Iron oxide enhanced MR imaging of the liver and spleen: review of the first five years.

Superparamagnetic iron oxide (SPIO) particles are a potent new class of MR contrast agents affording improved detection of hepatic and splenic neoplasms. In this report we review the development of this agent through preclinical studies and early clinical results at Massachusetts General Hospital during a 5 year investigation. SPIO particles are sequestered by normal reticuloendothelial system (RES) phagocytic Kupffer cells but are not retained in tumor tissue. Consequently, there is a five fold increase in T2 relaxation between normal RES tissue and tumor with a comparable advantage in quantitative signal to noise ratio, contrast to noise ratio and lesion detectibility in the liver and spleen at MR imaging. Increased lesion conspicuity can be exploited to decrease threshold size for lesion detection to less than 3 mm. Clinically beneficial effects occur with a variety of mildly T2-weighted spin-echo pulse sequences; gradient-echo techniques show even greater benefit after administration of SPIO. Metabolically, pharmaceutical grade preparations are biodegradable and bioavailable, being rapidly turned over into body iron stores and incorporated into erythrocyte hemoglobin. Early dose escalation clinical trials have identified a probable clinical dose range of 10-20 mumol Fe/kg body weight. SPIO compounds evaluated to date are still investigational in the United States. Newer commercial formulations currently being evaluated may extend clinical safety margins.

Liver tumor imaging: current concepts.

With the increasing availability of curative surgical techniques for primary and secondary hepatic neoplasms, the tasks for clinical imaging of liver cancer suspects have become more exacting. Detection of tumor, differential diagnosis of individual nodules, and mapping the anatomic extensions of malignant disease are now routinely required. Related and unrelated liver substrate abnormalities such as cavernous hemangioma and focal fatty deposits are often discovered in liver cancer suspects and must be differentiated from metastatic deposits. Moreover, modern imaging methods frequently display tiny subcentimeter nodules which often prove difficult to adequately characterize (micrometastases vs other). The most sensitive imaging techniques are CT after arterial portography and intraoperative ultrasound, but because of their invasiveness, these are reserved exclusively for staging. For primary screening MR imaging is increasingly preferred over CT because of its superiority in discriminating hemangiomas and cysts from metastases without the need for iodinated contrast material.

In vitro evaluation of a mechanical injector for infusion of magnetic resonance contrast media.

The authors evaluated the performance of a prototype mechanical injector developed for infusion of magnetic resonance (MR) contrast media. The injector was installed in a 0.6-T clinical MR scanner, and evaluation was made using saline (viscosity: 1.0 cP) and gadopentetate dimeglumine (viscosity: 4.9 cP) with 16-, 21-, and 25-gauge needles, and 244- and 366-cm connecting tubing. At a fixed flow rate of 1 mL/second, volume infused was within 10% of the desired volume except for infusions less than 1 mL. Reproduction of flow rates was less reliable. With saline, maximal flow rates were 5.5 mL/second, 4.2 mL/second, and 1.1 mL/second for the 16-, 21-, and 25-gauge needles, respectively, and 3.7 mL/second, 2.4 mL/second, and 0.9 mL/second, respectively, for gadopentetate dimeglumine. Needle size was identified as the major factor limiting flow rate. The magnet was reshimmed after the injector was installed, and no deleterious effects were identified on gradient echo (TR: 250/TE:18/flip angle 60 degrees) MR images.

Dissolution of calcified gallstones. Part I. Correlation of in vitro dissolution kinetics in methyl tert-butyl ether with patterns of calcification by computed tomography.

