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2.
Radiographics ; 43(4): e220087, 2023 04.
Article in English | MEDLINE | ID: mdl-36952256

ABSTRACT

Gadoxetic acid is an MRI contrast agent that has specific applications in the study of hepatobiliary disease. After being distributed in the vascular and extravascular spaces during the dynamic phase, gadoxetic acid is progressively taken up by hepatocytes and excreted to the bile ducts during the hepatobiliary phase. The information derived from the enhancement characteristics during dynamic and hepatobiliary phases is particularly relevant in the detection and characterization of focal liver lesions and in the evaluation of the structure and function of the liver and biliary system. The use of new MRI sequences and advanced imaging techniques (eg, relaxometry, multiparametric imaging, and analysis of heterogeneity), the introduction of artificial intelligence, and the development of biomarkers and radiomic and radiogenomic tools based on gadoxetic acid-enhanced MRI findings will play an important role in the future in assessing liver function, chronic liver disease, and focal liver lesions; in studying biliary pathologic conditions; and in predicting treatment responses and prognosis. © RSNA, 2023 Quiz questions for this article are available in the supplemental material.


Subject(s)
Contrast Media , Digestive System Diseases , Gadolinium DTPA , Magnetic Resonance Imaging , Humans , Artificial Intelligence , Carcinoma, Hepatocellular , Contrast Media/administration & dosage , Gadolinium DTPA/administration & dosage , Gallbladder Diseases , Liver Neoplasms , Magnetic Resonance Imaging/methods , Retrospective Studies , Sensitivity and Specificity , Digestive System Diseases/diagnostic imaging , Diagnostic Techniques, Digestive System
3.
BMC Cancer ; 21(1): 1116, 2021 Oct 18.
Article in English | MEDLINE | ID: mdl-34663243

ABSTRACT

BACKGROUND: Abdominal computed tomography (CT) is the standard imaging method for patients with suspected colorectal liver metastases (CRLM) in the diagnostic workup for surgery or thermal ablation. Diffusion-weighted and gadoxetic-acid-enhanced magnetic resonance imaging (MRI) of the liver is increasingly used to improve the detection rate and characterization of liver lesions. MRI is superior in detection and characterization of CRLM as compared to CT. However, it is unknown how MRI actually impacts patient management. The primary aim of the CAMINO study is to evaluate whether MRI has sufficient clinical added value to be routinely added to CT in the staging of CRLM. The secondary objective is to identify subgroups who benefit the most from additional MRI. METHODS: In this international multicentre prospective incremental diagnostic accuracy study, 298 patients with primary or recurrent CRLM scheduled for curative liver resection or thermal ablation based on CT staging will be enrolled from 17 centres across the Netherlands, Belgium, Norway, and Italy. All study participants will undergo CT and diffusion-weighted and gadoxetic-acid enhanced MRI prior to local therapy. The local multidisciplinary team will provide two local therapy plans: first, based on CT-staging and second, based on both CT and MRI. The primary outcome measure is the proportion of clinically significant CRLM (CS-CRLM) detected by MRI not visible on CT. CS-CRLM are defined as liver lesions leading to a change in local therapeutical management. If MRI detects new CRLM in segments which would have been resected in the original operative plan, these are not considered CS-CRLM. It is hypothesized that MRI will lead to the detection of CS-CRLM in ≥10% of patients which is considered the minimal clinically important difference. Furthermore, a prediction model will be developed using multivariable logistic regression modelling to evaluate the predictive value of patient, tumor and procedural variables on finding CS-CRLM on MRI. DISCUSSION: The CAMINO study will clarify the clinical added value of MRI to CT in patients with CRLM scheduled for local therapy. This study will provide the evidence required for the implementation of additional MRI in the routine work-up of patients with primary and recurrent CRLM for local therapy. TRIAL REGISTRATION: The CAMINO study was registered in the Netherlands National Trial Register under number NL8039 on September 20th 2019.


Subject(s)
Colorectal Neoplasms/pathology , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/secondary , Magnetic Resonance Imaging , Multimodal Imaging , Tomography, X-Ray Computed , Adult , Contrast Media/administration & dosage , Gadolinium DTPA/administration & dosage , Humans , Liver Neoplasms/surgery , Prospective Studies
4.
Anticancer Res ; 41(9): 4411-4416, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34475062

ABSTRACT

BACKGROUND/AIM: Detection of hepatocellular carcinoma using intraoperative ultrasonography (IOUS) is indispensable for successful laparoscopic hepatectomy (LH). This study was performed to evaluate patients with intraoperatively unidentified tumours undergoing LH. PATIENTS AND METHODS: Seven patients who underwent LH for hepatocellular carcinoma and whose tumours were not detected using IOUS were included in this study. Clinical features, preoperative imaging, intraoperative imaging, surgical procedures, and pathological findings were evaluated. RESULTS: Using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging, all the tumours were enhanced in the arterial phase and rapidly washed out, becoming hypointense to the remainder of the liver. All tumours except one were <2 cm in size. Severe liver fibrosis was observed in all cases. Tumours that were invisible on preoperative ultrasonography also could not be detected using IOUS or indocyanine green fluorescence imaging. Five patients underwent hepatectomy based on anatomical landmarks and achieved curative resection, whereas curative resection failed in two patients. CONCLUSION: When tumours cannot be identified by IOUS, LH based on anatomical landmarks should be preferred. Importantly, invisible tumours on preoperative ultrasonography may not be identified intraoperatively during LH.


