Gadolinium-based Contrast Research Articles

Relationship Between Patient-Friendly Audiovisual Systems and MRI Contrast Agent to Adverse Reactions.

Patient-friendly audiovisual (AV) systems in head MRI examinations can potentially reduce patient anxiety and contrast-enhanced MRI (CE-MRI) adverse reactions to gadolinium. To evaluate whether a patient-friendly AV system reduces the rate of adverse reactions to gadolinium-based contrast agents. Retrospective. Four thousand eight hundred thirty-two outpatients (2462 female) attending for clinical CE-MRI studies. (Gadoteridol: 1971, Meglumine gadoterate: 2733, Gadobutrol: 128.) FIELD STRENGTH/SEQUENCE: Routine CE-MRI of head and neck using a 1.5 T or 3 T scanner with or without a patient-friendly AV system. One thousand one hundred fifty-nine patients were scanned on MRI machines equipped with patient-friendly AV systems (AV group) and 3673 on MRI machines without AV systems (control group). Adverse reaction rate and symptoms were reviewed by referring to the system database and electronic medical records and compared between the two groups. Adverse reactions were defined as physiological reactions, such as vomiting and allergic-like reactions, such as urticaria, occurring within 1 hour of contrast injection. We compare patient backgrounds, adverse reaction rate, adverse reactions symptoms and the severity between the two groups. Adverse reaction rate with and without a patient-friendly AV system were compared using Fisher's exact test. The relationship between patient-friendly AV systems and the occurrence of adverse reactions was evaluated with logistic regression. Statistical significance was set at P < 0.05. Of the 4832 patients enrolled, 65 (1.35%) experienced adverse reactions. The most common adverse reactions in both groups were urticaria and pruritus. Adverse reaction rate was significantly lower in the AV group than in the control group (0.7% vs. 1.6%). No significant difference was observed in the severity (P = 1.000) of adverse reactions and symptoms (allergic-like reaction: P = 0.08, physiologic reaction: P = 1.000) between the two groups. The patient-friendly AV system significantly reduce adverse reaction occurrence to gadolinium-based contrast agents. 4 TECHNICAL EFFICACY: Stage 1.

Review of the Efficacy and Safety of Gadopiclenol: A Newly Emerging Gadolinium-Based Contrast Agent.

Gadolinium-based contrast agents (GBCAs) are one of the most commonly used agents in magnetic resonance imaging. Gadopiclenol is a new GBCA aimed at providing improved diagnostic efficacy with a favorable safety profile. The proposed advantages are due to its specific pharmacological properties, one of which is high relaxivity values. The aim of this review is to assess the efficacy, diagnostic accuracy, and safety of gadopiclenol in comparison to other currently used gadolinium-based contrast agents. PubMed and other database systems were used to identify relevant studies. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed, resulting in 10 articles that were included in the review. The outcomes were reviewed according to several factors regarding efficacy and accuracy in terms of qualitative and quantitative descriptors relative to properties of enhancement provided by the contrast agent. In terms of safety profile, a number of outcomes were assessed such as the occurrence of serious adverse effects, severe kidney injury, and organ-based contrast retention. Gadopiclenol was found to provide outcomes comparable to other commonly used GBCAs at lower doses with further favorable results at higher doses while maintaining an acceptable safety profile. However, it was found to have high rates of retention within the liver and can cause nonsignificant QT prolongation in healthy individuals, which arguably creates the need for further research regarding more long-term implications of these possible adverse effects.

NEIM-15 AN EXCEPTION TO THE METASTATIC RULE: A NON-ENHANCING MIDBRAIN LESION DUE TO METASTATIC FIBROMYXOID SARCOMA WITH EXTENSIVEINFLAMMATORY INFILTRATE

