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Objectives: To determine the contribution of comorbidities on the reported widespread myocardial abnormalities in patients with recent COVID-19.Methods: In a prospective two-centre observational study, patients hospitalised with confirmed COVID-19 underwent gadolinium and manganese-enhanced MRI and CT coronary angiography (CTCA). They were compared with healthy and comorbidity-matched volunteers after blinded analysis.Results: In 52 patients (median age: 54 (IQR 51-57) years, 39 males) who recovered from COVID-19, one-third (n=15, 29%) were admitted to intensive care and a fifth (n=11, 21%) were ventilated. Twenty-three patients underwent CTCA, with one-third having underlying coronary artery disease (n=8, 35%). Compared with younger healthy volunteers (n=10), patients demonstrated reduced left (ejection fraction (EF): 57.4±11.1 (95% CI 54.0 to 60.1) versus 66.3±5 (95 CI 62.4 to 69.8)%; p=0.02) and right (EF: 51.7±9.1 (95% CI 53.9 to 60.1) vs 60.5±4.9 (95% CI 57.1 to 63.2)%; p≤0.0001) ventricular systolic function with elevated native T1 values (1225±46 (95% CI 1205 to 1240) vs 1197±30 (95% CI 1178 to 1216) ms;p=0.04) and extracellular volume fraction (ECV) (31±4 (95% CI 29.6 to 32.1) vs 24±3 (95% CI 22.4 to 26.4)%; p<0.0003) but reduced myocardial manganese uptake (6.9±0.9 (95% CI 6.5 to 7.3) vs 7.9±1.2 (95% CI 7.4 to 8.5) mL/100 g/min; p=0.01). Compared with comorbidity-matched volunteers (n=26), patients had preserved left ventricular function but reduced right ventricular systolic function (EF: 51.7±9.1 (95% CI 53.9 to 60.1) vs 59.3±4.9 (95% CI 51.0 to 66.5)%; p=0.0005) with comparable native T1 values (1225±46 (95% CI 1205 to 1240) vs 1227±51 (95% CI 1208 to 1246) ms; p=0.99), ECV (31±4 (95% CI 29.6 to 32.1) vs 29±5 (95% CI 27.0 to 31.2)%; p=0.35), presence of late gadolinium enhancement and manganese uptake. These findings remained irrespective of COVID-19 disease severity, presence of myocardial injury or ongoing symptoms.Conclusions: Patients demonstrate right but not left ventricular dysfunction. Previous reports of left ventricular myocardial abnormalities following COVID-19 may reflect pre-existing comorbidities.Trial Registration Number: NCT04625075. [ABSTRACT FROM AUTHOR]

Objectives: Ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced MRI can detect tissue-resident macrophage activity and identify cellular inflammation within tissues. We hypothesised that USPIO-enhanced MRI would provide a non-invasive imaging technique that would improve the diagnosis and management of patients with acute myocarditis.Methods: Ten volunteers and 14 patients with suspected acute myocarditis underwent T2, T2* and late gadolinium enhancement (LGE) 3T MRI, with further T2* imaging at 24 hours after USPIO (ferumoxytol, 4 mg/kg) infusion, at baseline and 3 months. Myocardial oedema and USPIO enhancement were determined within areas of LGE as well as throughout the myocardium.Results: Myocarditis was confirmed in nine of the 14 suspected cases of myocarditis. There was greater myocardial oedema in regions of LGE in patients with myocarditis when compared with healthy volunteer myocardium (T2 value, 57.1±5.3 vs 46.7±1.6 ms, p<0.0001). There was no demonstrable difference in USPIO enhancement between patients and volunteers even within regions displaying LGE (change in R2*, 35.0±15.0 vs 37.2±9.6 s-1, p>0.05). Imaging after 3 months in patients with myocarditis revealed a reduction in volume of LGE, a reduction in oedema measures within regions displaying LGE and improvement in ejection fraction (mean -19.7 mL, 95% CI (-0.5 to -40.0)), -5.8 ms (-0.9 to -10.7) and +6% (0.5% to 11.5%), respectively, p<0.05 for all).Conclusion: In patients with acute myocarditis, USPIO-enhanced MRI does not provide additional clinically relevant information to LGE and T2 mapping MRI. This suggests that tissue-resident macrophages do not provide a substantial contribution to the myocardial inflammation in this condition.Clinical trial registration NCT02319278; Results. [ABSTRACT FROM AUTHOR]

