Dynamic contrast‐enhanced magnetic resonance imaging of abdominal solid organ and major vessel: Comparison of enhancement effect between Gd‐EOB‐DTPA and Gd‐DTPA

Purpose

To evaluate the differences in enhancement of the abdominal solid organ and the major vessel on dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) obtained with gadolinium ethoxybenzyldiethylenetriamine pentaacetic acid (Gd‐EOB‐DTPA: EOB) and gadolinium diethylenetriamine pentaacetic acid (Gd‐DTPA) in the same patients.

Materials and Methods

A total of 13 healthy volunteers underwent repeat assessments of abdominal MR examinations with DCE‐MRI using either Gd‐DTPA at a dose of 0.1 mmol/kg body weight or EOB at a dose of 0.025 mmol/kg body weight. DCE images were obtained at precontrast injection and in the arterial phase (AP: 25 seconds), portal phase (PP: 70 seconds), and equilibrium phase (EP: 3 minutes). The signal intensities (SIs) of liver at AP, PP, and EP; the SIs of spleen, renal cortex, renal medulla, pancreas, adrenal gland, aorta at AP; and the SIs of portal vein and inferior vena cava (IVC) at PP were defined using region‐of‐interest measurements, and were used for calculation of signal intensity ratio (SIR).

Results

The mean SIRs of liver (0.195 ± 0.140), spleen (1.35 ± 0.353), renal cortex (1.58 ± 0.517), renal medulla (0.548 ± 0.259), pancreas (0.540 ± 0.183), adrenal gland (1.04 ± 0.405), and aorta (2.44 ± 0.648) at AP as well as the mean SIRs of portal vein (1.85 ± 0.477) and IVC (1.16 ± 0.187) at PP in the EOB images were significantly lower than those (0.337 ± 0.200, 1.99 ± 0.443, 2.01 ± 0.474, 0.742 ± 0.336, 0.771 ± 0.227, 1.26 ± 0.442, 3.22 ± 1.20, 2.73 ± 0.429, and 1.68 ± 0.366, respectively) in the Gd‐DTPA images (P < 0.05 each). There was no significant difference in mean SIR of liver at PP between EOB (0.529 ± 0.124) and Gd‐DTPA (0.564 ± 0.139). Conversely, the mean SIR of liver at EP was significantly higher with EOB (0.576 ± 0.167) than with Gd‐DTPA (0.396 ± 0.093) (P < 0.001).

Conclusion

Lower arterial vascular and parenchymal enhancement with Gd‐EOB, as compared with Gd‐DTPA, may require reassessment of its dose, despite the higher late venous phase liver parenchymal enhancement. J. Magn. Reson. Imaging 2009;29:636–640. © 2009 Wiley‐Liss, Inc.     

Detection of apoptotic cell death in vitro in the presence of Gd‐DTPA‐BMA

Due to variability in patient response to cancer therapy, there is a growing interest in monitoring patient progress during treatment. Apoptotic cell death is one early marker of tumor response to treatment. Using known extracellular concentrations of gadolinium diethylenetriamine pentaacetic acid bismethylamide (Gd‐DTPA‐BMA) to vary the exchange regime, T₁ and T₂ relaxation data for acute myeloid leukemia (AML) cell samples were obtained and then analyzed using a two‐pool model of relaxation with exchange. Leukemia cells treated with cisplatin to induce apoptosis exhibited a statistically significant (P < 0.05) decrease in intracellular longitudinal relaxation time, T_1I, from 1030 ms to 940 ms, a decrease (P < 0.001) in the intracellular water fraction, M_0I, from 0.86 to 0.68 and a statistically significant increase (P < 0.01) in transmembrane water exchange rate, k_IE, from 1.4 s^?1 to 6.8 s^?1. The changes in MR parameters correlated with quantitative histology, such as cellular cross‐sectional area and average nuclear area measurements. The results of this study emphasize the importance of accounting for water exchange in dynamic contrast‐enhanced MRI (DCE‐MRI) studies, particularly those that examine tumor response to therapies in which apoptotic changes occur. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Photochemical activation of endosomal escape of MRI‐Gd‐agents in tumor cells

