Dr Negar AsdaghiNegar Asdaghi, MD
This is the second of a 2-part interview. For part 1, click here.

In a pro-con debate around thrombolysis at the 2020 International Stroke Conference, in Los Angeles, California, the ongoing discussion around the use of perfusion imaging in the treatment of stroke was highlighted by a pair of experts.

One, arguing the pro side, was Anna Ranta, MD, PhD, associate professor, and head, Department of Medicine, University of Otago Wellington, in New Zealand. Ranta emphasized and highlighted the role of perfusion in recent years and how it has aided in streamlining workflow and changing the philosophy of ischemic stroke acute therapies. The other, on the con side, was Negar Asdaghi, MD, assistant professor of neurology, Stroke Division, Department of Neurology, University of Miami Miller School of Medicine. Asdaghi highlighted the existing pitfalls in the ability to define ischemic core and ischemic penumbra using advanced imaging, including perfusion imaging.

To find out more about this discussion, NeurologyLive spoke with Asdaghi in an interview. She shared her insight into her side of the debate and shared insight into how the EXPAND clinical trial data fit into the conversation.

NeurologyLive: What exactly were you arguing in your portion of the conversation?

Negar Asdaghi, MD: Nowadays, stroke neurologists receive automated perfusion analyses on their smartphone or on a commercially available perfusion software. The first set of images gives a quick volumetric calculation of ischemic penumbra and ischemic core and a mismatch ratio. The problem is that these volumetric assessments are estimates and not definitive measurements. Clinicians need to know this when interpreting these images.  What I emphasized during the debate was how often these numbers can be erroneously high or low. The volumetric estimates of ischemic penumbra and core are intimately related to time from symptom onset to image acquisition, infarct severity, and recanalization status of the patient. In other words, these volumes of ischemic core and penumbra can overcall or undercall the regions that are thought to be dead or at risk of dying and knowledge of these factors will help to put perfusion imaging in the context of the information obtained from all other images including the simple non-contrast CT of the head.

Also, perfusion images are extremely sensitive to artifacts. I showed many examples of where and when perfusion can get it wrong. Things can be as simple as motion artifact—which occurs when the patient moves during image acquisition—or artifacts created because of issues with the bolus (insufficient amount of bolus or contrast administered at an insufficient rate), or the acquisition time was shortened (truncation artifact).

I emphasized the 2 big pitfalls of perfusion imaging. The first is overcalling the volume of the ischemic core if perfusion imaging is obtained in the hyper-early phase. This is referred to as the “ghost infarct core” (large regions of the brain thought to be dead based on perfusion parameters, but these regions are still alive and potentially salvageable with reperfusion therapies). This occurs because the automated thresholds that we use to define ischemic core are different early in the ischemic cascade as compared to late in the ischemic window. A second pitfall is an entity referred to as CBF normalization, when perfusion imaging under-calls ischemic infarct (usually a region that is visibly infarcted on a non-contrast CT head is not thought to be dead by perfusion parameters), the perfusion images are usually acquired late in this scenario. So, the patient may be considered a candidate for reperfusion therapies, whereas in reality, those brain regions are completely dead.

How widespread is this debate in the clinical community?

There has been cumulatively more and more evidence of how we should use advanced imaging to replace the actual time of symptom onset when it comes to the treatment of patients with ischemic stroke. In the past 10 years, the success of randomized trials resulting in changes in the treatment guidelines has led to drastic practice changes across the U.S. and globally. Perfusion imaging is an easy way of defining dead versus not dead brain tissue, and as long as the clinicians are aware of the shortcomings of perfusion, then this is a powerful tool that has significantly changed the landscape of stroke treatment.

How does the data from EXTEND and other trials fit into this discussion?

The EXTEND trial looked at perfusion imaging to see whether a selective group of ischemic stroke patients with a particular perfusion profile may benefit from intravenous thrombolytic therapy outside of the conventional 4.5 hour time window. Essentially, the results of EXTEND confirmed that if the patient has a favorable perfusion ischemic core-penumbra mismatch, he/she would benefit from intravenous alteplase therapy up until 9 hours from symptom onset, which is way longer than the original 4.5 hours’ time limit. That's a substantial increase in available time to start intravenous thrombolysis.

Other trials, DIFFUSE 3 and DAWN, looked at the safety and efficacy of endovascular therapy in patients presenting late to the hospital and similarly showed that those with a favorable perfusion profile and a large vessel occlusion can benefit from thrombectomy up to 24 hours from symptom onset.

What should the clinician community take away from this debate?

The take-home message is that we have powerful therapies that are very effective in the treatment of patients with ischemic stroke. A patient with stroke-like symptoms should be taken to the closest stroke center. Patients should always call 911 and be taken by the EMS.

Urgent assessment, stroke evaluations, use of advanced imaging —CT angiogram, CT perfusion, MR angiogram, and MR perfusion—can help us determine who is eligible to receive reperfusion treatments

This concept of time is dead has really changed the philosophy of stroke treatment across the globe and has given many, many stroke patients a chance to survive and to thrive and to recover from stroke. This is thanks to hundreds, if not thousands, of dedicated stroke neurologists, scientists, clinicians, radiologists, and neuro-interventionalists, who dedicated their lives to advancing our field. Where we stand today is because of them, and I think that every person who deals with stroke should be excited to be working in this field that has arguably changed more than any other field in medicine over the past 2 decades. Your brain is the only non-transplantable organ in the body, so every effort to save every brain cell is really precious.

Transcript edited for clarity.
REFERENCE
Time Is Brain Is Dead: Only Dead Brain Is Dead (Debate) (an ASA and Stroke Society of Australasia Joint Symposium). Presented at: 2020 International Stroke Conference. February 19-21, 2020; Los Angeles, CA. Session 169.