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Resumen Introduccion y objetivo Se han notificado resultados contradictorios sobre un aumento en la intensidad de la senal (IS) en las imagenes de resonancia magnetica (RM) ponderadas en T1 no realzadas en el globo palido y/o el nucleo dentado (ND) despues de la exposicion a varios agentes de contraste con gadolinio (ACG). Este cambio en la senal varia en funcion del ACG especifico. Nuestro objetivo fue investigar si existe un aumento en la IS del ND en imagenes ponderadas en T1 no realzadas en pacientes sometidos a multiples administraciones del ACG macrociclico gadoterato de meglumina. Se realizo una revision exhaustiva de la bibliografia para corroborar nuestros resultados. Materiales y metodos Se incluyeron pacientes que se habian sometido a mas de 10 estudios de RM con contraste y administracion exclusiva de gadoterato de meglumina. Se llevo a cabo un analisis cuantitativo mediante el uso de mediciones de regiones de interes en el ND y el puente en imagenes no realzadas ponderadas en T1. Se calcularon las proporciones ND-puente y las diferencias en las proporciones entre el inicio y la ultima RM realizada. Se utilizo una prueba de la t de una muestra para evaluar si las diferencias en la proporcion de la IS difieren de 0. Se realizo un analisis de subgrupos de pacientes con Resultados 54 pacientes (26 hombres) recibieron una media de 13,8 dosis ± 3,47 (desviacion estandar [DE]) (rango, 10-23 dosis). La diferencia en la proporcion de la IS ND-puente entre la primera y la ultima exploracion de RM fue de -0,0275 ± 0,1917 y no difirio significativamente de 0 P = 0,2968) en el analisis general y en el analisis de subgrupos [( Conclusiones Mas de 10 administraciones de gadoterato de meglumina no se asociaron a un aumento de la IS en el ND.

The aim of this study was to report early clinical experience with various forms of immune dampening to mitigate the expected flare reaction in patients suffering from gadolinium deposition disease (GDD) receiving DTPA chelation.All patients were clinical subjects, and no prospective research was performed on them. The study included 31 consecutive patients (21 women; age, 46.2 ± 12.5 years). The diagnosis of GDD was clinically made. The severity of the flare over the week after each chelation session was rated on a scale from 1 to 10 (where 1 is negligible, 10 is intolerably severe). Patients were followed for up to 5 chelation sessions. Four immune dampening strategies were used: (1) no concurrent treatment; (2) antihistamine plus montelukast (AH); (3) steroid/antihistamine taper postchelation (SAHT); and (4) steroid/antihistamine extending from prechelation to 5 days postchelation (extended hypersensitivity medication regimen; EHMR). The data were analyzed with generalized linear mixed models and with linear regression.A total of 102 flare scores were obtained at different time points. Ten patients underwent 5 chelations. The severity of the flare after the first chelation was significantly higher in cases of no concurrent therapy (8.4 ± 2.6) and AH (7 ± 1.4) compared with SAHT (6 ± 1.3) and EHMR (5 ± 1.1). Patients who underwent SAHT and EHMR experienced less severity of flare after the first chelation (P = 0.0049 and P = 0.0005, respectively). Considering all time points, the results were also significantly better with SAHT and EHMR.Based on early clinical experience, EHMR seems to manage flare reactions in DTPA chelation well. This strategy may represent the first standard therapy in patients with GDD.

Purpose The aim of this study was to investigate the feasibility of measuring early changes in serum cytokine levels after intravenous diethylenetriaminepentaacetic acid (Ca-DTPA) chelation in patients manifesting either gadolinium deposition disease (GDD) or gadolinium storage condition (GSC) and the possible usefulness of this method in further research. Methods Four patients with recent-onset GDD (≤1 year) and 2 patients with long-standing GSC (4 and 9 years) underwent chelation with intravenous bolus administration of Ca-DTPA. Multiple blood draws were performed to measure serum cytokines: at T = 0 (before Ca-DTPA injection) and 1, 5, 10, 30, 60 minutes, and 24 hours after Ca-DTPA injection. Patients rated the severity of GDD symptom flare at 24 hours. The 24-hour urine Gd amounts were measured prechelation and for the 24 hours after chelation. Serum samples were analyzed blind to whether patients had GDD or GSC but with knowledge of the time points characterizing each sample. Results Urine samples for both GDD and GSC patients showed increases in Gd postchelation. All GDD patients experienced flare reactions postchelation; the 2 GSC patients did not. Two cytokines, EGF and sCD40L, peaked at 30 minutes postchelation in at least 4 of the 6 participants. Three cytokines, ENA78/CXCL5, EOTAXIN/CCL11, and LEPTIN, peaked at 24 hours in at least 4 of the 6 participants. Two participants were high outliers for a large number of cytokines across time points. No clear distinction between GDD and GSC was apparent from the cytokine patterns, although differences were present. Conclusions This pilot study describes precise temporal resolution (in the range of minutes) after a cytokine-inciting event. Select cytokines exhibited peak values at different time points. At this preliminary stage of investigation, peak cytokine release seems to reflect the amount of Gd mobilized rather than the severity of the patient symptomatic reaction. Too few subjects were studied to support statistical analysis between GDD and GSC groups, although differences were observed through visual data analysis.

There is a constantly evolving knowledgebase regarding the safety of MRI in pregnant patients, as well as the safety of gadolinium administration, given potential fetal risks. This review provides an overview of national and international recommendations for patient screening and safety by trimester, evaluates the most recent literature regarding administration of gadolinium in pregnant patients, and discusses technical requirements when imaging pregnant patients. A protocol for imaging pregnant patients is provided, and multiple common indications for MRI in pregnancy are discussed. Level of Evidence 5. Technical Efficacy Stage 5. J. Magn. Reson. Imaging 2019;49:621-631.