Subject(s)
Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/surgery , Liver Cirrhosis/pathology , Liver Cirrhosis/surgery , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Aged , Carcinoma, Hepatocellular/diagnostic imaging , Female , Gadolinium DTPA/administration & dosage , Hepatectomy , Humans , Indocyanine Green/administration & dosage , Laparoscopy , Liver Cirrhosis/diagnostic imaging , Liver Neoplasms/diagnostic imaging , Magnetic Resonance Imaging, Interventional , Male , Middle Aged , Tumor Burden , Ultrasonography, Interventional
5.
Mol Pharm ; 18(8): 2997-3009, 2021 08 02.
Article in English | MEDLINE | ID: mdl-34283621

ABSTRACT

Physiologically based pharmacokinetic (PBPK) models are increasingly used in drug development to simulate changes in both systemic and tissue exposures that arise as a result of changes in enzyme and/or transporter activity. Verification of these model-based simulations of tissue exposure is challenging in the case of transporter-mediated drug-drug interactions (tDDI), in particular as these may lead to differential effects on substrate exposure in plasma and tissues/organs of interest. Gadoxetate, a promising magnetic resonance imaging (MRI) contrast agent, is a substrate of organic-anion-transporting polypeptide 1B1 (OATP1B1) and multidrug resistance-associated protein 2 (MRP2). In this study, we developed a gadoxetate PBPK model and explored the use of liver-imaging data to achieve and refine in vitro-in vivo extrapolation (IVIVE) of gadoxetate hepatic transporter kinetic data. In addition, PBPK modeling was used to investigate gadoxetate hepatic tDDI with rifampicin i.v. 10 mg/kg. In vivo dynamic contrast-enhanced (DCE) MRI data of gadoxetate in rat blood, spleen, and liver were used in this analysis. Gadoxetate in vitro uptake kinetic data were generated in plated rat hepatocytes. Mean (%CV) in vitro hepatocyte uptake unbound Michaelis-Menten constant (Km,u) of gadoxetate was 106 µM (17%) (n = 4 rats), and active saturable uptake accounted for 94% of total uptake into hepatocytes. PBPK-IVIVE of these data (bottom-up approach) captured reasonably systemic exposure, but underestimated the in vivo gadoxetate DCE-MRI profiles and elimination from the liver. Therefore, in vivo rat DCE-MRI liver data were subsequently used to refine gadoxetate transporter kinetic parameters in the PBPK model (top-down approach). Active uptake into the hepatocytes refined by the liver-imaging data was one order of magnitude higher than the one predicted by the IVIVE approach. Finally, the PBPK model was fitted to the gadoxetate DCE-MRI data (blood, spleen, and liver) obtained with and without coadministered rifampicin. Rifampicin was estimated to inhibit active uptake transport of gadoxetate into the liver by 96%. The current analysis highlighted the importance of gadoxetate liver data for PBPK model refinement, which was not feasible when using the blood data alone, as is common in PBPK modeling applications. The results of our study demonstrate the utility of organ-imaging data in evaluating and refining PBPK transporter IVIVE to support the subsequent model use for quantitative evaluation of hepatic tDDI.


Subject(s)
Contrast Media/pharmacokinetics , Gadolinium DTPA/pharmacokinetics , Liver/diagnostic imaging , Liver/metabolism , Magnetic Resonance Imaging/methods , Rifampin/pharmacokinetics , Animals , Biological Transport, Active/drug effects , Biomarkers/metabolism , Cells, Cultured , Contrast Media/administration & dosage , Contrast Media/metabolism , Drug Interactions , Gadolinium DTPA/administration & dosage , Gadolinium DTPA/metabolism , Hepatocytes/drug effects , Hepatocytes/metabolism , Male , Models, Animal , Organic Anion Transporters/antagonists & inhibitors , Organic Anion Transporters/metabolism , Rats , Rifampin/administration & dosage , Rifampin/metabolism
6.
Sci Rep ; 11(1): 13950, 2021 07 06.
Article in English | MEDLINE | ID: mdl-34230532

ABSTRACT

Gadolinium based contrast agents (GBCA) are used to image patients using magnetic resonance (MR) imaging. In recent years, there has been controversy around gadolinium retention after GBCA administration. We sought to evaluate the potential toxicity of gadolinium in the rat brain up to 1-year after repeated gadodiamide dosing and tissue retention kinetics after a single administration. Histopathological and ultrastructural transmission electron microscopy (TEM) analysis revealed no findings in rats administered a cumulative dose of 12 mmol/kg. TEM-energy dispersive X-ray spectroscopy (TEM-EDS) localization of gadolinium in the deep cerebellar nuclei showed ~ 100 nm electron-dense foci in the basal lamina of the vasculature. Laser ablation-ICP-MS (LA-ICP-MS) showed diffuse gadolinium throughout the brain but concentrated in perivascular foci of the DCN and globus pallidus with no observable tissue injury or ultrastructural changes. A single dose of gadodiamide (0.6 mmol/kg) resulted in rapid cerebrospinal fluid (CSF) and blood clearance. Twenty-weeks post administration gadolinium concentrations in brain regions was reduced by 16-72-fold and in the kidney (210-fold), testes (194-fold) skin (44-fold), liver (42-fold), femur (6-fold) and lung (64-fold). Our findings suggest that gadolinium does not lead to histopathological or ultrastructural changes in the brain and demonstrate in detail the kinetics of a human equivalent dose over time in a pre-clinical model.


