Berend Hillen

Relation of arterial geometry to luminal narrowing and histologic markers for plaque vulnerability: the remodeling paradox ☆

OBJECTIVE To relate local arterial geometry with markers that are thought to be related to plaque rupture. BACKGROUND Plaque rupture often occurs at sites with minor luminal stenosis and has retrospectively been characterized by colocalization of inflammatory cells. Recent studies have demonstrated that luminal narrowing is related with the mode of atherosclerotic arterial remodeling. METHODS We obtained 1,521 cross section slices at regular intervals from 50 atherosclerotic femoral arteries. Per artery, the slices with the largest and smallest lumen area, vessel area and plaque area were selected for staining on the presence of macrophages (CD68), T-lymphocytes (CD45RO), smooth muscle cells (alpha-actin) and collagen. RESULTS Inflammation of the cap or shoulder of the plaque was observed in 33% of all cross sections. Significantly more CD68 and CD45RO positive cells, more atheroma, less collagen and less alpha-actin positive staining was observed in cross sections with the largest plaque area and largest vessel area vs. cross sections with the smallest plaque area and smallest vessel area, respectively. No difference in the number of inflammatory cells was observed between cross sections with the largest and smallest lumen area. CONCLUSION Intraindividually, pathohistologic markers previously reported to be related to plaque vulnerability were associated with a larger plaque area and vessel area. In addition, inflammation of the cap and shoulder of the plaque was a common finding in the atherosclerotic femoral artery.

Paradoxical arterial wall shrinkage may contribute to luminal narrowing of human atherosclerotic femoral arteries

BACKGROUND This study was done to assess how local changes in vessel size, together with plaque load, determine luminal narrowing in atherosclerotic arteries. Fifty-one human femoral arteries were analyzed: 32 postmortem and 19 in vivo by 30-MHz intravascular ultrasound. METHODS AND RESULTS Histological and intravascular ultrasound cross sections were examined every 0.5 cm over an arterial segment 10 to 15 cm long. In each cross section we measured the lumen area and the area circumscribed by the internal elastic lamina (the IEL area). In each arterial segment, the cross section that contained the least amount of plaque was the reference site. For each cross section, the lumen area stenosis was expressed as percent of the lumen area in the reference site. Similarly, the IEL area was expressed as percent of the IEL area in the reference site (the relative IEL area). There was a significant negative correlation between the relative IEL area and the lumen area stenosis percentage (r = -.62, P < .001 for histology and r = -.66, P < .001 for intravascular ultrasound). When lumen area stenosis was less than about 25%, mainly compensatory enlargement was observed. When lumen area stenosis exceeded about 25%, however, mainly a decrease of the IEL area was observed, which is consistent with arterial wall shrinkage. Furthermore, the increase in plaque area does not account for the total loss of luminal area. There was a moderate correlation between an increase in plaque area and reduction of the corresponding lumen area (r = .49 and r = .56 for histology and intravascular ultrasound, respectively). CONCLUSIONS The decrease in luminal area cannot be attributed to plaque increase alone. Arterial wall shrinkage is a paradoxical mechanism that may contribute to severe luminal narrowing of the atherosclerotic human femoral artery.

Anatomy and functionality of leptomeningeal anastomoses: a review.

Background— This review seeks to provide a structured presentation of existing knowledge of leptomeningeal anastomoses from anatomic and functional points of view and to identify problems and possible research directions to foster a better understanding of the subject and of stroke mechanisms. Summary of Review— Available data show that leptomeningeal anastomoses may be important in understanding stroke mechanisms and that leptomeningeal anastomoses play an important role in penumbra outcome. However, the literature shows no consensus between statements on the existence of leptomeningeal anastomoses and compensatory capacity. Conclusions— By analyzing the available literature and identifying the factors that contribute to this confusion, we found that variability and the functional consequences thereof are important but that quantitative data are lacking. Moreover, vascular remodeling is an issue to consider.

