Dynamic gadolinium-enhanced echo-planar MR imaging of the liver: Effect of pulse sequence and dose on enhancement

To develop guidelines for clinical magnetic resonance imaging of the liver, the authors undertook an animal study to investigate the effect of dose and pulse sequence on liver signal intensity in gadopentetate dimeglumine—enhanced echo-planar imaging. Serial imaging of the liver was performed in anesthetized rats after intravenous administration of five different doses (0.01, 0.05, 0.1, 0.2, and 0.5 mmol/kg) of contrast agent, with six different pulse sequences. The results show that gadopentetate dimeglumine—enhanced echo-planar images obtained during the perfusion phase can yield either positive (due to increased T1 relaxation rates) or negative (due to susceptibility-induced increased T2 relaxation rates) liver enhancement depending on choice of pulse sequence and dose. At the current clinically recommended dose of 0.1 mmol/kg, maximal liver signal enhancement was seen with a T1-weighted inversion-recovery sequence, while maximal liver signal diminution was seen with a T2*-weighted gradient-echo sequence. The authors conclude that gadopentetate dimeglumine—enhanced echo-planar imaging can provide T1, T2, and T2* contrast that may be exploited for both lesion detection and lesion characterization.     

Contrast-enhanced MR imaging of liver and spleen: First experience in humans with a new superparamagnetic iron oxide

The aim of this prospective study was to obtain the first human safety and magnetic resonance (MR) imaging results with a new formulation of superparamagnetic iron oxide (SPIO) (SHU 555 A). The SPIO was tested at four iron doses, from 5 to 40 μmol/kg. Laboratory tests and clinical measurements were done in 32 healthy volunteers for up to 3 weeks after administration. MR imaging at 1.5 T was performed before and 8 hours to 14 days after fast intravenous injection (500 μmol Fe/min) of the SPIO (six subjects per dose). Results of this phase I study demonstrate that SHU 555 A at a concentration of 0.5 mol Fe/L was well tolerated. A dose-dependent minor increase in activated partial thromboplastin time, which remained within the normal range, was seen. All doses of SPIO caused a signal loss in both liver and spleen (P <.05) with a spin-echo sequence (TR = 2,300 msec, TE = 45 msec). The signal losses in the liver 8 hours after contrast agent injection were 58%, 79%, 82%, and 87% for the 5, 10, 20, and 40 μmol Fe/kg doses, respectively. The corresponding signal losses in the spleen were 23%, 45%, 65%, and 78%, respectively. The doses that reduced signal intensity by half were 3.1 μmol Fe/kg for the liver and 12.8 μmol Fe/kg for the spleen. The results suggest that the new SPIO formulation is a safe and efficient MR contrast agent.     

Prolonged positive contrast enhancement with Gd-EOB-DTPA in experimental liver tumors: Potential value in tissue characterization

To evaluate the potential of the hepatobiliary magnetic resonance (MR) imaging contrast agent gadolinium EOB-DTPA (ethoxybenzyl diethylenetria-minepentaacetic acid) for the characterization of hepatic tumors, 79 primary and six implanted hepatomas in 38 rats were studied. MR imaging findings after administration of Gd-DTPA (0.3 mmol/kg) and Gd-EOB-DTPA (30 μmol/kg) were correlated with microangiographic and histologic findings. Gd-EOB-DTPA produced a strong liver enhancement, which caused prompt negative contrast enhancement (CE) in all implanted hepatomas and in 77 of 79 primary hepatomas. A positive CE that lasted up to 2 hours was found in two of 79 primary hepatomas, both of which were highly differentiated (grade I) hepatocellular carcinomas (HCCs). The rest were moderately differentiated to undifferentiated HCCs (grades II-IV). Rim enhancement, which corresponded histologically to peritumoral malignant infiltration sequestering normal hepatocytes, was seen around all implanted and some primary hepatomas. Positive tumor CE after administration of Gd-EOB-DTPA in this study is much less frequent but much more specific in comparison with the results of previous studies with manganese-DPDP (N, N′-dipyridoxylethylenediamine-N,N′-diacetate 5,5′-bis[phosphate]). These findings may help further discriminate hepatic tumors.     