Objectives The aim of this study was to determine the following in patients who have undergone magnetic resonance imaging with gadolinium-based contrast agents (GBCAs) and meet the proposed diagnostic criteria for gadolinium deposition disease (GDD): (1) the effectiveness of chelation therapy (CT) with intravenous Ca-diethylenetriaminepentaacetic acid in removing retained gadolinium (Gd) and factors affecting the amount removed; (2) the frequency of CT-induced Flare, that is, GDD diagnostic symptom worsening, and factors affecting Flare intensity; (3) whether, as reported in a separate cohort, GDD patients' serum cytokine levels differ significantly from those in healthy normal controls and change significantly in response to CT; and (4) whether urine Gd, Flare reaction, and serum cytokine findings in GDD patients are mimicked in non-ill patients described as having gadolinium storage condition (GSC). Materials and methods Twenty-one GDD subjects and 3 GSC subjects underwent CT. Patients provided pre-CT and post-CT 24-hour urine samples for Gd content determination along with pre-CT and 24-hour post-CT serum samples for cytokine analysis. Patients rated potential Flare 24 hours after CT. Pre-CT and post-CT 24-hour urine Gd analyses and Luminex serum cytokine assays were performed blind to patients' GDD and GSC status and all other data except age and sex. Serum cytokine levels in a healthy normal control group of age- and sex-matched subjects drawn from Stanford influenza vaccination studies were measured once, contemporaneously with those of GDD and GSC patients, using the same Luminex assay. Results Urine Gd amounts increased post-CT by 4 times or more after 87% of the 30 CT sessions. The most important factors appeared to be the time since the last GBCA dose and the cumulative dose received. Urine Gd amounts for GDD and GSC patients fell in the same ranges. All GDD patients, and no GSC patient, reported a Flare 24 hours post-CT. Linear regression found that Flare intensity was significantly predicted by a model including pre- and post-CT Gd amounts and the number of GBCA-enhanced magnetic resonance imaging. Post-CT, multiple cytokines showed strong positive relationships with GDD patients' Flare intensity in multivariable models. The pre-CT serum levels of 12 cytokines were significantly different in GDD patients compared with healthy flu vaccine controls. The small number of GSC patients precluded analogous statistical testing. Post-CT, GDD patients' serum levels of 20 cytokines were significantly decreased, and 2 cytokines significantly increased. These cytokines did not exhibit the same change pattern in the 3 GSC patients. The small number of GSC patients precluded statistical comparisons of GSC to GDD patients' results. Conclusions In this preliminary study, 24-hour urine Gd content increased markedly and similarly in GDD and GSC patients after Ca-diethylenetriaminepentaacetic acid CT. Post-CT Flare reaction developed only in GDD patients. The current study is the second finding significantly different serum cytokine levels in GDD patients compared with healthy normal controls. These differences and the difference between GDD and GSC patients' Flare and cytokine responses to CT suggest some inflammatory, immunologic, or other physiological differences in patients with GDD. Further research into the treatment and physiological underpinnings of GDD is warranted.

Objective: To determine whether individuals with proposed gadolinium deposition disease (GDD) have elevated serum levels of pro-inflammatory and pro-fibrotic cytokines, and whether specific cytokines are correlated with certain symptoms. Materials and Methods: Twenty-four participants recruited between May 2016 and June 2017 met GDD diagnostic criteria. The 64 control subjects provided serum samples before prophylactic flu vaccination. Serum cytokine levels were obtained with Luminex serum cytokine assay using eBiosciences/Affymetrix human 62-plex kits. Wilcoxon rank-sum tests were performed to assess the difference between the median fluorescence intensity values for the participants and the control group. Generalized linear models were built to evaluate the association between each cytokine of interest and selected participant symptoms. Results: Serum levels of 14 cytokines, including nine pro-inflammatory cytokines, were statistically significantly elevated compared to controls (p ≤ 0.05). Hypotheses regarding pro-fibrotic cytokines and cytokine links to specific symptoms’ intensity were not confirmed. Conclusion: The statistically significantly elevated cytokines may be markers of susceptibility to GDD or agents of symptom induction. These findings suggest that individuals developing symptoms characteristic of GDD after a contrast-assisted magnetic resonance imaging should be studied to investigate whether gadolinium retention and elevated cytokines may be related to their symptoms. Resumo Objetivo: Determinar se indivíduos com doença de deposição de gadolínio (DDG) apresentam níveis séricos elevados de citocinas pró-inflamatórias e pró-fibróticas e se citocinas específicas estão correlacionadas com determinados sintomas. Materiais e Métodos: Vinte e quatro participantes recrutados entre maio/2016 e junho/2017 cumpriram os critérios de diagnóstico de DDG. Amostras de soro de 64 indivíduos controles foram obtidas antes de vacinação profilática contra a gripe. Os níveis de citocinas séricas foram mensurados com o ensaio Luminex usando kits 62-plex humanos. Foram realizados testes de Wilcoxon para avaliar a diferença dos valores médios de intensidade de fluorescência entre os participantes e o grupo controle. Foram construídos modelos lineares generalizados para avaliar a associação entre cada citocina de interesse e os sintomas dos participantes selecionados. Resultados: Níveis séricos de 14 citocinas, incluindo 9 citocinas pró-inflamatórias, foram estatisticamente significantes em comparação aos controles (p ≤ 0,05). Hipóteses sobre as citocinas pró-fibróticas e associação das citocinas com a intensidade de sintomas específicos não foram confirmadas. Conclusão: Citocinas estatisticamente elevadas podem ser marcadores de suscetibilidade para DDG ou agentes de indução de sintomas. Esses achados sugerem que indivíduos que desenvolvem sintomas da DDG após ressonância magnética com contraste devem ser estudados para investigar se a retenção de gadolínio e citocinas elevadas podem estar relacionadas aos seus sintomas.

The aim of this study was to report the use of intravenous calcium (Ca)-/zinc (Zn)-diethylene triamine penta-acetic acid (DTPA) for the treatment of 25 symptomatic patients diagnosed with gadolinium deposition disease (GDD).Written informed consent was obtained. Twenty-five patients (18 women; mean age, 46.8 ± 15.3 years) with a diagnosis of GDD were included. All patients had received at least 1 administration of a gadolinium (Gd)-based contrast agent. Patients received 3 treatment sessions with Ca-/Zn-DTPA, 15 with treatments spaced 1 month apart, and 10 with treatments spaced 1 week apart. In all cases, every treatment consisted of an application of Ca-DTPA and Zn-DTPA separated by 24 hours. Measurements of 24-hour urine Gd content before dosing and on the first and second days of therapy were performed. Symptomatic improvement of patients was determined by use of a 10-point scale of patient symptoms. Serum electrolytes were quantified.Gadolinium content increased in the urine, with an overall mean of 30.3-fold increase in the monthly regimen (P0.001) and 12.9-fold in the weekly regimen (P0.001). Eleven patients experienced transient worsening of at least some of their symptoms, termed a "flare-up" phenomenon, in most of whom symptoms improved or receded. Overall, symptoms improved in 13 patients, unchanged in 10, and worse in 2. Significant clinical improvement was present for headache, brain fog, and bone pain for the monthly regimen and arm pain and leg pain for the weekly regimen. There were no significant changes in major serum electrolytes.Three courses of intravenous Ca-/Zn-DTPA therapy results in significantly increased urine content of Gd after treatment and moderate symptomatic improvement.