Abstract Metastases from extra-CNS sites typically enhance on MR after the administration of gadolinium-based contrast agents due to disruption of the blood-brain barrier. Fibromyxoid sarcoma involving the brain is extremely rare, with only a few reported cases manifesting as well-circumscribed enhancing masses. Here, we report an extremely rare non-enhancing brain metastasis secondary to an already rare sarcoma. A 44-year-old woman with gluteal fibromyxoid sarcoma metastatic to cervical paraspinal muscles and adrenal gland treated with ipilimumab/nivolumab presented with diplopia and was found to have an 8 mm T2-hyperintense midbrain lesion without enhancement or mass effect. An inflammatory etiology associated with checkpoint inhibitor therapy was suspected, and she was treated with IV methylprednisolone 1 g daily for 3 days followed by an oral prednisone taper, IV immunoglobulin, and plasma exchange without improvement. The midbrain lesion steadily grew over 15 months of follow up, eventually involving the bilateral medial thalami and demonstrating diffusion restriction in the midbrain, but never showing gadolinium enhancement. The imaging was reminiscent of peripheral brainstem non-enhancing band-like lesions reported in leptomeningeal lung cancer, however CSF cytology was repeatedly normal, as was extensive infectious and inflammatory testing. Her neurologic disability continued to progress, with development of bilateral oculomotor nerve palsies, dysarthria, and depressed level of alertness, devolving into non-convulsive status epilepticus requiring intubation. She died six months after onset of neurologic symptoms. At autopsy, histologic and immunohistochemical evaluation revealed fibromyxoid sarcoma (MUC-4 positive, TAOK1-FUS fusion) centered on the periventricular aqueduct with accompanying disseminated single-cell infiltration throughout the midbrain. The background midbrain and periventricular parenchyma were notable for voluminous microglial activation and histiocytic infiltrate. In sum, this case represents a radiographically unique sarcoma brain metastasis which on pathologic exam showed robust inflammatory changes far out of proportion to the tumor present.

Krackow Suture Technique effect on Patella Tendon Vascularity: Quantitative-MRI Analysis.

To assess the effects of Krackow suture technique on the vascularity of the patellar tendon. Six fresh-frozen matched pair cadaveric knee specimens were utilized. The superficial femoral arteries were cannulated in all knees. The experimental knee underwent an anterior approach, patellar tendon transection from the inferior pole of the patella, four-strand Krackow stitch placement, patellar tendon repair via 3-bone tunnels, and standard skin closure. The control knee underwent the identical procedure without Krackow stitching. All specimens then underwent pre- and post-contrast enhanced quantitative magnetic resonance imaging (qMRI) assessment (with gadolinium-based contrast agent). Region of interest (ROI) analysis was performed to assess for variation in signal enhancement between the experimental and control limbs in various patellar tendon regions and subregions. Latex infusion and anatomical dissection were performed to further evaluate vessel integrity and assess extrinsic vascularity. qMRI analysis demonstrated no statistically significant difference in overall arterial contributions. A small but non-significant decrease of 7.5% (SD ±7.1%) in arterial contributions to the entire tendon was observed. Small non-statistically significant regional decreases throughout the tendon were also detected. In the regional analysis, the largest to smallest decreases in arterial contributions following suture placement were found in the inferomedial, superolateral, lateral, and inferior tendon subregions. In the anatomical dissection, nutrient branches were seen dorsally and posteroinferiorly. The vascularity of the patellar tendon was not significantly affected by Krackow suture placement. Analysis demonstrated small and not statistically significant decreases in arterial contributions suggesting this technique does not significantly compromise arterial perfusion.

Biomonitoring of rare earth elements in Southern Norway: Distribution, fractionation, and accumulation patterns in the marine bivalves Mytilus spp. and Tapes spp.

Growing extraction and usage of rare earth elements and yttrium (REY) for medical and industrial applications has resulted in increased discharges into the marine environment. Using Mytilus spp. Mussels and Tapes spp. clams as bioindicator organisms, we analyzed 15 REY in soft tissues of specimens collected at two potentially polluted sites in Southern Norway: in the vicinity of an industry producing gadolinium-based MRI contrast agents (GBCAs) (Lindesnes) and in an industrially-affected fjord (Porsgrunn). The spatial distribution of REY and shale-normalized fractionation patterns were determined to assess the potential anthropogenic contribution of REY at the sites. At both sites, the REY fractionation pattern in soft tissue was characterized by enrichment of light rare earth elements (LREE) over heavy rare earth elements (HREE), while also displaying negative cerium and small positive gadolinium (Gd) anomalies. LREEs contributed to over 80% of the total REY concentrations, with increasing relative enrichment following higher total REY. Gd anomalies remained conserved in most sites despite significant differences in total REY; however, a high Gd anomaly (Gd/Gd* = 4.4) was found downstream of the GBCA industry spillwater outlet, indicating biotic uptake of excess anthropogenic Gd at this site. Total REY concentrations in clams in Porsgrunn were one order of magnitude higher than in mussels in Lindesnes. This may be attributable to freshwater influences in Porsgrunn, where clams collected closer to the river mouth had significantly higher total REY concentrations. This study constitutes the first assessment of REY concentrations in marine bivalves in Norway and can provide useful information for future biomonitoring studies on REY contamination.

Influence of gadolinium, field-strength and sequence type on quantified perfusion values in phase-resolved functional lung MRI.

