J Magn Reson Imaging

Malignant hepatic tumors: changes on MRI after hepatic arterial chemoembolization--preliminary findings.

Year 1998
Semelka RC. Worawattanakul S. Mauro MA. Bernard SA. Cance WG.
Department of Radiology, University of North Carolina at Chapel Hill, 27599-7510, USA.
This study describes the MR appearances of malignant hypervascular liver lesions pre- and post-hepatic-arterial chemoembolization, with correlation to serial imaging and clinical responses. Eight patients with malignant hypervascular liver lesions underwent pretreatment and posttreatment MR examination on a 1.5-T MR imager. MR sequences included T1-weighted spoiled gradient echo (SGE), T2-weighted fat-suppressed spin echo or turbo spin echo, and dynamic gadolinium-enhanced SGE images. All patients underwent pretreatment, initial posttreatment, and subsequent posttreatment MR studies. The histology of primary tumors included various types of hepatocellular carcinoma (HCC) (four patients: fibrolamellar HCC [one patient], HCC [two patients], mixed HCC/cholangiocarcinoma [one patient]) and liver metastases (four patients: untyped islet cell tumor [two patients], gastrinoma [one patient], carcinoid [one patient]). Response to chemoembolization was determined by three assessments: MR response, serial imaging response, and clinical response. The appearance of MR response to chemoembolization was determined based on the correlation with clinical and serial imaging response. The MR response of lesions that showed good clinical response included: increase in signal intensity on T1-weighted images (three patients), decrease in signal intensity on T2-weighted images (three patients), and negligible or minimal enhancement on immediate postgadolinium images (four patients) after chemoembolization. The most marked change in lesion appearance was observed in lesions < or = 1 cm, which had intense homogeneous enhancement on pretreatment MR studies and negligible enhancement on initial posttreatment MR examinations. MR response of lesions that showed moderate clinical response demonstrated a variety of lesion appearances from substantial change to minimal change. MR response of lesions that showed poor clinical response demonstrated no change in lesion appearances compared with the pretreatment MR study. Our results demonstrated change in appearance of liver lesions between pre- and post-hepatic-arterial chemoembolization MR studies. MR response correlated with response determined by serial imaging studies and clinical findings.

Evaluation of 3D image registration as applied to MR-guided thermal treatment of liver cancer.

Year 1998
Wilson DL. Carrillo A. Zheng L. Genc A. Duerk JL. Lewin JS.
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA. dlw@po.cwru.edu
There are many potential applications of three-dimensional (3D) image registration in MR-guided radiofrequency (RF) thermal ablation of tumors. For example, after registration of image volumes obtained before and after thermal ablation, a variety of quantitative and visual assessments of therapy were performed. For liver tumors, the accuracy of rigid body, manual registration on 19 pairs of image volumes was evaluated, almost all of which were obtained during thermal treatment sessions. Registration error was estimated as a distance between anatomical landmarks, including both internal vascular structures as well as the surface of the liver. Over all image pairs and throughout a large portion of the liver, the registration error was 3.1 mm (mean + 1 SD). From the bottom to the top of the liver, error increased on the order of 13%, probably because of liver motion and deformation resulting from respiration. Although probably insufficient for blind guidance of therapy, registration accuracy was undoubtedly sufficient for interesting applications in the planning, assessment, and optimization of interventional MR-guided thermal treatment of liver tumors.

Preliminary clinical experience with laser-induced interstitial thermotherapy in patients with hepatocellular carcinoma.

Year 1998
Bremer C. Allkemper T. Menzel J. Sulkowski U. Rummeny E. Reimer P.
Institute for Clinical Radiology, Westfaelische Wilhelms University, Meunster, Germany. bremerc@uni-muenster.de
The purpose of this preliminary study was to evaluate whether laser-induced interstitial thermotherapy (LITT) may be used for palliative treatment of localized hepatocellular carcinomas (HCC). We applied LITT to two patients suffering from unresectable localized hepatocellular carcinomas of different sizes (2.5 and 4 cm). LITT was performed with an Nd:YAG laser (1,064 nm) at 5 W laser power (15-20 minutes). Thermometry during LITT was performed by MRI using a temperature-sensitive T1-weighted fast low-angle shot (FLASH) sequence. Follow-up for local tumor control was performed by MRI and ultrasound. LITT was well tolerated and no adverse events occurred during or after LITT; no secondary liver lesions were seen in the follow-up (11 or 12 months, respectively). Only minimal tumor growth was observed in the larger HCC (from 4 to 5 cm), whereas the smaller HCC remained unchanged in size during 11 months of follow-up. We conclude that LITT might be an effective minimally invasive palliative treatment option for patients with small unresectable HCC.

