Glenn A. Krinsky

Advanced Liver Fibrosis: Diagnosis with 3D Whole-Liver Perfusion MR Imaging—Initial Experience

Institutional review board approval and informed consent were obtained for this HIPAA-compliant study. The purpose of this study was to prospectively evaluate sensitivity and specificity of various estimated perfusion parameters at three-dimensional (3D) perfusion magnetic resonance (MR) imaging of the liver in the diagnosis of advanced liver fibrosis (stage >or= 3), with histologic analysis, liver function tests, or MR imaging as the reference standard. Whole-liver 3D perfusion MR imaging was performed in 27 patients (17 men, 10 women; mean age, 55 years) after dynamic injection of 8-10 mL of gadopentetate dimeglumine. The following estimated perfusion parameters were measured with a dual-input single-compartment model: absolute arterial blood flow (F(a)), absolute portal venous blood flow (F(p)), absolute total liver blood flow (F(t)) (F(t) = F(a) + F(p)), arterial fraction (ART), portal venous fraction (PV), distribution volume (DV), and mean transit time (MTT) of gadopentetate dimeglumine. Patients were assigned to two groups (those with fibrosis stage <or= 2 and those with fibrosis stage >or= 3), and the nonparametric Mann-Whitney test was used to compare F(a), F(p), F(t), ART, PV, DV, and MTT between groups. Receiver operating characteristic curve analysis was used to assess the utility of perfusion estimates as predictors of advanced liver fibrosis. There were significant differences for all perfusion MR imaging-estimated parameters except F(p) and F(t). There was an increase in F(a), ART, DV, and MTT and a decrease in PV in patients with advanced fibrosis compared with those without advanced fibrosis. DV had the best performance, with an area under the receiver operating characteristic curve of 0.824, a sensitivity of 76.9% (95% confidence interval: 46.2%, 94.7%), and a specificity of 78.5% (95% confidence interval: 49.2%, 95.1%) in the prediction of advanced fibrosis.

MR imaging of cirrhotic nodules

Cirrhosis is a progressive, diffuse process of liver fibrosis, characterized by architectural distortion and the development of a spectrum of nodules, ranging from benign regenerative nodules (RNs) to hepatocellular carcinoma (HCC) [1]. The incidence of HCC is rising in the United States and has almost doubled over the past 20 years [2]. This rise is caused in part by the epidemic of hepatitis C virus, which can lead to both cirrhosis and HCC [2]. Like hepatitis B virus, the relative risk of HCC for patients with cirrhosis due to hepatitis C is approximately 100 times the risk for patients with cirrhosis who are not infected [3]. Cirrhosis due to hepatitis C causes 70% of cases of HCC in Japan and 30–50% in the United States [3]. In contrast, patients who have cirrhosis resulting from autoimmune chronic hepatitis, primary biliary cirrhosis, or alcohol abuse but who do not have coexisting hepatitis C infection have only a twoto fivefold increased risk of HCC [3]. HCC is the most common primary cancer of the liver. The overall 5-year survival rate is less than 5% [2]. The high mortality rate is due in part to the late clinical presentation of the disease, when tumor burden is large, performance status is poor, and patients are incurable. Early diagnosis with subsequent transplantation before the development of large or infiltrative tumors offers the most effective treatment for HCC because it can cure both the cancer and the underlying cirrhosis [4]. In one study, patients transplanted with either one lesion measuring 5 cm or less without vascular invasion or three lesions measuring 3 cm or less had a 4-year survival rate of 92% [4]. Therefore, it is critical to detect nodules that contain HCC at an early stage ( #3 cm) and to attempt to differentiate them from RNs and dysplastic nodules (DNs). Recent advances in magnetic resonance (MR) technology, including hardware and pulse sequence implementations, have allowed acquisition times to be reduced to 25 s or less, the time frame of a breath-hold. For T1-weighted imaging, short acquisition times not only reduce respiratory artifacts but also allow dynamic contrast-enhanced imaging during select phases of enhancement, such as the hepatic arterial phase. Alternate imaging techniques can also be used to obtain diagnosticquality hepatic MR examinations in patients who are not able to perform breath-holding by using single-shot T2weighted and magnetization-prepared gradient-echo T1weighted imaging. These sequences are invaluable when imaging cirrhotic patients with encephalopathy and/or massive ascites who may be noncompliant or obtunded. One of the most confusing aspects of the MR imaging literature on cirrhotic nodules has been the terminology. Until recently, most lesions had more than one name, which made comparing radiologic and pathologic studies performed across centers in different geographic locations difficult. The terminology also included such oxymorons as “early advanced” HCC. The need to standardize the nomenclature of hepatocellular nodules was recognized in 1994 by the World Congress of Gastroenterology, where an “international language” was proposed that greatly simplified the interpretation of the radiologic and pathologic literature [5]. The termdysplastic nodulereplaces previously used terms such asdenomatous hyperplasia and macroregenerative nodule(Table 1) [5]. DNs are now considered neoplastic, clonal lesions that represent an intermediate step in the pathway of hepatocarcinogenesis in cirrhotic livers (Fig. 1) [6, 7]. The other problem with the MR imaging literature is the lack of complete pathologic correlation with imaging findings. Virtually all publications have relied on biopsy or surgical resection specimens to evaluate the accuracy of imaging detection and characterization of cirrhotic nodules, with the resulting bias toward positive studies. For a true assessment of the diagnostic sensitivity and specificity of imaging of nodular lesions in a cirrhotic liver, ideally, the entire liver would be available for the pathologist to sample. This could be achieved with whole explant correlation after transplantation; however, to date no such results have been published in the MR literature. Detection and characterization of cirrhotic nodules reCorrespondence to: G. A. Krinsky Abdom Imaging 25:471–482 (2000) DOI: 10.1007/s002610000015 Abdominal Imaging

