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To be or not 2b? To see or not 2c? Alas, the clock is ticking on TICI
  1. David F Kallmes1,
  2. Alejandro A Rabinstein2,
  3. Matthew J Gounis3
  1. 1 Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA
  2. 2 Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA
  3. 3 Department of Radiology, University of Massachusetts, Worcester, Massachusetts, USA
  1. Correspondence to Dr David F Kallmes, Department of Radiology, Mayo Clinic, Rochester, MN 55902, USA; kallmes.david{at}mayo.edu

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The time has come to throw the flag on the Thrombolysis in Cerebral Infarction (TICI) scale. Conceived in surrogacy from our cardiology brethren and sistren’s Thrombolysis in Myocardial Infarction (TIMI) score,1 TICI’s birth was anything but smooth. However, even though plagued by internal inconsistencies,2 confusing nomenclature,3 unclear pronunciation (are you a ‘tissy’ or ‘tiki’ person?), and modifications and more modifications, TICI emerged from a small cohort of recanalization scales (does anyone remember AOL?4) to become the coin of the realm in research and clinical practice. But, heck, we don’t even use thrombolysis anymore, having entered the era of embolectomy years ago.

Before turning to how we might fix this situation, we must acknowledge that TICI—and mTICI and oTICI—have served their purpose. TICI started out as a six-point scale that gradually collapsed to a dichotomous scale (2b or better) that was a simple and useful, yet surrogate, outcome for clinical and device-related trials. But our community can—and must—do better. The three of us are not the first to lament the limitations of TICI. In 2012, a working group led by Dr Zaidat concluded, ‘Until further technical and imaging advances can incorporate real-time reliable perfusion studies in the angio-suite to delineate regional perfusion more accurately, the TICI grading system is the best defined and most widely used scheme … A new scale that combines primary site occlusion, lesion location, and perfusion should be explored in the future.’5 That future is now.6

Let us explain

More is better

Multiple recent studies have shown strong correlation between ≥TICI 2b subcategories and outcome.7 Surprise, TICI 3 is better than TICI 2c, which is better than TICI 2b,8 9 but the inter-reader agreement, especially for TICI 2c, has room for improvement, likely because of vague criteria.8 Furthermore, the thresholds among these various groups are arbitrary, based on long-ago choices of percent recanalization that had—and have—no clinical correlate. The old standard of TICI 2b or better must go.

Location, location, location

Stroke location (especially in eloquent regions) is an independent predictor of both cognitive and global deficits,10 and innovative neurologists have begun testing the analysis of communication deficits as an adjunct to the NIH Stroke Scale.11 And yet, in TICI, as in many widely-applied stroke scales (including Alberta Stroke Program Early CT Score (ASPECTS)12 and RAPID13) eloquence is roundly ignored. We are behind the surgeons and their Spetzler–Martin arteriovenous malformation scale developed 30 years ago!14 We downgrade an embolectomy outcome as much for defects in the right anterior frontal region as much as the left Rolandic area. Why? Of course, for simplicity and reproducibility, but reproducibly wrong remains wrong.

The denominator problem (or, it is not all relative after all)

Inherent in TICI is use of the relative rather than absolute outcome measures. As such, a 60% ongoing defect in a (small) presenting M2 occlusion might result in the same ischemic burden as a 20% ongoing defect in a (large) presenting internal carotid artery terminus occlusion, yet the former would be TICI 2a (failure!) and the latter TICI 2b (success!). Only the final, absolute ischemic burden matters to our patients.

It’s not just the pictures

Recent data indicate that, in addition to final angiographic outcome, the number of passes may also impact clinical outcomes.15 Thus, technical features beyond percent recanalization should be acknowledged. Furthermore, infarcts in new territories (INT)16 that may have profound impact on tenuous collaterals should be factored into future outcome assessments.

Recanalization, reperfusion, and ongoing confusion

Tissue perfusion can be achieved by antegrade and retrograde flow, yet TICI is used by most practitioners to denote antegrade flow only. Even if we could coalesce around the goal of reperfusion rather than recanalization, clearly there are ‘good’ reperfusion and ‘bad’ reperfusion scenarios, the latter indicating reperfusion injury. Parsing among the good, the bad, and the ugly might require more than angiographic evaluation; perfusion scans may be necessary to assess for luxury or misery perfusion.

