Assessment of dynamic susceptibility contrast cerebral blood flow response to amphetamine challenge: A human pharmacological magnetic resonance imaging study at 1.5 and 4 T

Pharmacological MRI (phMRI) techniques can be used to monitor the neurophysiological effects of central nervous system (CNS) active drugs. In this study, we investigated whether dynamic susceptibility contrast (DSC) perfusion imaging employing the use of superparamagnetic iron oxide nanoparticles (Resovist) could be used to measure hemodynamic response to d-amphetamine challenge in human subjects at both 1.5 and 4 T. Significant changes in cerebral blood flow (CBF) were found in focal regions associated with the nigrostriatal circuit and mesolimbic and mesocortical dopaminergic pathways. More significant CBF responses were found at higher field strength, mainly within striatal structures. The results from this study indicate that DSC perfusion imaging using Resovist can be used to assess the efficacy of CNS-active drugs and may play a role in the development of novel psychiatric therapies at the preclinical level. © 2005 Wiley-Liss, Inc.

Diffusion indices on magnetic resonance imaging and neuropsychological performance in amnestic mild cognitive impairment

Background: Magnetic resonance diffusion tensor imaging (DTI) shows promise in the early detection of microstructural pathophysiological changes in the brain. Objectives: To measure microstructural differences in the brains of participants with amnestic mild cognitive impairment (MCI) compared with an age-matched control group using an optimised DTI technique with fully automated image analysis tools and to investigate the correlation between diffusivity measurements and neuropsychological performance scores across groups. Methods: 34 participants (17 participants with MCI, 17 healthy elderly adults) underwent magnetic resonance imaging (MRI)-based DTI. To control for the effects of anatomical variation, diffusion images of all participants were registered to standard anatomical space. Significant statistical differences in diffusivity measurements between the two groups were determined on a pixel-by-pixel basis using gaussian random field theory. Results: Significantly raised mean diffusivity measurements (p<0.001) were observed in the left and right entorhinal cortices (BA28), posterior occipital-parietal cortex (BA18 and BA19), right parietal supramarginal gyrus (BA40) and right frontal precentral gyri (BA4 and BA6) in participants with MCI. With respect to fractional anisotropy, participants with MCI had significantly reduced measurements (p<0.001) in the limbic parahippocampal subgyral white matter, right thalamus and left posterior cingulate. Pearson's correlation coefficients calculated across all participants showed significant correlations between neuropsychological assessment scores and regional measurements of mean diffusivity and fractional anisotropy. Conclusions: DTI-based diffusivity measures may offer a sensitive method of detecting subtle microstructural brain changes associated with preclinical Alzheimer's disease.

Tuning the resonance properties of 2D carbon nanotube networks towards a mechanical resonator

The capabilities of the mechanical resonator-based nanosensors in detecting ultra-small mass or force shifts have driven a continuing exploration of the palette of nanomaterials for such application purposes. Based on large-scale molecular dynamics simulations, we have assessed the applicability of a new class of carbon nanomaterials for nanoresonator usage, i.e. the single-wall carbon nanotube (SWNT) network. It is found that SWNT networks inherit excellent mechanical properties from the constituent SWNTs, possessing a high natural frequency. However, although a high quality factor is suggested from the simulation results, it is hard to obtain an unambiguous Q-factor due to the existence of vibration modes in addition to the dominant mode. The nonlinearities resulting from these extra vibration modes are found to exist uniformly under various testing conditions including different initial actuations and temperatures. Further testing shows that these modes can be effectively suppressed through the introduction of axial strain, leading to an extremely high quality factor in the order of 109 estimated from the SWNT network with 2% tensile strain. Additional studies indicate that the carbon rings connecting the SWNTs can also be used to alter the vibrational properties of the resulting network. This study suggests that the SWNT network can be a good candidate for applications as nanoresonators.

