Magnetic Resonance Angiography Signal Intensity as a Marker of Hemodynamic Impairment in Intracranial Arterial Stenosis

Background

Intracranial arterial stenosis (ICAS) is the predominant cause of ischemic stroke and transient ischemic attack in Asia. Change of signal intensities (SI) across an ICAS on magnetic resonance angiography (MRA) may reflect its hemodynamic severity.

Methods

In-patients with a symptomatic single ICAS detected on 3D time-of-flight MRA were recruited from 2 hospitals. Baseline and 1-year follow-up data were collected. Signal intensity ratio (SIR) [ =  (mean post-stenotic SI -mean background SI)/(mean pre-stenotic SI - mean background SI)] was evaluated on baseline MRA to represent change of SIs across an ICAS. Acute infarct volume was measured on baseline diffusion-weighted images (DWI). Relationships between SIR and baseline characteristics as well as 1y outcomes were evaluated.

Results

Thirty-six subjects (86.1% males, mean age 55.0) were recruited. Overall, mean SIR was 0.84±0.23. Mean SIRs were not significantly different between the 23 (63.9%) anatomically severe stenoses and the 13 (36.1%) anatomically moderate stenoses (0.80±0.23 versus 0.92±0.21, p = 0.126). SIR was significantly, linearly and negatively correlated to acute infarct volume on DWI (Spearman correlation coefficient −0.471, p = 0.011). Two patients (5.6%) had recurrent ischemic strokes at 1y, not related to SIR values.

Conclusions

Change of signal intensities across an ICAS on MRA may reflect its hemodynamic and functional severity. Future studies are warranted to further verify the relationships between this index and prognosis of patients with symptomatic ICAS.     

Response of Retinal Blood Flow to Systemic Hyperoxia as Measured with Dual-Beam Bidirectional Doppler Fourier-Domain Optical Coherence Tomography

Purpose

There is a long-standing interest in the study of retinal blood flow in humans. In the recent years techniques have been established to measure retinal perfusion based on optical coherence tomography (OCT). In the present study we used a technique called dual-beam bidirectional Doppler Fourier-domain optical coherence tomography (FD-OCT) to characterize the effects of 100% oxygen breathing on retinal blood flow. These data were compared to data obtained with a laser Doppler velocimeter (LDV).

Methods

10 healthy subjects were studied on 2 study days. On one study day the effect of 100% oxygen breathing on retinal blood velocities was studied using dual-beam bidirectional Doppler FD-OCT. On the second study day the effect of 100% oxygen breathing on retinal blood velocities was assessed by laser Doppler velocimetry (LDV). Retinal vessel diameters were measured on both study days using a commercially available Dynamic Vessel Analyzer. Retinal blood flow was calculated based on retinal vessel diameters and red blood cell velocity.

Results

As expected, breathing of pure oxygen induced a pronounced reduction in retinal vessel diameters, retinal blood velocities and retinal blood flow on both study days (p<0.001). Blood velocity data correlated well between the two methods applied under both baseline as well as under hyperoxic conditions (r = 0.98 and r = 0.75, respectively). Data as obtained with OCT were, however, slightly higher.

Conclusion

A good correlation was found between red blood cell velocity as measured with dual-beam bidirectional Doppler FD-OCT and red blood cell velocity assessed by the laser Doppler method. Dual-beam bidirectional Doppler FD-OCT is a promising approach for studying retinal blood velocities in vivo.     

Performance of Cryptococcal Antigen Lateral Flow Assay Using Saliva in Ugandans with CD4 <100

Background

Cryptococcal meningitis can best be diagnosed by cerebrospinal fluid India ink microscopy, cryptococcal antigen detection, or culture. These require invasive lumbar punctures. The utility of cryptococcal antigen detection in saliva is unknown. We evaluated the diagnostic performance of the point-of-care cryptococcal antigen lateral flow assay (CrAg LFA) in saliva.

Methods

We screened HIV-infected, antiretroviral therapy naïve persons with symptomatic meningitis (n = 130) and asymptomatic persons with CD4+<100 cells/µL entering into HIV care (n = 399) in Kampala, Uganda. The diagnostic performance of testing saliva was compared to serum/plasma cryptococcal antigen as the reference standard.

