CT and MR Imaging in the Diagnosis of Hepatocellular Carcinoma - Essay Example

? Hepatocellular carcinoma Introduction: Hepatocellular carcinoma (HCC) is one of the primary malignant tumors of liver. It is caused due to the heavy exposure to the hepatitis B and C viruses and also by the environmental factors. The patients with the hereditary hemochromatosis have the greatest risks of developing hepatocellular carcinoma. Hepatocellular carcinoma develops in the cell when the cell is mutated in its cell machinery. The mutation at the cellular metabolism level prevents the cell from undergoing apoptosis and thus leads to the higher rate of replication. Chronic hepatitis C causes HCC through cirrhosis and hepatitis B virus genome enters into the cells and causes infection leading to the non-cirrhotic liver HCC. The environmental factors are also found to have a greater influence on HCC. The higher level of consumption of alcohol also causes HCC. (Carr 2009). The recent advances in the tissue specific image analysis have made the diagnosis of the diseases at the inner organs very easy with high sensitivity. MRI and CT are the two techniques that use the image analysis. HCC is a very chronic liver disease with several levels. Hence the diagnostic of each level is very essential for the complete treatment and also for resection of the part. (Kamel and Bluemke 2002). Any destruction to the liver parenchyma, biliary ducts and vascular structures must be analyzed properly to study the liver dysfunction. HCC can occur as an infectious or inflammatory disease resulting in storage and metabolic disorders and sometimes may lead to vascular diseases or neoplastic disease. Diagnosis of HCC: When a person is suspected with HCC, the ultra sound diagnosis is done first and if the case is found to be much severe then contrast medium – enhanced helical computed tomography (CT) along with dynamic magnetic resonance (MR) imaging is used. Combination of CT and MR is found to give accurate non-invasive screening modalities. At the time of diagnosis, the tumor may be small or large. The infection level may be small or chronic. The diagnosis must be able to provide complete information regarding the condition of the tumor and the level of treating it. For this we require a proper diagnostic technique. The studies have found that MRI or CT can provide better diagnostic results. But it was also found that MRI can predict results only to certain limit and so do CT. So a further analysis of these techniques will provide a good idea of what to use and when to use. As HCC are hyper vascular disease, contrast agent is used for the diagnosis. There are four phases in the liver CT scanning. They are pre contrast, arterial phase, portal venous phase and delayed phase. The CT scan is performed for these phases based on the disease condition whether it is hyper vascular or hypo vascular. In CT scan, the pre contrast phase imaging helps us to detect the calcifications in the liver and they are also able to demonstrate the hyper vascular lesions present hypo attenuating to the parenchyma liver cells. (Hayashida et al. 2007). The arterial phase imaging is done after 30 seconds from the injection of contrast phase. The arterial phase scanning is used to demonstrate the hyper vascular lesions that are present in the liver by the enhancement of the liver. This arterial phase imaging helps the doctors to decide whether to go for operation of the tumor or treat it with medicines. This imaging is done as a 3D imaging and thus is of more useful in diagnosis. The portal venous phase is done after 70-90 seconds of injecting the contrast medium and they help to evaluate the hypovascular lesions in the body. (Kamel and Bluemke 2002). The last phase is the delayed phase where the lesions are characterized further after 5 – 10 minutes of injection. The HCC can be seen as hypodense lesions as the contrast pahse is washed out completely. Pathologic changes in the hepatic cirrhosis: Cirrhosis occurs due to the hepatic injury and results in the fibrosis diffusion. The nodules are regenerated from the liver cell necrosis and degeneration. (Kamel and Bluemke 2002). The fibrosis causes the cell degeneration and results in the formation of the nodules starting from the benign regenerating nodules to the HCC. (Kojiro 2006). In the early stage of liver cirrhosis, all the diagnostic results seem to be normal but at the later stage the nodules and the later hyper vascularisation may seem to be higher resulting in the decrease in the size of the right lobe in the liver and enlargement of the other lobes in the liver mainly the caudate lobe and left lobe. (Schiff, Sorrell and Maddrey 2007). Steatosis and inflammation leads to cirrhosis followed by cell and nodule regeneration. The nodules are of two types: macro nodular and micro nodular of size greater than 3 mm and less than 3 mm respectively. Micro nodules may be of uniform size but macro nodules vary in size from 3 mm to 20 mm. the macro nodules are more common in HCC patients. (Livraghi, Makuuchi and Buscarini 1997). The best diagnostic method to detect HCC is the use of CT and MR scanning methods. The fibrosis that is formed can affect the sensitivity of the imaging. Hence the use of contrast phase is practiced. The contrast phase will give us the clear picture of the normal liver parenchyma cells and cirrhosis liver. (El–Serag and Rudolph. 