Gadolinium Deposition Disease: Current State of Knowledge and Expert Opinion.

ABSTRACT: This review describes the current knowledge of a form of gadolinium toxicity termed gadolinium deposition disease (GDD), supplemented with the opinions of the authors developed during 6 years of clinical experience treating GDD. Gadolinium deposition disease can also be considered a subset under the symptoms associated with gadolinium exposure rubric. Young and middle-aged White women of central European genetic origin are the most affected. The most common symptoms are fatigue, brain fog, skin pain, skin discoloration, bone pain, muscle fasciculations, and pins and needles, but a long list of additional symptoms is reported herein. The time of onset of symptoms ranges from immediate to 1 month after gadolinium-based contrast agent (GBCA) administration. The primary treatment is to avoid further GBCAs and metal removal through chelation. Presently, the most effective chelating agent is DTPA because of its high affinity with gadolinium. Flare development is an expected outcome, amenable to concurrent immune dampening. We emphasize in this review the critical nature of recognizing GDD when it first arises, as the disease becomes progressively more severe with each subsequent GBCA injection. It is generally very treatable after the first symptoms of GDD, often arising after the first GBCA injection. Future directions of disease detection and treatment are discussed.

Dynamic Serial Cytokine Measurements During Intravenous Ca-DTPA Chelation in Gadolinium Deposition Disease and Gadolinium Storage Condition: A Pilot Study.

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.

Severity of Flare Reactions in Diethylenetriamine Pentaacetate Chelations: Report on Different Immune Dampening Strategies in Clinical Practice.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Physicians with self-diagnosed gadolinium deposition disease: a case series.

OBJECTIVE: The objective of this study was to allow physicians with self-diagnosed gadolinium deposition disease symptoms to report their own experience. MATERIALS AND METHODS: Nine physicians (seven females), with a mean age of 50.5 ± 8.3 years, participated in this case series. Nationalities were American (n = 6), British, Portuguese, and Romanian. Medical practices included internal medicine (n = 2), trauma surgery, ophthalmology, gastroenterology, psychiatry, family medicine, obstetrics/gynecology, and general practice. RESULTS: Genetically, eight of the physicians were of central European origin. Underlying autoimmune conditions were present in four. Symptoms developed after a single injection in one physician and after multiple injections in eight. The precipitating agent was gadobenate dimeglumine in four physicians, gadobutrol in three, gadoterate meglumine in one, and gadopentetate dimeglumine in one. The most consistent symptoms were a burning sensation, brain fog, fatigue, distal paresthesia, fasciculations, headache, and insomnia. Eight of the physicians were compelled to change their practice of medicine. CONCLUSION: In the various physicians, gadolinium deposition disease showed common features and had a substantial impact on daily activity. Physicians are educated reporters on disease, so their personal descriptions should spark interest in further research.

OBJETIVO: O objetivo deste estudo foi possibilitar que médicos com sintomas de doença de deposição de gadolínio autodiagnosticada relatassem sua própria experiência. MATERIAIS E MÉTODOS: Nove médicos (sete mulheres), com média de idade de 50,5 ± 8,3 anos, participaram desta série de casos. As nacionalidades foram americana (n = 6), britânica, portuguesa e romena. As práticas médicas incluíram medicina interna (n = 2), traumatologia, oftalmologia, gastroenterologia, psiquiatria, medicina de família, ginecologia/obstetrícia e clínica geral. RESULTADOS: Geneticamente, oito dos médicos tinham origem europeia central. Condições autoimunes subjacentes estavam presentes em quatro médicos. Os sintomas se desenvolveram após uma única injeção em um médico e após várias injeções em oito. O agente precipitante foi gadobenato dimeglumina em quatro médicos, gadobutrol em três, gadoterato meglumina em um e gadopentetato dimeglumina em um. Os sintomas mais consistentes foram sensação de queimação, confusão mental, fadiga, parestesia distal, fasciculações, cefaleia e insônia. Oito dos médicos foram forçados a alterar a sua prática médica. CONCLUSÃO: Em vários médicos, a doença de deposição de gadolínio mostrou características comuns e teve um impacto substancial na atividade diária. Os médicos são repórteres treinados sobre doenças, assim, suas descrições pessoais devem despertar interesse em pesquisas futuras.