MRI of the liver.

Year 1998
Laing AD. Gibson RN.
Department of Radiology, The University of Melbourne, The Royal Melbourne Hospital, Parkville, VIC, Australia.
MRI of the liver is a powerful imaging modality for detection and characterization of liver pathology. MRI technology continues to evolve with developments in scanner hardware performance and refinements in imaging sequences, particularly in respect to fast imaging techniques, improving the quality of images that can be routinely achieved. Fast imaging techniques allow dynamic contrast-enhanced scanning to assist in lesion detection and characterization. An array of tissue-specific contrast agents are also becoming available; the clinical utility of some of these agents is yet to be fully established. An overview of scanning technique, contrast media, and the role of MRI in liver lesion detection and characterization is presented, with a review of the typical imaging characteristics of common focal and diffuse hepatic diseases. Where possible, emphasis has been placed on features that allow distinction between the various pathologic entities described.

Hepatitis, cirrhosis, and hepatoma.

Year 1998
Murakami T. Kim T. Nakamura H.
Department of Radiology, Toyonaka Municipal Hospital, Osaka, Japan.
Virus hepatitis and liver cirrhosis are found at high incidence in Asia, and they require not only biochemical examination of blood but also subsequent imaging, because they are often complicated by hepatocellular carcinoma (HCC). It is, therefore, very important to know the specific appearances of hepatitis, liver cirrhosis, and HCC when we diagnose these diffuse liver diseases. Liver necrosis due to severe hepatitis is seen as high intensity on T2-weighted spin echo images. Regeneration is seen as low intensity on T2-weighted images. Morphologic and pathologic changes of cirrhotic liver are well demonstrated by MR imaging techniques. Fibrotic septum with inflammatory cell infiltration or rich pseudo bile duct show high intensity on T2-weighted images, and regenerating nodules shows low intensity. Gradient echo images show regenerating nodules with iron deposition as low-intensity nodules due to susceptibility artifact. MRI also has the potential to evaluate function of diffuse liver disease, cirrhosis, and hepatitis. MRI can visualize and diagnose HCC objectively. Dynamic MRI is very useful for diagnosing HCC. It is also applied for evaluation of effect after transcatheter arterial chemoembolization, because it shows enhancement only in the viable region at an arterial phase. MRI is less invasive and is thus an extremely important form of liver imaging.

MRI of clonorchiasis and cholangiocarcinoma.

Year 1998
Choi BI. Kim TK. Han JK.
Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Korea.
Intrahepatic cholangiocarcinomas are usually categorized as peripheral cholangiocarcinoma or hilar cholangiocarcinoma on the basis of the site of origin. Clonorchiasis is a trematodiasis caused by chronic infestation of liver flukes, which are largely confined to the Orient, from Japan to Vietnam. The close relationship between clonorchiasis and cholangiocarcinoma has long been emphasized. This paper discusses the efficacy and possible roles of MRI for imaging clonorchiasis and cholangiocarcinoma of the liver. Although sonography, CT, and direct cholangiography have been used traditionally to diagnose these diseases, the role of MRI has been increasing rapidly with dramatic progress of the MRI techniques. We review MRI findings of clonorchiasis and cholangiocarcinoma and discuss the potential usefulness of MRI.

Ultrafast MR imaging of the abdomen: echo planar imaging and diffusion-weighted imaging.

