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El Niño Southern Oscillation (ENSO) influences multi-year variation in sea-surface temperature and the intensity of upwelling in many Pacific regions. However, it is currently unknown how El Niño conditions will affect the concentration and elemental ratios of particulate organic matter (POM). To investigate this, we have quantified POM weekly for 6 years (2012 to 2017) at the MICRO time-series station in the Southern California Bight. We found a strong influence of the 2015 El Niño on sea-surface temperature and phosphate concentration but to a lesser extent on nitrate availability. The 2015 El Niño also resulted in a short-term depression in POC and POP concentrations, whereas PON concentrations displayed an independent long-term decline regardless of the El Niño event. Reduced POM concentrations resulting from the 2015 El Niño occurred in parallel to high C:P and N:P ratios. Following the changes in PON, C:N continued to climb reaching ~9.4 at the end of our sampling period. We suggest that an Eastern Pacific- vs. a Central Pacific-type El Niño as well as a switch in the Pacific Decadal Oscillation phase significantly altered the local response in POM concentrations and ratios.

Seasonal and El Niño-Southern Oscillation (ENSO) warming result in similar ocean changes as predicted with climate change. Climate-driven environmental cycles have strong impacts on microbiome diversity, but impacts on microbiome function are poorly understood. We quantified changes in microbial genomic diversity and functioning over 11 years covering seasonal and ENSO cycles at a coastal site in the southern California Current. We observed seasonal oscillations between large genome lineages during cold, nutrient rich conditions in winter and spring versus small genome lineages, including Prochlorococcus and Pelagibacter, in summer and fall. Parallel interannual changes separated communities depending on ENSO condition. Biodiversity shifts translated into clear oscillations in microbiome functional potential. Ocean warming induced an ecosystem with less iron but more macronutrient stress genes, depressed organic carbon degradation potential and biomass, and elevated carbon-to-nutrient biomass ratios. The consistent microbial response observed across time-scales points towards large climate-driven changes in marine ecosystems and biogeochemical cycles., Competing Interests: Additional Declarations: There is NO Competing Interest.

Background: The imaging of patients with implanted electrically-conductive devices via magnetic resonance imaging at ultra-high fields is hampered by uncertainties relating to the potential for inducing tissue heating adjacent to the implant due to coupling of energy from the incident electromagnetic field into the implant. Existing data in the peer-reviewed literature of comparisons across field strengths of tissue heating and its surrogate, the specific absorption rate (SAR), is scarce and contradictory, leading to further doubts pertaining to the safety of imaging patients with such devices., Purpose: The radiofrequency-induced SAR adjacent to orthopedic screws of varying length and at frequencies of 64 to 498 MHz was investigated via full-wave electromagnetic simulations, to provide an accurate comparison of SAR across MRI field strengths., Methods: Dipole antennas were used for RF transmission to achieve a uniform electric field tangential to the screws located 120 mm above the antenna midpoints, embedded in a bone-mimicking material. The input power to the antennas was constrained to achieve the following targets without the screw present: (i) E = 100 V/m, (ii) B 1 +  = 2 μT, and (iii) global-average-SAR = 3.2 W/kg. Simulations were performed with a spatial resolution of 0.2 mm in the volume surrounding the screws, resulting in 76-137 MCells, noting the maximum 1 g-averaged SAR value in each case. Simulations were repeated at 128 and 297 MHz for screws embedded in muscle tissue., Results: The peak SAR, occurring at the resonant screw length, substantially increased as the frequency decreased when the input power to the dipole antenna was constrained to achieve constant electric field in background tissue at the screws' locations. A similar pattern was observed when constraining input power to achieve constant B 1 + and global-average-SAR. The dielectric properties of the tissue in which the screws were embedded dominated the SAR comparisons between 297 and 128 MHz., Conclusions: The study design allowed for a direct comparison to be performed of SAR across frequencies and implant lengths without the confounding effect of variable incident electric field. Lower frequencies produced substantially larger SAR values for implants approaching the resonant length for the worst-case uniform incident electric field along the screws' length. The data may inform risk-benefit assessments for imaging patients with orthopedic implants at the new clinical field strength of 7 Tesla., (© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: Dental amalgam contains mercury and is commonly used in dental restorations. The impact of MRI on mercury excretion from dental amalgam is not well understood across clinical field strengths, especially 7T. We investigated the effects of MRI exposure on mercury excretion using fresh, lab-created dental amalgam restorations and in extracted teeth with old, pre-existing restorations., Methods: Donated, unfilled human teeth (n = 120) were restored with amalgam before being stored in saline, artificial saliva, or a dry box prior to MRI scanning. The teeth were placed in individual tubes of fresh artificial saliva and scanned at 1.5T, 3T, or 7T or left unscanned as controls. Mercury concentrations were measured 24-30 h later. Donated teeth with pre-existing restorations (n = 40) were stored in artificial saliva, scanned at 7T or left unscanned as controls, and mercury concentration tested., Results: For teeth extracted and restored in a laboratory, no significant difference was found (F = 2.42, P = 0.072) between mean mercury concentrations of unscanned teeth (13.72 μg/L) and teeth scanned at 1.5T (10.88 μg/L), 3T (12.65 μg/L), or 7T (8.88 μg/L). For teeth extracted with previously placed restorations, no significant difference (P = 0.288) was found between unscanned controls (4.28 μg/L) and teeth scanned at 7T (6.63 μg/L)., Conclusion: MRI of dental amalgam does not significantly increase mercury excretion at 1.5T, 3T, or 7T compared to unscanned teeth. This holds true for controlled laboratory restorations as well as for those placed and lived with prior to extraction and scanning, demonstrating no added risk to the clinical patient or research subject., (© 2023 International Society for Magnetic Resonance in Medicine.)

Purpose: MRI has become an essential diagnostic imaging modality for peripheral nerve pathology. Early MR imaging for peripheral nerve depended on inferred nerve involvement by visualizing downstream effects such as denervation muscular atrophy; improvements in MRI technology have made possible direct visualization of the nerves. In this paper, we share our early clinical experience with 7T for benign neurogenic tumors., Materials: Patients with benign neurogenic tumors and 7T MRI examinations available were reviewed. Cases of individual benign peripheral nerve tumors were included to demonstrate 7T MRI imaging characteristics. All exams were performed on a 7T MRI MAGNETOM Terra using a 28-channel receive, single-channel transmit knee coil., Results: Five cases of four pathologies were selected from 38 patients to depict characteristic imaging features in different benign nerve tumors and lesions using 7T MRI., Conclusion: The primary advantage of 7T over 3T is an increase in signal-to-noise ratio which allows higher in plane resolution so that the smallest neural structures can be seen and characterized. This improvement in MR imaging provides the opportunity for more accurate diagnosis and surgical planning in selected cases. As this technology continues to evolve for clinical purposes, we anticipate increasing applications and improved patient care using 7T MRI for the diagnosis of peripheral nerve masses., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Cardiovascular pathology is the leading cause of death and disability in the Western world, and current diagnostic testing usually evaluates the anatomy of the vessel to determine if the vessel contains blockages and plaques. However, there is a growing school of thought that other measures, such as wall shear stress, provide more useful information for earlier diagnosis and prediction of atherosclerotic related disease compared to pulsed-wave Doppler ultrasound, magnetic resonance angiography, or computed tomography angiography. A novel algorithm for quantifying wall shear stress (WSS) in atherosclerotic plaque using diagnostic ultrasound imaging, called Multifrequency ultrafast Doppler spectral analysis (MFUDSA), is presented. The development of this algorithm is presented, in addition to its optimisation using simulation studies and in-vitro experiments with flow phantoms approximating the early stages of cardiovascular disease. The presented algorithm is compared with commonly used WSS assessment methods, such as standard PW Doppler, Ultrafast Doppler, and Parabolic Doppler, as well as plane-wave Doppler. Compared to an equivalent processing architecture with one-dimensional Fourier analysis, the MFUDSA algorithm provided an increase in signal-to-noise ratio (SNR) by a factor of 4-8 and an increase in velocity resolution by a factor of 1.10-1.35. The results indicated that MFUDSA outperformed the others, with significant differences detected between the typical WSS values of moderate disease progression ( p = 0.003) and severe disease progression ( p = 0.001). The algorithm demonstrated an improved performance for the assessment of WSS and has potential to provide an earlier diagnosis of cardiovascular disease than current techniques allow.

