CT perfusion for stroke: Should you use it?: Page 2 of 3
CT perfusion for stroke: Should you use it?: Page 2 of 3
YES: CT perfusion proves its value in planning treatment for acute ischemic stroke
Careful patient selection is crucial, but CT perfusion can be key in making a decision whether to proceed with intravascular tPA
BY CAROL P. GEER, M.D., AND CHRISTOPHER T. WHITLOW, M.D., Ph.D.
Ischemic stroke remains a common cause of substantial morbidity and mortality in the U.S., and great effort has been expended to better evaluate and treat affected patients. The FDA has approved the use of intravenous tissue plasminogen activator in eligible patients presenting for treatment of ischemic stroke within three hours of symptom onset and without evidence of intracerebral hemorrhage on CT of the brain, which has improved clinical outcomes in some patients.1
However, there remain a significant number of patients who do not derive benefit from IV tPA, possibly due to substantial clot burden in larger vessels, such as the internal carotid artery and proximal middle cerebral artery (MCA). There are also a number of patients who present to the healthcare system after the three-hour—or now the 4.5-hour—window has passed.2-5 Although many patients present outside of the standard treatment window for IV tPA, there is evidence that delayed recanilization may have clinical benefit in some of these patients. Of these, patients who have brain tissue that is ischemic but not irreversibly damaged, or so-called ischemic penumbra, are those who stand to benefit most. Diagnostic imaging methods designed to accurately measure penumbra and therapies directed at preserving this tissue in patients who present after the IV tPA window are targets of active research across the globe.6-13
CT perfusion has become a key imaging modality to qualitatively determine the amount of penumbra present relative to completed infarct in patients with occlusive cerebrovascular thrombus.7-9,14,15 CT perfusion defines penumbra as a mismatch between the mean transit time (MTT) and cerebral blood volume (CBV).16 Cerebral blood flow (CBF) is subsequently calculated from the measured MTT and CBV. MRI diffusion and perfusion imaging has also been used to evaluate for significant salvageable brain tissue.17 But in most emergency departments, CT perfusion can be obtained more quickly.
Patients presenting with stroke symptoms generally first undergo head CT without contrast to evaluate for the presence of intracranial hemorrhage and imaging signs of acute ischemia. In many centers, including ours, patients then undergo head and neck CT angiography to evaluate for occlusive cerebrovascular thrombus. Because the patient is already on the CT table, obtaining CT perfusion data to evaluate for penumbra, as opposed to transferring the patient for MRI examination, makes good clinical sense, given that time is the critical factor for preserving brain. The main disadvantages to obtaining CT perfusion rather than MRI diffusion-perfusion data are the radiation exposure and the IV contrast administration. The critical question faced by diagnostic and treating clinicians is whether the decrease in radiation and contrast exposure gained by performing MRI diffusion-perfusion rather than CT perfusion is worth the increase in time to reperfusion and potential infarct expansion.
Indeed, several studies have demonstrated that there is an increased risk of infarct expansion if there is a large penumbra.17,18 Furthermore, some recently published data suggest that patients presenting with large penumbra and relatively small completed infarcts longer than eight hours after symptom onset, as well as some patients with wake-up strokes, may benefit from intra-arterial thrombolysis.6,10,12 This being so, many centers, including our own, have started to be more aggressive in treating patients with substantial ischemic penumbra, using intra-arterial thrombolysis to recanalize obstructed arteries.
The critical information necessary for evaluating the viability of intra-arterial thrombolysis as a treatment option is based on perfusion imaging data and includes penumbra size and degree of completed tissue infarction. Endovascular recanalization of patients who already have a large completed infarct increases their risk of complications due to edema and reperfusion hemorrhage.19 CT perfusion and MRI data, therefore, are used to identify patients who may benefit from intra-arterial thrombolysis, and those in whom recanalization may be of questionable benefit or even be harmful. Although CT and MRI can both be useful for evaluation of penumbra and infarct completion, in our hospital and many others, it is much faster to obtain CT perfusion. MRI scanners at our institution are not located in, or even very close to, our emergency department, making transport time a serious issue.