Results

The saliva lateral flow assay performance was overall more sensitive in symptomatic patients (88%) than in asymptomatic patients (27%). The specificity of saliva lateral flow assay was excellent at 97.8% in the symptomatic patients and 100% in asymptomatic patients. The degree of accuracy of saliva in diagnosing cryptococcosis and the level of agreement between the two sample types was better in symptomatic patients (C-statistic 92.9, κ-0.82) than in asymptomatic patients (C-statistic 63.5, κ-0.41). Persons with false negative salvia CrAg tests had lower levels of peripheral blood CrAg titers (P<0.001).

Conclusion

There was poor diagnostic performance in testing saliva for cryptococcal antigen, particularly among asymptomatic persons screened for preemptive treatment of cryptococcosis.     

Indocyanine Green Video Angiography Predicts Outcome of Extravasation Injuries

Background

Extravasation of cytotoxic drugs is a serious complication of systemic cancer treatment. Still, a reliable method for early assessment of tissue damage and outcome prediction is missing. Here, we demonstrate that the evaluation of blood flow by indocyanine green (ICG) angiography in the extravasation area predicts for the need of surgical intervention.

Methods

Twenty-nine patients were evaluated by ICG angiography after extravasation of vesicant or highly irritant cytotoxic drugs administered by peripheral i.v. infusion. Tissue perfusion as assessed by this standardized method was correlated with clinical outcome.

Results

The perfusion index at the site of extravasation differed significantly between patients with reversible tissue damage and thus healing under conservative management (N = 22) versus those who needed surgical intervention due to the development of necrosis (N = 7; P = 0.0001). Furthermore, in patients benefiting from conservative management, the perfusion index was significantly higher in the central extravasation area denoting hyperemia, when compared with the peripheral area (P = 0.0001).

Conclusions

In this patient cohort, ICG angiography as indicator of local perfusion within the extravasation area was of prognostic value for tissue damage. ICG angiography could thus be used for the early identification of patients at risk for irreversible tissue damage after extravasation of cytotoxic drugs.     

Hemodynamic Effects of Stent Struts versus Straightening of Vessels in Stent-Assisted Coil Embolization for Sidewall Cerebral Aneurysms

Background

Recent clinical studies have shown that recanalization rates are lower in stent-assisted coil embolization than in coiling alone in the treatment of cerebral aneurysms.

Objective

This study aimed to assess and compare the hemodynamic effect of stent struts and straightening of vessels by stent placement on reducing flow velocity in sidewall aneurysms, with the goal of reducing recanalization rates.

Methods

We evaluated 16 sidewall aneurysms treated with Enterprise stents. We performed computational fluid dynamics simulations using patient-specific geometries before and after treatment, with or without stent struts.

Results

Stent placement straightened vessels by a mean (±standard deviation) of 12.9°±13.1° 6 months after treatment. Placement of stent struts in the initial vessel geometries reduced flow velocity in aneurysms by 23.1%±6.3%. Straightening of vessels without stent struts reduced flow velocity by 9.6%±12.6%. Stent struts had significantly stronger effects on reducing flow velocity than straightening (P = 0.004, Wilcoxon test). Deviation of the effects was larger by straightening than by stent struts (P = 0.01, F-test). The combination of stent struts and straightening reduced flow velocity by 32.6%±12.2%. There was a trend that larger inflow angles produced a larger reduction in flow velocity by straightening of vessels (P = 0.16).

Conclusion

In sidewall aneurysms, stent struts have stronger effects (approximately 2 times) on reduction in flow velocity than straightening of vessels. Hemodynamic effects by straightening vary in each case and can be predicted by inflow angles of pre-operative vessel geometry. These results may be useful to design a treatment strategy for reducing recanalization rates.     

Influence of Acute Jugular Vein Compression on the Cerebral Blood Flow Velocity,Pial Artery Pulsation and Width of Subarachnoid Space in Humans

Purpose

The aim of this study was to assess the effect of acute bilateral jugular vein compression on: (1) pial artery pulsation (cc-TQ); (2) cerebral blood flow velocity (CBFV); (3) peripheral blood pressure; and (4) possible relations between mentioned parameters.

Methods

Experiments were performed on a group of 32 healthy 19–30 years old male subjects. cc-TQ and the subarachnoid width (sas-TQ) were measured using near-infrared transillumination/backscattering sounding (NIR-T/BSS), CBFV in the left anterior cerebral artery using transcranial Doppler, blood pressure was measured using Finapres, while end-tidal CO₂ was measured using medical gas analyser. Bilateral jugular vein compression was achieved with the use of a sphygmomanometer held on the neck of the participant and pumped at the pressure of 40 mmHg, and was performed in the bend-over (BOPT) and swayed to the back (initial) position.