Lateralization of temporal lobe epilepsy based on resting-state functional magnetic resonance imaging and machine learning

Lateralization of temporal lobe epilepsy (TLE) is critical for successful outcome of surgery to relieve seizures. TLE affects brain regions beyond the temporal lobes and has been associated with aberrant brain networks, based on evidence from functional magnetic resonance imaging. We present here a machine learning-based method for determining the laterality of TLE, using features extracted from resting-state functional connectivity of the brain. A comprehensive feature space was constructed to include network properties within local brain regions, between brain regions, and across the whole network. Feature selection was performed based on random forest and a support vector machine was employed to train a linear model to predict the laterality of TLE on unseen patients. A leave-one-patient-out cross validation was carried out on 12 patients and a prediction accuracy of 83% was achieved. The importance of selected features was analyzed to demonstrate the contribution of resting-state connectivity attributes at voxel, region, and network levels to TLE lateralization.

Efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis: Results of a randomised placebo-controlled trial (ABILITY-1)

Purpose: To evaluate the efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis (nr-axSpA). Methods: Patients fulfilled Assessment of Spondyloarthritis international Society (ASAS) criteria for axial spondyloarthritis, had a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of ≥ 4, total back pain score of ≥ 4 (10 cm visual analogue scale) and inadequate response, intolerance or contraindication to non-steroidal anti-inflammatory drugs (NSAIDs); patients fulfilling modified New York criteria for ankylosing spondylitis were excluded. Patients were randomised to adalimumab (N=91) or placebo (N=94). The primary endpoint was the percentage of patients achieving ASAS40 at week 12. Efficacy assessments included BASDAI and Ankylosing Spondylitis Disease Activity Score (ASDAS). MRI was performed at baseline and week 12 and scored using the Spondyloarthritis Research Consortium of Canada (SPARCC) index. Results: Significantly more patients in the adalimumab group achieved ASAS40 at week 12 compared with patients in the placebo group (36% vs 15%, p<0.001). Significant clinical improvements based on other ASAS responses, ASDAS and BASDAI were also detected at week 12 with adalimumab treatment, as were improvements in quality of life measures. Inflammation in the spine and sacroiliac joints on MRI significantly decreased after 12 weeks of adalimumab treatment. Shorter disease duration, younger age, elevated baseline C-reactive protein or higher SPARCC MRI sacroiliac joint scores were associated with better week 12 responses to adalimumab. The safety profile was consistent with what is known for adalimumab in ankylosing spondylitis and other diseases. Conclusions: In patients with nr-axSpA, adalimumab treatment resulted in effective control of disease activity, decreased inflammation and improved quality of life compared with placebo. Results from ABILITY-1 suggest that adalimumab has a positive benefit-risk profile in active nr-axSpA patients with inadequate response to NSAIDs.

Spinal inflammation in the absence of sacroiliac joint inflammation on magnetic resonance imaging in patients with active nonradiographic axial spondyloarthritis

Objective: To evaluate the presence of spinal inflammation with and without sacroiliac (SI) joint inflammation on magnetic resonance imaging (MRI) in patients with active nonradiographic axial spondyloarthritis (SpA), and to compare the disease characteristics of these subgroups. Methods: ABILITY-1 is a multicenter, randomized, controlled trial of adalimumab versus placebo in patients with nonradiographic axial SpA classified using the Assessment of SpondyloArthritis international Society axial SpA criteria. Baseline MRIs were centrally scored independently by 2 readers using the Spondyloarthritis Research Consortium of Canada (SPARCC) method for the SI joints and the SPARCC 6-discovertebral unit method for the spine. Positive evidence of inflammation on MRI was defined as a SPARCC score of >2 for either the SI joints or the spine. Results: Among patients with baseline SPARCC scores, 40% had an SI joint score of >2 and 52% had a spine score of >2. Forty-nine percent of patients with baseline SI joint scores of <2, and 58% of those with baseline SI joint scores of >2, had a spine score of >2. Comparison of baseline disease characteristics by baseline SI joint and spine scores showed that a greater proportion of patients in the subgroup with a baseline SPARCC score of >2 for both SI joints and spine were male, and patients with spine and SI joint scores of <2 were younger and had shorter symptom duration. SPARCC spine scores correlated with baseline symptom duration, and SI joint scores correlated negatively with the baseline Bath Ankylosing Spondylitis Disease Activity Index, but neither correlated with the baseline Ankylosing Spondylitis Disease Activity Score, total back pain, the patient's global assessment of disease activity, the Bath Ankylosing Spondylitis Functional Index, morning stiffness, nocturnal pain, or C-reactive protein level. Conclusion: Assessment by experienced readers showed that spinal inflammation on MRI might be observed in half of patients with nonradiographic axial SpA without SI joint inflammation.

