Micro Embolus In Intracranial Arteries Through: Rats After Unilateral Cerebral Microemboli Experimental Observation

Background. Much of the brain is perfused by penetrating arteries that are the "single source" of blood to their surrounding tissues. These tissues should be equally vulnerable to ischemia from embolic occlusion, but there are questions about whether emboli have access to the penetrating arteries serving the deep brain tissues. To examine this issue in humans we recorded the number and distribution of new ischemic lesions on diffusion-weighted magnetic resonance imaging (DWMRI) after carotid artery stenting (CAS), a procedure producing showers of numerous small atheroemboli.Methods. Twenty-nine men (aged62-81) underwent30CAS procedures with distal protection in place, and DWMRI48hours after the procedure documented new lesions had developed. Thirteen patients were asymptomatic, and16had experienced recent symptoms ipsilateral to the treated carotid stenosis. A DWMRI study was done in each patient<72hours before the procedure. All MRI studies were read by the same neuroradiologist.Results. One patient sustained a minor stroke, which resolved. DWMRI found131new lesions (median,3; range,1-17). Lesion size was<5mm in96.6%and5to10mm in3.1%. Lesions were ipsilateral in83.1%and contralateral in16.9%. Lesions were in the distribution of the middle cerebral artery (91.6%), posterior cerebral artery (6.1%), and superior cerebellar artery subclavian artery (2.0%). Most lesions were in the cortex but at a depth where they were best described as cortical/subcortical (90.8%). The rest were in the periventricular white matter (6.1%) and deep gray matter (3.0%).Conclusions. The ischemic areas developing after CAS were predominately in the deeper layers of the cortex in the distribution of the middle cerebral artery, but lesions were seen throughout the brain. The distribution of lesions caused by CAS-induced embolization coincided with estimates of blood flow to the respective areas of the brain. These data add to the evidence implicating microemboli in ischemic pathologies throughout the brain.Part TwoObjectives. Choices for embolic protection during carotid stent procedures include distal filtration (DF) and proximal occlusion with flow reversal (POFR). DF devices are widely used but have produced only modest improvements in clinical outcomes. There is less experience with POFR devices but single center reports suggest reduced emboli detected by transcranial Doppler (TCD). To determine if POFR offers a significant improvement in embolic protection, we tested five DF devices and two POFR devices with8F and10F sheath design in an ex vivo angioplasty system using human carotid plaques excised en bloc. Physiologic pressures and flows were used and the efficiency of plaque fragment removal by these devices compared.Methods. Thirty-three human carotid plaques removed en bloc were secured in tailored polytetrafluoroethylene (PTFE) grafts. The distal PTFE was either6mm or5mm inner diameter (ID). Saline was delivered through the excised carotid plaque as follows:a cleaning50mL flush was done prior to the angioplasty procedure and discarded; further flushes of forward flow were done with five pressurized "pulsations" of10mL each (50mL), peak pressure140mm Hg. Balloon angioplasty was done with a4mm and then a6mm balloon. DF flushes were applied after each angioplasty and "postprocedure" after the device was removed. With POFR,50mL were collected through the sheath after balloon angioplasty by either back-pressure of20mmHg,40mmHg or60mmHg, or by aspiration. Postangioplasty pressurized forward flush of50or100mL was done as described. Each flush was collected, centrifuged, and examined for plaque fragments. Fragments greater than60microns were sized and counted on a100micron grid.Results. When DF devices were used in6mm lumen PTFE, the percent of fragments trapped was poor (13.7%to27.8%). There were no statistically significant differences between the devices. The capture of fragments improved (22%vs51.4%,P<.001) when devices appropriate for a6mm lumen were used in a5mm PTFE "ICA", functionally over-sizing the devices. POFR efficiency improved with increasing back-pressures and with repeated aspirations. Postprocedure, successive flushes of pressurized forward flow yielded additional plaque fragments and when the efficiency of POFR was assessed with forward flushing volumes similar to those used for DF, the efficiencies were similar, although larger fragments were more efficiently removed with POFR.Conclusion. In our model, both protection strategies were less than ideal. For POFR, high back pressures or multiple aspirations improve the efficiency of cerebral protection but additional fragments were released by pressurized flow even after aspiration of150mL of saline. DF devices create a pressure gradient and fragments apparently went around the device with pressurized flow in our PTFE lumen. Over-sizing of DF devices partially corrected this problemand increased over all DF efficiency to be comparable to POFR for smaller fragments but not for larger fragments.Part ThreeBackground. As they are "end arteries", microembolic obstruction of brain penetrating arteries would be expected to create ischemia. Yet the mammalian brain appears to have an impressive tolerance to experimental microembolization with ischemia occurring only after the injection of large numbers of particulates. Potential explanations could be that the majority of these particulates marginate along the pial vasculature or escape the cerebral circulation via arteriovenous (AV) fistulae.Methods. To test these theories, we first established the level of injury created by the injection of20,45, and90μm fluorescent microspheres in Sprague-Dawley rats. Brains were examined by immunohistochemistry for injury and for infarction. We then injected1000size20μm,500size45μm, and150size90μm and harvested the brains and lungs for assays of fluorescence. The location of microemboli within the brain was established by determining the percent of20and45μm fluorescent microspheres entering the superficial versus deeper layers of the brain. The location of larger microemboli was established by2T-MRI after injection of60-100μm microthrombi labeled with supra paramagnetic iron oxide (SPIO) particles.Results. With20μm microspheres there were no areas of injury or infarction after injection of500and rare areas of injury and no infarctions after injection of1000microspheres. With either250or500size45μm microspheres there were a few (<6) small areas of injury per animal with≤2areas of infarction. After injection,93%-96%of injected microspheres remained in the brain. Approximately40%of either fluorescent or SPIO labeled microthrombi were found on the brain surface.Conclusions. As in humans, the rat brain has an impressive tolerance to microemboli, although this clearly varies with emboli size and number. Wash out of particulates through AV connections is not a major factor in brain tolerance in this model. Approximately40%of microemboli remain in the larger pial vasculature where the more extensive collateralization may limit their effects on distal perfusion. However, the remaining60%enter penetrating arteries but few create ischemia.