Blood-brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment.

Vascular disruption has been implicated in coronavirus disease 2019 (COVID-19) pathogenesis and may predispose to the neurological sequelae associated with long COVID, yet it is unclear how blood-brain barrier (BBB) function is affected in these conditions. Here we show that BBB disruption is evident during acute infection and in patients with long COVID with cognitive impairment, commonly referred to as brain fog. Using dynamic contrast-enhanced magnetic resonance imaging, we show BBB disruption in patients with long COVID-associated brain fog. Transcriptomic analysis of peripheral blood mononuclear cells revealed dysregulation of the coagulation system and a dampened adaptive immune response in individuals with brain fog. Accordingly, peripheral blood mononuclear cells showed increased adhesion to human brain endothelial cells in vitro, while exposure of brain endothelial cells to serum from patients with long COVID induced expression of inflammatory markers. Together, our data suggest that sustained systemic inflammation and persistent localized BBB dysfunction is a key feature of long COVID-associated brain fog.

Radiogenomics: Contemporary Applications in the Management of Rectal Cancer.

Radiogenomics, a sub-domain of radiomics, refers to the prediction of underlying tumour biology using non-invasive imaging markers. This novel technology intends to reduce the high costs, workload and invasiveness associated with traditional genetic testing via the development of 'imaging biomarkers' that have the potential to serve as an alternative 'liquid-biopsy' in the determination of tumour biological characteristics. Radiogenomics also harnesses the potential to unlock aspects of tumour biology which are not possible to assess by conventional biopsy-based methods, such as full tumour burden, intra-/inter-lesion heterogeneity and the possibility of providing the information of tumour biology longitudinally. Several studies have shown the feasibility of developing a radiogenomic-based signature to predict treatment outcomes and tumour characteristics; however, many lack prospective, external validation. We performed a systematic review of the current literature surrounding the use of radiogenomics in rectal cancer to predict underlying tumour biology.

Perspective: The Case for Acute Large Vessel Ischemic Stroke in COVID-19 Originating Within Thrombosed Pulmonary Venules.

The main burden of SARS-CoV-2 falls on the lungs but neurological manifestations, the most disabling of which are strokes and which correlate with disease severity, are common. We proffer a novel mechanism for acute COVID-19 stroke whereby pulmonary vein clots developing within the characteristic pulmonary intravascular thrombotic lesions can embolize to the brain. Appreciation of this mechanism requires an understanding of the tricompartmental model of lung parenchyma oxygenation (the alveolus, the bronchial artery, and the pulmonary artery), all of which are compromised in COVID-19. Of these 3 sources, the bronchial artery plays a crucial role in COVID-19 stroke because the unique collaterals from bronchial artery to pulmonary vein which exist under normal physiological conditions (and which maintain venous patency when the pulmonary artery is blocked by embolus) are occluded, thus leading to venular thrombosis in the presence of hypercoagulability. Dislodgement of clots from this source translocates the pathology to the brain and is a disease mechanism, formerly rare, which may account for many cases of large vessel occlusion stroke in COVID-19. This mechanism extends the concept of cardioembolic stroke from endocardium retrogradely into the pulmonary circulation with which the left cardiac chambers lie in direct continuity, and which is an accepted stroke mechanism under other circumstances such as lung lobectomy, where surgical ligation of the pulmonary vein creates a blind sac from which thrombi can embolize. The proposed model is supported by postmortem studies which have demonstrated venular thrombosis and by case reports of pulmonary vein thrombosis in COVID-19. This concept provides a more plausible cause for COVID-19 associated large vessel occlusion stroke than other putative mechanisms, such as cerebral endotheliitis, cytokine storm, and hypercoagulopathy, although it is acknowledged that the latter mechanism contributes to the genesis of pulmonary vein clots. Recognizing that extrapulmonary manifestations including stroke arise within thrombosed pulmonary veins is key to understanding of neurological manifestations of SARS-CoV-2 infection.

A tricompartmental model of lung oxygenation disruption to explain pulmonary and systemic pathology in severe COVID-19.

The emergent 21st century betacoronaviruses, including SARS-CoV-2, lead to clinicopathological manifestations with unusual features, such as early-onset chest pain, pulmonary infarction, and pulmonary and systemic thromboembolism that is pathologically linked to extensive capillary, arteriolar, and venular thrombosis. Early ground glass opacities detected by CT, which are reminiscent of lung infarcts associated with pulmonary embolism, point to a novel vascular pathology in COVID-19. Under physiological conditions, normal parenchymal oxygenation is maintained by three sources: the alveolus itself and dual oxygen supply from the pulmonary and bronchial artery circulations. We propose a model in which these three components are disrupted in COVID-19 pneumonia, with severe viral alveolitis and concomitant immunothrombotic obstruction of the pulmonary and bronchiolar circulation. Tricompartmental disruption might have two main consequences: systemic clot embolisation from pulmonary vein territory immunothrombosis, and alveolar-capillary barrier disruption with systemic access of thrombogenic viral material. Our model encompasses the known pathological and clinical features of severe COVID-19, and has implications for understanding patient responses to immunomodulatory therapies, which might exert an anti-inflammatory effect within the vascular compartments.