2007). CT Scan: Conventional CT scan and Spiral CT scan are performed for HCC. In the conventional method, the imaging is done at 7 -10 mm interval and the imaging is done by holding the breathe every time. In the spiral CT scanning method, continuous scanning is done and the slices are obtained in a single breath itself. This imaging is done very quickly (15 – 30 seconds are enough for the imaging). (Park et al. 2005). The important advantage of this method is that, the analysis can be finished in the arterial phase where high contrast medium concentration is present. The computed imaging gives very clear description about the relationship between the blood vessels and the tumors. Thus the CT scan is able to give the complete information about the liver as a thin slice. There are many imaging techniques. CT without contrast medium administration, single phase contrast – enhanced CT, multiphase hepatic CT, Angiography assisted CT and CT after injection of iodized oil. Magnetic resonance Imaging is the next type of imaging technique. MRI with and without contrast medium is performed. CT without contrast medium enhancing is done only at specific conditions. It is mainly done to identify calcification, pre contrast imaging and iron deposition. The Single- phase contrast – enhance CT is used for identifying the regular liver abnormalities and the portal venous phase condition more effectively. For single phase CT, the contrast medium is inversely proportional to the weight of the patients and usually a concentration of 3ml per second is used. 350 mg of the contrast medium is diluted as per the patient’s body weight with the saline and injected into the body. The saline is given as a continuous phase after injection in order to remove the contrast medium from the body. Figure: the Arterial phase dominant CT imaging. (Park et al. 2005). Multiphase contrast CT scanning is more advantageous than the single phase contrast imaging in many points. The hyper vascular lesions are easily detected and are characterized with the combination of other image analysis techniques. The MDCT are more advantageous in the way that they require only very short acquisition times and have greater spatial resolution. (Andersen et al. 2006). The hepatic arterial anatomy is well understood by using this technique. The multi phase scanning is used for obtaining the images at the arterial phase, the portal venous phase and the late phase images very accurately and more precisely. The portal venous phase images are used to view the hepatic veins more clearly than the other stages. The tracking software is used to track the path of the contrast medium to the liver. (Andersen et al. 2006). The rapid injection rate helps to identify the enlargement of the arterial vessels and also to separate the portal and arterial phases during the injection. (Lee et al. 2006). Angiography assisted CT method uses a catheter for the administration of the contrast material through the hepatic artery. The malignant hepatic neoplasms are seen as hyper dense masses. The images are seen larger than their true size due to the injection of the contrast medium (which is usually a corono enhancer). (Lee et al.2006). Computed Tomography was performed after one week of injection of the iodized oil up to four weeks of time. This technique is used to detect the small tumors that are present in the liver. The vascular hepatic neoplasm retains this iodized oil when the other parenchymal cells clear them. (Lee et al. 2006). The main drawback of this technique is that it is not able to find out hypo vascular HCC. (Fujita et al. 2008). The use of micro CT for the analysis of the HCC was done at the laboratory level initially. The scanners were found to have an excellent spatial resolution of less than 50 µm. initially this micro CT was used in the laboratory for the tumor identification and monitoring. The small animals used in the lab experiments were analyzed using this micro CT. (Weber et al. 2004). ITG (1,3-bis [7-(3-amino-2,4,6-triiodophenyl) heptanoyl]2- oleoyl-glycerol) is the contrast medium that is used for the analysis of the tumors in rats, rabbits and not for mice. (Weber et al. 2004). This ITG is hepatocyte selective chemical because it is taken up by the ApoE receptor- mediated pathway. The disadvantage of this method is that the acquisition time is very long. As the renal clearance is very fast and the time is very long, the sensitivity of the results is very less. The only big advantage of the use of MicroCT is that very small tumors can be easily identified. (Weber et al. 2004). Now