Double diffusive Marangoni convection flow of electrically conducting fluid in a square cavity with chemical reaction

Double diffusive Marangoni convection flow of viscous incompressible electrically conducting fluid in a square cavity is studied in this paper by taking into consideration of the effect of applied magnetic field in arbitrary direction and the chemical reaction. The governing equations are solved numerically by using alternate direct implicit (ADI) method together with the successive over relaxation (SOR) technique. The flow pattern with the effect of governing parameters, namely the buoyancy ratio W, diffusocapillary ratio w, and the Hartmann number Ha, is investigated. It is revealed from the numerical simulations that the average Nusselt number decreases; whereas the average Sherwood number increases as the orientation of magnetic field is shifted from horizontal to vertical. Moreover, the effect of buoyancy due to species concentration on the flow is stronger than the one due to thermal buoyancy. The increase in diffusocapillary parameter, w caus

Graphene quantum dots and the resonance light scattering technique for trace analysis of phenol in different water samples

A novel, highly selective resonance light scattering (RLS) method was researched and developed for the analysis of phenol in different types of industrial water. An important aspect of the method involved the use of graphene quantum dots (GQDs), which were initially obtained from the pyrolysis of citric acid dissolved in aqueous solutions. The GQDs in the presence of horseradish peroxidase (HRP) and H2O2 were found to react quantitatively with phenol such that the RLS spectral band (310 nm) was quantitatively enhanced as a consequence of the interaction between the GQDs and the quinone formed in the above reaction. It was demonstrated that the novel analytical method had better selectivity and sensitivity for the determination of phenol in water as compared to other analytical methods found in the literature. Thus, trace amounts of phenol were detected over the linear ranges of 6.00×10−8–2.16×10−6 M and 2.40×10−6–2.88×10−5 M with a detection limit of 2.20×10−8 M. In addition, three different spiked waste water samples and two untreated lake water samples were analysed for phenol. Satisfactory results were obtained with the use of the novel, sensitive and rapid RLS method.

Performance assessment in a heat exchanger tube fitted with double counter twisted tape inserts

The present study explored the effects of the double counter twisted tapes on heat transfer and fluid friction characteristics in a heat exchanger tube. The double counter twisted tapes were used as counter-swirl flow generators in the test section. The experiments were performed with double counter twisted tapes of four different twist ratios (y = 1.95, 3.85, 5.92 and 7.75) using air as the testing fluid in a circular tube turbulent flow regime where the Reynolds number was varied from 6950 to 50,050. The experimental results demonstrated that the Nusselt number, friction factor and thermal enhancement efficiency were increased with decreasing twist ratio. The results also revealed that the heat transfer rate in the tube fitted with double counter twisted tape was significantly increased with corresponding increase in pressure drop. In the range of the present work, heat transfer rate and friction factor were obtained to be around 60 to 240% and 91 to 286% higher than those of the plain tube values, respectively. The maximum thermal enhancement efficiency of 1.34 was achieved by the use of double counter twisted tapes at constant blower power. In addition, the empirical correlations for the Nusselt number, friction factor and thermal enhancement efficiency were also developed, based on the experimental data.

Multimodal polymer nanoparticles with combined 19F magnetic resonance and optical detection for tunable, targeted, multimodal imagingin vivo

Understanding the complex nature of diseased tissue in vivo requires development of more advanced nanomedicines, where synthesis of multifunctional polymers combines imaging multimodality with a biocompatible, tunable, and functional nanomaterial carrier. Here we describe the development of polymeric nanoparticles for multimodal imaging of disease states in vivo. The nanoparticle design utilizes the abundant functionality and tunable physicochemical properties of synthetically robust polymeric systems to facilitate targeted imaging of tumors in mice. For the first time, high-resolution 19F/1H magnetic resonance imaging is combined with sensitive and versatile fluorescence imaging in a polymeric material for in vivo detection of tumors. We highlight how control over the chemistry during synthesis allows manipulation of nanoparticle size and function and can lead to very high targeting efficiency to B16 melanoma cells, both in vitro and in vivo. Importantly, the combination of imaging modalities within a polymeric nanoparticle provides information on the tumor mass across various size scales in vivo, from millimeters down to tens of micrometers.

