Switching from linear to macrocyclic gadolinium‐based contrast agents halts the relative T 1 ‐Weighted signal increase in deep gray matter of children with brain tumors: A retrospective study

BackgroundStudies have shown signal intensity (SI) changes in the brains of children exposed to repeated doses of a gadolinium‐based contrast agent (GBCA).HypothesisThe trajectory of changes in relative dentate nucleus (DN) and globus pallidus (GP) SI in children receiving multiple doses of GBCA will alter when switched from linear to macrocyclic agents.Study TypeRetrospective longitudinal.PopulationThirty‐five children, age range 0.5–17.0 years, undergoing brain tumor follow‐up between 2006 and 2017.Field Strength/SequenceUnenhanced T1WI, serial scans at both 1.5T and 3T.AssessmentRegions of interest were drawn on DN, GP, and SIs normalized to middle cerebellar peduncle (DN/MCP) and cerebral white matter (GP/CWM), respectively. A change in SI ratios as a function of dose (slope gradient) calculated according to the type of contrast agent received: linear only, macrocyclic only, or switchover from linear to macrocyclic. For the latter, gradients were compared before and after switchover. The effect of anticancer treatment on slope gradient was tested.Statistical TestsOne‐sample t‐test or Mann–Whitney U‐test for slope gradients differing from zero. Independent samples t‐tests to compare slope gradient groups. Paired sample t‐tests to compare slope gradients before and after switchover.ResultsA significant (P < 0.05) increase in SI ratio was observed following multiple doses of linear but not macrocyclic agents: mean percentage increase per dose in SI was 0.063% vs. –0.034% for DN/MCP, and 0.078% vs. 0.004% for GP/CWM ratios. A significant (P < 0.05) change of SI trajectory in the DN/MCP ratio was demonstrated when switching from a linear to macrocyclic agent. There was no difference in SI trajectory between patients who had anticancer therapies and those who did not, DN/MCP P = 0.740; GP/BWM P = 0.694.Data ConclusionSwitching from linear to macrocyclic gadolinium‐based contrast agents seems to halt the relative T1 signal increase in deep gray matter in children. Anticancer treatments appeared to have no impact on the trajectory of T1 SI

Technical Aspects of MRI Signal Change Quantification After Gadolinium-Based Contrast Agents' Administration

Over the last 2years several studies have been published regarding gadolinium deposition in brain structures in patients with normal renal function after repeated administrations of gadolinium-based contrast agents (GBCAs). Most of the publications are magnetic resonance imaging (MRI) based retrospective studies, where gadolinium deposition may be indirectly measured by evaluating changes in T1 signal intensity (SI) in brain tissue, particularly in the dentate nucleus (DN) and/or globus pallidi (GP). The direct correlation between T1 signal changes and gadolinium deposition was validated by human pathology studies. However, the variability of the MR equipment and parameters used across different publications, along with the inherent limitations of MRI to assess gadolinium in human tissues should be acknowledged when interpreting those studies. Nevertheless, MRI studies remain essential regarding gadolinium bio-distribution knowledge. The aim of this paper is to overview current knowledge of technical aspects of T1 signal intensity evaluation by MRI and describe confounding factors, with the intention to achieve higher accuracy and maximize reproducibility.info:eu-repo/semantics/publishedVersio

Intensidad de la Senal ˜ en T1 en el Núcleo Dentado Tras la Administración del Agente de Contraste con Gadolinio Macrocíclico Gadoterato de Meglumina: un Estudio Observacional

