colorectal cancer is one of the most common cancers worldwide with nearly one million people diagnosed each year . to 70% of all patients with colorectal cancer will develop hepatic metastases at some point in their lifetime , and one - third of these will have metastases confined only to the liver [ 1 , 2 ] .   in metastases from colorectal adenocarcinoma , locoregional therapies are available including radiofrequency ablation and resection , which provide a survival benefit for patients with limited disease . hepatectomy for liver metastases from colorectal cancer is the gold standard of treatment and provides the only chance for cure . complete resection of all disease has been associated with a five - year survival ranging between 22% and 58% . however , median survival for patients with untreated but potentially resectable metastases is 8 months , with a 5-year survival of less than 5% . the paradigm for resection of colorectal metastases has changed from excluding patients with more than 3 - 4 liver metastases , periportal lymphadenopathy , or metastases within 1  cm of major vessels to only excluding those in which a margin - free resection can not be achieved without preserving at least a 20% future liver remnant , or 30% if the patient has undergone chemotherapy [ 68 ] . identification and resection of liver lesions often rely on high - quality cross - sectional imaging studies , and these images are an indispensable tool in the treatment planning process .   historically , computed tomography ( ct ) has been used to stage and evaluate the liver in patients with colorectal adenocarcinoma . however , the introduction of magnetic resonance imaging ( mri ) has proven to be a highly effective way to evaluate liver parenchyma [ 1012 ] . in 1997 , the introduction of specific hepatobiliary contrast agents for mri further enhanced and strengthened this imaging modality . in addition to a more sensitive way to image metastatic lesions , the introduction of mri allowed radiologists to avoid the risk of contrast - induced nephropathy in patients with egfr < 40  ml / min in healthy patients and < 60  ml / min in diabetic patients . early publications evaluating the use of gadolinium - based contrast agents showed an advantage of mri over ct . recently , multiple studies have demonstrated the superiority of gd - eob - dtpa - enhanced mr over ct for detection of liver metastases . an adjunct to mri in patients to enhance the t1w images used in the detection , localization , characterization , and evaluation of lesions in the liver mt is a manganese - based agent , which shows hepatic enhancement as well as some biliary contrast . the agent had limited assessment of vascular structures due to its inability to be administered as a bolus and the agent was taken off the market in the united states in 2005 due to concerns regarding toxicity [ 16 , 17 ] . gadobenate dimeglumine ( multihance , gd - bopta ) was approved by the fda in 2004 for use as an mri contrast agent . gd - bopta acts as both an extracellular agent as well as a hepatobiliary contrast agent . while it is approved for hepatobiliary imaging in europe , it is used off - label in the united states . 3% to 5% is taken up by hepatocytes and excreted into the biliary system which allows for its hepatobiliary specificity [ 18 , 19 ] .   in 2008 , gadoxetic acid ( gd - eob - dtpa , eovist , primovist ) was fda approved in the united states for the detection and characterization of liver lesions . eovist is a gadolinium - based contrast agent with approximately 50% uptake into hepatocytes and subsequent biliary excretion . after administration , it is distributed into the vascular and extravascular spaces allowing for arterial , portal venous , and late dynamic phases . this is similar to nonspecific extracellular gadolinium contrasts ; however , it adds information during the hepatobiliary phases [ 2023 ] . it offers strong , early intravascular contrast allowing for dynamic phase imaging facilitated by 11% protein binding . this leads to increased relaxivity , thereby leading to increased signal enhancement in the blood and liver . due to its high relaxivity , dosing is also much lower than with other gadolinium compounds . gd - eob - dtpa is approved at a dose of 0.1  ml / kg to 0.025  mmol / kg body weight , this is one - fourth the dose of other gadolinium agents used in liver mri . it is thought to be absorbed into hepatocytes by the canalicular multispecific organic anion transporter 8 ( oatp8 ) with subsequent excretion into the bile via multidrug resistant protein 3 ( mrp3 ) . the hepatobiliary phase contrast enhancement peaks at 20 minutes and persists for more than 2 hours . gd - eob - dtpa demonstrates earlier onset , as well as longer duration of contrast than gd - bopta , which facilitates imaging and image quality . gd - eob - dtpa 's elimination half - life in healthy patients is roughly 55 to 57 minutes . it is eliminated equally ( 50% ) through