Objective To evaluate the age-stratified prevalence of upper tract urothelial malignancies diagnosed on computed tomography urography in a large cohort of patients referred for initial evaluation of hematuria. Materials and Methods A total of 1123 consecutive adults without a history of urothelial cancer underwent initial computed tomography urography for gross hematuria (n = 652), microscopic hematuria (n = 457), or unspecified hematuria (n = 14) at a single institution from October 2006 to October 2012. Imaging findings suggestive of urothelial lesions were correlated with clinical information, including cystoscopy, cytology, and surgical pathology reports. Patients subsequently diagnosed with urothelial cancer following a normal radiographic evaluation were identified and analyzed. Age, gender, smoking history, and location and type of malignancy were analyzed. Results Upper tract urothelial cancer was detected in 4 (0.36%) patients, with a mean age of 66.5 years. All 4 patients presented with gross hematuria and were current or former smokers. None of the 535 patients under age 55 who underwent computed tomography urography were diagnosed with upper tract disease regardless of age, smoking history, or degree of hematuria. Likewise, no upper tract cancers were detected in patients referred for microscopic hematuria, regardless of age. Conclusion Detection of upper tract urothelial cancer by computed tomography urography is exceedingly rare in patients presenting at a tertiary referral center with hematuria, particularly in the lower risk strata (younger age, microscopic hematuria). Further investigation into risk-stratified approaches to imaging for hematuria workup is warranted to minimize unnecessary costs and radiation exposure.

Objective: To describe a modified approach to the evaluation of adrenal nodules using a standard abdominal magnetic resonance imaging protocol. Materials and Methods: Our sample comprised 149 subjects (collectively presenting with 132 adenomas and 40 nonadenomas). The adrenal signal intensity index was calculated. Lesions were grouped by pattern of enhancement (PE), according to the phase during which the wash-in peaked: arterial phase (type 1 PE); portal venous phase (type 2 PE); and interstitial phase (type 3 PE). The relative and absolute wash-out values were calculated. To test for mean differences between adenomas and nonadenomas, Student's t-tests were used. Receiver operating characteristic curve analysis was also performed. Results: The mean adrenal signal intensity index was significantly higher for the adenomas than for the nonadenomas (p < 0.0001). Chemical shift imaging showed a sensitivity and specificity of 94.4% and 100%, respectively, for differentiating adenomas from nonadenomas. Of the adenomas, 47.6%, 48.5%, and 3.9%, respectively, exhibited type 1, 2, and 3 PEs. For the mean wash-in proportions, significant differences were found among the enhancement patterns. The wash-out calculations revealed a trend toward better lesion differentiation for lesions exhibiting a type 1 PE, showing a sensitivity and specificity of 71.4% and 80.0%, respectively, when the absolute values were referenced, as well as for lesions exhibiting a type 2 PE, showing a sensitivity and specificity of 68.0% and 100%, respectively, when the relative values were referenced. The calculated probability of a lipid-poor lesion that exhibited a type 3 PE being a nonadenoma was > 99%. Conclusion: Subgrouping dynamic enhancement patterns yields high diagnostic accuracy in differentiating adenomas from nonadenomas. Resumo Objetivo: Descrever uma abordagem modificada para a avaliação de nódulos adrenais utilizando um protocolo padrão de ressonância magnética abdominal. Materiais e Métodos: A nossa amostra foi composta de 149 indivíduos (132 adenomas e 40 não adenomas). O índice de intensidade do sinal adrenal foi calculado. As lesões foram agrupadas em três grupos de acordo com o tempo de wash-in até atingir o pico de realce (arterial, tipo 1 PE; portal-venoso, tipo 2 PE; ou intersticial, tipo 3 PE). O wash-out relativo e o absoluto foram calculados. O teste t de Student foi utilizado para examinar diferenças entre adenomas e não adenomas. A análise da curva ROC foi realizada. Resultados: O índice de intensidade médio do sinal adrenal dos adenomas adrenais foi significativamente maior (p < 0,0001). A imagem de fora-de-fase teve sensibilidade de 94,4% e especificidade de 100% para diferenciar adenomas de não adenomas. Do total de adenomas, 47,6% exibiram tipo 1 PE, 48,5% tipo 2 PE e 3,9% tipo 3 PE. Para todos os padrões de realce foram encontradas diferenças significativas para as porcentagens médias de wash-out. Houve tendência para uma melhor diferenciação da lesão utilizando o cálculo absoluto de wash-out para lesões apresentando tipo 1 PE e wash-out relativo para lesões apresentando tipo 2 PE, com sensibilidade e especificidade de 71,4% e 80% e 68% e 100%, respectivamente. A probabilidade calculada de uma lesão pobre em lipídios exibir um padrão tipo 3 PE de ser um não adenoma foi superior a 99%. Conclusão: O agrupamento de padrões dinâmicos de realce proporciona elevada precisão diagnóstica na diferenciação de adenomas de não adenomas adrenais.

