Arterial Tortuosity: An Imaging Biomarker of Childhood Stroke Pathogenesis?

Abstract

Background and purpose: Arteriopathy is the leading cause of childhood arterial ischemic stroke. Mechanisms are poorly understood but may include inherent abnormalities of arterial structure. Extracranial dissection is associated with connective tissue disorders in adult stroke. Focal cerebral arteriopathy is a common syndrome where pathophysiology is unknown but may include intracranial dissection or transient cerebral arteriopathy. We aimed to quantify cerebral arterial tortuosity in childhood arterial ischemic stroke, hypothesizing increased tortuosity in dissection.

Methods: Children (1 month to 18 years) with arterial ischemic stroke were recruited within the Vascular Effects of Infection in Pediatric Stroke (VIPS) study with controls from the Calgary Pediatric Stroke Program. Objective, multi-investigator review defined diagnostic categories. A validated imaging software method calculated the mean arterial tortuosity of the major cerebral arteries using 3-dimensional time-of-flight magnetic resonance angiographic source images. Tortuosity of unaffected vessels was compared between children with dissection, transient cerebral arteriopathy, meningitis, moyamoya, cardioembolic strokes, and controls (ANOVA and post hoc Tukey). Trauma-related versus spontaneous dissection was compared (Student t test).

Results: One hundred fifteen children were studied (median, 6.8 years; 43% women). Age and sex were similar across groups. Tortuosity means and variances were consistent with validation studies. Tortuosity in controls (1.346±0.074; n=15) was comparable with moyamoya (1.324±0.038; n=15; P=0.998), meningitis (1.348±0.052; n=11; P=0.989), and cardioembolic (1.379±0.056; n=27; P=0.190) cases. Tortuosity was higher in both extracranial dissection (1.404±0.084; n=22; P=0.021) and transient cerebral arteriopathy (1.390±0.040; n=27; P=0.001) children. Tortuosity was not different between traumatic versus spontaneous dissections (P=0.70).

Conclusions: In children with dissection and transient cerebral arteriopathy, cerebral arteries demonstrate increased tortuosity. Quantified arterial tortuosity may represent a clinically relevant imaging biomarker of vascular biology in pediatric stroke.

Keywords: arterial tortuosity; child; dissection; magnetic resonance angiography; pediatric stroke; stroke.

Figure 1

Tortuosity Measurement. The distance factor metric was calculated to quanitfy relative tortuosity. Dashed arrows represent Euclidian distances (d) to local points along artery path length (L). Distance Factor Metric (DFM) = L/d. Using a bifurcation point as the definite start, an iteration is performed through every voxel along path calculating a local DFM until the endpoint is reached.

Figure 2

MRA tortuosity measures. Representative examples from across the range of tortuosities calculated are demonstrated. Original clinical maximum intensity projection (MIP) of time-of-flight (TOF) MR angiogram (MRA) images (top row) and their corresponding reconstructed centerline skeletons (bottom row) depict the bottom (1.237), mean (1.460) and top (1.608) range tortuosity scores.

Figure 3

Arterial tortuosity by location. Box plots for tortuosity scores across the entire sample are demonstarted for each major artery measured. Tortuosity was symmetrical for paired arteries, greatest in the internal carotids, and lowest in the basilar artery. ICA, internal carotid artery; M1, first segment of middle cerebral artery; L, left; R, right.

Figure 4

Effects of age and gender on arterial tortuosity. A scatter lot depicts mean tortuosity scores for all subjects across the full age range with seperation of male and female subjects. No association was demonstrated with age or sex.

Figure 5

Tortuosity by disease. The normal range of arterial tortuosity in children is depicted by the controls (left box plot, n=15) with the 5^th and 95^th percentiles marked with the shaded box. Dissection (n=22) and TCA (n=25) groups demonstrated abnormally elevated tortuosity and increased variance of tortuosity scores. No difference was found between traumatic (n=9) and spontaneous (n=13) dissection.