RATIONALE AND OBJECTIVES: The authors evaluated the relationship between stone computed tomography (CT) attenuation patterns and the kinetics of dissolution with methyl tertbutyl ether (MTBE). METHODS: Single moderately and heavily calcified gallstones from 40 patients were selected from a gallstone library and classified for pattern of calcification by in vitro CT scan (dense, rim, core, and laminated). Each stone was placed in a 10-mL aliquot of MTBE for 24 hours. Stone residue was blotted dry and weighted at 8, 16, and 24 hours. Results were normalized with respect to stone size. RESULTS: Only 1 of 40 (4%) specimens dissolved to particulate matter that was smaller than 2 mm. All (6 of 6) stones that were densely calcified showed virtually no dissolution. The rate of gallstone dissolution varied temporally within the rim, core, and laminated stone categories and was related to the composition of the layer exposed to the solvent at any given time. CONCLUSION: The success and rate of dissolution may be predicted by the pattern of calcification as determined by computed tomography (CT).

Cellular uptake and trafficking of a prototypical magnetic iron oxide label in vitro.

RATIONALE AND OBJECTIVES: Target-specific magnetic resonance (MR) contrast agents are being developed to improve the accuracy of MR imaging. The purpose of this study was to determine the mechanism of cell uptake, and modes of intracellular trafficking of a prototypical iron oxide label (RMA) used in the synthesis of some target-specific MR contrast agents. METHODS: The prototypical agent (RMA) consisted of a dextran-coated monocrystalline iron oxide that was modified with rhodamine (fluorescent label) and opsonized with albumin. Fluorescence microscopy was performed in a phagocytic C6 cell line and in murine bone marrow macrophages. Immunohistochemistry against lysosomal markers was used to confirm the intracellular location of the label. RESULTS: RMA was identified inside cells after incubation at concentrations as low as 4.0 x 10(-10) M Fe, typically observed with receptor mediated endocytosis and several orders of magnitude lower than that expected with fluid phase pinocytosis. Cell uptake could be inhibited by excess protein but not by dextran. RMA localized initially to tubular and to round intracellular organelles and co-localized with an antibody against a murine lysosomal glycoprotein antibodies (LGP-A) in macrophages. Three days after incubation, RMA was concentrated in perinuclear vesicles, which most likely represent terminal lysosomes where final breakdown appears to occur. CONCLUSIONS: The mechanism of cellular uptake of a prototypical opsonized iron oxide label is consistent with receptor-mediated endocytosis. Immediately after cell contact, RMA localizes to the lysosomal compartment and at long time points reside in vesicles that by morphology and distribution appear to be terminal lysosomes. Iron oxides therefore demonstrate metabolism via the lysosomal pathway.

Dissolution of calcified gallstones. Part II. Evaluation of edetic acid preparations for dissolution of residue after in vitro methyl tert-butyl ether treatment.

RATIONALE AND OBJECTIVES: The authors assessed the potential of edetic acid (EDTA) preparations to dissolve the residue of calcified gallstones partially treated with methyl tert-butyl ether (MTBE). METHODS: Nineteen triplets (57 gallstones) were submitted to dissolution in EDTA, urea-EDTA, and an MTBE control for 48 hours after initial partial dissolution in MTBE for 24 hours. Results were compared with findings at specimen computed tomography and crystallographic analysis. All data were corrected for differences in stone size. RESULTS: In all three treatment groups (EDTA, urea-EDTA, MTBE), almost identical dissolution outcomes were observed within each triplet. Most triplets that dissolved displayed a laminated or a core-calcification pattern and consisted primarily of cholesterol. Specimens that dissolved poorly in all three groups displayed dense calcifications or thick calcified rims and were classified as pigment stones. CONCLUSION: Because no statistically significant differences in dissolution were found among the EDTA, urea-EDTA, and MTBE treatments, we conclude that EDTA preparations are not superior to the continued use of MTBE for dissolution of residue after initial MTBE treatment.

Eclectic drainage of subphrenic abscesses.