COVID-19 vasculitis and novel vasculitis mimics.

COVID-19 has been occasionally linked to histologically confirmed cutaneous vasculitis and a Kawasaki-like vasculitis, with these entities generally having minimal or no lung involvement and a good prognosis. Unlike these vasculitis types, patients with severe COVID-19 pneumonia can develop cutaneous vasculitis-like lesions and systemic arterial and venous thromboemboli, including cryptogenic strokes and other vasculopathy features. Proposed underlying mechanisms for these severe manifestations have encompassed immune dysregulation, including an anti-phospholipid syndrome-like state, complement activation, viral dissemination with direct systemic endothelial infection, viral RNAaemia with immunothrombosis, clotting pathway activation mediated by hypoxaemia, and immobility. In this Viewpoint, we highlight how imaging and post-mortem findings from patients with COVID-19 indicate a novel thrombosis in the pulmonary venous territory distal to the alveolar capillary bed, a territory that normally acts as a clot filtration system, which might represent an unappreciated nidus for systemic microembolism. Additionally, we suggest that this mechanism represents a novel vasculitis mimic related to COVID-19 that might lead to cryptogenic strokes across multivessel territories, acute kidney injury with haematuria, a skin vasculitis mimic, intestinal ischaemia, and other organ ischaemic manifestations. This finding is supported by pathological reports of extensive pulmonary venular thrombosis and peripheral organ thrombosis with pauci-immune cellular infiltrates. Therefore, severe COVID-19 pneumonia with extensive pulmonary intravascular coagulopathy might help to explain the numerous systemic complications of COVID-19, in which the demonstration of direct organ infection has not adequately explained the pathology.

Whole Body MRI in the Staging of Esophageal Cancer--A Prospective Comparison with Whole Body 18F-FDG PET-CT.

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.

Prevalence of renal artery stenosis in flash pulmonary oedema: determination using gadolinium-enhanced MRA.

PURPOSE: The primary purpose was to determine the prevalence of renal artery stenosis (RAS) in patients presenting with acute ("flash") pulmonary oedema (FPE), without identifiable cause using contrast-enhanced magnetic resonance angiography (CE-MRA) of renal arteries. A secondary goal was to correlate clinical parameters at presentation with the presence or absence of RAS. MATERIALS AND METHODS: Patients presenting with acute pulmonary oedema without identifiable cause prospectively underwent CE-MRA. >50% renal artery stenosis was considered significant. Clinical parameters (blood pressure, serum creatinine, history of hypertension/hyperlipidaemia) were compared in patients with and without RAS using an unpaired t-test. Results expressed; mean (+/-SD). RESULTS: 20 patients (4 male, 16 female, age 78.5+/-11 years) underwent CE-MRA. 9 patients (45%) had significant RAS (6 (30%) bilateral, 3 (15%) unilateral). Systolic BP was higher in patients with RAS (192+/-38 mm Hg) than those without (134+/-30 mm Hg) (p<.005). Diastolic BP was higher in patients with RAS (102+/-23 mm Hg) than those without (76+/-17 mm Hg) (p<.01). All patients with RAS and 6/11(55%) patients without RAS had a history of hypertension. No significant difference in creatinine or hyperlipidaemia history was observed. CONCLUSION: The prevalence of RAS in patients presenting with FPE is 45%. The diagnosis should be considered in patients presenting with unexplained acute pulmonary oedema, particularly if hypertensive at presentation.

Whole-body MR imaging in a multimodality world: current applications, limitations, and future potential for comprehensive musculoskeletal imaging.

Whole-body imaging offers the promise of global disease assessment. This article reviews clinical status, and technical limitations and future prospects of this exciting technology. In particular, it describes technical aspects of magnetic resonance (MR) angiography, MR lymphography, and, in particular, total-body MR imaging.

Giant iliopsoas bursitis: a complication of chronic arthritis.

Iliopsoas bursitis is a poorly recognized cause of hip pain that requires early recognition to avoid potentially serious complications caused by compression of adjacent structures. It can occur in the setting of trauma in athletes or those who engage in heavy labor and is also associated with acute or chronic arthritis. We describe the cases of 2 patients, one of whom developed a femoral neuropathy, while the other had marked venous compression of the lower limb resulting from enlargement of the iliopsoas bursa. Magnetic resonance imaging offers the most accurate information on the extent of the problem. Recalcitrant cases may require bursectomy in addition to treatment of the underlying cause.