Subject(s)
Cells/ultrastructure , Gadolinium DTPA/administration & dosage , Gadolinium DTPA/pharmacology , Gadolinium/metabolism , Animals , Brain/drug effects , Brain/metabolism , Cells/drug effects , Cerebellum/drug effects , Cerebellum/ultrastructure , Dose-Response Relationship, Drug , Gadolinium DTPA/blood , Gadolinium DTPA/cerebrospinal fluid , Kidney/drug effects , Kidney/metabolism , Male , Rats, Sprague-Dawley , Spectrophotometry, Atomic , Time Factors
7.
Radiology ; 300(2): 279-284, 2021 08.
Article in English | MEDLINE | ID: mdl-34060939

ABSTRACT

A 66-year-old male patient with end-stage chronic kidney disease undergoing maintenance dialysis and with a history of group I intravenous gadolinium-based contrast media (GBCM) administration presented with clinical and pathologic findings consistent with nephrogenic systemic fibrosis. A summary of the evidence and recommendations for use of intravenous GBCM in patients with kidney disease is presented. © RSNA, 2021.


Subject(s)
Contrast Media/adverse effects , Gadolinium DTPA/adverse effects , Kidney Failure, Chronic/complications , Nephrogenic Fibrosing Dermopathy/chemically induced , Administration, Intravenous , Aged , Contrast Media/administration & dosage , Gadolinium DTPA/administration & dosage , Humans , Kidney Failure, Chronic/therapy , Male , Renal Dialysis , Risk Factors
8.
Sci Rep ; 11(1): 10778, 2021 05 24.
Article in English | MEDLINE | ID: mdl-34031487

ABSTRACT

The implementation of radiomics in radiology is gaining interest due to its wide range of applications. To develop a radiomics-based model for classifying the etiology of liver cirrhosis using gadoxetic acid-enhanced MRI, 248 patients with a known etiology of liver cirrhosis who underwent 306 gadoxetic acid-enhanced MRI examinations were included in the analysis. MRI examinations were classified into 6 groups according to the etiology of liver cirrhosis: alcoholic cirrhosis, viral hepatitis, cholestatic liver disease, nonalcoholic steatohepatitis (NASH), autoimmune hepatitis, and other. MRI examinations were randomized into training and testing subsets. Radiomics features were extracted from regions of interest segmented in the hepatobiliary phase images. The fivefold cross-validated models (2-dimensional-(2D) and 3-dimensional-(3D) based) differentiating cholestatic cirrhosis from noncholestatic etiologies had the best accuracy (87.5%, 85.6%), sensitivity (97.6%, 95.6%), predictive value (0.883, 0.877), and area under curve (AUC) (0.960, 0.910). The AUC was larger in the 2D-model for viral hepatitis, cholestatic cirrhosis, and NASH-associated cirrhosis (P-value of 0.05, 0.05, 0.87, respectively). In alcoholic cirrhosis, the AUC for the 3D model was larger (P = 0.01). The overall intra-class correlation coefficient (ICC) estimates and their 95% confident intervals (CI) for all features combined was 0.68 (CI 0.56-0.87) for 2D and 0.71 (CI 0.61-0.93) for 3D measurements suggesting moderate reliability. Radiomics-based analysis of hepatobiliary phase images of gadoxetic acid-enhanced MRI may be a promising noninvasive method for identifying the etiology of liver cirrhosis with better performance of the 2D- compared with the 3D-generated models.


Subject(s)
Cholestasis/diagnostic imaging , Gadolinium DTPA/administration & dosage , Liver Cirrhosis/etiology , Radiographic Image Interpretation, Computer-Assisted/methods , Adolescent , Adult , Aged , Aged, 80 and over , Area Under Curve , Cholestasis/complications , Diagnosis, Differential , Female , Humans , Liver Cirrhosis/diagnostic imaging , Magnetic Resonance Imaging , Male , Middle Aged , Young Adult
9.
Medicine (Baltimore) ; 100(20): e25804, 2021 May 21.
Article in English | MEDLINE | ID: mdl-34011043