Year 1998
Yamashita Y. Tang Y. Takahashi M.
Department of Radiology, Kumamoto University School of Medicine, Honjo, Japan. yama@kaiju.medic.kumamoto-u.ac.jp
Ultrafast MRI technique has become available with the introduction of new generation MR scanners for abdominal imaging. However, there is no consensus about the optimal imaging acquisition at the present time. Because single shot echo planar imaging (EPI) technique is based on high technology and had just applied in clinical imaging, further clinical investigation will be needed. Currently, the hypersensitivity to magnetic inhomogeneity and local magnetic susceptibility and the low spatial resolution may limit the widespread application of EPI technique. In addition to providing information for morphologic diagnosis, EPI will be more widely used for functional and qualitative diagnosis. Diffusion-weighted imaging can be used for differentiation of solid tumors according to their different cellular construction, evaluation of cystic lesions based on the different viscosity of their contents, and assessment of diffused pathologic changes in the parenchyma of solid organs. In addition to the previous parameters such as proton density and T1 and T2 values, diffusion factors may provide important information for the qualitative and dynamic evaluation of abdominal pathologic changes. Even though there are many difficulties that must be solved for diffusion-weighted imaging, a more wide application of this technique is expected through technologic improvement.

Application of MRI for small intestinal diseases.

Year 1998
Ha HK. Lee EH. Lim CH. Shin YM. Jeong YK. Yoon KH. Lee MG. Min YI. Auh YH.
Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Until recently, MRI has not been considered to be suitable for the evaluation of the small intestine due to artifacts associated with bowel peristalsis or respiration. However, recent advances of MR techniques enable the acquisition of clear images of the small intestine. Therefore, the purpose of this article is to review the details for the application of MRI in patients with small intestinal diseases. This article discusses bowel preparation and oral contrast agents as well as MR techniques and pulse sequences. Thereafter, the usefulness of MRI for the lesions in the peritoneal cavity or in the gastrointestinal tract are discussed. Small intestinal lesions are categorized into inflammatory, neoplastic, ischemic, and obstructive bowel diseases. In conclusion, MRI can be used as an alternate modality of choice for imaging various diseases of the small intestine.

Comparison of breath-hold multishot echo-planar and respiratory triggered fast-spin-echo sequences for T2-weighted MRI of liver lesions.

Year 1998
Yamakado K. Sakuma H. Murashima S. Nakatsuka A. Matsumura K. Takeda K.
Department of Radiology, Mie University School of Medicine, Tsu, Japan.
The purpose of this study was to evaluate the usefulness of multishot echo-planar imaging in detecting liver tumors in comparison with respiratory triggered T2-weighted fast-spin-echo (FSE) imaging. Thirty-two patients with 70 focal liver lesions were imaged using a 1.5-T high speed MR imager. Eight-shot echo-planar images covering the whole liver were acquired during a single breath-hold period. FSE images were acquired with respiratory triggering in approximately 4 minutes. Lesion detectability and image quality of the two pulse sequences were analyzed qualitatively. Quantitative analysis was performed by means of signal-to-noise and tumor-liver contrast-to-noise analysis. Lesion detectability was comparable in both solid (86.3% vs 90.2%: .3 < P < .5) and nonsolid lesions (89.5% vs 100%: .3 < P < .5) between echo-planar and FSE images. Echo-planar imaging provided significantly reduced image artifact, better lesion conspicuity, and anatomic detail compared with FSE imaging. The signal-to-noise and contrast-to-noise ratios of echo-planar images were significantly higher than those of FSE images. Breath-hold eight-shot echo-planar imaging can be an alternative to T2-weighted FSE imaging because it can provide comparable image quality in a substantially decreased acquisition time.

Characterization of focal liver lesions with half-fourier acquisition single-shot turbo-spin-echo (HASTE) and inversion recovery (IR)-HASTE sequences.