the renal and hepatobiliary systems . in patients with one impaired pathway , for this reason , patients with renal or hepatic impairment do not require dose adjustment . it does carry the black box warning given to all gadolinium - based contrast agents because of its association with nephrogenic fibrosing dermopathy . this is a rare occurrence and tends to affect those with end - stage renal disease already on dialysis , and therefore it is recommended to avoid the use of gd - eob - dpta in patients with an egfr < 25 . the most frequent adverse reactions include nausea , vasodilation , headache , taste perversion , and injection site pain . eleven patients out of 162 ( 6.8% ) in a phase iii trial reported a total of 21 adverse events . of these , one was determined to be definitely related to gd - eob - dpta administration , 5 probably related , seven possibly related , one unlikely to be related , and seven not related . eovist - enhanced mri is invaluable in patients with severe allergies to iodinated contrast agents , such as prior anaphylaxis , who should not receive iodine during ct imaging . the use of dynamic contrast - enhanced mri with gadolinium - based contrast agents for the characterization of benign and malignant liver lesions has been well described in a growing body of literature [ 30 , 31 ] . these lesions include cysts , hemangiomas , metastases , the majority of hepatocellular carcinomas , and hepatic adenomas . in these cases , liver lesions will be more easily detected secondary to increased contrast between the lesions and the normal enhancing hepatocytes in the liver . on the other hand , hepatic lesions with functioning hepatocytes  including focal nodular hyperplasia and a small percentage of well - differentiated hepatocellular carcinomas  generally take up eovist during the hepatocyte phase . these lesions will be enhanced during the hepatocyte phase and demonstrate a distinct pattern of enhancement . from this , a variety of algorithms to characterize liver lesions based on enhancement patterns have been developed . however , when interpreting images acquired with gadolinium - based contrast agents , understanding the pathophysiology and pharmacokinetics is important for image interpretation . gd - eob - dtpa has unusual pharmacokinetics in that it is the only gadolinium agent which is taken up in equal amounts by the extracellular space and functioning hepatocytes , demonstrating a biphasic action . the dynamic phase of gadoxetic acid occurs during the first 2 minutes after injection . during this phase , normal hepatocytes as well as lesions containing hepatocytes exhibit contrast enhancement due to hepatocellular uptake . the enhancement pattern depends on vascular supply , the presence of functioning hepatocytes , and characteristics of the biliary structures within the lesion . the normal hepatocytes then slowly excrete the contrast agent into the biliary tree , which is referred to as the  hepatobiliary phase .  for gadoxetic acid , the duration of this phase is 20120 minutes where hepatocytes have excreted the contrast into the bile and have reached a level optimal for interpreting images of both the biliary system and hepatic lesions [ 26 , 27 , 32 ] . metastatic lesions are typically present on gadolinium - based contrast - enhanced imaging with peripheral rim enhancement and lack of central enhancement in the dynamic phase when central tumor necrosis is present . during the hepatobiliary phase , contrast uptake by hepatocytes provides contrast between the liver parenchyma and metastatic disease causing metastases to appear hypointense . in addition , during the hepatobiliary phase , rim enhancement   and a  target sign    have been described in metastases . initially , as mentioned previously , gadopentetate dimeglumine was the only gadolinium - based contrast available . the introduction of gd - eob - dpta allowed for increased uptake by hepatocytes , and vogl et al . ( 1996 ) demonstrated lesion to liver contrast superiority of gd - eob - dpta over gadopentetate dimeglumine , and a statistically significant improvement in detection rate in metastases , hepatocellular carcinoma , and hemangiomas . initial studies using gadolinium - based contrast agents showed advantages of mr over ct , but with some mixed results . since the initial studies , multiple groups have evaluated gd - eob - dpta - enhanced mri for detecting liver metastases .   in 2004 , kim et al . demonstrated improved tumor to liver contrast using gadobenate dimeglumine in the hepatobiliary phase , leading to detection of more metastases compared to dynamic imaging alone . in their paper , they describe the appearance of a  target sign  with central hyperenhancement and a hypointense rim . the european eob study group ( huppertz et al . 