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Funder: National Institute of Health Research Academic Clinical Fellowship, Introduction: Severe COVID‐19 has been anecdotally associated with high insulin requirements. It has been proposed that this may be driven by a direct diabetogenic effect of the virus that is unique to SARS‐CoV‐2, but evidence to support this is limited. To explore this, we compared insulin requirements in patients with severe COVID‐19 and non‐COVID‐19 viral pneumonitis. Methods: This is a retrospective cohort study of patients with severe COVID‐19 admitted to our intensive care unit between March and June 2020. A historical control cohort of non‐COVID‐19 viral pneumonitis patients was identified from routinely collected audit data. Results: Insulin requirements were similar in patients with COVID‐19 and non‐COVID‐19 viral pneumonitis after adjustment for pre‐existing diabetes and severity of respiratory failure. Conclusions: In this single‐centre study, we could not find evidence of a unique diabetogenic effect of COVID‐19. We suggest that high insulin requirements in this disease relate to its propensity to cause severe respiratory failure in patients with pre‐existing metabolic disease.

Background Atherosclerosis is a systemic inflammatory disease intertwined with neovascularization. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) enables the assessment of plaque neovascularization. This study aimed to explore the systemic nature of atherosclerosis by assessing difference in severity of neovascularization as quantified by DCE-MRI of vertebral arteries (VAs) between patients with symptomatic and asymptomatic carotid artery disease. Methods Ten consecutive patients with asymptomatic VA stenosis and concomitant symptomatic carotid artery disease (group 1) and 10 consecutive patients with asymptomatic VA stenosis and concomitant asymptomatic carotid artery disease (group 2) underwent 3-dimensional DCE-MRI of their cervical segment of VAs. A previously validated pharmacokinetic modeling approach was used for DCE-MRI analysis. Ktrans was calculated in the adventitia and plaque as a measure of neovessel permeability. Results Both patient groups were comparable for demographics and comorbidities. Mean luminal stenosis was comparable for both groups (54.4% versus 52.27%, P = .32). Group 1 had higher adventitial Ktrans and plaque Ktrans (.08 ± .01 min−1, .07 ± .01 min−1) compared with Group 2 (.06 ± .01 min−1, .06 ± .01 min−1) (P = .004 and .03, respectively). Good correlation was present among the two image analysts (intraclass correlation coefficient = .78). Conclusions Vertebral Artery atheroma of patients with symptomatic carotid artery disease had increased neovessel permeability compared with the patients with asymptomatic carotid artery disease. These findings are consistent with the hypothesis that atherosclerosis is a systemic inflammatory disease. The VA atherosclerosis is likely to have increased severity of neovascularization if another arterial territory is symptomatic in the same patient cohort.

The purpose of this work is to evaluate the repeatability of a compressed sensing (CS) accelerated multi-contrast carotid protocol at 3 T. Twelve volunteers and eight patients with carotid disease were scanned on a 3 T MRI scanner using a CS accelerated 3-D black-blood multi-contrast protocol which comprises T 1w, T 2w and PDw without CS, and with a CS factor of 1.5 and 2.0. The volunteers were scanned twice, the lumen/wall area and wall thickness were measured for each scan. Eight patients were scanned once, the inter/intra-observer reproducibility of the measurements was calculated. In the repeated volunteer scans, the interclass correlation coefficient (ICC) for the wall area measurement using a CS factor of 1.5 in PDw, T 1w and T 2w were 0.95, 0.81, and 0.97, respectively. The ICC for lumen area measurement using a CS factor of 1.5 in PDw, T 1w and T 2w were 0.96, 0.92, and 0.96, respectively. In patients, the ICC for inter/intra-observer measurements of lumen/wall area, and wall thickness were all above 0.81 in all sequences. The results show a CS accelerated 3-D black-blood multi-contrast protocol is a robust and reproducible method for carotid imaging. Future protocol design could use CS to reduce the scanning time.