Circle of Willis Collateral Flow Investigated by Magnetic Resonance Angiography

BACKGROUND AND PURPOSE The circle of Willis (CW) is considered an important collateral pathway in maintaining adequate cerebral blood flow in patients with internal carotid artery (ICA) obstruction. We aimed to investigate the anatomic variation of the CW in patients with severe symptomatic carotid obstructive disease and to analyze diameter changes of its components in relation to varying grades of ICA obstruction and in relation to the presence or absence of (retrograde) collateral flow. METHODS Seventy-five patients with minor disabling neurological deficits and with ICA stenoses or occlusions were categorized into 4 groups according to the severity of ICA obstruction. This patient population reflected a relatively favorable subgroup of cerebral infarction (considering their minor neurological deficits). All subjects underwent magnetic resonance angiography, including magnetic resonance angiography sensitive to flow direction. CW morphology and the size of its components were determined and compared with those values in control subjects (n=100). RESULTS Compared with control subjects, patients demonstrated a significantly higher percentage of entirely complete CW configurations (55% versus 36%, P=0.02), complete anterior configurations (88% versus 68%, P=0.002), and complete posterior CW configurations (63% versus 47%, P=0.04). Patients with severe ICA stenosis did not show significantly increased CW vessel diameters. Patients with ICA occlusion demonstrated a high prevalence of collateral flow through the anterior CW and significantly increased diameters of the communicating channels. Patients with bilateral ICA occlusion relied on collateral flow via the posterior CW and demonstrated a bilateral increase in posterior communicating artery diameters (P<0.05). CONCLUSIONS The anatomic and functional configuration of the CW reflects the degree of ICA obstruction.

The Impact of Atherosclerotic Arterial Remodeling on Percentage of Luminal Stenosis Varies Widely Within the Arterial System A Postmortem Study

Luminal stenosis can be based on large atherosclerotic plaques in compensatory enlarged segments or on relatively little plaques in shrunken segments. In the present study, the contribution of plaque formation and remodeling to luminal narrowing was compared among six types of arteries prone to symptomatic atherosclerosis. Cross-sections (n = 5195) were obtained at regular intervals from 329 arteries. For each artery, the cross-section that contained the least amount of plaque was considered to be the reference. For each cross-section, the percentage of lumen area decrease was expressed as a percentage of the lumen area at the reference site (luminal stenosis). Similarly, the area encompassed by the internal elastic lamina (IEL area) was expressed as a percentage of the IEL area at the reference site (relative IEL area). All cross-sections were categorized in three groups: relative IEL area > 105% (enlargement), 95% to 105% (no remodeling), and < 95% (shrinkage). The prevalence of enlargement (50% to 75%) was significantly higher compared with shrinkage (8% to 25%). Shrinkage was observed most frequently in the femoral arteries (25%) and infrequently in the renal arteries (8%). For all types of arteries, the relative IEL area correlated negatively with luminal stenosis (P < .001). Regression analysis of relative IEL area on luminal stenosis, however, showed significant differences in the first-order regression coefficients among artery types. On average, plaque increase was more compensated for by enlargement in the coronary, common carotid, and renal arteries compared with the arteries obtained from the lower extremities. Anatomic regional differences were observed in the impact of arterial wall remodeling on percent luminal stenosis in de novo atherosclerotic lesions.

Review of the variability of the territories of the major cerebral arteries.

The results of recent model studies indicate that the variability in territorial distribution of the major cerebral arteries may be much greater than has been previously recognized. We review the literature on the cortical and intracerebral territories of the anterior, middle, and posterior cerebral arteries. Although most authors claim that these territories are relatively consistent, the results of their studies show many and considerable discrepancies. The variability described by Beevor has been neither excluded nor completely confirmed, yet somehow the concept of a relatively unchanging pattern of the peripheral cerebral vascularization has gradually settled into the literature. We discuss the considerable variability of the cerebral territories, as well as the discrepancies in investigation techniques, injection materials, and specimen conditions that could be factors producing these dissimilar results. Our study shows that there are no arguments in the literature to negate the variability of the cerebral territories.

Atherosclerotic Arterial Remodeling in the Superficial Femoral Artery Individual Variation in Local Compensatory Enlargement Response

BACKGROUND In previous studies on atherosclerotic arterial remodeling, compensatory enlargement of the artery in response to plaque accumulation was inferred from pooled data based on one cross section per artery. We assessed local arterial remodeling individually by analyzing 45 artery segments at 0.5-cm intervals over a length of 10 to 15 cm. METHODS AND RESULTS Twenty patients were studied by 30-MHz intravascular ultrasound (IVUS) before balloon angioplasty of the superficial femoral artery (370 cross sections), and 25 femoral artery segments were studied postmortem (551 cross sections). In each cross section, the area surrounded by the internal elastic lamina (IEL area) and the plaque area were measured. The IEL area was larger in the cross section with the largest plaque area than in the cross section with the smallest plaque area (32.5+/-13.0 and 32.0+/-11.5 mm2 versus 28.9+/-9.7 [P=NS] and 26.7+/-10.1 [P<.05] mm2 for IVUS and histology, respectively [mean+/-SD]). A significant positive correlation was found between plaque area and IEL area for the pooled data (r=.61 and r=.47 and slope=1.07 and 0.90 for IVUS and histology, respectively; both P<.001). In 12 of 20 and 16 of 25 individual arterial segments, however, no significant correlation was observed between plaque area and IEL area for IVUS and histology, respectively. A large variation was found in the correlation of the regression of plaque to IEL area (IVUS, r=-.40 to .89; histology, r=-.13 to .91) and slope (IVUS, -0.28 to 1.29; histology, -0.18 to 1.32). CONCLUSIONS In the majority of atherosclerotic femoral arteries, significant compensatory enlargement could not be determined. It is inferred that arterial remodeling in response to plaque formation may vary among individuals.