Background: 7T MRI offers significant benefits to spatial and contrast resolution compared to lower field strengths. This superior image quality can help better delineate targets in stereotactic neurosurgical procedures; however, the potential for increased geometric distortions at 7T has impaired its widespread use for these applications. Image geometric distortions can be due to distortions of B 0 arising from tissue magnetic susceptibility effects or inherent field inhomogeneities, and nonlinearity of the magnetic field gradients., Purpose: The purpose of this study was to investigate the use of 7T MRI for neurosurgical frameless stereotactic navigation procedures. Image geometric distortions at the skin surface in 7T images were minimized and compared to results from clinical 3T frameless imaging protocols., Methods: A 3D-printed grid phantom filled with oil was designed to perform a fine calibration of the 7T imaging gradients, and an oil-filled head phantom with internal targets was used to determine ground truth (from computed tomography [CT]) positioning errors. Three volunteers and the head phantom were imaged consecutively at 3T and 7T. Ten skin-adhesive fiducial markers were placed on each subject's exposed skin surface at standard clinical placement locations for frameless procedures. Imaging sequences included MPRAGE (three bandwidths at 7T: 400, 690, and 1020 Hz/pixel, and one at 3T: 400 Hz/pixel), T2 SPACE, and T2 SPACE FLAIR acquisitions. An additional GRE field map was acquired on both scanners using a multi-echo GRE sequence. Custom Matlab code was used to perform additional distortion correction of the images using the unwrapped field maps. Fiducial localization was performed with 3D Slicer, with absolute fiducial positioning errors determined in phantom experiments following rigid registration to the CT images. For human experiments, 3T and 7T images were registered and relative differences in fiducial locations were compared using two-tailed paired t-tests., Results: Phantom measurements at 7T yielded gradient distance scaling errors of 1.1%, 2.2%, and 1.0% along the x-, y-, and z-axes, respectively. These system miscalibrations were traced back to phantom manufacturing deviations in the sphericity of the vendor's gradient calibration phantom. Correction factors along each gradient axis were applied, and afterward, geometric distortions of less than 1 mm were obtained in the 7T MR head phantom images for the 1020 Hz/pixel bandwidth MPRAGE sequence. For the human subjects, four fiducial locations were excluded from the analysis due to patient positioning differences. Differences between 3T and 7T MPRAGE with low/medium/high bandwidth were 2.2 /2.6/2.3 mm, respectively, before the correction, reducing to 1.6/1.3/1.0 mm after the correction (p < 0.001). T2 SPACE and T2 SPACE FLAIR yielded a similar pattern when the correction was applied, decreasing from 2.1 to 0.8 mm, and 2.6 to 1.0 mm, respectively., Conclusions: 7T MRI can be used to perform frameless presurgical planning with skin-adhesive fiducials. Geometric distortions can be reduced to a clinically relevant level (errors < ∼1 mm) with no significant susceptibility-related distortions, by using high receiver bandwidth, ensuring gradients are properly calibrated, and placing skin fiducials in areas where distortions from patient positioning are minimal., (© 2022 American Association of Physicists in Medicine.)

Concentrations and elemental stoichiometry of suspended particulate organic carbon, nitrogen, phosphorus, and oxygen demand for respiration (C:N:P:-O 2 ) play a vital role in characterizing and quantifying marine elemental cycles. Here, we present Version 2 of the Global Ocean Particulate Organic Phosphorus, Carbon, Oxygen for Respiration, and Nitrogen (GO-POPCORN) dataset. Version 1 is a previously published dataset of particulate organic matter from 70 different studies between 1971 and 2010, while Version 2 is comprised of data collected from recent cruises between 2011 and 2020. The combined GO-POPCORN dataset contains 2673 paired surface POC/N/P measurements from 70°S to 73°N across all major ocean basins at high spatial resolution. Version 2 also includes 965 measurements of oxygen demand for organic carbon respiration. This new dataset can help validate and calibrate the next generation of global ocean biogeochemical models with flexible elemental stoichiometry. We expect that incorporating variable C:N:P:-O 2 into models will help improve our estimates of key ocean biogeochemical fluxes such as carbon export, nitrogen fixation, and organic matter remineralization., (© 2022. The Author(s).)

Background: Iron-overload cardiomyopathy initially manifests with diastolic dysfunction and can progress to dilated cardiomyopathy if untreated. Previous studies have shown that patients with primary and secondary hemochromatosis can have subclinical left ventricle dysfunction with abnormalities on strain imaging. This study aimed to evaluate the relationship between cardiac T2* values and myocardial-wall strain in patients with hereditary hemochromatosis (HH) at the time of diagnosis and after a course of venesection treatment., Materials and Methods: Baseline cardiac magnetic resonance (CMR) at 3 T was performed in 19 patients with newly diagnosed HH with elevated serum ferritin levels and repeated after a course of treatment with venesection. Quantitative T2* mapping and strain analysis were performed offline using dedicated relaxometry fitting and feature-tracking software., Results: The majority (84%) of patients had normal baseline myocardial T2* values (mean 19.3 ms, range 8.9 to 31.2 ms), which improved significantly after venesection (mean 24.1 ms, range 11 to 38.1 ms) ( P =0.021). Mean global radial strain significantly improved from 25.0 (range: 15.6 to 32.9) to 28.3 (range: 19.8 to 35.8) ( P =0.001) and mean global circumferential strain improved, decreasing from -15.7 (range: -11.1 to -19.2) to -17.1 (range: -13.0 to -20.1) ( P =0.001)., Conclusion: Patients with HH may have normal T2* values in the presence of subclinical left ventricle dysfunction, which can be detected by abnormal radial and circumferential strain. As strain imaging improves following venesection in HH, it may serve as a useful biomarker to guide treatment., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Magnetic resonance imaging at 7T offers improved image spatial and contrast resolution for visualization of small brain nuclei targeted in neuromodulation. However, greater image geometric distortion and a lack of compatible instrumentation preclude implementation. In this report, the authors detail the development of a stereotactic image localizer and accompanying imaging sequences designed to mitigate geometric distortion, enabling accurate image registration and surgical planning of basal ganglia nuclei., Methods: Magnetization-prepared rapid acquisition with gradient echo (MPRAGE), fast gray matter acquisition T1 inversion recovery (FGATIR), T2-weighted, and T2*-weighted sequences were optimized for 7T in 9 human subjects to visualize basal ganglia nuclei, minimize image distortion, and maximize target contrast-to-noise and signal-to-noise ratios. Extracranial spatial distortions were mapped to develop a skull-contoured image localizer embedded with spherical silicone fiducials for improved MR image registration and target guidance. Surgical plan accuracy testing was initially performed in a custom-developed MRI phantom (n = 5 phantom studies) and finally in a human trial., Results: MPRAGE and T2*-weighted sequences had the best measures among global measures of image quality (3.8/4, p < 0.0001; and 3.7/4, p = 0.0002, respectively). Among basal ganglia nuclei, FGATIR outperformed MPRAGE for globus pallidus externus (GPe) visualization (2.67/4 vs 1.78/4, p = 0.008), and FGATIR, T2-weighted imaging, and T2*-weighted imaging outperformed MPRAGE for substantia nigra visualization (1.44/4 vs 2.56/4, p = 0.04; vs 2.56/4, p = 0.04; vs 2.67/4, p = 0.003). Extracranial distortion was lower in the head's midregion compared with the base and apex ( 1.17-1.33 mm; MPRAGE and FGATIR, p < 0.0001; T2-weighted imaging, p > 0.05; and T2*-weighted imaging, p = 0.013). Fiducial placement on the localizer in low distortion areas improved image registration (fiducial registration error, 0.79-1.19 mm; p < 0.0001) and targeting accuracy (target registration error, 0.60-1.09 mm; p = 0.04). Custom surgical software and the refined image localizer enabled successful surgical planning in a human trial (fiducial registration error = 1.0 mm)., Conclusions: A skull-contoured image localizer that accounts for image distortion is necessary to enable high-accuracy 7T imaging-guided targeting for surgical neuromodulation. These results may enable improved clinical efficacy for the treatment of neurological disease.