Results

In the first group (n = 10) during BOPT, sas-TQ and pulse pressure (PP) decreased (−17.6% and −17.9%, respectively) and CBFV increased (+35.0%), while cc-TQ did not change (+1.91%). In the second group, in the initial position (n = 22) cc-TQ and CBFV increased (106.6% and 20.1%, respectively), while sas-TQ and PP decreases were not statistically significant (−15.5% and −9.0%, respectively). End-tidal CO₂ remained stable during BOPT and venous compression in both groups. Significant interdependence between changes in cc-TQ and PP after bilateral jugular vein compression in the initial position was found (r = −0.74).

Conclusions

Acute bilateral jugular venous insufficiency leads to hyperkinetic cerebral circulation characterised by augmented pial artery pulsation and CBFV and direct transmission of PP into the brain microcirculation. The Windkessel effect with impaired jugular outflow and more likely increased intracranial pressure is described. This study clarifies the potential mechanism linking jugular outflow insufficiency with arterial small vessel cerebral disease.     

The Normal Transverse Mesocolon and Involvement of the Mesocolon in Acute Pancreatitis: An MRI Study

Objective

To study the MRI findings of the normal transverse mesocolon and the involvement of the mesocolon in acute pancreatitis (AP) as well as the relationship between the involvement of the mesocolon and the severity of AP.

Materials and Methods

Forty patients without pancreatic disorders were retrospectively analyzed to observe the normal transverse mesocolon using MRI; 210 patients with AP confirmed by clinical and laboratory tests were retrospectively analyzed using MRI to observe transverse-mesocolon involvement (TMI). The severity of TMI was recorded as zero points (no abnormalities and transverse-mesocolon vessel involvement), one point (linear and patchy signal in the transverse mesocolon) or two points (transverse-mesocolon effusion). The AP severity was graded by the MRI severity index (MRSI) and the Acute Physiology And Chronic Healthy Evaluation II (APACHE II) scoring system. The correlations of TMI with MRSI and APACHE-II were analyzed.

Results

In a normal transverse mesocolon, the display rates of the middle colic artery, the middle colic vein and the gastrocolic trunk on MRI were 95.0%, 82.5% and 100.0%, respectively. Of the 210 patients with AP, 130 patients (61.9%) had TMI. According to the TMI grading, 40%, 39% and 20% of the patients were graded at zero, one and two points, respectively. TMI was strongly correlated with the MRSI score (r = 0.759, P = 0.000) and the APACHE-II score (r = 0.384, P = 0.000).

Conclusion

MRI could be used to visualize transverse-mesocolon involvement. The severity of TMI could reflect that of AP in the clinical setting and imaging. TMI might be a supplementary indicator of the severity of AP.     

Outcomes of Middle Cardiac Vein Arterialization via Internal Mammary/Thoracic Artery Anastomosis

Objective

Cardiac vein arterialization is seldom applied for treating right coronary artery disease. This study aimed to improve outcomes of cardiac vein arterialization in a porcine model using intramammary artery anastomosis.

Methods

A chronic, stenotic coronary artery model was established in 12 of 14 Chinese experimental miniature pigs of either sex, which were randomly divided into equal control (n = 6) and experimental (n = 6) groups. In experimental animals, blood flow was reconstructed in the right coronary artery using intramammary artery. Arterialization involved dissection of right internal mammary artery from bifurcation to apex of thorax followed by end-to-side anastomosis of internal mammary artery and middle cardiac vein plus posterior descending branch of right coronary artery. Intraoperative heart rate was maintained at 110 beats/min. Graft flow assessment and echocardiography were performed when blood pressure and heart rate normalized.

Results

The experimental group had significantly higher mean endocardial and epicardial blood flow postoperatively than control group (mean endocardial blood flow: 0.37 vs. 0.14 ml/(g*min), p<0.001; mean epicardial blood flow: 0.29 vs. 0.22, p = 0.014). Transmural blood flow was also higher in experimental group than in control group (0.33 vs. 0.19, p<0.001); ejection fraction increased from 0.46% at baseline to 0.51% (p = 0.0038) at 6 hours postoperatively, and mean blood flow of internal mammary artery was 44.50, perfusion index 0.73 at postoperative 6 months, 43.33 and 0.80 at 3 months.