ABSTRACT

ABSTRACT: The aim of the study was to assess the potential role of preoperative gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) dynamic enhanced MR imaging for diagnosing microvascular invasion (MVI) and pathological grade of hepatocellular carcinoma (HCC).A total of 113 consecutive HCC patients confirmed by histopathology underwent preoperative Gd-EOB-DTPA dynamic enhanced MRI were included. Signal intensity (SI) of peritumoral, normal liver tissue and tumor parenchyma during arterial phase and hepatobiliary phase (HBP) were analyzed. The receiver operating characteristic (ROC) curves were performed to assess the potential diagnostic capability for MVI and pathological grade of HCC. Kaplan-Meier method was performed to estimate the recurrence-free survival rate and compared using the log rank test.SI ratio of peritumoral tissue to normal liver in arterial phase (SIAp/Al) was independently associated with MVI [odds ratio (OR) = 3.115, 95% confidence interval (CI): 1.867-5.198] and pathological grades (OR = 1.437, 95% CI: 1.042-1.981). The area under the curve (AUC) of SIAp/Al was equivalent to the SI of tumor parenchyma on arterial phase (SIAt) in distinguishing low and high pathological grades. However, the AUC of SIAp/Al (0.851) was larger than peritumoral hypointensity on HBP (0.668) for distinguishing MVI. The recurrence-free survival rate of HCC patients with SIAp/Al<1.1 was higher than HCC with SIAp/Al≥1.1(P = .025).The SIAp/Al in preoperative Gd-EOB-DTPA dynamic enhanced MR imaging is a potential diagnosis marker for MVI and pathological grade of HCC noninvasively. The higher SIAp/Al may predict the poor prognosis of HCC after surgery.


Subject(s)
Carcinoma, Hepatocellular/diagnosis , Liver Neoplasms/diagnosis , Liver/diagnostic imaging , Magnetic Resonance Imaging/methods , Neoplasm Recurrence, Local/epidemiology , Adult , Aged , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/surgery , Contrast Media/administration & dosage , Disease-Free Survival , Female , Follow-Up Studies , Gadolinium DTPA/administration & dosage , Hepatectomy , Humans , Liver/blood supply , Liver/pathology , Liver/surgery , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Male , Microvessels/diagnostic imaging , Microvessels/pathology , Middle Aged , Neoplasm Grading , Neoplasm Invasiveness/diagnostic imaging , Neoplasm Invasiveness/pathology , Neoplasm Recurrence, Local/pathology , Predictive Value of Tests , Preoperative Period , Prognosis , ROC Curve , Retrospective Studies
10.
J Comput Assist Tomogr ; 45(3): 359-366, 2021.
Article in English | MEDLINE | ID: mdl-33661153

ABSTRACT

OBJECTIVES: This study aimed to compare the accuracy of assessing the arterial hypervascularity of hepatocellular carcinoma (HCC) on dynamic computed tomography (CT) scans and gadoxetic acid (EOB)-enhanced magnetic resonance imaging (MRI) scans performed with radial sampling. METHODS: We studied the images of 40 patients with hypervascular HCC. A radiologist recorded the standard deviation of the attenuation (or the signal intensity [SI]) in subcutaneous fat tissue as the image noise (N) and calculated the contrast-to-noise ratio (CNR) as follows: (CNR) = (n-ROIT - n-ROIL)/N, where n-ROIT is the mean attenuation (or SI) of the tumor divided by the mean attenuation (or SI) of the aorta and n-ROIL is the mean attenuation (or SI) of the liver parenchyma divided by the mean attenuation (or SI) of the aorta. RESULTS: The CNR was significantly higher on EOB-enhanced MRI than on dynamic CT scans. CONCLUSIONS: For the assessment of HCC vascularity, EOB-enhanced MRI scans acquired with radial sampling were more accurate than dynamic CT images.


Subject(s)
Angiography/methods , Carcinoma, Hepatocellular/blood supply , Gadolinium DTPA/administration & dosage , Hepatic Artery/diagnostic imaging , Liver Neoplasms/blood supply , Radiographic Image Interpretation, Computer-Assisted/methods , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/diagnostic imaging , Female , Humans , Liver Neoplasms/diagnostic imaging , Magnetic Resonance Imaging , Male , Middle Aged , Retrospective Studies , Signal-To-Noise Ratio , Tomography, X-Ray Computed
11.
Int J Med Sci ; 18(3): 652-659, 2021.
Article in English | MEDLINE | ID: mdl-33437200

ABSTRACT

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


Subject(s)
Anesthetics, General/administration & dosage , Caudate Nucleus/drug effects , Extracellular Fluid/metabolism , Putamen/drug effects , Thalamus/drug effects , Administration, Inhalation , Animals , Caudate Nucleus/cytology , Caudate Nucleus/diagnostic imaging , Caudate Nucleus/metabolism , Extracellular Space/drug effects , Extracellular Space/metabolism , Gadolinium DTPA/administration & dosage , Infusions, Parenteral , Isoflurane/administration & dosage , Magnetic Resonance Imaging/methods , Models, Animal , Propofol/administration & dosage , Putamen/cytology , Putamen/diagnostic imaging , Putamen/metabolism , Rats , Rats, Sprague-Dawley , Thalamus/cytology , Thalamus/diagnostic imaging , Thalamus/metabolism
12.
Pediatr Cardiol ; 42(3): 492-500, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33515326

