MR elastography of liver disease : State of the art

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MR ELASTOGRAPHY OF LIVER DISEASE
tissue, which through a process known as mechanotransduction promotes the activation of stellate cells and the sub-VHTXHQW GHYHORSPHQW RI ÀEURVLV 32,49,50 which in turn further increases liver stiffness.The persistent elevation in stiffness of the mechanical environment is then believed to accelerate fibrosis progression to more advanced stages.To date, the data have shown that, in chronic liver diseases with different causes, MRE has high diagnostic accuracy (AUROC = 92%-100%) for detect-LQJ DQG VWDJLQJ KHSDWLF ÀEURVLV DV VHHQ in Table 1.Within our institution, we use a liver stiffness value of 2.93 kPa (kilopascals) as the threshold for detect-LQJ QRQÀEURWLF OLYHU WLVVXH ZKHUH DQ DEnormal liver stiffness is > 2.93 kPa.The diagnostic accuracy, sensitivity, speci-ÀFLW\ SRVLWLYH DQG QHJDWLYHSUHGLFWLYH values of this cut-off value are no lower than 97%. 3 Several groups have shown that hepatic MRE has excellent reproducibility and inter-operator consistency.The coefficient of variation between hepatic stiffness measurements conducted on different days among the same individuals ranged between 7% and 12%, [54][55][56] while the intra-class cor-UHODWLRQ FRHIÀFLHQW IRU KHSDWLF VWLIIQHVV measured by 2 different operators was 97% to 99% (100% means exactly the same reading). 57,58

Chronic hepatitis C virus
Approximately 150,000 new cases of chronic liver disease were diagnosed in the U.S. adult population each year from 1999 through 2001, with twothirds of individuals affected by hepatitis C. 60 Determining the presence and GHJUHH RI OLYHU ÀEURVLV LV LPSRUWDQW IRU planning treatment in patients with chronic hepatitis C viral infection. 5,6erum tests are routinely performed to assess liver damage due to HCV, but  ) in HCV patients. 16 combined data review from 4 studies showed that ultrasound-based transient elastography (UTE) had an AUROC of 0.83 to detect significant fibrosis (F2-F4) in HCV-related patients, but was less accurate for earlier stages of ÀEURVLV 62 In one MRE study of subjects with HCV (METAVIR F2-F4) and healthy volunteers, the mean liver stiffness was significantly greater in patients with HCV than in healthy volunteers, and the correlation between liver stiffness and ÀEURVLV VWDJH FRQÀUPHG E\ OLYHU ELRSV\ was 0.89.54 MRE scan examples of HCV patients with biopsy-proven fibrosis stages 0 and 3 as shown in Figure 2.

Nonalcoholic steatohepatitis
][65][66][67] The spectrum of NAFLD ranges from simple steatosis to necro-inflammation DQG ÀEURVLV 6LPSOH VWHDWRVLV LV WKRXJKW to have a benign long-term prognosis.0][71][72][73] It is anticipated that NASH-induced cirrhosis will also become the most common indication for liver transplantation in the future. 65herefore, early liver biopsy has been suggested in all NAFLD patients to stratify the disease so that earlier interventions and more aggressive treatment can be applied to reduce overall mortality. 73ue to the invasive nature of liver biopsies, however, noninvasive methods have been evaluated for the diagnosis and serial assessment of NASH; these include novel serological and imaging tests.5][76][77] UTE had high accuracy (AUROC = 79-0.98%)][25] However, UTE scans in patients with NAFLD showed unreliable measurements in 14% of patients due to obesity and decreased diagnostic accuracy. 28,78n addition, UTE was not sensitive in identifying steatohepatitis without fibrosis in patients with NAFLD. 25In

Obese patients and bariatric surgery
Bariatric surgery has been shown to be a very effective treatment for medically-complicated obesity.In turn, patients undergoing bariatric surgery who are also affected by NAFLD and NASH have experienced improvements in liver