Conclusion

Successful cardiac vein arterialization via intramammary artery in a porcine model suggests that this may be a viable method for reconstructing blood flow in chronic, severe coronary artery disease.     

3D Contrast Enhancement-MR Angiography for Imaging of Unruptured Cerebral Aneurysms: A Hospital-Based Prevalence Study

Background and Purpose

Contrast enhanced MRA (CE-MRA) can help to overcome the limitations of other techniques to clearly display the details of cerebral aneurysms at 1.5-T MR system. We investigated the prevalence of unruptured cerebral aneurysms (UCAs) using three dimensional (3D) CE-MRA in a tertiary comprehensive hospital in China.

Materials and Methods

The cases were prospectively recorded at our hospital between February 2009 and October 2010. 3D CE-MRA, interpreted by 2 observers blinded to the participants’ information, was used to identify the location and size of UCAs and to estimate the overall, age-specific, and sex-specific prevalence.

Results

Of the 3993 patients (men: women = 2159∶1834), 408 UCAs were found in 350 patients (men: women = 151∶199). The prevalence was 8.8% overall (95% CI, 8.0–10.0%), with 7.0% for men (CI, 6.0–8.0%) and 10.9% for women (CI, 9.0–12.0%). The overall prevalence of UCAs was higher in women than in men (P<0.001) and increased with age both in men and women. Prevalence peaked at age group 75–80 years. Forty-two patients (11.7%) had multiple aneurysms, including 10 (2.9%) male patients and 32 (9.1%) female patients. The most common site of aneurysm was the carotid siphon, and most lesions (71.3%) had a maximum diameter of 3−5 mm.

Conclusion

This hospital-based prevalence study suggested a high prevalence (8.8%) of UCAs and most lesions (71.3%) had a maximum diameter of 3–5 mm observed by 3D CE-MRA. Because the rupture of small cerebral aneurysms was not uncommon, an appropriate follow-up care strategy must be formulated.     

Non-Enhanced MR Imaging of Cerebral Aneurysms: 7 Tesla versus 1.5 Tesla

Purpose

To prospectively evaluate 7 Tesla time-of-flight (TOF) magnetic resonance angiography (MRA) in comparison to 1.5 Tesla TOF MRA and 7 Tesla non-contrast enhanced magnetization-prepared rapid acquisition gradient-echo (MPRAGE) for delineation of unruptured intracranial aneurysms (UIA).

Material and Methods

Sixteen neurosurgical patients (male n = 5, female n = 11) with single or multiple UIA were enrolled in this trial. All patients were accordingly examined at 7 Tesla and 1.5 Tesla MRI utilizing dedicated head coils. The following sequences were obtained: 7 Tesla TOF MRA, 1.5 Tesla TOF MRA and 7 Tesla non-contrast enhanced MPRAGE. Image analysis was performed by two radiologists with regard to delineation of aneurysm features (dome, neck, parent vessel), presence of artifacts, vessel-tissue-contrast and overall image quality. Interobserver accordance and intermethod comparisons were calculated by kappa coefficient and Lin''s concordance correlation coefficient.

Results

A total of 20 intracranial aneurysms were detected in 16 patients, with two patients showing multiple aneurysms (n = 2, n = 4). Out of 20 intracranial aneurysms, 14 aneurysms were located in the anterior circulation and 6 aneurysms in the posterior circulation. 7 Tesla MPRAGE imaging was superior over 1.5 and 7 Tesla TOF MRA in the assessment of all considered aneurysm and image quality features (e.g. image quality: mean MPRAGE7T: 5.0; mean TOF7T: 4.3; mean TOF1.5T: 4.3). Ratings for 7 Tesla TOF MRA were equal or higher over 1.5 Tesla TOF MRA for all assessed features except for artifact delineation (mean TOF7T: 4.3; mean TOF1.5T 4.4). Interobserver accordance was good to excellent for most ratings.

Conclusion

7 Tesla MPRAGE imaging demonstrated its superiority in the detection and assessment of UIA as well as overall imaging features, offering excellent interobserver accordance and highest scores for all ratings. Hence, it may bear the potential to serve as a high-quality diagnostic tool for pretherapeutic assessment and follow-up of untreated UIA.     