Objectives: Macrophages play a central role in the cellular inflammatory response to myocardial infarction (MI) and predict subsequent clinical outcomes. We aimed to assess temporal changes in cellular inflammation and tissue oedema in patients with acute MI using ultrasmallsuperparamagnetic particles of iron oxide (USPIO)-enhanced MRI.Methods: Thirty-one patients were recruited following acute MI and followed up for 3 months with repeated T2 and USPIO-enhanced T2*-mapping MRI. Regions of interest were categorised into infarct, peri-infarct and remote myocardial zones, and compared with control tissues.Results: Following a single dose, USPIO enhancement was detected in the myocardium until 24 hours (p<0.0001). Histology confirmed colocalisation of iron and macrophages within the infarcted, but not the non-infarcted, myocardium. Following repeated doses, USPIO uptake in the infarct zone peaked at days 2-3, and greater USPIO uptake was detected in the infarct zone compared with remote myocardium until days 10-16 (p<0.05). In contrast, T2-defined myocardial oedema peaked at days 3-9 and remained increased in the infarct zone throughout the 3-month follow-up period (p<0.01).Conclusion: Myocardial macrophage activity can be detected using USPIO-enhanced MRI in the first 2 weeks following acute MI. This observed pattern of cellular inflammation is distinct, and provides complementary information to the more prolonged myocardial oedema detectable using T2 mapping. This imaging technique holds promise as a non-invasive method of assessing and monitoring myocardial cellular inflammation with potential application to diagnosis, risk stratification and assessment of novel anti-inflammatory therapeutic interventions.Trial Registration Number: Trial registration number: 14663. Registered on UK Clinical Research Network (http://public.ukcrn.org.uk) and also ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT02319278?term=DECIFER&rank=2). [ABSTRACT FROM AUTHOR]

MRSI permits the non-invasive mapping of brain temperature in vivo, but information regarding its reliability is lacking. We obtained MRSI data from 31 healthy male volunteers [age range, 22-40 years; mean ± standard deviation (SD), 30.5 ± 5.0 years]. Eleven subjects (age range, 23-40 years; mean ± SD, 30.5 ± 5.2 years) were invited to receive four point-resolved spectroscopy MRSI scans on each of 3 days in both 1.5-T (TR/TE = 1000/144 ms) and 3-T (TR/TE = 1700/144 ms) clinical scanners; a further 20 subjects (age range, 22-40 years; mean ± SD, 30.5 ± 4.9 years) were scanned on a single occasion at 3 T. Data were fitted in the time domain to determine the water- N-acetylaspartate chemical shift difference, from which the temperature was estimated. Temperature data were analysed using a linear mixed effects model to determine variance components and systematic temperature changes during the scanning sessions. To characterise the effects of instrumental drift on apparent MRSI brain temperature, a temperature-controlled phantom was constructed and scanned on multiple occasions. Components of apparent in vivo temperature variability at 1.5 T/3 T caused by inter-subject (0.18/0.17 °C), inter-session (0.18/0.15 °C) and within-session (0.36/0.14 °C) effects, as well as voxel-to-voxel variation (0.59/0.54 °C), were determined. There was a brain cooling effect during in vivo MRSI of 0.10 °C [95% confidence interval (CI): -0.110, -0.094 °C; p < 0.001] and 0.051 °C (95% CI: -0.054, -0.048 °C; p < 0.001) per scan at 1.5 T and 3 T, respectively, whereas phantom measurements revealed minimal drift in apparent MRSI temperature relative to fibre-optic temperature measurements. The mean brain temperature at 3 T was weakly associated with aural ( R = 0.55, p = 0.002) and oral ( R = 0.62, p < 0.001) measurements of head temperature. In conclusion, the variability associated with MRSI brain temperature mapping was quantified. Repeatability was somewhat higher at 3 T than at 1.5 T, although subtle spatial and temporal variations in apparent temperature were demonstrated at both field strengths. Such data should assist in the efficient design of future clinical studies. © 2013 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article presents the study which examined the effects of ultrasmall superparamagnetic particles of iron oxide (USPIO) in patients with acute myocardial infarction (MI). The study is intended to prove the effectiveness of USPIO for the assessment of cellular myocardial inflammation after acute MI in humans. Based on the results, USPIO has potential for evaluating cellular myocardial inflammation and left ventricular remodelling.