Given the necessity for CT perfusion in the evaluation of ischemic stroke, at our institution we attempt to employ strict adherence to ALARA (as low as reasonably achievable) principles. In particular, we have optimized our CT scan technique to use a low-dose perfusion protocol that maintains a radiation dose at less than 200 mGy. Attention to technique, as well as oversight by experienced radiologists and a dedicated physicist, are critical elements we have employed to avoid the complications that other centers have reported with radiation exposure, including hair loss and scalp injury.20
Furthermore, we work in close collaboration with the primary clinical referral services at our institution (emergency medicine, neurology, and neurosurgery) to carefully select patients in whom the use of CT perfusion is important for treatment planning. Indeed, performing CT perfusion on every stroke patient as a standard protocol is probably not good medicine and is not being responsible with radiation exposure. Using CT perfusion in a careful and judicious manner, when the results may change clinical management, is likely to be the safest and most efficacious way to use this technology.
To elucidate the above discussion, we present examples in which CT perfusion data were collected during the evaluation of two patients presenting to our hospital for treatment of acute ischemic stroke 4.5 hours after symptom onset.
Case 1: A 64-year-old woman presented with acute left hemiplegia and neglect four hours and 46 minutes after symptom onset. Head CT was negative for acute hemorrhage, and no large area of low density was identified to suggest infarct. Head and neck CTA demonstrated a large occlusive thrombus in the M1 segment of the right MCA. CT perfusion demonstrated elevated MTT in the entire right MCA, with only a small area of decreased blood volume in this vascular territory, compatible with a large penumbra (Figure 1). Studies have shown these patients to have an increased risk of infarct expansion. This patient was, therefore, recanalized using a combination of intra-arterial tPA and mechanical thrombolysis, including the Penumbra System (Penumbra, Alameda, CA) and balloon angioplasty. She made a complete recovery.
Case 2: An 84-year-old man presented with acute right hemiplegia, aphasia, and neglect four hours and 30 minutes after symptom onset. Head CT was negative for acute hemorrhage, and no large area of low density was identified to suggest infarct. Head and neck CTA demonstrated a large occlusive thrombus in the left M1 segment. CT perfusion was obtained, but due to a computer malfunction immediately after the study was acquired, the data could not be processed and viewed. The patient was nonetheless taken for intra-arterial recanalization, as the head CT suggested the absence of a large completed infarct, and we could not wait any longer for the perfusion data. Recanalization of the left MCA was performed using mechanical thrombolysis.
Following the procedure, the computer was fixed and the CT perfusion data were processed and subsequently reviewed. They demonstrated elevated MTT in the entire distribution of the left MCA with a matched decrease in CBV and CBF, suggesting completed infarct (Figure 2). Postoperatively, the patient developed severe edema in the left MCA distribution and expired.
Although outcomes from these two cases, and others in the literature, are certainly insufficient to direct policy and change standards of care, they do highlight the potential clinical utility of CT perfusion data in directing the delayed recanalization of occlusive cerebrovascular thrombus, and serve as a basis for further evaluation of these technologies. Case 2 is particularly important, as it demonstrates the importance of careful patient selection before application of endovascular recanalization techniques. Indeed, had the CT perfusion data driven subsequent management of this patient, intra-arterial thrombolysis would not have been performed, given the presence of a large completed infarct. The patient in case 2 was obviously not helped by recanalization, and it is possible that intra-arterial treatment resulted in worsening cerebral edema, among other negative consequences, such as raising false hope among the family, and adding unnecessary expense to the healthcare system.
In summary, new data continue to support attempting endovascular recanalization of occlusive cerebrovascular thrombus if patients present with a large penumbra and small infarct after the systemic IV tPA treatment window. Establishing penumbra versus completed infarct appears to be important in the decision tree for determining who might be helped or potentially hurt with delayed thrombolysis. CT perfusion in many medical centers is faster to obtain than MRI, which is important when time to reperfusion is a critical factor in successfully salvaging brain tissue.
We do recognize, however, that increased radiation exposure and the potential for adverse long-term consequences accompany the use of CT perfusion. For this reason, CT perfusion should be used judiciously in those patients with the appropriate clinical presentation, and when head CT and CT angiography data suggest that it may be helpful in directing further therapy, such as intra-arterial thrombolysis. In particular, we strongly urge avoiding the broad application of CT perfusion as a standard imaging protocol for all patients presenting with stroke-like symptoms.
There is no question that the use of CT perfusion in guiding intra-arterial thrombolysis remains controversial,12,13 and that prospective, randomized, controlled clinical trials will be necessary to determine the true utility of CT perfusion and endovascular thrombolytic techniques for the diagnosis and treatment of ischemic stroke. Until then, careful evaluation of each individual patient is critical to guide the appropriate use of CT perfusion, which will lead to the most judicious, conservative, and, hopefully, safest application of this technology.
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