The purpose of this study is to evaluate the influences of gadolinium-based contrast agents, field-strength and different sequences on perfusion quantification in Phase-Resolved Functional Lung (PREFUL) MRI. Four cohorts of different subjects were imaged to analyze influences on the quantified perfusion maps: 1) at baseline and after 2 weeks to obtain the reproducibility (26 COPD patients), 2) before and after the administration of gadobutrol (11 COPD, 2 PAH and 1 asthma), 3) at 1.5T and 3T (12 healthy, 4 CF), and 4) with different acquisition sequences spoiled gradient echo (SPGR) and balanced steady-state free precession (bSSFP) (11 COPD, 7 healthy). Wilcoxon-signed rank test, Bland-Altman plots, voxelwise Pearson correlations, normalized histogram analyses with skewness and kurtosis and two-sample Kolmogorov-Smirnov tests were performed. P value ≤ 0.05 was considered statistically significant. In all cohorts, linear correlations of the perfusion values were significant with correlation coefficients of at least 0.7 considering the entire lung (P<0.01). The reproducibility cohort revealed stable results with a similar distribution. In the gadolinium cohort, the quantified perfusion increased significantly (P<0.01), and no significant change was detected in the histogram analysis. In the field-strength cohort, no significant change of the quantified perfusion was shown, but a significant increase of skewness and kurtosis at 3T (P = 0.01). In the sequence cohort, the quantified perfusion decreased significantly in the bSSFP sequence (P<0.01) together with a significant decrease of skewness and kurtosis (P = 0.02). The field-strength and sequence cohorts had differing probability distribution in the two-sample Kolmogorov-Smirnov tests. We observed a high susceptibility of perfusion quantification to gadolinium, field-strength or MRI sequence leading to distortion and deviation of the perfusion values. Future multicenter studies should strictly adhere to the identical study protocols to generate comparable results.

Half-Dose versus Single-Dose Gadobutrol for Extracellular Volume Measurements in Cardiac Magnetic Resonance.

Cardiac magnetic resonance (CMR) imaging with gadolinium-based contrast agents offers unique non-invasive insights into cardiac tissue composition. Myocardial extracellular volume (ECV) has evolved as an objective and robust parameter with broad diagnostic and prognostic implications. For the gadolinium compound gadobutrol, the recommended dose for cardiac imaging, including ECV measurements, is 0.1 mmol/kg (single dose). This dose was optimized for late enhancement imaging, a measure of focal fibrosis. Whether a lower dose is sufficient for ECV measurements is unknown. We aim to evaluate the accuracy of ECV measurements using a half dose of 0.05 mmol/kg gadobutrol compared to the standard single dose of 0.1 mmol/kg. From a contemporary trial (NCT04747366, registered 10 February 2021), a total of 25 examinations with available T1 mapping before and after 0.05 and 0.1 mmol/kg gadobutrol were analyzed. ECV values were calculated automatically from pre- and post-contrast T1 relaxation times. T1 and ECV Measurements were performed in the midventricular septum. ECV values after 0.05 and 0.1 mmol/kg gadobutrol were correlated (R2 = 0.920, p < 0.001). ECV values after 0.05 mmol/kg had a bias of +0.9% (95%-CI [0.4; 1.4], p = 0.002) compared to 0.1 mmol/kg gadobutrol, with limits of agreement from -1.5 to 3.3%. CMR with a half dose of 0.05 mmol/kg gadobutrol overestimated ECV by 0.9% compared with a full dose of 0.1 mmol/kg, necessitating adjustment of normal values when using half-dose ECV imaging.

Arterial Spin Labeling (ASL) in Neuroradiological Diagnostics - Methodological Overview and Use Cases.

Arterial spin labeling (ASL) is a magnetic resonance imaging (MRI)-based technique using labeled blood-water of the brain-feeding arteries as an endogenous tracer to derive information about brain perfusion. It enables the assessment of cerebral blood flow (CBF). This review aims to provide a methodological and technical overview of ASL techniques, and to give examples of clinical use cases for various diseases affecting the central nervous system (CNS). There is a special focus on recent developments including super-selective ASL (ssASL) and time-resolved ASL-based magnetic resonance angiography (MRA) and on diseases commonly not leading to characteristic alterations on conventional structural MRI (e. g., concussion or migraine). ASL-derived CBF may represent a clinically relevant parameter in various pathologies such as cerebrovascular diseases, neoplasms, or neurodegenerative diseases. Furthermore, ASL has also been used to investigate CBF in mild traumatic brain injury or migraine, potentially leading to the establishment of imaging-based biomarkers. Recent advances made possible the acquisition of ssASL by selective labeling of single brain-feeding arteries, enabling spatial perfusion territory mapping dependent on blood flow of a specific preselected artery. Furthermore, ASL-based MRA has been introduced, providing time-resolved delineation of single intracranial vessels. Perfusion imaging by ASL has shown promise in various diseases of the CNS. Given that ASL does not require intravenous administration of a gadolinium-based contrast agent, it may be of particular interest for investigations in pediatric cohorts, patients with impaired kidney function, patients with relevant allergies, or patients that undergo serial MRI for clinical indications such as disease monitoring. · ASL is an MRI technique that uses labeled blood-water as an endogenous tracer for brain perfusion imaging.. · It allows the assessment of CBF without the need for administration of a gadolinium-based contrast agent.. · CBF quantification by ASL has been used in several pathologies including brain tumors or neurodegenerative diseases.. · Vessel-selective ASL methods can provide brain perfusion territory mapping in cerebrovascular diseases.. · ASL may be of particular interest in patient cohorts with caveats concerning gadolinium administration..