Physicians with self-diagnosed gadolinium deposition disease: a case series / Médicos com doença de deposição de gadolínio autodiagnosticada: relato de série

Abstract Objective: The objective of this study was to allow physicians with self-diagnosed gadolinium deposition disease symptoms to report their own experience. Materials and Methods: Nine physicians (seven females), with a mean age of 50.5 ± 8.3 years, participated in this case series. Nationalities were American (n = 6), British, Portuguese, and Romanian. Medical practices included internal medicine (n = 2), trauma surgery, ophthalmology, gastroenterology, psychiatry, family medicine, obstetrics/gynecology, and general practice. Results: Genetically, eight of the physicians were of central European origin. Underlying autoimmune conditions were present in four. Symptoms developed after a single injection in one physician and after multiple injections in eight. The precipitating agent was gadobenate dimeglumine in four physicians, gadobutrol in three, gadoterate meglumine in one, and gadopentetate dimeglumine in one. The most consistent symptoms were a burning sensation, brain fog, fatigue, distal paresthesia, fasciculations, headache, and insomnia. Eight of the physicians were compelled to change their practice of medicine. Conclusion: In the various physicians, gadolinium deposition disease showed common features and had a substantial impact on daily activity. Physicians are educated reporters on disease, so their personal descriptions should spark interest in further research.

Resumo Objetivo: O objetivo deste estudo foi possibilitar que médicos com sintomas de doença de deposição de gadolínio autodiagnosticada relatassem sua própria experiência. Materiais e Métodos: Nove médicos (sete mulheres), com média de idade de 50,5 ± 8,3 anos, participaram desta série de casos. As nacionalidades foram americana (n = 6), britânica, portuguesa e romena. As práticas médicas incluíram medicina interna (n = 2), traumatologia, oftalmologia, gastroenterologia, psiquiatria, medicina de família, ginecologia/obstetrícia e clínica geral. Resultados: Geneticamente, oito dos médicos tinham origem europeia central. Condições autoimunes subjacentes estavam presentes em quatro médicos. Os sintomas se desenvolveram após uma única injeção em um médico e após várias injeções em oito. O agente precipitante foi gadobenato dimeglumina em quatro médicos, gadobutrol em três, gadoterato meglumina em um e gadopentetato dimeglumina em um. Os sintomas mais consistentes foram sensação de queimação, confusão mental, fadiga, parestesia distal, fasciculações, cefaleia e insônia. Oito dos médicos foram forçados a alterar a sua prática médica. Conclusão: Em vários médicos, a doença de deposição de gadolínio mostrou características comuns e teve um impacto substancial na atividade diária. Os médicos são repórteres treinados sobre doenças, assim, suas descrições pessoais devem despertar interesse em pesquisas futuras.

Acute Chelation Therapy-Associated Changes in Urine Gadolinium, Self-reported Flare Severity, and Serum Cytokines in Gadolinium Deposition Disease.

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.

An initial investigation of serum cytokine levels in patients with gadolinium retention.

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.

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.

An initial investigation of serum cytokine levels in patients with gadolinium retention / Uma investigação inicial dos níveis séricos de citocinas em pacientes com retenção de gadolínio

Abstract 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.

MRI in pregnancy: Indications and practical considerations.

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.

Influence of excess ligand on Nephrogenic Systemic Fibrosis associated with nonionic, linear gadolinium-based contrast agents.

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®.

Intravenous Calcium-/Zinc-Diethylene Triamine Penta-Acetic Acid in Patients With Presumed Gadolinium Deposition Disease: A Preliminary Report on 25 Patients.

OBJECTIVES: 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). MATERIALS AND METHODS: 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. RESULTS: Gadolinium content increased in the urine, with an overall mean of 30.3-fold increase in the monthly regimen (P < 0.001) and 12.9-fold in the weekly regimen (P < 0.001). 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. CONCLUSIONS: Three courses of intravenous Ca-/Zn-DTPA therapy results in significantly increased urine content of Gd after treatment and moderate symptomatic improvement.

Multiple focal nodular hyperplasia: MRI features.