Comparison between in-phase and opposed-phase T1-weighted breath-hold FLASH sequences for hepatic imaging

PURPOSE Our goal was to compare in-phase (IP) and opposed-phase (OP) sequences for GRE breath-hold hepatic imaging. METHOD Non-contrast-enhanced IP and OP GRE breath-hold images were obtained in 104 consecutive patients referred for abdominal MRI at 1.0 T. For both sequences, the TR, FA, matrix, FOV, slice thickness, interslice gap, and measurements were kept constant. Images were compared quantitatively [liver/spleen and liver/lesion signal difference/noise ratio, (SD/N)] and qualitatively (artifacts, lesion detection and conspicuity, and intrahepatic anatomy). RESULTS There was no statistically significant difference when comparing IP and OP sequences for liver/spleen and liver/lesion SD/N or for the qualitative parameters. In patients with fatty infiltration, the OP sequences yielded substantially lower values for liver/spleen and liver/lesion SD/N (0.9 and -1.2, respectively) than the IP sequences (20 and 17, respectively). Furthermore, in several cases with fatty infiltration, many more lesions were identified using IP images. CONCLUSION The use of IP and OP GRE sequences provides complementary diagnostic information. Focal liver lesions may be obscured in the setting of fatty infiltration if only OP sequences are employed. A complete assessment of the liver with MR should include both IP and OP imaging.

Diagnostic imaging of hepatocellular carcinoma in patients with cirrhosis before liver transplantation

Key Concepts: 1 The lack of whole‐liver explant correlation has led to an overestimation of the sensitivity of imaging tests for the diagnosis of HCC in the radiological literature. 2 Ultrasound is insensitive for the diagnosis of HCC in the cirrhotic liver and should not be used for the detection of focal liver lesions in this setting. 3 Although magnetic resonance (MR) imaging is more sensitive than multidetector 3‐phase computed tomography (CT) for the diagnosis of regenerative and dysplastic nodules it is probably no better than CT for detection of HCC and has a lower false‐positive rate. 4 Approximately 10–30% of nodules measuring <2 cm seen only on the hepatic arterial phase at CT or MR imaging represent small HCC and vigilant surveillance imaging is required as interval growth is the best indicator of malignancy. Liver Transpl 12:S1–S7, 2006.