The combination of non-contrast abbreviated MRI and alpha foetoprotein has high performance for hepatocellular carcinoma screening

ObjectivesThis study aimed to compare two abbreviated MRI (AMRI) protocols to complete MRI for HCC detection: non-contrast (NC)-AMRI without/with alpha foetoprotein (AFP) and dynamic contrast-enhanced (Dyn)-AMRI.MethodsThis retrospective single-center study included 351 patients (M/F: 264/87, mean age: 57y) with chronic liver disease, who underwent MRI for HCC surveillance between 2014 and 2020. Two reconstructed AMRI sets were obtained based on complete MRI: NC-AMRI (T2-weighted imaging (WI) + diffusion-WI) and Dyn-AMRI (T2-WI + dynamic T1-WI) and were assessed by 2 radiologists who reported all suspicious lesions, using LI-RADS/adapted LI-RADS classification. The reference standard was based on all available patient data. Inter-reader agreement was assessed and MRI diagnostic performance was compared to the reference standard.ResultsThe reference standard demonstrated 83/351 HCC-positive patients (prevalence: 23.6%, median size: 22 mm, and positive MRIs: 83/631). Inter-reader agreement was substantial for all sets. Sensitivities of Dyn-AMRI and complete MRI (both 92.8%) were similar, higher than NC-AMRI (72.3%, p < 0.001). Specificities were not different between sets. NC-AMRI + AFP (92.8%) had similar sensitivity to Dyn-AMRI and complete MRI. In patients with small size HCCs (≤ 2 cm), sensitivities of Dyn-AMRI (85.3%) and complete MRI (88.2%) remained similar (p = 0.564), also outperforming NC-AMRI (52.9%, p < 0.05). NC-AMRI + AFP had similar sensitivity (88.2%) to Dyn-AMRI and complete MRI (p = 0.706 and p = 1, respectively).ConclusionsDyn-AMRI has similar diagnostic performance to complete MRI for HCC detection, while both outperform NC-AMRI, especially for small size HCCs. NC-AMRI + AFP demonstrates similar sensitivity to Dyn-AMRI and complete MRI.Clinical relevance statementDue to the low sensitivity of ultrasound for hepatocellular screening, new screening methods are needed. Abbreviated MRI (AMRI) is a candidate, especially non-contrast AMRI with serum alpha foetoprotein as the acquisition time is low, without the need for contrast medium injection.Key Points• Dynamic contrast-enhanced abbreviated MRI using extracellular gadolinium-based contrast agent and complete MRI have similar diagnostic performance for hepatocellular carcinoma detection in an at-risk population.• Non-contrast abbreviated MRI with alpha foetoprotein has similar diagnostic performance to dynamic contrast-enhanced abbreviated MRI and complete MRI, including when considering small size hepatocellular carcinoma ≤ 2 cm.• Non-contrast abbreviated MRI and dynamic contrast-enhanced abbreviated MRI can be performed in 7 and 10 min, excluding patient setup time.

Analysis of the elemental species-dependent uptake of lanthanide complexes in Arabidopsis thaliana plants by LA-ICP-MS