BACKGROUND: Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging enables the identification of inflammation within the atheroma, predominantly by USPIO uptake by macrophages present in atherosclerotic tissue. Diabetic patients, however, may have dysfunctional macrophage activity, which may affect utilization of USPIO in identifying plaque inflammation in this patient cohort. METHODS: Fifteen diabetic and fifteen nondiabetic patients underwent USPIO-enhanced carotid MR imaging using 1.5T MR system. Pre- and post-USPIO carotid MR images were manually coregistered. The percentage decrease in the signal intensity after USPIO administration was calculated as a relative measure of the USPIO uptake. RESULTS: Diabetic and nondiabetic patients had comparable demographics and comorbidities. The mean global, maximum quadrant, and maximum slice changes showing change in relative signal intensity as a result of USPIO administration were comparable for the two patient cohorts (P > .05). CONCLUSIONS: USPIO can identify inflammatory burden with carotid atheroma in both diabetic and nondiabetic patients.

Purpose To develop a 3D black-blood T 2 mapping sequence with a combination of compressed sensing (CS) and parallel imaging (PI) for carotid wall imaging. Materials and methods A 3D black-blood fast-spin-echo (FSE) sequence for T 2 mapping with CS and PI was developed and validated. Phantom experiments were performed to assess T 2 accuracy using a Eurospin Test Object, with different combination of CS and PI acceleration factors. A 2D multi-echo FSE sequence was used as a reference to evaluate the accuracy. The concordance correlation coefficient and Bland-Altman statistics were calculated. Twelve volunteers were scanned twice to determine the repeatability of the sequence and the intraclass correlation coefficient (ICC) was reported. Wall-lumen sharpness was calculated for different CS and PI combinations. Six patients with carotid stenosis > 50% were scanned with optimised sequence. The T 2 maps were compared with multi-contrast images. Results Phantom scans showed good correlation in T 2 measurement between current and reference sequence (r = 0.991). No significant difference was found between different combination of CS and PI accelerations (p = 0.999). Volunteer scans showed good repeatability of T 2 measurement (ICC: 0.93, 95% CI 0.84–0.97). The mean T 2 of the healthy wall was 48.0 ± 9.5 ms. Overall plaque T 2 values from patients were 54.9 ± 12.2 ms. Recent intraplaque haemorrhage and fibrous tissue have higher T 2 values than the mean plaque T 2 values (88.1 ± 6.8 ms and 62.7 ± 9.3 ms, respectively). Conclusion This study demonstrates the feasibility of combining CS and PI for accelerating 3D T 2 mapping in the carotid artery, with accurate T 2 measurements and good repeatability.

Purpose Imaging carotid artery plaques to identify features of vulnerability typically requires a multicontrast MRI protocol. The identification of regions of inflammation with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles requires separate pre- and postcontrast scans. We propose a method of joint water-fat separation and quantitative susceptibility mapping (QSM) to aid classification of atherosclerotic plaques and offer a positive contrast mechanism in USPIO-imaging. Methods Ten healthy volunteers (3 women and 7 men; aged, 30.7 ± 10.7 years) were imaged at 1.5T to develop an acquisition and postprocessing protocol. Five patients (1 woman and 4 men; mean age, 71 ± 7.5 years) with moderate to severe luminal stenosis were imaged pre- and postadministration of a USPIO contrast agent. We used a multiecho gradient echo acquisition to perform water/fat separation and subsequently QSM. The results were compared with a conventional multicontrast MRI protocol, CT images, and histopathology data. Results In the volunteer scans, a multiecho gradient echo acquisition with bipolar readout gradients demonstrated to be a reliable acquisition methodology to produce high-quality susceptibility maps in conjunction with the proposed postprocessing methodology. In the patient study, water/fat separation provided a tool to identify lipid-rich necrotic cores and QSM provided a qualitative and quantitative evaluation of plaque features and positive contrast when evaluating USPIO uptake. Plaque calcification could be identified by strong diamagnetism (-1.27 ± 0.71 ppm), while USPIO uptake demonstrated a strong paramagnetism (1.32 ± 0.61 ppm). Conclusion QSM was able to identify multiple plaque features in a single acquisition, providing positive contrast for plaques demonstrating USPIO uptake and negative contrast for calcification.

Arterial calcification in different arterial beds has been observed to be an independent predictor of mortality. The association of abdominal visceral artery calcium with all-cause mortality remains unexplored. Patients who had undergone contrast-enhanced computerized tomography (CT) imaging for routine assessment of peripheral arterial disease (PAD) were considered for this study. A novel calcium score (abdominal visceral arteries calcium [AVAC]) for the abdominal visceral arteries (celiac axis, superior mesenteric, and renal arteries) was calculated using a modified Agatston score. Cumulative AVAC was defined as sum total of the calcium score of above individual arteries. The primary outcome was all-cause mortality. The association of AVAC with all-cause mortality was assessed. Of the 134 consecutive patients, 89 were included for analysis. Median follow-up duration was 72 (47-91) months since CT imaging; 35 (39%) patients died during this period. Hypertension and cumulative AVAC score had a significant association with all-cause mortality ( P < .05). Cumulative visceral abdominal artery calcification is associated with all-cause mortality in patients with PAD. Future prospective studies are warranted to investigate this relationship in PAD and other patient cohorts.