The article presents a study which aimed to develop a safe method of labeling competent peripheral blood mononuclear cells using superparamagnetic particles of iron oxide (SPIO) and to evaluate its potential for magnetic resonance cell tracking in humans. The researchers used a phased-dosing study. They found that human peripheral mononuclear cells can be labeled with SPIO without affecting their efficacy and safe for magnetic resonance cell tracking.

The variation of the native T1 ( T10) of different tissues and B1 transmission-field inhomogeneity at 3 T are major contributors of errors in the quantification of breast dynamic contrast-enhanced MRI. To address these issues, we have introduced new enhancement indices derived from saturation-recovery snapshot-FLASH (SRSF) images. The stability of the new indices, i.e., the SRSF enhancement factor (EFSRSF) and its simplified version (EF′SRSF) with respect to differences in T10 and B1 inhomogeneity was compared against a typical index used in breast dynamic contrast-enhanced MRI, i.e., the enhancement ratio (ER), by using computer simulations. Imaging experiments with Gd-DTPA-doped gel phantoms and a female volunteer were also performed. A lower error was observed in the new indices compared to enhancement ratio in the presence of typical T10 variation and B1 inhomogeneity. At changes of relaxation rate (Δ R1) of 8 s−1, the differences between a T10 of 1266 and 566 ms are <1, 12, and 58%, respectively, for EFSRSF, EF′SRSF, and ER, whereas differences of 20, 8, and 51%, respectively, result from a 50% B1 field reduction at the same Δ R1. These quantification techniques may be a solution to minimize the effect of T10 variation and B1 inhomogeneity on dynamic contrast-enhanced MRI of the breast at 3 T. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose: To quantify B(1) transmission-field inhomogeneity in breast imaging of normal volunteers at 3T using 3D T(1)-weighted spoiled gradient echo and to assess the resulting errors in enhancement ratio (ER) measured in dynamic contrast-enhanced MRI (DCE-MRI) studies of the breast.Materials and Methods: A total of 25 volunteers underwent breast imaging at 3T and the B(1) transmission-fields were mapped. Gel phantoms that simulate pre- and postcontrast breast tissue T(1) were developed. The effects of B(1)-field inhomogeneity on ER, as measured using a 3D spoiled gradient echo sequence, were investigated by computer simulation and experiments on gel phantoms.Results: It was observed that by using the patient orientation and MR scanner employed in this study, the B(1) transmission-field field is always reduced toward the volunteer's right side. The median B(1)-field in the right breast is reduced around 40% of the expected B(1)-field. For some volunteers the amplitude was reduced by more than 50%. Computer simulation and experiment showed that a reduction in B(1)-field decreases ER. This reduction increases with both B(1)-field error and contrast agent uptake.Conclusion: B(1) transmission-field inhomogeneity is a critical issue in breast imaging at 3T and causes errors in quantifying ER. These errors would be sufficient to reduce the conspicuity of a malignant lesion and could result in reduced sensitivity for cancer detection. [ABSTRACT FROM AUTHOR]