Magnetic resonance angiography of abdominal vessels at 3 T.

Magnetic resonance angiography (MRA) has evolved significantly since first described in the early 1990s. Unrivaled image quality and freedom from artifacts has made it a reliable and widely utilized technique. Imaging at 3 T offers the potential for higher resolutions images with better temporal resolution compared to 1.5 T. This article will review the technique and contrast agents required to perform MRA at 3 T and the relevant clinical applications. We also discuss non-contrast enhanced MRA in the era of nephrogenic systemic fibrosis and future prospect for MRA at 3 T.

Recent advances in contrast-enhanced magnetic resonance angiography.

Magnetic resonance angiography (MRA) provides a means of visualizing vascular structures noninvasively and is increasingly replacing conventional X-ray angiography in routine use. Contrast-enhanced MRA (CE-MRA), in which gadolinium contrast agents are used to shorten the T1 relaxation, offers increased resolution and higher signal-to-noise ratio compared with earlier flow-dependent [time-of-flight (TOF) or phase-contrast (PC)] techniques. Currently available contrast agents differ in their ability to lower T1 values, and hence the choice of contrast agent is an important consideration in the successful use of CE-MRA. Gadofosveset trisodium (Vasovist, Bayer Schering Pharma AG, Berlin, Germany) is the first of a new class of intravascular contrast agents. This agent is extensively (approximately 85%) and reversibly bound to human serum albumin and is retained within the vasculature thus allowing steady-state imaging to be perform-ed. An additional benefit is that gadofosveset offers higher relaxivity compared with other contrast agents, thus giving a lower blood T1 values which also makes it ideal for first-pass imaging. Clinical trials have consistently shown that gadofosveset enhanced MRA is more sensitive, specific and accurate than time-of-flight MRA, gives fewer uninterpretable scans and affords greater diagnostic confidence. Intravascular contrast agents such as gadofosveset, therefore, offer the potential for improved vascular imaging.

Magnetic resonance angiography of the head and neck vessels.

Stroke, a major cause of death and disability in the developed world, is usually caused by atherosclerosis, most commonly an arterioocclusive lesion at the carotid bifurcation. Numerous multicentre trials have demonstrated that carotid endarterectomy can reduce the risk of stroke in these patients. However, because of the morbidity of catheter angiography coupled with the risks of surgery, the benefits outweigh the risks of surgery only for those with >70% carotid artery stenosis. The gold standard method for assessing the degree of stenosis is catheter-directed cerebral digital subtraction angiography; however, this is associated with a small but substantial stroke risk in addition to inherent risks associated with use of ionizing radiation and nephrotoxic contrast agents. The requirement for alternative imaging techniques that do not contribute to morbidity is ideally met by contrast-enhanced magnetic resonance angiography, which eliminates the need for direct catheterization and therefore eliminates stroke risk associated with a patient work-up. Advances in contrast-enhanced magnetic resonance angiography technology have led to a technique that achieves the goals of high spatial and temporal resolution required for stenosis assessment and streamlining of patients along surgical or medical lines. With the advent of a novel contrast agent, gadofosveset trisodium (Vasovist, Bayer Schering Pharma AG, Berlin, Germany), which has a high relaxivity and an extended imaging time, improved diagnosis of carotid artery stenoses with magnetic resonance angiography can be expected. Gadofosveset trisodium facilitates improved first-pass imaging and also delays steady-state imaging with one injection. Although developed for vascular imaging, gadofosveset trisodium may also allow assessment of brain vascularity, blood-brain barrier breakdown and neurodegenerative disease.

Expanding role of MR angiography in clinical practice.

MRA has higher accuracy, less operator dependence, a larger field-of-view, three-dimensionality and superior contrast resolution than ultrasonography. Additionally, MRA offers a safer alternative to the patient than CTA as neither ionizing radiation nor iodinated contrast agents are used. Contrast-enhanced MRA with extra cellular contrast agents is fast and flow-independent, offers substantially higher spatial and temporal resolution compared to non-contrast techniques and has become the standard of practice. The highly accurate but static anatomical road-map thus generated can be supplemented with time-resolved MRA and blood flow measurement techniques for a more comprehensive assessment of systemic vascular disease. In the context of burgeoning technological advances with rapid translation into clinical MRA practice, this review explores the current position of MRA and the potential role for the new and exciting blood-pool contrast agents for diagnosing and characterizing vascular disease. Blood-pool agents offer the potential to take MRA to the next level by combining first-pass arterial phase imaging with steady state high-resolution images that exploit the persistent high intravascular enhancement generated by blood-pool agents and which is significantly greater than with extra cellular agents. Additional benefits derive from the ability to characterize plaque and to detect internal bleeding. These advantages place MRA in a prime position to comprehensively and non-invasively evaluate both vascular anatomy and function with anticipated further expansion into more and more clinical applications.