In 196 cases of subphrenic abscess from 1964 through 1979, 56% were attributable to gastric, hepatic, and colonic disease or surgery. Posttraumatic abscesses in younger patients became more frequent. Synchronous suprahepatic and subhepatic abscesses or bilateral abscesses accounted for 19%. Streptococci, Escherichia coli, Klebsiella, and Bacteroides species were the most frequently isolated organisms. Although the overall mortality rate was 40%, the surgical mortality rate decreased from 33% initially to 17% recently. The mortality rate of transperitoneal drainage decreased from 41% to 16%. From 1980 through early 1983, a success rate of 84%, with no fatalities, was achieved in percutaneous radiologic drainage of 25 unilocular abscesses. At present, radiologically guided drainage should be considered for unilocular abscesses and some bilocular ones. Although extraperitoneal, extrapleural surgical drainage remains an expeditious form of treatment, it may give way to radiologic drainage. Transperitoneal drainage is preferable for multifocal abscesses and for many abscesses secondary to complications of intraabdominal surgery.

Liver tumor imaging. Current concepts.

With the increasing availability of curative surgical techniques for primary and secondary hepatic neoplasms, the tasks for clinical imaging of patients suspected of having liver cancer have become more exacting. Detection of tumor, differential diagnosis of individual nodules, and mapping the anatomic extensions of malignant disease are now required routinely. The most sensitive imaging techniques are computed tomography and arterial portography and intraoperative sonography, but because of their invasiveness, there are reserved exclusively for cancer staging. For primary screening, magnetic resonance imaging is increasingly preferred over computed tomography because of its superiority in discriminating hemangiomas and cysts from metastases without the need for iodinated contrast material.

Screening for colon cancer: controversies and recommendations.

Colorectal cancer is the second most common cause of overall cancer mortality in the United States. This article review pertinent clinical and policy issues, details current colorectal cancer screening concepts, summarizes American College of Radiology achievements to date, and outlines projects in the next phase of the effort.

Radiology of the pancreas, 1976: sonography and ductography.

In recent years ultrasonography and endoscopic retrograde cholangiopancreatography (ERCP) have assumed pre-eminent roles in the radiographic evaluation of patients with pancreatic disease. This article survays the present status of these techniques based on clinical experience at the Massachusetts General Hospital and a review of the literature.

Objective evaluation of ampullary stenosis with ultrasonography and pancreatic stimulation.

Ultrasonography can detect changes in pancreatic and bile duct sizes after pancreatic stimulation by secretin or morphine and prostigmine. The effects of the two pharmacologic regimens on pancreatic duct dilatation were comparable and correlated with papillary stenosis determined at surgery, but the morphine and prostigmine combination produced more false-positive responses than did secretin. After administration of intravenous secretin (1 unit/kg), the pancreatic duct dilated in 83 percent of 12 symptomatic patients found at surgery to have a stenotic sphincter of Oddi and in 72 percent of 17 symptomatic patients found to have a stenotic accessory papilla associated with the pancreas divisum anomaly. Comparable dilatation occurred in 14 percent of 14 control subjects without suspected ampullary disease and in none of 10 patients with surgically disproved stenosis (p less than 0.001). The morphine and prostigmine combination produced more false-positive results in both the pancreatic duct and bile duct. Concomitant elevation of the serum amylase level and reproduction of pain were found to be of no discriminatory value. In patients whose pancreatic duct dilated preoperatively during secretin stimulation, dilatation did not occur after surgical sphincteroplasty. A positive test result was associated with a 90 percent success rate in preventing recurrent pancreatitis and ameliorating pain. A negative test result was associated with a 29 percent success rate. Ultrasonography of the pancreatic duct with secretin stimulation may provide objective criteria to supplement clinical judgment in selecting patients for sphincteroplasty to treat stenosis of either the sphincter of Oddi or the accessory papilla in pancreas divisum.

Pancreatitis.

Recent technologic advances in ultrasonography and computed tomography have revolutionized the diagnostic evaluation of pancreatic disease. More important, these imaging modalities provide an unprecedented opportunity to detect at an early stage the complications of pancreatitis, such as phlegmon, pseudocyst, and abscess, and to follow their response to therapy.

Cholecystitis: diagnosis by MR imaging.

Morphologic features which allow the diagnosis of acute cholecystitis by ultrasound and CT have now been observed by MR. When present, thickening of the gallbladder wall, intramural abscess, pericholecystic fluid, and the presence of gallstones may be more specific than MR characterization of gallbladder bile.

MRI of hepatic lymphoma.