Endocytosis is a common internalization pathway for cellular labeling with MRI contrast agents. However, the entrapment of the Gd(III) complexes into endosomes results in a “quenching” of the attainable relaxivity when the number of Gd(III) complexes reaches the number of ca. 1 × 10⁹/cell. Herein we show that the use of the newly developed photochemical internalization technique provides an efficient method for attaining the endosomal escape of GdHPDO3A molecules entrapped by pinocytosis into different kind of cells. Furthermore, it has been found that a new “quenching” limit is observed when the number of Gd‐HPDO3A complexes is ca. five times higher than the value observed for the endosome entrapped conditions. The observed behavior is explained in terms of the attainment of the conditions in which the difference in proton relaxation rates between the cytoplasmic and the extracellular compartment is higher than the exchange rate of water molecules across the cellular membrane. The experimental data points have been reproduced by using a properly designed theoretical compartment T₁‐relaxation model. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Usefulness of Gd‐EOB‐DTPA‐enhanced MR imaging in the evaluation of simple steatosis and nonalcoholic steatohepatitis

Purpose:

To evaluate the usefulness of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd‐EOB‐DTPA)‐enhanced MR imaging (EOB‐MRI) in differentiating between simple steatosis and nonalcoholic steatohepatitis (NASH), as compared with MR in‐phase/out‐of‐phase imaging. The correlations between the MR features and histological characteristics were preliminarily investigated.

Materials and Methods:

From April 2008 to October 2011, 25 patients (13 simple steatosis and 12 NASH) who underwent both EOB‐MRI and in‐phase/out‐of‐phase imaging were analyzed. The hepatobiliary‐phase enhancement ratio and signal intensity loss on opposed‐phase T1‐weighted images (fat fraction) were compared between the simple steatosis and NASH groups. In the simple steatosis and NASH groups, the correlations between enhancement ratio and histological grade/stage were explored. In the NASH group, fat fraction was correlated with the steatosis score.

Results:

The enhancement ratio in NASH was significantly lower than that in simple steatosis (P = 0.03). In the simple steatosis and NASH groups, the enhancement ratio was significantly correlated with the fibrosis stage (r = ?0.469, P = 0.018). Fat fraction in NASH was strongly correlated with the steatosis score (r = 0.728, P = 0.007).

Conclusion:

In simple steatosis and NASH, the hepatobiliary‐phase enhancement ratio of EOB‐MRI showed significant association with fibrosis stage, and may be a useful discriminating parameter compared with the fat fraction measured by in‐phase/out‐of‐phase imaging. J. Magn. Reson. Imaging 2012;37:1137–1143. © 2012 Wiley Periodicals, Inc.

     

Assessment of fast dynamic imaging and the use of Gd‐EOB‐DTPA for MR‐guided liver interventions

Purpose:

1) To analyze and compare fast dynamic imaging sequences to biopsy suspect liver lesions. 2) To evaluate the additional use of hepatocyte‐specific contrast agent compared to the nonenhanced fast dynamic scans and diagnostic liver imaging.

Materials and Methods:

Image acquisition was performed using a 1T open‐configured scanner suitable for interventional purposes. Transversal postcontrast T1‐weighted (T1w) fat‐saturated 3D high‐resolution examination (THRIVE) images were acquired >20 minutes postintravenous application of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd‐EOB‐DTPA). A single slice, crossing the level of the lesion, was acquired using intermediate‐weighted steady‐state free‐precession (bTFE), T1w‐gradient echo and spin echo (T1FFE/TSE), T2w‐spin echo (sshTSE) sequences. T1w imaging was acquired prior and after contrast media application. Diagnostic and fast dynamic images were compared based on a 10‐point rating scale. In addition, the liver‐to‐lesion‐contrast ratio was measured.

Results:

A total of 39 malignant lesions with a mean diameter of 13 mm (5–30 mm) in 39 patients were included. Concerning a test of noninferiority, there was no significant difference between rating score values of fast dynamic imaging employing contrast‐enhanced T1FFE‐sequences compared to diagnostic THRIVE (P = 0.001). Calculated liver‐to‐lesion contrast also showed no difference for either imaging sequence (P = 1.0). All other sequences tested showed significant inferiority (P ≤ 0.001).

Conclusion:

T1w Gd‐EOB‐DTPA contrast‐enhanced fast dynamic GRE imaging significantly improves the contrast behavior of malignant liver lesions comparable to diagnostic imaging and is best suited for liver intervention, especially at 1T open magnetic resonance imaging. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.     

Effect of Gd‐EOB‐DTPA on T2‐weighted and diffusion‐weighted images for the diagnosis of hepatocellular carcinoma

Purpose:

To evaluate the effect of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd‐EOB‐DTPA) on T2‐weighted imaging (T2WI) and diffusion‐weighted imaging (DWI) for the diagnosis of hepatocellular carcinoma (HCC).

