Propofol rather than Isoflurane Accelerates the Interstitial Fluid Drainage in the Deep Rat Brain.

Objective: Different anesthetics have distinct effects on the interstitial fluid (ISF) drainage in the extracellular space (ECS) of the superficial rat brain, while their effects on ISF drainage in the ECS of the deep rat brain still remain unknown. Herein, we attempt to investigate and compare the effects of propofol and isoflurane on ECS structure and ISF drainage in the caudate-putamen (CPu) and thalamus (Tha) of the deep rat brain. Methods: Adult Sprague-Dawley rats were anesthetized with propofol or isoflurane, respectively. Twenty-four anesthetized rats were randomly divided into the propofol-CPu, isoflurane-CPu, propofol-Tha, and isoflurane-Tha groups. Tracer-based magnetic resonance imaging (MRI) and fluorescent-labeled tracer assay were utilized to quantify ISF drainage in the deep brain. Results: The half-life of ISF in the propofol-CPu and propofol-Tha groups was shorter than that in the isoflurane-CPu and isoflurane-Tha groups, respectively. The ECS volume fraction in the propofol-CPu and propofol-Tha groups was much higher than that in the isoflurane-CPu and isoflurane-Tha groups, respectively. However, the ECS tortuosity in the propofol-CPu and propofol-Tha groups was much smaller than that in isoflurane-CPu and isoflurane-Tha groups, respectively. Conclusions: Our results demonstrate that propofol rather than isoflurane accelerates the ISF drainage in the deep rat brain, which provides novel insights into the selective control of ISF drainage and guides selection of anesthetic agents in different clinical settings, and unravels the mechanism of how general anesthetics function.

Nonhomogeneous Gadolinium Retention in the Cerebral Cortex after Intravenous Administration of Gadolinium-based Contrast Agent in Rats and Humans.

Background Gadolinium retention after repeated gadolinium-based contrast agent (GBCA) exposure has been reported in subcortical gray matter. However, gadolinium retention in the cerebral cortex has not been systematically investigated. Purpose To determine whether and where gadolinium is retained in rat and human cerebral cortex. Materials and Methods The cerebral cortex in Sprague-Dawley rats treated with gadopentetate dimeglumine (three doses over 4 weeks; cumulative gadolinium dose, 7.2 mmol per kilogram of body weight; n = 6) or saline (n = 6) was examined with antemortem MRI. Two human donors with repeated GBCA exposure (three and 15 doses; 1 and 5 months after exposure), including gadopentetate dimeglumine, and two GBCA-naive donors were also evaluated. Elemental brain maps (gadolinium, phosphorus, zinc, copper, iron) for rat and human brains were constructed by using laser ablation inductively coupled plasma mass spectrometry. Results Gadopentetate dimeglumine-treated rats showed region-, subregion-, and layer-specific gadolinium retention in the neocortex (anterior cingulate cortex: mean gadolinium concentration, 0.28 µg ∙ g-1 ± 0.04 [standard error of the mean]) that was comparable (P > .05) to retention in the allocortex (mean gadolinium concentration, 0.33 µg ∙ g-1 ± 0.04 in piriform cortex, 0.24 µg ∙ g-1 ± 0.04 in dentate gyrus, 0.17 µg ∙ g-1 ± 0.04 in hippocampus) and subcortical structures (0.47 µg ∙ g-1 ± 0.10 in facial nucleus, 0.39 µg ∙ g-1 ± 0.10 in choroid plexus, 0.29 µg ∙ g-1 ± 0.05 in caudate-putamen, 0.26 µg ∙ g-1 ± 0.05 in reticular nucleus of the thalamus, 0.24 µg ∙ g-1 ± 0.04 in vestibular nucleus) and significantly greater than that in the cerebellum (0.17 µg ∙ g-1 ± 0.03, P = .01) and white matter tracts (anterior commissure: 0.05 µg ∙ g-1 ± 0.01, P = .002; corpus callosum: 0.05 µg ∙ g-1 ± 0.02, P = .001; cranial nerve: 0.02 µg ∙ g-1 ± 0.01, P = .004). Retained gadolinium colocalized with parenchymal iron. T1-weighted MRI signal intensification was not observed. Gadolinium retention was detected in the cerebral cortex, pia mater, and pia-ensheathed leptomeningeal vessels in two GBCA-exposed human brains but not in two GBCA-naive human brains. Conclusion Repeated gadopentetate dimeglumine exposure is associated with gadolinium retention in specific regions, subregions, and layers of cerebral cortex that are critical for higher cognition, affect, and behavior regulation, sensorimotor coordination, and executive function. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Kanal in this issue.

Gadoxetate-enhanced dynamic contrast-enhanced MRI for evaluation of liver function and liver fibrosis in preclinical trials.