Thirteen patients with biopsy proven hepatic lymphoma (2 Hodgkin, 11 Non-Hodgkin) and a control group of 15 patients with hepatic metastases were analyzed quantitatively and qualitatively by MRI. Focal hepatic lymphoma was most reliably detected (eight of eight patients) and appeared hypointense relative to liver on T1 weighted (CNR - 7.4 +/- 2.3) and hyperintense on T2 weighted (CNR + 8.4 +/- 2.9) images. The mean T1 and T2 relaxation times of focal hepatic lymphoma (T1 = 832 +/- 234 msec, T2 = 84 +/- 16 ms) differed significantly from adjacent non-tumorous liver (T1 = 420 +/- 121 ms, T2 = 51 +/- 9 ms; p less than 0.05), however CNR values and relaxation times were similar to those of hepatic metastases. Diffuse hepatic lymphoma (microscopic periportal infiltration) was undetectable by MRI in three patients by either morphologic features or quantitative criteria. A mixed pattern of hepatic lymphoma (focal lesions and diffuse infiltration) showed focal areas of slightly decreased signal intensity on T1 weighted images (CNR = -1.7 +/- 0.4) while T2 weighted images revealed multiple regions of focal hyperintensity (CNR = +13.3 +/- 8.4) superimposed on a diffusely hyperintense liver. Our experience demonstrates that either T1 or T2 weighted techniques are useful in detecting focal and that T2 weighted techniques are useful in detecting mixed hepatic lymphoma. Conventional image derived relaxation time measurements and quantitative parameters were of no additional diagnostic value.

Hepatic metastases: rat models for imaging research.

Improved rat liver tumor models with solitary or multiple metastatic tumors were developed for radiological imaging research. Unlike previous studies which employed trocar inoculation of tumor fragments, an enzymatically disaggregated cell suspension of mammary cancer was injected by fine needle either directly into the liver to produce solitary cancer nodules, or indirectly via the spleen or mesenteric vein to produce multiple liver metastases. Tumor size was proportional to the time elapsed after implantation. The operative mortality of direct liver, splenic parenchymal, and mesenteric inoculations were 8%, 4%, and 27%, respectively. MR tissue characteristics, image contrast, and pharmaceutical enhancement of these tumors closely resembles human hepatic metastases. The availability of reproducible, inexpensive animal models of metastatic cancer allows efficient evaluation of new liver imaging techniques.

Perfusion characteristics of hepatic cavernous hemangioma using intravenous CT angiography (IVCTA).

Thirty-three patients with 35 proven hepatic cavernous hemangiomas (HCH) were studied with intravenous CT angiography (IVCTA). 15 scans were performed during the first 30 s after bolus (6 ml/s) injection of 50 ml iodinated contrast material. Thereafter 2 scans/min were obtained up to 30 min. Three criteria were utilized at IVCTA to make a specific diagnosis of HCH: (1) detection of an intense mural nodular enhancement in the arterial phase. The density in the nodular region(s) should have a density level similar to that of the aorta or hepatic arteries; (2) well-defined nodular area(s); and (3) centripetally oriented enlargement of the nodular region(s). These criteria were seen in 31 of 35 hemangiomas. In contrast the 'typical' Freeny-Marks criteria were present in only 23 of 35 hemangiomas. The results show that our criteria may provide greater specificity.

[Abscess and intra-abdominal fluid collections. Diagnosis and percutaneous drainage]. / Abcès et collections liquidiennes intra-abdominales. Diagnostic et drainage percutané.

The diagnosis of intraabdominal abscess or fluid collections is considerably helped by the precise anatomic delineation yielded by ultrasound and CT-scan. However, the lack of complete specificity of these modalities necessitates needle aspiration for diagnosis. The indications of CT-scan or US guided percutaneous drainage have been expanded with operator experience. Most of intra-abdominal collection, purulent or not, intra or retroperitoneal can be percutaneously treated. Percutaneous drainage can either replace surgery or "temporarize" a critically ill patient until he is able to undergo surgical treatment.