Patrick J.H. de Koning

Magnetic resonance angiography of intracranial and extracranial arteries in patients with spontaneous migraine without aura: a cross-sectional study

BACKGROUND Extracranial arterial dilatation has been hypothesised to be the cause of pain in patients who have migraine without aura. To test that hypothesis, we aimed to measure extracranial and intracranial arteries during attacks of migraine without aura. METHODS In this cross-sectional study, we recruited patients aged 18-60 years from the Danish Headache Centre and via announcements on a Danish website. We did magnetic resonance angiography during spontaneous unilateral migraine attacks. Primary endpoints were difference in circumference of extracranial and intracranial arterial segments comparing attack and attack-free days and the pain and the non-pain side. The extracranial arterial segments measured were the external carotid (ECA), the superficial temporal (STA), the middle meningeal (MMA), and the cervical part of the internal carotid (ICAcervical) arteries. The intracranial arterial segments were the cavernous (ICAcavernous) and cerebral (ICAcerebral) parts of the internal carotid, the middle cerebral (MCA), and the basilar (BA) arteries. This study is registered at Clinicaltrials.gov, number NCT01471314. FINDINGS Between Oct 12, 2010, and Feb 8, 2012, we recruited 78 patients, of whom 19 women had a scan during migraine and were included in the final analysis. On migraine compared with non-migraine days, we detected no statistically significant dilatation of the extracranial arteries on the pain side (ECA, mean difference 1·2% [95% CI -5·7 to 8·2] p=0·985, STA 3·6% [-3·7 to 11·0] p=0·532, MMA 1·7% [-1·7 to 5·2] p=0·341, and ICAcervical 2·3% [-0·3 to 4·9] p=0·093); the intracranial arteries were more dilated during attacks (MCA, 13·0% [6·4 to 19·6] p=0·001, ICAcerebral 11·5% [5·6 to 17·3] p=0·0004, and ICAcavernous 11·4% [5·3 to 17·5] p=0·001), except for the BA (1·6% [-2·7 to 5·9] p=0·621). Compared with the non-pain side, during attacks we detected dilatation on the pain side of the intracranial arteries (MCA, mean difference 10·5% [0·7-20·3] p=0·044, ICAcerebral (14·4% [4·6-24·1] p=0·013), and ICAcavernous (9·1% [3·9-14·4] p=0·003) but not of the extracranial arteries (ECA, 2·1% [-3·8 to 9·2] p=0·238, STA, 3·6% [-3·7 to 10·8] p=0·525, MMA, 2·7% [-1·3 to 5·6] p=0·531, and ICAcervical, 5·0% [-0·5 to 10·4] p=0·119). INTERPRETATION Migraine pain was not accompanied by extracranial arterial dilatation, and by only slight intracranial dilatation. Future migraine research should focus on the peripheral and central pain pathways rather than simple arterial dilatation. FUNDING University of Copenhagen, the Lundbeck Foundation, the Research Foundation of the Capital Region of Denmark, Danish Council for Independent Research-Medical Sciences, and the Novo Nordisk Foundation.

Headache and prolonged dilatation of the middle meningeal artery by PACAP38 in healthy volunteers

Aim: To explore a possible relationship between vasodilatation and delayed headache we examined the effect of pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) on the middle meningeal artery (MMA) and middle cerebral artery (MCA) using high resolution magnetic resonance angiography (MRA). Methods: In a double-blind, randomized, placebo-controlled study 14 healthy volunteers were scanned repeatedly after infusion (20 min) of 10 pmol/kg/min PACAP38 or placebo. In addition, four participants were scanned following subcutaneous sumatriptan (6 mg). Results: We found significant dilatation of the MMA (p = 0.00001), but not of the MCA (p = 0.50) after PACAP38. There was no change after placebo (p > 0.40). Vasodilatation (range 16–23%) lasted more than 5 h. Sumatriptan selectively contracted the MMA by 12.3% (p = 0.043). Conclusion: PACAP38-induced headache is associated with prolonged dilatation of the MMA but not of the MCA. Sumatriptan relieves headache in parallel with contraction of the MMA but not of the MCA.