Year 1998
Tang Y. Yamashita Y. Namimoto T. Takahashi M.
Department of Radiology, Kumamoto University School of Medicine, Honjo, Japan. yama@kaiju.medic.kumamoto-u.ac.jp
The half-Fourier acquisition single-shot turbo-spin-echo (HASTE) sequence allows for heavily T2-weighted images, and the inversion recovery (IR)-HASTE sequence represents the T1 value of the tissue in a very short time. This study was undertaken to determine whether characterizing focal liver lesions can be made by combination with these very fast sequences. Seventy-four patients (33 cysts, 28 hemangiomas, and 33 malignant solid liver masses [15 metastatic tumors, 14 hepatocellular carcinomas, and 4 cholangiocarcinomas) underwent dynamic CT and breath-hold abdominal MRI using turbo-spin-echo (TSE), HASTE, and IR-HASTE sequences with variable T1 values on a 1.5-T MR unit. The imaging time for each slice was 2 seconds for HASTE imaging and 2 to 4 seconds for IR-HASTE imaging. Lesion detection and qualitative characterization were evaluated. Quantitative analysis was performed by measuring the contrast-to-noise ratios (CNRs) as well as visual analysis. The inversion time (TI) nulling values were also statistically analyzed. All cystic lesions were detected on both TSE and HASTE imagings. For solid lesions, TSE failed to detect one small solid lesion and HASTE sequence failed to detect three lesions. With HASTE sequences, all cysts and hemangiomas were markedly hyperintense in comparison with malignant solid masses. CNRs of hemangiomas or cysts were significantly higher than those of malignant solid masses (P < .01), and there was no overlap. The TI nulling value was 1,100+/-100 msec for hemangiomas, 1,900+/-110 msec for cysts, and 740+/-140 msec for malignant solid masses. There was no overlap between the TI nulling values of hemangiomas and cysts (P < .01). By combining the CNR from the HASTE sequence and the TI nulling value from the IR-HASTE sequence, complete discrimination among malignant solid masses, hemangiomas, and cysts of the liver could be made. Application of HASTE (representing T2 values) and IR-HASTE (representing T1 values) sequences provided a rapid and reliable imaging method for characterizing focal liver lesions without the use of contrast medium.

Microwave coagulation therapy on hepatomas: CT and MR appearance after therapy.

Year 1998
Hyodoh H. Hyodoh K. Takahashi K. Furuse M. Kawamoto C. Isoda N. Hozumi M. Ido K. Hirota N.
Department of Radiology, Jichi Medical School, Tochigi-Ken, Japan.
Laparoscopic microwave coagulation (LMC) for hepatocellular carcinomas (HCCs) was performed on 26 HCCs in 17 patients. Contrast-enhanced CT (CECT) and MR images (T1-weighted imaging [T1WI], T2WI, gadolinium-diethylenetriamine pentaacetic acid [Gd-DTPA] T1WI) were obtained to determine changes over time. The irradiated center exhibited low to moderate intensity with surrounded high intensity (HI) on T2WI and Gd-DTPA T1WI. On T1WI, lesions showed four patterns of intensity: uniform HI (30.8%), arcuate HI (26.9%), mainly low with spot HI (30.8%), and isointensity to hypointensity (11.5%). Follow-up imaging at more than 170 days revealed isointensity to hypointensity on T1WI (96.2%) and reduced HI on T2-weighted imaging (T2WI) and Gd-DTPA T1WI. All lesions became less conspicuous and were reduced in volume. HCC shows time-related changes in signals and size after LMC. Identifying the irradiated lesion is necessary to estimate the adequacy of treatment by comparison with the pretherapeutic image.

Improvement of MR cholangiopancreatography at .5 T: three-dimensional half-averaged single-shot fast spin echo with multi-breath-hold technique.

Year 1998
Ichikawa T. Haradome H. Hanaoka H. Kassai Y. Nitatori T. Hachiya J. Araki T.
Department of Radiology, Yamanashi Medical University, Nakakoma, Japan.
The purpose of this study was to determine the advantage of a three-dimensional (3D) single-shot fast-spin-echo (SSFSE) sequence to obtain MR cholangiopancreatography (MRCP) with a .5-T MR unit by comparison with a two-dimensional (2D) SSFSE sequence. MRCP with 2D-SSFSE and with 3D-SSFSE with 128 echo train lengths was performed on 15 volunteers and 38 patients with pancreatobiliary disease using a .5-T MR unit. For maximum intensity projection (MIP) reconstruction, the section thickness of source images was 4 mm in the 2D-SSFSE and 3 mm in the 3D-SSFSE. 3D volume data in 3D-SSFSE were obtained using repeated short breath-hold of 2 seconds for every repetition time throughout the examination. The image quality, duct conspicuity, signal-intensity ratio (SIR), and contrast-to-noise ratio (CNR) were evaluated. In 23 of the patients who underwent both MRCP and direct cholangiopancreatography (endoscopic retrograde cholangiopancreatography [ERCP]/percutaneous transhepatic cholangiography [PTC]), a comparison between these two modalities was also conducted. The image quality of the MIP image with 3D-SSFSE (49 of 53, 92.5% graded excellent or good) was superior to that with 2D-SSFSE (31 of 53, 58.4%). Duct conspicuity, SIR, and CNR were significantly higher with 3D-SSFSE than with 2D-SSFSE. 3D-SSFSE also showed a stronger relationship with the ERCP/PTC findings compared to 2D-SSFSE. 3D-SSFSE provided satisfactory quality, SIR, and CNR of MRCP images, even when a .5-T MR unit was used, because the breath-hold technique used during 3D data sampling minimized all types of motion effects.

