**3. Radiologic imaging techniques in the diagnostics of liver metastases of colorectal cancer**

The radiologic techniques of liver examination comprise computed tomography, magnetic resonance imaging, ultrasound evaluation and fluorodeoxyglucose positron emission tomog‐ raphy [17]. CT and MRI represent the cornerstone in the diagnostics of liver metastases of colorectal cancer [1, 18]. US has the benefits of wide accessibility and lack of irradiation. However, it is considered a historical method in developed countries as USA [18] due to lower sensitivity and specificity. These parameters can be improved by contrast-enhanced US [19]. Positron emission tomography (PET) has certain indications.

MRI is characterised by the highest specificity and sensitivity, especially regarding metastases smaller than 1 cm in diameter [1, 20]. The imaging technology is based on different physical status of water and fat protons [18]. To identify liver metastases, MRI routinely includes T1, T2 and diffusion-weighted sequences before and after administration of gadolinium-contain‐ ing contrast agent. The CRC metastases are hypointense on T1 but hyperintense on T2 and diffusion-weighted imaging sequences. The contrasting reveals metastasis as a hypovascular focus with an irregular rim of enhancement [18].

In the identification of liver metastases, MRI is characterised by the highest sensitivity that reaches 76.0–85.7% if enhancement by extracellular contrast agents and dynamic acquisition is used. The sensitivity can be further improved by diffusion-weighted imaging. Diffusionweighted imaging is based on the assessment of Brownian motion of water molecules and water diffusion within a voxel (a tridimensional pixel). As cell membranes limit the diffusion, greater cellularity results in diffusion restriction [21]. Thus, the metastasis creates an obstacle in water molecule diffusion and is revealed by diffusion-weighted imaging at higher sensi‐ tivity and specificity than routine MRI [17, 22, 23]. The hepatobiliary phase MRI represents another improvement in the diagnostics of liver metastases by contrast agents that are absorbed by hepatocytes and excreted in biliary system, e.g., gadoxetate disodium and gadobenate dimeglumine. These agents differ from the traditional MRI contrast agents by the dual elimination, including both biliary excretion (50%) and renal glomerular filtration, while the traditional agents, as gadopentetic acid, are almost completely excreted via kidneys [1, 18]. The hepatobiliary phase of MRI corresponds to the peak parenchymal enhancement due to contrast uptake in hepatocytes. It is observed 20 min after injection. Metastatic foci lack liver cells and therefore do not absorb hepatobiliary contrast agents. In the diagnostics of colorectal cancer liver metastases, the sensitivity of hepatobiliary phase MRI reaches even 90–97% [1, 24, 25]. In comparison with diffusion-weighted imaging, hepatobiliary phase MRI enhances sensitivity for the detection of colorectal cancer metastasis, e.g., from 78.3–97.5% to 94.4– 100.0%. The combination of diffusion-weighted imaging with hepatobiliary phase MRI yields better results than isolated techniques [26].

also several screening methods, including guaiac-based or immunochemical test for occult blood in stools, faecal DNA test, virtual colonoscopy by computed tomography imaging, double-contrast barium enema, flexible sigmoidoscopy and colonoscopy [2]. MicroRNA stool test could appear in the nearest future. Despite the possibilities of prevention and screening, metastatic disease is common. Metastatic spread to liver occurs in 70–75% of patients, and 20– 35% of CRC patients are diagnosed with synchronous liver metastases [1, 3, 4]. Although the presence of metastatic disease significantly adversely affects the survival, a wide scope of

**3. Radiologic imaging techniques in the diagnostics of liver metastases of**

The radiologic techniques of liver examination comprise computed tomography, magnetic resonance imaging, ultrasound evaluation and fluorodeoxyglucose positron emission tomog‐ raphy [17]. CT and MRI represent the cornerstone in the diagnostics of liver metastases of colorectal cancer [1, 18]. US has the benefits of wide accessibility and lack of irradiation. However, it is considered a historical method in developed countries as USA [18] due to lower sensitivity and specificity. These parameters can be improved by contrast-enhanced US [19].

MRI is characterised by the highest specificity and sensitivity, especially regarding metastases smaller than 1 cm in diameter [1, 20]. The imaging technology is based on different physical status of water and fat protons [18]. To identify liver metastases, MRI routinely includes T1, T2 and diffusion-weighted sequences before and after administration of gadolinium-contain‐ ing contrast agent. The CRC metastases are hypointense on T1 but hyperintense on T2 and diffusion-weighted imaging sequences. The contrasting reveals metastasis as a hypovascular

In the identification of liver metastases, MRI is characterised by the highest sensitivity that reaches 76.0–85.7% if enhancement by extracellular contrast agents and dynamic acquisition is used. The sensitivity can be further improved by diffusion-weighted imaging. Diffusionweighted imaging is based on the assessment of Brownian motion of water molecules and water diffusion within a voxel (a tridimensional pixel). As cell membranes limit the diffusion, greater cellularity results in diffusion restriction [21]. Thus, the metastasis creates an obstacle in water molecule diffusion and is revealed by diffusion-weighted imaging at higher sensi‐ tivity and specificity than routine MRI [17, 22, 23]. The hepatobiliary phase MRI represents another improvement in the diagnostics of liver metastases by contrast agents that are absorbed by hepatocytes and excreted in biliary system, e.g., gadoxetate disodium and gadobenate dimeglumine. These agents differ from the traditional MRI contrast agents by the dual elimination, including both biliary excretion (50%) and renal glomerular filtration, while the traditional agents, as gadopentetic acid, are almost completely excreted via kidneys [1, 18]. The hepatobiliary phase of MRI corresponds to the peak parenchymal enhancement due to contrast uptake in hepatocytes. It is observed 20 min after injection. Metastatic foci lack liver

Positron emission tomography (PET) has certain indications.

focus with an irregular rim of enhancement [18].

treatment options exist.

