Characterization Of Liver Tumors Research Articles

New RES-Specific Contrast Agents for CT

Several liver-specific contrast media have been developed for improved detection and characterization of liver tumors. Most of these agents were designed for magnetic resonance imaging (MRI) (1–5). However, up to now, computed tomography (CT) remains the primary imaging modality for most patients with suspected liver disease (6,7). Therefore, development of organ-specific contrast media for CT, that are both safe and efficacious, is of great clinical importance. One approach of liver targeting has been the encapsulation of a water-soluble iodinated contrast agent inside liposomes. Like other particulate agents, liposomal contrast media are taken up by the reticuloendothelial system (RES), which should give them an advantage over conventional extracellular contrast agents for liver imaging. Several studies have described liposomal encapsulation with several iodinated contrast agents, such as iopromide, iopromidol, iotrolan, diatrizoate, and others (8–13). Although some of these agents have been shown to be effective contrast media for liver imaging, results have been not entirely satisfactory, mostly because of safety reasons (high rates of adverse events). Therefore, further research is needed to develop a safe and efficacious liposomal contrast agent for CT imaging. In this study, we explored the enhancement efficacy of two new liposomal formulations, BR 23 and BR 24 (Bracco Research, Geneva, Switzerland), which contain iomeprol, a low viscous nonionic dimer, for CT imaging of liver and spleen in primates. These preparations contain both encapsulated and unencapsulated iomeprol. An additional aim of this study was to compare these two new agents to Imeron 300, which is already in clinical use.

Preclinical assessment of hepatocyte-targeted MR contrast agents in stable human liver cell cultures.

Much effort has been expended in the search for hepatocyte-specific MR contrast agents to improve the detection and characterization of liver tumors. The purpose of this study was to establish human hepatocyte cell cultures to preclinically assess hepatocyte-targeted magnetopharmaceuticals. Cultured human hepatocytes were sandwiched between two layers of collagen preserving both hepatocyte function and morphology over prolonged period of time. Cultures (n = 37) were subsequently used to test different fluorescinated MR contrast agents. Plain and rhodaminated monocrystalline iron oxide particles (MION and MION-rh) and asialoglycoprotein-receptor-specific rhodaminated asialofetuin coupled to MION (MION-ASF-rh) were prepared. Competition experiments of these agents were performed with D(+)-galactose to study the specificity of galactose-mediated cell uptake. To assess the impact of cell integrity on cell uptake, functional experiments with CCl4 were performed. Normal cell cultures showed significantly higher fluorescence light emission after incubation with hepatocyte-directed ASF-MION-rh than after incubation with MION-rh. Competition experiments of ASF-MION-rh with galactose showed a dose-dependent decrease of calibrated fluorescence light emission. Cell cultures treated with CCl4 demonstrated a dose-dependent significant reduction of calibrated fluorescence light emission, indicating reduced uptake of ASF-MION-rh. Our data demonstrate that stable human hepatocyte cell cultures can be used to preclinically assess novel magnetopharmaceuticals. Different contrast agents may be directly compared to each other and may accelerate their preclinical design. Because the assay can be applied to cells from any species, it may represent an ideal test system before clinical trials of new cell-directed MR contrast agents.

Liver imaging. Clinical applications and future perspectives.

Primary hepatocellular carcinoma and liver metastases affect several million people each year. The main imaging modalities to detect and assist diagnosis of primary and secondary liver tumours include MR imaging, CT, and US. The value of these techniques is further increased by the use of contrast agents which increase the sensitivity, and sometimes also the specificity, of the investigations. The relative advantages and drawbacks of the different contrast agents and imaging modalities in the detection and characterisation of liver tumours are discussed. Currently there is no consensus amongst investigators as to which is superior, due to the technical complexities and number of combinations possible within each of the different modalities. There continues to be advances in the hardware and software of imaging equipment, as well as a trend to develop new contrast agents with more organ-specificity. These include those targeting the hepatocytes, such as mangafodipir trisodium (MnDPDP, Teslascan), and those with reticuloendothelial cell specificity, such as the superparamagnetic iron oxides. These developments have the potential for making significant contributions to the diagnostic value of imaging procedures and, by reducing the number of investigations necessary to reach a final diagnosis, having a significant and beneficial impact on the pharmaco-economics of patient health care.

Focal liver masses: characterization with diffusion-weighted echo-planar MR imaging.

To evaluate diffusion-weighted echo-planar magnetic resonance (MR) imaging for improving the specificity of characterization of liver tumors. Diffusion-weighted echo-planar imaging was performed with a 1.5-T whole-body imager with use of a body phased-array coil in 51 patients with 59 hepatic masses (41 malignant tumors, nine hemangiomas, and nine cysts). Apparent diffusion coefficient (ADC) values were obtained with two motion-probing gradients (b = 30 and 1,200 sec/mm2) during each of the breath-hold periods, and an ADC map was constructed. The T2 was derived from spin-echo echo-planar images with echo times of 47 and 99 msec. The ADC value of malignant masses (1.04 x 10(-3) mm2/sec) was significantly lower (P < .01) than that of benign masses (hemangiomas [1.95 x 10(-3) mm2/sec] and cysts [3.05 x 10(-3) mm2/sec]), although the T2s showed considerable overlap. A small amount of overlap in ADC values occurred among malignant tumors, hemangiomas, and cysts. ADC values of two cystic masses from ovarian carcinomas were within the range of those of hemangiomas. These preliminary results indicate that diffusion-weighted MR imaging can be useful in characterizing focal liver masses. With the exception of cystic metastatic tumors, the technique may be especially useful in tumors that appear markedly hyperintense on T2-weighted images due to a long T2.

Methodological assessment of combined spiral CT angiography and CT arterial portography

To assess an optimal methodology of combined spiral computed tomographic (CT) angiography (CTA) and CT arterial portography (CTAP) for detection and characterization of liver tumors. We performed spiral CTAP only in five patients with 30-32% contrast (subset A), CTAP combined with preceding spiral CTA using 30-32% contrast in 19 (subset B), and CTAP combined with preceding spiral CTA with 60-64% contrast in seven (subset C). The CT numbers of the aorta immediately before preceding CTA and subsequent CTAP and the CT numbers of malignant tumor and liver parenchyma with CTAP were measured. The differences of the CT number between the malignant tumor and liver parenchyma on CTAP were 61.1-161.8 (mean +/- SD, 114.5 +/- 39.3) HU, 50.7-164.8 (104.2 +/- 31.2) HU, and 101.2-368.3 (219.5 +/- 90.5) HU in subsets A, B, and C, respectively. Two cavernous hemangiomas showed pathognomonic findings with preceding CTA. Combination of preceding spiral CTA and subsequent spiral CTAP using 30% contrast with a 5-min interval is an optimal method for detection and characterization of liver tumors.

MR imaging characteristics of hepatic tumors.

There is no doubt that radiologists play an increasingly important role in the detection of focal liver lesions, and in the evaluation of persistent or recurrent malignant disease after treatment. The characterization of focal liver lesions depends on the clinical integration of the information generated by different radiologic techniques. Most often, MR imaging is quite effective in liver tumor characterization. Our purpose is to provide an overview of the MR characteristics of the most commonly encountered liver tumors and their differential diagnosis, with the most accepted reliable proof of the lesion type in a clinical environment. Radiologists must know the level of confidence they can reach in a given diagnosis, and the influence that this diagnosis has in the patient's management. With this knowledge, radiologists decide whether to leave or follow-up the lesion, perform tissue samples, or carry out therapeutic procedures.