BACKGROUND: To facilitate translational drug development for liver fibrosis, preclinical trials need to be run in parallel with clinical research. Liver function estimation by gadoxetate-enhanced dynamic contrast-enhanced MRI (DCE-MRI) is being established in clinical research, but still rarely used in preclinical trials. We aimed to evaluate feasibility of DCE-MRI indices as translatable biomarkers in a liver fibrosis animal model. METHODS: Liver fibrosis was induced in Sprague-Dawley rats by thioacetamide (200 mg, 150 mg, and saline for the high-dose, low-dose, and control groups, respectively). Subsequently, DCE-MRI was performed to measure: relative liver enhancement at 3-min (RLE-3), RLE-15, initial area-under-the-curve until 3-min (iAUC-3), iAUC-15, and maximum-enhancement (Emax). The correlation coefficients between these MRI indices and the histologic collagen area, indocyanine green retention at 15-min (ICG-R15), and shear wave elastography (SWE) were calculated. Diagnostic performance to diagnose liver fibrosis was also evaluated by receiver-operating-characteristic (ROC) analysis. RESULTS: Animal model was successful in that the collagen area of the liver was the largest in the high-dose group, followed by the low-dose group and control group. The correlation between the DCE-MRI indices and collagen area was high for iAUC-15, Emax, iAUC-3, and RLE-3 but moderate for RLE-15 (r, - 0.81, - 0.81, - 0.78, - 0.80, and - 0.51, respectively). The DCE-MRI indices showed moderate correlation with ICG-R15: the highest for iAUC-15, followed by iAUC-3, RLE-3, Emax, and RLE-15 (r, - 0.65, - 0.63, - 0.62, - 0.58, and - 0.56, respectively). The correlation coefficients between DCE-MRI indices and SWE ranged from - 0.59 to - 0.28. The diagnostic accuracy of RLE-3, iAUC-3, iAUC-15, and Emax was 100% (AUROC 1.000), whereas those of RLE-15 and SWE were relatively low (AUROC 0.777, 0.848, respectively). CONCLUSION: Among the gadoxetate-enhanced DCE-MRI indices, iAUC-15 and iAUC-3 might be bidirectional translatable biomarkers between preclinical and clinical research for evaluating histopathologic liver fibrosis and physiologic liver functions in a non-invasive manner.

Gadoxetic Acid-Enhanced Hepatobiliary-Phase Magnetic Resonance Imaging for Pyrrolizidine Alkaloid-Induced Hepatic Sinusoidal Obstruction Syndrome and Association with Liver Function.

Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by pyrrolizidine alkaloids(PAs)-containing herbals. In this study, the aim of our study was to investigate the imaging features of PAs-induced HSOS on gadoxetic acid-enhanced magnetic resonance imaging (MRI), susceptibility-weighted imaging(SWI) and T2* weighted imaging (T2* WI). We analyzed medical records and MR images of 28 PAs-induced HSOS patients enrolled from Feb, 2013, to Apr, 2017. Abnormal liver function was observed in most of the PAs-induced HSOS patients. Heterogeneity of liver parenchyma in hepatobillary phase (HBP) of gadoxetic acid-enhanced MR scan was observed in 100% of the PAs-induced HSOS patients. Distributional patterns of heterogeneous hypointensity were multifocal distribution (mild) in 4 patients (14.29%), multifocal distribution (severe) in 15 cases (53.57%), and diffuse distribution in 9 patients (32.14%). Hypointense in SWI and T2*WI was observed in the patients of PAs-induced HSOS, and the distribution of hypointense in SWI and T2*WI was similar to that of portal-venous phase of MR scan. The severity of heterogeneous hypointensity scored by volume fraction in hepatobillary phase of gadoxetic acid-enhanced MRI was positively correlated with PT and INR, the severity of hypointensity in HBP was a risk factor of death events. In conclusion: Heterogenous hypointensity of liver parenchyma was an imaging sign of hepatobillary phase in gadoxetic acid-enhanced MRI; thus, it will provide evidences for the diagnosis of PA-induced HSOS.

