Our review reveals that observations for mild traumatic brain injury remain inconclusive, whereas observations for moderate-to-severe traumatic brain injury converge towards robust patterns: brain tissue loss is on the order of 5% per year, and occurs in the form of generalized atrophy, across the entire brain, or focal atrophy, in specific brain regions. The most common regions of focal atrophy are the thalamus, hippocampus, and cerebellum in gray matter and the corpus callosum, corona radiata, and brainstem in white matter. We illustrate the differences of generalized and focal gray and white matter atrophy on emerging deformation and stress profiles across the whole brain using computational simulation. The characteristic features of our atrophy simulations-a widening of the cortical sulci, a gradual enlargement of the ventricles, and a pronounced cortical thinning-agree well with clinical observations. Understanding region-specific atrophy patterns in response to traumatic brain injury has significant implications in modeling, simulating, and predicting injury outcomes. Computational modeling of brain atrophy could open new strategies for physicians to make informed decisions for whom, how, and when to administer pharmaceutical treatment to manage the chronic loss of brain structure and function.

Keywords: Cerebral atrophy; Computational simulation; Finite element modeling; Neurodegeneration; Traumatic brain injury.

Figure 1

Characteristic features of cerebral atrophy following traumatic brain injury. Compared to the healthy brain, left, the brain in cerebral atrophy following traumatic brain injury experiences a widening of the cortical sulci, a gradual enlargement of the ventricles, a pronounced cortical thinning, and a shrinking of the hippocampus, right.

Figure 2

Cerebral atrophy in neurodegeneration. Longitudinal magnetic resonance imaging of an Alzheimer’s patient reveals the characteristic pattern of progressive atrophy in the hippocampus, a widening of the cortical sulci, a gradual enlargement of the ventricles, a pronounced cortical thinning, and a shrinking of the hippocampus. Adopted with permission from Ref. .

Figure 3

Finite element models for cerebral atrophy. Two-dimensional sagittal model with 6182 gray and 5701 white matter linear triangular elements, 6441 nodes, and 12,882 degrees of freedom, left, and coronal model with 7106 gray and 14,196 white matter linear triangular elements, 11,808 nodes, and 23,616 degrees of freedom, right, created from the magnetic resonance images in Fig. 1.

Figure 4

General atrophy induces sagittal gray and white matter deformation. With progressive atrophy, from − 5% in gray and − 2.5% in white matter, top left, to − 20% in gray and − 10% in white matter, bottom right, the overall deformation increases up to 8 mm. For reference, the atrophied sagittal sections are overlaid on top of the initial geometry shown in gray. In agreement with clinical pathologies, cerebral atrophy induces a marked widening of the cortical sulci, here visible through a pronounced widening of the paracentral and marginal sulci.

Figure 5

General atrophy induces sagittal shear stresses at the gray and white matter interface. With progressive atrophy, from − 5% in gray and − 2.5% in white matter, top left, to − 20% in gray and − 10% in white matter, bottom right, the von Mises stress increases up to 0.4 kPa. For reference, the atrophied sagittal sections are overlaid on top of the initial geometry shown in gray. In agreement with clinical pathologies, stress concentrations originate at the bottom of cortical sulci where lesions are concentrated.

Figure 6

General atrophy induces coronal gray and white matter deformation. With progressive atrophy, from − 5% in gray and − 2.5% in white matter, top left, to − 20% in gray and − 10% in white matter, bottom right, the overall deformation increases up to 4 mm. For reference, the atrophied coronal sections are overlaid on top of the initial geometry shown in gray. In agreement with clinical pathologies, cerebral atrophy induces a widening of the cortical sulci, here visible through a pronounced widening of the Sylvian fissure, the superior and inferior temporal sulci, and the collateral sulcus. In agreement with the time line of atrophy in Fig. 1, the coronal model predicts a gradual enlargement of the ventricles and a notable progressive hippocampal atrophy.

Figure 7

General atrophy induces coronal shear stresses at the gray and white matter interface. With progressive atrophy, from − 5% in gray and − 2.5% in white matter, top left, to − 20% in gray and − 10% in white matter, bottom right, the von Mises stress increases up to 0.2 kPa. For reference, the atrophied coronal sections are overlaid on top of the initial geometry shown in gray. In agreement with clinical pathologies, stress concentrations originate at the bottom of cortical sulci where lesions are concentrated.

Figure 8

Focal gray and white matter atrophy induces coronal gray and white matter deformation and shear stresses. Pure gray matter atrophy, left, and pure white matter atrophy, right, generate markedly different deformation profiles, top, and stress profiles, bottom. Focal gray matter atrophy induces cortical thinning, a widening of the cortical sulci, and an enlargement of the ventricles. Focal matter atrophy induces a contraction of the whole brain toward the brain stem. For reference, the atrophied coronal sections are overlaid on top of the initial geometry shown in gray.