PURPOSE: To describe MRI features of multiple Focal Nodular Hyperplasia (FNHs). METHODS: 40 consecutive subjects (37 females, mean age, 38.8years) were included. All studies were independently reviewed. This was an observational study to define the radiological features of multifocal FNH. RESULTS: 130 lesions were evaluated. The majority (88.5%), were peripheral in location. 92.3% lesions were lobulated. Marked enhancement was present in 94.6% lesions. In the portal venous and delayed phase, 46.2% and 47.7% lesions were mildly hyperintense. Central scar was present in 77% lesions. CONCLUSIONS: Distinctive features included predominant subcapsular location and mild hyperintensity in the delayed phase, seen in nearly 50% of FNHs.

MRI features of primary rare malignancies of the liver: A report from four university centres.

PURPOSE: To determine if rare primary malignancies of the liver may have consistent features on magnetic resonance imaging (MRI). MATERIALS AND METHODS: This IRB-compliant retrospective study reviewed the records from the pathology departments of four university centres over an 11-year period from 2005-2016 to identify rare primary malignant tumours, which were cross-referenced with MRI records. MRI studies of these patients were reviewed to determine if these tumours exhibited consistent and distinctive features. RESULTS: Sixty patients were identified with rare primary liver tumours. The following distinctive features and frequency of occurrence were observed: mixed hepatocellular carcinoma-cholangiocarcinoma showed regions of wash-out in 7/19 of patients; 6/6 of fibrolamellar carcinomas demonstrated large heterogeneous lesions with large heterogeneous central scars; epithelioid haemangioendothelioma larger than 2 cm showed target-like enhancement in late-phase enhancement in 9/13; sarcomas excluding angiosarcoma had central necrosis in 3/9 and haemorrhage in 5/9; angiosarcomas showed centripedal progressive nodular enhancement in 3/6 and showed regions of haemorrhage in 3/6; and 7/7 of primary hepatic lymphomas showed encasement of vessels. CONCLUSION: Although helpful features for the differentiation of rare primary malignancies of the liver are identified, no MRI features appear to be specific and therefore histopathological confirmation is usually required for definitive diagnosis. KEY POINTS: • No MRI features appear to be specific for rare primary liver malignancies. • Haemorrhage is a helpful sign in diagnosis of primary hepatic sarcomas. • Angiosarcomas may show progressive nodular enhancement towards the centre mimicking haemangioma. • Vessel encasement is a helpful sign in diagnosis of primary hepatic lymphoma.

Comparison of Cartesian and radial acquisition on short-tau inversion recovery (STIR) sequences in breast MRI.

OBJECTIVE: The purpose of this study was to compare two short-tau inversion recovery (STIR) sequences, Cartesian and radial (BLADE) acquisitions, for breast magnetic resonance imaging (MRI) examinations. MATERIALS AND METHODS: Ninety-six women underwent 1.5 T breast MRI exam (48 Cartesian and 48 BLADE). Qualitative analysis including image artifacts, image quality, fat-suppression, chest-wall depiction, lesion detection, lymph node depiction and overall impression were evaluated by three blinded readers. Signal to noise ratios (SNRs) were calculated. Cronbach's alpha test was used to assess inter-observer agreement. Subanalyses of image quality, chest-wall depiction and overall impression in 15 patients with implants and image quality in 31 patients with clips were correlated using Pearson test. Wilcoxon rank sum test and t-test were performed. RESULTS: Motion artifacts were present in 100% and in 0% of the Cartesian and the BLADE exams, respectively. Chemical-shift artifacts were present in 8% of the Cartesian exams. Flow artifacts were more frequent on BLADE. BLADE sequence was statistically superior to Cartesian for all qualitative features (p < 0.05) except for fat-suppression (p = 0.054). In the subanalysis, BLADE was superior for implants and clips (p < 0.05). SNR was statistically greater for BLADE (48.35 vs. 16.17). Cronbach ranged from 0.502 to 0.813. CONCLUSION: BLADE appears to be superior to Cartesian acquisition of STIR imaging as measured by improved image quality, fewer artifacts, and improved chest wall and lymph node depiction.