Wait, I just want to take out clots, so what do I care about a few distal emboli?

It is true that current embolectomy devices are limited to use in proximal vasculature and thus a simple angiogram—even without any reference to TICI—might guide in-angiogram-suite decision-making. But improved understanding in the angio suite of angiographic and tissue perfusion outcomes can have profound relevance. First, new tools that target more distal emboli may depend on our knowledge of whether a specific distal territory will succumb over time; conversely, identifying distal areas as non-viable will guide operators away from potentially risky maneuvers. Second, clinical trials of large vessel occlusion are becoming more common, and are going to require characterization of outcomes far beyond TICI 2b alone. Third, we probably need to get away from offering each other ’high 5s' after pulling out clots to careful management in the minutes, hours, and days following embolectomy. A complete understanding of brain-at-risk, potential for reperfusion injury, and ongoing clot burden will help optimize patient care. Finally, we will hopefully soon enter the world of neuroprotectants,17 so a clear understanding of brain that is salvageable or at least at risk of reperfusion injury may help guide therapy.

Where do we go from here?

The first step in any recovery is admitting one has a problem. Our current pain point is the use of a gross score that is agnostic to eloquence (eTICI?), uses blunt thresholds not chosen to track with outcomes, ignores technical features such as number of passes (npTICI?) and INT (iTICI?), values relative rather than absolute ongoing perfusion defects (aTICI?), and cannot distinguish good from bad reperfusion anyway. Maybe we should, again, copy the cardiologists, who years ago added a risk assessment TIMI score, completely separate from the angiographic TIMI score, for prediction of ischemic events and mortality based on clinical symptoms, known risk factors, ECG findings, laboratory values, and recent aspirin use.18 We propose that these risk assessment factors should be examined in future randomized clinical trials in order to determine the influence of each on futile recanalization and the way in which it should be incorporated into a more nuanced, outcome-sensitive, and consistent recanalization scale.

A complete reboot

To solve all of the problems above we need a new perspective and also new technology. The prescient publication by Zaidat et al predicted in-angiogram-suite advanced imaging that can provide robust, spatially localized perfusion and viability data.5 A variety of old technologies have been revamped (eg, bioimpedance,19 transcranial ultrasound) by leveraging advances in artificial intelligence and robotics to monitor brain health. The primary goal of these retooled devices is pre-hospital triage, but their role for monitoring in the angio suite is an unexplored opportunity. However, these new tools are not yet ready for prime time. Numerous groups are at work developing such tools using cone beam (CB) CT to generate CT perfusion (CTP) data.6 To date, such CB-CTP is being proposed primarily for use in triaging patients to embolectomy (Go/no go); perhaps we should be pursuing the same technology for understanding when we are done (Stop/don’t stop) and what to do afterwards. These tools may allow us to create useful adjuncts to TICI, but what is really needed is to develop a physiologically and clinically relevant outcome scale that integrates measures of true reperfusion, tissue eloquence, and patient characteristics (such as severity of neurological deficits, age, etc). Only that way can we reach the goal of refining our therapeutic decisions and optimizing our prognostic acumen. If we work towards that goal, TICI’s days as the stand-alone recanalization metric will be numbered.

References

Footnotes

  • Contributors All authors contributed to the conception, drafting, revisions and approval of this commentary. DFK is the guarantor of this work.

  • Competing interests DFK: Consulting for Medtronic (all funds to the institution), ownership stake in Marblehead Medical, and has received research support from Medtronic, MicroVention, NeuroSigma, Shape Memory Therapeutics, IndumedX, Sequent Medical, Neurogami, and NeuroSave. AAR: Received funding from DJO Global. MJG: Has been consultant on a fee-per-hour basis for Codman Neurovascular, InNeuroCo, Medtronic Neurovascular, and Stryker Neurovascular; holds stock in InNeuroCo; and has received research support from the National Institutes of Health (NIH), Anaconda, Codman Neurovascular, Gentuity, InNeuroCo, Microvention, Medtronic Neurovascular, MIVI Neurosciences, Neuravi, Philips Healthcare, InNeuroCo, Rapid Medical, R92M, Stryker Neurovascular, The Stroke Project, and the Wyss Institute.

  • Provenance and peer review Not commissioned; externally peer reviewed.