Superparamagnetic iron oxide: Detection of focal liver lesions at high-field-strength MR imaging

AMI-25 was evaluated at 1.5 T as a superparamagnetic iron oxide contrast agent for the liver. Sixteen patients with up to five suspected focal liver lesions were examined with T1-, proton-density—, and T2-weighted spin-echo sequences before and after intravenous administration of AMI-25 (15 μmol/kg iron). The contrast-to-noise ratio (C/N) increased from 1.8 to 3.5 on 600/15 (TR msec/TE msec) images and from 1.7 to 7.9 on 2,500/15 images after AMI-25 administration (P <.01). C/N did not change significantly on 2,500/90 images. Two blinded readers counted the number of lesions visible on unenhanced and contrast-enhanced images, with the 32 sets of images of the 16 patients presented in random order. Both readers identified more lesions on AMI-25–enhanced images, but the difference was not statistically significant (P >.05). Two patients reported minor side effects (flushing, sensation of heat, lower back pain). On the basis of the results obtained in a limited number of patients, the authors conclude that at 1.5 T, AMI-25 does not significantly improve the detection of focal liver lesions on conventional spin-echo images.     

Evaluation of the hepatocyte-specific contrast agent gadobenate dimeglumine for MR imaging of acute hepatitis in a rat model

This work was conducted to test the hypothesis that contrast-enhanced MRI with hepatocyte-specific contrast agents facilitates quantitation and mapping of diffuse liver diseases such as hepatitis and cirrhosis. Gadobenate dimeglumine (Gd-BOPTA/Dimeg, Bracco SpA, Milano, Italy) is a new paramagnetic hepatocytespecific contrast agent currently undergoing clinical trials. We have assessed the usefulness of gadobenate dimeglumine for the diagnosis of diffuse liver diseases in a rat model of chemically induced hepatitis. The study was based on the measurements of in vivo liver relaxation times as well as on the acquisition of standard SE images. Acute hepatitis considerably reduced the degree of T1 shortening of liver parenchyma caused by intravenous injection of .25 mmol/kg of gadobenate dimeglumine. Analogously, the enhancement of the MRI signal intensity of the liver of rats with hepatitis observed in T1-weighted spin-echo (SE) images was inferior, in terms of both strength and duration, to that recorded in control rats at doses of .25 mmol/kg and .075 mmol/kg of gadobenate dimeglumine. Our results show that gadobenate dimeglumine enhanced MR imaging has the potential for visualization of hepatitis and for assessment of liver function. Our conclusions differ from those previously published on this subject by other authors. The reasons that led to differing conclusions are discussed.     

Enhancement effects of a hepatocyte receptor—specific MR contrast agent in an animal model

The enhancement characteristics of the liver and spleen produced by a hepatocyte-specific magnetic resonance imaging agent, an arabinogalactan-coated ultrasmall superparamagnetic iron oxide derivative, BMS 180550, were evaluated. Both heavily T1- and T2-weighted sequences were used. Imaging was performed in the farm pig model, as a function of contrast agent concentration (5, 10, and 20 μmol of iron per kilogram) and delay (immediate, 0.5, 2.5, 5.0, 7.5, and 9.0 hours) after bolus injection of BMS 180550. BMS 180550 provided excellent contrast enhancement characteristics by producing marked positive enhancement with T1-weighted sequences and marked negative enhancement with T2-weighted sequences. The T1-weighted enhancement immediately after contrast agent injection was of greater magnitude in the spleen (329% ± 83) than in the liver (66% ± 16). Postcontrast negative enhancement with T2-weighted sequences was largely hepatocyte specific at 5 and 10 μmol/kg but was also seen within the spleen at 20 μmol/kg. The authors discuss the possible mechanisms that produce these changes and conclude that 10 μmol/kg BMS 180550 is near the optimum dose for maximizing the enhancement properties of this agent with all sequences in the farm pig.     

Nodular sarcoidosis of the liver and spleen: Appearance on MR images

Small nodular lesions in the liver and spleen have been reported as an infrequent manifestation of sarcoidosis. Five patients with this appearance on either dynamic contrast material—enhanced computed tomographic (CT) or ultrasound scans underwent magnetic resonance (MR) imaging with and without dynamic gadolinium enhancement. The lesions were relatively uniform in size, ranging from 0.5 to 1.5 cm. On CT scans, they were hypoattenuating relative to surrounding parenchyma. On MR images, the lesions were hypointense relative to background parenchyma with all sequences. No substantial enhancement was observed in the lesions, although lesion conspicuity decreased over time on serial postcontrast images. Lesion conspicuity was greatest on either T2-weighted fat-suppressed (T2FS) images or early-phase dynamic contrast-enhanced images. Abdominal adenopathy was seen in three of the five patients and was hyperintense relative to liver on T2FS images in two and intermediate in intensity in one patient.     