MR ELASTOGRAPHY OF LIVER DISEASE
measure liver stiffness more accurately because it captures 2-dimensional cross-sectional images; UTE may have sampling errors due to its 1-dimensional nature.7][28] UTE scans in 14% of patients with NAFLD showed unreliable measurements and decreased diagnostic accuracy due to obesity. 28,78ecently, extra-large probes have been developed to address the technical limitations of UTE for imaging obese patients, but these still require validation.MRE is not limited by such factors, yet the approach also has its own technical limitations, including claustrophobia and other typical contraindications for MRI, such as magnetically susceptible implants.Low liver signal related to increased hepatic iron from hemochromatosis or advanced chronic liver disease is also problematic. 3,57However, continued developments in MRE technology indicate that patients with low liver signal can potentially undergo liver stiffness assessment using short-echo time and spin-echo MRE sequences. 82n characterizing liver tumors, MRE is the only technique capable of noninvasively measuring tumor stiffness because it reports any masses along with cross-sectional stiffness information about the liver.Tumor assessment is currently not possible with UTE be-FDXVH LWV À[HG DFRXVWLF ZLQGRZ FDQQRW specifically target tumors, which can occur at any location in the liver.

Conclusions
Based on growing evidence in the scientific literature, quantitative elasticity imaging is being increasingly recognized by the hepatology community as a useful tool for noninvasively assessing and diagnosing chronic liver disease.MR elastography has moved from the laboratory to the clinic and is increasingly available as an FDA-approved option for MRI systems.Over the past 4 years, > 1700 patients have undergone hepatic MRE exams as a part of clinical practice at the authors' institution.Similar experience is accumulating at many other centers around the world.For many patients, MRE is emerging as an effective, more comfortable, and less expensive diagnostic alternative to biopsy for assessing KHSDWLF ÀEURVLV
MR elastography is a technology for FKDUDFWHUL]LQJ WKH ELRPHFKDQLFDO SURS-erties (eg, stiffness) of tissues in vivo.It uses MR phase-contrast techniques to acquire images of wave propagation LQ WLVVXH ZKLFK DUH SURGXFHG E\ DQ H[-WHUQDO VRXUFH RI PHFKDQLFDO YLEUDWLRQ The images of wave propagation are LQWHUSUHWHG DQG SURFHVVHG E\ LQYHUVLRQ algorithms, which results in a tissue stiffness map called an elastogram from which the tissue stiffness is measured. 33MRE exams of normal livers have vis-LEO\ VKRUWHU ZDYHOHQJWKV LQ WKH ZDYH images and lower liver stiffness values in the elastograms, which means normal OLYHUV DUH VRIW )LEURWLF DQG FLUUKRWLF OLYers have longer wavelengths and higher liver stiffness values, which means diseased livers are hard. 3,21,26,27,29-31This is consistent with the experience of clini-FLDQV ZKRVH SDOSDWLRQV ZLWK WKH ÀQJHUV DUH XVHG WR VXEMHFWLYHO\ H[DPLQH DQG IHHO the stiffness of the liver.Details of the MRE technique and scan parameters can EH IRXQG LQ WKH OLWHUDWXUH 3,30,31 A typical MRE procedure is summarized here.As shown in Figure 1, a patient lies RQ WKH VFDQQHU WDEOH LQ WKH VXSLQH SRVLtion and a drum-like acoustic passive GULYHU LV SRVLWLRQHG DJDLQVW WKH ERG\ ZDOO FORVH WR WKH OLYHU DQG VHFXUHG E\ DQ HODVWLF EHOW QRW VKRZQ LQ WKH ÀJXUH IRU D clear view) wrapped around the patient's ERG\ 7KH SDVVLYH GULYHU LV FRQQHFWHG to an acoustic speaker system located RXWVLGH WKH VFDQQHU URRP YLD D IOH[LEOH SRO\YLQ\OFKORULGH 39& WXEH ZKLFK provides a programmed external me-FKDQLFDO YLEUDWLRQ 7KH DFRXVWLF VSHDNHU SURGXFHV YLEUDWLRQV DW DXGLEOH IUHTXHQcies (typically 40Hz-80Hz), which are transmitted to the passive driver through WKH WXEH $ JUDGLHQWHFKR 05( LPDJing sequence is used to acquire images of ZDYH SURSDJDWLRQ ZLWKLQ WKH OLYHU 6XEsequently, elastograms are calculated using a direct inversion of the differential HTXDWLRQV GHVFULELQJ WKH ZDYH SURSDJDtion.
primary sclerosing cholangitis, unknown Note -Biopsy criteria a: METAVIR b: Brunt for NASH and alcoholic hepatitis and METAVIR for others c: generalized method UHDO SDUW RI OLYHU VWLIIQHVV 6HQV 6HQVLWLYLW\ 6SHF 6SHFLÀFLW\ 139 1HJDWLYH 3UHGLFWLYH 9DOXH 339 3RVLWLYH 3UHGLFWLYH 9DOXH $852& $UHD 8QGHU 5HFHLYHU 2SHUDWLQJ &KDUDFWHULVWLF &XUYH 1$ QRW DYDLODEOH MR ELASTOGRAPHY OF LIVER DISEASE they have low specificity for disease severity.Therefore, liver biopsy is the only reference method to confirm and stage fibrosis in HCV patients.Utilizing multiple parameters from serum tests and clinical risk factors in a model could improve diagnostic accuracy.One study using a model that included 4 readily available characteristics to predict the presence of cirrhosis in HCV patients (platelet count, presence of spider nevi, aspartate transaminase (AST), and gender) resulted in an AUROC of 0.94 for the training set and 0.93 for the validation patient group. 61However, a model using combined data from serum tests and clinical information needs further validation because of the different patient demographics between the training patient group and the tested patients.For example, the AUROC value of such a model dropped from 0.84 in a training patient group to 0.77 in a validation pa-WLHQW JURXS IRU GHWHFWLQJ VLJQLÀFDQW Àbrosis (stages F2-F4 FIGURE 2. MRI/MRE exams of 2 patients with chronic HCV infection.Upper row: A 47-yearold man: (A) T2-weighted image revealed no abnormality; (B) elastogram demonstrated a mean hepatic stiffness of 2.1 kPa, which is well within the normal range of < 2.9 kPa.Liver biopsy demonstrated no fibrosis.Bottom row: A 68-year-old man: (C) T2-weighted image demonstrated no abnormality, with smooth liver margins; (D) elastogram demonstrated elevated hepatic stiffness, averaging 4.5 kPa.Liver biopsy demonstrated Stage 3 fibrosis.