Purpose To identify demographic and imaging features in magnetic resonance imaging (MRI) that are associated with upgrade of Liver Imaging Reporting and Data System (LI-RADS) category 4 (LR-4) observations to category 5 (LR-5), and to assess their effects on risk of upgrade and time to upgrade. Materials and Methods Institutional Review Board approval was obtained for this retrospective, dual-institution Health Insurance Portability and Accountability Act (HIPAA)-compliant study. Radiologists reviewed 1.5T and 3T MRI examinations for 181 LR-4 observations in 139 patients, as well as follow-up computed tomography (CT) and MRI examinations and treatment. A stepwise multivariate Cox proportional hazards model analysis was performed to identify predictive risk factors for upgrade to LR-5, including patient demographics and LI-RADS imaging features. Overall cumulative risk of upgrade was calculated by using the Kaplan–Meier method. The cumulative risks were compared in the presence/absence of significant predictive risk factors using the log-rank test. Results The independent significant predictive risk factors in the 56 LR-4 observations that upgraded to LR-5 were mild–moderate T2 hyperintensity (P

Magnetic resonance imaging (MRI) is the modern gold standard for the noninvasive evaluation of the cirrhotic liver. The combination of arterial phase hyperenhancement and delayed wash-out allows a definitive diagnosis of hepatocellular carcinoma (HCC) in patients with liver cirrhosis or chronic liver disease, without the requirement for confirmatory biopsy. That pattern is highly specific and has been endorsed in Western and Asian diagnostic guidelines. However, the sensitivity of the combination is relatively low for small HCCs. In this two-part review paper, we will address MRI of the cirrhotic liver. In this first part, we provide a brief background on liver cirrhosis and HCC, followed by descriptions of imaging surveillance of liver cirrhosis and the diagnostic performance of the different imaging modalities used in clinical settings. We then describe some of the requirements for the basic MRI technique, as well as the standard MRI protocol, and provide a detailed description of the appearance of various types of hepatocellular nodules encountered in the setting of the carcinogenic pathway in the cirrhotic liver, ranging from regenerative nodules to HCC.A ressonância magnética (RM) é o método padrão para a avaliação não invasiva do fígado cirrótico. A combinação de hiper-realce arterial e

The aim of this study was to examine and report 4 patients who developed symptomatology shortly after gadolinium-based contrast agent (GBCA) administration.History taking and targeted physical examination were performed on 4 subjects who reported development of new disease features within hours to 4 weeks of having received an intravenous administration of GBCA.Two subjects were assessed at 2 months (patient P2mo) and at 3 months (patient P3mo) after GBCA administration (early stage), and 2 subjects were assessed at 7 years (patient P7yr) and 8 years (patient P8yr) after having received GBCA administration (late stage). Clinical features were similar between subjects, and included central torso pain (all), peripheral arm and leg pain (all), clouded mentation (n = 2), and distal arm and leg skin thickening and rubbery subcutaneous tissue (one early and both late subjects). Gadolinium was detected as follows: in a 24-hour urine specimen, 1 month after disease development (18 μg/24 hours and 82 μg/24 hours in patients P2mo and P3mo, respectively); hair (0.0007 μg/g) and urine (0.0644 μg/g) samples, 7 years after disease development (late stage, patient P7yr); and saphenous vein sample, 8 years after disease development (0.27 ± 0.007 ng/62 mg sample) (late stage, patient P8yr).Gadolinium toxicity may occur in subjects with normal renal function. Central torso and peripheral arm and leg distribution pain were common features. Distal arm and leg skin thickening and rubbery subcutaneous tissue were seen in late stages. Clouded mentation is also common. Vigilance to identify additional cases and investigate strategies for prevention and treatment is warranted to increase even further the safety of a very safe diagnostic procedure, GBCA-enhanced magnetic resonance imaging.

OBJECTIVE. The literature informs us that gadolinium can cause health issues. At least four major gadolinium disorders, including the two well-recognized nephrogenic systemic fibrosis and severe acute adverse event, have been identified. CONCLUSION. We propose naming the histopathologically proven presence of gadolinium in brain tissue “gadolinium storage condition,” and we describe a new entity that represents symptomatic deposition of gadolinium in individuals with normal renal function, for which we propose the designation “gadolinium deposition disease.”

To quantitatively compare the extent of enhancement of abdominal structures on MRI in an intraindividual fashion at 1.5 and 3 T. HIPAA-compliant, retrospective, longitudinal, intraindividual, crossover study, with waived informed consent, of consecutive individuals scanned at both 1.5 and 3 T closed-bore magnets using gadobenate dimeglumine during different phases of enhancement at tightly controlled arterial phase timing. Quantitative ROI measurements and qualitative sub-phase arterial phase assignments were independently performed by two radiologists. Qualitative discrepancies were resolved by a senior radiologist. Final population included 60 patients [41 female and 19 male; age, 49.35 ± 18.31 years (range 16–81); weight, 78.88 ± 20.3 kg (range 44.5–136)]. Similar enhancement peak patterns were noted at both field strengths. Interobserver agreement of quantitative evaluations was substantial. Significantly higher amplitudes of enhancement peaks were noted for all abdominal solid organs during all phases at 3 T, except for the pancreas (p = 0.17–0.30). Significantly higher amplitudes of enhancement peaks of the abdominal aorta at 1.5 T were noted. Similar peak patterns of enhancement for abdominal structures were observed at 1.5 and 3 T, with solid abdominal organs showing a higher percentage enhancement at 3 T, while unexpectedly higher aortic higher percentage enhancement was observed at 1.5 T. • Similar enhancement peak patterns at both field strengths for studied abdominal structures. • Significantly higher percentage enhancement of most abdominal organs at 3 T. • Non-statistically significant trend of higher pancreatic percentage enhancement at 3 T. • Significantly lower abdominal aortic percentage enhancement at 3 T.

To evaluate the occurrence rate of lobulated margination of hepatic hemangiomas.The study population included 585 hemangiomas in 261 patients (161 females; mean age: 51.9years). Two readers independently reviewed all cases.Hemangiomas with lobulated margins accounted for 74.7% of all lesions. The incidence of lobulated margins was significantly higher (P.001) in medium- and large-sized hemangiomas (77.6% and 99.5%, respectively). The majority of hemangiomas with type-3 enhancement showed lobulated margins (83.5%) (P.001).Virtually, all hemangiomas18mm show lobulated margins. The majority of hemangiomas with type-3 enhancement show lobulated margins. Lack of lobulated margins in larger lesions lowers the likelihood ratio for being hemangiomas.