Malignant lesions of the liver identified on T1- but not T2-weighted MR images at 1.5 T

The authors reviewed their 21/2-year experience with a magnetic resonance (MR) imaging protocol for a 1.5-T MR imager that included T2-weighted fat-suppressed spin-echo, T1-weighted breath-hold gradient-echo, and serial dynamic gadolinium-enhanced T1-weighted gradient-echo imaging to identify histologic types of malignant liver lesions more apparent on T1- than on T2-weighted images. MR images of 212 consecutive patients with malignant liver lesions were reviewed. T2-weighted, T1-weighted, and dynamic contrast-enhanced T1-weighted images were examined separately in a blinded fashion. Seven patients demonstrated liver lesions (lymphoma [two patients] and carcinoid, hepatocellular carcinoma, colon adenocarcinoma, transitional cell carcinoma, and melanoma [one patient each]) on T1-weighted images that were inconspicuous on T2-weighted images. In all cases, the lesions were most conspicuous on T1-weighted images obtained immediately after administration of contrast agent. Histologic confirmation was present for all seven patients. The consistent feature among these lesions was that they were hypovascular, due either to a fibrous stroma or to dense monoclonal cellularity. These results suggest that in some patients with hypovascular primary neoplasms, the lesions may be identified only on T1-weighted images, and that immediate postcontrast T1-weighted images are of particular value in demonstrating lesions.     

Enhanced tumor detection in the presence of fatty liver disease: Cell-specific contrast agents

It is assumed that hepatobiliary, cell-specific contrast agents will be adversely affected by the presence of diffuse liver disease. The diagnostic efficacy for tumor detection in the presence of fatty liver disease was experimentally studied at contrast-enhanced magnetic resonance (MR) imaging with manganese-DPDP (N,N′-dipyridoxylethylenediamine-N,N′-diacetate 5,5′-bis[phosphate]) and gadobenate dimeglumine (Gd-BOPTA/dimeg) and compared with conventional and chemical shift imaging. Carcinosarcoma was implanted into the liver of rats, and fatty liver was induced with L-ethionine. Without contrast agents, the tumor-fatty liver contrast-to-noise ratio (C/N) was increased on T1-weighted and decreased on T2-weighted MR images relative to tumor-bearing control rats without fatty liver. Chemical shift imaging (phase-contrast method) increased the tumor—fatty liver C/N from 2.3 ± 1.0 to 6.1 ± 1.7 (P <.001). Mn-DPDP and Gd-BOPTA/dimeg increased the tumor—fatty liver C/N from -5.4 ± 1.6 to -11.0 ± 1.9 and ?9.8 ± 3.4, respectively (P <.001). The hepatobiliary, cell-specific contrast agents were equally effective in both fatty and nonfatty liver and outperformed both chemical shift and conventional MR imaging in detecting liver tumors.     

High-dose gadoteridol in MR imaging of intracranial neoplasms.

Twelve patients with a high suspicion of brain metastases by previous clinical or radiologic examinations were studied in a phase III investigation with magnetic resonance (MR) imaging at 1.5 T after a bolus intravenous injection of 0.1 mmol/kg gadoteridol followed at 30 minutes by a second bolus injection of 0.2 mmol/kg gadoteridol. All lesions were best demonstrated (showed greatest enhancement) at the 0.3-mmol/kg (cumulative) dose, with image analysis confirming signal intensity enhancement in the majority of cases after the second gadoteridol injection. More lesions were detected with the 0.3-mmol/kg dose than with the 0.1-mmol/kg dose, and more lesions were detected with the 0.1-mmol/kg dose than on precontrast images. In this limited clinical trial, high-dose gadoteridol injection (0.3-mmol/kg cumulative dose) provided improved lesion detection on MR images specifically in intracranial metastatic disease.     