FIGURE 3 .FIGURE 4 .
FIGURE 3. MRI/MRE exams of three NFALD patients.Figures A and B: A 62-year-old female patient with obesity (BMI 41) and clinical evidence of fatty liver disease: (A) T2-weighted images demonstrated no abnormality; (B) elastogram demonstrated normal mean hepatic stiffness of 2.1 kPa.Liver biopsy demonstrated no necroinflammation or fibrosis.Figures C and D: A 44-year-old male patient with obesity (BMI 39) and clinical evidence of fatty liver disease: (C) T2-weighted image demonstrated a normal hepatic contour; (D) elastogram demonstrated increased hepatic stiffness, averaging 4.48 kPa.Liver biopsy demonstrated grade 1 necroinflammation without fibrosis.Figures E and F: A 60-year-old female patient with obesity (BMI 31) and clinical evidence of fatty liver disease: (E) T2-weighted images revealed hepatic nodularity; (F) elastogram demonstrated markedly elevated hepatic stiffness, averaging 10.2 kPa.Hepatic biopsy demonstrated grade 2 necroinflammation and stage 4 fibrosis.

FIGURE 5 .
FIGURE 5. MRI/MRE exams of 2 patients with rheumatoid arthritis.Upper row: A 70-yearold woman treated with methotrexate for 24 years: (A) conventional T1-weighted MR imaging of the liver revealed no abnormality; (B) elastography demonstrated normal hepatic stiffness of 2.1 kPa.This patient continued to receive methotrexate therapy.Bottom row: A 66-yearold man treated with methotrexate for 4 years: (C) conventional T1-weighted MR imaging revealed no abnormality; (D) elastography demonstrated mildly elevated hepatic stiffness of 3.1 kPa.Liver biopsy demonstrated mild periportal fibrosis.