Regional Strain by Cardiac Magnetic Resonance Imaging Improves Detection of Right Ventricular Scar Compared With Late Gadolinium Enhancement on a Multimodality Scar Evaluation in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy is an inherited cardiomyopathy characterized by fibrofatty replacement of right ventricular myocardium resulting in reentrant ventricular tachycardia (VT). Cardiac magnetic resonance imaging (CMR) can noninvasively measure regional abnormalities using tissue-tracking strain as well as late gadolinium enhancement (LGE). In this study, we examine arrhythmogenic substrate using regional CMR strain, LGE, and electroanatomic mapping (EAM) in arrhythmogenic right ventricular cardiomyopathy patients presenting for VT ablation. METHODS AND RESULTS: Twenty-one patients underwent right ventricular endocardial EAM, whereas 17 underwent epicardial EAM, to detect dense scar (<0.5 mV) as well as CMR study within 12 months. Quantitative regional strain analysis was performed in all 21 patients, although the presence of LGE was visually examined in 17 patients. Strain was lower in segments with dense scar on endocardial and epicardial EAM (-9.7±4.1 versus -7.3±4.0, and -9.8±2.8 versus -7.6±3.8; P<0.05), in segments with LGE scar (-9.9±4.4 versus -6.0±3.6; P=0.001), and at VT culprit sites (-7.4±3.7 versus -10.1±4.1; P<0.001), compared with the rest of right ventricular. On patient-clustered analysis, a unit increase in strain was associated with 21% and 18% decreased odds of scar on endocardial and epicardial EAM, respectively, 17% decreased odds of colocalizing VT culprit site, and 43% decreased odds of scar on LGE-CMR ( P<0.05 for all). LGE and EAM demonstrated poor agreement with κ=0.18 (endocardial, n=17) and κ=0.06 (epicardial, n=13). Only 8 (15%) VT termination sites exhibited LGE. CONCLUSIONS: Regional myocardial strain on cine CMR improves detection of arrhythmogenic VT substrate compared with LGE. This may enhance diagnostic accuracy of CMR in arrhythmogenic right ventricular cardiomyopathy without the need for invasive procedures and facilitate the planning of VT ablation procedures.

Does renal function affect gadolinium deposition in the brain?

OBJECTIVE: Was to compare T1 signal intensity ratios of dentate nucleus to cerebellar white matter (DN/cerebellum), dentate nucleus to pons (DN/pons) and globus pallidus to thalamus (GP/thalamus) in patients with normal renal function and in patients on chronic hemodialysis. To find out if renal function affects the deposition of gadolinium in brain after administration of linear gadolinium based contrast agents (GBCA). METHODS: Seventy eight contrast enhanced brain MRIs (Magnetic Resonance Imaging) with linear GBCA of 13 patients on chronic hemodialysis and 13 patients with normal renal function retrospectively evaluated. The DN/pons, DN/cerebellum and GP/thalamus signal intensity ratios were measured from each brain MRI on unenhanced axial T1 weighted images. RESULTS: In hemodialysis group statistically significant increase in the signal intensity ratios of DN/pons, DN/cerebellum and GP/thalamus were found between the first and the last brain MRIs (p = .001). The increase in the signal intensity ratios of DN/pons, DN/cerebellum and GP/thalamus between the first and the last brain MRIs in control group were not significant (p > 0.05). The signal intensity increase in DN and globus pallidus were significantly higher in hemodialysis group than control group (p < 0.05). CONCLUSIONS: Patients on hemodialysis had significantly higher DN and GP signal intensity increase compared to the patients with normal renal function. Renal function affects the rate of gadolinium deposition in the brain after administration of linear GBCA.

Epicardial electroanatomical mapping, radiofrequency ablation, and lesion imaging in the porcine left ventricle under real-time magnetic resonance imaging guidance-an in vivo feasibility study.

Aims: Magnetic resonance imaging (MRI) is the gold standard for defining myocardial substrate in 3D and can be used to guide ventricular tachycardia ablation. We describe the feasibility of using a prototype magnetic resonance-guided electrophysiology (MR-EP) system in a pre-clinical model to perform real-time MRI-guided epicardial mapping, ablation, and lesion imaging with active catheter tracking. Methods and results: Experiments were performed in vivo in pigs (n = 6) using an MR-EP guidance system research prototype (Siemens Healthcare) with an irrigated ablation catheter (Vision-MR, Imricor) and a dedicated electrophysiology recording system (Advantage-MR, Imricor). Following epicardial access, local activation and voltage maps were acquired, and targeted radiofrequency (RF) ablation lesions were delivered. Ablation lesions were visualized in real time during RF delivery using MR-thermometry and dosimetry. Hyper-acute and acute assessment of ablation lesions was also performed using native T1 mapping and late-gadolinium enhancement (LGE), respectively. High-quality epicardial bipolar electrograms were recorded with a signal-to-noise ratio of greater than 10:1 for a signal of 1.5 mV. During epicardial ablation, localized temperature elevation could be visualized with a maximum temperature rise of 35 °C within 2 mm of the catheter tip relative to remote myocardium. Decreased native T1 times were observed (882 ± 107 ms) in the lesion core 3-5 min after lesion delivery and relative location of lesions matched well to LGE. There was a good correlation between ablation lesion site on the iCMR platform and autopsy. Conclusion: The MR-EP system was able to successfully acquire epicardial voltage and activation maps in swine, deliver, and visualize ablation lesions, demonstrating feasibility for intraprocedural guidance and real-time assessment of ablation injury.

