Vascular permeability may spatially predict subsequent hemorrhages in stroke-prone spontaneous hypertensive rats

Abstract

Increases of vascular extravasations of MR contrast agent have been implicated to be predictive of hemorrhagic transformation in acute stroke patients. However, systemic studies are lacking. In this study, we aim to determine how the increased vascular extravasations of MR contrast agent can be used to predict the presence of subsequent hemorrhages in Stroke-prone spontaneous hypertensive rats (SHRsp). SHRsp rats (n=12), fed a high-salt low-protein diet after weaning, were imaged weekly on a 3 T SIEMENS Allegra head-only scanner beginning at 12 week of age and continuing for five weeks. Three sequences were used to acquire images, including a T2-weighted, a T2*-weighted, and a turboFLASH sequence. The acquired T2-weighted images provided anatomical data as well as an indication of brain edema. T2*-weighted images allowed assessment of hemorrhage and were acquired using a 3D gradient echo sequence (TE=25 ms). To obtain estimates of vascular permeability, the Look-Locker (L-L) technique employing the T-one by multiple read-out pulses (TOMROP) sequence (1) was used for pixel-by-pixel estimates of T1. The TOMROP sequence was repeated 10 times post-contrast. Finally, the PATLAK approach was utilized with the images acquired using the TOMROP sequence for obtaining permeability maps for each rat (2). All 12 rats developed asymmetric T2 hyperintensities by 14 weeks of age; 5 rats developed 7 regions of intracerebral hemorrhage (detected by T2*) at later time-points. Four hemorrhages were located within the striatum; three were located in the cortex. All rats that developed spontaneous hemorrhages demonstrated concurrent or prior vascular permeability (determined by Gd as described above) at the site of the hemorrhage. In 4 of the 7 hemorrhages, evidence of vascular permeability was found prior to the detection of hemorrhage, preceding it by up to 2 weeks. The remaining three temporally coincided with the hemorrhage. The temporal evolution of vascular permeability, T2 and T2* images of a representative rats are shown in Fig. 1. It is immediately evident that the presence of vascular leak precedes the hemorrhage by one week. Although blood-brain-barrier (BBB) breakdown, cerebral edema, and hemorrhage have been well-described in this model, the spatial and temporal relationship between these events has not been well-delineated. Although increased vascular permeability did not precede 3 of 7 hemorrhages but rather appeared concurrently, we believe that this may be due to the poor temporal resolution of our imaging scheme. These data suggest that hypertensive intracerebral hemorrhage is preceded by focal vasculopathy resulting in breakdown of the BBB.