The increasing threats of nuclear terrorism have made the development of medical countermeasures a priority for international security. Injectable formulations of diethylenetriaminepentaacetic acid (DTPA) have been approved by the FDA; however, an oral formulation is more amenable in a mass casualty situation. Here, the diethyl ester of DTPA, named C2E2, is investigated for potential as an oral treatment for internal radionuclide contamination. C2E2 was synthesized and characterized using NMR, MS, and elemental analysis. The physiochemical properties of solubility, lipophilicity, and stability were investigated in order to predict its oral bioavailability. Finally, an animal efficacy study was conducted in Sprague Dawley rats pre-contaminated by intramuscular injection with (241)Am(NO3)3 to establish effectiveness of the therapy via the oral route. Synthesis of C2E2 yielded a crystalline powder with high solubility and improved lipophilicity over DTPA. The ester was stable in both simulated gastric and intestinal fluids over the anticipated time course of absorption. Capsules containing C2E2 were demonstrated to be stable for 12 months under accelerated stability conditions. After a single dose, C2E2 enhanced the elimination of (241)Am in a dose-dependent manner. Significant improvement was seen in both total (241)Am decorporation and reduction of (241)Am liver and skeletal burden. C2E2 was concluded to be effective when orally administered to (241)Am-contaminated rats. It may therefore have potential for medical countermeasure in treating humans contaminated with (241)Am or other transuranic elements. An oral capsule or powder for reconstitution may be suitable formulations for future development based on the physiochemical properties and anticipated dose required for efficacy.

Recently, there have been numerous major peer-reviewed publications reporting deposition of gadolinium in the dentate nucleus and globus pallidus in subjects with normal renal function. This review takes a retrospective look back through the development of gadolinium-based contrast agents to describe the historical evidence of gadolinium deposition in vivo and shows that deposition in the basal ganglia should come as no surprise. Evidence for gadolinium deposition in both animal models and human patients is described. Stability differences among gadolinium contrast agents have long been recognized in vitro, and deposition of gadolinium in tissues has been described in animal models since at least 1984. The first major study that showed deposition in humans appeared in 1998 regarding patients with renal failure and in 2004 in patients with normal renal function. The historical literature indicates that gadolinium retention in healthy patients is occurring, although the clinical consequences of deposition remain unknown.

BACKGROUND AND PURPOSE: Different T1-weighted sequences have been used for qualitative and quantitative evaluation of T1 signal intensity related to gadolinium deposition in the dentate nucleus in patients who underwent several enhanced MR imaging studies. Our purpose was to perform an intraindividual qualitative and quantitative comparison between T1-weighted spin-echo and 3D magnetization-prepared rapid acquisition of gradient echo sequences in patients who had multiple exposures to gadodiamide. MATERIALS AND METHODS: Our retrospectively selected population included 18 patients who underwent at least 3 administrations of gadodiamide and had a baseline and a final MR imaging performed with both T1-weighted sequences. Qualitative and quantitative analyses were independently performed. Dentate nucleus/middle cerebellar peduncle signal-intensity ratios and signal changes between the baseline and final examinations were compared by using the Wilcoxon signed rank test. Correlation between quantitative and qualitative evaluations was assessed by using a polyserial correlation test. RESULTS: The differences between the 2 sequences for both baseline and last examination dentate nucleus/middle cerebellar peduncle ratios were statistically significant (P = .008 and P = .006, respectively); however, the signal-intensity changes of the ratios with time were not (P = .64). The correlation between the qualitative and quantitative analysis was very strong (near-perfect) (r = 0.9) for MPRAGE and strong (r = 0.63) for spin-echo sequences. CONCLUSIONS: T1-weighted spin-echo and MPRAGE sequences cannot be used interchangeably for qualitative or quantitative analysis of signal intensity in the dentate nucleus in patients who received gadodiamide. Baseline and final examination ratios should be evaluated across time by using the same sequence. Qualitative analysis performed with MPRAGE correlated better with quantitative analysis and may offer advantages over spin-echo sequences for research purposes.

In current practice, gadolinium-based contrast agents have been considered safe when used at clinically recommended doses in patients without severe renal insufficiency. The causal relationship between gadolinium-based contrast agents and nephrogenic systemic fibrosis in patients with renal insufficiency resulted in new policies regarding the administration of these agents. After an effective screening of patients with renal disease by performing either unenhanced or reduced-dose-enhanced studies in these patients and by using the most stable contrast agents, nephrogenic systemic fibrosis has been largely eliminated since 2009. Evidence of in vivo gadolinium deposition in bone tissue in patients with normal renal function is well-established, but recent literature showing that gadolinium might also deposit in the brain in patients with intact blood-brain barriers caught many individuals in the imaging community by surprise. The purpose of this review was to summarize the literature on gadolinium-based contrast agents, tying together information on agent stability and animal and human studies, and to emphasize that low-stability agents are the ones most often associated with brain deposition. info:eu-repo/semantics/publishedVersion

This summary attempts to provide forward-looking concepts regarding gadolinium related toxicity, as discussed in further detail in this issue.

Background The molecular structure, charge, thermodynamic and kinetic stability are approximately the same for gadodiamide and gadoversetamide, the main substantive difference is that gadodiamide is manufactured with 5% free ligand to form Omniscan® and gadoversetamide with 10% free ligand to form OptiMARK®. Purpose To determine the relative risk of Nephrogenic Systemic Fibrosis (NSF) between gadodiamide (Omniscan®) and gadoversetamide (OptiMARK®) and to explore the potential contribution of the amount of excess ligand added to their commercial formulations. Materials and methods In this retrospective observational study, the number of doses and NSF cases associated with these agents were calculated based on two different approaches: the number of doses was determined based on pharmaceutical companies' information, and the number of unconfounded NSF cases was obtained from the previously published literature based on a legal database. A second analysis estimates the number of doses and NSF cases from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Results Approximately 87 million and 12 million doses of Omniscan® and OptiMARK®, respectively, have been administered worldwide since their original approval for use in the various countries throughout the world. A total of 197 and 8 unconfounded cases of NSF have been reported with Omniscan® and OptiMARK®, rendering an incidence of 2.3/million and 0.7/million for these agents, respectively. The FAERS analysis suggested reported incidences of 13.1/million and 5.0/million. Conclusion There is an approximately 3-fold greater incidence of NSF from Omniscan® than OptiMARK®. The difference in incidence might reflect the lesser quantity of added free ligand to the formulation of Omniscan®.

