Summary 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.
The origin of migraine pain is unknown, but may involve the dura mater. In unilateral migraine without aura, Khan et al. report that the middle meningeal artery is the only artery with greater ...circumference increase on the pain side versus non-pain side, suggesting a meningeal contribution to migraine headache.
Abstract
The origin of migraine pain is unknown but possibly implicates the dura mater, which is pain sensitive in proximity to the meningeal arteries. Therefore, subtle changes in vessel calibre on the head pain side could reflect activation of dural perivascular nociceptors that leads to migraine headache. To test this hypothesis, we measured circumference changes of cranial arteries in patients with cilostazol-induced unilateral migraine without aura using 3 T high resolution magnetic resonance angiography. The middle meningeal artery was of key interest, as it is the main supply of the dura mater. We also measured the superficial temporal and external carotid arteries as additional extracranial segments, and the middle cerebral, the cerebral and cavernous parts of the internal carotid (ICAcerebral and ICAcavernous), and the basilar arteries as intracranial arterial segments. Magnetic resonance angiography scans were performed at baseline, migraine onset, after sumatriptan, and ≥27 h after migraine onset. Thirty patients underwent magnetic resonance angiography scans, of which 26 patients developed unilateral attacks of migraine without aura and were included in the final analysis. Eleven patients treated their migraine with sumatriptan while the remaining 15 patients did not treat their attacks with analgesics or triptans. At migraine onset, only the middle meningeal artery exhibited greater circumference increase on the pain side (0.24 ± 0.37 mm) compared to the non-pain side (0.06 ± 0.38 mm) (P = 0.002). None of the remaining arteries revealed any pain-side specific changes in circumference (P > 0.05), but exhibited bilateral dilation. Sumatriptan constricted all extracerebral arteries (P < 0.05). In the late phase of migraine, we found sustained bilateral dilation of the middle meningeal artery. In conclusion, onset of migraine is associated with increase in middle meningeal artery circumference specific to the head pain side. Our findings suggest that vasodilation of the middle meningeal artery may be a surrogate marker for activation of dural perivascular nociceptors, indicating a meningeal site of migraine headache.
10.1093/brain/awy300_video1
awy300media1
5983750185001
Migraine with aura is prevalent in high-altitude populations suggesting an association between migraine aura and hypoxia. We investigated whether experimental hypoxia triggers migraine and aura ...attacks in patients suffering from migraine with aura. We also investigated the metabolic and vascular response to hypoxia. In a randomized double-blind crossover study design, 15 migraine with aura patients were exposed to 180 min of normobaric hypoxia (capillary oxygen saturation 70-75%) or sham on two separate days and 14 healthy controls were exposed to hypoxia. Glutamate and lactate concentrations in the visual cortex were measured by proton magnetic resonance spectroscopy. The circumference of cranial arteries was measured by 3 T high-resolution magnetic resonance angiography. Hypoxia induced migraine-like attacks in eight patients compared to one patient after sham (P = 0.039), aura in three and possible aura in 4 of 15 patients. Hypoxia did not change glutamate concentration in the visual cortex compared to sham, but increased lactate concentration (P = 0.028) and circumference of the cranial arteries (P < 0.05). We found no difference in the metabolic or vascular responses to hypoxia between migraine patients and controls. In conclusion, hypoxia induced migraine-like attacks with and without aura and dilated the cranial arteries in patients with migraine with aura. Hypoxia-induced attacks were not associated with altered concentration of glutamate or other metabolites. The present study suggests that hypoxia may provoke migraine headache and aura symptoms in some patients. The mechanisms behind the migraine-inducing effect of hypoxia should be further investigated.
Purpose
To evaluate the in‐scan and scan–rescan consistency of left ventricular (LV) in‐ and outflow assessment from 1) 2D planimetry; 2) 4D flow magnetic resonance imaging (MRI) with retrospective ...valve tracking, and 3) 4D flow MRI with particle tracing.
Materials and Methods
Ten healthy volunteers (age 27 ± 3 years) underwent multislice cine short‐axis planimetry and whole‐heart 4D flow MRI on a 3T MRI scanner twice with repositioning between the scans. LV in‐ and outflow was compared from 1) 2D planimetry; 2) 4D flow MRI with retrospective valve tracking over the mitral valve (MV) and aortic valve (AV), and 3) 4D flow MRI with particle tracing through forward and backward integration of velocity data.
Results
In‐scan consistency between MV and AV flow volumes is excellent for both 4D flow MRI methods with r ≥ 0.95 (P ≤ 0.001). In‐scan AV and MV flow by retrospective valve tracking shows good to excellent correlations versus AV and MV flow by particle tracing (r ≥ 0.81, P ≤ 0.004). Scan–rescan SV assessment by 2D planimetry shows excellent reproducibility (intraclass correlation ICC = 0.98, P < 0.001, coefficient of variation CV = 7%). Scan–rescan MV and AV flow volume assessment by retrospective valve tracking shows strong reproducibility (ICCs ≥ 0.89, P ≤ 0.05, CVs = 12%), as well as by forward and backward particle tracing (ICCs ≥ 0.90, P ≤ 0.001, CVs ≤ 11%). Multicomponent particle tracing shows good scan–rescan reproducibility (ICCs ≥ 0.81, P ≤ 0.007, CVs ≤ 16%).
