Daniel Korya, MD

Bauer S, Wagner M, Seiler A, Hattingen E, Deichmann R, Nöth U, and Singer OC. Quantitative T2′-Mapping in Acute Ischemic Stroke. Stroke. 2014

According to an article published in Nature Medicine in 2008 by Eng Lo, we are in the 4th decade of penumbral science. The first decade mostly focused on ischemic regulation of electrophysiology, cerebral blood flow and metabolism. The progress made in the second decade was largely due to molecular mechanisms that mediated penumbral cell death. The third decade is when neuroimaging became important clinically to isolate dead brain from salvageable penumbra. Now we are in the 4th decade, and indicated by Bauer and her colleagues, we may be closer to drawing a more precise boundary between dead brain and penumbra. 

As the authors point out, the aim of obtaining advanced imaging in the setting of acute stroke is to reliably detect the severity of ischemic changes with regard to irreversibly damaged and potentially salvageable brain tissue. That is why diffusion and perfusion weighted (DWI, PWI) imaging has become so important in recent clinical practice. The DWI provides a good estimate for the infarct core and the PWI is good at telling us the extent and severity of perfusion deficits. However, there is a small problem with PWI: although it tells you about perfusion to a certain area of the brain, it doesn’t tell you much about metabolic dysfunction.

We know from prior studies that the penumbra is an area around the stroke that has a cerebral blood flow of less than 20 ml/100g/min, but the oxygen consumption is preserved.  So, that means that the oxygen extraction fraction (OEF) must be significantly increased.  The T2’ relaxation time on the MRI is influenced by oxygen levels in hemoglobin since oxy-Hb is diamagnetic and deoxy-Hb is paramagnetic. So, it is ideal for telling us which parts of the ischemic brain are extracting more oxygen than others and therefor are still alive, but at risk. But, there is one problem with the T2’: it is highly susceptible to movement artifact and stroke patients (especially aphasic ones) are not very likely to follow commands and lay still in the MRI.

Bauer and her colleagues implemented a new “in-house developed” method to solve the problem of motion artifacts in T2’ imaging. They used this same method for subarachnoid hemorrhage patients and were successful, so they tried it in 11 ischemic stroke patients in this proof-of-concept study. 

The authors provided a technical, yet short, explanation of the method used to correct for motion. It’s a three-step algorithm: motion is detected with the correlation coefficient of the pixel-dependent exponential T2* fit. Then, T2* fitting is performed for three different input data sets based on resolution in the phase encoding direction. Finally, for each data set (100%, 50% and 25% resolutions), the best fit is chosen based on the constructed image with reduced movement. T2′ maps were calculated using the equation: 1/T2’ = 1/T2* – 1/T2. In order to exclude zero-voxels and voxels with cerebrospinal fluid, only T2` values between 1 ms and 300 ms were included for further analysis.

The bottom line is that it’s a complicated algorithm written in MATLAB that seemed to work before for SAH and it was worth a shot in ischemic stroke. 

The results were consistent with the concept of T2’ imaging and showed lower values within the ADC lesions (restricted diffusion) as well as lower values in the perfusion-restricted tissue (based on TTP). Accordingly, within the restricted diffusion lesions, the T2’ times were significantly slower than they were within the perfusion-restricted areas. 

This study is important to note for a few reasons: 1) It emphasizes the importance of MRI in acute ischemic stroke; 2) It suggests a solution to a known problem of motion artifact on T2’ imaging, and 3) It opens the door to potentially quantifying the level of ischemia in a stroke and could help in directing treatment. 

In an attempt to go “full circle” with this blog, it appears that Bauer and her colleagues have found a way to meld efforts made in the 4thdecade of penumbra science with those of the 1st decade: i.e. advanced neuroimaging can now detect oxygen consumption and metabolism in the ischemic brain more accurately.