2004 ) looked at 302 lesions in 13 patients with biopsy or intraoperative ultrasound proven focal liver lesions . t1 and t2 phase mris , pre- and post - gd - eob - dtpa , were performed and evaluated in a blinded fashion by three radiologists . in 21 of the 129 patients , results differed between pre- and postcontrast mri , and 19 of these were correct in the gd - eob - dtpa group , resulting in a significant ( p < it also showed a 7% increase in correct lesion classification with gd - eob - dtpa as compared to precontrast mri . ( 2005 ) showed that the percentage of lesions that were correctly classified as malignant or benign was 215% greater for blinded readers comparing mr images with gd - eob - dtpa with helical ct images of the same patients , with an increase in false positive lesions identified using ct . false positive results in liver imaging for metastases from colorectal cancer can impact surgical planning , delay excision of the primary tumor , and result in unnecessary surgery .   in 2006 , halavaara et al . showed superiority of gd - eob - dpta compared to ct and diffusion weighted mr . they found increased lesion identification ( 95% versus 89% ) , sensitivity ( 95 versus 92% ) , and specificity ( 94 versus 90% ) with mri compared to ct . ( 2008 ) who looked at 302 lesions and showed that the frequency of correctly detected lesions was significantly higher ( 10.44% ) on gd - eob - dpta - enhanced mri compared with biphasic helical ct scan using histopathology or intraoperative ultrasound as confirmation . this superiority held true when looking at lesions with a diameter < 1  cm . interestingly , a change in surgical therapy was documented in 19 of 131 patients ( 14.5% ) after gd - eob - dtpa - enhanced mri . this superiority of gd - eob - dtpa to ct scan has been witnessed in multiple studies , as well as at our own institution . contrast of metastases from colorectal cancer on ct imaging versus gd - eob - dtpa - enhanced mri is clearly demonstrated in figures 1 and 2 . ( 2010 ) have demonstrated superiority of gadoxetic - acid - enhanced mr over unenhanced mr and triphasic contrast - enhanced spiral ct for detection of metastases with regard to sensitivity . this was true for lesions < 20  mm in diameter ; however , the lesions < 20  mm were not broken down by lesion type . in the same year , shimada et al . looked at 45 patients undergoing abdominal mri . 7 of these lesions were seen on gd - eob - dtpa but were missed on dwi by both observers . 2 metastases very close in proximity to hepatic vessels were difficult to detect on gd - eob - dtpa but were seen clearly on dwi . in this study , gd - eob - dtpa - enhanced mri showed statistically significant higher accuracy in detection of small lesions ( < 2  cm ) than dwi . however , only slightly more than half of these metastases were confirmed histologically ; the remainder were considered to be metastases on the basis of tumor growth on follow - up radiologic examinations . two studies have compared gd - eob - dtpa - enhanced mri with pet / ct . when looking at the lesions as a whole , there was a significant difference in lesion detection between pet / ct and gd - eob - dtpa mri ( 64% and 85% resp . there was also a significant difference in detection ( 29% and 71% p = 0.013 ) for lesions less than 1  cm in diameter . this study is very limited by the fact that it did not differentiate between benign and malignant lesions . following this study , seo et al . ( 2011 ) compared the diagnostic accuracy of gd - eob - dtpa mri to 18f - flourodeoxyglucose positron emission tomography / computed tomography ( ce - pet / ct ) for the detection of liver metastases , specifically from colorectal cancer . this study retrospectively looked at 135 metastases from 68 patients who underwent both imaging studies and were reviewed by 2 radiologists independently . they found significantly higher diagnostic accuracy and sensitivity of eob - mri than ce - pet / ct ( p < 0.001 ) . on subset analysis , 25 small lesions less than 1  cm in diameter were detected only with eob - mri . this difference in lesion detection between pet / ct and gd - eob - dtpa - enhanced mri is clearly demonstrated from a patient at our own institution as seen in figure 3 . ( 2011 ) demonstrated the superiority of gd - eob - dta - enhanced mr in the hepatobiliary phase to mr - dwi and mr for the detection of focal liver lesions when looking at 332 lesions ( 94.4%/100% , 78.3%/97.5% , and 81.5%/89.9% resp . ) . , this study did note that sensitivity for lesions < 1  cm was higher for mr - dwi than for mr hepatobiliary phase images ( 0.98 versus 0.92 ) . ( 2011 ) looked at a series of 47 patients with a total of 78 confirmed colorectal metastases comparing dwi and gd - eob - dtpa - enhanced mri . in this study , regardless of lesion size ( greater or less than 2  cm in diameter ) , significantly more lesions were detected when looking at both dwi and gd - eob - dtpa - enhanced images than with dwi imaging alone . interestingly , in this study , positive predictive value was higher in the dwi group compared to gd - eob - dtpa or the combined dwi and gd - eob - dtpa . muhi et al . ( 2011 ) broadened the comparison and looked at the diagnostic accuracy of contrast - enhanced ct ( ce - ct ) , contrast - enhanced ultrasound ( ce - us ) , and superparamagnetic iron oxide - enhanced mri ( spio - mri ) for detecting colorectal hepatic metastases . 