Isotropic 3D T2-Weighted MR Cholangiopancreatography with Parallel Imaging: Feasibility Study

OBJECTIVE The aim of this study was to compare the quality of images obtained with fast 3D T2-weighted turbo spin-echo (TSE) MR cholangiopancreatography (MRCP) sequences and 1-mm isotropic voxels with the quality of conventional 2D MRCP images. SUBJECTS AND METHODS Thirty consecutively registered patients (14 women, 16 men; average age, 60.2 years; age range, 32-87 years) underwent imaging at 1.5 T with a 6-element body array coil. All imaging was performed with three MRCP techniques: free-breathing 3D T2-weighted TSE (TR/TE, 1,300/680; flip angle, 180 degrees; field of view, 250-300 mm; matrix size, 256 x 256; slice thickness, 1 mm; parallel acquisition technique factor, 2); breath-hold 3D T2-weighted TSE (same parameters as the free-breathing 3D technique); breath-hold coronal and oblique coronal thick-slab 2D TSE without parallel acquisition technique (2,800/1,100; flip angle, 150-180 degrees). Quantitative measures of image signal and contrast were evaluated by analysis of variance and paired Students t tests. A 5-point scale (1, nondiagnostic, to 5, high diagnostic confidence) was used to compare the 3D and 2D data sets for image quality and definition of biliary and pancreatic ductal anatomic features. Friedmans nonparametric and Wilcoxons rank sum tests were performed for statistical analysis of the qualitative assessments. RESULTS Quantitative results showed free-breathing and breath-hold 3D TSE images had significantly higher relative signal intensity and contrast than 2D TSE images (p < 0.0001). The qualitative findings showed that both free-breathing and breath-hold 3D TSE techniques gave better delineation of biliary anatomy (p < 0.0001) than the 2D technique. The overall quality of 3D images was better than that of 2D images, and 3D imaging was better at depicting pancreatic ducts, although the difference did not reach statistical significance. CONCLUSION Three-dimensional volumetric MRCP images are of superior quality and give better delineation of pancreaticobiliary anatomy than conventional 2D images and have the added advantage of multiplanar and postprocessing capabilities.

Gadolinium-enhanced 3D MRA of the aortic arch vessels in the detection of atherosclerotic cerebrovascular occlusive disease

PURPOSE Our goal was to evaluate non-breath-hold Gd-enhanced 3D MR angiography (MRA) for the detection of atherosclerotic occlusive disease of the aortic arch vessels and to compare image quality with two breath-hold techniques. METHOD One hundred sixty consecutive patients with known or clinically suspected atherosclerotic cerebrovascular occlusive disease underwent Gd-enhanced 3D MRA of the aortic arch and great vessels. One hundred twenty-six examinations were performed with the body coil after infusion of 40 ml of Gd-DTPA; 89 of these were performed without breath-holding and 37 were acquired during suspended respiration. Thirty-four examinations were performed in a body phased-array coil with breath-holding, a timing examination, and 20 ml of contrast agent by manual (n = 17) or power (n = 17) injection. Images were evaluated for the presence of blurring and ghosting artifacts and venous enhancement. Of the 27 patients who underwent non-breath-hold MRI and digital subtraction angiography (DSA), two readers blinded to the DSA results retrospectively evaluated the MRA examinations for the presence of occlusive disease of the innominate, carotid, subclavian, and vertebral arteries. DSA correlation was not evaluated for the 71 breath-hold studies. RESULTS Sensitivity and specificity for arch vessel occlusive disease with non-breath-hold MRA were 38 and 94% for Reader A and 38 and 95% for Reader B. Breath-holding significantly reduced blurring and ghosting artifacts (p < 0.001) when compared with non-breath-hold imaging, and use of 20 ml of contrast medium, with a timing examination, resulted in significantly less venous enhancement than seen with 40 ml (p < 0.001). CONCLUSION Non-breath-hold Gd-enhanced 3D MRA is insensitive for detecting arch vessel occlusive disease. Breath-hold imaging, in conjunction with a timing examination and a lower dose of contrast agent, improves image quality, but further studies are needed to assess diagnostic accuracy.

Interrupted aortic arch: diagnosis with gadolinium-enhanced 3D MRA.