172 Recent Advances in Liver Diseases and Surgery

**colorectal cancer**

Gadolinium-containing contrast agents can induce nephrogenic systemic fibrosis in a subfrac‐ tion of patients (2.9–4%) with severe renal insufficiency [1, 27, 28]. Sufficient enhancement quality can be reached by half-dose gadoxetic acid [29]. However, other research groups have not observed any case of gadoxetate-related nephrogenic systemic fibrosis in a prospective multicentre study [30]. The risk of nephrogenic systemic fibrosis also varies by different contrast agents [1].

In comparison with CT, MRI has advantage in the diagnostics of lesions measuring less than 1 cm and shows better ability to discriminate metastases on the background of spontaneous or treatment-induced (e.g., 5-fluoruracil and irinotecane) liver steatosis [1, 17, 31]. However, CT provides better resolution of anatomic details that are necessary to plan the surgery [18]. Consequently, controversies have been expressed if the liver imaging in colorectal cancer patient should be started with CT or MRI [1, 18].

MRI is contraindicated in patients having incompatible implants, e.g., pacemakers; affected by claustrophobia or impaired glomerular filtration rate, or unable to hold the breath for longer than 20 seconds. CT should be performed in these patients [1, 18].

Multidetector CT can be used for chest, abdominal and pelvic imaging to reveal the total visceral metastatic burden. Contrasting with intravenous iodinated agents is necessary to reveal liver metastases that represent hypodense hypovascular foci with variable heterogene‐ ity, seen in portal venous phase [18]. Rim enhancement can be observed [17]. Due to low tumour vascularity, arterial phase is more important for detection of arterial anatomy than for identification of metastases. In nonenhanced CT, the metastases are hypointense but can be inconspicuous [17, 18]. The possibilities of CT are limited in detection of small lesions and inhassessment of steatotic liver. MRI is helpful in these situations. The benefits of multidetector CT include high spatial and temporal resolution exceeding that of MRI. Thus, CT is useful for planning before surgery. The individual anatomic features can also be detailed by CT [18].

PET-CT reflects the metabolic activity in tumour cells by analysing glucose uptake. It has advantage in detecting extrahepatic metastatic spread [1] or local recurrence and in evaluation of indeterminate liver lesions [17]. In a prospective study of 133 consecutive patients, PET-CT had a major impact on staging of extrahepatic spread in 20% of patients. It resulted in upstaging (from surgically treatable to inoperable) in 6% of patients and downstaging (from indetermi‐ nate or suspected inoperable to operable) in another 6% of patients [32]. As extrahepatic spread is more likely in patients who already have liver metastases, PET-CT should be considered a standard evaluation prior to curative liver surgery for metastatic colorectal cancer. PET-CT reduces futile laparotomies by 38% [33]. Combination with diagnostic intravenous contrastenhanced CT is strongly advised as opposed to noncontrast low-dose CT providing anatomic data only [1, 34]. The sensitivity of PET-CT is impaired after chemotherapy [1, 35].

In the early studies, liver US was considered effective in the follow-up after surgical treatment of colorectal cancer metastases as it disclosed all the resectable cancer metastases as it disclosed all the resectable with thoracic X-ray [36]. However, more recent data evidence that transab‐ dominal US has limited sensitivity in the diagnostics of CRC liver metastases: 50–75% [17]. Despite the serious shortcoming, US still can be used for screening purposes by experienced specialist who is aware of these limitations and will combine US by more sensitive methods of radiologic diagnostics. Intravenous contrast-enhanced US imaging using microbubbles to contrast blood increases the sensitivity of US by 20% [17, 19] and exceeds the sensitivity of CT, especially for small lesions [17]. Contrast-enhanced US affords diagnostic benefit in 13.7% patients with liver mass lesions [19]. The increased sensitivity of contrast-enhanced US in detection of tumours is explained by the vascularisation pattern and the phagocytosis of contrasting microbubbles by Kupffer cells that are present in liver parenchyma but absent in liver tumours. Thus, CRC metastases would be an adequate object for contrast US. The tumours are hypoechoic. The sensitivity and specificity of US and contrast-enhanced US in diagnosing malignant liver tumours is around 58.8% and 50.7% for US versus 68.7–90% and 67–88% for the contrast-enhanced modality. Deep lesions, small metastases and liver steatosis are known limiting factors. Colorectal cancer metastases may occasionally be hyperechogenic and lack hypoechoic structure on contrast-enhanced US embarrassing differential diagnosis with benign lesions, e.g., haemangioma [19].

Hepatic lesions can be missed even by combined radiologic investigation, including US, CT and MRI. The proportion of such lesions can be as high as 30% [19]. Intraoperatively, US can be applied. The sensitivity of intraoperative imaging is again enhanced by contrast US [37].
