Redefining the pericontusional penumbra following traumatic brain injury: evidence of deteriorating metabolic derangements based on positron emission tomography

Abstract

Abstract The pathophysiological changes in the pericontusional region after traumatic brain injury (TBI) have classically been considered to be ischemic. Using [F-18]fluorodeoxyglucose (FDG) and triple-oxygen PET studies, we examined the pericontusional "penumbra" to assess for increased oxygen extraction fraction (OEF), anaerobic metabolism, and tissue viability. Acute (≤4 days) CT, MRI, and PET studies were performed in eight patients with TBI who had contusions. Four regions-of-interest (ROI) containing the contusion core, pericontusional hypodense gray matter (GM), pericontusional normal-appearing GM, and remote normal-appearing GM, were defined using a semi-automatic method. The correlations of cerebral blood flow (CBF) with OEF, cerebral metabolic rate of oxygen (CMRO2), and cerebral metabolic rate of glucose (CMRglc) were examined. The oxygen-glucose ratio (OGR) in each brain region was evaluated for anaerobic metabolism. The results show that pericontusional tissue had progressively diminishing OEF, CBF, CMRO2, or CMRglc approaching the contusion core. In general, there was a preserved ratio of CBF to CMRO2 in pericontusional hypodense GM. The OGR of the pericontusional hypodense GM was low (<4.0) and was inversely correlated (r=-0.68) with time after injury. A large proportion (%area: 22-76%) of pericontusional hypodense GM tissue had CMRO2 values less than 35 μmol/100 g/min, with this percentage increased with time after injury.

FIG. 1.

Comparison of the regional cerebral blood flow (CBF) values obtained from the clustering and the traditional regions of interest method, respectively. Plot A shows the individual patient (n=8) data of the four regions in different colors: Region 1, remote normal-appearing GM (purple dots); region 2, pericontusional normal-appearing gray matter (GM) (green dots); region 3, pericontusional hypodense GM (red dots); region 4, contusion core (blue dots). Plot B shows the mean values (±1 standard deviation) of the eight patients from each type of region.

FIG. 2.

CT, FLAIR MRI, and initial cluster image corresponding to the patients shown in Figure 2. The cluster images were first generated from CT and MR images by the computer program. Subsequently, the program used the regions of interest (outlined in white; manually drawn earlier) to confine the data analysis to the four centrifugal pericontusional regions—contusional core (blue), pericontusional hypodense GM (red), and pericontusional normal-appearing GM (green).

FIG. 3.

Parametric images of cerebral metabolic rate of glucose (CMR_glc), cerebral blood flow (CBF), oxygen extraction faction (OEF), and cerebral metabolic rate of oxygen (CMRO₂) for Patients 1 and 2 corresponding to Table 1.

FIG. 4.

Mean values of (A) oxygen extraction fraction (OEF), (B) cerebral blood flow (CBF), (C) cerebral metabolic rate of oxygen (CMRO₂), and (D) cerebral metabolic rate of glucose (CMR_glc) calculated from the four regions (region 1, remote normal-appearing gray matter [GM]; region 2, pericontusional normal-appearing GM; region 3, pericontusional hypodense GM; region 4, contusion core) of the eight patients.

FIG. 5.

Scatter plots (left: Patient 1; right: Patient 2) showing concurrent changes of cerebral blood flow (CBF) and oxygen extraction fraction (OEF) (upper row), CBF and cerebral metabolic rate of oxygen (CMRO₂) (middle row), and CBF and cerebral metabolic rate of glucose (CMR_glc) (lower row) voxels of the contusional core (blue), the pericontusional hypodense GM (red), the pericontusional normal-appearing GM (green), and the remote normal-appearing GM (purple). Regression lines for the voxels in remote normal-appearing GM are shown in purple. The “+” labels mean values of the four regions.

FIG. 6.

(A) Mean oxygen-to-glucose ratio (OGR) values in the four regions (region 1, remote normal-appearing GM; region 2, pericontusional normal-appearing GM; region 3, pericontusional hypodense GM; region 4, contusion core) of the eight subjects. The “*” labels the regions that had significantly (p<0.05) different OGR as compared with the remote normal-appearing GM. (B) Correlation between time after injury and the mean OGR of pericontusional hypodense GM.

FIG. 7.

(A) Representative example (Patient 2) showing the brain region with cerebral metabolic rate of oxygen (CMRO₂) values less or greater than 35 μmol/100 g/min, respectively. The region of interest (in black) shown in the CT image was the same as shown in Figure 2. (B) Correlation between time after injury and the %area of tissue with CMRO₂ less than 35 μmol/100 g/min (eight brains; solid circles for pericontusional hypodense gray matter [GM] and open circles for the pericontusional normal-appearing GM).