Materials and Methods:

The phantom signal intensity was measured. We also evaluated 72 patients including 30 patients with HCC. T2WI and DWI were obtained before and then 4 and 20 min after injecting the contrast medium. The signal to noise ratio (SNR), contrast to noise ratio (CNR), and apparent diffusion coefficient (ADC) were calculated in the tumor and liver parenchyma.

Results:

The phantom signal intensity increased on T2WI at a concentration of contrast medium less than 0.2 mmol/L but decreased when the concentration exceeded 0.4 mmol/L. SNR of the liver parenchyma on T2WI was significantly different between before and 4 min after injecting the contrast medium, while there were no significant differences between before and 4 and 20 min after injection. On T2WI, SNR, and CNR of HCC showed no significant differences at any time. SNR, CNR, and ADC of the liver parenchyma and tumor on DWI also showed no significant differences at any time.

Conclusion:

It is acceptable to perform T2WI and DWI after injection of Gd‐EOB‐DTPA for the diagnosis of HCC. J. Magn. Reson. Imaging 2010;32:229–234. © 2010 Wiley‐Liss, Inc.     

Cardiovascular phenotyping of the mouse heart using a 4D radial acquisition and liposomal Gd‐DTPA‐BMA

MR microscopy has enormous potential for small‐animal cardiac imaging because it is capable of producing volumetric images at multiple time points to accurately measure cardiac function. MR has not been used as frequently as ultrasound to measure cardiac function in the small animal because the MR methods required relatively long scan times, limiting throughput. Here, we demonstrate four‐dimensional radial acquisition in conjunction with a liposomal blood pool agent to explore functional differences in three populations of mice: six C57BL/6J mice, six DBA/2J mice, and six DBA/2J CSQ+ mice, all with the same gestational age and approximately the same weight. Cardiovascular function was determined by measuring both left ventricular and right ventricular end diastolic volume, end systolic volume, stroke volume, and ejection fraction. Statistical significance was observed in end diastolic volume, end systolic volume, and ejection fraction for left ventricular measurements between all three populations of mice. No statistically significant difference was observed in stroke volume in either the left or right ventricle for any of the three populations of mice. This study shows that MRI is capable of efficient, high‐throughput, four‐dimensional cardiovascular phenotyping of the mouse. Magn Reson Med 63:979–987, 2010. © 2010 Wiley‐Liss, Inc.     

Assessing liver function using dynamic Gd‐EOB‐DTPA‐enhanced MRI with a standard 5‐phase imaging protocol

Purpose:

To evaluate liver function obtained by tracer‐kinetic modeling of dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) data acquired with a routine gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd‐EOB‐DTPA)‐enhanced protocol.

Materials and Methods:

Data were acquired from 25 cases of nonchronic liver disease and 94 cases of cirrhosis. DCE‐MRI was performed with a dose of 0.025 mmol/kg Gd‐EOB‐DTPA injected at 2 mL/sec. A 3D breath‐hold sequence acquired 5 volumes of 72 slices each: precontrast, double arterial phase, portal phase, and 4‐minute postcontrast. Regions of interest (ROIs) were selected semiautomatically in the aorta, portal vein, and whole liver on a middle slice. A constrained dual‐inlet two‐compartment uptake model was fitted to the ROI curves, producing three parameters: intracellular uptake rate (UR), extracellular volume (Ve), and arterial flow fraction (AFF).

Results:

Median UR dropped from 4.46 10^?2 min^?1 in the noncirrhosis to 3.20 in Child–Pugh A (P = 0.001), and again to 1.92 in Child–Pugh B (P < 0.0001). Median Ve dropped from 6.64 mL 100 mL^?1 in the noncirrhosis to 5.80 in Child–Pugh A (P = 0.01). Other combinations of Ve and AFF changes were not significant for any group.

Conclusion:

UR obtained from tracer kinetic analysis of a routine DCE‐MRI has the potential to become a novel index of liver function. J. Magn. Reson. Imaging 2013;37:1109–1114. © 2012 Wiley Periodicals, Inc.

     

The MRI‐measured arterial input function resulting from a bolus injection of Gd‐DTPA in a rat model of stroke slightly underestimates that of Gd‐[14C]DTPA and marginally overestimates the blood‐to‐brain influx rate constant determined by Patlak plots