Introduction and aims: Contradictory results have been reported about hyperintensity of the globus pallidus and/or dentate nucleus on unenhanced T1-weighted magnetic resonance (MR) images after exposure to various gadolinium-based contrast agents. This change in signal intensity varies with different gadolinium-based contrast agents. We aimed to determine whether signal intensity in the dentate nucleus is increased in unenhanced T1-weighted images in patients who have undergone multiple studies with the macrocyclic gadolinium-based contrast agent gadoterate meglumine. We thoroughly reviewed the literature to corroborate our results. Materials and methods: We included patients who had undergone more than 10 MR studies with gadoterate meglumine. We quantitatively analyzed the signal intensity in unenhanced T1-weighted MR images measured in regions of interest placed in the dentate nucleus and the pons, and we calculated the dentate nucleus-to-pons signal intensity ratios and the differences between the ratio in the first MR study and the last MR study. We used t-tests to evaluate whether the differences between the signal intensity ratios were different from 0. We also analyzed the subgroups of patients who had been administered <15 and ≥15 doses of gadoterate meglumine. We used Pearson correlation to determine the relationships between the differences in the signal intensity ratios and the number of doses of gadoterate meglumine administered. Results: The 54 patients (26 men) had received a mean of 13.8±3.47 doses (range, 10-23 doses). The difference in the dentate nucleus-pons signal intensity ratio between the first and last MR study was -0.0275±0.1917 (not significantly different from 0; p=0.2968) in the entire group, -0.0357±0.2204 (not significantly different from 0; p = 0.351 in the patients who had received <15 doses (n=34), and -0.0135±0.1332 (not significantly different from 0; p = 0.655) in those who had received ≥15 doses (n=20). Differences in signal intensity ratios did not correlate significantly with the accumulated dose of gadoterate meglumine (P = 0.9064; ρ = -0.0164 [95%]). Conclusions: Receiving more than 10 doses of gadoterate meglumine was not associated with increased signal intensity in the dentate nucleus.Introducción y objetivo: Se han notificado resultados contradictorios sobre un aumento en la intensidad de la se˜nal (IS) en las imágenes de resonancia magnética (RM) ponderadas en T1 no realzadas en el globo pálido y/o el núcleo dentado (ND) después de la exposición a varios agentes de contraste con gadolinio (ACG). Este cambio en la se˜nal varía en función del ACG específico. Nuestro objetivo fue investigar si existe un aumento en la IS del ND en imágenes ponderadas en T1 no realzadas en pacientes sometidos a múltiples administraciones del ACG macrocíclico gadoterato de meglumina. Se realizó una revisión exhaustiva de la bibliografía para corroborar nuestros resultados. Materiales y métodos: Se incluyeron pacientes que se habían sometido a más de 10 estudios de RM con contraste y administración exclusiva de gadoterato de meglumina. Se llevó a cabo un análisis cuantitativo mediante el uso de mediciones de regiones de interés en el ND y el puente en imágenes no realzadas ponderadas en T1. Se calcularon las proporciones ND-puente y las diferencias en las proporciones entre el inicio y la última RM realizada. Se utilizó una prueba de la t de una muestra para evaluar si las diferencias en la proporción de la IS difieren de 0. Se realizó un análisis de subgrupos de pacientes con <15 y ≥15 dosis. Se utilizó el análisis de correlación de Pearson para determinar las correlaciones entre las diferencias de las proporciones de la IS y el número de administraciones del ACG. Resultados: 54 pacientes (26 hombres) recibieron una media de 13,8 dosis ± 3,47 (desviación estándar [DE]) (rango, 10−23 dosis). La diferencia en la proporción de la IS ND-puente entre la primera y la última exploración de RM fue de -0,0275 ± 0,1917 y no difirió significativamente de 0 P = 0,2968) en el análisis general y en el análisis de subgrupos [(<15 (n = 34), -0,0357 ± 0,2204, P = 0,351 y ≥15 (n = 20), -0,0135 ± 0,1332, p = 0,655)]. Las diferencias en la proporción de la IS no se correlacionaron significativamente Pon la dosis acumulada de gadoterato de meglumina (P = 0,9064; = -0,0164 [95%]). Conclusiones: Más de 10 administraciones de gadoterato de meglumina no se asoció a un aumento de la IS en el ND.info:eu-repo/semantics/publishedVersio