Towards quantitative analysis of coronary CTA

The current high spatial and temporal resolution, multi-slice imaging capability, and ECG-gated reconstruction of multi-slice computed tomography (MSCT) allows the non-invasive 3D imaging of opacified coronary arteries. MSCT coronary angiography studies are currently carried out by the visual inspection of the degree of stenosis and it has been shown that the assessment with sensitivities and specificities of 90% and higher can be achieved. To increase the reproducibility of the analysis, we present a method that performs the quantitative analysis of coronary artery diseases with limited user interaction: only the positioning of one or two seed points is required. The method allows the segmentation of the entire left or right coronary tree by the positioning of a single seed point, and an extensive evaluation of a particular vessel segment by placing a proximal and distal seed point. The presented method consists of: (1) the segmentation of the coronary vessels, (2) the extraction of the vessel centerline, (3) the reformatting of the image volume, (4) a combination of longitudinal and transversal contour detection, and (5) the quantification of vessel morphological parameters. The method is illustrated in this paper by the segmentation of the left and right coronary trees and by the analysis of a coronary artery segment. The sensitivity of the positioning of the seed points is studied by varying the position of the proximal and distal seed points with a standard deviation of 6 and 8 mm (along the vessel’s course) respectively. It is shown that only close to the individual seed points the vessel centerlines deviate and that for more than 80% of the centerlines the paths coincide. Since the quantification depends on the determination of the centerline, no user variability is expected as long as the seed points are positioned reasonably far away from the vessel lesion. The major bottleneck of MSCT imaging of the coronary arteries is the potential lack of image quality due to limitations in the spatial and temporal resolution, irregular or high heart beat, respiratory effects, and variations of the distribution of the contrast agent: the number of rejected vessel segments in diagnostic studies is currently still too high for implementation in routine clinical practice. Also for the automated quantitative analysis of the coronary arteries high image quality is required. However, based upon the trend in technological development of MSCT scanners, there is no doubt that the quantitative analysis of MSCT coronary angiography will benefit from these technological advances in the near future.

An Integrated Automated Analysis Method for Quantifying Vessel Stenosis and Plaque Burden From Carotid MRI Images: Combined Postprocessing of MRA and Vessel Wall MR

Background and Purpose— We report the evaluation of a semiautomated method for in vivo assessment of the severity of carotid atherosclerosis with minimal user interaction that combines 3-dimensional contrast-enhanced magnetic resonance angiography (CE-MRA) and vessel wall magnetic resonance imaging (MRI). Methods— Lumen and outer-wall contours were automatically detected, and stenosis and plaque burden were estimated. The method was tested on 22 subjects (352 postcontrast, T1-weighted cross sections and 3-dimensional CE-MRA). Results— We observed good correlation with expert contours: lumen and outer-wall area (r=0.96) and the degree of stenosis (r=0.97). Conclusions— The fusion of MRA and MRI reduces user interaction and improves contour detection, providing reproducible parameters to assess the severity of atherosclerosis.

Automatic lumen and outer wall segmentation of the carotid artery using deformable three‐dimensional models in MR angiography and vessel wall images

To develop and validate an automated segmentation technique for the detection of the lumen and outer wall boundaries in MR vessel wall studies of the common carotid artery.

MRI-assessed regional pulse wave velocity for predicting absence of regional aorta luminal growth in marfan syndrome.

BACKGROUND In patients with Marfan syndrome (MFS), increased aortic wall stiffening may lead to progressive aortic dilatation. Aortic Pulse Wave Velocity (PWV), a marker of wall stiffness can be assessed regionally, using in-plane multi-directional velocity-encoded MRI. This study examined the diagnostic accuracy of regional PWV for prediction of regional aortic luminal growth during 2-year follow-up in MFS patients. METHODS In twenty-one MFS patients (mean age 36 ± 15 years, 11 male) regional PWV and aortic luminal areas were assessed by 1.5 T MRI. At 2-year follow-up, the incidence of luminal growth, defined as mean luminal diameter increase >2mm was determined for five aortic segments (S1, ascending aorta; S2, aortic arch; S3, thoracic descending aorta, S4, supra-renal and S5, infra-renal abdominal aorta). Regional PWV at baseline was considered increased when exceeding age-related normal PWV (healthy volunteers (n=26; mean age 30 ± 10 years, 15 male)) by two standard-errors. Sensitivity and specificity of regional PWV-testing for prediction of regional luminal growth were determined. RESULTS Regional PWV at baseline was increased in 17 out of 102 segments (17%). Significant luminal growth at follow-up was reported in 14 segments (14%). The specificity of regional PWV-testing was ≥ 78% for all aortic segments, sensitivity was ≤ 33%. CONCLUSIONS Regional PWV was significantly increased in MFS patients as compared to healthy volunteers within similar age range, in all aortic segments except the ascending aorta. Furthermore, regional PWV-assessment has moderate to high specificity for predicting absence of regional aortic luminal growth for all aortic segments in MFS patients.