ABSTRACT

An ECG risk-score has been described that predicts high risk of subsequent cardiac arrest in young patients with hypertrophic cardiomyopathy (HCM). Myocardial fibrosis measured by cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) also affects prognosis. We assessed whether an ECG risk-score could be used as an indicator of myocardial fibrosis or perfusion deficit on CMR in HCM. In total 42 individuals (7-31 years); 26 HCM patients, seven genotype-positive, phenotype-negative individuals at risk of HCM (first-degree relatives) and nine healthy volunteers, underwent CMR to identify, and grade extent of, myocardial fibrosis and perfusion defect. 12-lead ECG was used for calculating the ECG risk-score (grading 0-14p). High-risk ECG (risk-score > 5p) occurred only in the HCM group (9/26), and the proportion was significantly higher vs mutation carriers combined with healthy volunteers (0/16, p = 0.008). Extent of LGE correlated to the ECG-score (R2 = 0.47, p = 0.001) in sarcomeric mutations. In low-risk ECG-score patients (0-2p), median percent of myocardium showing LGE (LGE%LVM) were: 0% [interquartile range, IQR, 0-0%], in intermediate-risk (3-5p): 5.4% [IQR 0-13.5%] and in high-risk (6-14p): 10.9% [IQR 4.2-12.3%]. ECG-score > 2p had a sensitivity and specificity of 79% and 84% to detect positive LGE on CMR and 77% vs. 75% to detect perfusion defects in sarcomeric mutations carriers. In patients with myocardial fibrosis as identified by LGE, median ECG risk-score was 8p [range 3-10p]. In conclusions, ECG risk-score > 2 p could be used as a cut-off for screening of myocardial fibrosis. Thus ECG risk-score is an inexpensive complementary tool in risk stratification of HCM in the young.


Subject(s)
Cardiomyopathy, Hypertrophic/diagnostic imaging , Electrocardiography/methods , Fibrosis/diagnostic imaging , Magnetic Resonance Imaging, Cine/methods , Myocardium/pathology , Adolescent , Adult , Cardiomyopathy, Hypertrophic/genetics , Cardiomyopathy, Hypertrophic/pathology , Child , Contrast Media/administration & dosage , Female , Gadolinium DTPA/administration & dosage , Heart/diagnostic imaging , Humans , Male , Mutation , Phenotype , Prognosis , Risk Factors , Sarcomeres/genetics , Sarcomeres/pathology , Sensitivity and Specificity , Young Adult
13.
Jpn J Radiol ; 39(2): 165-177, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33025339

ABSTRACT

PURPOSE: To identify predictive factors for truncation artifacts (TAs) in the arterial phase of Gd-EOB-DTPA-enhanced MRI in a multicenter study in Japan. MATERIALS AND METHODS: Data on patient factors (age, sex, weight, presence of viral hepatitis, and other conditions) and imaging parameters (e.g., triggering, voxel size, matrix, k-space ordering, acquisition time, reduction factor, flip angle, fat suppression, field strength, injection rate, and saline volume) were obtained. Univariate and multivariate analyses were performed to investigate the correlation of these parameters. RESULTS: We evaluated 1444 patients from 43 institutions who were scanned using GE, Siemens, Philips, or Toshiba MRI equipment (501, 354, 349, and 240 patients, respectively). The total incidence of TAs was 12.5% (17.2, 3.6, 15.7, and 12.1%, respectively). The matrix [odds ratio (OR) 0.13], flip angle (OR 5.77), use of fat suppression (OR 0.106), and field strength (OR 0.092) used in the Philips equipment significantly increased the incidence of TAs in MRI examination. CONCLUSIONS: The incidence of TAs in the arterial phase is influenced by several patient factors and imaging parameters. Especially, Siemens and Toshiba equipment had a significantly lower frequency of TAs. This indicates that such vendor-specific technology used in the dynamic sequence may have a TA-resistant effect.


Subject(s)
Contrast Media , Gadolinium DTPA , Liver/diagnostic imaging , Magnetic Resonance Imaging/methods , Aged , Analysis of Variance , Arteries/diagnostic imaging , Artifacts , Contrast Media/administration & dosage , Female , Gadolinium DTPA/administration & dosage , Humans , Liver/blood supply , Magnetic Resonance Imaging/instrumentation , Male , Middle Aged
14.
Jpn J Radiol ; 39(2): 178-185, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32959222

ABSTRACT

PURPOSE: To compare the occurrence of transient respiratory motion artifacts (TRMAs) in multiple arterial phases on abdominal magnetic resonance (MR) images between those obtained using gadobutrol and gadoxetate disodium. MATERIALS AND METHODS: Two hundred and fourteen abdominal MR examinations (101 with gadoxetate disodium, 113 with gadobutrol) were evaluated. Dynamic three-dimensional contrast-enhanced T1-weighted imaging (CAIPIRINHA-Dixon-TWIST-VIBE) including single-breath-hold six arterial phase acquisitions was performed on a 3.0-T MRI scanner. The TRMAs frequency and the mean TRMA scores were compared between patients assessed with gadoxetate disodium and those assessed with gadobutrol. In addition, the timing of TRMAs appearing for the first time was also recorded and compared between the two groups. RESULTS: The mean TRMA scores in all arterial phases using gadoxetate disodium were significantly worse than in those using gadobutrol (1.49 ± 0.78 vs. 1.18 ± 0.53, P < .001). Regarding the timing of the occurrence of TRMAs, the severe TRMAs frequency after the third arterial phase was significantly higher in patients using gadoxetate disodium (10/101, 10%) than in those using gadobutrol (0/113, 0%) (P < .001). CONCLUSION: In multiple-arterial-phase dynamic MRI, the TRMAs frequency when using gadoxetate disodium increased compared with gadobutrol, due to intolerable respiratory suspension after the third arterial phase.