Utility of magnetic resonance imaging-based finite element analysis for the biomechanical stress analysis of hemorrhagic and non-hemorrhagic carotid plaques

Background: Biomechanical stress analysis has been used for plaque vulnerability assessment. The presence of plaque hemorrhage (PH) is a feature of plaque vulnerability and is associated with thromboembolic ischemic events. The purpose of the present study was to use finite element analysis (FEA) to compare the stress profiles of hemorrhagic and non-hemorrhagic profiles. Methods and Results: Forty-five consecutive patients who had suffered a cerebrovascular ischemic event with an underlying carotid artery disease underwent high-resolution magnetic resonance imaging (MRI) of their symptomatic carotid artery in a 1.5-T MRI system. Axial images were manually segmented for various plaque components and used for FEA. Maximum critical stress (M-CstressSL) for each slice was determined. Within a plaque, the maximum M-CstressSL for each slice of a plaque was selected to represent the maximum critical stress of that plaque (M-CstressPL) and used to compare hemorrhagic and non-hemorrhagic plaques. A total of 62% of plaques had hemorrhage. It was observed that plaques with hemorrhage had significantly higher stress (M-CstressPL) than plaques without PH (median [interquartile range]: 315 kPa [247-434] vs. 200 kPa [171-282], P=0.003). Conclusions: Hemorrhagic plaques have higher biomechanical stresses than non-hemorrhagic plaques. MRI-based FEA seems to have the potential to assess plaque vulnerability.

Association between biomechanical structural stresses of atherosclerotic carotid plaques and subsequent ischaemic cerebrovascular events - A longitudinal in vivo magnetic resonance imaging-based finite element study

Background: High-resolution magnetic resonance (MR) imaging has been used for MR imaging-based structural stress analysis of atherosclerotic plaques. The biomechanical stress profile of stable plaques has been observed to differ from that of unstable plaques; however, the role that structural stresses play in determining plaque vulnerability remains speculative. Methods: A total of 61 patients with previous history of symptomatic carotid artery disease underwent carotid plaque MR imaging. Plaque components of the index artery such as fibrous tissue, lipid content and plaque haemorrhage (PH) were delineated and used for finite element analysis-based maximum structural stress (M-C Stress) quantification. These patients were followed up for 2 years. The clinical end point was occurrence of an ischaemic cerebrovascular event. The association of the time to the clinical end point with plaque morphology and M-C Stress was analysed. Results: During a median follow-up duration of 514 days, 20% of patients (n=12) experienced an ischaemic event in the territory of the index carotid artery. Cox regression analysis indicated that M-C Stress (hazard ratio (HR): 12.98 (95% confidence interval (CI): 1.32-26.67, pZ0.02), fibrous cap (FC) disruption (HR: 7.39 (95% CI: 1.61e33.82), p Z 0.009) and PH (HR: 5.85 (95% CI: 1.27e26.77), p Z 0.02) are associated with the development of subsequent cerebrovascular events. Plaques associated with future events had higher M-C Stress than those which had remained asymptomatic (median (interquartile range, IQR): 330 kPa (229e494) vs. 254 kPa (166-290), p Z0.04). Conclusions: High biomechanical structural stresses, in addition to FC rupture and PH, are associated with subsequent cerebrovascular events.

