Paradoxic uptake of Gd‐EOB‐DTPA by hepatocellular carcinoma in mice: Quantitative image analysis

Fujita, Makoto; Yamamoto, Reiko; Takahashi, Masaya; Tsuji, Takashi; Yamanaka, T.; Miyazawa, Tomoaki; Fritz‐Zieroth, Bernhard; Terada, Nobuyuki; Kuroda, C

doi:10.1002/jmri.1880070426

Cited by 27 publications

(18 citation statements)

References 10 publications

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“…However, by studying only 31 patients without positive TCE encountered, Vogl et al in their first clinical report attempted to challenge our initial findings and concluded that similar to Gd-DTPA, Gd-EOB-DTPA could not provide ''differential diagnostic information" [64]. By confusing early dynamic and delayed CE without realizing the true positive TCE, an early animal study also claimed that positive TCE with Gd-EOB-DTPA occurred ''independently of cellular differentiation" [65]. Over ten years later, with cumulating cases in both animal studies and clinical applications, the role of Gd-OA-CAs in liver tumor characterization has been gradually recognized [58][59][60]66].…”

Section: +mentioning

confidence: 99%

Tumor models and specific contrast agents for small animal imaging in oncology

Chen

et al. 2009

Methods

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a b s t r a c tDespite the widespread use of various imaging modalities in clinical and experimental oncology without or with combined application of commercially available nonspecific contrast agents (CAs), development of tissue-or organ-or disease-specific CAs has been a continuing effort for pursuing ever-improved sensitivity, specificity, and applicability. This is particularly true with magnetic resonance imaging (MRI) due to its intrinsic superb spatial/temporal/contrast resolutions and adequate detectability for tiny amount of substances. In this context, research using small animal tumor models has played an indispensible role in preclinical exploration of tissue specific CAs. Emphasizing more on methodological and practical aspects, this article aims to share our cumulated experiences on how to create tumor models for evaluation and development of new tissue specific MRI CAs and how to apply such models in imaging-based research studies. With the results that are repeatedly confirmed by later clinical applications in cancer patients, some of our early preclinical studies have contributed to the designs of subsequent clinical trials on the new CAs, some studies have predicted new utilities of these CAs; and other studies have led to the discoveries of new tissue-or disease-specific CAs with novel diagnostic or even therapeutic potentials. Among commonly adopted tumor models, the chemically induced and surgically implanted nodules in the liver prove very useful to simulate primary and metastatic intrahepatic tumors, respectively in clinical patients. The methods to create tumor models have eased procedures and yielded high success rates. The specific properties of the new CAs could be outshined by intraindividual comparison to the commercial CAs as nonspecific controls. Meticulous imaging-microangiography-histology matching techniques guaranteed colocalization of the lesion on in vivo MRI and postmortem tissue specimen, hence correct imaging interpretation and longstanding conclusions. As exemplified in the real study cases, the present experimental set-up proves applicable in small animals for imaging-based oncological investigations, and may provide a platform for the currently booming molecular imaging in a multimodality environment.

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Section: +mentioning

confidence: 99%

Tumor models and specific contrast agents for small animal imaging in oncology

Chen

et al. 2009

Methods

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“…Some investigators have reported hepatocellular carcinomas (HCCs) with isointensity or hyperintensity relative to the surrounding liver parenchyma on gadoxetic acid-enhanced hepatobiliary-phase images (3,(10)(11)(12). Although the reason for an HCC to uptake gadoxetic acid as seen on gadoxetic acid-enhanced hepatobiliary-phase images is not clear, isointensity or hyperintensity in an HCC may be attributed to retained hepatobiliary function or retention of the agent in an abundant extracellular fluid space including fibrosis or a sinusoid-like vascular space.…”

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confidence: 99%

Comparison between areas with Gd‐EOB‐DTPA uptake and without in hepatocellular carcinomas on Gd‐EOB‐DTPA‐enhanced hepatobiliary‐phase MR imaging: Pathological correlation