Subject(s)
Abdomen/diagnostic imaging , Artifacts , Contrast Media , Gadolinium DTPA , Liver/diagnostic imaging , Magnetic Resonance Imaging/methods , Organometallic Compounds , Adult , Aged , Aged, 80 and over , Arteries/diagnostic imaging , Breath Holding , Contrast Media/administration & dosage , Female , Gadolinium DTPA/administration & dosage , Humans , Imaging, Three-Dimensional , Liver/blood supply , Magnetic Resonance Spectroscopy , Male , Middle Aged , Motion , Organometallic Compounds/administration & dosage , Retrospective Studies , Risk Factors
15.
Drug Chem Toxicol ; 44(5): 508-517, 2021 Sep.
Article in English | MEDLINE | ID: mdl-31179770

ABSTRACT

Medications show their biological effects by interaction with enzymes, which have been known to play an essential role in the pathogenesis of many diseases. Inhibition or induction of drug metabolizing enzymes has an essential place in the drug design for many kinds of diseases including cardiovascular, neurological, metabolic, and cancer. The main goal of the current study is to contribute to this growing drug design field by observing PON1-drug interactions. In recent years, the safety of gadolinium-based contrast agents (GBCAs) used in magnetic resonance imaging (MRI) has discussed. In the present study, paraoxonase 1 (PON1) enzyme was purified from human serum by simple chromatographic methods with 4095.24 EU mg-1 protein specific activity. The inhibitory activities of gadoteric acid, gadopentetic acid, gadoxetate disodium, and gadodiamide were investigated on PON1 activity of the enzyme. IC50 values were found in the range of 51.28 ± 0.14 to 285.80 ± 0.96 mM. Ki constants were found as 67.95 ± 0.60 mM, 104.97 ± 0.96 mM, 202.33 ± 1.75 mM, and 299.43 ± 2.64 mM for gadoteric acid, gadopentetic acid, gadoxetate disodium, and gadodiamide, respectively. While the inhibition types are determined as competitive of gadoxetate disodium and gadodiamide by the Lineweaver-Burk curves, it was noncompetitive for other compounds. In addition, the molecular docking analyses of gadoxetate disodium and gadodiamide were carried out to understand the binding interactions on the active site of the PON1 enzyme. The structure-activity relationship (SAR) of the drugs was established on the basis of different substituents and their positions in the compounds.


Subject(s)
Aryldialkylphosphatase/antagonists & inhibitors , Contrast Media/pharmacology , Gadolinium DTPA/pharmacology , Computer Simulation , Contrast Media/administration & dosage , Contrast Media/chemistry , Drug Design , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Gadolinium DTPA/administration & dosage , Gadolinium DTPA/chemistry , Humans , Inhibitory Concentration 50 , Molecular Docking Simulation , Structure-Activity Relationship
16.
Histochem Cell Biol ; 155(1): 19-73, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33040183

ABSTRACT

This multidisciplinary study examined the pharmacokinetics of nanoparticles based on albumin-DTPA-gadolinium chelates, testing the hypothesis that these nanoparticles create a stronger vessel signal than conventional gadolinium-based contrast agents and exploring if they are safe for clinical use. Nanoparticles based on human serum albumin, bearing gadolinium and designed for use in magnetic resonance imaging, were used to generate magnet resonance images (MRI) of the vascular system in rats ("blood pool imaging"). At the low nanoparticle doses used for radionuclide imaging, nanoparticle-associated metals were cleared from the blood into the liver during the first 4 h after nanoparticle application. At the higher doses required for MRI, the liver became saturated and kidney and spleen acted as additional sinks for the metals, and accounted for most processing of the nanoparticles. The multiple components of the nanoparticles were cleared independently of one another. Albumin was detected in liver, spleen, and kidneys for up to 2 days after intravenous injection. Gadolinium was retained in the liver, kidneys, and spleen in significant concentrations for much longer. Gadolinium was present as significant fractions of initial dose for longer than 2 weeks after application, and gadolinium clearance was only complete after 6 weeks. Our analysis could not account quantitatively for the full dose of gadolinium that was applied, but numerous organs were found to contain gadolinium in the collagen of their connective tissues. Multiple lines of evidence indicated intracellular processing opening the DTPA chelates and leading to gadolinium long-term storage, in particular inside lysosomes. Turnover of the stored gadolinium was found to occur in soluble form in the kidneys, the liver, and the colon for up to 3 weeks after application. Gadolinium overload poses a significant hazard due to the high toxicity of free gadolinium ions. We discuss the relevance of our findings to gadolinium-deposition diseases.