the multi detector row CT is also used for acquiring sliced image analysis in a shorter time. It is possible, to detect the smaller lesions with better resolution. (Akai et al. 2010). The CT scan technique image fusion was tried for optimization by using the F-18-FDG- PET with the CT. Here the images were obtained with the contrast enhanced CT and the image was optimized using the PET. The sensitivity was 100% for this technique and the detection rate was 100% when the solitary primary nodules were greater than 4mm. This protocol was recommended for detection of tumor in the body. (Juergens et al. 2006). Magnetic resonance imaging (MRI): The rapid isolation techniques with tissue specific advanced contrast medium usage provide excellent image quality with the MR imaging. MRI is considered to be advanced than CT because of its clarity in the imaging tasks. The MR is performed by using T1 and T2 weighed sequences that are followed by the image acquisitions. Tanimoto and Kuribayashi 2006). The T1 weighed image analysis is done by the injection of the gadolinium chelate to the bolus rapidly. Then the images are taken within 15 minutes. By MRI the breathing artifacts and the magnetic susceptibility artifacts are minimized. The blood supply to the nodules is from the portal venous system and to that of HCC is from the arterial system. Breathe hold spoiled gradient echo (SGE sequence) is performed in the T1 weighed sequence image analysis. MRI is able to give a more definitive diagnostic measure of iron deposition in the patients. (Pedersen, Fisher and van Beck 2006). MRI is used when the iodized oil CT cannot be performed for the patients and for those, liver is the region of concern. MRI is also able to provide the images with cirrhosis. (Danet, Semelka and Braga 2003).The early cirrhosis is detectable in the 98% of the patients. Hilar periportal enlargement which is the main manifestation of early cirrhosis is found out easily. MRI is useful for diagnosis of small hepato hemangioma. The focal lesion location in the liver identification is another important part performed by MRI, which is not possible for the CT. Thus MRI provides early detection of cirrhosis which enables the patients with treatment opportunities. (Danet, Semelka and Braga 2003). The interlobular enlargement is followed by the gall bladder fossa sign. This is a high specificity is symbol and the positive predictive value (PPV) for this sign is about 98%. The advanced stage of cirrhosis cannot be identified easily using the T1 weighted image analysis because of the low intensity of the signals. T2 weighed image analysis is performed for the advanced stages because of its high signal intensity. The fibrotic tissues are not easily identified using the MRI at the earlier stage and the combination of the atrophic and the hypertrophic changes becomes very complex parenchymal distortion. As each and every method has specificity for the different stages of cirrhosis, a combination of the T1 weighed, T2 weighed and the serial gadolinium enhanced SGE are used for accurate analysis of the lesions. (Danet, Semelka and Braga 2003). The MR imagining can provide images with great sensitivity. The dysplastic nodules characteristic appearance can be easily found using the MR imaging as T1 weighed images can provide the hyperintensity and T2 weighed images the hypointenstiy characteristic images. (Danet, Semelka and Braga 2003). The small lesions of HCC are difficult to be identified form the non-malignant nodular masses using the CT and this creates difficulty in providing the right medicine and therapy. This differentiation is possible with MRI. (Danet, Semelka and Braga 2003).The regenerated nodules appear very intense using the T1-weighed images and isointense on the T2- weighed images. Volumetric interpolated breath-hold examination [VIBE] along with the mSENSE technique was used to analyze the dynamic images of the MRI. This is a three dimensional gradient echo sequence. VIBE with T1 weighed analysis can provide high spatial resolution, multi planar display of the hepatic vessels and the thinner section detection for the lesions.(Danet, Semelka and Braga, 2003). The MRI had the combination of the T1weighed imaging and Gadolinium based agents for the contrast medium. It was found that this combination helped them to identify the hyper vascular HCC and the noneoplastic hyper vascular pseudo lesions in the liver cirrhosis. (Kim et al. 2008). Thus this combination helped them to find out the smaller lesion at the beginning of the HCC itself. The disadvantage of this method is that all the studies were not histologicaly confirmed. They were done so only after the follow up image analysis. This MRI combination was thus able to prove that the small lesions that are present in the initial stage of HCC can be identified only at the arterial phase of MRI analysis. The patients with mild hepatitis b virus induced cirrhosis can be identified as HCC. (Kim et al. 2008). Figure: T2 weighed