Behaviour of Non-Donor Specific Antibodies during Rapid Re-Synthesis of Donor Specific HLA Antibodies after Antibody Incompatible Renal Transplantation

Background

HLA directed antibodies play an important role in acute and chronic allograft rejection. During viral infection of a patient with HLA antibodies, the HLA antibody levels may rise even though there is no new immunization with antigen. However it is not known whether the converse occurs, and whether changes on non-donor specific antibodies are associated with any outcomes following HLA antibody incompatible renal transplantation.

Methods

55 patients, 31 women and 24 men, who underwent HLAi renal transplant in our center from September 2005 to September 2010 were included in the studies. We analysed the data using two different approaches, based on; i) DSA levels and ii) rejection episode post transplant. HLA antibody levels were measured during the early post transplant period and corresponding CMV, VZV and Anti-HBs IgG antibody levels and blood group IgG, IgM and IgA antibodies were quantified.

Results

Despite a significant DSA antibody rise no significant non-donor specific HLA antibody, viral or blood group antibody rise was found. In rejection episode analyses, multiple logistic regression modelling showed that change in the DSA was significantly associated with rejection (p = 0.002), even when adjusted for other antibody levels. No other antibody levels were predictive of rejection. Increase in DSA from pre treatment to a post transplant peak of 1000 was equivalent to an increased chance of rejection with an odds ratio of 1.47 (1.08, 2.00).

Conclusion

In spite of increases or decreases in the DSA levels, there were no changes in the viral or the blood group antibodies in these patients. Thus the DSA rise is specific in contrast to the viral, blood group or third party antibodies post transplantation. Increases in the DSA post transplant in comparison to pre-treatment are strongly associated with occurrence of rejection.     

Associations of Maternal Iron Intake and Hemoglobin in Pregnancy with Offspring Vascular Phenotypes and Adiposity at Age 10: Findings from the Avon Longitudinal Study of Parents and Children

Background

Iron deficiency is common during pregnancy. Experimental animal studies suggest that it increases cardiovascular risk in the offspring.

Objective

To examine the relationship between maternal pregnancy dietary and supplement iron intake and hemoglobin, with offspring’s arterial stiffness (measured by carotid-radial pulse wave velocity), endothelial function (measured by brachial artery flow mediated dilatation), blood pressure, and adiposity (measured by body mass index), test for mediation by cord ferritin, birth weight, gestational age, and child dietary iron intake, and for effect modification by maternal vitamin C intake and offspring sex.

Design

Prospective data from 2958 mothers and children pairs at 10 years of age enrolled in an English birth cohort, the Avon Longitudinal Study for Parents and Children (ALSPAC), was analysed.

Results

2639 (89.2%) mothers reported dietary iron intake in pregnancy below the UK reference nutrient intake of 14.8 mg/day. 1328 (44.9%) reported taking iron supplements, and 129 (4.4%) were anemic by 18 weeks gestation. No associations were observed apart from maternal iron intake from supplements with offspring systolic blood pressure (−0.8 mmHg, 99% CI −1.7 to 0, P = 0.01 in the sample with all relevant data observed, and −0.7 mmHg, 99% CI −1.3 to 0, P = 0.008 in the sample with missing data imputed).

Conclusion

There was no evidence of association between maternal pregnancy dietary iron intake, or maternal hemoglobin concentration (which is less likely to be biased by subjective reporting) with offspring outcomes. There was a modest inverse association between maternal iron supplement intake during pregnancy with offspring systolic blood pressure at 10 years.     

The Cost-Utility of CT Angiography and Conventional Angiography for People Presenting with Intracerebral Hemorrhage

Objective

To determine the optimal imaging strategy for ICH incorporating CTA or DSA with and without a NCCT risk stratification algorithm.

Methods

A Markov model included costs, outcomes, prevalence of a vascular lesion, and the sensitivity and specificity of a risk stratification algorithm from the literature. The four imaging strategies were: (a) CTA screening of the entire cohort; (b) CTA only in those where NCCT suggested a high or indeterminate likelihood of a lesion; (c) DSA screening of the entire cohort and (d) DSA only for those with a high or indeterminate suspicion of a lesion following NCCT. Branch d was the comparator.

