Post mortem computed tomography is highly sensitive for pyelonephritis. A radiologic-pathologic correlation series.

Pyelonephritis is a potentially lethal disease occasionally encountered in the forensic setting. Post mortem computed tomography (PMCT) is an important investigative tool for the forensic pathologist. In particular, it may be used to document and screen disease prior to traditional autopsy methods. While the sensitivity and specificity of computed tomography for pyelonephritis is well studied in the antemortem clinical setting, the test characteristics of PMCT are not yet described in the forensic pathology literature. A series of all cases of fatal pyelonephritis identified at the Ontario Forensic Pathology Service, over the course of 1 year was studied. Radiologic, clinical and pathologic findings were reviewed. A fulsome autopsy, including histopathologic examination, was considered the gold standard for sensitivity and specificity calculations. A control group consisting of 16 cases without pyelonephritis (ex: opiate toxicity) in which both PMCT and histologic data were available by way of comparison. Sixteen cases of pyelonephritis were identified. Post mortem computed tomographical signs of pyelonephritis included asymmetric renal enlargement, perinephric fat stranding, and ectopic renal air. The most (57%) individually sensitive of these findings was perinephric fat stranding but sensitivity increased to 100% if any of the three signs were present. The control group analysis revealed the specificity of air asymmetry (81%), asymmetric renal enlargement (81%), and fat stranding (69%). PMCT findings may rule in a diagnosis of pyelonephritis, and should prompt the pathologist to grossly and microscopically examine the kidneys.

Validation of Artificial Intelligence Cardiac MRI Measurements: Relationship to Heart Catheterization and Mortality Prediction.

Background Cardiac MRI measurements have diagnostic and prognostic value in the evaluation of cardiopulmonary disease. Artificial intelligence approaches to automate cardiac MRI segmentation are emerging but require clinical testing. Purpose To develop and evaluate a deep learning tool for quantitative evaluation of cardiac MRI functional studies and assess its use for prognosis in patients suspected of having pulmonary hypertension. Materials and Methods A retrospective multicenter and multivendor data set was used to develop a deep learning-based cardiac MRI contouring model using a cohort of patients suspected of having cardiopulmonary disease from multiple pathologic causes. Correlation with same-day right heart catheterization (RHC) and scan-rescan repeatability was assessed in prospectively recruited participants. Prognostic impact was assessed using Cox proportional hazard regression analysis of 3487 patients from the ASPIRE (Assessing the Severity of Pulmonary Hypertension In a Pulmonary Hypertension Referral Centre) registry, including a subset of 920 patients with pulmonary arterial hypertension. The generalizability of the automatic assessment was evaluated in 40 multivendor studies from 32 centers. Results The training data set included 539 patients (mean age, 54 years ± 20 [SD]; 315 women). Automatic cardiac MRI measurements were better correlated with RHC parameters than were manual measurements, including left ventricular stroke volume (r = 0.72 vs 0.68; P = .03). Interstudy repeatability of cardiac MRI measurements was high for all automatic measurements (intraclass correlation coefficient range, 0.79-0.99) and similarly repeatable to manual measurements (all paired t test P > .05). Automated right ventricle and left ventricle cardiac MRI measurements were associated with mortality in patients suspected of having pulmonary hypertension. Conclusion An automatic cardiac MRI measurement approach was developed and tested in a large cohort of patients, including a broad spectrum of right ventricular and left ventricular conditions, with internal and external testing. Fully automatic cardiac MRI assessment correlated strongly with invasive hemodynamics, had prognostic value, were highly repeatable, and showed excellent generalizability. Clinical trial registration no. NCT03841344 Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Ambale-Venkatesh and Lima in this issue. An earlier incorrect version appeared online. This article was corrected on June 27, 2022.

Training and clinical testing of artificial intelligence derived right atrial cardiovascular magnetic resonance measurements.

BACKGROUND: 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. METHODS: 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). RESULTS: 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 cm2, 91.2 ± 4.5 cm2 and 93.2 ± 3.2 cm2, 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 cm2, 87.0 ± 5.8 cm2 and 91.8 ± 4.8 cm2. 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. CONCLUSION: Automatic artificial intelligence CMR derived RA size and function are accurate, have excellent repeatability, moderate associations with invasive haemodynamics and predict mortality.

Valve-in-valve prosthesis-late morphological findings.