Contrast-enhanced MR angiography of subclavian steal syndrome: value of the 2D time-of-flight "localizer" sign.

OBJECTIVE: Our objective was to determine if direction of flow within the vertebral artery could be reliably determined by evaluation of flow-sensitive, low-resolution 2D time-of-flight (TOF) localizer images taken before 3D contrast-enhanced MR angiography (3D CEMRA) sequences in patients with unsuspected subclavian steal syndrome. CONCLUSION: Vertebral artery patency on 3D CEMRA in cases in which the vessel is absent on the TOF localizer in association with ipsilateral subclavian artery stenosis indicates reversal of flow in the vertebral artery and confirms the subclavian steal phenomenon. The combination of anatomic imaging with 3D CEMRA with functional information provided by the low-resolution TOF localizer confirms the diagnosis of subclavian steal without additional imaging.

Normal anterior spinal arteries within the cervical region: high-spatial-resolution contrast-enhanced three-dimensional MR angiography.

PURPOSE: To determine retrospectively whether the anterior spinal artery (ASA) is visualized in the cervical region with contrast material-enhanced high-spatial-resolution three-dimensional magnetic resonance (MR) angiography of the extracranial carotid and vertebral arteries. MATERIALS AND METHODS: The institutional research ethics committee approved this study and provided a waiver for informed consent. Data sets were evaluated in 50 consecutive patients referred for contrast-enhanced three-dimensional MR angiography of the carotid arteries (32 male and 18 female patients; age range, 15-80 years; mean age, 59 years). The ASA was defined as a linear area of high signal intensity that is seen anterior to the spinal cord in an arterial phase of enhancement and connects directly to a known arterial structure. If the linear area of high signal intensity was seen in the arterial phase but did not connect to a known arterial structure, it was considered a probable ASA. Venous enhancement was graded on a five-point scale (0-4) with grade 0 (no venous enhancement) or grade 1 (trace venous enhancement) considered to be in the arterial phase. RESULTS: The ASA was identified with certainty in 37 of 50 patients. A vessel visualized anterior to the spinal cord, which probably represented the ASA, was seen in another 11 of 50 patients. In 29 of 50 patients the vessel was visualized only on the full-volume maximum intensity projection (MIP) image. In the remainder of cases the artery was identified on operator-defined subvolume MIP images. Continuity between the vessel and the vertebrobasilar arterial structures was identified in 35 of 50 patients. The vessel was seen as a continuous structure throughout its length in 34 patients and appeared discontinuous in 14. Radiculomedullary feeders were identified in 24 of 50 patients. CONCLUSION: The normal cervical ASA was visualized in 48 of 50 of subjects with contrast-enhanced high-spatial-resolution three-dimensional MR angiography.

Renal artery aneurysms: diagnosis and surveillance with 3D contrast-enhanced magnetic resonance angiography.

The use of contrast-enhanced magnetic resonance angiography (CE-MRA) in screening for suspected renovascular disease may result in increased detection of renal artery aneurysms. We report the CE-MRA findings at diagnosis and follow-up in nine hypertensive patients with unsuspected renal artery aneurysms. A search of renal CE-MRAs of suspected renal artery stenosis at two tertiary referral institutions over 5 1/2 years was performed. All patients underwent CE-MRA using a fast spoiled gradient echo technique (TR/TE/flip 5.1-6 ms/1.6 ms/40 degrees), scan matrix 512 x 196-224, 1 excitation, FOV 400-450 mm x 266-360 mm, 32-50 mm x 1.5-2 mm interpolated slices. Gadolinium-enhanced 3D images were obtained during breath holding. Images were evaluated and post-processed on a workstation by a single operator. Nine patients with renal artery aneurysms out of a total of 912 cases were found, all involving the main artery or divisions proximal to the renal hilum. Renal arteries distal to the hilum were not consistently visualized. The aneurysm was bilobed in one patient, multilocular in another and unilocular in all others. Severe stenosis of the renal artery proximal to the aneurysm was present in two. Four patients underwent follow-up showing no change in aneurysm size. CE-MRA reliably identifies aneurysms involving the main renal arteries and proximal branches. Once diagnosed, CE-MRA offers a safe, non-invasive modality for surveillance of aneurysm if active intervention is not planned.