PURPOSE Our goal was to describe the use of gadolinium-enhanced 3D MR angiography (MRA) in the diagnosis of interrupted aortic arch (IAA). METHOD A review of our MR data base from a 1 year period yielded three patients (1 day, 8 days, and 16 years old) with IAA. All were referred for evaluation of aortic arch abnormalities, only one of whom had suspected IAA. Patients were imaged at 1.5 T with a 3D spoiled gradient echo pulse sequence (TR/TE 3.8-8/1.3-2.7 ms) following the administration of intravenous gadolinium chelates. Surgical correlation was available in all cases. RESULTS In the patient with clinically suspected IAA, a previously unsuspected aberrant right subclavian artery was identified that was not seen on preoperative echocardiography. In another patient with a history of previous mediastinal surgery, IAA was diagnosed without concomitant cardiac anomalies, suggesting surgical ligation. In the remaining patient, IAA was detected as well as a patent truncus arteriosus. CONCLUSION Gadolinium-enhanced 3D MRA may provide for a rapid diagnosis of IAA that may not be possible with other noninvasive modalities. The rapid acquisition time enables unstable pediatric patients to spend minimal time in the MR suite.

Liver transplant donor candidates: Associations between vascular and biliary anatomic variants

Our objective was to investigate the coexistence of vascular and biliary anatomic variants, the latter of which are known to increase the risk of biliary complications in living liver donor transplantation. A total of 108 consecutive liver donor candidates were examined by magnetic resonance (MR) imaging that included 2 MR cholangiography methods, T2‐weighted MR cholangiography and mangofodipir‐enhanced T1‐weighted three‐dimensional (3D) MR cholangiography, as well as gadoliniumenhanced MR angiography and venography of the liver. Images were interpreted by at least 2 investigators in consensus for definition of hepatic arterial, portal venous, and biliary anatomy. A subset of 51 subjects underwent laparotomy for right hepatectomy. Of the 108 subjects examined, 50 (46%) demonstrated normal hepatic artery, portal vein, and biliary anatomy. Variants of the hepatic artery were found in 27 of 108 (25%) subjects, of the portal vein in 12 of 108 (11%) subjects, and of the bile ducts in 30 of 108 (28%) subjects. Of the 27 subjects with hepatic arterial variants, 8 (30%) also had variant biliary anatomy. The association between hepatic arterial variants and biliary variants was not statistically significant (P > .5). However, of the 12 subjects with portal vein variants, 7 (58%) had biliary variants, and in 6 of 7 cases, the right posterior hepatic duct was anomalous. By chi‐square analysis, the association between portal venous and biliary variants was significant (P = .012). In conclusion, over half of subjects with portal vein variants were found to have anomalous biliary anatomy, which always involved the hepatic ducts of the right lobe. The association between portal venous and biliary variants is statistically significant, while there is no significant association between hepatic arterial and biliary variants. (Liver Transpl 2004;10:1049–1054.)

Siderotic nodules at MR imaging: regenerative or dysplastic?

Objective To determine if iron containing “siderotic” nodules detected at magnetic resonance (MR) imaging are regenerative (RN) or dysplastic (DN) and to attempt to identify features that may distinguish them. Material and Methods MR imaging (1.5 T) was performed on 77 cirrhotic patients who underwent orthotopic liver transplantation within 0–117 days (mean 30 days) of MR imaging. Two readers retrospectively evaluated breath-hold gradient-echo pulse sequences (echo time ≥9.0 ms, flip angle ≤45°) for the presence of hypointense nodules, which were classified as micronodular (≤3 mm), macronodular (>3 mm), or mixed. Nodule distribution was classified as focal (<5), scattered (5–20), or diffuse (>20) per slice. Thin section pathologic correlation was available in all cases, and Prussian blue iron stains were performed. Results Of 35 patients with pathologically proven siderotic nodules, 10 (29%) had at least 2 siderotic DN. MR detected siderotic nodules in 10 of 10 (100%) patients with siderotic DN and RN, and in 18 of 25 patients (72%) with siderotic RN only. Conclusion Siderotic RN cannot be reliably distinguished from siderotic DN with MR imaging, and therefore the widely used term “siderotic regenerative nodule” should be avoided and replaced by “siderotic nodule.”

Imaging of Dysplastic Nodules and Small Hepatocellular Carcinomas: Experience with Explanted Livers

Differentiation of benign from malignant nodules in the end-stage cirrhotic liver can be challenging, due to the presence of fibrosis, necrosis and altered blood supply. Whole liver explant pathologic correlation provides a unique opportunity to evaluate the sensitivity and specificity of current imaging modalities for the diagnosis of HCC and dysplastic nodules in the cirrhotic liver. This chapter will explore and critique the imaging literature with an emphasis on studies performed with timely explanted liver correlation.