OBJETIVO: Comparar duas sequências de aquisição, cartesiana e radial (BLADE) ponderadas em short-tau inversion recovery (STIR), em exames de ressonância magnética de mama. MATERIAIS E MÉTODOS: Noventa e seis pacientes foram submetidas a exame de ressonância magnética de mama em 1,5 T (48 aquisições STIR cartesianas e 48 aquisições STIR BLADE). A análise qualitativa incluindo artefatos, qualidade de imagem, supressão de gordura, avaliação da parede torácica, detecção de lesões, linfonodos e impressão geral foi avaliada independentemente por três leitores. Os signal to noise ratios (SNRs) foram calculados. Foi utilizado o teste alfa de Cronbach para avaliar a concordância interobservador. Subanálises da qualidade de imagem, avaliação da parede torácica e impressão geral em 15 pacientes com implantes e qualidade de imagem em 31 pacientes com clipes cirúrgicos foram correlacionadas aplicando o teste de Pearson. Os testes de Wilcoxon rank sum test e Student t foram utilizados para comparação qualitativa e quantitativa entre as duas sequências. RESULTADOS: Os artefatos de movimento estavam presentes em 100% e 0% dos exames de aquisição cartesiana e de BLADE, respectivamente. Os artefatos de desvio químico estavam presentes em 8% dos exames cartesianos. Artefatos de fluxo foram mais frequentes nas sequências BLADE. A sequência BLADE foi estatisticamente superior para todos os atributos qualitativos (p < 0,05), exceto na supressão de gordura (p = 0,054). O BLADE foi superior na avaliação dos implantes e clipes cirúrgicos (p < 0,05). O SNR foi estatisticamente superior na sequência BLADE (48,35 versus 16,17). Cronbach variou entre 0,502 e 0,813. CONCLUSÃO: A sequência BLADE foi superior à sequência de aquisição cartesiana de imagens na ponderação STIR, comprovada por uma melhor qualidade de imagem, menos artefatos e melhor avaliação da parede torácica e de linfonodos.

Comparison of Cartesian and radial acquisition on short-tau inversion recovery (STIR) sequences in breast MRI / Comparação de aquisições cartesiana e radial nas sequências short tau inversion recovery (STIR) na RM de mama

Abstract Objective: The purpose of this study was to compare two short-tau inversion recovery (STIR) sequences, Cartesian and radial (BLADE) acquisitions, for breast magnetic resonance imaging (MRI) examinations. Materials and Methods: Ninety-six women underwent 1.5 T breast MRI exam (48 Cartesian and 48 BLADE). Qualitative analysis including image artifacts, image quality, fat-suppression, chest-wall depiction, lesion detection, lymph node depiction and overall impression were evaluated by three blinded readers. Signal to noise ratios (SNRs) were calculated. Cronbach's alpha test was used to assess inter-observer agreement. Subanalyses of image quality, chest-wall depiction and overall impression in 15 patients with implants and image quality in 31 patients with clips were correlated using Pearson test. Wilcoxon rank sum test and t-test were performed. Results: Motion artifacts were present in 100% and in 0% of the Cartesian and the BLADE exams, respectively. Chemical-shift artifacts were present in 8% of the Cartesian exams. Flow artifacts were more frequent on BLADE. BLADE sequence was statistically superior to Cartesian for all qualitative features (p < 0.05) except for fat-suppression (p = 0.054). In the subanalysis, BLADE was superior for implants and clips (p < 0.05). SNR was statistically greater for BLADE (48.35 vs. 16.17). Cronbach ranged from 0.502 to 0.813. Conclusion: BLADE appears to be superior to Cartesian acquisition of STIR imaging as measured by improved image quality, fewer artifacts, and improved chest wall and lymph node depiction.