Effects of Anterior Communicating Artery Diameter on Cerebral Hemodynamics in Internal Carotid Artery Disease A Model Study

BACKGROUND Collateral circulatory pathways are considered the primary determinant of cerebral hemodynamics in patients with obstructive lesions of the internal carotid arteries (ICaAs). However, the hemodynamic effects of the diameter of the anterior communicating artery (ACoA) have never been assessed quantitatively in humans. METHODS AND RESULTS Two different mathematical models were used to simulate changes affecting blood pressures and flows in cerebral arteries as a function of ACoA diameter and ICaA stenoses or occlusions. Small changes in ACoA diameter were found to have marked hemodynamic effects when they occurred within the range of 0.4 to 1.6 mm, a situation observed in 80% of the cases. Outside this range, changes in ACoA diameter had no effect. Simulated pressure drops through a stenotic ICaA were consistent with those observed. They were found to depend on the degrees of the stenoses in both ICaAs and on ACoA diameter according to a simple equation. Pressure reserve in the middle and anterior cerebral arteries decreased to below the lower limit of autoregulation, despite a normal mean arterial blood pressure, when the arteries were distal to a unique 70% ICaA stenosis associated with a small-diameter ACoA or to a 50% ICaA stenosis associated with a contralateral ICaA occlusion and a large-diameter ACoA. Above these thresholds, the circle of Willis allowed for an almost complete global cerebral blood flow compensation that involved all the afferent and communicating vessels. CONCLUSIONS ACoA diameter strongly modulates the effects of ICaA lesions on cerebral hemodynamics. Some proposals for endarterectomy indications can be derived from our study.

A functional anatomic study of the relationship of the nasal cartilages and muscles to the nasal valve area

The functioning of the nasal valve area is largely determined by the stability and the mobility of the lateral nasal wall. To gain insight into the kinematics of the lateral nasal wall, we studied the functional anatomy of the nasal muscles and the intercartilaginous and osseous‐cartilaginous junctions. We performed gross and microscopic nasal dissection and serial sectioning in 15 human cadaveric noses. In addition, two noses were used for three‐dimensional reconstruction of the nasal cartilages. We conclude that the lateral nasal wall can be seen as made up of three parts. At the level of the osseous‐cartilaginous chain of bone, lateral nasal cartilage, and lateral crus, the lateral nasal wall is relatively stable, limited mobility being allowed by translation and rotation in the intercartilaginous joint and a coupled distortion of the cartilages. At the level of the hinge area the lateral nasal wall is supported by one or more accessory cartilages, embedded in soft tissue, and therefore much more compliant. The alar part of the nasalis muscle, which originates from the maxilla and inserts on these cartilages, may dilate the valve area by drawing this hinge area laterally. The third and most compliant part of the lateral nasal wall is the part that is not supported by cartilage, the ala. The dilatator naris muscle largely occupies the ala and is attached to the lateral crus; it opens the vestibule and nostril. The third nasal muscle that influences the lateral nasal wall is the transverse part of the nasalis muscle. It overlies the nose but is not attached to it. This muscle stabilizes the lateral nasal wall, in particular, the lateral nasal cartilage, the intercartilaginous junction, and the hinge area, by moving the nasal skin.

Is plaque formation in the common carotid artery representative for plaque formation and luminal stenosis in other atherosclerotic peripheral arteries? A post mortem study

The atherosclerotic carotid artery is easily accessible for non-invasive duplex investigation. The aim of the present post mortem study was to examine whether plaque accumulation and luminal stenosis in the common carotid artery is representative for atherosclerotic plaque accumulation and luminal stenosis in other peripheral arteries. A total of 3765 cross-sections were obtained at regular intervals from 240 arteries (24 individuals). Five types of peripheral arteries were investigated: common carotid, femoral, common iliac, external iliac and renal arteries. In each cross-section, the lumen area, vessel area, plaque area and maximal plaque thickness was measured. For each location, the percentage luminal stenosis and relative plaque area was calculated. Relative plaque area was defined as the percentage of the vessel area which was occupied by plaque. Weak correlations (r=0.41-0.59) were observed between percentage relative plaque area or maximal plaque thickness in the common carotid artery and percentage relative plaque area in other peripheral arteries. Neither plaque accumulation nor luminal stenosis in the common carotid artery correlated with the percentage luminal stenosis in other peripheral arteries (P > 0.05). We conclude that plaque area in the common carotid artery is weakly correlated with plaque area and not correlated with luminal stenosis in other peripheral arteries.