Biliary cystadenoma with mesenchymal stroma of the liver: correlation between unusual MR appearance and pathologic findings.

Year 1998
Gabata T. Kadoya M. Matsui O. Yamashiro M. Takashima T. Mitchell DG. Nakamura Y. Takeuchi K. Nakanuma Y.
Department of Radiology, Kanazawa University, School of Medicine, Kanazawa City, Ishikawa, Japan.
We reported a case of the biliary cystadenoma of the liver. The cystic mass had lobulation and septation and showed marked hyperintensity on T1-weighted images and hypointensity on T2-weighted images; MR findings were very unusual for cystadenoma. The content of the cystic mass was jelly-like, thick mucinous fluid without intracystic hemorrhage. We concluded that these unusual signal intensities of the cyst were due to hyperproteinous mucinous fluid.

Can MRCP replace ERCP?

Year 1998
Takehara Y.
Department of Radiology, Hamamatsu University School of Medicine, Handa, Japan. takehara@hama-med.ac.jp
Magnetic resonance cholangiopancreatography (MRCP) has replaced direct cholangiography and pancreatography in many instances. Its complete noninvasiveness and flexibility are less onerous for patients. For the use of screening as well as scrutiny, MRCP has played an important role in diagnosing various pathologies in this field. The usefulness of MRCP is not limited to anatomical evaluations; it can also yield physiologic and functional information. From a cost-performance basis, MRCP is undoubtedly superior to direct methods. Coupled with a cutting-edge MR system, MRCP has the potential to limit the use of invasive transpapillary and percutaneous methods merely to interventional purposes. In the near future, the emergence of interventional MR scanners will make MRCP even more competitive, and the replacement will be accelerated.

Hepatic T2-weighted MRI: a prospective comparison of sequences, including breath-hold, half-Fourier turbo spin echo (HASTE).

Year 1998
Coates GG. Borrello JA. McFarland EG. Mirowitz SA. Brown JJ.
Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
The purpose of this study was to quantitatively compare the hepatic contrast characteristics of conventional spin-echo (CSE) and fast spin-echo (FSE) sequences with breath-hold T2-weighted images acquired with half-Fourier turbo spin echo (HASTE). Forty-five patients were examined with a phased-array surface coil. Nineteen patients had focal hepatic lesions, including eight malignant tumors, 10 cavernous hemangiomas, and one hepatic adenoma. Twenty-six patients had no focal hepatic lesions. T2-weighted images with comparable TE were acquired with CSE, FSE, and HASTE pulse sequences. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) for liver, spleen, and lesions were measured. FSE demonstrated significantly better quantitative performance than CSE for liver-spleen CNR (P .0084). No statistically significant difference was demonstrated between FSE and CSE for liver or spleen SNR. FSE demonstrated clear scan time and resolution advantages over CSE. HASTE performed significantly poorer than CSE and FSE for liver-spleen CNR (P < .0001), liver SNR (P = .0002 for CSE and P < .0001 for FSE), and spleen SNR (P < .0001). Optimized FSE images with a short echo train length performed comparably to CSE images of equivalent TE. Liver-lesion CNR was suppressed on HASTE images, suggesting that long echo train length FSE sequences could diminish solid lesion detection compared to CSE and short echo train length FSE.

Assessment of hepatic portal perfusion using T2 measurements of Gd-DTPA.