Since its implantation in 2002, transcatheter aortic valve implantation (TAVI) has become the preferred intervention for patients with severe aortic stenosis and significant co-morbidities. In 2007, it was adopted as a rescue procedure for failed bioprosthetic valves, now known as the valve-in-valve (VIV) procedure. Unlike other modes of treatment with a multitude of phase 4 post-marketing surveillance (PMS) data, use of these valves have increased rapidly even without long term durability data on this procedure and the near lack of information on the pathology of failed transcatheter aortic valve replacement (TAVR) bioprosthesis and especially after the VIV procedure. We present a case of a late explanted VIV bioprosthesis (ten (10) years post-initial aortic valve replacement and five (5) years post-VIV procedure) in a 65-year-old male with multiple morphologic findings. Further availability of standardized morphologic data from explanted bioprosthetic valves is essential to aid in understanding the pathophysiology of tissue degeneration of the TAVI valve, and ultimately to improve patient outcomes by identifying possible early interventional strategies.

Reduced scan time and superior image quality with 3D flow MRI compared to 4D flow MRI for hemodynamic evaluation of the Fontan pathway.

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.

Meningeal contribution to migraine pain: a magnetic resonance angiography study.

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_video1awy300media15983750185001.

Energetics of Blood Flow in Cardiovascular Disease: Concept and Clinical Implications of Adverse Energetics in Patients With a Fontan Circulation.

Visualization and quantification of the adverse effects of distorted blood flow are important emerging fields in cardiology. Abnormal blood flow patterns can be seen in various cardiovascular diseases and are associated with increased energy loss. These adverse energetics can be measured and quantified using 3-dimensional blood flow data, derived from computational fluid dynamics and 4-dimensional flow magnetic resonance imaging, and provide new, promising hemodynamic markers. In patients with palliated single-ventricular heart defects, the Fontan circulation passively directs systemic venous return to the pulmonary circulation in the absence of a functional subpulmonary ventricle. Therefore, the Fontan circulation is highly dependent on favorable flow and energetics, and minimal energy loss is of great importance. A focus on reducing energy loss led to the introduction of the total cavopulmonary connection (TCPC) as an alternative to the classical Fontan connection. Subsequently, many studies have investigated energy loss in the TCPC, and energy-saving geometric factors have been implemented in clinical care. Great advances have been made in computational fluid dynamics modeling and can now be done in 3-dimensional patient-specific models with increasingly accurate boundary conditions. Furthermore, the implementation of 4-dimensional flow magnetic resonance imaging is promising and can be of complementary value to these models. Recently, correlations between energy loss in the TCPC and cardiac parameters and exercise intolerance have been reported. Furthermore, efficiency of blood flow through the TCPC is highly variable, and inefficient blood flow is of clinical importance by reducing cardiac output and increasing central venous pressure, thereby increasing the risk of experiencing the well-known Fontan complications. Energy loss in the TCPC will be an important new hemodynamic parameter in addition to other well-known risk factors such as pulmonary vascular resistance and can possibly be improved by patient-specific surgical design. This article describes the theoretical background of mechanical energy of blood flow in the cardiovascular system and the methods of calculating energy loss, and it gives an overview of geometric factors associated with energy efficiency in the TCPC and its implications on clinical outcome. Furthermore, the role of 4-dimensional flow magnetic resonance imaging and areas of future research are discussed.

In-scan and scan-rescan assessment of LV in- and outflow volumes by 4D flow MRI versus 2D planimetry.

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.

Learning-based automated segmentation of the carotid artery vessel wall in dual-sequence MRI using subdivision surface fitting.

PURPOSE: The quantification of vessel wall morphology and plaque burden requires vessel segmentation, which is generally performed by manual delineations. The purpose of our work is to develop and evaluate a new 3D model-based approach for carotid artery wall segmentation from dual-sequence MRI. METHODS: The proposed method segments the lumen and outer wall surfaces including the bifurcation region by fitting a subdivision surface constructed hierarchical-tree model to the image data. In particular, a hybrid segmentation which combines deformable model fitting with boundary classification was applied to extract the lumen surface. The 3D model ensures the correct shape and topology of the carotid artery, while the boundary classification uses combined image information of 3D TOF-MRA and 3D BB-MRI to promote accurate delineation of the lumen boundaries. The proposed algorithm was validated on 25 subjects (48 arteries) including both healthy volunteers and atherosclerotic patients with 30% to 70% carotid stenosis. RESULTS: For both lumen and outer wall border detection, our result shows good agreement between manually and automatically determined contours, with contour-to-contour distance less than 1 pixel as well as Dice overlap greater than 0.87 at all different carotid artery sections. CONCLUSIONS: The presented 3D segmentation technique has demonstrated the capability of providing vessel wall delineation for 3D carotid MRI data with high accuracy and limited user interaction. This brings benefits to large-scale patient studies for assessing the effect of pharmacological treatment of atherosclerosis by reducing image analysis time and bias between human observers.