Purpose: Contrast-detail (C-D) and anechoic-target (A-T) detectability are measures of an ultrasound scanner's ability to image lesions of varying contrast and size from background tissue and, as such, they are important tools for grading the imaging capabilities of ultrasound scanners. The objective of this study was to develop a range of contrast- and anechoic-detail phantoms with clinically relevant lesions, of various contrast and sizes, for performance testing of breast ultrasound equipment., Methods: Tissue mimicking materials that represent the acoustic properties of breast fibroglandular tissue were produced and moulded to construct a range of C-D and A-T phantoms. Two phantom designs were produced, containing cylindrical and spherical targets. Both phantom types were constructed with contrast targets covering the range anechoic, -1, -2, -3 and -4 dB, with lesion diameters of 1-4 mm, positioned at four clinically relevant depths (10, 25, 40 and 55 mm). An image analysis program was developed to objectively analyse the lesion images and to determine the lesion-signal-noise-ratio (LSNR)., Results: Both phantoms were used to evaluate the performance of a breast ultrasound scanner. The use of cylindrical phantoms led to an artificially higher image quality performance compared with the more clinically relevant spherical lesion phantom, thus indicating the importance of using the appropriate targets in ultrasound phantoms., Conclusion: The spherical lesion phantoms, coupled with the quantitative metric of LSNR, provides a comprehensive approach for performance and quality control testing, as well as the evaluation of advanced ultrasound imaging modes and technologies., (Copyright © 2021 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Oceanic nutrient cycles are coupled, yet carbon-nitrogen-phosphorus (C:N:P) stoichiometry in marine ecosystems is variable through space and time, with no clear consensus on the controls on variability. Here, we analyze hydrographic, plankton genomic diversity, and particulate organic matter data from 1970 stations sampled during a global ocean observation program (Bio-GO-SHIP) to investigate the biogeography of surface ocean particulate organic matter stoichiometry. We find latitudinal variability in C:N:P stoichiometry, with surface temperature and macronutrient availability as strong predictors of stoichiometry at high latitudes. Genomic observations indicated community nutrient stress and suggested that nutrient supply rate and nitrogen-versus-phosphorus stress are predictive of hemispheric and regional variations in stoichiometry. Our data-derived statistical model suggests that C:P and N:P ratios will increase at high latitudes in the future, however, changes at low latitudes are uncertain. Our findings suggest systematic regulation of elemental stoichiometry among ocean ecosystems, but that future changes remain highly uncertain., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2022.)

This study examined the associations of body mass index (BMI), waist-to-hip ratio (WHR), waist circumference (WC), and physical activity (PA) with gray matter cerebral blood flow (CBF GM ) in older adults. Cross-sectional data was used from the Irish Longitudinal Study on Ageing (n = 495, age 69.0 ±7.4 years, 52.1% female). Whole-brain CBF GM was quantified using arterial spin labeling MRI. Results from multivariable regression analysis revealed that an increase in BMI of 0.43 kg/m 2 , WHR of 0.01, or WC of 1.3 cm were associated with the same reduction in CBF GM as 1 year of advancing age. Participants overweight by BMI or with high WHR/WC reporting low/moderate PA had up to 3 ml/100g/min lower CBF GM (p ≤ .011); there was no significant reduction for those reporting high PA. Since PA could potentially moderate obesity/CBF associations, this may be a cost-effective and relatively easy way to help mitigate the negative impact of obesity in an older population, such as cerebral hypoperfusion, which is an early mechanism in vascular dementia and Alzheimer's disease., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Multisensory perception might provide an important marker of brain function in aging. However, the cortical structures supporting multisensory perception in aging are poorly understood. In this study, we compared regional gray matter volume in a group of middle-aged (n = 101; 49-64 years) and older (n = 116; 71-87 years) adults from The Irish Longitudinal Study on Aging using voxel-based morphometry. Participants completed a measure of multisensory integration, the sound-induced flash illusion, and were grouped as per their illusion susceptibility. A significant interaction was observed in the right angular gyrus; in the middle-aged group, larger gray matter volume corresponded to stronger illusion perception while in older adults larger gray matter corresponded to less illusion susceptibility. This interaction remained significant even when controlling for a range of demographic, sensory, cognitive, and health variables. These findings show that multisensory integration is associated with specific structural differences in the aging brain and highlight the angular gyrus as a possible "cross-modal hub" associated with age-related change in multisensory perception., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To establish normative reference values for total grey matter cerebral blood flow (CBF GM ) measured using pseudo-continuous arterial spin labelling (pCASL) MRI in a large cohort of community-dwelling adults aged 54 years and older., Background: Quantitative assessment of CBF GM may provide an imaging biomarker for the early detection of those at risk of neurodegenerative diseases, such as Alzheimer's and dementia. However, the use of this method to differentiate normal age-related decline in CBF GM from pathological reduction has been hampered by the lack of reference values for cerebral perfusion., Methods: The study cohort comprised a subset of wave 3 (2014-2015) participants from The Irish Longitudinal Study on Ageing (TILDA), a large-scale prospective cohort study of individuals aged 50 and over. Of 4309 participants attending for health centre assessment, 578 individuals returned for 3T multi-parametric MRI brain examinations. In total, CBF GM data acquired from 468 subjects using pCASL-MRI were included in this analysis. Normative values were estimated using Generalised Additive Models for Location Shape and Scale (GAMLSS) and are presented as percentiles, means and standard deviations., Results: The mean age of the cohort was 68.2 ± 6.9 years and 51.7% were female. Mean CBF GM for the cohort was 36.5 ± 8.2 ml/100 g/min. CBF GM decreased by 0.2 ml/100 g/min for each year increase in age (95% CI = -0.3, -0.1; p ≤ 0.001) and was 3.1 ml/100 g/min higher in females (95% CI = 1.6, 4.5; p ≤ 0.001)., Conclusions: This study is by far the largest single-site study focused on an elderly community-dwelling cohort to present normative reference values for CBF GM measured at 3T using pCASL-MRI. Significant age- and sex-related differences exist in CBF GM ., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: We investigated the hypothesis that increasing fMRI temporal resolution using a multiband (MB) gradient echo-echo planar imaging (GRE-EPI) pulse sequence provides fMRI language maps of higher statistical quality than those acquired with a traditional GRE-EPI sequence., Methods: This prospective study enrolled 29 consecutive patients receiving language fMRI prior to a potential brain resection for tumor, AVM, or epilepsy. A 4-min rhyming task was performed at 3.0 Tesla with a traditional GRE-EPI pulse sequence (TR = 2000, TE = 30, matrix = 64/100%, slice = 4/0, FOV = 24, slices = 30, time points = 120) and an additional MB GRE-EPI pulse sequence with an acceleration factor of 6 (TR = 333, TE = 30, matrix 64/100%, slice = 4/0, FOV = 24, time points = 720). Spatially filtered t statistical maps were generated. Volumes of interest (VOIs) were drawn around activations at Broca's, dorsolateral prefrontal cortex, Wernicke's, and the visual word form areas. The t value maxima were measured for the overall brain and each of the VOIs. A paired t test was performed for the corresponding traditional and MB GRE-EPI measurements., Results: The mean age of subjects was 42.6 years old (18-75). Sixty-two percent were male. The average overall brain t statistic maxima for the MB pulse sequence (t = 15.4) was higher than for the traditional pulse sequence (t = 9.3, p = < .0001). This also held true for Broca's area (p < 0.0001), Wernicke's area (p < .0001), dorsolateral prefrontal cortex (p < .0001), and the visual word form area (p < .0001)., Conclusion: A MB GRE-EPI fMRI pulse sequence employing high temporal resolution provides clinical fMRI language maps of greater statistical significance than those obtained with a traditional GRE-EPI sequence.

Magnetic resonance imaging and spectroscopy (MRI/MRS) at 7T represents an exciting advance in MR technology, with intriguing possibilities to enhance image spatial, spectral, and contrast resolution. To ensure the safe use of this technology while still harnessing its potential, clinical staff and researchers need to be cognizant of some safety concerns arising from the increased magnetic field strength and higher Larmor frequency. The higher static magnetic fields give rise to enhanced transient bioeffects and an increased risk of adverse incidents related to electrically conductive implants. Many technical challenges remain and the continuing rapid pace of development of 7T MRI/MRS is likely to present further challenges to ensuring safety of this technology in the years ahead. The recent regulatory clearance for clinical diagnostic imaging at 7T will likely increase the installed base of 7T systems, particularly in hospital environments with little prior ultrahigh-field MR experience. Informed risk/benefit analyses will be required, particularly where implant manufacturer-published 7T safety guidelines for implants are unavailable. On behalf of the International Society for Magnetic Resonance in Medicine, the aim of this article is to provide a reference document to assist institutions developing local institutional policies and procedures that are specific to the safe operation of 7T MRI/MRS. Details of current 7T technology and the physics underpinning its functionality are reviewed, with the aim of supporting efforts to expand the use of 7T MRI/MRS in both research and clinical environments. Current gaps in knowledge are also identified, where additional research and development are required. Level of Evidence 5 Technical Efficacy 2 J. MAGN. RESON. IMAGING 2021;53:333-346., (© 2020 International Society for Magnetic Resonance in Medicine.)