Study of reproducibility of human arterial plaque reconstruction and its effects on stress analysis based on multispectral in vivo magnetic resonance imaging

Purpose: To quantify the uncertainties of carotid plaque morphology reconstruction based on patient-specific multispectral in vivo magnetic resonance imaging (MRI) and their impacts on the plaque stress analysis. Materials and Methods: In this study, three independent investigators were invited to reconstruct the carotid bifurcation with plaque based on MR images from two subjects to study the geometry reconstruction reproducibility. Finite element stress analyses were performed on the carotid bifurcations, as well as the models with artificially modified plaque geometries to mimic the image segmentation uncertainties, to study the impacts of the uncertainties to the stress prediction. Results: Plaque reconstruction reproducibility was generally high in the study. The uncertainties among interobservers are around one or the subpixel level. It also shows that the predicted stress is relatively less sensitive to the arterial wall segmentation uncertainties, and more affected by the accuracy of lipid region definition. For a model with lipid core region artificially increased by adding one pixel on the lipid region boundary, it will significantly increase the maximum Von Mises Stress in fibrous cap (>100%) compared with the baseline model for all subjects. Conclusion: The current in vivo MRI in the carotid plaque could provide useful and reliable information for plaque morphology. The accuracy of stress analysis based on plaque geometry is subject to MRI quality. The improved resolution/quality in plaque imaging with newly developed MRI protocols would generate more realistic stress predictions.

Carotid arterial plaque stress analysis using fluid-structure interactive simulation based on in-vivo magnetic resonance images of four patients

The rupture of atherosclerotic plaques is known to be associated with the stresses that act on or within the arterial wall. The extreme wall tensile stress (WTS) is usually recognized as a primary trigger for the rupture of vulnerable plaque. The present study used the in-vivo high-resolution multi-spectral magnetic resonance imaging (MRI) for carotid arterial plaque morphology reconstruction. Image segmentation of different plaque components was based on the multi-spectral MRI and co-registered with different sequences for the patient. Stress analysis was performed on totally four subjects with different plaque burden by fluid-structure interaction (FSI) simulations. Wall shear stress distributions are highly related to the degree of stenosis, while the level of its magnitude is much lower than the WTS in the fibrous cap. WTS is higher in the luminal wall and lower at the outer wall, with the lowest stress at the lipid region. Local stress concentrations are well confined in the thinner fibrous cap region, and usually locating in the plaque shoulder; the introduction of relative stress variation during a cycle in the fibrous cap can be a potential indicator for plaque fatigue process in the thin fibrous cap. According to stress analysis of the four subjects, a risk assessment in terms of mechanical factors could be made, which may be helpful in clinical practice. However, more subjects with patient specific analysis are desirable for plaque-stability study.

Comparison of the inflammatory burden of truly asymptomatic carotid atheroma with atherosclerotic plaques in patients with asymptomatic carotid stenosis undergoing coronary artery bypass grafting: An ultrasmall superparamagnetic iron oxide enhanced magnetic resonance study

Introduction: Inflammation is a recognized risk factor for the vulnerable atherosclerotic plaque. The aim of this study was to explore whether there is a difference in the degree of Magnetic Resonance (MR) defined inflammation using Ultra Small Super-Paramagnetic Iron Oxide (USPIO) particles, within carotid atheroma in completely asymptomatic individuals and the asymptomatic carotid stenosis in a cohort of patients undergoing coronary artery bypass grafting (CABG). Methods: 10 patients awaiting CABG with asymptomatic carotid disease and 10 completely asymptomatic individuals with no documented coronary artery disease underwent multi-sequence MR imaging before and 36 hours post USPIO infusion. Images were manually segmented into quadrants and signal change in each quadrant, normalised to adjacent muscle signal, was calculated following USPIO administration. Results: The mean percentage of quadrants showing signal loss was 94% in the CABG group, compared to 24% in the completely asymptomatic individuals (p < 0.001). The carotid plaques from the CABG patients showed a significant mean signal intensity decrease of 16.4% after USPIO infusion (95% CI 10.6% to 22.2%; p < 0.001). The truly asymptomatic plaques showed a mean signal intensity increase (i.e. enhancement) after USPIO infusion of 8.4% (95% CI 2.6% to 14.2%; p = 0.007). The mean signal difference between the two groups was 24.9% (95% CI 16.7% to 33.0%; p < 0.001). Conclusions: These findings are consistent with the hypothesis that inflammatory atheroma is a systemic disease. The carotid territory is more likely to take up USPIO if another vascular territory is symptomatic.