Spin-echo and dynamic gadoliniumenhanced flash MR imaging of hepatocellular carcinoma: Correlation with histopathologic findings

Evaluation of histologic subtype and degree of differentiation in hepatocellular carcinoma (HCC) is essential because it affects patient prognosis and treatment planning. To evaluate the histologic subtype of HCC with magnetic resonance (MR) imaging, conventional spin-echo and dynamic studies were correlated with histopathologic and angiographic findings in 72 HCCs. Dynamic MR imaging was performed with the fast low-angle shot (FLASH) technique after administration of gadopentetate dimeglumine. There was considerable overlap in signal intensity between various tumor grades on both T1- and T2-weighted images. On dynamic MR images, the peak contrast enhancement ratio correlated with tumor grade (well-differentiated, 29.5 ± 24.7; moderately differentiated, 63.5 ± 24.1; poorly differentiated, 86.9 ± 26.4) or degree of dilatation of the sinusoidlike vascular space between tumor cells. The maximum contrast-to-noise ratio in tumor (relative to surrounding liver) was achieved within 60 seconds in 45 HCCs (mostly of the trabecular or pseudoglandular type). Enhancement was slight or minimal in 17 tumors (mostly small, well-differentiated tumors). In 10 tumors, the degree of enhancement increased with time, with maximum enhancement in the delayed phase (most frequently in scirrhous HCC). These dynamic patterns correlated with angiographic findings. These data indicate that the degree and pattern of enhancement on dynamic MR images reflect tumor differentiation and architecture of HCC.     

MR imaging assessment of experimental hepatic dysfunction with mn-DPDP

Manganese (II) N, N'-dipyridoxylethylenediamine-N, N'-diacetate 5,5′-bis(phosphate) (DPDP) is a paramagnetic magnetic resonance (MR) contrast agent that enhances the liver and is predominantly excreted through the biliary tree. The authors evaluated its utility in diffuse liver disease by assessing liver and gallbladder enhancement in 24 rabbits. Total (n = 6) or segmental (n = 6) biliary occlusion or galactosamine-induced hepatitis (n = 6) was induced 3 days before imaging. Six rabbits served as normal controls. T1- and T2-weighted axial MR images were acquired at baseline, followed by T1-weighted images every 10 minutes for 1 hour after the intravenous administration of 20 μmol/kg Mn-DPDP. Except for the segmental occlusion group, the baseline study did not allow distinction between normal and abnormal livers. The temporal hepatic enhancement pattern was statistically different for each group. The normal, segmental occlusion, and hepatitis groups showed patterns similar to one another but markedly higher signal intensity than the total-occlusion group throughout the observation period. In contrast, the gallbladder showed a greater difference in both degree of enhancement and time to peak enhancement among the four groups. Mn-DPDP produces a temporal hepatic enhancement pattern that allows recognition of markedly impaired livers, and gallbladder enhancement patterns that allow distinction of more subtly impaired livers.     

Contrast-enhanced MR imaging of the liver: Comparison between Gd-BOPTA and mangafodipir

The purpose of the study was to evaluate the MR contrast agents gadolinium benzyloxypropionictetro-acetate (Gd-BOPTA) and Mangafodipir for liver enhancement and the lesion-liver contrast on T1W spin-echo (SE) and gradient-recalled-echo (GRE) images. Fifty-one patients (three groups of 17 patients each) with known or suspected liver lesions were evaluated with T1W SE (300/12) and GRE (77-80/2.3-2.5/80°) images before and after intravenous (IV) Gd-BOPTA (0.1 or 0.05 mmol/kg) or Mangafodipir (5 μmol/kg) in phase II to III clinical trials. Quantitative analysis by calculating liver signal-to-noise ratio (SNR), lesion-liver contrast-to-noise ratio (CNR), and spleen-liver CNR was performed. Liver SNR and spleen-liver CNR were always significantly increased postcontrast. SNR was highest after application of 0.1 mmol/kg Gd-BOPTA (51.3 ± 3.6, P < .05). CNR was highest after Mangafodipir (?22.6 ± 2.7), but this was not significantly different from others (P = .07). Overall, GRE images were superior to SE images for SNR and CNR. Mangafodipir and Gd-BOPTA (0.1 mmol/kg) provide equal liver enhancement and lesion conspicuity postcontrast. By all criteria, contrast-enhanced T1-weighted GRE were comparable to SE images.     

