Recombinant tissue plasminogen activator increases blood-brain barrier disruption in acute ischemic stroke: an MR imaging permeability study

Abstract

Background and purpose: Although thrombolytic therapy (recombinant tissue plasminogen activator [rtPA]) represents an important step forward in acute ischemic stroke (AIS) management, there is a clear need to identify high-risk patients. The purpose of this study was to investigate the role of quantitative permeability (KPS) MR imaging in patients with AIS treated with and without rtPA. We hypothesized that rtPA would increase KPS and that KPS MR imaging can be used to predict the risk of hemorrhagic transformation (HT).

Materials and methods: Thirty-six patients with AIS were examined within a mean of 3.6 hours of documented symptom onset. KPS MR imaging was performed as part of our AIS protocol. KPS coefficients in the stroke lesion were estimated for all patients, and the relationship between KPS and both HT and rtPA was investigated by using Student t tests. Receiver operating characteristic (ROC) curves were computed for predicting HT from KPS.

Results: The occurrence rate of HT for patients who received rtPA and those who did not was 43% and 37%, respectively. Assessment of KPS in the lesion revealed significant differences between those who hemorrhaged and those who did not (P < .0001) as well as between rtPA-treated and untreated patients (P = .008). ROC analysis indicated a KPS threshold of 0.67 mL/100 g/min, with a sensitivity of 92% and a specificity of 78%.

Conclusions: The results of this study indicate that KPS is able to identify patients at higher risk of HT and may allow use of physiologic imaging rather than time from onset of symptoms to guide treatment decision.

Fig 1.

A, A 50-year old female patient with acute ischemic stroke (AIS), visible as an area of reduced diffusion (dark region) on the apparent diffusion coefficient (ADC) map obtained at 4 hours 50 minutes post-symptom onset. Recombinant tissue plasminogen activator (rtPA) is administered during MR imaging. B and C, A region of interest is placed within the infarct, defined as the core area of reduced ADC, and then copied to the equivalent dynamic contrast-enhanced (DCE) image set (B), to generate permeability (KPS) maps (C). D, In this patient, the infarct region of interest demonstrates a positive slope of best fit with KPS = 1.59 mL/100 g/min. A region of hyperintensity is also visible on the equivalent postcontrast T1-weighted section obtained 20 minutes after completion of the KPS scan. E, Follow-up CT (obtained 48 hours later) shows an area of hypointensity characteristic of hemorrhagic transformation (HT) colocalized with the region of elevated KPS.

Fig 2.

Mean microvascular KPS values of the infarct obtained at the time of presentation for all patient groups. Significantly elevated KPS values are seen in patients who subsequently proceed to HT, compared with those who do not (P < .0001). Patients receiving rtPA also have significantly greater KPS compared with those who do not receive rtPA (P = .008).

Fig 3.

A, An 81-year old male patient with AIS, visible as an area of reduced diffusion (dark region) on the ADC map obtained at 2 hours 47 minutes post-symptom onset. B and C, rtPA is administered during MR imaging. A region of interest is placed within the infarct, defined as the core area of reduced ADC, and then is copied to the equivalent DCE image set (B), to generate KPS maps (C). In this patient, the mean infarct KPS is 0.84 mL/100 g/min. D and E, A region of hyperintensity is also clearly visible on the equivalent diffusion-weighted image (D), but not on the postcontrast T1-weighted image obtained 20 minutes after completion of the KPS scan (E). F, Follow-up T2-weighted MR image obtained 48 hours later reveals 2 “hotspots,” or areas of hypointensity, characteristic of HT colocalized with the zones of hyper-KPS on the KPS map.