Gadolinium-based contrast agents (GBCAs) are found increasingly in different water bodies, making the investigation of their uptake and distribution behavior in plants a matter of high interest to assess their potential effects on the environment. Depending on the used complexing agent, they are classified into linear or macrocyclic GBCAs, with macrocyclic complexes being more stable. In this study, by using TbCl3, Gd-DTPA-BMA, and Eu-DOTA as model compounds for ionic, linear, and macrocyclic lanthanide species, the elemental species-dependent uptake into leaves of Arabidopsis thaliana under identical biological conditions was studied. After growing for 14 days on medium containing the lanthanide species, the uptake of all studied compounds was confirmed by means of laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). Furthermore, the uptake rate of TbCl3 and the linear Gd-DTPA-BMA was similar, with Tb and Gd hotspots colocated in the areas of hydathodes and the trichomes of the leaves. In contrast, in the case of the macrocyclic Eu-DOTA, Eu was mainly located in the leaf veins. Additionally, Eu was colocated with Tb and Gd in the hydathode at the tip of the leave. Removal of the lanthanide species from the medium led to a decrease in signal intensities, indicating their subsequent release to some extent. However, seven days after the removal, depositions of Eu, Gd, and Tb were still present in the same areas of the leaves as before, showing that complete elimination was not achieved after this period of time. Overall, more Eu was present in the leaves compared to Gd and Tb, which can be explained by the high stability of the Eu-DOTA complex, potentially leading to a higher transport rate into the leaves, whereas TbCl3 and Gd-DTPA-BMA could interact with the roots, reducing their mobility.

Noninvasive investigations of human glymphatic dynamics in a diseased model.

To explore human glymphatic dynamics in a diseased model via a noninvasive technique. Patients with reversible vasoconstriction syndrome (RCVS) presenting with blood-brain barrier disruption, i.e., para-arterial gadolinium leakage on 3-T 3-dimensional isotropic contrast-enhanced T2-fluid-attenuated inversion recovery (CE-T2-FLAIR) magnetic resonance imaging (MRI), were prospectively enrolled. Consecutive 9-min-CE-T2-FLAIR for 5-6 times (early panel) after intravenous gadolinium-based contrast agent (GBCA) administration and one time-varying deferred scan of noncontrast T2-FLAIR (delayed panel) were performed. In Bundle 1, we measured the calibrated signal intensities (cSIs) of 10 different anatomical locations. In Bundle 2, brain-wide measurements of para-arterial glymphatic volumes, means, and medians of the signal intensities were conducted. We defined mean (mCoIs) or median (mnCoIs) concentration indices as products of volumes and signal intensities. Eleven subjects were analyzed. The cSIs demonstrated early increase (9min) in perineural spaces: (cranial nerve [CN] V, p = 0.008; CN VII + VII, p = 0.003), choroid plexus (p = 0.003), white matter (p = 0.004) and parasagittal dura (p = 0.004). The volumes, mCoIs, and mnCoIs demonstrated increasing rates of enhancement after 9 to 18min and decreasing rates after 45 to 54min. The GBCA was transported centrifugally and completely removed within 961-1086min after administration. The exogenous GBCA leaked into the para-arterial glymphatics could be completely cleared around 961 to 1086min after administration in a human model of BBB disruption. The tracer enhancement started variously in different intracranial regions but was eventually cleared centrifugally to brain convexity, probably towards glymphatic-meningeal lymphatics exits. Glymphatic clearance time intervals and the centrifugal directions assessed by a noninvasive approach may have implications for clinical glymphatic evaluation in the near future. • This study aimed to investigate the human glymphatic dynamics in a noninvasive diseased model. • The intracranial MR-detectable gadolinium-based contrast agents were removed centrifugally within 961 to 1086min. • The glymphatic dynamics was demonstrable by enhancing MRI in an in vivo diseased model noninvasively.

Gadolinium-based contrast agents suppress adipocyte differentiation in 3T3-L1 cells

Gadolinium-based contrast agents (GBCAs) are widely used in magnetic resonance imaging (MRI) to improve the sensitivity and enhance diagnostic performance. GBCAs are mostly eliminated from the body through the kidney after administration; however small amounts of gadolinium are retained in the brain and other tissues. Although there is increasing concern about the adverse health effects of gadolinium, the cellular effects of GBCAs remains poorly understood. Here, we elucidated the potential cytotoxicity of the GBCAs Omniscan and Gadovist in 12 different cell lines, especially 3T3-L1 adipocyte cell line. Omniscan and Gadovist treatments significantly increased intracellular gadolinium levels in 3T3-L1 cells in a time- and dose-dependent manner. Additionally, Omniscan and Gadovist treatments downregulated the expression of adipocyte differentiation markers, including peroxisome proliferator-activated receptor γ (PPARG), adiponectin (ADIPOQ), and fatty acid-binding protein (FABP4), in 3T3-L1 cells, especially during early differentiation (day 0–2). Moreover, histological analysis using Oil red O staining showed that gadolinium chloride (GdCl3) treatment suppressed lipid droplet accumulation and the expression of adipocyte differentiation markers. Overall, the results showed that Omniscan and Gadovist treatment suppressed adipocyte differentiation in 3T3-L1 cells, contributing to the understanding of the potential toxic effects of GBCA exposure.

Tissue characterization of benign cardiac tumors by cardiac magnetic resonance imaging, a review of core imaging protocol and benign cardiac tumors.