Atherosclerosis remains the leading cause of long term morbidity and mortality worldwide, despite significant advances in its management. Vulnerable atherothrombotic plaques are predominantly responsible for thromboembolic ischaemic events in arterial beds, such as the carotid, coronary and lower limb arteries. MRI has emerged as a non-invasive, non-irradiating and highly reproducible imaging technique which allows detailed morphological and functional assessment of such plaques. It also has the potential to monitor the efficacy of established and evolving anti-atherosclerosis drugs. It is envisaged that by careful identification and understanding of the underlying cellular and molecular mechanisms that govern atherosclerosis, novel treatment strategies can be formulated which may reduce the persistent high mortality and morbidity rates associated with this disease. MRI shows promise in achieving this goal.

Based on the results of histopathological studies, inflammation within atherosclerotic tissue is now widely accepted as a key determinant of the disease process. Conventional imaging methods can highlight the location and degree of luminal stenosis but not the inflammatory activity of the plaque. Iron oxide-based MRI contrast media particularly ultrasmall supermagnetic particles of iron oxide have shown potential in assessing atheromatous plaque inflammation and in determining efficacy of antiatherosclerosis pharmacological treatments. In this paper, we review current data on the use of ultrasmall superparamagnetic iron oxides in atherosclerosis imaging with focus on ferumoxtran-10 and ferumoxytol. The basic chemistry, pharmacokinetics and dynamics, potential applications, limitations and future perspectives of these contrast media nanoparticles are discussed.

Contrast medium-induced acute kidney injury (CI-AKI) is a predominant cause of hospital-acquired renal insufficiency. With an increasing number of contrast medium-enhanced radiological procedures being performed in a rapidly increasing ageing population in the Western world, it is imperative that more attention is given to understand the aetiology of CI-AKI to devise novel diagnostic methods and to formulate effective prophylactic and therapeutic regimens to reduce its incidence and its associated morbidity and mortality. This article presents high-yield information on the above-mentioned aspects of CI-AKI, primarily based on results of randomised controlled trials, meta-analyses, systematic reviews and international consensus guidelines.

This study aims to explore the relationship between plaque surface morphology and neovascularization using a high temporal and spatial resolution 4D contrast-enhanced MRI/MRA sequence. Twenty one patients with either recent symptoms or a carotid artery stenosis ≥40% were recruited in this study. Plaque surface morphology and luminal stenosis were determined from the arterial phase MRA images. Carotid neovascularization was evaluated by a previously validated pharmacokinetic (PK) modeling approach. K trans (transfer constant) and v p (partial plasma volume) were calculated in both the adventitia and plaque. Image acquisition and analysis was successfully performed in 28 arteries. Mean luminal stenosis was 44% (range 11–82%). Both adventitial and plaque K trans in ulcerated/irregular plaques were significantly higher than smooth plaques (0.079 ± 0.018 vs. 0.064 ± 0.011 min−1, p = 0.02; 0.065 ± 0.013 vs. 0.055 ± 0.010 min−1, p = 0.03, respectively). Positive correlations between adventitial K trans and v p against stenosis were observed (r = 0.44, p = 0.02; r = 0.55, p = 0.01, respectively). This study demonstrates the feasibility of using a single sequence to acquire both high resolution 4D CE-MRA and DCE-MRI to evaluate both plaque surface morphology and function. The results demonstrate significant relationships between lumen surface morphology and neovascularization.

PURPOSE OF REVIEW To provide brief overview of the developments regarding use of ultrasmall superparamagnetic particles of iron oxide in imaging pathobiology of carotid atherosclerosis. RECENT FINDINGS MRI is a promising technique capable of providing morphological and functional information about atheromatous plaques. MRI using iron oxide particles, called ultrasmall superparamagnetic iron oxide (USPIO) particles, allows detection of macrophages in atherosclerotic tissue. Ferumoxytol has emerged as a new USPIO agent, which has an excellent safety profile. Based on the macrophage-selective properties of ferumoxytol, there is increasing number of recent reports suggesting its effectiveness to detect pathological inflammation. SUMMARY USPIO particles allow magnetic resonance detection of macrophages in atherosclerotic tissue. Ferumoxytol has emerged as a new USPIO agent, with an excellent safety profile. This has the potential to be used for MRI of the pathobiology of atherosclerosis.