MR evaluation of CNS tumors: dose comparison study with gadopentetate dimeglumine and gadoteridol

In phase II and III trials of gadoteridol (Gd-HP-D03A), a new nonionic, low-osmolar contrast agent, 40 patients with intracranial neoplasms underwent magnetic resonance (MR) imaging with experimental doses of 0.05-0.3 mmol/kg. Fifteen patients also underwent contrast studies with the standard dose (0.1 mmol/kg) of gadopentetate dimeglumine. Both gadopentetate dimeglumine and gadoteridol appear to have a similar effect when given in equal doses (0.1 mmol/kg, n = 5). Lesion enhancement and delineation were better at higher experimental doses (0.2 or 0.3 mmol/kg, n = 7) and worse at a lower experimental dose (0.05 mmol/kg, n = 3). Quantitative analysis of 10 lesions examined with identical imaging protocols revealed a directly proportional relationship (r = .975) between lesion contrast ratio and dose over a range of 0.05-0.3 mmol/kg. Phantom experiments support the clinical results. Improved enhancement, detection, and delineation of central nervous system (CNS) neoplasms resulting from increased injected doses of gadoteridol have the potential to be clinically significant and may justify the possibly higher cost of increased contrast material dosage. Lower doses may not be adequate for the evaluation of most CNS tumors.     

MR portography: Preliminary comparison with CT portography and conventional MR imaging

Magnetic resonance (MR) imaging with arterial portography (MRAP) was compared with computed tomography with arterial portography (CTAP) and conventional MR imaging for preoperative evaluation of hepatic masses in eight patients (nine studies). Twenty contiguous, 10-mm-thick-section CTAP images were obtained. MR imaging included T1- and T2-weighted spin-echo and fast multiplanar SPGR (spoiled gradient-recalled acquisition in the steady state) techniques. For MRAP, 0.1 mmol/kg gadopentetate dimeglumine was injected into the superior mesenteric artery. Portographic-phase, 8-mm-thick-section, axial SPGR images were first obtained, followed by “systemic phase” SPGR images. Lesions were seen best on the portographic-phase MRAP images and were less conspicuous on the systemic-phase MRAP, CTAP and conventional MR images. Of 19 visualized lesions, 18 were seen with MRAP; however; five subcentimeter lesions seen with MRAP were not seen with conventional MR imaging or CTAP. Systemic recirculation of iodinated contrast material from the bolus and from previous angiography is a potential limitation of CTAP. For both CTAP and MRAP, optimal results are expected if all images are obtained during a single breath hold, within seconds of the onset of contrast agent administration.     

Sclerosed liver hemangioma mimicking malignant tumor at MR imaging: Pathologic correlation

This case report illustrates atypical magnetic resonance (MR) imaging findings in a liver hemangioma mimicking a malignant lesion—lower signal intensity than cerebrospinal fluid on T2-weighted spin-echo images and lack of early enhancement on dynamic contrast material—enhanced gradient-echo images. Pathologic analysis demonstrated nearly total replacement of the vascular cavities by dense fibrous tissue. In this rare, sclerosed form, this lesion could not be defined as a hemangioma with MR imaging.     

Gadobenate dimeglumine-enhanced liver MR imaging: value of dynamic and delayed imaging for the characterization and detection of focal liver lesions

The aim of this study was to determine the value of delayed-phase imaging (DPI) of gadobenate dimeglumine (Gd-BOPTA)-enhanced MR imaging for the evaluation of focal hepatic tumors compared with precontrast imaging and early dynamic phase imaging. The MR images were obtained in 48 patients with 98 focal hepatic tumors. Three-dimensional gradient-echo (GRE) imaging obtained before and 30, 60, and 1 h after administration of 0.1 mmol/kg of gadobenate dimeglumine. Each image set was analyzed qualitatively (lesion detection, conspicuity, delineation, and enhancement pattern on DPI) and quantitatively [signal-to-noise ratio (SNR), tumor–liver contrast-to-noise ratio (CNR)]. Improved lesion-to-liver contrast during the dynamic phase imaging was observed compared with precontrast images. The DPI showed a homogeneous enhancement of liver parenchyma and distinctive enhancement features of focal liver lesions: metastases (85%) showed a target shaped enhancement, and hepatocellular carcinomas (HCCs) showed an inhomogeneous (58%) or homogeneous enhancement (21%). The DPI showed better performance for the detection of metastases than other images by increasing lesion delineation (p<0.05). The absolute CNR of metastasis measured from periphery of the tumors on DPI was greater than precontrast and arterial phase imaging (p<0.05). The Gd-BOPTA during both dynamic and delayed phases provides valuable information for the characterization of focal liver lesions, and furthermore, Gd-BOPTA-enhanced DPI contributed to the improved detection of liver metastasis compared to precontrast and early dynamic imaging.     

