DWI detects early cytotoxic edema by measuring the random motion of water protons, a process that is reduced by failure of the energy-requiring active water transport mechanism. DWI studies in animal models have demonstrated a decline in brain ADC values during cardiac arrest, which then reverse after successful resuscitation.16-18
In spite of successful reperfusion, however, secondary energy failure and ADC decrease follow after several hours.19
It has been shown in preliminary studies that quantitative MRI brain changes correlate with functional outcome in comatose post-cardiac arrest survivors.14, 20
The percentage of brain tissue below a threshold of 650-700 ×10−6
/sec was found to correlate with functional outcome at 3 months after the arrest.14
Based on whole brain quantitative DWI analyses the ideal time-window for prognostication appears to be between 49 and 108 hours after the arrest, when the ADC reductions are most apparent. None of the patients with more than ten percent of brain tissue with an ADC value below 650-700 ×10−6
/sec during this time-window regained consciousness.
In this prospective study, we analyzed in detail which brain structures at what time-point were most severely affected by ADC reduction, comparing good and poor outcome patients with normal controls and with each other. Our results show that ADC changes caused by global ischemic brain injury in humans are much delayed as compared to ADC changes caused by focal cerebral ischemia. In severe global ischemic brain injury associated with poor outcome, reduced diffusion may not be apparent in the initial hours after the arrest.
Since physicians are increasingly using brain MRI with DWI for prognostic purposes in post-cardiac arrest patients, it is important to be aware that ADC changes in these patients are both time- and region-dependent during the first week. We found that both the qualitative and quantitative MRI changes in poor outcome patients were most severe in the cortical regions and most apparent between 3-5 days after the arrest. Although ADC changes occur globally, they most profoundly affect the cortical gray matter structures in the poor outcome patients in the first week after the arrest. None of the patients with moderate-to-severe cortical abnormalities on their MRI awoke from their coma. Importantly, the three poor outcome patients who did not display substantial cortical abnormalities on their DWI MRI were imaged at 2, 7 and 14 hours after their arrests, suggesting that these changes are not apparent early after the arrest. In contrast to the gray matter structures, reduced diffusion in the white matter structures was not observed until the end of the first week. This DWI pattern likely reflects differences in tissue response to ischemic injury between various brain structures.21
Most patients who regained consciousness were qualitatively read as having normal cortical structures, with the exception of four patients who had mild-to-moderate abnormalities on the FLAIR and/or DWI sequence in one or more cortical gray matter structures. Furthermore, half of the good outcome patients had qualitative changes in the deep gray nuclei. Thus, mild-to-moderate cortical abnormalities and abnormalities in the deep gray nuclei did not exclude the possibility of regaining consciousness. Since qualitative interpretation of symmetrical and potentially subtle MRI changes is likely to vary between observers, we suspect that quantitative ADC changes may be more specific for prognostication.
Prior data on the temporal and spatial profile of brain ADC changes in the first week following cardiac arrest are scarce.20, 22
A recently published retrospective study confirms our observation that regional brain ADC values differ between good and poor outcome cardiac arrest patients and are time dependent.20
Comparisons with normal controls were not performed. To our surprise, when compared to normal controls, we observed increased or facilitated (rather than reduced or restricted) diffusion in good outcome patients who awoke from their coma. This change was only apparent on our quantitative ADC analyses and most pronounced in the cortical structures, the hippocampus, the putamen and the corona radiata. Increased diffusion has to our knowledge not been reported previously in humans in this context. We hypothesize that this increased diffusivity may represent mild global vasogenic edema caused by transient increased blood-brain barrier permeability.
While diffusivity in the hippocampus of the good outcome patients was consistently increased, no difference was observed in the poor outcome patients as compared to controls. One possible explanation is that severe hippocampal hypoxic-ischemic injury is associated with both vasogenic and cytotoxic edema counterbalancing each other’s effects on the hippocampal ADC values.
The differences in the DWI data of individual structures between good and poor outcome patients were very similar in the quantitative and qualitative analyses when all time-windows were combined. The only exception was the caudate nucleus, which was rated distinctly different in the two groups with the qualitative DWI readings, but not with the quantitative measurements. The most likely explanation for this observation is that there is increased T2 signal effect in the DWI maps observed qualitatively but not measured by the quantitative ADC maps.
An important limitation of this study is a limited number of MRI observations in each time-window, in particular in the very early time-window of 0-48 hours. The main reason why patients were not scanned during this time was because they were undergoing therapeutic hypothermia and we wanted to avoid any possible effect of hypothermia on the quantitative DWI MRI results. Additionally, patients who were taken off life support without meeting specific clinical criteria for poor outcome were excluded from this study. We decided not to include these patients because their outcomes were considered uncertain. Lastly, the results of this study only apply to patients who undergo brain MR imaging within 8 days following cardiac arrest. We are aware that some patients are too unstable from a critical care standpoint to undergo MR imaging during this early time period. MRI changes caused by severe hypoxic-ischemic brain injury are different after the first week.7
In summary, we found that moderate-to-severe reduced diffusion in cortical regions is strongly associated with the inability to regain consciousness and that this finding is most apparent on MRI between 3 and 5 days after the arrest. In contrast, patients who are able to wake up from their coma exhibit increased diffusion involving the temporal and occipital lobes, the corona radiata, and the hippocampus. As brain MRI is increasingly used for prognostic purposes in critically ill neurologic patients, physicians need to be aware that brain diffusion changes are both time and region dependent in the context of diffuse hypoxic-ischemic brain injury during the first week.