Generally, cardiac masses are initially suspected on routine echocardiography. Cardiac magnetic resonance (CMR) imaging is further performed to differentiate tumors from pseudo-tumors and to characterize the cardiac masses based on their appearance on T1/T2-weighted images, detection of perfusion and demonstration of gadolinium-based contrast agent uptake on early and late gadolinium enhancement images. Further evaluation of cardiac masses by CMR is critical because unnecessary surgery can be avoided by better tissue characterization. Different cardiac tissues have different T1 and T2 relaxation times, principally owing to different internal biochemical environments surrounding the protons. In CMR, the signal intensity from a particular tissue depends on its T1 and T2 relaxation times and its proton density. CMR uses this principle to differentiate between various tissue types by weighting images based on their T1 or T2 relaxation times. Generally, tumor cells are larger, edematous, and have associated inflammatory reactions. Higher free water content of the neoplastic cells and other changes in tissue composition lead to prolonged T1/T2 relaxation times and thus an inherent contrast between tumors and normal tissue exists. Overall, these biochemical changes create an environment where different cardiac masses produce different signal intensity on their T1- weighted and T2- weighted images that help to discriminate between them. In this review article, we have provided a detailed description of the core CMR imaging protocol for evaluation of cardiac masses. We have also discussed the basic features of benign cardiac tumors as well as the role of CMR in evaluation and further tissue characterization of these tumors.

Quantification of extracellular volume with cardiac computed tomography in patients with left ventricle dysfunction

Abstract Funding Acknowledgements Type of funding sources: None. Background Myocardial fibrosis (MF) is a common endpoint in the majority of pathological mechanisms affecting cardiac muscle, ultimately resulting in cardiac failure. Cardiovascular magnetic resonance (CMR) with gadolinium-based contrast agent and T1 mapping technique is able to deliver a non-invasive quantification of the extracellular volume (ECV) expansion. Recently, ECV estimation with cardiac computed tomography (ECV-CCT) has been validated in the setting of cardiac amyloidosis, showing good agreement with ECV-CMR. However, no evidence is available with last generation single source single energy CT scanner in the clinical context of newly diagnosed left ventricular dysfunction. Therefore, the aim of this study is to test the diagnostic accuracy of ECV-CCT for the detection of MF in patients with recent diagnosis of reduced left ventricle ejection fraction (LVEF), having ECV-CMR as reference technique. Methods A consecutive cohort of 41 patients with newly diagnosed left ventricle dysfunction (LVEF &amp;lt; 50%) was enrolled. Time interval of maximum 30 days was present between CCT and CMR. Myocardial segment evaluability with each technique, agreement between ECV-CMR and ECV-CCT, regression analysis and Bland-Altman analysis were performed. Results Age of enrolled patients was 62 ± 11 years, and mean LVEF at CMR was 35.2 ± 10.7%. Mean total amount of administrated iodinated contrast was 112.6 ± 22.2 ml, while overall radiation exposure for ECV estimation was 2.1 ± 1.1 mSv. Out of 656 myocardial segments available, 656 (100%) segments were evaluable at CCT while 640 (97.6%) were evaluable at CMR. ECV-CCT demonstrated slightly lower values compared to ECV-CMR both at global and region-based comparison (all segments, 33.1 ± 8.5% vs 35.5 ± 10.7%, p &amp;lt; 0.001). At regression analysis, strong correlations were described both at global and region-based analysis (all segments, r = 0.877, 95%CI: 0.840 to 0.914). On Bland-Altman analysis, bias between ECV-CMR and ECV-CCT for global analysis was 2.4 (95%CI: −7.8 to 12.7). Conclusions ECV estimation with last-generation single source single energy CT scanner is feasible and accurate. Integration of ECV measurement in comprehensive CCT evaluation of patients with newly diagnosed left ventricular dysfunction can be performed with a small increase in overall radiation exposure.

Quantification of myocardial blood flow using stress cardiac magnetic resonance for the detection of coronary artery disease