Migraine induced by hypoxia: an MRI spectroscopy and angiography study.

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.

Acute hemorrhagic leukoencephalomyelitis in a man with viral myocarditis.

We report a case of acute hemorrhagic leukoencephalomyelitis in a man with viral myocarditis. A 48-year-old previously healthy male was found dead in his locked apartment. At autopsy he was found to be malnourished, and his lungs showed gross evidence of bilateral pneumonia with abscess formation and bullous emphysema. Multiple petechial hemorrhages were observed in the brain and mainly involved white matter in the cerebral hemispheres including the corpus callosum and internal capsule, as well as the cerebellum, brainstem, and spinal cord. Microscopy of the brain and spinal cord revealed perivenular hemorrhages, central microthrombi in venules with fibrin exudation into the subcortical white matter, and early perivenular demyelination associated with scanty mixed cellular infiltrates. Other microscopic features included widespread diffuse viral myocarditis, extensive suppurative bronchopneumonia, and chronic bronchitis. This case illustrates the death of a man with a rare fatal disease associated with two other potentially lethal diseases. The case also illustrates the importance of a holistic approach when determining the cause of death, especially when there are competing causes of death.

Disturbed Intracardiac Flow Organization After Atrioventricular Septal Defect Correction as Assessed With 4D Flow Magnetic Resonance Imaging and Quantitative Particle Tracing.

OBJECTIVES: Four-dimensional (3 spatial directions and time) velocity-encoded flow magnetic resonance imaging with quantitative particle tracing analysis allows assessment of left ventricular (LV) blood flow organization. Corrected atrioventricular septal defect (AVSD) patients have an abnormal left atrioventricular valve shape. We aimed to analyze flow organization in corrected AVSD patients and healthy controls. METHODS: A total of 32 patients (age, 25 ± 14 years), 21 after partial AVSD correction and 11 after complete/intermediate AVSD correction, and 30 healthy volunteers (26 ± 12 years) underwent whole-heart four-dimensional velocity-encoded flow magnetic resonance imaging. Particle tracing in the 16-segment LV cavity model was used to quantitatively evaluate blood flow organization discriminating multiple components. RESULTS: Patients showed a smaller percentage of direct flow compared with controls (30% ± 9% vs 44% ± 11%; P < 0.001). In patients, more inflow was observed in the basal inferior segment (22% ± 11% vs controls, 17% ± 5%; P = 0.005), with less direct but more retained inflow (ie, part of inflow that is not ejected from LV in subsequent systole). In patients, more inflow reached the midventricular level (68% ± 13% vs controls, 58% ± 9%; P < 0.001), most notably as retained inflow in the lateral segments. Subsequently, in patients, more (mostly retained) inflow reached the apex (23% ± 13% vs 14% ± 7%; P < 0.001), which correlated with early peak filling velocity (r = 0.637, P < 0.001). Patients with a corrected complete or intermediate AVSD presented with less direct flow (24% ± 8% vs 33% ± 8%; P = 0.003) and more apical inflow (30% ± 14% vs 18% ± 12%; P = 0.014) compared with a corrected partial AVSD. CONCLUSION: Multicomponent particle tracing combined with 16-segment analysis quantitatively demonstrated altered LV flow organization after AVSD correction, with less direct and more retained inflow in apical and lateral LV cavity segments, which may contribute to decreased cardiac pumping efficiency.

Association of acetazolamide infusion with headache and cranial artery dilation in healthy volunteers.