Subject(s)
Albumins/pharmacokinetics , Chelating Agents/pharmacokinetics , Contrast Media/pharmacokinetics , Gadolinium DTPA/pharmacokinetics , Magnetic Resonance Imaging , Nanoparticles/chemistry , Albumins/administration & dosage , Animals , Chelating Agents/administration & dosage , Contrast Media/administration & dosage , Female , Gadolinium DTPA/administration & dosage , Injections, Intravenous , Male , Mice , Mice, Inbred BALB C , Nanoparticles/administration & dosage , Rats , Rats, Sprague-Dawley , Tissue Distribution
17.
J Comput Assist Tomogr ; 45(1): 121-127, 2021.
Article in English | MEDLINE | ID: mdl-32976269

ABSTRACT

OBJECTIVE: This study aimed to ascertain the minimum gadolinium dosage on contrast-enhanced (CE) T2 fluid-attenuated inversion recovery (FLAIR) at appropriate imaging time. METHODS: Different dosages of gadodiamide were imaged with a 3.0-T magnetic resonance scanner for T2-FLAIR and T1WI. Twenty glioma-induced rat models were randomly assigned into 4 groups (1/2, 1/4, 1/6, 1/8 of routine dosage) and imaged for T2-FLAIR and T1WI preinjection and postinjection of gadodiamide. Contrast-enhanced T2-FLAIR was acquired for 8 repetitions postinjection. Enhancement effects were assessed by calculating contrast-noise ratio and contrast ratio using Kruskal-Wallis and Mann-Whitney rank sum test. RESULTS: The in vitro experiment showed that gadodiamide at 1/4 of the T1WI dosage presented the best contrast on CE-T2-FLAIR. For in vivo study, the best enhancement effect on CE-T2-FLAIR was achieved at 1/2 of the routine dosage at 8 to 12 minutes of delayed scanning. Compared with CE-T1WI at routine dosage, CE-T2-FLAIR at 1/2 gadodiamide dosage presented similar enhancement effects with no statistical difference (P = 0.244 and 0.090 for contrast-noise ratio and contrast ratio, respectively). CONCLUSIONS: Contrast-enhanced T2-FLAIR imaging with half of T1WI routine gadodiamide dosage can produce similar enhancement effects to CE-T1WI when characterizing brain gliomas. The cut-down of contrast agent dosage may help reduce gadolinium accumulation in certain tissues.


Subject(s)
Brain Neoplasms/diagnostic imaging , Contrast Media/administration & dosage , Gadolinium DTPA/administration & dosage , Glioma/diagnostic imaging , Animals , Cell Line, Tumor , Drug Dosage Calculations , Female , In Vitro Techniques , Magnetic Resonance Imaging , Neoplasm Transplantation , Radiographic Image Interpretation, Computer-Assisted , Random Allocation , Rats , Signal-To-Noise Ratio
18.
Acta Otolaryngol ; 141(2): 117-121, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33176531

ABSTRACT

BACKGROUND: Intravenous gadolinium injection (IV-method) can be used to visualize endolymphatic hydrops. AIMS/OBJECTIVES: This study was designed to use a three-dimensional inversion-recovery sequence with real reconstruction (3 D-real IR) sequence 4 h after the IV-method, images of the perilymph space were scored for endolymphatic hydrops in cases of suspected Meniere's disease (MD) in children to investigate its diagnostic value of MD in children. MATERIALS AND METHODS: We collected 28 suspected MD children aged ≤17 years old, all of whom underwent the IV-method. After 4 h, inner ear 3 D-real IR magnetic resonance imaging (MRI) was performed and results were analyzed. RESULTS: Gadolinium contrast agent was seen distributed in the perilymphatic space with perilymphatic enhancement on 3 D-real IR MRI, allowing differentiation between the perilymphatic and endolymphatic spaces. Based on perilymph MRI diagnostic scoring, 64.3% (18/28) of the patients were categorized as having endolymphatic hydrops, who were followed and eventually diagnosed with confirmed MDs. CONCLUSIONS AND SIGNIFICANCE: Suspected MD children should undergo gadolinium-enhanced examinations of the inner ear while taking dynamic audiology examinations for the confirmed diagnosis.


Subject(s)
Contrast Media/administration & dosage , Ear, Inner/diagnostic imaging , Gadolinium DTPA/administration & dosage , Magnetic Resonance Imaging/methods , Meniere Disease/diagnostic imaging , Adolescent , Audiometry , Child , Endolymphatic Hydrops/diagnostic imaging , Female , Humans , Imaging, Three-Dimensional , Injections, Intravenous , Male , Perilymph
19.
J Cardiovasc Magn Reson ; 22(1): 73, 2020 10 08.
Article in English | MEDLINE | ID: mdl-33028350