Gadoxetic acid-enhanced high temporal-resolution hepatic arterial-phase imaging with view-sharing technique: Impact on the LI-RADS category.

PURPOSE: To evaluate the value of view-sharing multi-hepatic arterial-phase (mHAP) imaging for diagnosis of hypervascular hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Forty-seven consecutive patients with HCC underwent gadoxetic acid-enhanced magnetic resonance (MR) imaging before angiographic and lipiodol CT. Hepatic arterial-phase images were obtained at 5 consecutive phases with shared central k-space of 25%, followed by portal venous, late (2 and 3min), and hepatobiliary phase imaging. One-hundred-eight HCC nodules (size: 5-88mm, mean size: 18.2mm) confirmed on angiographic CT and lipiodol CT were evaluated for LI-RADS category and compared with single arterial-phase and mHAP findings regarding wash out, capsule, corona enhancement, and image quality. RESULTS: Twenty-four HCCs (22.2%) (size: 6-19mm, mean size: 12.3mm) were categorized as LR-3 based on the single arterial-phase. Capsule appearance (25.9%) and washout (57.4%) were most frequently observed in late phase (2min). Corona enhancement was observed in 73.1% of all HCCs on mHAP. For the 24 HCCs of LR-3, corona enhancement was observed in 75% on mHAP and contributed to upgrade category. No significant difference was found in the frequency of corona enhancement between mHAP and angiographic CT (P=0.11). Image quality was valued as good or excellent in all cases. CONCLUSION: View-sharing mHAP was feasible without compromising image quality and contributed to the improvement in diagnostic confidence for hypervascular HCC in gadoxetic acid-enhance MR imaging.

Signal intensity change on unenhanced T1-weighted images in dentate nucleus and globus pallidus after multiple administrations of gadoxetate disodium: an intraindividual comparative study.

PURPOSE: To investigate whether there is an increased signal intensity (SI) of dentate nucleus (DN) and globus pallidus (GP) on unenhanced T1-weighted magnetic resonance imaging (MRI), in patients who had undergone multiple administrations of gadoxetate disodium. MATERIALS AND METHODS: We retrospectevely included stage III melanoma patients, who had been previously enrolled in a trial of adjuvant therapy and who had undergone whole-body contrast-enhanced MRIs with gadoxetate disodium every three months for their follow-up. The SI ratios of DN-to-pons and GP-to-thalamus on unenhanced T1-weighted images were calculated. The difference in SI ratios between the first and the last MRI examinations was assessed and a linear mixed model was performed to detect how SI ratios varied with the number of administrations. RESULTS: Eighteen patients were included in our study. The number of gadoxetate disodium administrations ranged from 2 to 18. Paired t-test did not show any significant difference in DN-to-pons (p=0.21) and GP-to-thalamus (p=0.09) SI ratios by the end of the study. DN-to-pons SI ratio and GP-to-thalamus SI ratio did not significantly increase with increasing the number of administrations (p=0.14 and p=0.06, respectively). CONCLUSION: Multiple administrations of gadoxetate disodium are not associated with increased SI in DN and GP in the brain. KEY POINTS: • Gadolinium may deposit in the human brain after multiple GBCA administrations. • Gadolinium deposition is associated with increased T1W signal intensity • Increase in signal intensity is most apparent within the DN and GP • Multiple administrations of gadoxetate disodium do not increase T1W signal.

Molecular MR Imaging of Myeloperoxidase Distinguishes Steatosis from Steatohepatitis in Nonalcoholic Fatty Liver Disease.

Purpose To test whether MPO-Gd, an activatable molecular magnetic resonance (MR) imaging agent specific for myeloperoxidase (MPO) activity, could detect MPO activity in nonalcoholic steatohepatitis (NASH) mouse models and human liver biopsy samples. Materials and Methods In this study, 20 leptin receptor-deficient and three MPO knockout mice were injected with endotoxin (lipopolysaccharide) or fed a methionine and choline-deficient (MCD) diet to induce experimental NASH and underwent MR imaging with MPO-Gd. Saline-injected and control diet-fed leptin receptor-deficient mice were used as respective controls. MPO protein and activity measurements and histologic analyses were performed. Eleven human liver biopsy samples underwent MPO-Gd-enhanced MR imaging ex vivo and subsequent histologic evaluation. Results were compared with Student t test or Mann-Whitney U test. Results With endotoxin, a significantly increased contrast-to-noise ratio (CNR) was found compared with sham (mean CNR, 1.81 [95% confidence interval {CI}: 1.53, 2.10] vs 1.02 [95% CI: 0.89, 1.14]; P = .03) at MPO-Gd MR imaging. In the diet-induced NASH model, an increased CNR was also found compared with sham mice (mean CNR, 1.33 [95% CI: 1.27, 1.40] vs 0.98 [95% CI: 0.83, 1.12]; P = .008). Conversely, CNR remained at baseline in NASH mice imaged with gadopentetate dimeglumine and in MPO knockout NASH mice with MPO-Gd, which proves specificity of MPO-Gd. Ex vivo molecular MR imaging of liver biopsy samples from NASH and control patients confirmed results from animal studies (mean CNR for NASH vs control patients, 2.61 [95% CI: 1.48, 3.74] vs 1.29 [95% CI: 1.06, 1.52]; P = .004). Conclusion MPO-Gd showed elevated MPO activity in NAFLD mouse models and human liver biopsy samples. © RSNA, 2017 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on April 6, 2017.