The carbonic anhydrase inhibitor acetazolamide causes extracellular acidosis and dilatation of cerebral arterioles. In this study, we tested the hypothesis that acetazolamide also may induce headache and dilatation of cranial arteries. In a randomized double-blind crossover study design, 12 young healthy women were allocated to injection of 1 g acetazolamide or placebo on 2 separate days. We recorded headache on a verbal rating scale from 0 to 10 during an immediate phase (0-90 minutes) and a delayed phase (2-12 hours). The circumference of cranial arteries was measured using 3T high-resolution magnetic resonance angiography 30 and 60 minutes after injection. Acetazolamide provoked immediate headache in 9 participants compared to 3 participants after placebo (P=.031). Eleven participants reported headache in the delayed phase after acetazolamide, compared with 4 after placebo (P=.016). The area under the curve for headache was increased after acetazolamide compared to placebo in the delayed phase (2-12 h) (P=.005). Compared to placebo, arterial circumference increased after acetazolamide in the basilar artery (P=.002) as well as the cerebral (P=.003), cavernous (P=.002), and cervical (P=.005) parts of the internal carotid artery, but no other extracranial arteries changed after acetazolamide. In conclusion, acetazolamide caused immediate and delayed headache as well as dilatation of intracranial arteries in healthy volunteers. It is possible that extracellular acidosis induced by acetazolamide causes sensitization of cephalic perivascular nociceptors, which, in combination with vasodilatation, leads to delayed headache.

Investigation of the pathophysiological mechanisms of migraine attacks induced by pituitary adenylate cyclase-activating polypeptide-38.

Pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) and vasoactive intestinal polypeptide are structurally and functionally closely related but show differences in migraine-inducing properties. Mechanisms responsible for the difference in migraine induction are unknown. Here, for the first time, we present a head-to-head comparison study of the immediate and long-lasting observations of the migraine-inducing, arterial, physiological and biochemical responses comparing PACAP38 and vasoactive intestinal polypeptide. In a double-blind crossover study 24 female migraine patients without aura were randomly allocated to intravenous infusion of PACAP38 (10 pmol/kg/min) or vasoactive intestinal polypeptide (8 pmol/kg/min) over 20 min. We recorded incidence of migraine during and after infusion (0-24 h). Magnetic resonance angiography of selected extra- and intracranial arteries, blood samples (plasma PACAP38 and vasoactive intestinal polypeptide and serum tryptase), and vital signs (blood pressure, heart rate, respiratory frequency, and end-tidal pressure of CO2) was recorded before and up to 5 h after infusion. Twenty-two patients [mean age 24 years (range 19-36)] completed the study on both days. Sixteen patients (73%) reported migraine-like attacks after PACAP38 and four after vasoactive intestinal polypeptide (18%) infusion (P = 0.002). Three of four patients, who reported migraine-like attacks after vasoactive intestinal polypeptide, also reported attacks after PACAP38. Both peptides induced marked dilatation of the extracranial (P < 0.05), but not intracranial arteries (P > 0.05). PACAP38-induced vasodilatation was longer lasting (>2 h), whereas vasoactive intestinal polypeptide-induced dilatation was normalized after 2 h. We recorded elevated plasma PACAP38 at 1 h after the start of PACAP38 infusion only in those patients who later reported migraine attacks. Blood levels of vasoactive intestinal polypeptide and tryptase were unchanged after PACAP38 infusion. In conclusion, PACAP38-induced migraine was associated with sustained dilatation of extracranial arteries and elevated plasma PACAP38 before onset of migraine-like attacks. PACAP38 has a much higher affinity for the PAC1 receptor and we therefore suggest that migraine induction by PACAP38 may be because of activation of the PAC1 receptor, which may be a future anti-migraine drug target.

3D assessment of stent cell size and side branch access in intravascular optical coherence tomographic pullback runs.

We present a semi-automatic approach to assess the maximum circular unsupported surface area (MCUSA) of selected stent cells and the side branch access through stent cells in intravascular optical coherence tomography (IVOCT) pullback runs. Such 3D information may influence coronary interventions, stent design, blood flow analysis or prognostic evaluation. First, the stent struts are detected automatically and stent cells are reconstructed with users' assistance. Using cylinder fitting, a 2D approximation of the stent cell is generated for MCUSA detection and measurement. Next, a stent surface is reconstructed and stent-covered side branches are detected. Both the stent cell contours and side branch lumen contours are projected onto the stent surface to indicate their areas, and the overlapping regions are measured as the side branch access through these stent cells. The method was evaluated on phantom data sets and the accuracy of the MCUSA and side branch access was found to be 95% and 91%, respectively. The usability of this approach for clinical research was proved on 12 in vivo IVOCT pullback runs.

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.

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.