Since the relatively recent regulatory approval for clinical use in both Europe and North America, 7-Tesla (T) MRI has been adopted for clinical practice at our institution. Based on this experience, this article reviews the unique features of 7-T MRI neuroimaging and addresses the challenges of establishing a 7-T MRI clinical practice. The underlying fundamental physics principals of high-field strength MRI are briefly reviewed. Scanner installation, safety considerations, and artifact mitigation techniques are discussed. Seven-tesla MRI case examples of neurologic diseases including epilepsy, vascular abnormalities, and tumor imaging are presented to illustrate specific applications of 7-T MRI. The advantages of 7-T MRI in conjunction with advanced neuroimaging techniques such as functional MRI are presented. Seven-tesla MRI produces more detailed information and, in some cases, results in specific diagnoses where previous 3-T studies were insufficient. Still, persistent technical issues for 7-T scanning present ongoing challenges for radiologists.

Purpose: A 7T magnetic resonance thermometry (MRT) technique was developed to validate the conversion factor between the system-measured transmitted radiofrequency (RF) power into a home-built RF wrist coil with the system-predicted SAR value. The conversion factor for a new RF coil developed for ultra high magnetic field MRI systems is used to ensure that regulatory limits on RF energy deposition in tissue, specifically the local 10g-averaged specific absorption rate (SAR 10g ), are not exceeded. MRT can be used to validate this factor by ensuring that MRT-measured SAR values do not exceed those predicted by the system., Methods: A 14-cm diameter high-pass birdcage RF coil was built to image the wrist at 7T. A high spatial and temporal resolution dual-echo gradient echo MRT technique, incorporating quasi-simultaneous RF-induced heating and temperature change measurements using the proton resonance frequency method, was developed. The technique allowed for high-temperature resolution measurements (~±0.1°C) to be performed every 20 s over a 4-min heating period, with high spatial resolution (2.56 mm 3 voxel size) and avoiding phase discontinuities arising from severe magnetic susceptibility-induced B 0 inhomogeneities. Magnetic resonance thermometry was performed on a phantom made from polyvinylpyrrolidone to mimic the dielectric properties of muscle tissue at 297.2 MHz. Temperature changes measured with MRT and four fiber optic temperature sensors embedded in the phantom were compared. Electromagnetic simulations of the coil and phantom were developed and validated via comparison of simulated and measured B 1 + maps in the phantom. The position of maximum SAR within the coil was determined from simulations, and MRT was performed within a wrist-sized piece of meat positioned at that SAR hotspot location. MRT-measured and system-predicted SAR values for the phantom and meat were compared., Results: Temperature change measurements from MRT matched closely to those from the fiber optic temperature sensors. The simulations were validated via close correlation between the simulated and MRT-measured B 1 + and SAR maps. Using a coil conversion factor of 2 kg -1 , MRT-measured point-SAR values did not exceed the system-predicted SAR 10g in either the uniform phantom or in the piece of meat mimicking the wrist located at the SAR hotspot location., Conclusions: A highly accurate MRT technique with high spatial and temporal resolution was developed. This technique can be used to ensure that system-predicted SAR values are not exceeded in practice, thereby providing independent validation of SAR levels delivered by a newly built RF wrist coil. The MRT technique is readily generalizable to perform safety evaluations for other RF coils at 7T., (© 2020 American Association of Physicists in Medicine.)

The arrival of 7T MR imaging into the clinic represents a significant step-change in MR technology. This article describes safety concerns associated with imaging at 7T, including the increased magnetic forces on magnetic objects at 7T and the interaction of the 300 MHz (Larmor) radiofrequency energy with tissue in the body. A dedicated multidisciplinary 7T Safety team should develop safety policies and procedures to address these safety challenges and keep abreast of best practice in the field. The off-label imaging of implanted devices is discussed, and also the need for staff training to deal with complexities of patient handling and image interpretation., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In the California Current Ecosystem, El Niño acts as a natural phenomenon that is partially representative of climate change impacts on marine bacteria at timescales relevant to microbial communities. Between 2014-2016, the North Pacific warm anomaly (a.k.a., the "blob") and an El Niño event resulted in prolonged ocean warming in the Southern California Bight (SCB). To determine whether this "marine heatwave" resulted in shifts in microbial populations, we sequenced the rpoC1 gene from the biogeochemically important picocyanobacteria Prochlorococcus and Synechococcus at 434 time points from 2009-2018 in the MICRO time series at Newport Beach, CA. Across the time series, we observed an increase in the abundance of Prochlorococcus relative to Synechococcus as well as elevated frequencies of ecotypes commonly associated with low-nutrient and high-temperature conditions. The relationships between environmental and ecotype trends appeared to operate on differing temporal scales. In contrast to ecotype trends, most microdiverse populations were static and possibly reflect local habitat conditions. The only exceptions were microdiversity from Prochlorococcous HLI and Synechococcus Clade II that shifted in response to the 2015 El Niño event. Overall, Prochlorococcus and Synechococcus populations did not return to their pre-heatwave composition by the end of this study. This research demonstrates that extended warming in the SCB can result in persistent changes in key microbial populations., Competing Interests: The authors have declared that no competing interests exist.

The aim of this work was to develop multimodal anthropomorphic breast phantoms suitable for evaluating the imaging performance of a recently-introduced Microwave Imaging (MWI) technique in comparison to the established diagnostic imaging modalities of Magnetic Resonance Imaging (MRI), Ultrasound (US), mammography and Computed Tomography (CT). MWI is an emerging technique with significant potential to supplement established imaging techniques to improve diagnostic confidence for breast cancer detection. To date, numerical simulations have been used to assess the different MWI scanning and image reconstruction algorithms in current use, while only a few clinical trials have been conducted. To bridge the gap between the numerical simulation environment and a more realistic diagnostic scenario, anthropomorphic phantoms which mimic breast tissues in terms of their heterogeneity, anatomy, morphology, and mechanical and dielectric characteristics, may be used. Key in this regard is achieving realism in the imaging appearance of the different healthy and pathologic tissue types for each of the modalities, taking into consideration the differing imaging and contrast mechanisms for each modality. Suitable phantoms can thus be used by radiologists to correlate image findings between the emerging MWI technique and the more familiar images generated by the conventional modalities. Two phantoms were developed in this study, representing difficult-to-image and easy-to-image patients: the former contained a complex boundary between the mammary fat and fibroglandular tissues, extracted from real patient MRI datasets, while the latter contained a simpler and less morphologically accurate interface. Both phantoms were otherwise identical, with tissue-mimicking materials (TMMs) developed to mimic skin, subcutaneous fat, fibroglandular tissue, tumor and pectoral muscle. The phantoms' construction used non-toxic materials, and they were inexpensive and relatively easy to manufacture. Both phantoms were scanned using conventional modalities (MRI, US, mammography and CT) and a recently introduced MWI radar detection procedure called in-coherent Multiple Signal Classification (I-MUSIC). Clinically realistic artifact-free images of the anthropomorphic breast phantoms were obtained using the conventional imaging techniques as well as the emerging technique of MWI.

