Only Dead Brain Is Dead: Debating Perfusion Imaging in the Thrombolysis Window

Negar Asdaghi, MD, assistant professor of neurology, Stroke Division, Department of Neurology, University of Miami Miller School of Medicine

Negar Asdaghi, MD

This is Part 1 of a 2-part interview. Stay tuned for Part 2 later this week.

At this year’s annual International Stroke Conference, in Los Angeles, California, a topic of discussion among presenters and attendees alike was the use of thrombolysis in the late time window of more than 4.5 hours from symptom onset. A panel featuring several experts assessed the proposition that perfusion imaging should replace time in this paradigm of thrombolysis.

Featuring a pair of experts debating the pros and cons of each side of the discussion, the session also showcased the current research, most notably data from the EXTEND trial. One of these experts was Negar Asdaghi, MD, assistant professor of neurology, Stroke Division, Department of Neurology, University of Miami Miller School of Medicine, who debated the con side.

To find out more about this discussion, which is ongoing in the stroke treatment landscape, NeurologyLive connected with Asdaghi. She shared her insight into the debate at ISC 2020, and what role perfusion imaging currently plays in the field.

NeurologyLive: Could you expand on what your debate at ISC 2020 centered around?

Negar Asdaghi, MD: For the purposes of the debate, there were many things that were a little bit over-embellished, so to speak, so that we could make our cases, but the idea is that 25 years ago, we got a treatment that works beautifully for stroke and we only had 3 hours to implement it. Fast forward 25 years later, we now have multiple forms of reperfusion therapies. One of them is the same treatment we had 25 years ago, that we could administer intravenously. We now can administer the same therapy intraarterially inside the brain, and better yet, we can use many thrombectomy devices, from stent retrievers to suction devices to actually go to the site of the intracranial occlusion and open them.

It is important to remember that time is brain—if you have a large vessel occlusion, for every minute that passes, the brain loses somewhere around 1-2 million neurons depending on where that blockage is. The idea is that the faster we open this blockage, the faster we restore the blood flow to the brain and the more brain cells we are able to save. We used to think that we only have 3 hours to safely administer reperfusion therapies to patients and that was very limiting.

Today, 25 years after the publication of the seminal National Institute of Neurological Disorders and Stroke (NINDS) paper that showed the intravenous administration of thrombolysis was safe and efficacious within 3 hours of symptom onset, we now know that reperfusion treatments can safely and effectively be offered to a highly selective group of patients up to 24 hours from the onset of their symptoms. To be able to make this selection, advanced imaging is used to try and determine what is the infarct core (brain regions that have died) and what is still salvageable (ischemic penumbra), and if the volume of infarct core is low and the ratio of dead brain (core) to salvageable brain (penumbra) is high, then we're able to safely administer these therapies. No longer do we just look at the clock and make time-based decisions, rather we do brain-based decisions.

The majority of the recently completed and published randomized trials, that confirmed the safety and efficacy of reperfusion therapies up to 24 hours from symptom onset, in 1 way or another used perfusion imaging to try to determine the volume of ischemic core and that of the ischemic penumbra for patient selection. So, the topic of the debate was how do we best move forward using imaging-based criteria over time-based criteria.

I debated Anna Ranta, MD, PhD, associate professor and head, Department of Medicine, University of Otago Wellington, in New Zealand, who nicely summarized the results of the recently completed randomized trials and other large-scale studies. She emphasized and highlighted the role of perfusion in the increase in the use of reperfusion therapies in the recent years and it has helped us streamline our workflow and change the philosophy of ischemic stroke acute therapies —all of which is absolutely correct.

What I was trying to highlight on my end was that, even in 2020, we are still not very good at defining the exact regions of ischemic core and ischemic penumbra using any form of advanced imaging, including perfusion imaging. Therefore, it is imperative that the practicing stroke neurologists be aware of some common perfusion pitfalls when interpreting these images in routine practice.

What should physicians know about perfusion imaging?

It's a tool. It's an important imaging tool, but like every other tool, 1 needs to understand some of the nuances of perfusion imaging from its acquisition, to image post-processing and interpretation. I briefly reviewed how perfusion (CT or MR perfusion) is acquired and the different perfusion maps produced. I summarized how we currently arrive at the automated volumetric analyses of ischemic core, ischemic penumbra and their absolute difference (ischemic mismatch) or the ratio between the 2. I also briefly reviewed which perfusion maps were used in the past to define these parameters and how over time we realized the pitfalls of using certain maps or certain thresholds in those maps.

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.