A novel approach for the detection of pathlines in X-Ray angiograms: the wavefront propagation algorithm

This article presents a new pathline approach, based on the wavefront propagation principle, and developed in order to reduce the variability in the outcomes of the quantitative coronary artery analysis. This novel approach, called wavepath, reduces the influence of the user-defined start- and endpoints of the vessel segment and is therefore more robust and improves the reproducibility of the lesion quantification substantially. The validation study shows that the wavepath method is totally constant in the middle part of the pathline, even when using the method for constructing a bifurcation or sidebranch pathline. Furthermore, the number of corrections needed to guide the wavepath through the correct vessel is decreased from an average of 0.44 corrections per pathline to an average of 0.12 per pathline. Therefore, it can be concluded that the wavepath algorithm improves the overall analysis substantially.

The effect of sumatriptan on cephalic arteries: A 3T MR-angiography study in healthy volunteers.

Aim To explore a possible differential effect of sumatriptan on extracerebral versus cerebral arteries, we examined the superficial temporal (STA), middle meningeal (MMA), extracranial internal carotid (ICAextra), intracranial internal carotid (ICAintra), middle cerebral (MCA) and basilar arteries (BA). Methods The arterial circumferences were recorded blindly using high-resolution magnetic resonance angiography before and after subcutaneous sumatriptan injection (6 mg) in 18 healthy volunteers. Results We found significant constrictions of MMA (16.5%), STA (16.4%) and ICAextra (15.2%) (p ≤ 0.001). Smaller, but statistically significant, constrictions were seen in MCA (5.5%) and BA (2.1%) (p ≤ 0.012). ICAintra change 1.8% was not significant (p = 0.179). The constriction of cerebral arteries was significantly smaller than the constriction of extracerebral arteries (p < 0.000001). Conclusion Sumatriptan constricts extracerebral arteries more than cerebral arteries. We suggest that sumatriptan may exert its anti-migraine action outside of the blood–brain barrier.

Measurement precision and biological variation of cranial arteries using automated analysis of 3 T magnetic resonance angiography

BackgroundNon-invasive magnetic resonance angiography (MRA) has facilitated repeated measurements of human cranial arteries in several headache and migraine studies. To ensure comparability across studies the same automated analysis software has been used, but the intra- and interobserver, day-to-day and side-to-side variations have not yet been published. We hypothesised that the observer related, side-to-side, and day-to-day variations would be less than 10%.MethodsTen female participants were studied using high-resolution MRA on two study days separated by at least one week. Using the automated LKEB-MRA vessel wall analysis software arterial circumferences were measured by blinded observers. Each artery was analysed twice by each of the two different observers. The primary endpoints were to determine the intraclass correlation coefficient (ICC) and intra- an inter-observer, the day-to-day, and side-to-side variations of the circumference of the middle meningeal (MMA) and middle cerebral (MCA) arteries.ResultsWe found an excellent intra- and interobserver agreement for the MMA (ICC: 0.909-0.987) and for the MCA (ICC: 0.876-0.949). The coefficient of variance within observers was ≤1.8% for MMA and ≤3.1% for MCA; between observers ≤3.4% (MMA) and ≤4.1% (MCA); between days ≤6.0% (MMA) and ≤8.0% (MCA); between sides ≤9.4% (MMA) and ≤6.5% (MCA).ConclusionThe present study demonstrates a low (<5%) inter- and intraobserver variation using the automated LKEB-MRA vessel wall analysis software. Furthermore, the study also suggests that the day-to-day and side-to-side variations of the MMA and MCA circumferences are less than 10%.

Validation of a new method for the detection of pathlines in vascular X-ray images

This article presents the validation of a new pathline approach, based on the wavefront propagation principle, on a large variety of vascular images. The purpose of the novel approach, called wavepath, was to minimize the variability of the measurements in the quantitative vascular analysis by reducing the variability that is introduced by manually placing the start and end points of the vessel segment. This results in a robust and reproducible pathline detection that is subsequently used in the analysis and lesion quantification. The validation study that was performed concerned a large variety of vessel segments and showed that the approach results in a pathline that is totally constant in its middle part. This holds not only for the straight segment version but also for the bifurcation version and ostial version of the algorithm. Moreover, the average number of additional points per pathline needed to guide the wavepath through the correct vessel is minimized to 0 for the straight segments, 0.06 for aortic bifurcations, 0.25 for carotid bifurcations, and 0.08 for the ostial segments. In conclusion, our new approach performs very well in all types of vascular x-ray images, resulting in a stable and robust pathline detection.