Lee

Kim

Park

et al. 2010

Magnetic Resonance Imaging

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Purpose: To determine histological and MR imaging differences between areas with Gd-EOB-DTPA (gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid) uptake and without in hepatocellular carcinomas (HCCs) as seen on Gd-EOB-DTPA-enhanced hepatobiliary-phase MR images. Materials and Methods:This study included nine patients with nine histopathologically proven HCCs (mean size, 1.9 cm) that consisted of two portions of a non-hypointense (Gd-EOB-DTPA uptake) and hypointense area (no Gd-EOB-DTPA uptake) in one tumor as depicted on hepatobiliary-phase MR images. Two radiologists and one pathologist compared the histological and MR finding differences between the two portions in consensus.Results: In eight specimens, non-hypointense areas of six specimens showed a green color and two specimens did not show a green color. Microscopically, two of nine showed a higher percentage of bile pigments in the nonhypointense area as compared to the hypointense area and the remaining seven showed no difference. Six were homogeneous Edmondson-Steiner grade II, and one was grade I. In two, non-hypointense areas were grade II and hypointense areas were grade I. No difference between the two portions was found for necrosis, hemorrhage, fibrosis, and a fibrous capsule. Seven on T1/T2-weighted images and eight on arterial and portal phase images showed no different signal intensity between the two portions. Conclusion:Although macroscopically, a non-hypointense area of an HCC seen on GD-EOB-DTPA-enhanced hepatobiliary-phase images may be associated with the area with a green color, no definite microscopic and MR imaging findings that could discriminate a non-hypointense from a hypointense area of an HCC was found.

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“…The mean of the three ROI measurements was recorded as the SI of the liver in each phase. For each of the 2, 10, and 20 min phases, the enhancement ratio based on the SI (ER-SI) for each patient was calculated by each of the following three algorithms: the SI of the liver parenchyma was adjusted by the SI of the spleen (ER-SI-s), the erector spinae muscle (ER-SI-m), and by the scale and rescale slopes (ER-SI-c) [21,22]. The following equations show the calculation methods:…”

Section: Image Analysismentioning

confidence: 99%

Optimizing signal intensity correction during evaluation of hepatic parenchymal enhancement on gadoxetate disodium-enhanced MRI: Comparison of three methods

Onoda

Hyodo

Murakami

et al. 2015

European Journal of Radiology

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a b s t r a c tObjective: To compare signal intensity (SI) correction using scale and rescale slopes with SI correction using SIs of spleen and muscle for quantifying multiphase hepatic contrast enhancement with Gd-EOB-DTPA by assessing their correlation with T 1 values generated from Look-Locker turbo-field-echo (LL-TFE) sequence data (ER-T 1 ). Materials and methods: Thirty patients underwent Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) in this prospective clinical study. For each patient, breath-hold T 1 -weighted fat-suppressed three-dimensional (3D) gradient echo sequences (e-THRIVE) were acquired before and 2 (first phase), 10 (second phase), and 20 min (third phase) after intravenous Gd-EOB-DTPA. Look-Locker turbo-fieldecho (LL-TFE) sequences were acquired before and 1.5 (first phase), 8 (second phase), and 18 min (third phase) postcontrast. The liver parenchyma enhancement ratios (ER) of each phase were calculated using the SI from e-THRIVE sequences (ER-SI) and the T 1 values generated from LL-TFE sequence data (ER-T 1 ) respectively. ER-SIs were calculated in three ways: (1) comparing with splenic SI (ER-SI-s), (2) comparing with muscle SI (ER-SI-m), (3) using scale and rescale slopes obtained from DICOM headers (ER-SI-c), to eliminate the effects of receiver gain and scaling. For each of the first, second and third phases, correlation and agreement were assessed between each ER-SI and ER-T 1 . Results: In the first phase, all ER-SIs correlated weakly with ER-T 1 . In the second and third phases, ER-SI-c showed a stronger linear correlation with ER-T 1 (r 2 = 0.71-0.72, p < 0.01) than did ER-SI-s (r 2 = 0.37-0.39, p < 0.01) or ER-SI-m (r 2 = 0.30-0.41, p < 0.01). Conclusion: SI correction using scale and rescale slopes from DICOM data is the most acceptable algorithm for evaluating delayed-phase Gd-EOB-DTPA hepatic enhancement.

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Paradoxic uptake of Gd‐EOB‐DTPA by hepatocellular carcinoma in mice: Quantitative image analysis

Cited by 27 publications

References 10 publications

Tumor models and specific contrast agents for small animal imaging in oncology

Tumor models and specific contrast agents for small animal imaging in oncology

Comparison between areas with Gd‐EOB‐DTPA uptake and without in hepatocellular carcinomas on Gd‐EOB‐DTPA‐enhanced hepatobiliary‐phase MR imaging: Pathological correlation

Optimizing signal intensity correction during evaluation of hepatic parenchymal enhancement on gadoxetate disodium-enhanced MRI: Comparison of three methods

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