Gadolinium deposition in the brain: association with various GBCAs using a generalized additive model.

OBJECTIVES: To determine the relationship between the number of administrations of various gadolinium-based contrast agents (GBCAs) and increased T1 signal intensity in the globus pallidus (GP) and dentate nucleus (DN). METHODS: This retrospective study included 122 patients who underwent double-dose GBCA-enhanced magnetic resonance imaging. Two radiologists calculated GP-to-thalamus (TH) signal intensity ratio, DN-to-pons signal intensity ratio and relative change (Rchange) between the baseline and final examinations. Interobserver agreement was evaluated. The relationships between Rchange and several factors, including number of each GBCA administrations, were analysed using a generalized additive model. RESULTS: Six patients (4.9%) received linear GBCAs (mean 20.8 number of administration; range 15-30), 44 patients (36.1%) received macrocyclic GBCAs (mean 26.1; range 14-51) and 72 patients (59.0%) received both types of GBCAs (mean 31.5; range 12-65). Interobserver agreement was almost perfect (0.99; 95% CI: 0.99-0.99). Rchange (DN:pons) was associated with gadodiamide (p = 0.006) and gadopentetate dimeglumine (p < 0.001), but not with other GBCAs. Rchange (GP:TH) was not associated with GBCA administration. CONCLUSIONS: Previous administration of linear agents gadoiamide and gadopentetate dimeglumine is associated with increased T1 signal intensity in the DN, whereas macrocyclic GBCAs do not show an association. KEY POINTS: • Certain linear GBCAs are associated with T1 signal change in the dentate nucleus. • The signal change is related to the administration number of certain linear GBCAs. • Difference in signal change may reflect differences in stability of agents.

In vitro chondrocyte toxicity following long-term, high-dose exposure to Gd-DTPA and a novel cartilage-targeted MR contrast agent.

OBJECTIVE: To determine the concentrations exhibiting toxicity of a cartilage-targeted magnetic resonance imaging contrast agent compared with gadopentetate dimeglumine (Gd-DT-PA) in chondrocyte cultures. MATERIALS AND METHODS: A long-term Swarm rat chondrosarcoma chondrocyte-like cell line was exposed for 48 h to 1.0-20 mM concentrations of diaminobutyl-linked nitroxide (DAB4-DLN) citrate, 1.0-20 mM Gd-DTPA, 1.0 µM staurosporine (positive control), or left untreated. Cell appearance, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays of metabolic activity, quantitative PicoGreen assays of DNA content, and calcein-AM viability assays were compared. RESULTS: At 1.0-7.5 mM, minimal decrease in cell proliferation was found for both agents. At all doses of both agents, cell culture appearances were similar after 24 h of treatment. At the higher doses, differences in cell culture appearance were found after 48 h of treatment, with dose-dependent declines in chondrocyte populations for both agents. Concentration-dependent declines in DNA content and calcein fluorescence were found after 48 h of treatment, but beginning at a lower dose of DAB4-DLN citrate than Gd-DTPA. Dose-dependent decreases in MTT staining (cell metabolism) were apparent for both agents, but larger effects were evident at a lower dose for DAB-DLN citrate. Poor MTT staining of cells exposed for 48 h to 20 mM DAB4-DLN citrate probably indicates dead or dying cells. CONCLUSION: The minimal effect of the long-term exposure of model chondrocyte cell cultures to DAB4-DLN citrate and Gd-DTPA concentrations up to 7.5 mM (3x typical arthrographic administration) is supporting evidence that these doses are acceptable for MR arthrography. The findings are reassuring given that the experimental exposure to the contrast agents at sustained concentrations was much longer than when used clinically.