Improving postoperative MR imaging of pituitary macroadenomas: comparison of full and reduced dose of gadopentetate dimeglumine

The aim of this study was to evaluate the efficacy of contrast-medium (CM)-enhanced MR imaging of operated pituitary macroadenomas with reduced dose of gadopentetate dimeglumine. In a prospective study 18 patients were examined with coronal T1-weighted MR imaging prior to and following intravenous CM injections. Two sets of contrast-enhanced coronal images were obtained in each patient; the first set after 50 % of the recommended dose of 0.1 mmol/kg body weight (b. w.) had been administered, and the second set immediately after additional CM had been given to make up a total dose of 0.1 mmol/kg b. w. The images were evaluated by three neuroradiologists. The SIPAP classification system was used to evaluate tumour extension, whereas tumour margin conspicuity was scored using an arbitrary scale of 1–5 (1 = indistinct, 5 = well defined). Signal intensity measurements obtained from the most enhancing part of the adenomas demonstrated increased enhancement with increased CM dose. Tumour delineation scores were significantly better on the reduced- and full-dose images than on pre-CM injection images, but, with one exception, tumour extension was identified as the same on all imaging sequences. Postoperative MR imaging of large macroadenoma residues can routinely be performed without intravenous CM. When CM is indicated a reduced dose of gadopentetate dimeglumine should provide sufficient diagnostic information. Received: 29 June 1999; Revised: 2 December 1999; Accepted: 14 March 2000     

Gd-EOB-DTPA enhancement pattern of hepatocellular carcinomas in rats: Comparison with Tc-99m-IDA uptake

The enhancement pattern of chemically induced hepatocellular carcinomas (HCCs) after intravenous administration of the hepatobiliary magnetic resonance (MR) contrast agent gadolinium-EOB-DTPA (ethoxybenzyl-diethylenetriaminepentaacetic acid) was compared with the uptake pattern of technetium-99m-labeled iminodiacetic acid (IDA), a hepatobiliary radioactive tracer. The hepatocyte uptake of both the contrast agent and the scintigraphic agent has been shown to be driven by the organic anion transporter. The tumors enhanced less than the liver after Gd-EOB-DTPA administration, whereas the Tc-99m-IDA uptake of differentiated HCCs exceeded that of the liver at 30 minutes and 3 hours after administration. The enhancement pattern of a differentiated HCC with Gd-EOB-DTPA does not mirror that seen with Tc-99m-IDA.     

Mn-DPDP–enhanced MR imaging of malignant liver lesions: Efficacy and safety in 20 patients

Twenty patients with malignant liver lesions underwent magnetic resonance (MR) imaging with manganese (II) DPDP [N,N′-dipyridoxylethylenediamine-N,N′-diacetate 5,5′-bis(phosphate)] to evaluate the safety and efficacy of the contrast agent. In two groups of 10 patients each, 5 μmol/kg Mn-DPDP was administered intravenously (3 mL/min) at a concentration of either 50 or 10 μmol/mL. T1- and T2-weighted images were obtained with a 1.5-T imager. Six patients reported a total of eight instances of side effects (flush, feeling of warmth, metallic taste) of which seven occured at the 50 μmol/mL concentration. A significant decrease in alkaline phosphatase levels 2 hours after injection was recorded. On T1-weighted images, the 10 μmol/mL formulation yielded significantly greater increases in contrast-to-noise ratio (79.8%–137.5%) than the 50 μmol/mL formulation (46.2%–86.6%). In a blinded reader study of 10 patients with one to five lesions each, no lesion was missed on Mn-DPDP–enhanced T1-weighted images; however, four false-positive foci were identified. The authors conclude that slow administration of 5 μmol/kg Mn-DPDP at a concentration of 10 μmol/mL is safe and efficient enough to proceed to further clinical trials.