Year 1998
Uematsu H. Yamada H. Sadato N. Muramoto S. Inoue H. Hayashi K. Yonekura Y. Kimura H. Sakuma H. Matsuda T. Hayashi N. Yamamoto K. Ishii Y.
Department of Radiology and Biomedical Imaging Research Center, Fukui Medical School, Japan.
Recently, perfusion imaging has been of increasing interest in MRI. We applied this method for semiquantitative evaluation of hepatic parenchymal portal blood flow in patients with diffuse liver damage. Twenty patients with diffuse hepatic damage were divided according to the Child's Classification and studied. Gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) was administered into the superior mesenteric artery (SMA), and a dynamic series of T2*-weighted fast low angle shot (FLASH) images was obtained. We evaluated relative regional portal blood volume (rrPBV), mean transit time (MTT), and relative regional portal blood flow (rrPBF). The relationship between the rrPBV, rrPBF, and plasma indocyanine green retention rate test at 15 minutes (ICGR15 was also evaluated in 12 patients. Both rrPBF and rrPBV are significantly decreased in Child B & C patients compared with Child A patients. On the other hand, the MTT is significantly prolonged in Child B & C patients compared with Child A patients. Significant correlations were also noted between rrPBV and ICGR15 and between rrPBF and ICGR15. By means of selective catheterization into the SMA, we were able to estimate rrPBV, rrPBF, and MTT. This method may play a clinical role for assessment of regional portal perfusion in various diseases with diffuse liver damage.

The value of respiratory triggered T2-weighted turbo spin-echo imaging of the liver using a phased array coil.

Year 1998
Namimoto T. Yamashita Y. Mitsuzaki K. Takahashi M.
Department of Radiology, Kumamoto University School of Medicine, Japan.
The purpose of this study was to evaluate the value of the respiratory triggered turbo spin-echo (TSE) technique for T2-weighted MRI of liver lesions. Fifty-nine patients (32 men, 27 women; mean age, 63.3 years) with focal hepatic lesions were prospectively studied with MRI at 1.5 T with use of a body phased array coil. In the first 15 patients, breath-hold TSE, respiratory triggered TSE, and conventional nonrespiratory triggered TSE T2-weighted imaging were compared. Because nonrespiratory triggered TSE imaging was significantly inferior (P < .01) to breath-hold or respiratory triggered images, breath-hold and respiratory triggered TSE T2-weighted images were compared in the remaining 44 patients. Images were analyzed quantitatively by measuring the liver signal-to-noise ratio and the lesion-liver and spleen-liver contrast-to-noise ratios and qualitatively by evaluating the lesion conspicuity, liver parenchymal homogeneity, and sharpness of intrahepatic vessels. The imaging time was 26 seconds for breath-hold TSE imaging, 49 to 219 seconds (mean, 149 seconds) for the respiratory triggered TSE imaging, and 79 to 379 seconds (mean, 239 seconds) for the nonrespiratory triggered TSE imaging. Quantitatively, the signal-to-noise ratio of the liver for breath-hold imaging was comparable to that for respiratory triggered imaging. The lesion-liver and liver-spleen contrast-to-noise ratios for the respiratory triggered images were greater by 37% and 39%, respectively, than for the breath-hold T2-weighted TSE images. Qualitatively, the respiratory triggered images showed lower frequency of image artifact, better lesion conspicuity, and greatly superior depiction of intrahepatic structures compared with the breath-hold T2-weighted TSE images. The respiratory triggered T2-weighted TSE technique provides better quality liver images than the breath-hold TSE technique or nonrespiratory triggered technique within a reasonable acquisition time.

Sequential use of ferumoxide particles and gadolinium chelate for the evaluation of focal liver lesions on MRI.