Pancreatic cross-sectional imaging has been widely used to diagnose and stage pancreatic neoplasms. The most commonly used techniques include multidetector CT, MRI, and endoscopic ultrasonography. Hybrid imaging including positron emission tomography combined with CT has a limited role. Dedicated imaging applications of these modalities for the evaluation of pancreatic neoplasms and their accuracies for different neoplasms are summarized in this review. Critical and differential imaging findings of the most common neoplasms of the pancreas, including adenocarcinoma, neuroendocrine tumors, cystic neoplasms, lymphoma, and metastases, emphasizing the most accurate imaging techniques are also discussed. Additionally, the most common mimics of the pancreatic neoplasms and their imaging findings are reviewed. This review contains 32 references, 13 figures, and 5 tables. Key words: adenocarcinoma, CT, EUS, intraductal papillary mucinous neoplasm, mucinous cystic neoplasm, MRI, neuroendocrine tumors, PET-CT, serous cystadenoma

There is a constantly evolving knowledgebase regarding the safety of MRI in pregnant patients, as well as the safety of gadolinium administration, given potential fetal risks. This review provides an overview of national and international recommendations for patient screening and safety by trimester, evaluates the most recent literature regarding administration of gadolinium in pregnant patients, and discusses technical requirements when imaging pregnant patients. A protocol for imaging pregnant patients is provided, and multiple common indications for MRI in pregnancy are discussed. Level of Evidence 5. Technical Efficacy Stage 5. J. Magn. Reson. Imaging 2019;49:621-631.

Evaluation of liver metastases is one of the most common indications for liver imaging. Imaging plays a key role in the of assessment liver metastases. A variety of imaging techniques, including ultrasonography, computed tomography, MRI and PET combined with CT scan are available for diagnosis, planning treatment, and follow-up treatment response. In this paper, the authors present the role of imaging for the assessment of liver metastases and the contribution of each of the different imaging techniques for their evaluation and management. Following recent developments in the field of oncology, the authors also present the importance of imaging for the assessment of liver metastases response to therapy. Finally, future perspectives on imaging of liver metastases are presented.

To determine if a correlation exists between the number of previous enhanced magnetic resonance (MR) imaging examinations and high signal intensity in the globus pallidus (GP) and dentate nucleus (DN) in patients who received gadodiamide (Omniscan), a linear nonionic gadolinium-based contrast agent, and in those who received gadobenate dimeglumine (MultiHance), a linear ionic contrast agent.Institutional review board approval was obtained for this single-center retrospective study, with waiver of informed consent. The study population included 69 patients divided into two groups: Group 1 included patients who underwent gadodiamide-enhanced MR imaging, and group 2 included patients who underwent gadobenate dimeglumine-enhanced MR imaging. Two radiologists conducted a quantitative analysis of unenhanced T1-weighted images by using region of interest measurements. The GP-to-thalamus (TH) signal intensity ratio, DN-to-middle cerebellar peduncle (MCP) signal intensity ratio and relative percentage change (Rchange) between the first and last examinations for each patient were calculated. Relation between the signal intensity ratios and Rchange and the number of enhanced MR imaging examinations was analyzed by using a generalized additive model. Inter- and intraobserver agreement was evaluated with the Lin concordance correlation coefficient test.Group 1 included 23 patients (19 female), with a mean of 5.0 doses ± 2.4 (standard deviation) (range, 3-11 doses) administered. Group 2 included 46 patients (24 female) with a mean of 4.6 doses ± 2.2 (range, 3-11 doses) administered. The interval between the first and last examination was 1500.1 days ± 780.2 (range, 98-3097 days) for group 1 and 1086.2 days ± 582.9 (range, 94-2633) for group 2. All patients had normal liver and renal function. Gadodiamide showed a significant increase in DN:MCP and GP:TH (P.001 for both) and in Rchange (P = .001 for GP:TH, P.001 for DN:MCP). In group 2, there was no significant increase in DN:MCP or GP:TH over time or in Rchange for GP:TH, but there was a significant trend toward an increase in Rchange for DN:MCP (P = .013). Interobserver agreement was almost perfect (0.99; 95% confidence interval: 0.99, 0.99) for all evaluated structures. Intraobserver agreement was substantial to almost perfect for both readers.A significant increase in GP:TH and DN:MCP is associated with multiple gadodiamide-enhanced studies but not with gadobenate dimeglumine-enhanced studies, likely reflecting differences in stability and elimination of both contrast agents. Rate-of-change data indirectly suggest gadolinium deposition in the DN with gadobenate dimeglumine use, although it is considerably less than that with gadodiamide use.

The purpose of this study was to determine the incidence of nephrogenic systemic fibrosis (NSF) in patients with chronic kidney disease (CKD) and moderate-to-severe impairment of kidney function who had not previously been exposed to gadolinium-based contrast agents (GBCAs) or referred to undergo contrast-enhanced MRI with gadobenate dimeglumine or gadoteridol.Two multicenter prospective cohort studies evaluated the incidence of unconfounded NSF in patients with stage 3 CKD (estimated glomerular filtration rate [eGFR] in cohort 1, 30-59 mL/min/1.73 m(2)) or stage 4 or 5 CKD (eGFR in cohort 2,30 mL/min/1.73 m(2)) after injection of gadobenate dimeglumine (study A) or gadoteridol (study B). A third study (study C) determined the incidence of NSF in patients with stage 4 or 5 CKD who had not received a GBCA in the 10 years before enrollment. Monitoring for signs and symptoms suggestive of NSF was performed via telephone at 1, 3, 6, and 18 months, with clinic visits occurring at 1 and 2 years.For studies A and B, the populations evaluated for NSF comprised 363 and 171 patients, respectively, with 318 and 159 patients in cohort 1 of each study, respectively, and with 45 and 12 patients in cohort 2, respectively. No signs or symptoms of NSF were reported or detected during the 2 years of patient monitoring. Likewise, no cases of NSF were reported for any of the 405 subjects enrolled in study C.To our knowledge, and consistent with reports in the literature, no association of gadobenate dimeglumine or gadoteridol with unconfounded cases of NSF has yet been established. Study data confirm that both gadoteridol and gadobenate dimeglumine properly belong to the class of GBCAs considered to be associated with the lowest risk of NSF.