Conclusion
LV in‐ and outflow assessment by 2D planimetry and 4D flow MRI with retrospective valve tracking and particle tracing show good in‐scan consistency and strong scan–rescan reproducibility, which indicates that both 4D flow MRI methods are reliable and can be used clinically.
Level of Evidence: 2
Technical Efficacy Stage: 2
J. Magn. Reson. Imaging 2018;47:511–522.
Right atrial (RA) area predicts mortality in patients with pulmonary hypertension, and is recommended by the European Society of Cardiology/European Respiratory Society pulmonary hypertension ...guidelines. The advent of deep learning may allow more reliable measurement of RA areas to improve clinical assessments. The aim of this study was to automate cardiovascular magnetic resonance (CMR) RA area measurements and evaluate the clinical utility by assessing repeatability, correlation with invasive haemodynamics and prognostic value.
A deep learning RA area CMR contouring model was trained in a multicentre cohort of 365 patients with pulmonary hypertension, left ventricular pathology and healthy subjects. Inter-study repeatability (intraclass correlation coefficient (ICC)) and agreement of contours (DICE similarity coefficient (DSC)) were assessed in a prospective cohort (n = 36). Clinical testing and mortality prediction was performed in n = 400 patients that were not used in the training nor prospective cohort, and the correlation of automatic and manual RA measurements with invasive haemodynamics assessed in n = 212/400. Radiologist quality control (QC) was performed in the ASPIRE registry, n = 3795 patients. The primary QC observer evaluated all the segmentations and recorded them as satisfactory, suboptimal or failure. A second QC observer analysed a random subcohort to assess QC agreement (n = 1018).
All deep learning RA measurements showed higher interstudy repeatability (ICC 0.91 to 0.95) compared to manual RA measurements (1st observer ICC 0.82 to 0.88, 2nd observer ICC 0.88 to 0.91). DSC showed high agreement comparing automatic artificial intelligence and manual CMR readers. Maximal RA area mean and standard deviation (SD) DSC metric for observer 1 vs observer 2, automatic measurements vs observer 1 and automatic measurements vs observer 2 is 92.4 ± 3.5 cm
, 91.2 ± 4.5 cm
and 93.2 ± 3.2 cm
, respectively. Minimal RA area mean and SD DSC metric for observer 1 vs observer 2, automatic measurements vs observer 1 and automatic measurements vs observer 2 was 89.8 ± 3.9 cm
, 87.0 ± 5.8 cm
and 91.8 ± 4.8 cm
. Automatic RA area measurements all showed moderate correlation with invasive parameters (r = 0.45 to 0.66), manual (r = 0.36 to 0.57). Maximal RA area could accurately predict elevated mean RA pressure low and high-risk thresholds (area under the receiver operating characteristic curve artificial intelligence = 0.82/0.87 vs manual = 0.78/0.83), and predicted mortality similar to manual measurements, both p < 0.01. In the QC evaluation, artificial intelligence segmentations were suboptimal at 108/3795 and a low failure rate of 16/3795. In a subcohort (n = 1018), agreement by two QC observers was excellent, kappa 0.84.
Automatic artificial intelligence CMR derived RA size and function are accurate, have excellent repeatability, moderate associations with invasive haemodynamics and predict mortality.
Long scan times prohibit a widespread clinical applicability of 4D flow MRI in Fontan patients. As pulsatility in the Fontan pathway is minimal during the cardiac cycle, acquiring non-ECG gated 3D ...flow MRI may result in a reduction of scan time while accurately obtaining time-averaged clinical parameters in comparison with 2D and 4D flow MRI. Thirty-two Fontan patients prospectively underwent 2D (reference), 3D and 4D flow MRI of the Fontan pathway. Multiple clinical parameters were assessed from time-averaged flow rates, including the right-to-left pulmonary flow distribution (main endpoint) and systemic-to-pulmonary collateral flow (SPCF). A ten-fold reduction in scan time was achieved 4D flow 15.9 min (SD 2.7 min) and 3D flow 1.6 min (SD 7.8 s), p < 0.001 with a superior signal-to-noise ratio mean ratio of SNRs 1.7 (0.8), p < 0.001 and vessel sharpness mean ratio 1.2 (0.4), p = 0.01 with 3D flow. Compared to 2D flow, good-excellent agreement was shown for mean flow rates (ICC 0.82-0.96) and right-to-left pulmonary flow distribution (ICC 0.97). SPCF derived from 3D flow showed good agreement with that from 4D flow (ICC 0.86). 3D flow MRI allows for obtaining time-averaged flow rates and derived clinical parameters in the Fontan pathway with good-excellent agreement with 2D and 4D flow, but with a tenfold reduction in scan time and significantly improved image quality compared to 4D flow.
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.
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.
Abstract 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 > 2 mm 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.
PDF