The aim of this work was to establish the optimum acoustic characterisation approach and insonation transmit beam parameters for subharmonic signal generation with 'native' and 'altered' populations of a commonly-used microbubble contrast agent. Dynamic contrast-enhanced (DCE) ultrasound is a non-invasive method of imaging the microvasculature, typically implemented using harmonic imaging. Subharmonic imaging, in which echoes at half the fundamental frequency are detected, detects signals which are generated by the ultrasound contrast agents (UCAs) but not by tissue. However, optimal transmission parameters and furthermore, the optimum acoustic characterisation method have not been established. The subharmonic response of 'native' and 'altered' UCA, altered through decantation, was investigated at transmit centre frequencies 1.8-5 MHz and pulse lengths 1-8 cycles. The 'altered' UCA had reduced polydispersity (1-4 µm: 82% bubble volume), compared to 'native' (4-10 µm: 57% bubble volume). A custom-built narrow-band acoustic characterisation system was found to be more appropriate for acoustic characterisation compared to the commonly used broadband pulse-echo approach. Both UCA generated the highest subharmonic signal at pulse length of 3-cycles. The maximum 'native' subharmonic signal was generated at a transmit centre frequency of 1.9 MHz, corresponding to a subharmonic at 0.95 MHz. This optimal frequency increased in the 'altered' population to 2.3-2.5 MHz, bringing the subharmonic above 1 MHz and hence into a range amenable to clinical abdominal imaging transducers. The use of subharmonic signal detection coupled with a modified UCA size distribution has potential to significantly improve the quantification sensitivity and accuracy of DCE ultrasound imaging., (Copyright © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Purpose: The stiffness of Polyvinyl-alcohol cryogel can be adjusted through application of consecutive freeze-thaw cycles. This material has potential applications in the production of tissue mimicking phantoms in diagnostic ultrasound. The aim of this study was to use PVA-c to produce a range of geometrically and acoustically identical vessel phantoms modelling stages of atherosclerosis which could be verified through mechanical testing, thus allowing for more precision in quantitative in-vitro flow analysis of atherosclerosis., Methods: A series of anatomically realistic walled renal artery flow phantoms were constructed using PVA-c. In order to ensure precise modelling of atherosclerosis, a modified procedure of ISO27:2017 was used to compare the mechanical properties of PVA-c. Results were compared for the standard "dumbbell" test object and a modified vessel test object. The geometric accuracy and reproducibility of the vessel models were tested before and after implantation in flow phantoms., Results: No significant difference was found between the mechanical properties of the dumbbell test samples and the vessels for any number of freeze thaw cycles, with a correlation coefficient of R 2  = 0.9767 across the dataset, indicating that a direct comparison between the mechanical properties of the dumbbell test samples and the phantom vessels was established. The geometric reproducibility showed that before and after implantation there was no significant difference between individual vessel geometries (p = 0.337 & p = 0.176 respectively)., Conclusions: Polyvinyl-alcohol cryogel is a useful material for the production of arterial flow phantoms. Care should be taken when using this material to ensure its mechanical properties have been correctly characterised. The guidelines of ISO37:2017 potentially provide the best procedure to ensure this., (Copyright © 2019 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Objectives: The aim of this work was to devise mitigation strategies for addressing a range of image artifacts on a clinical 7 T magnetic resonance imaging scanner using the regulatory-approved single-channel radiofrequency transmit mode and vendor-supplied radiofrequency coils to facilitate clinical scanning within reasonable scan times., Materials and Methods: Optimized imaging sequence protocols were developed for routine musculoskeletal knee and neurological imaging. Sources of severe image nonuniformities were identified, and mitigation strategies were devised. A range of custom-made high permittivity dielectric pads were used to compensate for B1 and B1 inhomogeneities, and also for magnetic susceptibility-induced signal dropouts particularly in the basal regions of the temporal lobes and in the cerebellum., Results: Significant improvements in image uniformity were obtained using dielectric pads in the knee and brain. A combination of small voxels, reduced field of view B0 shimming, and high in-plane parallel imaging factors helped to minimize signal loss in areas of high susceptibility-induced field distortions. The high inherent signal-to-noise ratio at 7 T allowed for high receiver bandwidths and thin slices to minimize chemical shift artifacts. Intermittent artifacts due to radiofrequency inversion pulse limitations (power, bandwidth) were minimized with dielectric pads. A patient with 2 implanted metallic cranial fixation devices located within the radiofrequency transmit field was successfully imaged, with minimal image geometric distortions., Conclusions: Challenges relating to severe image artifacts at 7 T using single-channel radiofrequency transmit functionality in the knee and brain were overcome using the approaches described in this article. The resultant high diagnostic image quality paves the way for incorporation of this technology into the routine clinical workflow. Further developmental efforts are required to expand the range of applications to other anatomical areas, and to expand the evidence- and knowledge-base relating to the safety of scanning patients with implanted metallic devices.

Background: MR image intensity nonuniformity is often observed at 7T. Reference scans from the body coil used for uniformity correction at lower field strengths are typically not available at 7T., Purpose: To evaluate the efficacy of a novel algorithm, Uniform Combined Reconstruction (UNICORN), to correct receive coil-induced nonuniformity in musculoskeletal 7T MRI without the use of a reference scan., Study Type: Retrospective image analysis study., Subjects: MRI data of 20 subjects was retrospectively processed offline. Field Strength/Sequence: Knees of 20 subjects were imaged at 7T with a single-channel transmit, 28-channel phased-array receive knee coil. A turbo-spin-echo sequence was used to acquire 33 series of images., Assessment: Three fellowship-trained musculoskeletal radiologists with cumulative experience of 42 years reviewed the images. The uniformity, contrast, signal-to-noise ratio (SNR), and overall image quality were evaluated for images with no postprocessing, images processed with N4 bias field correction algorithm, and the UNICORN algorithm., Statistical Tests: Intraclass correlation coefficient (ICC) was used for measuring the interrater reliability. ICC and 95% confidence intervals (CIs) were calculated using the R statistical package employing a two-way mixed-effects model based on a mean rating (k = 3) for absolute agreement. The Wilcoxon signed-rank test with continuity correction was used for analyzing the overall image quality scores., Results: UNICORN was preferred among the three methods evaluated for uniformity in 97.9% of the pooled ratings, with excellent interrater agreement (ICC of 0.98, CI 0.97-0.99). UNICORN was also rated better than N4 for contrast and equivalent to N4 in SNR with ICCs of 0.80 (CI 0.72-0.86) and 0.67 (CI 0.54-0.77), respectively. The overall image quality scores for UNICORN were significantly higher than N4 (P < 6 × 10 -13 ), with good to excellent interrater agreement (ICC 0.90, CI 0.86-0.93)., Data Conclusion: Without the use of a reference scan, UNICORN provides better image uniformity, contrast, and overall image quality at 7T compared with the N4 bias field-correction algorithm., Level of Evidence: 4 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1534-1544., (© 2019 International Society for Magnetic Resonance in Medicine.)

Purpose: To quantify the effects of DCE acquisition and pharmacokinetic modeling processing methodologies on the absolute accuracy and precision of derived pharmacokinetic (PK) parameter values using a novel anthropomorphic phantom test device in which "ground truth" values were known a priori., Methods: Ground truth arterial input function (AIF), tumor, and healthy tissue contrast agent concentration-time curves (CTCs) were established within the phantom and repeatedly measured on a 3T MRI scanner with varying temporal resolution (T res  = 1.22-30.6 s). Ground truth CTCs, K trans , v e , and k ep values were directly compared to measured values as a function of T res , with and without the application of voxel-wise flip-angle corrections applied to the data and PK modeling performed using linear and nonlinear forms of the standard Tofts model., Results: Measurement of the AIF was strongly affected by the T res used (AIF curve-shape feature errors: 3%-222% for T res : 1.22-30.6 s), which directly translated to errors in the derived K trans , v e , and k ep values of 1%-24%, 2%-5%, and 1%-26% respectively across this T res range (flip-angle correction applied). Further appreciable improvements in accuracy and precision arising from the use of flip angle corrections and nonlinear least squares fitting were quantified and used to identify optimal acquisition and analysis methodologies for which measurement errors could be constrained below threshold levels., Conclusion: This quantitative study provides insight into how errors in AIF measurement propagate to errors in PK parameter outputs. Absolute quantification of the accuracy and precision of MR-measured CTCs, and resultant PK parameter values, allowed for an optimal temporal resolution to be defined commensurate with maintaining K trans , v e , and k ep measurement errors below 5% and 10% levels. An appreciable gain in PK parameter estimation accuracy at the analysis stage was also demonstrated using flip-angle corrections and a linear approach to PK model fitting., (© 2019 American Association of Physicists in Medicine.)

Objective: The objective of the study was to investigate whether clinically used ultrasonic contrast agents improved the accuracy of spectral Doppler ultrasound in the detection of low grade (<50%) renal artery stenosis. Low grade stenoses in the renal artery are notoriously difficult to reliably detect using Doppler ultrasound due to difficulties such as overlying fat and bowel gas., Methods: A range of anatomically-realistic renal artery phantoms with varying low degrees of stenosis (0, 30 and 50%) were constructed and peak velocity data was measured from within the pre-stenotic and mid-stenotic regions in each phantom, for both unenhanced and contrast-enhanced spectral Doppler data acquisitions. The effect of a 20 mm overlying fat layer on the ultrasound beam distortion and phase aberration, and hence on the measured peak velocity data, was also investigated., Results: The overlying fat layer produced a statistically significant underestimation (p < 0.01) in both the peak velocity and peak velocity ratio [Stenotic Region(Vmax)/Pre-stenotic Region(Vmax)] for the 0% and 30% stenosis models, but not the 50% model. A statistically significant increase (p < 0.01) in the peak velocity was found in the contrast-enhanced Doppler spectra; however, no significant difference was found between the unenhanced and contrast enhanced peak velocity ratio data, which suggests that the ratio metric has better diagnostic accuracy. The peak velocity ratios determined for each of the contrast-enhanced phantoms correctly predicted if the phantom had a stenosis and furthermore correctly classified the degree of stenosis., Conclusion: Contrast-enhanced Doppler ultrasound could significantly assist in the early detection of renal artery disease., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: This study evaluated the training and assessment role of anthropomorphic breast ultrasound phantoms that simulated both the morphological and sonographic characteristics of breast tissue, including lesions, in a group of radiology residents at a large academic medical center., Methods: This was a prospective study involving nine residents across second to fourth years of a radiology residency program. Two devices (phantom 1 and phantom 2) were designed and constructed to produce similar realistic sonographic images of breast morphology with a range of embedded pathologies to provide a realistic training experience. Baseline assessments of all residents' ability to detect and characterize lesions in phantom 1 were carried out, followed by a 2-hour teaching session on the same phantom. All residents underwent a posttraining, final assessment on phantom 2 to evaluate changes in their lesion detection rate and ability to correctly characterize the lesions., Results: The results demonstrated there was a significant increase in both the pooled detection and correct characterization score for all residents pre- and posttraining of 26% ± 14% and 17% ± 8%, P < .0003, respectively. Posttraining assessment surveys revealed that residents rated the training experience highly., Conclusions: This study suggests that there is a benefit in including a simulation training workshop with a novel anthropomorphic breast ultrasound training device to a radiology resident education program. Finally, the phantoms used in this study are useful for training and assessment purposes because they provide a lifelike simulation of breast tissue to practice ultrasound imaging without direct exposure to patients, in an environment with no pressure., (Copyright © 2018 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Embolus Analogues (EAs) can provide understanding of the mechanical characteristics of blood clots of cardiac origin. Bovine EAs (n = 29) were fabricated with varying concentrations of thrombin (0-20 NIHU/ml blood). Histological staining confirmed that EA composition compared sufficiently with human samples reported in literature. EAs were mechanically described under seven testing conditions: tensile, compression, shear wave ultrasound elastography (SWE), parallel plate rheometry, indentation, creep and relaxation. The Young modulus of bovine EAs in tension varied from 7 kPa (5% strain) to 84 kPa (50% strain). The compressive Young modulus increased with increasing thrombin concentration, which was in agreement with the SWE results. There was no significant difference in Young modulus throughout the clot (p < 0.05). The EAs displayed a non-linear response under parallel plate rheometry, creep and stress relaxation. The 3rd order Mooney-Rivlin constitutive equation and Standard Linear Solid model were used to fit the non-linear stress-strain response and time-dependent properties, respectively. This is the first study in which bovine EAs, with and without addition of thrombin, are histologically and mechanically described with corresponding proposed constitutive equations. The equations and experimental data determined can be applied for future numerical and experimental testing of mammalian EAs and cardiac source clots.