Evaluación de la intensidad de señal en núcleo dentado, puente, globus pallidus y tálamo en pacientes con esclerosis múltiple: valoración de la retención de gadolinio / Evaluation of signal intensity in dentate nucleus, pons, globus pallidus and thalamus in patients with multiple sclerosis: assessment of gadolinium retention

Introduction: Recently, some studies have reported accumulation of gadolinium in the brain of patients with multiple administrations of gadolinium-based contrast. Patients with multiple sclerosis are subjected to multiple contrasting resonances and could become a population at risk. Objective: To determine whether repeated intravenous exposure to gadolinium is associated with more intensity in the thalamus, dentate nucleus, pons and the globus pallidus. Methods: A retrospective study of 60 patients with MS who had undergone two or more contrasted MRs between 2007 and 2015, was performed. The ratios calculated were: dentate nuclei-to-pons (DNP), thalamus-to-pons (TP), caudate nuclei-to-pons (CNP), globus pallidus-to-thalamus (GPT), globus pallidus-to-pons (GPP), by reviewing simple T1 axial sequences. Relative changes were calculated and compared with the number of contrasted MRs. The concordance between observers and the intraclass correlation coefficient was evaluated. Results: There was no evidence of increased signal intensity in T1 sequences (DNP 0.524, GPT 0.466, GPP 0.684, TP 0.771, CNP 0.352). As there were no differences, the Spearman coefficient showed no correlation between relative changes and the number of resonances performed. Inter-observer agreement was almost perfect (0.982) for all structures. Conclusion: Our study did not find a statistically significant increase in the T1 signal intensity in patients with multiple sclerosis. However, there are factors to consider, such as the type of gadolinium and the time lapse between administrations.

Introducción: Recientemente, algunos estudios han informado acumulación de gadolinio en el cerebro de los pacientes con múltiples administraciones de contraste basado en gadolinio. Los pacientes con esclerosis múltiple son sometidos a múltiples resonancias contrastadas y podrían convertirse en una población de riesgo. Objetivo: Determinar si la exposición repetida por vía intravenosa a gadolino se asocia con mayor intensidad en el tálamo, el dentado, el puente y el globo pálido. Métodos: Se realizó un estudio retrospectivo núcleo de 60 pacientes con EM que habían sido sometidos a dos o más RM contrastadas entre 2007 - 2015. Se calcularon las razones núcleo dentado - puente (DNP), tálamo-puente (TP), núcleo caudado- puente (CNP), globus pallidus - tálamo (GPT), globus pallidos - puente (GPP), revisando secuencias T1 axiales simples. Se calcularon los cambios relativos y se compararon con el número de RM contrastadas. Se evaluó la concordancia entre observadores con el coeficiente de correlación intraclase. Resultados: No hubo evidencia de aumento de la intensidad de la señal en secuencias T1 (DNP 0,524, 0,446 GPT, GPP 0,684, 0,771 PT, CNP 0.352). Al no existir diferencias, el coeficiente de Spearman no mostró correlación entre los cambios relativos y el número de resonancias realizadas. La concordancia interobservador fue casi perfecta (0.982) para todas las estructuras. Conclusión: Nuestro estudio no encontró un aumento estadísticamente significativo en la intensidad de la señal T1 en pacientes con esclerosis múltiple. Sin embargo, hay factores a considerar, tales como el tipo de gadolinio y el lapso de tiempo entre las administraciones.

Association of Left Atrial Local Conduction Velocity With Late Gadolinium Enhancement on Cardiac Magnetic Resonance in Patients With Atrial Fibrillation.

BACKGROUND: Prior studies have demonstrated regional left atrial late gadolinium enhancement (LGE) heterogeneity on magnetic resonance imaging. Heterogeneity in regional conduction velocities is a critical substrate for functional reentry. We sought to examine the association between left atrial conduction velocity and LGE in patients with atrial fibrillation. METHODS AND RESULTS: LGE imaging and left atrial activation mapping were performed during sinus rhythm in 22 patients before pulmonary vein isolation. The locations of 1468 electroanatomic map points were registered to the corresponding anatomic sites on 469 axial LGE image planes. The local conduction velocity at each point was calculated using previously established methods. The myocardial wall thickness and image intensity ratio defined as left atrial myocardial LGE signal intensity divided by the mean left atrial blood pool intensity was calculated for each mapping site. The local conduction velocity and image intensity ratio in the left atrium (mean ± SD) were 0.98 ± 0.46 and 0.95 ± 0.26 m/s, respectively. In multivariable regression analysis, clustered by patient, and adjusting for left atrial wall thickness, conduction velocity was associated with the local image intensity ratio (0.20 m/s decrease in conduction velocity per increase in unit image intensity ratio, P<0.001). CONCLUSIONS: In this clinical in vivo study, we demonstrate that left atrial myocardium with increased gadolinium uptake has lower local conduction velocity. Identification of such regions may facilitate the targeting of the substrate for reentrant arrhythmias.