Results

Age of the cohort and the probability of an underlying lesion influenced the choice of optimal imaging strategy. With a low suspicion for a lesion (<12%), branch (a) was the optimal strategy for a willingness-to-pay of $100,000/QALY. Branch (a) remained the optimal strategy in younger people (<35 years) with a risk below 15%. If the probability of a lesion was >15%, branch (b) became preferred strategy. The probabilistic sensitivity analysis showed that branch (b) was the optimal choice 70–72% of the time over varying willingness-to-pay values.

Conclusions

CTA has a clear role in the evaluation of people presenting with ICH, though the choice of CTA everyone or CTA using risk stratification depends on age and likelihood of finding a lesion.     

Clinical Utility of the Cryptococcal Antigen Lateral Flow Assay in a Diagnostic Mycology Laboratory

Background

Cryptococcus neoformans causes life-threatening meningitis. A recently introduced lateral flow immunoassay (LFA) to detect cryptococcal antigen (CRAG) is reportedly more rapid and convenient than standard latex agglutination (LA), but has not yet been evaluated in a diagnostic laboratory setting.

Methods

One hundred and six serum, 42 cerebrospinal fluid (CSF), and 20 urine samples from 92 patients with known or suspected cryptococcosis were tested by LA and LFA, and titres were compared. Results were correlated with laboratory-confirmed cryptococcosis. Serial samples were tested in nine treated patients.

Results

Twenty-five of 92 patients had confirmed cryptococcosis; all sera (n = 56) from these patients were positive by LFA (sensitivity 100%, 95% confidence interval (CI) 93.6–100%) compared with 51/56 positive by LA (sensitivity 91.1%, 95% CI 80.7–96.1%). Fifty sera from 67 patients without cryptococcosis tested negative in both assays. While LA yielded more false negative results (5/56) this did not reach statistical significance (p = 0.063). Nine CSF samples from patients with cryptococcal meningitis yielded positive results using both assays while 17/18 urine samples from patients with cryptococcosis were positive by the LFA. The LFA detected CRAG in C. gattii infection (n = 4 patients). Agreement between titres obtained by both methods (n = 38 samples) was imperfect; correlation between log-transformed titres (r) was 0.84. Turn-around-time was 20 minutes for the LFA and 2 h for LA. The cost per qualitative sample was 18USD and 91 USD, respectively and per quantitative sample was 38USD and 144USD, respectively.

Conclusions

Qualitative agreement between the LFA and LA assays performed on serum and CSF was good but agreement between titres was imperfect. Ease of performance of the LFA and the capacity for testing urine suggest it has a role in the routine laboratory as a rapid diagnostic test or point-of-care test.     

Improved Flow Cytometric Assessment Reveals Distinct Microvesicle (Cell-Derived Microparticle) Signatures in Joint Diseases

Introduction

Microvesicles (MVs), earlier referred to as microparticles, represent a major type of extracellular vesicles currently considered as novel biomarkers in various clinical settings such as autoimmune disorders. However, the analysis of MVs in body fluids has not been fully standardized yet, and there are numerous pitfalls that hinder the correct assessment of these structures.

Methods

In this study, we analyzed synovial fluid (SF) samples of patients with osteoarthritis (OA), rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). To assess factors that may confound MV detection in joint diseases, we used electron microscopy (EM), Nanoparticle Tracking Analysis (NTA) and mass spectrometry (MS). For flow cytometry, a method commonly used for phenotyping and enumeration of MVs, we combined recent advances in the field, and used a novel approach of differential detergent lysis for the exclusion of MV-mimicking non-vesicular signals.

Results

EM and NTA showed that substantial amounts of particles other than MVs were present in SF samples. Beyond known MV-associated proteins, MS analysis also revealed abundant plasma- and immune complex-related proteins in MV preparations. Applying improved flow cytometric analysis, we demonstrate for the first time that CD3⁺ and CD8⁺ T-cell derived SF MVs are highly elevated in patients with RA compared to OA patients (p = 0.027 and p = 0.009, respectively, after Bonferroni corrections). In JIA, we identified reduced numbers of B cell-derived MVs (p = 0.009, after Bonferroni correction).

Conclusions

Our results suggest that improved flow cytometric assessment of MVs facilitates the detection of previously unrecognized disease-associated vesicular signatures.     

High-Resolution Postcontrast Time-of-Flight MR Angiography of Intracranial Perforators at 7.0 Tesla

Background and Purpose

Different studies already demonstrated the benefits of 7T for precontrast TOF-MRA in the visualization of intracranial small vessels. The aim of this study was to assess the performance of high-resolution 7T TOF-MRA after the administration of a gadolinium-based contrast agent in visualizing intracranial perforating arteries.