To assess the feasibility of high-resolution 3D-gradient-recalled echo (GRE) fat-suppressed T1-weighted images using controlled aliasing acceleration technique (CAIPIRINHA-VIBE), and compare image quality and lesion detection to standard-resolution 3D-GRE images using conventional acceleration technique (GRAPPA-VIBE). Eighty-four patients (41 males, 43 females; age range: 14–90 years, 58.8 ± 15.6 years) underwent abdominal MRI at 1.5 T with CAIPIRINHA-VIBE [spatial resolution, 0.76 ± 0.04 mm] and GRAPPA-VIBE [spatial resolution, 1.17 ± 0.14 mm]. Two readers independently reviewed image quality, presence of artefacts, lesion conspicuity, and lesion detection. Kappa statistic was used to assess interobserver agreement. Wilcoxon signed-rank test was used for image qualitative pairwise comparisons. Logistic regression with post-hoc testing was used to evaluate statistical significance of lesions evaluation. Interobserver agreement ranged between 0.45-0.93. Pre-contrast CAIPIRINHA-VIBE showed significantly (p

The purpose of the study was to evaluate the feasibility and protocol optimization of whole-body hybrid MR–PET system performed 1-month after post-locoregional thermoablative procedures for hepatocellular carcinomas (HCCs). Eight patients (6 men and 2 women; mean age, 56.6 ± 5.5 years) with 9 ablated HCCs constituted our study population. Three readers interpreted the studies to determine the presence or absence of residual malignancy. Two readers independently assessed the fused MR–PET images to compare registration accuracy of two types of T2-weighted (triggered T2 half-Fourier acquisition single-shot turbo spin-echo and turbo spin-echo) and T1-weighted [Cartesian and radial 3D gradient echo (GRE)]. Image quality evaluation of both 3D-GRE T1-weighted sequences was evaluated. Kappa statistics were used to measure inter-observer agreement. Non-parametric Kruskal–Wallis and Wilcoxon signed-rank tests were used for qualitative data analysis. Definite residual tumor was observed in 3/9 ablations; two were PET positive. All residual tumors were isovascular on MRI. Radial 3D-GRE demonstrated significantly superior MR–PET subjective co-registration in comparison with the remaining sequences and showed a non-significant trend toward higher image quality scores than Cartesian GRE. Whole-body hybrid MR–PET is feasible as a part of 1-month follow-up post-locoregional thermoablative treatment for HCC. Radial 3D-GRE offers improved co-registration with PET data, with overall good image quality.

Purpose This study aims to describe the self-reporting symptoms experienced by individuals with self-reported normal renal function after gadolinium based contrast agent (GBCA) administration. Materials and methods This HIPAA-compliant, IRB-approved study consisted of an anonymous online survey of patients who believe that they suffer from gadolinium toxicity. 50 respondents completed the nine-question survey. Results Fifty (100%) of the subjects ascribed their complaints to gadolinium exposure. Thirty-three (66%) described the onset immediately following GBCA administration and 16 (32%) within 6 weeks. The most common symptoms included bone/joint pain and head/neck symptoms including headache, vision change, and hearing change (77.6% each). Other symptoms occurred with lesser incidence. Conclusions This survey represents an initial description of patients with normal renal function who self-described toxicity related to GBCA administration. Bone and joint complaints and skin changes are two of the most common complaints.

Until 2006, the main considerations regarding safety for all gadolinium-based contrast agents (GBCAs) were related to short-term adverse reactions. However, the administration of certain "high-risk" GBCAs to patients with renal failure resulted in multiple reported cases of nephrogenic systemic fibrosis. Findings have been reported regarding gadolinium deposition within the body and various reports of patients who report suffering from acute and chronic symptoms secondary to GBCA's exposure. At the present state of knowledge, it has been proved that gadolinium deposits also occur in the brain, irrespective of renal function and GBCAs stability class. To date, no definitive clinical findings are associated with gadolinium deposition in brain tissue. Gadolinium deposition disease is a newly described and probably infrequent entity. Patients presenting with gadolinium deposition disease may show signs and symptoms that somewhat follows a pattern similar but not identical, and also less severe, to those observed in nephrogenic systemic fibrosis. In this review, we will address gadolinium toxicity focusing on these 2 recently described concerns.

Resumen Objetivo Analizar si el aumento de la resolucion temporal utilizando mayores factores de reduccion (FR) de imagen en paralelo (IP), tanto en apnea como con respiracion libre, utilizando una secuencia 3D con eco de gradiente (EG) potenciada en T1, sin contraste y una bobina de multiples elementos (phased array) de 32 canales, proporciona una calidad de imagen diagnostica, con posibilidad de ser aplicada en pacientes que no puedan cooperar para mantener la apnea. Material y metodos Se incluyeron en el estudio 9 sujetos sanos (5 mujeres y 4 varones; rango de edad: 20-49; media: 36 anos). Se les realizo un estudio de RM abdominal con secuencias 3D EG en un equipo de 1,5T con bobina de multiples elementos (phased-array) de 32 canales con FR de imagen en paralelo de 2, 4 y 6, en apnea y con respiracion libre. Dos revisores evaluaron retrospectiva y cualitativamente la calidad de imagen de las secuencias, la magnitud de los artefactos, incluyendo los artefactos de movimiento por reduccion de senales, de solapamiento (aliasing) , de granulado de los pixeles y la heterogeneidad de la senal. Los resultados se compararon mediante la prueba de Wilcoxon de los rangos con signo y la correccion de Bonferroni para comparaciones multiples. Resultados La adquisicion en apnea proporciono mejor calidad de imagen y menos artefactos que la adquisicion con respiracion libre. La tasa de artefactos fue mayor para FR mas altos. La mejor calidad se obtuvo con secuencias en apnea con un FR = 2. Un FR = 4 presento tasas menores pero diagnosticas (p = 0,004). La severidad de los artefactos, en especial el granulado de los pixeles (p = 0,004), hizo que las secuencias con un FR = 6 no fueran diagnosticas. Ninguna de las secuencias obtenidas con respiracion libre fue diagnostica. Conclusion Las secuencias obtenidas en apnea con un FR = 2 presentaron una calidad de imagen excelente, y aquellas con un FR = 4 presentaron una calidad buena y potencialmente se pueden aplicar en pacientes poco colaboradores. Ninguna de las secuencias obtenidas con respiracion libre se considero diagnostica.