In vivo evaluation of neutron capture therapy effectivity using calcium phosphate-based nanoparticles as Gd-DTPA delivery agent.

PURPOSE: A more immediate impact for therapeutic approaches of current clinical research efforts is of major interest, which might be obtained by developing a noninvasive radiation dose-escalation strategy, and neutron capture therapy represents one such novel approach. Furthermore, some recent researches on neutron capture therapy have focused on using gadolinium as an alternative or complementary for currently used boron, taking into account several advantages that gadolinium offers. Therefore, in this study, we carried out feasibility evaluation for both single and multiple injections of gadolinium-based MRI contrast agent incorporated in calcium phosphate nanoparticles as neutron capture therapy agent. METHODS: In vivo evaluation was performed on colon carcinoma Col-26 tumor-bearing mice irradiated at nuclear reactor facility of Kyoto University Research Reactor Institute with average neutron fluence of 1.8 × 10(12) n/cm(2). Antitumor effectivity was evaluated based on tumor growth suppression assessed until 27 days after neutron irradiation, followed by histopathological analysis on tumor slice. RESULTS: The experimental results showed that the tumor growth of irradiated mice injected beforehand with Gd-DTPA-incorporating calcium phosphate-based nanoparticles was suppressed up to four times higher compared to the non-treated group, supported by the results of histopathological analysis. CONCLUSION: The results of antitumor effectivity observed on tumor-bearing mice after neutron irradiation indicated possible effectivity of gadolinium-based neutron capture therapy treatment.

MRI Brain Signal Intensity Changes of a Child During the Course of 35 Gadolinium Contrast Examinations.

We describe the observed and quantitative signal intensity changes in the brain on baseline precontrast T1-weighted MRI data of a pediatric patient who received 35 MRI examinations with gadolinium-based contrast agent (GBCA) between the ages of 8 and 20 years. The contrast agent this patient received belongs to a class of agents with linear molecular structures, which has been recently investigated in studies of gadolinium deposition in the brains of adult patients. Visual changes in signal intensity were assessed by 3 pediatric neuroradiologists, and progressive increases were the most evident in the dentate nuclei, the globus pallidus, and the thalamus. Quantitative measurements as determined from signal intensity ratios confirmed visual findings. The pattern of regional brain hyperintensity observed in this pediatric patient is consistent with findings from adult studies.

Distribution of abnormal potentials in chronic myocardial infarction using a real time magnetic resonance guided electrophysiology system.

BACKGROUND: Identification of viable slow conduction zones manifested by abnormal local potentials is integral to catheter ablation of ventricular tachycardia (VT) sites. The relationship between contrast patterns in cardiovascular magnetic resonance (CMR) and local electrical mapping is not well characterized. The purpose of this study was to identify regions of isolated, late and fractionated diastolic potentials in sinus rhythm and controlled-paced rhythm in post-infarct animals relative to regions detected by late gadolinium enhancement CMR (LGE-CMR). METHODS: Using a real-time MR-guided electrophysiology system, electrogram (EGM) recordings were used to generate endocardial electroanatomical maps in 6 animals. LGE-CMR was also performed and tissue classification (dense infarct, gray zone and healthy myocardium) was then correlated to locations of abnormal potentials. RESULTS: For abnormal potentials in sinus rhythm, relative occurrence was equivalent 24%, 27% and 22% in dense scar, gray zone and healthy tissue respectively (p = NS); in paced rhythm, the relative occurrence of abnormal potentials was found to be different with 30%, 42% and 21% in dense scar, gray zone and healthy myocardium respectively (p = 0.001). For location of potentials, in the paced case, the relative frequency of abnormal EGMs was 19.9%, 65.4% and 14.7% in the entry, central pathway and exit respectively (p = 0.05), putative regions being defined by activation times. CONCLUSIONS: Our data suggests that gray zone quantified by LGE-CMR exhibits abnormal potentials more frequently than in healthy tissue or dense infarct when right ventricular apex pacing is used.

In vitro toxicity in long-term cell culture of MR contrast agents targeted to cartilage evaluation.