Quantifying Regional and Global Liver Function Via Gadoxetic Acid Uptake

Liver function is a dominant factor in the survival of patients with hepatocellular carcinoma (HCC). Measures of regional and global liver function are critical in guiding treatments for intrahepatic cancers. Regional and global liver function assessments important for defining the magnitude and spatial distribution of radiation dose to preserve functional liver parenchyma and reduce incidence of hepatotoxicity from radiation therapy (RT) for intrahepatic cancer treatment. This individualized liver function-guided RT strategy is critical for patients with heterogeneous and poor liver function, often observed in cirrhotic patients treated for HCC. Dynamic gadoxetic-acid enhanced (DGAE) magnetic resonance imaging (MRI) allows investigation of liver function through observation of the uptake of contrast agent into the hepatocytes. This work seeks to determine if gadoxetic uptake rate can be used as a reliable measure of liver function, and to develop robust methods for uptake estimation with an interest in the therapeutic application of this knowledge in the case of intrahepatic cancers. Since voxel-by voxel fitting of the preexisting nonlinear dual-input two-compartment model is highly susceptible to over fitting, and highly dependent on data that is both temporally very well characterized and low in noise, this work proposes and validates a new model for quantifying the voxel-wise uptake rate of gadoxetic acid as a measure of regional liver function. A linearized single-input two-compartment (LSITC) model is a linearization of the pre-existing dual-input model but is designed to perform uptake quantification in a more robust, computationally simpler, and much faster manner. The method is validated against the preexisting dual-input model for both real and simulated data. Simulations are used to investigate the effects of noise as well as issues related to the sampling of the arterial peak in the characteristic input functions of DGAE MRI. Further validation explores the relationship between gadoxetic acid uptake rate and two well established global measures of liver function, namely: Indocyanine Green retention (ICGR) and Albumin-Bilirubin (ALBI) score. This work also establishes the relationships between these scores and imaging derived measures of whole liver function using uptake rate. Additionally, the same comparisons are performed for portal venous perfusion, a pharmacokinetic parameter that has been observed to correlate with function in patients with relatively good liver function, and has been used as a guide for individualized liver function-guided RT. For the patients assessed, gadoxetic acid uptake rate performs significantly better as a predictor of whole liver function than portal venous perfusion. This work also investigates the possible gains that could be introduced through use of gadoxetic uptake rate maps in the creation of function-guided RT plans. To this end, plans were created using both perfusion and uptake, and both were compared to plans that did not use functional guidance. While the plans were generally broadly similar, significant differences were observed in patients with severely compromised uptake that did not correspond with compromised perfusion. This dissertation also deals with the problem of quantifying uptake rate in suboptimal very temporally sparse or short DGAE MRI acquisitions. In addition to testing the limits of the LSITC model for these limited datasets (both realistic and extreme), a neural network-based approach to quantification of uptake rate is developed, allowing for increased robustness over current models.PHDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/163264/1/jjsimeth_1.pd

The Safety and Clinical Applications of Intrathecal Gadolinium-Enhanced MRI : A Systematic Review and Case Report