A protocol for evaluating ultrasmall superparamagnetic particles of iron oxide (USPIO) uptake and elimination in cerebral small vessel disease patients was developed and piloted. B1-insensitive R1 measurement was evaluated in vitro. Twelve participants with history of minor stroke were scanned at 3-T MRI including structural imaging, and R1 and R2* mapping. Participants were scanned (i) before and (ii) after USPIO (ferumoxytol) infusion, and again at (iii) 24–30 h and (iv) one month. Absolute and blood-normalised changes in R1 and R2* were measured in white matter (WM), deep grey matter (GM), white matter hyperintensity (WMH) and stroke lesion regions. R1 measurements were accurate across a wide range of values. R1 (p < 0.05) and R2* (p < 0.01) mapping detected increases in relaxation rate in all tissues immediately post-USPIO and at 24–30 h. R2* returned to baseline at one month. Blood-normalised R1 and R2* changes post-infusion and at 24–30 h were similar, and were greater in GM versus WM (p < 0.001). Narrower distributions were seen with R2* than for R1 mapping. R1 and R2* changes were correlated at 24–30 h (p < 0.01). MRI relaxometry permits quantitative evaluation of USPIO uptake; R2* appears to be more sensitive to USPIO than R1. Our data are explained by intravascular uptake alone, yielding estimates of cerebral blood volume, and did not support parenchymal uptake. Ferumoxytol appears to be eliminated at 1 month. The approach should be valuable in future studies to quantify both blood-pool USPIO and parenchymal uptake associated with inflammatory cells or blood-brain barrier leak. [ABSTRACT FROM AUTHOR]

Objective. Training deep learning models for image registration or segmentation of dynamic contrast enhanced (DCE) MRI data is challenging. This is mainly due to the wide variations in contrast enhancement within and between patients. To train a model effectively, a large dataset is needed, but acquiring it is expensive and time consuming. Instead, style transfer can be used to generate new images from existing images. In this study, our objective is to develop a style transfer method that incorporates spatio-temporal information to either add or remove contrast enhancement from an existing image. Approach. We propose a temporal image-to-image style transfer network (TIST-Net), consisting of an auto-encoder combined with convolutional long short-term memory networks. This enables disentanglement of the content and style latent spaces of the time series data, using spatio-temporal information to learn and predict key structures. To generate new images, we use deformable and adaptive convolutions which allow fine grained control over the combination of the content and style latent spaces. We evaluate our method, using popular metrics and a previously proposed contrast weighted structural similarity index measure. We also perform a clinical evaluation, where experts are asked to rank images generated by multiple methods. Main Results. Our model achieves state-of-the-art performance on three datasets (kidney, prostate and uterus) achieving an SSIM of 0.91 ± 0.03, 0.73 ± 0.04, 0.88 ± 0.04 respectively when performing style transfer between a non-enhanced image and a contrast-enhanced image. Similarly, SSIM results for style transfer from a contrast-enhanced image to a non-enhanced image were 0.89 ± 0.03, 0.82 ± 0.03, 0.87 ± 0.03. In the clinical evaluation, our method was ranked consistently higher than other approaches. Significance. TIST-Net can be used to generate new DCE-MRI data from existing images. In future, this may improve models for tasks such as image registration or segmentation by allowing small training datasets to be expanded., (Creative Commons Attribution license.)

Inflammation detected through the uptake of ultrasmall superparamagnetic particles of iron oxide (USPIO) on magnetic resonance imaging (MRI) and finite element (FE) modelling of tissue stress both hold potential in the assessment of abdominal aortic aneurysm (AAA) rupture risk. This study aimed to examine the spatial relationship between these two biomarkers. Patients (n = 50) > 40 years with AAA maximum diameters > = 40 mm underwent USPIO-enhanced MRI and computed tomography angiogram (CTA). USPIO uptake was compared with wall stress predictions from CTA-based patient-specific FE models of each aneurysm. Elevated stress was commonly observed in areas vulnerable to rupture (e.g. posterior wall and shoulder). Only 16% of aneurysms exhibited co-localisation of elevated stress and mural USPIO enhancement. Globally, no correlation was observed between stress and other measures of USPIO uptake (i.e. mean or peak). It is suggested that cellular inflammation and stress may represent different but complimentary aspects of AAA disease progression.

