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Nanoscaled Iodized Oil Emulsion as a CT Contrast Agent for the Detection of Experimental Liver Tumors in a Rat Model

Posted Jul 31, 2010 Updated Apr 7, 2023
By Soo-Jeong Lim PhD , Joon Seok Lim MD , Junjeong Choi MD , Jin-Young Choi MD , Woo Jin Hyung MD , Hong Sik Kim BS , Jinsuk Suh MD , Ki Whang Kim MD
7 min read

Rationale and Objectives

To characterize an iodized oil emulsion for computed tomography (CT) imaging of experimental hepatic tumors in rat models.

Materials and Methods

For characterizing the agents in normal rats, three rats were intravenously infused and imaged with clinical CT up to 1 week. Iopamidol solution was also used as controls ( n = 3). For evaluating the feasibility of diagnosis of hepatic tumors, 12 rats were injected with C6 glial tumor cells into the liver 11, 9, 7, and 5 days before CT ( n = 3 per day). After CT imaging, gross and histopathologic correlation of liver tumors with CT images were performed.

Results

CT numbers of aorta and inferior vena cava (IVC) increased immediately after injection of the emulsion and remained above 200 Hounsfield units for 1 hour (maximum: 295.67 ± 27.65 in aorta and 347.07 ± 10.58 in IVC). The mean attenuation in liver and spleen was relatively stable between 30 and 180 minutes (maximum: 188.84 ± 18.70 in liver and 210.97 ± 15.83 in spleen). All 20 tumors later confirmed by pathology were detected as hypodense lesions on CT (sensitivity: 100%; range, 2.0–16.4 mm). The mean enhancement ratios of liver at all time points were significantly higher than those of tumors ( P < .05).

Conclusion

The hepatic enhancement achieved by the iodized oil emulsion is reticuloendothelial system–specific with the property of blood pool enhancement and longer lasting than that achievable with the current water soluble agents. Thus, this agent may offer significant advantages for diagnosis of hepatic metastases.

Computed tomography (CT) imaging enhanced with water-soluble iodinated contrast is an important diagnostic modality in the preoperative evaluation of patients with suspected hepatic metastases. The choice between surgical or palliative treatment depends on the size, number, and location of metastases as determined by imaging . However, the limitations of these contrast agents include their extravasation and accumulation in both normal hepatic parenchyma and metastatic tumors, precluding accurate diagnosis of small hepatic metastases . The lack of accurate and early detection of metastatic lesions in many cases remains the major obstacle to effective patient treatment and ultimately to survival.

In comparison to water soluble agents, contrast agents consisting of particles selectively enhance the liver and spleen because the particles are sequestered by the phagocytic reticuloendothelial system (RES) . Therefore, they may provide enhanced diagnostic accuracy for hepatic metastatic lesions, because all metastatic liver lesions do not contain Kupffer cells constituting the RES. For CT imaging, several particulate contrast agents, including perfluorooctylbromide , ethiodol oil emulsion-13 , and liposomal agents , have been investigated.

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Materials and methods

Preparation of Nanoscale Particulate Iodized Oil Emulsion

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Animal Subjects, Anesthesia, and Injection Technique

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CT Image Acquisition and Parameters

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Imaging of Normal Rats for Evaluating the Time Enhancement Curve in the Blood Pool and RES

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Imaging of Tumor Model

Tumor model

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CT imaging and analysis

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Pathologic Evaluation

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Statistical Analysis

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Results

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Imaging of Normal Rat for Evaluation of the Time Enhancement Curve in the Blood Pool and RES

Time course of enhancement in the aorta, IVC, liver, and spleen

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Figure 1, Time enhancement curves for the aorta, inferior vena cava, liver, and spleen after infusion of an iodized oil emulsion or iopamidol solution. Each point represents mean ± standard deviation. Please note that the scale of the X-axis is logarithmic.

Figure 2, Axial computed tomography images of the liver ( upper row ) and spleen ( lower row ) show organ enhancement after iodized oil emulsion injection (left to right: precontrast, and 1, 10, 60, 180 minutes, and 1 week after contrast infusion). Intrahepatic vessels and inferior vena cava show strong and sustained enhancement until 60 minutes. After180 minutes, the intrahepatic vessels display relative isoattenuation with the hepatic parenchyma. Liver and spleen ( arrows ) shows rapid and progressive enhancement until 180 minutes. Complete washout in all organs is seen 1 week after infusion.

Figure 3, Coronal computed tomography images for organ enhancement after iopamidol injection (left to right: precontrast, and immediately and 30 minutes after injection). Rapid enhancement and washout of the contrast are seen in the aorta, inferior vena cava, liver, and spleen ( arrowheads ) on serial images. In comparison to iodized emulsion, weaker enhancement is seen in the aorta and IVC ( arrows ).

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Tumor Model Evaluation

Detection of tumors and correlation with pathologic results

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Figure 4, Radiologic-pathologic correlation (left to right: computed tomography [CT] image, gross specimen, and pathological slide). Coronal CT images of 22-mm-sized (a) and 2-mm-sized (b) tumors are well defined in the hepatic parenchyma. The gross specimen shows the corresponding lesions ( arrows ) and C6-glial cell tumors are pathologically confirmed ( arrows ) (original magnification, ×100 (a) and ×200 (b) ; hematoxylin-eosin stain).

Figure 5, Diameters of the tumor according to the duration of growth after the hepatic injection of tumor cells.

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Quantitative analysis of contrast enhancement on CT images

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Figure 6, Enhancement ratios of the tumor and normal hepatic parenchyma after injection of iodized oil emulsion (a) ; change of contrast-to-noise ratios in relation to the time of the contrast injection (b) .

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Discussion

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Academic Radiology, Volume 17, Issue 8
Journals General Radiology
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