Purpose To investigate whether increasing temporal resolution with higher parallel imaging (PI) reduction factors (RF) in both breath-hold and free breathing approaches, using a non-contrast T1-weighted 3D gradient echo (GRE) sequence and a 32-channel phased array coil, permits diagnostic image quality, with potential application in patients unable to cooperate with breath-hold requirements. Materials and methods The 9 healthy subjects (5 females and 4 males; age range was 20–49, mean 36 yrs) were recruited. A 3D GRE MR imaging of the abdomen was performed on 1.5 T MR system using a 32-element phased-array torso coil with PI RFs of 2, 4 and 6, breath hold and free breathing. Two reviewers retrospectively qualitatively evaluated all sequences for image quality, extent of artifacts, including motion, truncation, aliasing, pixel graininess and signal heterogeneity. The results were compared using Wilcoxon signed rank and a Bonferroni adjustment was applied for multiple comparisons. Results Image quality and extent of artifacts were better with breath hold than with free breathing acquisitions. The rate of artifacts increased with higher RF. The best quality was acquired with breath hold sequence using RF = 2. RF = 4 had lower but diagnostic rates (p = 0.004). The severity of artifacts, mainly pixel graininess (p = 0.004), rendered sequences with RF = 6 non-diagnostic. All sequences were non-diagnostic in free breathing acquisitions. Conclusion Breath hold sequences with RF = 2 had excellent quality and RF = 4 had good quality and may be potentially used in partially cooperative patients. None of the sequences was considered diagnostic in free breathing acquisitions.

The aim of the study was to evaluate the acute adverse events rate and enhancement properties of gadoterate meglumine (Dotarem(®)) and gadobenate dimeglumine (MultiHance(®)) in a small-scale controlled double-blinded study, using inter- and intra-individual comparisons.Forty-one randomly selected patients were scanned with Dotarem(®). The rate of adverse reactions, qualitative and quantitative image evaluation was performed vs. a control group of 46 patients who underwent MultiHance(®) over the same 1-month time period (population 1), and 27 patients who underwent both Dotarem(®) and MultiHance(®)-enhanced body MRI studies within an 18-month period (population 2). Data were subjected to statistical analysis.Only 1 mild acute adverse event (vomiting) was observed in population 1 (with Dotarem(®)). Blinded assessment of image quality was good for both agents in all patients. Population 1 showed significantly higher liver percentage enhancement with MultiHance(®) (p0.0001). There was a trend to higher pancreas-to-liver enhancement with Dotarem(®), significant in population 2 (p = 0.0333).This small-scale multi-blinded study characterizes a strategy to objectively assess intravenous contrast agents, which may be an ideal method to evaluate whether a new contrast agent should be introduced for clinical use at any institution, and to re-evaluate the agent in standard use. Whenever available, intra-individual assessment may be ideal.

Magnetic resonance (MR) imaging plays an important role in assessment of the full range of abdominal disease. The appropriate use of cooperative and motion-resistant protocols can allow accurate determination of the character of focal lesions in the abdomen under most circumstances. This article discusses current MR techniques and the proper use of MR imaging in the diagnostic evaluation of cooperative and noncooperative patients.

The purpose of this study was to retrospectively evaluate early dynamic serial gadolinium-enhanced and chemical-shift imaging (CSI) MRI to distinguish benign from malignant adrenal tumors.Between July 2007 and December 2011, 205 patients with 239 adrenal lesions (177 adenomas, 54 metastases, 5 pheochromocytomas, and 3 adrenal cortical carcinomas) underwent early dynamic serial gadolinium-enhanced MRI and CSI. CSI was assessed qualitatively and by calculating the adrenal index, and enhancement patterns were evaluated qualitatively and quantitatively. Statistical analyses were performed.Most adenomas exhibited either an arterial blush or homogeneous enhancement, whereas most metastases showed early peripheral or heterogeneous enhancement. Visualization of higher enhancement on arterial and venous phases enabled differentiation of adenomas from metastases in most cases. Moderate to high signal intensity drop on CSI was seen in 95.4% of adenomas and 14.8% of metastases. In lesions with this level of signal intensity drop, 87 of 88 lesions with a capillary blush were adenomas. Early dynamic serial imaging alone was a significant (p0.0001) indicator of nonadenoma (area under the curve [AUC], 0.912) with optimal sensitivity of 81% and specificity of 93% for differentiating adenomas from nonadenomas. Combined analysis (CSI and early dynamic serial imaging) was also significant (p0.0001 and p=0.0014, respectively) for diagnosing nonadenomas (AUC, 0.983) with optimal sensitivity of 94% and specificity of 98%.Early dynamic serial gadolinium-enhanced MRI aids in characterization of adrenal tumors, especially lesions that are categorized as indeterminate on the basis of CSI.

Magnetic resonance (MR) imaging is a robust imaging modality for evaluation of vascular diseases. Technological advances have made MR imaging widely available for accurate and time-efficient vascular assessment. In this article the clinical usefulness of MR imaging techniques and their application are reviewed, using examples of vascular abnormalities commonly encountered in clinical practice, including abdominal, pelvic, and thoracic vessels. Common pitfalls and problem solving in interpretation of vascular findings in body MR imaging are also discussed.

BACKGROUND Patients are being exposed to increasing levels of ionizing radiation, much of it from computed tomography (CT) scans. METHODS Adults without a cancer diagnosis who received 10 or more CT scans in 2010 were identified from North Carolina Medicaid claims data and were sent a letter in July 2011 informing them of their radiation exposure; those who had undergone 20 or more CT scans in 2010 were also telephoned. The CT scan exposure of these high-exposure patients during the 12 months following these interventions was compared with that of adult Medicaid patients without cancer who had at least 1 CT scan but were not in the intervention population. RESULTS The average number of CT scans per month for the high-exposure population decreased over time, but most of that reduction occurred 6-9 months before our interventions took place. At about the same time, the number of CT scans per month also decreased in adult Medicaid patients without cancer who had at least 1 CT scan but were not in the intervention population. LIMITATIONS Our data do not include information about CT scans that may have been performed during times when patients were not covered by Medicaid. Some of our letters may not have been received or understood. Some high-exposure patients were unintentionally excluded from our study because organization of data on Medicaid claims varies by setting of care. CONCLUSION Our patient education intervention was not temporally associated with significant decreases in subsequent CT exposure. Effecting behavior change to reduce exposure to ionizing radiation requires more than an educational letter or telephone call.