112 metastases in 46 patients were evaluated . for all lesions combined , sensitivity and area under the receiver operating characteristic curve of gd - eob - dtpa - enhanced mri were significantly greater ( 95% ) than ce - ct ( 63% ) and ce - us ( 73% ) . for lesions less than 1 cm in diameter , sensitivity of gd - eob - dtpa - enhanced mri was significantly greater than for ce - ct and ce - us . however , they did not find a significant difference in positive predictive value between any of the imaging modalities . most recently , chen et al . performed a meta - analysis of 1900 lesions from 13 studies showing the sensitivity of gd - eob - dtpa - enhanced mri for detection of liver metastases to be 93% and specificity 95% with statistically significant decreased sensitivities with lesions less than 10  mm in size ( p = 0.001 ) . the issue of imaging patients following neo - adjuvant chemotherapy who have developed hepatic steatosis was evaluated by berger - kulemann et al . 68 metastases were evaluated with triphasic mdct and gd - eob - dtpa - enhanced mri . all patients underwent surgical resection of liver metastases after evaluation . for lesions < 1  cm diameter , mdct detected only 41.9% while mri detected 93% of metastases ( p < 0.001 ) . there was not a significant difference in lesions > 1  cm in diameter between mdct and gd - eob - dpta enhanced mri ( 97% and 100% resp . ) . while there have been multiple studies looking at the sensitivities and specificities of gd - eob - dpta contrast enhanced mri compared to other imaging techniques , economic considerations have become an increasingly important aspect of patient care in the united states . performed a cost analysis comparing mri with eovist , extracellular enhanced mri , and three - phase mdct as the initial evaluation of patients with metachronous colorectal liver metastases in germany , italy , and sweden . it demonstrated that mri with eovist required fewer additional imaging studies ( 8.6% ) than extracelluar - enhanced mri ( 18.5% ) and mdct ( 23.5% ) . while mri with eovist has the highest initial imaging cost of the three modalities studied , it was in fact cost saving when reimaging , and the cost of modified and unnecessary surgical procedures was factored into the equation . the ideal preoperative imaging study would provide diagnostic information which is highly sensitive and has a low rate of false positives . the studies described above have shown that hepatobiliary phase imaging with gadoxetic acid is safe and offers increased sensitivity in the detection of metastases due to the superior liver - lesion contrast generated by the avid uptake of gadolinium into the background of liver parenchyma . in addition , it has a lower rate of false positives than helical ct scan . these are important aspects of imaging in preoperative planning for resection of metastases from colorectal cancer .   accurately mapping the location and number of metastases from colorectal cancer is crucial for the surgeon 's preoperative planning process . not only can it dramatically alter an operation from a minor wedge resection to a much larger anatomic procedure , but also it allows the surgeon to counsel the patient more accurately regarding the procedure they will require to excise the metastases . this is supported by the studies discussed previously where operative plans changed after reviewing gd - eob - dpta enhanced mri imaging . in addition , false positive results can lead to unnecessary procedures for patients , and in a time when surgery is accepted and increasingly popular , it can unnecessarily delay the resection of the primary tumor . eovist - enhanced mri is superior to other imaging modalities in the detection , localization , delineation , and management of patients with liver metastases from colorectal cancer .
colorectal cancer affects over one million people worldwide annually , with the liver being the most common site of metastatic spread . 
 adequate resection of hepatic metastases is the only chance for a cure in a subset of patients , and five - year survival increases to 35% with complete resection . 
 traditionally , computed tomographic imaging ( ct ) was utilized for staging and to evaluate metastases in the liver . 
 recently , the introduction of hepatobiliary contrast - enhanced magnetic resonance imaging ( mri ) agents including gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid ( eovist in the united states , primovist in europe , or gd - eob - dtpa ) has proved to be a sensitive method for detection of hepatic metastases . 
 accurate detection of liver metastases is critical for staging of colorectal cancer as well as preoperative planning .