OBJECTIVE: Contrast-enhanced magnetic resonance (MR) imaging methods have been proposed for non-invasive evaluation of osteoarthritis (OA). We measured cell toxicities of cartilage-targeted low-generation dendrimer-linked nitroxide MR contrast agents and gadopentetate dimeglumine (Gd-DTPA) on cultured chondrocytes. DESIGN: A long-term Swarm rat chondrosarcoma chondrocyte-like cell line was exposed for 48-h to different salts (citrate, maleate, tartrate) and concentrations of generation one or two diaminobutyl-linked nitroxides (DAB4-DLN or DAB8-DLN), Gd-DTPA, or staurosporine (positive control). Impact on microscopic cell appearance, MTT spectrophotometric assays of metabolic activity, and quantitative PicoGreen assays of DNA content (cell proliferation) were measured and compared to untreated cultures. RESULTS: Chondrocyte cultures treated with up to 7.5 mM Gd-DTPA for 48-h had no statistical differences in DNA content or MTT reaction compared to untreated cultures. At all doses, DAB4-DLN citrate treated cultures had results similar to untreated and Gd-DTPA-treated cultures. At doses >1 mM, DAB4-DLN citrate treated cultures showed statistically greater DNA and MTT reaction than maleate and tartrate DAB4-DLN salts. Cultures exposed to 5 mM or 7.5 mM DAB8-DLN citrate exhibited rounded cells, poor cell proliferation, and barely detectable MTT reaction. Treatment with 0.1 µM staurosporine caused chondrocyte death. CONCLUSION: Long-term exposure, greater than clinically expected, to either DAB4-DLN citrate or Gd-DTPA had no detectable toxicity with results equivalent to untreated cultures. DAB4-DLN citrate was more biocompatible than either the maleate or tartrate salts. Cells exposed for 48-h to 5 mM or 7.5 mM DAB8-DLN salts demonstrated significant cell toxicity. Further evaluation of DAB8-DLN with clinically appropriate exposure times is required to determine the maximum useful concentration.

Dynamic contrast-enhanced MR lymphangiography: feasibility study in swine.

PURPOSE: To demonstrate the feasibility of dynamic four-dimensional ( 4D four-dimensional ) intranodal contrast material-enhanced magnetic resonance (MR) lymphangiography with inguinal lymph node injection of gadopentetate dimeglumine. MATERIALS AND METHODS: All procedures were performed in accordance with the guidelines on the use of animals in research and were approved by the animal care and use committee. Five swine underwent nonenhanced MR lymphangiography with a heavily T2-weighted MR sequence, bilateral inguinal lymph node injection of 2 mL of undiluted gadopentetate at a rate of 1 mL/min, and 60 minutes of MR imaging with T1-weighted high-spatial- and high-temporal-resolution MR angiography. Images were reviewed by a radiologist with expertise in lymphatic imaging and a pediatric cardiac MR imaging specialist for visualization of the thoracic duct ( TD thoracic duct ). Categorical variables were compared by using the exact conditional McNemar test. A difference with a P value less than .05 was considered significant. RESULTS: The TD thoracic duct was visualized in three of the five animals (60%) on T2-weighted images. In contrast, the TD thoracic duct was visualized in all five of the animals (100%) after contrast agent injection (P = .25). The median time for flow of the contrast agent through the lymphatic system to the TD thoracic duct outlet was 244 seconds (range, 201-387 seconds). Enhancement was seen in the TD thoracic duct up to 1 hour after injection. All animals survived without any complications. CONCLUSION: Dynamic 4D four-dimensional contrast-enhanced MR lymphangiography with intranodal injection of gadopentetate dimeglumine is feasible, produces good images of the central lymphatic system, and demonstrates the time course of flow of contrast agent up the central lymphatic ducts. On the basis of the results of this initial animal experiment, it appears that dynamic 4D four-dimensional contrast-enhanced MR lymphangiography is potentially feasible and safe with commercially available contrast agents.

Non-ionic Gd-based MRI contrast agents are optimal for encapsulation into phosphatidyldiglycerol-based thermosensitive liposomes.

Thermosensitive liposomes (TSL) with encapsulated magnetic resonance imaging (MRI) longitudinal relaxation time (T(1)) contrast agents (CAs) have been proposed for MRI assisted interventional thermotherapy in solid tumors. Here the feasibility of 6 clinically approved CAs (Gd-DTPA, Gd-BOPTA, Gd-DOTA, Gd-BT-DO3A, Gd-DTPA-BMA, and Gd-HP-DO3A) for formulation into TSL was investigated. CAs were passively encapsulated with 323 mOs kg(-1) into 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/1,2-distearoyl-sn-glycero-3-phosphocholine/1,2-dipalmitoyl-sn-glycero-3-phosphodiglycerol 50/20/30 (mol/mol) TSL (DPPG(2)-TSL) to obtain stable formulations. T(1) relaxivity (r(1)) and diffusive permeability to water (P(d)) across the membrane were determined. Shelf life at 4°C was investigated by determining lysolipid content up to 10 weeks after preparation. All preparations were monodispersed with comparable small vesicle sizes (~135 nm). Neither zeta potential nor phase transition temperature (T(m)) was affected by the CA. The formulations showed an increase in r(1) in the temperature range between 38 and 44°C. This correlated with the phase transition. Change in r(1) (Δr(1)=r(1)(45.3°C)-r(1)(37.6°C)) and r(1) (T