Objectives This study sought to perform a systematic review with meta-analysis of randomized controlled trials comparing the use of ascorbic acid with placebo or other treatment options for the treatment of contrast induced-acute kidney injury (CI-AKI) in patients undergoing coronary angiography. Background CI-AKI remains the most widely discussed and debated topic in cardiovascular medicine, with its incidence increasing due to an increasing number of contrast media-enhanced radiological procedures being performed. Methods MEDLINE, Embase, and Cochrane central databases were searched from inception to May 2013, without language restrictions. For a study to be selected, it had to report the incidence of CI-AKI as an outcome measure. Studies were excluded if at least 1 study arm did not have ascorbic acid administered alone or with saline solution hydration. Data were extracted by 1 author, and random checks were made by another author. Results Nine randomized, controlled trials reported data on the incidence of CI-AKI in 1,536 patients who had completed the trial and were included in the final analysis. Patients receiving ascorbic acid had 33% less risk of CI-AKI compared with patients receiving placebo or an alternate pharmacological treatment (risk ratio by random-effects model: 0.672; 95% confidence interval, 0.466 to 0.969; p = 0.034). Conclusions Ascorbic acid provides effective nephroprotection against CI-AKI and may form a part of effective prophylactic pharmacological regimens.

Aim To assess the effect of low-(10 mg) or high-(80 mg) dose atorvastatin on carotid artery distensibility in patients with asymptomatic carotid artery disease using carotid magnetic resonance imaging. Methods Eighteen patients underwent initial 2-dimensional ECG gated-phase contrast carotid MR imaging and off-line applanation tonometry for distensibility assessment before randomisation to receive low- or high-dose statins and this was repeated at 12 weeks. Phase and magnitude images from the 2-D phase contrast acquisitions were used for quantification of distensibility and compliance coefficients and were compared between the low- and high-dose statin groups. Results Both groups were comparable with regards to their demographics, co-morbidities and baseline cholesterol levels. After 12 weeks of high-dose statin administration, a significant decrease in LDL (p=0.003) and CRP (p=0.03) was observed. At 12 weeks, the distensibility coefficient of the common and internal carotid artery was found to be significantly higher (with respect to baseline) in the high-dose group (p=0.004 and p=0.007, respectively). The compliance coefficient was likewise found to be raised in the high-dose group when compared with the low-dose group [common carotid (p=0.002), internal carotid (p=0.009)]. Conclusions High-dose atorvastatin tends to reduce carotid arterial stiffness, as suggested by increased distensibility and compliance coefficients; however, these results need validation through large-scale trials to fully establish their possible use in clinical practice.

Atherosclerosis remains the leading cause of long-term mortality and morbidity worldwide, despite remarkable advancement in its management. Vulnerable atherosclerotic plaques are principally responsible for thromboembolic events in various arterial territories such as carotid, coronary, and lower limb vessels. Carotid plaque ulceration is one of the key features associated with plaque vulnerability and is considered a notable indicator of previous plaque rupture and possible future cerebrovascular events. Multiple imaging modalities have been used to assess the degree of carotid plaque ulceration for diagnostic and research purposes. Early diagnosis and management of carotid artery disease could prevent further cerebrovascular events. In this review, we highlight the merits and limitations of various imaging techniques for identifying plaque ulceration.

Acute kidney injury (AKI) is a recognized complication post-endovascular aneurysm repair (EVAR). Neutrophil gelatin-associated lipocalin (NGAL), interleukin 18 (IL-18), and retinol-binding protein are emerging urinary biomarkers that have shown promise in detecting subclinical and clinical renal impairment. In this study, we assessed changes in these urinary biomarkers as well as serum creatinine (SCr) in patients undergoing EVAR. Urine samples were collected prospectively at 5 time points for each recruited patient: pre-EVAR (baseline) and 6, 12, 24, and 48 hours after the procedure for serial assessment of urinary biomarkers. Serum creatinine was quantified preoperatively and at 24 and 48 hours postoperatively. Serial changes of urinary biomarkers and SCr were assessed. A significant increase in NGAL and IL-18 from baseline was observed ( P < .05), as early as 6 hours for NGAL. A significant rise in levels of NGAL and IL-18 precedes the significant rise in SCr. These findings highlight the potential of emerging urinary biomarkers in detecting early AKI following EVAR.