In abdominal aortic aneurysm disease, the aortic wall is exposed to intense biological activity involving inflammation and matrix metalloproteinase-mediated degradation of the extracellular matrix. These processes are orchestrated by monocytes and rather than affecting the aorta uniformly, damage and weaken focal areas of the wall leaving it vulnerable to rupture. This study attempts to model numerically the deposition of monocytes using large eddy simulation, discrete phase modelling and near-wall particle residence time. The model was first applied to idealised aneurysms and then to three patient-specific lumen geometries using three-component inlet velocities derived from phase-contrast magnetic resonance imaging. The use of a novel, variable wall shear stress-limiter based on previous experimental data significantly improved the results. Simulations identified a critical diameter (1.8 times the inlet diameter) beyond which significant monocyte deposition is expected to occur. Monocyte adhesion occurred proximally in smaller abdominal aortic aneurysms and distally as the sac expands. The near-wall particle residence time observed in each of the patient-specific models was markedly different. Discrete hotspots of monocyte residence time were detected, suggesting that the monocyte infiltration responsible for the breakdown of the abdominal aortic aneurysm wall occurs heterogeneously. Peak monocyte residence time was found to increase with aneurysm sac size. Further work addressing certain limitations is needed in a larger cohort to determine clinical significance.

Aims: To examine the relative and combined value of late gadolinium enhancement (LGE) and low-dose dobutamine (LDD) cardiac magnetic resonance (CMR) to predict 'adverse remodelling' (AR) following acute myocardial infarction (AMI)., Methods and Results: Forty-five patients with AMI were recruited. CMR was performed 2-4 days after presentation and at 6 months. Ventricular wall motion and volume were recorded at rest and following dobutamine infusion. Measures of first pass perfusion, persistent microvascular obstruction (PMO), and LGE were obtained following contrast administration. Quantitation was performed using the MEDIS 6.2 software. Regression analysis was employed to determine the univariables and multivariate models most predictive of AR at 6 months. The incremental and relative value of LDD over LGE was investigated. The most predictive univariable was 'volume of PMO' (r = 0.51, r2 = 0.26, P < 0.001). The optimal 'combined' multivariate model, utilizing data from all components, was highly predictive of AR (r = 0.82, r2 = 0.67, P < 0.001). The optimal model using parameters only from the LGE component also predicted remodelling (r = 0.65, r2 = 42.0, P = 0.001) but with less accuracy. In contrast, the optimal model using variables from the LDD component alone predicted remodelling with a similar accuracy to the optimal combined model (r = 0.82, r2 = 0.67, P < 0.001)., Conclusion: A comprehensive CMR examination accurately predicts AR following AMI. LDD is superior to LGE CMR in this respect. These data suggest that LDD not only adds incremental value to LGE in the prediction of remodelling post-AMI but also may be utilized alone with the same predictive power.

Objectives/hypothesis: Traditional voice research occurs within a phonetic context. Accordingly, pitch-related contributions are inseparable from those due to articulator input. In humming, articulator input is negligible. Using magnetic resonance imaging, we test the hypothesis that voice production is accompanied by pitch-related adjustments unrelated to articulatory or postural input., Study Design/method: In this cross-sectional study, 10 healthy volunteers (five men, five women, aged 20-47 years, median 25 years), including singers (6 months to 10 years tuition, median 2 years) and non-singers, were assessed to establish the lowest and highest notes they could comfortably sustain while humming over 20 seconds. With head position stable, midsagittal images were acquired while volunteers hummed these predetermined low and high notes. Twenty-two craniocervical, angular, and linear dimensions defined on these images were compared using one-way repeated-measures analysis of variance. Correlations between variables were sought using Pearson correlation coefficient., Results: We found significant differences between low- and high-note conditions in six of 22 measures and widespread pitch-related correlations between variables (r≥0.63, P<0.05). Compared with low-note humming, high-note humming was accompanied by increased craniocervical angles opt/nsl and cvt/nsl (P=0.008 and 0.002, respectively); widening of the C3-menton distance (P=0.003), a rise of the larynx and hyoid in relation to the cranial base (P=0.012 and <0.001, respectively), and an increased sternum-hyoid distance (P<0.001)., Conclusion: Voice production is accompanied by pitch-related adjustments that are currently being masked by, or mistakenly attributed to, articulatory or postural input, identification of which could improve understanding of mechanisms underlying speech and song., (Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.)