Materials and Methods

Ten consecutive patients (7 male; mean age, 50.4 ± 9.9 years) who received TOF-MRA at 7T after contrast administration were retrospectively included in this study. Intracranial perforating arteries, branching from the parent arteries of the circle of Willis, were identified on all TOF-MRA images. Provided a TOF-MRA before contrast administration was present, a direct comparison between pre- and postcontrast TOF-MRA was made.

Results

It was possible to visualize intracranial perforating arteries branching off from the entire circle of Willis, and their proximal branches. The posterior cerebral artery (P1 and proximal segment of P2) appeared to have the largest number of visible perforating branches (mean of 5.1 in each patient, with a range of 2–7). The basilar artery and middle cerebral artery (M1 and proximal segment M2) followed with a mean number of 5.0 and 3.5 visible perforating branches (range of 1–9 and 1–8, respectively). Venous contamination in the postcontrast scans sometimes made it difficult to discern the arterial or venous nature of a vessel.

Conclusion

High-resolution postcontrast TOF-MRA at 7T was able to visualize multiple intracranial perforators branching off from various parts of the circle of Willis and proximal intracranial arteries. Although confirmation in a larger study is needed, the administration of a contrast agent for high-resolution TOF-MRA at 7T seems to enable a better visualization of the distal segment of certain intracranial perforators.     

Migraine with Aura Is Associated with an Incomplete Circle of Willis: Results of a Prospective Observational Study

Objective

To compare the prevalence of an incomplete circle of Willis in patients with migraine with aura, migraine without aura, and control subjects, and correlate circle of Willis variations with alterations in cerebral perfusion.

Methods

Migraine with aura, migraine without aura, and control subjects were prospectively enrolled in a 1∶1∶1 ratio. Magnetic resonance angiography was performed to examine circle of Willis anatomy and arterial spin labeled perfusion magnetic resonance imaging to measure cerebral blood flow. A standardized template rating system was used to categorize circle of Willis variants. The primary pre-specified outcome measure was the frequency of an incomplete circle of Willis. The association between circle of Willis variations and cerebral blood flow was also analyzed.

Results

170 subjects were enrolled (56 migraine with aura, 61 migraine without aura, 53 controls). An incomplete circle of Willis was significantly more common in the migraine with aura compared to control group (73% vs. 51%, p = 0.02), with a similar trend for the migraine without aura group (67% vs. 51%, p = 0.08). Using a quantitative score of the burden of circle of Willis variants, migraine with aura subjects had a higher burden of variants than controls (p = 0.02). Compared to those with a complete circle, subjects with an incomplete circle had greater asymmetry in hemispheric cerebral blood flow (p = 0.05). Specific posterior cerebral artery variants were associated with greater asymmetries of blood flow in the posterior cerebral artery territory.

Conclusions

An incomplete circle of Willis is more common in migraine with aura subjects than controls, and is associated with alterations in cerebral blood flow.     

Coronary Flow Reserve in Pregnant Rats with Increased Left Ventricular Afterload

Background

Coronary flow reserve (CFR) is used as a measure of coronary endothelial function. We investigated the effect of increased afterload on CFR of pregnant and non-pregnant rats.

Methods

Afterload increase in Wister rats (both pregnant and non-pregnant) was achieved by the infusion of angiotensin II (Ang II) for ∼10 days or by subjecting them to transverse aortic constriction (TAC) for ∼14 days. Control groups were infused with 0.9% NaCl or had sham surgery, respectively. In pregnant rats, the experiments were performed close to term gestation. Doppler velocity waveforms of the left main coronary artery were recorded using a high resolution ultrasound imaging system (Vevo 770, VisualSonics, Canada) at baseline while the animals were anesthetized with 1.5% inhaled isoflurane, and during maximal coronary dilatation obtained by the inhalation of 3.5% of isoflurane. CFR was calculated as the ratio between the peak coronary flow velocities (CFR_peak) and the velocity-time integrals (CFR_VTI) recorded at hyperemia and at baseline.