Working memory-based cognitive remediation therapy (CT) for psychosis has recently been associated with broad improvements in performance on untrained tasks measuring working memory, episodic memory and IQ, and changes in associated brain regions. However, it is unclear whether these improvements transfer to the domain of social cognition and neural activity related to performance on social cognitive tasks. We examined performance on the Reading the Mind in the Eyes test (Eyes test) in a large sample of participants with psychosis who underwent working memory-based CT (N = 43) compared to a control group of participants with psychosis (N = 35). In a subset of this sample, we used functional magnetic resonance imaging (fMRI) to examine changes in neural activity during a facial emotion recognition task in participants who underwent CT (N = 15) compared to a control group (N = 15). No significant effects of CT were observed on Eyes test performance or on neural activity during facial emotion recognition, either at p < 0.05 family-wise error or at a p < 0.001 uncorrected threshold, within a priori social cognitive regions of interest. This study suggests that working memory-based CT does not significantly impact an aspect of social cognition which was measured behaviourally and neurally. It provides further evidence that deficits in the ability to decode mental state from facial expressions are dissociable from working memory deficits, and suggests that future CT programmes should target social cognition in addition to working memory for the purposes of further enhancing social function., (© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: Cognitive remediation (CR) training has emerged as a promising approach to improving cognitive deficits in schizophrenia and related psychosis. The limited availability of psychological services for psychosis is a major barrier to accessing this intervention however. This study investigated the effectiveness of a low support, remotely accessible, computerised working memory (WM) training programme in patients with psychosis., Methods: Ninety patients were enrolled into a single blind randomised controlled trial of CR. Effectiveness of the intervention was assessed in terms of neuropsychological performance, social and occupational function, and functional MRI 2 weeks post-intervention, with neuropsychological and social function again assessed 3-6 months post-treatment., Results: Patients who completed the intervention showed significant gains in both neuropsychological function (measured using both untrained WM and episodic task performance, and a measure of performance IQ), and social function at both 2-week follow-up and 3-6-month follow-up timepoints. Furthermore, patients who completed MRI scanning showed improved resting state functional connectivity relative to patients in the placebo condition., Conclusions: CR training has already been shown to improve cognitive and social function in patient with psychosis. This study demonstrates that, at least for some chronic but stable outpatients, a low support treatment was associated with gains that were comparable with those reported for CR delivered entirely on a 1:1 basis. We conclude that CR has potential to be delivered even in services in which psychological supports for patients with psychosis are limited.

A device for the training and quantitative assessment of the competency of trainee radiologists in the technically challenging area of breast sonography was developed and evaluated. Currently, suitable commercially available devices are lacking, and there is a growing realization that the reliance on direct exposure to patients for learning may not represent best practice from either the trainees' or patients' perspective. Three devices (PI, PII and PIII) were designed to produce very realistic sonographic images of breast morphology with a range of embedded pathologies. The pilot evaluation used a case study research design to evaluate the role of the anthropomorphic breast sonography training device in training and assessment in a clinical environment. Through the case study, it was possible to evaluate the process and relationships when using this type of training intervention for a small group of radiology resident trainees. The investigation involved a baseline assessment of trainees' (n = 4) ability to detect and characterize all lesions in PI, followed by a 4-wk training period on PII and a post-training assessment using PIII. The evaluation revealed an improvement of 30% ± 8% in the trainee's performance from pre- to post-training. It was expected that the performance of the trainees would improve as the training phantom described in this study aligns with the learning theory of constructivism and fits the ideal specifications of a medical training device in terms of its realism and facilitation of self-directed learning and deliberate practice of the trainees. The device provides a useful platform upon which training and assessment can be facilitated., (Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to investigate the effect of the temporal resolution (T res ) and acquisition duration (AD) on the measurement accuracy of contrast concentration-time curves (CTCs), and derived phenomenological and pharmacokinetic parameter values, in a dynamic contrast-enhanced MRI experiment using a novel phantom test device., Materials and Methods: 'Ground truth' CTCs were established using a highly precise optical imaging system. These precisely known CTCs were produced in an anthropomorphic environment, which mimicked the male pelvic region, and presented to the MRI scanner for measurement. The T res was varied in the range [2-24.4 s] and the AD in the range [30-600 s], and the effects on the measurement accuracy were quantified., Results: For wash-in parameter measurements, large underestimation errors (up to 40%) were found using T res values ≥16.3 s; however, the measured wash-out rate did not vary greatly across all T res values tested. Errors in derived K trans and v e values were below 14 and 12% for acquisitions with {T res  ≤ 8.1 s, AD ≥ 360 s} and {T res  ≤ 16.3 s, AD ≥ 360 s}, respectively, but increased dramatically outside these ranges., Conclusions: Errors in measured wash-in, wash-out, K trans , and v e parameters were minimised using T res  ≤ 8.1 s and AD ≥ 360 s, with large errors recorded outside of this range.

Background: Nystagmus in patients with multiple sclerosis (MS) is generally attributed to brainstem disease. Lesions in other regions may result in nystagmus. The identification of these other sites is enhanced by using 3-Tesla magnetic resonance imaging (3TMRI) due to increased signal-to-noise ratio., Objective: We sought to evaluate the distribution of structural lesions and disruption of tracts in patients with horizontal nystagmus secondary to MS using 3TMRI., Methods: Twenty-four patients (20 women, 4 men; age range 26-55 years) with horizontal nystagmus secondary to MS underwent 3TMRI brain scans; and 18 patients had diffusion tensor imaging (DTI) for tractography., Results: Nystagmus was bidirectional in 11, right-sided in 6 and left-sided in 7. We identified 194 lesions in 20 regions within the neural integrator circuit in 24 patients; 140 were within the cortex and 54 were within the brainstem. Only two patients had no lesions in the cortex, and 9 had no lesions in the brainstem. There was no relationship between side of lesion and direction of nystagmus. Thirteen of 18 (72 %) had tract disruption with fractional anisotropy (FA) values below 0.2. FA was significantly lower in bidirectional compared to unidirectional nystagmus (p = 0.006)., Conclusion: In MS patients with horizontal nystagmus, lesions in all cortical eye fields and their descending connections were evident. Technical improvements in tractography may help identify the specific site(s) resulting in nystagmus in MS.