Year 1998
Semelka RC. Lee JK. Worawattanakul S. Noone TC. Patt RH. Ascher SM.
Department of Radiology, University of North Carolina at Chapel Hill, 27599, USA.
This study describes the sequential use of ferumoxide (superparamagnetic iron oxide) particles and nonspecific extracellular gadolinium chelate (Gd) for evaluation of focal liver lesions on MRI to evaluate order of contrast administration and imaging effect of the first contrast agent on sequences acquired after the second contrast agent. Thirteen patients underwent MR examinations that included ferumoxide and Gd. The order and timing of administration were as follows: separate sessions (three patients; Gd study 4-19 days before ferumoxide study), same session, Gd first (seven patients; Gd study 1-2 hours before ferumoxide study), and same session, ferumoxide first (three patients; ferumoxide administered less than 1 hour before Gd study). Postcontrast sequences were reviewed in a randomized, blinded fashion by two separate investigators. Determination was made regarding whether (a) the presence of the first agent administered could be detected on sequences obtained after the second agent and (b) the presence of the first agent interfered with the image quality of those sequences. No evidence for the presence of Gd was appreciated by either observer on postferumoxide sequences acquired in separate session studies. In same session, Gd first studies, the presence of Gd was observed in six of seven patients on T1-weighted spoiled gradient-echo (SGE) images obtained after ferumoxide administration. The presence of Gd was not apparent in seven of seven patients on T2-weighted fat-suppressed images obtained after ferumoxide. In same session, ferumoxide first studies, the presence of ferumoxide was appreciated on post-Gd sequences in two of three patients. The presence of ferumoxide did not appreciably diminish image quality on those sequences. Exact agreement was achieved by the independent investigators. Our results suggest that Gd and ferumoxide can be administered sequentially within one study session without substantial loss of diagnostic information obtained on sequences performed after administration of the second contrast agent. Administrating Gd first resulted in less of an effect of the visualization of the first agent on sequences acquired after the second agent.

Uptake of mangafodipir trisodium in liver metastases from endocrine tumors.

Year 1998
Wang C. Ahlstrom H. Eriksson B. Lonnemark M. McGill S. Hemmingsson A.
Department of Diagnostic Radiology, Uppsala University Hospital, Sweden.
The purpose of the study was to investigate retrospectively whether mangafodipir trisodium (MnDPDP) can enhance the liver metastases from endocrine tumors. Thirteen patients with endocrine tumors and liver metastases underwent T1-weighted spin-echo (SE) and turbo gradient-echo (GRE) MRI conducted before and 20 to 60 minutes after i.v. infusion of MnDPDP. Additional 24-hour-delay scans were performed in 8 of 13 patients. MR signal intensity (SI) was measured in liver parenchyma and metastases, which was then related to that of paraspinal muscle. A total of 30 lesions on precontrast and postcontrast images and 18 lesions on 24-hour-delay images were measured. An enhancement by 49% in SE and 40% in GRE images (P = .0001) was observed in tumor tissues after MnDPDP infusion. In 24-hour-delay images, the SI of the lesions remained relatively high, but in liver parenchyma, it decreased significantly, and the tumor-liver tissue contrast was reduced.

Preclinical assessment of hepatocyte-targeted MR contrast agents in stable human liver cell cultures.

Year 1998
Reimer P. Bader A. Weissleder R.
Institute of Clinical Radiology, Westfalian-Wilhelms-University, Munster, Germany.
Much effort has been expended in the search for hepatocyte-specific MR contrast agents to improve the detection and characterization of liver tumors. The purpose of this study was to establish human hepatocyte cell cultures to preclinically assess hepatocyte-targeted magnetopharmaceuticals. Cultured human hepatocytes were sandwiched between two layers of collagen preserving both hepatocyte function and morphology over prolonged period of time. Cultures (n = 37) were subsequently used to test different fluorescinated MR contrast agents. Plain and rhodaminated monocrystalline iron oxide particles (MION and MION-rh) and asialoglycoprotein-receptor-specific rhodaminated asialofetuin coupled to MION (MION-ASF-rh) were prepared. Competition experiments of these agents were performed with D(+)-galactose to study the specificity of galactose-mediated cell uptake. To assess the impact of cell integrity on cell uptake, functional experiments with CCl4 were performed. Normal cell cultures showed significantly higher fluorescence light emission after incubation with hepatocyte-directed ASF-MION-rh than after incubation with MION-rh. Competition experiments of ASF-MION-rh with galactose showed a dose-dependent decrease of calibrated fluorescence light emission. Cell cultures treated with CCl4 demonstrated a dose-dependent significant reduction of calibrated fluorescence light emission, indicating reduced uptake of ASF-MION-rh. Our data demonstrate that stable human hepatocyte cell cultures can be used to preclinically assess novel magnetopharmaceuticals. Different contrast agents may be directly compared to each other and may accelerate their preclinical design. Because the assay can be applied to cells from any species, it may represent an ideal test system before clinical trials of new cell-directed MR contrast agents.