BACKGROUND: Functional magnetic resonance (MR) imaging of atheroma using contrast media enables assessment of the systemic severity of atherosclerosis in different arterial beds. Whether black-blood imaging has similar ability remains widely unexplored. In this study, we evaluate whether black-blood imaging can differentiate carotid plaques of patients with and without coronary artery disease (CAD) in terms of morphological and biomechanical features of plaque vulnerability, thereby allowing assessment of the systemic severity nature of atherosclerosis in different arterial beds. METHODS: Forty-one patients with CAD and 59 patients without CAD underwent carotid black-blood MR imaging. Plaque components were segmented to identify large lipid core (LC), ruptured fibrous cap (FC), and plaque hemorrhage (PH). These segmented contours of plaque components were used to quantify maximum structural biomechanical stress. RESULTS: Patients with CAD and without CAD had comparable demographics and comorbidities. Both groups had comparable prevalence of morphological features of plaque vulnerability (FC rupture, 44% versus 41%, P = .90; PH, 58% versus 47%, P = .78; large LC, 32% versus 47%, P = .17), respectively. The maximum biomechanical stress was not significantly different for both groups (241versus 278 kPa, P = .14) respectively. CONCLUSIONS: Black-blood imaging does not appear to have the ability to differentiate between the morphological and biomechanical features of plaque vulnerability when comparing patients with and without symptomatic atherosclerotic disease in a distant arterial territory such as coronary artery.

Atherosclerosis is a leading cause of mortality and long-term morbidity worldwide. It is a lipoprotein-driven disease that leads to plaque formation at focal areas in the arterial blood vessels through intimal inflammation, necrosis, fibrosis, and calcification. Adventitial and intimal angiogenesis contributes to the progression of intimal hyperplasia and the development of a necrotic core. The volatile nature of an atheromatous plaque is responsible for approximately 60% of symptomatic carotid artery diseases and about 75% of acute coronary events. In this review the pathogenesis of atherosclerosis is discussed from the initial step of lipid retention to advanced stages of immune-mediate inflammation and associated angiogenesis. Mechanisms of plaque rupture are also discussed.

Background Atherosclerosis is a systemic inflammatory disease that may affect multiple arterial beds simultaneously. Vascular distensibility is increasingly used in the clinical assessment of patients with atherosclerotic disease. In this study, we assess distensibility of symptomatic atherosclerotic carotid artery and of contralateral asymptomatic side. We also investigate the distensibility of bilaterally asymptomatic atherosclerotic carotid arteries using cine phase-contrast carotid magnetic resonance (MR) imaging. Methods Nineteen patients with bilateral carotid artery disease underwent cine phase-contrast carotid imaging on a 1.5 T MR system. Ten patients had ipsilateral symptomatic carotid artery disease and contralateral asymptomatic stenosis. Nine additional patients with bilateral asymptomatic carotid artery disease constituted historical control group. Cine phase-contrast MR imaging acquired at the common carotid artery, maximum luminal stenosis, and internal carotid artery was used to determine carotid distensibility bilaterally for carotid arteries in both patient groups. Results Symptomatic carotid arteries were found to be significantly less distensible (mean distensibility coefficient [DC] 35.4 ± 6.12 × 10−3/kPa) than the contralateral asymptomatic vessels (mean DC 54.4 ± 7.88 × 10−3/kPa, P = .03) at the level of the common carotid artery. A similar trend of high distensibility for asymptomatic side in the area of maximum stenosis and the internal carotid artery was seen, but it was not found to be statistically significant. Plaque burden was comparable between the 2 groups at all locations. DC was comparable for patients with bilateral asymptomatic carotid artery stenoses. Distensibility of bilaterally asymptomatic carotid arteries was greater than that of asymptomatic carotid artery contralateral to the symptomatic side. Conclusions Symptomatic carotid artery is stiffer than the contralateral asymptomatic side, despite comparable plaque burden. Patients with bilateral asymptomatic carotid artery disease have comparable stiffness. Larger studies are warranted to further investigate the findings of this MR study.