A novel anthropomorphic flow phantom device has been developed, which can be used for quantitatively assessing the ability of magnetic resonance imaging (MRI) scanners to accurately measure signal/concentration time-intensity curves (CTCs) associated with dynamic contrast-enhanced (DCE) MRI. Modelling of the complex pharmacokinetics of contrast agents as they perfuse through the tumour capillary network has shown great promise for cancer diagnosis and therapy monitoring. However, clinical adoption has been hindered by methodological problems, resulting in a lack of consensus regarding the most appropriate acquisition and modelling methodology to use and a consequent wide discrepancy in published data. A heretofore overlooked source of such discrepancy may arise from measurement errors of tumour CTCs deriving from the imaging pulse sequence itself, while the effects on the fidelity of CTC measurement of using rapidly-accelerated sequences such as parallel imaging and compressed sensing remain unknown. The present work aimed to investigate these features by developing a test device in which 'ground truth' CTCs were generated and presented to the MRI scanner for measurement, thereby allowing for an assessment of the DCE-MRI protocol to accurately measure this curve shape. The device comprised a four-pump flow system wherein CTCs derived from prior patient prostate data were produced in measurement chambers placed within the imaged volume. The ground truth was determined as the mean of repeat measurements using an MRI-independent, custom-built optical imaging system. In DCE-MRI experiments, significant discrepancies between the ground truth and measured CTCs were found for both tumorous and healthy tissue-mimicking curve shapes. Pharmacokinetic modelling revealed errors in measured K trans , v e and k ep values of up to 42%, 31%, and 50% respectively, following a simple variation of the parallel imaging factor and number of signal averages in the acquisition protocol. The device allows for the quantitative assessment and standardisation of DCE-MRI protocols (both existing and emerging).

Symptoms of attention deficit hyperactivity disorder (ADHD) in children often persist into adulthood and can lead to severe antisocial behavior. However, to-date it remains unclear whether neuro-functional abnormalities cause ADHD, which in turn can then provide a marker of persistent ADHD. Using event-related functional magnetic resonance imaging (fMRI), we measured blood oxygenation level dependent (BOLD) signal changes in subjects during a reversal learning task in which choice of the correct stimulus led to a probabilistically determined 'monetary' reward or punishment. Participants were diagnosed with ADHD during their childhood (N=32) and were paired with age, gender, and education matched healthy controls (N=32). Reassessment of the ADHD group as adults resulted in a split between either persistent (persisters, N=17) or remitted ADHDs (remitters, N=15). All three groups showed significantly decreased activation in the medial prefrontal cortex (PFC) and the left striatum during punished correct responses, however only remitters and controls presented significant psycho-physiological interaction between these fronto-striatal reward and outcome valence networks. Comparing persisters to remitters and controls showed significantly inverted responses to punishment (P<0.05, family-wise error corrected) in left PFC region. Interestingly, the decreased activation shown after punishment was located in different areas of the PFC for remitters compared with controls, suggesting that remitters might have learned compensation strategies to overcome their ADHD symptoms. Thus, fMRI helps understanding the neuro-functional basis of ADHD related behavior differences and differentiates between persistent and remittent ADHD., (© 2015 Wiley Periodicals, Inc.)

Objective: The identification of "endophenotypes"-measurable variations along the pathways between genes and distal disease state-may help deconstruct focal epilepsies into more sensitive phenomena and improve future efforts to map the genetic underpinnings of the disorder. In this study, we set out to determine if diffusion tensor imaging (DTI)-inferred white matter (WM) alterations represent a suitable structural endophenotype for focal epilepsy., Methods: We recruited 25 patients with sporadic mesial temporal lobe epilepsy (MTLE) with normal magnetic resonance imaging (MRI) findings, 25 of their gender-matched, asymptomatic siblings, and 60 control subjects. Whole-brain, voxelwise statistics were conducted to identify regions of microstructural degeneration in patients with MTLE and/or their asymptomatic siblings. WM tracts exhibiting evidence of microstructural disruption were then reconstructed using deterministic tractography. Diffusion metrics including fractional anisotropy (FA) and mean diffusivity (MD) were compared across groups using a series of one-way multivariate analyses of covariance (MANCOVAs)., Results: Voxelwise statistics revealed significant FA reductions in the corpus callosum (CC), bilateral superior longitudinal fasciculi (SLF), bilateral inferior longitudinal fasciculi (ILF), and left corticospinal tract (CST) in MTLE patients only. MD increases were observed in MTLE patients and their asymptomatic siblings in the left SLF and left CST. Deterministic tractography supported the voxelwise results, revealing significant FA alterations in the left SLF and CST in patients only and significant MD alterations in MTLE patients and their unaffected siblings. The diffusion scalars of MTLE patients and their asymptomatic siblings were highly correlated in the SLF and CST ipsilateral to patients' sides of seizure onset., Significance: These findings confirm the presence of microstructural WM alterations in patients with MRI-negative MTLE and provide preliminary support for a diffusion-based endophenotype in the disorder. Further studies of narrow-sense heritability in larger cohorts of first-degree relatives of MTLE patients are required to confirm these results., (Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.)

Although the visual system has been extensively investigated, an integrated account of the spatiotemporal dynamics of long-range signal propagation along the human visual pathways is not completely known or validated. In this work, we used dynamic causal modeling approach to provide insights into the underlying neural circuit dynamics of pattern reversal visual-evoked potentials extracted from concurrent EEG-fMRI data. A recurrent forward-backward connectivity model, consisting of multiple interacting brain regions identified by EEG source localization aided by fMRI spatial priors, best accounted for the data dynamics. Sources were first identified in the thalamic area, primary visual cortex, as well as higher cortical areas along the ventral and dorsal visual processing streams. Consistent with hierarchical early visual processing, the model disclosed and quantified the neural temporal dynamics across the identified activity sources. This signal propagation is dominated by a feedforward process, but we also found weaker effective feedback connectivity. Using effective connectivity analysis, the optimal dynamic causal modeling revealed enhanced connectivity along the dorsal pathway but slightly suppressed connectivity along the ventral pathway. A bias was also found in favor of the right hemisphere consistent with functional attentional asymmetry. This study validates, for the first time, the long-range signal propagation timing in the human visual pathways. A similar modeling approach can potentially be used to understand other cognitive processes and dysfunctions in signal propagation in neurological and neuropsychiatric disorders. Significance statement: An integrated account of long-range visual signal propagation in the human brain is currently incomplete. Using computational neural modeling on our acquired concurrent EEG-fMRI data under a visual evoked task, we found not only a substantial forward propagation toward "higher-order" brain regions but also a weaker backward propagation. Asymmetry in our model's long-range connectivity accounted for the various observed activity biases. Importantly, the model disclosed the timing of signal propagation across these connectivity pathways and validates, for the first time, long-range signal propagation in the human visual system. A similar modeling approach could be used to identify neural pathways for other cognitive processes and their dysfunctions in brain disorders., (Copyright © 2015 the authors 0270-6474/15/3513501-10$15.00/0.)