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): GE Healthcare. Background Myocardial blood flow (MBF) analysis using stress cardiac magnetic resonance (CMR) has been shown to detect obstructive coronary artery disease (CAD); however, evaluation of its diagnostic performance has primarily been limited to single-center studies. AQUA-MBF (Assessment of QUAntitative MBF using stress CMR) is an international study with the goal of assessing the diagnostic performance of stress MBF for the detection of CAD. In this study, we aim to determine how stress MBF assessment compared against visual analysis (VA) of stress CMR images for the detection of CAD. Methods. 144 individuals (89 (62%) men, age 62±16 years, 97 (68%) hypertension, 54 (38%) diabetes, 92 (64%) hyperlipidemia) from 9 centers who underwent dual sequence stress CMR (1.5T or 3.0T GE Healthcare) and also had either a coronary computed tomography angiography (CTA, n=31), invasive coronary angiogram (ICA, n=95), or low pre-test probability for CAD (n=18) were included. CAD was defined as the presence of: (1) a stenosis ≥50% in the left main coronary artery or ≥70% in the 1 major vessel based on ICA or CTA or (2) an invasive fractional flow reserve (FFR) ≤ 0.8. Absence of obstructive coronary disease (NOCAD) was defined as a no history of myocardial infarction and stenosis &amp;lt;50% by ICA or CTA, 50–70% stenosis with FFR&amp;gt;0.8, or a young individual with no cardiac risk factors. Myocardial perfusion imaging was performed during first pass perfusion of a gadolinium-based contrast agent following the administration of adenosine or regadenoson with a low-resolution image acquired to assess the arterial input function and 2–3 short axis slices acquired to assess myocardial perfusion. VA was performed by 2 experienced cardiologists who assigned a grade of 1–5 based on the probability a study was abnormal. Stress MBF values were determined for each of the 16 myocardial segments using Fermi deconvolution (CircleCVI). The global stress MBF was calculated as the average value of two segments with the lowest values from each of the three coronary artery territories. Unpaired t-test was used to compare stress MBF values between CAD vs NOCAD. Receiver-operating characteristics curves were used to determine diagnostic performance. Results. 60 patients had CAD (20: 1-vessel, 26: 2-vessel, and 14: 3-vessel) (Figure 1A) while 84 had NOCAD (Figure 1B). The global stress MBF in CAD was lower than in NOCAD (1.63±0.52ml/g/min vs 2.41±0.68ml/g/min, p&amp;lt;0.0001) (Figure 2A). Stress MBF had a higher AUC than VA (reader 1 – 0.83 vs 0.73, p = 0.07: reader 2–0.83 vs 0.71, p = 0.02). The optimal stress MBF cut-off value for detecting CAD was 2.05ml/g/min (Figure 2B). Conclusions. In this multicenter study, we show that global stress MBF reported as a single value can identify patients with CAD at least as accurately as VA performed by physicians experienced in the interpretation of stress CMR images.

Ultrasound-mediated blood–brain barrier opening uncovers an intracerebral perivenous fluid network in persons with Alzheimer’s disease

BackgroundFocused ultrasound (FUS)-mediated blood–brain barrier (BBB) opening is under investigation as a therapeutic modality for neurodegeneration, yet its effects in humans are incompletely understood. Here, we assessed physiologic responses to FUS administered in multifocal brain sites of persons with Alzheimer’s disease (AD).MethodsAt a tertiary neuroscience institute, eight participants with AD (mean age 65, 38% F) enrolled in a phase 2 clinical trial underwent three successive targeted BBB opening procedures at 2 week intervals using a 220 kHz FUS transducer in combination with systemically administered microbubbles. In all, 77 treatment sites were evaluated and encompassed hippocampal, frontal, and parietal brain regions. Post-FUS imaging changes, including susceptibility effects and spatiotemporal gadolinium-based contrast agent enhancement patterns, were analyzed using serial 3.0-Tesla MRI.ResultsPost-FUS MRI revealed expected intraparenchymal contrast extravasation due to BBB opening at all targeted brain sites. Immediately upon BBB opening, hyperconcentration of intravenously-administered contrast tracer was consistently observed around intracerebral veins. Following BBB closure, within 24–48 h of FUS intervention, permeabilization of intraparenchymal veins was observed and persisted for up to one week. Notably, extraparenchymal meningeal venous permeabilization and associated CSF effusions were also elicited and persisted up to 11 days post FUS treatment, prior to complete spontaneous resolution in all participants. Mild susceptibility effects were detected, however no overt intracranial hemorrhage or other serious adverse effects occurred in any participant.ConclusionsFUS-mediated BBB opening is safely and reproducibly achieved in multifocal brain regions of persons with AD. Post-FUS tracer enhancement phenomena suggest the existence of a brain-wide perivenous fluid efflux pathway in humans and demonstrate reactive physiological changes involving these conduit spaces in the delayed, subacute phase following BBB disruption. The delayed reactive venous and perivenous changes are consistent with a dynamic, zonal exudative response to upstream capillary manipulation. Further preclinical and clinical investigations of these FUS-related imaging phenomena and of intracerebral perivenous compartment changes are needed to elucidate physiology of this pathway as well as biological effects of FUS administered with and without adjuvant neurotherapeutics.Trial registration: ClinicalTrials.gov identifier: NCT03671889, registered 9/14/2018