Resumo Objetivo: Comparar duas sequências de aquisição, cartesiana e radial (BLADE) ponderadas em short-tau inversion recovery (STIR), em exames de ressonância magnética de mama. Materiais e Métodos: Noventa e seis pacientes foram submetidas a exame de ressonância magnética de mama em 1,5 T (48 aquisições STIR cartesianas e 48 aquisições STIR BLADE). A análise qualitativa incluindo artefatos, qualidade de imagem, supressão de gordura, avaliação da parede torácica, detecção de lesões, linfonodos e impressão geral foi avaliada independentemente por três leitores. Os signal to noise ratios (SNRs) foram calculados. Foi utilizado o teste alfa de Cronbach para avaliar a concordância interobservador. Subanálises da qualidade de imagem, avaliação da parede torácica e impressão geral em 15 pacientes com implantes e qualidade de imagem em 31 pacientes com clipes cirúrgicos foram correlacionadas aplicando o teste de Pearson. Os testes de Wilcoxon rank sum test e Student t foram utilizados para comparação qualitativa e quantitativa entre as duas sequências. Resultados: Os artefatos de movimento estavam presentes em 100% e 0% dos exames de aquisição cartesiana e de BLADE, respectivamente. Os artefatos de desvio químico estavam presentes em 8% dos exames cartesianos. Artefatos de fluxo foram mais frequentes nas sequências BLADE. A sequência BLADE foi estatisticamente superior para todos os atributos qualitativos (p < 0,05), exceto na supressão de gordura (p = 0,054). O BLADE foi superior na avaliação dos implantes e clipes cirúrgicos (p < 0,05). O SNR foi estatisticamente superior na sequência BLADE (48,35 versus 16,17). Cronbach variou entre 0,502 e 0,813. Conclusão: A sequência BLADE foi superior à sequência de aquisição cartesiana de imagens na ponderação STIR, comprovada por uma melhor qualidade de imagem, menos artefatos e melhor avaliação da parede torácica e de linfonodos.

Gadolinium Retention and Toxicity-An Update.

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.

Magnetic resonance imaging of the cirrhotic liver: diagnosis of hepatocellular carcinoma and evaluation of response to treatment - Part 2.

In the second part of this review, we will describe the ancillary imaging features of hepatocellular carcinoma (HCC) that can be seen on standard magnetic resonance imaging (MRI) protocol, and on novel and emerging protocols such as diffusion weighted imaging and utilization of hepatocyte-specific/hepatobiliary contrast agent. We will also describe the morphologic sub-types of HCC, and give a simplified non-invasive diagnostic algorithm for HCC, followed by a brief description of the liver imaging reporting and data system (LI-RADS), and MRI assessment of tumor response following locoregional therapy.

Na segunda parte desta revisão descreveremos os achados de imagem auxiliares para o diagnóstico de carcinoma hepatocelular (CHC) e que podem ser observados num protocolo de ressonância magnética (RM) padrão e em protocolos emergentes que incluem imagens de difusão e aplicação de contrastes hepatoespecíficos/hepatobiliares. Descreveremos também os subtipos morfológicos de CHC e um algoritmo diagnóstico não invasivo simplificado para o CHC, seguido de uma breve descrição do liver imaging reporting and data system (LI-RADS) e avaliação por RM após terapêutica locorregional.

Magnetic resonance imaging of the cirrhotic liver: diagnosis of hepatocellular carcinoma and evaluation of response to treatment – Part 2 / Ressonância magnética do fígado cirrótico: diagnóstico de carcinoma hepatocelular e avaliação da resposta ao tratamento – Parte 2

Abstract In the second part of this review, we will describe the ancillary imaging features of hepatocellular carcinoma (HCC) that can be seen on standard magnetic resonance imaging (MRI) protocol, and on novel and emerging protocols such as diffusion weighted imaging and utilization of hepatocyte-specific/hepatobiliary contrast agent. We will also describe the morphologic sub-types of HCC, and give a simplified non-invasive diagnostic algorithm for HCC, followed by a brief description of the liver imaging reporting and data system (LI-RADS), and MRI assessment of tumor response following locoregional therapy.

Resumo Na segunda parte desta revisão descreveremos os achados de imagem auxiliares para o diagnóstico de carcinoma hepatocelular (CHC) e que podem ser observados num protocolo de ressonância magnética (RM) padrão e em protocolos emergentes que incluem imagens de difusão e aplicação de contrastes hepatoespecíficos/hepatobiliares. Descreveremos também os subtipos morfológicos de CHC e um algoritmo diagnóstico não invasivo simplificado para o CHC, seguido de uma breve descrição do liver imaging reporting and data system (LI-RADS) e avaliação por RM após terapêutica locorregional.

Modified approach to the characterization of adrenal nodules using a standard abdominal magnetic resonance imaging protocol.

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.

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.