Objectives: Traditional voice research focuses on the vocal tract, articulators, and larynx. By ignoring their direct/indirect attachments (skull, cervical spine, and sternum) important information may be missed. We aim to investigate vocal structures within this wider context and assess the validity of this approach for subsequent voice production studies., Study Design/method: Using a cross-sectional study design, we obtained midsagittal MR images from 10 healthy adults (five males and five females) while at rest and breathing quietly. With reference points based on cephalometry, 17 craniocervical, craniocaudal, and anteroposterior variables were chosen to describe craniofacial morphology, craniocervical posture, and airway dimensions. Relationships between variables were sought using Pearson's correlation coefficient., Results: We found widespread correlations relating vocal structures to the craniofacial skeleton and cervical spine (r>0.6). Increasing airway size (hyocervical distance) was associated with greater distances from the cranial base of the hyoid, larynx, epiglottis tip and uvula tip, and of C3 from the menton. A wider velopharyngeal opening was associated with a shorter and higher soft palate, and a greater (lower) craniocervical angle was associated with a wider laryngeal tube opening, narrower airway at the uvula tip and shorter distances of the hyoid and uvula tip from the cranial base., Conclusion: Finding widespread correlations relating vocal structures to the craniofacial skeleton and cervical spine confirms the potential of this approach to uncover functional activity during voice production and demonstrates the importance of considering vocal structures and the airway within this wider context if important information is not to be missed., (Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.)

The motivation of the project was to investigate the use of oxygen-challenge magnetic resonance imaging (OC-MRI) as a method of diagnosing foetal growth restriction. Foetal growth restriction is associated with restricted foetal oxygen supply and is also associated with increased risks of perinatal mortality and morbidity, and a number of serious and chronic health problems. Measurements of T2* relaxation time, an MRI parameter which increases with blood oxygenation, were made in the right lobe of the foetal liver in 80 singleton pregnancies, before and after the mother breathed oxygen. The groups consisted of 41 foetuses with normal growth and 39 with apparent growth restriction. The mean +/- SD gestational age at scanning was 35 +/- 3 weeks. Changes in foetal liver T2* on maternal oxygen breathing showed no significant difference between the groups therefore the OC-MRI protocol used in this study has no value in the diagnosis of foetal growth restriction. A secondary finding was that a significant positive correlation of T2* change with gestational age was observed. Future studies on the use of oxygen-challenge MRI to investigate foetal growth restriction may therefore need to control for gestational age at the time of MR scanning in order to observe any underlying foetal growth-related effects.

Purpose: To investigate the combination of pharmacokinetic and radiologic assessment of dynamic contrast-enhanced magnetic resonance imaging (MRI) as an early response indicator in women receiving chemoradiation for advanced cervical cancer., Methods and Materials: Twenty women with locally advanced cervical cancer were included in a prospective cohort study. Dynamic contrast-enhanced MRI was carried out before chemoradiation, after 2 weeks of therapy, and at the conclusion of therapy using a 1.5-T MRI scanner. Radiologic assessment of uptake parameters was obtained from resultant intensity curves. Pharmacokinetic analysis using a multicompartment model was also performed. General linear modeling was used to combine radiologic and pharmacokinetic parameters and correlated with eventual response as determined by change in MRI tumor size and conventional clinical response. A subgroup of 11 women underwent repeat pretherapy MRI to test pharmacokinetic reproducibility., Results: Pretherapy radiologic parameters and pharmacokinetic K(trans) correlated with response (p < 0.01). General linear modeling demonstrated that a combination of radiologic and pharmacokinetic assessments before therapy was able to predict more than 88% of variance of response. Reproducibility of pharmacokinetic modeling was confirmed., Conclusions: A combination of radiologic assessment with pharmacokinetic modeling applied to dynamic MRI before the start of chemoradiation improves the predictive power of either by more than 20%. The potential improvements in therapy response prediction using this type of combined analysis of dynamic contrast-enhanced MRI may aid in the development of more individualized, effective therapy regimens for this patient group.