IMG-09. DETERMINING OPTIMAL IMAGING SCHEDULE FOR PLGG AND PHGG PATIENTS OFF-THERAPY

Abstract To this point there is no standard imaging schedule across all institutions in the surveillance of pediatric low-grade gliomas (pLGG) and pediatric high-grade gliomas (pHGG) after therapy completion. We at our institution use the Children’s Oncology Group (COG) protocols ACNS1831/ACNS1833 to guide our surveillance of pLGG. The MRI schedule is every 3 months for year 1 (after therapy), every 6 months for years 2 and 3, and annually for years 4 and 5. For pHGG we do MRI imaging every 3 months for year 1, every 4 months for year 2, every 6 months for years 3-5, and annually for years 6-10. It is uncertain if this imaging schedule is optimal in terms of tracking tumor evolution post-treatment. pLGG are a diverse group of tumors but generally tend have a slower progression rate when compared to pHGG. Studies have shown a 5-year progression-free survival (PFS) of 45% to 65% for residual tumor of any size for pLGG. 3-year PFS for pHGG at best is 18%. When possible, spacing imaging, decreasing sedations, and decreasing gadolinium-based contrast agents that can deposit in the body are key drivers in imaging schedules. Through retrospective analysis we are establishing if imaging schedules should be adjusted based on disease progression or recurrence.

Diagnostic utility of contrast-enhanced FLAIR MRI in imaging of demyelinating and infectious brain lesions

BackgroundContrast-enhanced MRI is frequently used as a baseline modality and indispensable tool for early diagnosis and follow-up of different brain lesions. Herein, we aimed to evaluate the diagnostic impact of contrast-enhanced FLAIR compared to the widely used post-contrast T1W sequence in terms of demyelinating and infectious brain lesions detection in clinical practice and explore its value in monitoring disease activity for selecting appropriate therapy. MR Imaging was performed using 1.5 Tesla device. Both T1W and FLAIR sequences were obtained prior to and after administration of intravenous gadolinium-based contrast agent. Both qualitative and quantitative approaches were used for image analysis by two independent radiologists.ResultsSixty patients were prospectively enrolled in this study. Our participants were subdivided into two categories, either demyelinating (45 multiple sclerosis) or infectious lesions (13 meningitis/meningoencephalitis and 2 pyogenic abscess). By comparing the two post-contrast sequences, CE-FLAIR revealed greater enhancement in 38 cases (63.34%), equal enhancement in 17 cases (28.33%) and less enhancement in 5 cases (8.33%). For lesion conspicuity: good delineation observed in (61.67%), fair delineation in (25%) and no delineation in (13.33%). Lesion-to-background contrast ratio was statistically significant in CE-FLAIR with excellent inter-class correlation.ConclusionCE-FLAIR should be added in conjunction with or as a superior alternative to conventional CE-T1W sequence to optimize lesion detection and improve diagnostic reliability particularly in demyelinating and infectious lesions.

Comparison of Methemoglobin, Deoxyhemoglobin, and Ferrous Nitrosyl Hemoglobin as Potential MRI Contrast Agents.

Gadolinium-based contrast agents (GBCAs) are in widespread use to enhance magnetic resonance imaging for evaluating vascular pathology. However, safety concerns and limitations regarding the use of GBCAs has led to an increased interest in alternative contrast agents. Previously, methemoglobin (metHb) and oxygen-free hemoglobin (HHb) have been shown to increase the T1-weighted signal intensity of blood, which is associated with a decrease in the T1 parameter and an enhanced contrast of the image. Thus, a lower T1 value compared to the baseline value is favorable for imaging. However, it is unknown as to whether metHb or HHb would be a stronger and more appropriate contrast agent and to what extent the T1-weighted signal is affected by concentration. This study evaluated T1-weighted images of blood samples over a range of metHb and HHb concentrations, as well as ferrous nitrosyl hemoglobin (HbIINO) concentrations. Comparison of T1 values from a baseline value of ~ 1500ms showed that metHb is the strongest contrast agent (T1 ~ 950ms at 20% metHb) and that HHb is a relatively weak contrast agent (T1 ~ 1450ms at 20% HHb). This study showed for the first time that HbIINO can provide a contrast effect, although not as strong as metHb but stronger than HHb (T1 estimated as 1250ms at 20% HbIINO). With metHb providing a viable contrast between 10 and 20%, metHb has the potential to be a safe and effective contrast agent since it can be naturally converted back to hemoglobin.

Histopathologic Validation of Stress T1 Mapping in Myocardial Ischemia: Another Step toward Clinical Translation?

Histopathologic Validation of Stress T1 Mapping in Myocardial Ischemia: Another Step toward Clinical Translation?