Gadoliniumpohjaisia kontrastiaineita käytetään magneettikuvauksessa lisäämään kuvien kontrastia ja parantamaan kudosten erottelukykyä. Intravaskulaarisessa käytössä niitä on pidetty erittäin turvallisina ja hyvin siedettyinä, mutta viime vuosina on havaittu, että gadoliniumia voi kertyä aivokudokseen. Vaikka gadoliniumpohjaisten kontrastiaineiden intratekaalinen käyttö ei ole virallisesti hyväksyttyä, menetelmän turvallisuus on osoitettu alustavasti useissa kliinisissä tutkimuksissa. Mahdollisia käyttöaiheita intratekaalisella gadoliniumilla tehostetulle magneettikuvaukselle (GdMK) ovat muun muassa likvorivuotojen ja likvorikierron häiriöiden diagnostiikka. Tämän katsauksen tavoite oli selvittää GdMK:n turvallisuutta ja hyödyllisyyttä aivojen ja selkäydinkanavan poikkeavuuksien diagnostiikassa. Kirjallisuushaussa Medline- ja Scopus-tietokannoista etsittiin alkuperäisartikkeleita ja tapausselostuksia, joissa 1) arvioitiin GdMK:n turvallisuutta ja/tai hyötyä kliinisessä käytössä, ja 2) kuvattiin toimenpiteen suoritus yksityiskohtaisesti. Täydentävää hakua tehtiin aihetta käsittelevien artikkelien kirjallisuusluetteloista. Katsaukseen otettiin mukaan 28 alkuperäisartikkelia ja 8 tapausselostusta. Neljässä tutkimuksessa GdMK:ta verrattiin suoraan yhteen tai useampaan muuhun kuvantamismenetelmään ja raportoitiin menetelmille diagnostisten testien tunnuslukuja (herkkyys, tarkkuus, PPV, NPV). Näiden neljän tutkimuksen laatua arvioitiin soveltaen QUADAS-2-kriteereitä. Meta-analyysiä ei tehty, koska aineisto oli heterogeeninen. Yhteensä 790 tutkimushenkilöä kuvannettiin GdMK:lla. Vakavia haittatapahtumia ei raportoitu. Yleisin haitta oli toimenpiteen jälkeinen päänsärky, jota esiintyi 83 potilaalla (11 %). Yhdelle potilaalle nousi toimenpiteen jälkeen kuume, yksi kärsi ohimenevästä täydellisestä muistin-menetyksestä (TGA) ja yksi sairastui bakteerimeningiittiin. GdMK:n herkkyys kallonpohjan likvorivuotojen diagnostiikassa oli 89-98 %. Kolme tutkimusta raportoi GdMK:n olevan varjoaine-TT:tä herkempi selkäydinkanavan likvorivuotojen diagnostiikassa. Lisäksi GdMK todettiin hyödylliseksi araknoidaalikystien, hydrokefaluksen ja neurokystiserkoosin diagnostiikassa. Gadoliniumpohjaisten kontrastiaineiden intratekaalinen käyttö vaikuttaa olevan turvallista ja hyvin siedettyä. Intravaskulaariseen käyttöön liittyvät haitat tulee kuitenkin huomioida myös intratekaalisessa käytössä, ja gadoliniumpohjaisia kontrastiaineita tulisi käyttää varoen potilailla, joilla on munuaisten vajaatoiminta. Vaikka intratekaaliset annokset ovat intravaskulaarisiin annoksiin nähden pieniä, intratekaaliseen käyttöön voi liittyä vaikeasti ennakoitavia haittoja, sillä annostelureitti vaikuttaa kontrastiaineen kinetiikkaan. GdMK:n etuja ovat säteilyrasituksen puuttuminen ja TT:tä parempi herkkyys muun muassa likvorivuotojen diagnostiikassa, mutta pitkäaikaishaittojen riski on huomioitava gadoliniumin intratekaalista käyttöä harkittaessa. Abstract Background: The intravenous use of gadolinium-based contrast agents (GBCAs) in MR imaging is well-established in clinical practice. GBCAs were long considered to be extremely safe, but in recent years some concerns have been raised over possible long-term adverse effects, including deposition of gadolinium in neural tissue. The intrathecal use of GBCAs is not approved by the EMA or FDA, but its relative safety and tolerability has been reported in several clinical studies. When administered intrathecally, GBCAs provide enhancement of CSF and good contrast between CSF and parenchyma. Therefore, potential clinical applications include evaluation of the subarachnoid space, CSF fistulas, and CSF flow dynamics. The objective of this review was to assess the safety and diagnostic value of intrathecal gadolinium-enhanced MRI (GdMRI) in clinical practice. Materials and methods: A search was carried out in the Medline and Scopus databases up to 30 November 2016. Original articles and case reports that 1) evaluated the safety and/or the diagnostic performance of GdMRI and 2) provided detailed information on the procedure were included. Data was collected on study design, sample size, patient demographics, GBCA type and dose, administration procedure, follow-up, adverse events, and diagnostic performance. Modified QUADAS-2 criteria were used to assess the methodological quality of four studies that compared GdMRI to other imaging modalities and reported diagnostic performance characteristics for GdMRI. Meta-analysis was not attempted due to the heterogeneity of the included studies. Results: A total of 36 studies with 790 subjects were included. There were no reports of serious adverse events associated with GdMRI. The most frequent adverse effect was mild to moderate postprocedural headache, which was reported in 83 patients (11 %). One patient developed a fever, one had an episode of TGA, and one developed pneumococcal meningitis after the procedure. In detection and localization of skull-base CSF leaks, four studies reported a sensitivity of 89-96 % for GdMRI. Three studies reported improved detection and localization of spinal CSF leaks by GdMRI compared to CECT. The diagnostic value of GdMRI for the evaluation of arachnoid cysts, hydrocephalus, and neurocysticercosis was also reported in small patient series. Conclusion: The intrathecal use of GBCAs appears to be safe and well-tolerated in the short term. Careful consideration is called for when performing GdMRI in patients with renal insufficiency, and the use of high-risk compounds should be avoided in all patients regardless of renal function. Although intrathecal doses of GBCAs are significantly lower than intravenous doses, no direct comparison can be made between the two due to differences in clearance kinetics. Because the experience on the intrathecal use of GBCAs is limited, the long-term safety of GdMRI remains unclear. In the diagnosis of CSF fistulas, GdMRI appears to have a higher sensitivity than CECT, and several small studies have shown the potential value of GdMRI in various other clinical situations. The benefits of improved diagnostics and lack of radiation exposure need to be weighed against the potential risk of long-term adverse effects when considering the intrathecal use of GBCAs, especially in young patients. More research is needed on the long-term safety of GdMRI before its widespread clinical use can be recommended