Background: Rs6265 single nucleotide polymorphism, which influences brain-derived neurotrophic factor (BDNF) levels in the cortical and subcortical brain structures, may result in distinguished patterns of neural activation during a major depressive disorder (MDD) episode. Valine homozygotes with high levels of BDNF and methionine carriers with lower levels of BDNF may present specific neural correlates of MDD. In our study we have tested differences in blood oxygen level dependant (BOLD) signal between individuals with MDD and healthy controls for both allelic variants., Methods: Individuals with MDD (N = 37) and healthy controls (N = 39) were genotyped for rs6265 and compared separately in each allelic variant for BOLD response in a functional magnetic resonance imaging experiment examining appraisal of emotional scenes. The two allelic variants were also compared separately for both individuals with MDD and healthy controls., Results: In the homozygous valine group MDD was associated with decreased neural activation in areas responsible for cognitive appraisal of emotional scenes. In the methionine group MDD was related to increased activation in subcortical regions responsible for visceral reaction to emotional stimuli. During an MDD episode methionine carriers showed more activation in areas associated with cognitive appraisal of emotional information in comparison to valine homozygotes., Limitations: Small sample size of healthy controls carrying methionine (N=8)., Conclusion: Our results suggest that allelic variations in the rs6265 gene lead to specific neural correlates of MDD which may be associated with different mechanisms of MDD in the two allelic groups. This may have potential importance for screening and treatment of patients., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: older subjects may require higher baseline blood pressures to maintain cerebral perfusion. We investigated whether episodic hypotension is associated with tissue infarction in subjects with syncopal symptoms at stroke onset., Methods: over 30 months, all acute strokes/TIAs were prospectively screened for symptoms of syncope or presyncope at stroke onset. Subjects with severe large vessel stenosis were excluded, while cases were referred for syncope unit investigation. All underwent 1.5 T MRI acutely, and suspected borderzone infarctions (BZI) were confirmed through Matlab-derived perfusion software. Case-control comparison was derived from stroke controls with no prior syncope history., Results: thirty-eight of 772 stroke patients described presyncope or syncope at stroke onset and had patent large vessels (4.9% of all strokes). Median age was 72 years (IQR 21.4). Twenty-two patients (58%) were prescribed antihypertensive agents at symptom onset. Twenty-six (68.4%) reported focal neurology <24 h in duration. 63.2% (n = 24) of cases reported prior syncope history, compared with 33% (N = 103) of controls, P < 0.001. Cases exhibited greater orthostatic BP drop than controls, P < 0.05 Twenty-four patients were diagnosed with vasovagal syncope through head-up tilt symptom reproduction, 9 with orthostatic hypotension, 4 with cardiac syncope and 1 with carotid sinus syndrome. Nineteen (50%) patients had an acute infarct on MRI, 14 of these were in the arterial borderzone (73.6%). The BZI group were significantly older than the non-BZI group, 79.2 yrs versus 63.3 yrs, P = 0.002., Conclusion: subjects reporting hypotensive symptoms at stroke onset have a higher prevalence of borderzone infarction, despite being normotensive or hypertensive at baseline., (© The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Previous diffusion tensor imaging (DTI) studies have shown that various factors can affect white matter (WM) tract diffusivity. The aim of the present study was to investigate the effects of childhood adversity (CA), age and gender on WM diffusivity in tracts that are thought to be involved in emotional regulation in individuals with major depressive disorder (MDD) and healthy controls (HC). DTI was obtained from 46 subjects with MDD and 46 HC subjects. Data were pre-processed and deterministic tractography was applied in the cingulum, uncinate fasciculus (UF), fornix, superior longitudinal fasciculus (SLF) and fronto-occipital fasciculus (FOF). In subjects with a history of CA, fractional anisotropy (FA) was greater in the rostral cingulum (RC) and dorsal cingulum, whereas radial diffusivity (RD) was smaller in the RC when compared with subjects with no history of CA. In the UF, FOF and parahippocampal cingulum, FA was greater in the left hemisphere in the subjects with CA when compared with those without CA. Age affected FA, longitudinal diffusivity and RD in the UF, fornix, FOF and SLF, reflecting axonal and myelin degeneration with increasing age. Depression or gender did not have any effects on the diffusivity measures. Due to the cross-sectional nature of the study, a recall bias for CA and possible effects of medical treatment on diffusivity measures could have played a role. CA and age could increase the likelihood to develop WM microstructural anomalies in the brain affective network. Moreover, subjects with CA could be more vulnerable to FA changes.

Background: Patient safety is fundamental to modern medical practice; safe surgery saves lives. Ensuring surgical competence is becoming more difficult at a time when surgeons are being trained in fewer hours. Accurate objective assessment of technical skills ability is lacking in standardization. Functional magnetic resonance imaging (fMRI) has a long history in neuroscience, psychiatry, and cognitive studies. Many studies have explored levels of perceived expertise in sports and musical ability. Little has been published on actual rather than perceived motor skills. This study sought to assess the feasibility of utilizing a novel assessment method by measuring blood oxygen level-dependent signal changes (BOLD) in specific brain regions via fMRI during a surgical skills task., Methods: Images were acquired using fMRI in a pilot study of 9 subjects (3 experts, 3 intermediates, and 3 novices) when performing and imagining performing a basic surgical procedure: hand tying of surgical knots. Level of expertise was based on years of experience and clinical grade. The quality and quantity of knots were assessed objectively by 2 experts who were independent of the study and blinded to the ability of the candidate. The effect of subject head motion caused by the task itself was assessed. The efficacy of fMRI data analyses in removing artifacts caused by this noise source in the data was explored., Results: Shifts of less than 1 voxel (3 × 3 × 3.55 mm(3)) were recorded in all participants and were successfully corrected in all cases in the fMRI preprocessing step. Decreased BOLD activity was observed in experts compared to novices when "knot tying" was compared with the control "finger tap." Increased BOLD activity was observed in experts compared with novices when "imagining a task" in the primary visual cortex, an area important in perceptual learning. Experts and intermediates performed consistently with 100% square knots. Novices had an average of 2 slip knots. Regarding knot quantity, the number of knots ranged from 14 to 26 in novices, 38 to 47 in intermediates, and 54 to 58 in experts. A Kruskal-Wallis rank sum test revealed that the difference between the 3 groups was statistically significant in the quantity of square knots tied (p = 0.147). Specific regions of interest identified concurred with findings of previous studies and included the left supramarginal, left rolandic operculum, and left postcentral regions., Conclusion: We found that fMRI is a feasible method of exploring actual and perceived motor skill abilities. Head motion during performance of a motor skill does not preclude the attainment of meaningful data. Larger numbers are needed to further investigate these early findings., (Copyright © 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Positron emission tomography and computed tomography (PET-CT) is established in the staging of esophageal cancer. In this study, an MRI protocol was designed to emulate the anatomical (T1-weighed (T1W) and T2W imaging) and functional information (diffusion-weighted imaging) provided by PET-CT., Methods: In all, 49 patients with carcinoma of the esophagus underwent PET-CT and whole-body MRI (WBMRI). WBMRI was carried out using dedicated sequences tailored to detect metastatic disease at each area corresponding to the anatomical coverage of PET-CT. Nodal status was determined from histopathology and endoscopic ultrasound biopsy (EUS)., Results: PET-CT and WBMRI identified the primary tumor in 46/49 (94%) and 48/49 (98%) patients, respectively. Nodal analysis in patients undergoing surgery (n = 18) yielded sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of 27, 100, 100, 47 and 56% for PET-CT, compared with 30, 100, 100, 53 and 61% for WBMRI. When nodal analysis included both surgical specimens and EUS criteria (n = 39), sensitivity, specificity, PPV, NPV and accuracy were 46, 91, 93, 40 and 59% for PET-CT compared with 59, 92, 94, 50 and 67% for WBMRI. Both imaging modalities identified distant metastases in 2 patients., Conclusion: WBMRI has similar accuracy to PET-CT in detecting the primary tumor, nodal deposits and for exclusion of systemic metastatic disease., (© 2015 S. Karger AG, Basel.)

Tissue sodium concentration increases in irreversibly damaged (core) tissue following ischemic stroke and can potentially help to differentiate the core from the adjacent hypoperfused but viable penumbra. To test this, multinuclear hydrogen-1/sodium-23 magnetic resonance imaging (MRI) was used to measure the changing sodium signal and hydrogen-apparent diffusion coefficient (ADC) in the ischemic core and penumbra after rat middle cerebral artery occlusion (MCAO). Penumbra and core were defined from perfusion imaging and histologically defined irreversibly damaged tissue. The sodium signal in the core increased linearly with time, whereas the ADC rapidly decreased by >30% within 20 minutes of stroke onset, with very little change thereafter (0.5-6 hours after MCAO). Previous reports suggest that the time point at which tissue sodium signal starts to rise above normal (onset of elevated tissue sodium, OETS) represents stroke onset time (SOT). However, extrapolating core data back in time resulted in a delay of 72 ± 24 minutes in OETS compared with actual SOT. At the OETS in the core, penumbra sodium signal was significantly decreased (88 ± 6%, P=0.0008), whereas penumbra ADC was not significantly different (92 ± 18%, P=0.2) from contralateral tissue. In conclusion, reduced sodium-MRI signal may serve as a viability marker for penumbra detection and can complement hydrogen ADC and perfusion MRI in the time-independent assessment of tissue fate in acute stroke patients.

Purpose: An investigation was carried out into the effect of three image registration techniques on the diagnostic image quality of contrast-enhanced magnetic resonance angiography (CE-MRA) images., Methods: Whole-body CE-MRA data from the lower legs of 27 patients recruited onto a study of asymptomatic atherosclerosis were processed using three deformable image registration algorithms. The resultant diagnostic image quality was evaluated qualitatively in a clinical evaluation by four expert observers, and quantitatively by measuring contrast-to-noise ratios and volumes of blood vessels, and assessing the techniques' ability to correct for varying degrees of motion., Results: The first registration algorithm ('AIR') introduced significant stenosis-mimicking artefacts into the blood vessels' appearance, observed both qualitatively (clinical evaluation) and quantitatively (vessel volume measurements). The two other algorithms ('Slicer' and 'SEMI'), based on the normalised mutual information (NMI) concept and designed specifically to deal with variations in signal intensity as found in contrast-enhanced image data, did not suffer from this serious issue but were rather found to significantly improve the diagnostic image quality both qualitatively and quantitatively, and demonstrated a significantly improved ability to deal with the common problem of patient motion., Conclusions: This work highlights both the significant benefits to be gained through the use of suitable registration algorithms and the deleterious effects of an inappropriate choice of algorithm for contrast-enhanced MRI data. The maximum benefit was found in the lower legs, where the small arterial vessel diameters and propensity for leg movement during image acquisitions posed considerable problems in making accurate diagnoses from the un-registered images., (Copyright © 2014 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)