Direct Observation of the Human Cerebral Microcirculation During Aneurysm Surgery Reveals Increased Arteriolar Contractility

Abstract

Background and Purpose-The effects of aneurysmal subarachnoid hemorrhage on morphology and function of the cerebral microcirculation are poorly defined, partly due to the lack of suitable techniques to visualize the microvessels in vivo. We used orthogonal polarization spectral (OPS) imaging on the brain cortex during aneurysm surgery to directly observe the small cortical blood vessels and quantify their responses to hypocapnia. Methods-In 16 patients undergoing aneurysm surgery, the diameter changes of small cortical vessels (15 to 180 m) were observed using OPS imaging. Ten patients were operated on early (within 48 hours after bleeding) and 6 underwent late surgery. Immediately after dura opening, the response to hyperventilation of arterioles and venules was observed with OPS imaging under sevoflurane anesthesia. Results-In patients operated on early, layers of subarachnoid blood were clearly visible. In this group, hyperventilation resulted in a 39Ϯ15% decrease in arteriolar diameter with a "bead-string" constriction pattern occurring in 60% of patients. In late surgery and in controls, no subarachnoid blood was seen. The arteriolar diameter decrease with hyperventilation was 17Ϯ20% in patients undergoing late surgery and 7Ϯ7% in controls. Venules were not affected by hyperventilation in any of the groups studied. Conclusions-OPS imaging allows direct in vivo observation of the cerebral microcirculation enabling us, for the first time, to visually observe and quantify microvascular reactivity in the human brain. The present study demonstrates increased contractile responses of the cerebral arterioles in the presence of subarachnoid blood, suggesting increased microvascular tonus with possibly greater susceptibility to ischemia.

Experimental Subarachnoid Hemorrhage Causes Early and Long-Lasting Microarterial Constriction and Microthrombosis: An in-vivo Microscopy Study

“…Taken together, the current study shows that in-vivo subarachnoid/pial arterioles show the same pearl string-like constrictions that have been previously observed in humans (Uhl et al, 2003;Pennings et al, 2004), that these constrictions are frequent (70% of all arterioles) and severe enough ( > 30%) to cause ischemia, and that arteriolar constrictions seem to trigger the formation of microthrombosis and microvascular stasis, thereby further aggravating tissue perfusion. Although the detailed molecular mechanisms underlying this phenomenon still need to be investigated, the current results suggest that long-lasting hemodynamic alterations at the microcirculatory level may be an important mechanism for the development of early post hemorrhagic ischemia, which is of utmost im portance for the prognosis of patients experiencing SAH.…”

“…This means that the cerebral microcirculation can be visualized without any previous mechanical alterations to the cerebral vasculature and under conditions of physiological cerebrospinal fluid flow. This procedure may explain why this is the first experimental study to observe the pearl string-like pattern of arteriolar constrictions so far only observed in humans (Uhl et al, 2003;Pennings et al, 2004).…”

“…Subarachnoid arterioles showed pearl stringlike contractions and capillary density was significantly reduced, indicating loss of perfusion at the microcirculatory level after subarachnoid bleeding (Uhl et al, 2003). These findings were later confirmed by another group using the same imaging technology (Pennings et al, 2004). Based on these experimental and clinical studies, it seems clear that arteriolar constrictions, which remain undetected by routine clinical imaging, may have an important role for the otherwise inexplicable early ischemia occurring after SAH.…”

Darkfield orthogonal polarized spectral imaging for studying endovascular laser-tissue interactions in vivo-a preliminary study

“…OPS has recently been introduced in the clinical setting to image distinctive microvascular and hematological pathologies associated with different disease states, including (cardio)vascular diseases, cancer, and sepsis [2][3][4]. The imaging technique allows the observation of vascular structures and endovascular constituents (red blood cells and leukocytes) at high contrast [5], and facilitates quantitative measurements of physiological parameters (red blood cell velocity, vasomotion) as well as pathophysiological conditions (ischemia/reperfusion, hemorrhage, tumor angiogenesis) without requiring contrast enhancers or fluorescent dyes [3,[6][7][8][9][10]. In OPS imaging, vascularized tissue is illuminated with linearly polarized light, while the remitted light is imaged through an analyzer (second polarizer) oriented orthogonally to the polarizer.…”

Microcirculatory assessment in daily clinical practice - not yet ready but not too far!

“…More importantly, microvascular spasms could be noticed during the surgery while vasospasm was not yet detected by usual techniques. Another study (40) showed increased contractile responses of the cerebral arterioles in the presence of subarachnoid blood (and induced by hypocapnia), suggesting increased microvascular tonus.…”