Results

CFR could be calculated in 60 of 75 (80%) animals. There were no differences in CFR between intervention and control groups irrespective of whether afterload was increased by Ang II or TAC. In the TAC-study CFR_peak (1.54±0.07 vs 1.85±0.17; p = 0.03) was decreased in pregnant compared to non-pregnant shams. When sham animals from both studies were pooled together both CFR_peak (1.42±0.07 vs 1.86±0.16; p = 0.005) as well as CFR_VTI (1.45±0.07 vs 1.78±0.12; p = 0.03) were significantly lower in pregnant rats compared to non-pregnant.

Conclusions

CFR can be measured non-invasively in rats using Doppler echocardiography and high concentrations of inhaled isoflurane as a coronary vasodilator. In pregnant rats, CFR is reduced close to term. CFR is not affected by increased left ventricular afterload caused by chronic Ang II infusion or TAC.     

Standardized Handwriting to Assess Bradykinesia,Micrographia and Tremor in Parkinson's Disease

Objective

To assess whether standardized handwriting can provide quantitative measures to distinguish patients diagnosed with Parkinson''s disease from age- and gender-matched healthy control participants.

Design

Exploratory study. Pen tip trajectories were recorded during circle, spiral and line drawing and repeated character ‘elelelel’ and sentence writing, performed by Parkinson patients and healthy control participants. Parkinson patients were tested after overnight withdrawal of anti-Parkinsonian medication.

Setting

University Medical Center Groningen, tertiary care, the Netherlands.

Participants

Patients with Parkinson''s disease (n = 10; mean age 69.0 years; 6 male) and healthy controls (n = 10; mean age 68.1 years; 6 male).

Interventions

Not applicable.

Main Outcome Measures

Movement time and velocity to detect bradykinesia and the size of writing to detect micrographia. A rest recording to investigate the presence of a rest-tremor, by frequency analysis.

Results

Mean disease duration in the Parkinson group was 4.4 years and the patients were in modified Hoehn-Yahr stages 1–2.5. In general, Parkinson patients were slower than healthy control participants. Median time per repetition, median velocity and median acceleration of the sentence task and median velocity of the elel task differed significantly between Parkinson patients and healthy control participants (all p<0.0014). Parkinson patients also wrote smaller than healthy control participants and the width of the ‘e’ in the elel task was significantly smaller in Parkinson patients compared to healthy control participants (p<0.0014). A rest-tremor was detected in the three patients who were clinically assessed as having rest-tremor.

Conclusions

This study shows that standardized handwriting can provide objective measures for bradykinesia, tremor and micrographia to distinguish Parkinson patients from healthy control participants.     

Reversal of Ophthalmic Artery Flow and Stroke Outcomes in Asian Patients with Acute Ischemic Stroke and Unilateral Severe Cervical Carotid Stenosis

Background

The aim of this study was to assess the clinical implications of reversed ophthalmic artery flow (ROAF) for stroke risk and outcomes in subjects with unilateral severe cervical carotid stenosis/occlusion.

Methods

We investigated 128 subjects (101 with acute stroke and 27 without), selected from a large hospital patients base (n  =  14,701), identified with unilateral high-grade cervical carotid stenosis/occlusion by using duplex ultrasonography and brain magnetic resonance imaging. All clinical characteristics were compared for stroke risk between acute stroke and nonstroke groups. Patients with acute stroke were divided into 4 subgroups according to ophthalmic artery flow direction and intracranial stenosis severity, and stroke outcomes were evaluated.

Results

The acute stroke group had significantly higher percentages of ROAF (52.5%, p  =  0.003), carotid occlusion (33.7%, p  =  0.046), and severe intracranial stenosis (74.3%, p<0.001). However, multivariate analysis demonstrated that intracranial stenosis was the only significant risk factor (odds ratio  =  10.38; 95% confidence interval  =  3.64–29.65; p<0.001). Analysis of functional outcomes among the 4 subgroups of patients with stroke showed significant trends (p  =  0.018 to 0.001) for better stroke outcomes from ROAF and mild or no intracranial stenosis. ROAF improved 10–20% stroke outcomes, as compared to forward ophthalmic artery flow, among the patients with stroke and the same degree of severities of intracranial stenosis.

Conclusions

Patients with acute stroke and severe unilateral cervical carotid stenosis/occlusion significantly have high incidence of intracranial stenosis and ROAF. Intracranial stenosis is a major stroke risk indicator as well as a predictor for worse stroke outcomes, and ROAF may provide partial compensation for improving stroke outcomes.