ABSTRACT

BACKGROUND: Although non-invasive assessment of coronary flow reserve (CFR) by cardiovascular magnetic resonance (CMR) provides prognostic information for patients with diabetes mellitus (DM), the incremental prognostic value of CMR-derived CFR remains unclear. PURPOSE: To evaluate the incremental prognostic value of CMR-derived CFR for patients with DM who underwent stress CMR imaging. MATERIALS AND METHODS: A total of 309 patients with type 2 DM [69 ± 9 years; 244 (78%) male] assessed between 2009 and 2019 were retrospectively reviewed. Coronary sinus blood flow (CSBF) was measured using phase contrast (PC) cine CMR. CFR was calculated as the CSBF during adenosine triphosphate infusion divided by that at rest. Major adverse cardiac events (MACE) were defined as death, acute coronary syndrome, hospitalization due to heart failure exacerbation, or sustained ventricular tachycardia. The incremental prognostic value of CFR over clinical and CMR variables was assessed by calculating the C-index and net reclassification improvement (NRI). RESULTS: During a median follow-up of 3.8 years, 42 patients (14%) experienced MACE. The annualized event rate was significantly higher among patients with CFR < 2.0, regardless of the presence of late gadolinium enhancement (LGE) (1.4% vs. 9.8%, p = 0.011 in the LGE (-) group; 1.8% vs. 16.9%, p < 0.001 in the LGE (+) group). In addition, this trend was maintained in the subgroups stratified by presence or absence of ischemia (0.3% vs. 6.7%, p = 0.007 in the ischemia (-) group; 3.9% vs. 17.1%, p = 0.001 in the ischemia (+) group). Adding CFR to the risk model (age + gender + left ventricular ejection fraction + %LGE + %ischemia) resulted in a significant increase of the C-index from 0.838 to 0.870 (p = 0.038) and an NRI of 0.201 (0.004-0.368, p = 0.012). CONCLUSION: PC cine CMR-derived CFR of the coronary sinus may be useful as a prognostic marker for DM patients, incremental to common clinical and CMR parameters. Due to the high prevalence of coronary microvascular dysfunction, the addition of CFR to conventional vasodilator stress CMR imaging may improve risk stratification for patients with DM.


Subject(s)
Cardiovascular Diseases/diagnostic imaging , Coronary Circulation , Coronary Sinus/diagnostic imaging , Diabetes Mellitus , Magnetic Resonance Imaging, Cine , Adult , Aged , Aged, 80 and over , Blood Flow Velocity , Cardiovascular Diseases/mortality , Cardiovascular Diseases/physiopathology , Cardiovascular Diseases/therapy , Contrast Media/administration & dosage , Coronary Sinus/physiopathology , Diabetes Mellitus/diagnosis , Diabetes Mellitus/mortality , Female , Gadolinium DTPA/administration & dosage , Humans , Male , Middle Aged , Predictive Value of Tests , Prognosis , Retrospective Studies , Risk Factors , Time Factors
20.
BMC Med Imaging ; 20(1): 119, 2020 10 20.
Article in English | MEDLINE | ID: mdl-33081713

ABSTRACT

BACKGROUND: Previous studies have used signal intensity (SI) to reflect liver function. However, few studies have evaluated liver function via the portal vein. Regarding the SI of the liver, spleen, and portal vein, no study has indicated which can best reflect liver function. Therefore, the aim of this study is to investigate whether these parameters can evaluate liver function in patients with cirrhosis and determine which is the best parameter. METHODS: 120 patients with normal livers (n = 41) or Child-Pugh class A (n = 50), B (n = 21) or C (n = 8) disease who had undergone Gd-EOB-DTPA-enhanced MRI were retrospectively reviewed. Comparisons of the MRI data (liver parenchyma SI, portal vein SI, and spleen SI and liver-to-portal vein contrast ratio (LPC), liver-to-spleen contrast ratio (LSC), and portal vein-to-spleen contrast ratio (PSC)) in the 15-min hepatobiliary phase images were performed among the groups, and the correlations among the liver function parameters (total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, albumin, creatinine, platelet count, prothrombin time and international normalized ratio), liver function scores and MRI data were also quantitatively analysed. RESULTS: Significant differences were observed in the liver parenchyma SI, LPC and LSC among the groups. These values all decreased gradually from normal livers to Child-Pugh class C cirrhotic livers (P < 0.001). The portal vein SI constantly and slightly increased from normal livers to Child-Pugh class C cirrhotic livers, but no differences were found among the groups in the portal vein SI and PSC (P > 0.05). LPC showed a stronger correlation with the Child-Pugh score and MELD score than LSC and the liver parenchyma SI. The order of the AUCs of these parameters, from largest to smallest, was as follows: LPC, LSC, and liver parenchyma SI (P > 0.05). CONCLUSION: The liver parenchyma SI, LSC and LPC may be used as alternative imaging biomarkers to assess liver function, while the portal vein SI and PSC do not reflect liver function. Furthermore, LPC values can more effectively distinguish severity among patients with cirrhosis than the liver parenchyma SI and LSC.


Subject(s)
Gadolinium DTPA/administration & dosage , Liver Cirrhosis/diagnostic imaging , Liver/diagnostic imaging , Magnetic Resonance Imaging/methods , Portal Vein/diagnostic imaging , Spleen/diagnostic imaging , Aged , Area Under Curve , Case-Control Studies , Contrast Media , Female , Humans , Liver/physiopathology , Liver Cirrhosis/physiopathology , Liver Function Tests , Male , Middle Aged , Portal Vein/physiopathology , Radiographic Image Interpretation, Computer-Assisted , Retrospective Studies , Spleen/physiopathology
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