The hypothesis that the arterial input function (AIF) of gadolinium‐diethylenetriaminepentaacetic acid injected by intravenous bolus and measured by the change in the T₁‐relaxation rate (ΔR₁; R₁ = 1/T₁) of superior sagittal sinus blood (AIF‐I) approximates the AIF of ¹⁴C‐labeled gadolinium‐diethylenetriaminepentaacetic acid measured in arterial blood (reference AIF) was tested in a rat stroke model (n = 13). Contrary to the hypothesis, the initial part of the ΔR₁‐time curve was underestimated, and the area under the normalized curve for AIF‐I was about 15% lower than that for the reference AIF. Hypothetical AIFs for gadolinium‐diethylenetriaminepentaacetic acid were derived from the reference AIF values and averaged to obtain a cohort‐averaged AIF. Influx rate constants (K_i) and proton distribution volumes at zero time (V_p + V_o) were estimated with Patlak plots of AIF‐I, hypothetical AIFs, and cohort‐averaged AIFs and tissue ΔR₁ data. For the regions of interest, the K_is estimated with AIF‐I were slightly but not significantly higher than those obtained with hypothetical AIFs and cohort‐averaged AIF. In contrast, V_p + V_o was significantly higher when calculated with AIF‐I. Similar estimates of K_i and V_p + V_o were obtained with hypothetical AIFs and cohort‐averaged AIF. In summary, AIF‐I underestimated the reference AIF; this shortcoming had little effect on the K_i calculated by Patlak plot but produced a significant overestimation of V_p + V_o. Magn Reson Med 63:1502–1509, 2010. © 2010 Wiley‐Liss, Inc.     

Dilution method of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd‐EOB‐DTPA)‐enhanced magnetic resonance imaging (MRI)

Purpose

To elucidate whether a contrast agent dilution method (dilution method), in which gadoxetate disodium (Gd‐EOB‐DTPA) is diluted with saline, is useful for good‐quality arterial‐phase images.

Materials and Methods

In this study we observed 494 hypervascular hepatocellular carcinomas (HCCs) in 327 patients with chronic liver disease. Three Gd‐EOB‐DTPA injection methods were adopted for comparison: 1) test injection method (undiluted Gd‐EOB‐DTPA and modified scan delay), in which a test dose of 0.5 mL of Gd‐EOB‐DTPA was injected to determine scan delay; 2) conventional method (undiluted Gd‐EOB‐DTPA and fixed scan delay); and ( 3 ) dilution method (diluted Gd‐EOB‐DTPA and fixed scan delay), in which Gd‐EOB‐DTPA was diluted to 20 mL with saline. Lesion‐liver contrast was calculated. Image quality and lesion detectability were evaluated by two radiologists blinded to the injection methods.

Results

The lesion‐liver contrast of the dilution method was significantly higher than that of the other two methods. Lesion detectability of the conventional method (64%) was significantly lower than that of the other two methods (contrast agent dilution method, 95%; test injection method, 93%). The image quality of the contrast agent dilution method was significantly better than that of the other two methods.

Conclusion

The dilution method contributed to improved image quality, high lesion‐liver contrast, and high lesion detectability in the arterial‐phase images of GD‐EOB‐DTPA‐enhanced MRI. J. Magn. Reson. Imaging 2009;30:849–854. © 2009 Wiley‐Liss, Inc.     

Gd‐EOB‐DTPA‐enhanced MR imaging: Prediction of hepatic fibrosis stages using liver contrast enhancement index and liver‐to‐spleen volumetric ratio

Purpose:

To develop and evaluate a quantitative parameter for staging hepatic fibrosis by contrast enhancement signal intensity and morphological measurements from gadoxetic acid (Gd‐EOB‐DTPA)‐enhanced MR imaging.

Materials and Methods:

MR images were obtained in 93 patients; 75 patients had histopathologically proven hepatic fibrosis and 18 patients who had healthy livers were evaluated. The liver‐to‐muscle signal intensity ratio (SI_post = SIliver/SImuscle), contrast enhancement index (CEI = SIpost/SIpre), and liver‐to‐spleen volumetric ratio (VR = Vliver/Vspleen) were evaluated for staging hepatic fibrosis.

Results:

VR was most strongly correlated with fibrosis stage (7.21; r = ?0.83; P < 0.001). Sensitivity, specificity, and area under the ROC curve demonstrated by linear regression formula generated by VR and CEI in predicting fibrous scores were 100%, 73%, and 0.91, respectively, for the detection of hepatic fibrosis F1 or greater (≥ F1),100%, 87%, and 0.96 for ≥ F2, 74%, 98%, and 0.93 for ≥ F3 and 91%, 100%, and 0.97 for F4.

Conclusion:

The liver‐to‐spleen volumetric ratio and contrast enhancement index were reliable biomarkers for the staging of hepatic fibrosis on Gd‐EOB‐DTPA‐enhanced MR imaging. J. Magn. Reson. Imaging 2012;36:1148–1153. © 2012 Wiley Periodicals, Inc.