sinlge shot echo- train spin photo. (Danet, Semelka and Braga 2003). Figure : SGE of the liver. (Danet, Semelka and Braga 2003). Figure : out of phase. (Danet, Semelka and Braga 2003). Figure: immediate post- galdonium image. (Danet, Semelka and Braga 2003). Figure: post –galdonium image after 45 seconds. (Danet, Semelka and Braga 2003). MRI works on the principle of detection of the energy released by the hydrogen protons after their alignment in the strong magnetic field. So this technique is not suited for the patients with the pace makers and metallic foreign bodies and for those who are pregnant. This has excellent contrast resolution and good spatial resolution and multiple planes are reconstructed according to the use. The reproducibility of the MRI is also very good. There are many MR pulse sequences available to diagnose tumor at different stages of HCC. e Gadolinium ethoxybenzyl diethylenetriamine penta acetic acid (Gd-EOB- DTPA) is developed as the new contrast liver specific T1 medium using the MRI. (Ito 2006).This method is an improved method of MRI for detecting liver lesions. This technique also used to diagnose better than the normal gadolinium chelates. Two dimensional gradient echo sequence is used with MRI for better analysis , now the three dimensional analysis with T1- weighed sequences are used for the analysis of the thin slices of the liver. The parallel imaging done at shorter times are sufficient for the detection of the smaller lesions. (Ito 2006). The use of supraparamagnetic iron oxide (SPIO) for the contrast medium along with dextran or carboxydexran for MRI was tried for better diagnosis than the traditional T1 and T2 weighed image analysis. This method was tried for better analysis of hepatic metastases. (Tanimato et al. 2006).The introduction of SPIO has enabled them to get more sensible test results for the HCC. The diagnosis was better as it enhances the RES containing tumors. The focal hepatocellular lesions were also diagnosed in a much better way than the traditional MRI. (Tanimato et al. 2006). CT and MRI: The use of CT separately and MRI separately aims at the production of the images with less accuracy and the prediction of the results vary. The combination of CT and MRI can produce better results and most of the lesions are identified. This combination is quiet costly and is less widely available. The HCC are usually diagnosed from dysplastic nodule by using either dynamic contrast enhanced CT or by using Gd- enhanced MRI. (Tomemori et al. 2001) Similarly the SPIO enhanced MRI is equivalent to the combined CTHA and CTAP. When the Gd-EOB- DTPA enhanced MRI was compared with the multi- row detector CT , it was found that Gd-EOB- DTPA enhanced MRI was able to give better image results for the HCC than the64 row detector CT. (Akai et al. 2010). In a study conducted by Akai et al, the patients were analyzed with both the CT and MRI images. It was found that the lesions were easily identified using the MRI much better than the CT. The sensitivity, the positive predictive value and the negative predictive value were calculated for both the methods CT and MRI. The sensitivity for the identification of the lesions in HCC were greater for MRI than CT and the positive predictive value(PPV) was higher for CT then MRI and negative predictive value (NPV) was greater for MRI than CT.(Akai et al. 2010). From this results it was concluded that the use of Gd-EOB- DTPA enhanced MRI by the observer gave maximum sensitivity than the CT technique. Summary: Hepatocellular carcinoma is a chronic disease that is caused by the environmental factors and also by the hepatitis B and C viral infections. The tumor caused in the liver must be properly diagnosed and treated. The studies have indicated that the survivals of the patient with poorly differentiated HCC are more prone for death than the chronic HCC patients. This tells us the importance of diagnosis of HCC. The poorly differentiated HCC which are around 3 cm is chronic. (Nishie et al. 2010). The histological grade must be found out for the patient’s condition for the proper selection of the treatment method. The use of magnetic resonance imaging using the specific contrast agent such as supraparamagnetic iron oxide (SPIO), or ethoxybenzyl diethylenetriamine penta acetic acid (Gd-EOB- DTPA) is used for the diagnosis of the well differentiated HCC. (Nishie et al. 2010). The CT imaging is also used for the analysis but the MRI is found to have greater resolution than CT. but a combination of CT and MRI can give greater results for better treatment for HCC. References: Akai, Hiroyuki., Shigeru Kiryu, Izuru Matsuda, Jirou Satou, Hidemasa Takao, Taku Tajima, Yasushi Watanabe, Hiroshi Imamura, Norihiro Kokudo, Masaaki Akahane and Kuni Ohtomo. 2010. “Detection of hepatocellular carcinoma by Gd-EOB-DTPA-enhanced liver MRI: Comparison with triple phase 64 detector row helical CT.” European Journal of Radiology. 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