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Biomedical subjects

J Wittenberg

Publications and source records attributed to J Wittenberg.

At least 55 records · Page 3Linked to original sources

Imaging of pancreatic neoplasms: comparison of MR and CT.

Thirty-two patients with pathologically proved pancreatic carcinomas or cystadenomas were evaluated with MR images obtained with T1-weighted spin echo (short TR/short TE), inversion recovery, and T2-weighted spin-echo (long TR/long TE) pulse sequences. CT was used as the reference standard to determine the ability of MR to delineate normal and abnormal pancreatic anatomy and thereby to exclude or detect pancreatic malignancy. Short TR/short TE spin-echo sequences were significantly better (p less than .05) than inversion recovery or T2-weighted spin-echo sequences in resolution of both normal and abnormal anatomy. Resolution of pancreatic anatomy correlated (r = .9) with the image signal-to-noise ratio. In seven (22%) of 32 cases, MR visualized pancreatic tumors better than CT did because it showed a signal intensity difference between the tumor and normal pancreatic tissue. Overall, the slight superiority of MR over CT for tumor visualization tended to occur in larger tumors and was not statistically significant. On T1-weighted images, 63% (20 of 32) of pancreatic tumors studied had lower signal intensities than normal pancreatic tissue, whereas on T2-weighted sequences (TE = 60, 120, and 180 msec) only 41% (13 of 32) of tumors had increased signal intensities. Currently available MR imaging techniques offer no significant advantages over CT for evaluating the pancreas for neoplasia.

Adult↗

Gd-DOTA: characterization of a new paramagnetic complex.

The relaxivity, biodistribution, and toxicity of the gadolinium-tetraazacyclododecanetetraacetic acid (Gd-DOTA) complex were evaluated. This cyclic complex has much greater in vitro stability (10(28)) than similar noncyclic complexes such as gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) (10(23)) or gadolinium-ethylenediaminetetraacetic acid (Gd-EDTA) (10(17)). The T1 relaxivity of Gd-DOTA (meglumine salt) determined in saline and in liver tissue at 20 MHz was similar to the relaxivity of Gd-DTPA. Tissue proton relaxation enhancement (PRE) correlated closely with chemical measurement of tissue gadolinium concentration. In rats, the biodistribution of Gd-DOTA was similar to Gd-DTPA with a distribution half-life of 3 minutes and an elimination half-life of 18 minutes. The median lethal dose (LD50) in mice of Gd-DOTA was 93% higher than that of Gd-DTPA; the calculated safety factor (ratio of LD50 to effective dose) was 53 for Gd-DOTA and 28 for Gd-DTPA. The data suggest that in vitro stability correlates with in vivo safety.

Animals↗

Hepatic micrometastases in the rat: ferrite-enhanced MR imaging.

A rat tumor model was used to evaluate the ability of ferrite-enhanced magnetic resonance (MR) imaging to demonstrate hepatic metastases smaller than 1 cm. Twenty-eight rat livers were inoculated with 5 X 10(5) mammary carcinoma cells and imaged with a 0.6-T MR system. Non-enhanced and ferrite-enhanced images were analyzed and correlated with autopsy findings for each rat. Lesion detection rates correlated closely with cancer-to-liver contrast-to-noise ratios. Ferrite-enhanced MR imaging demonstrated significantly more lesions than non-enhanced imaging (P less than .05) and decreased the threshold size for lesion detectability (less than 2 mm). Ferrite also enabled more accurate measurements of the lesions (r = .96).

Animals↗

Complicated pancreatic abscesses: problems in interventional management.

Twenty-five patients with grade D or E pancreatitis underwent percutaneous drainage. These patients required multiple computed tomography (CT) examinations, multiple catheter insertions, multiple catheter manipulations, and long-term catheter drainage. Eight of the 25 patients were successfully treated with catheter drainage alone. Sixteen underwent surgical drainage, ten after attempts at percutaneous drainage and six prior to radiologic drainage. Of the ten patients who had initial percutaneous drainage, only four were clinically improved from the drainage procedure alone. Although the fluid component of the abscess was often adequately drained in all ten patients, surgery was required to remove pieces of necrotic debris. Six patients who underwent surgical debridement had residual abscesses in the post-operative period and were all successfully treated with percutaneous drainage. One patient died from unrelated causes. Successful interventional management of patients with pancreatic abscesses requires intensive radiologic intervention and monitoring and may be better served by a combination of radiologic and surgical means.

Abscess↗

Superparamagnetic iron oxide: clinical application as a contrast agent for MR imaging of the liver.

Superparamagnetic iron oxide (ferrite) particles were evaluated as a contrast agent for magnetic resonance (MR) imaging. In this pilot study, doses ranging from 10 to 50 mumol/kg were administered intravenously to 15 patients. Ferrite-enhanced images of the liver obtained with standard pulse sequence techniques significantly increased the number of hepatic lesions detected (P less than .01) and reduced the threshold size for detection to 3 mm (P less than .01). The improved clinical performance of ferrite-enhanced images correlated with significant increases in measured contrast-to-noise ratios (P less than .01). Degradation of superparamagnetic activity and/or clearance of ferrite from the liver was demonstrated as early as 12 hours after injection, suggesting that the lack of chronic toxicity observed in animal studies may be reproduced in humans. These initial clinical results appear to confirm extensive preclinical data indicating that ferrite administered at a dose of 20 mumol/kg has the potential to significantly improve the performance of abdominal MR imaging.

Adult↗

Superparamagnetic iron oxide: enhanced detection of focal splenic tumors with MR imaging.

Superparamagnetic iron oxide (AMI-25), a reticuloendothelial cell-specific contrast agent for magnetic resonance (MR) imaging, was evaluated for its ability to permit detection of splenic metastases in 18 patients. Superparamagnetic iron oxide, at a dose of 30 mumol of iron per kilogram, decreased the signal intensity of spleen from 19.5 +/- 4.8 to 3.1 +/- 2.2 (spin-echo sequence, repetition time msec/echo time msec = 1,500/42; P less than .05), without changing the signal intensity of tumor. As a result, the tumor-spleen contrast-to-noise ratio increased from 0.2 (tumor isointense relative to spleen) to 18.0 (tumor hyperintense relative to spleen). As a consequence of increased contrast, splenic tumors were detected in four of 18 patients (45 individual lesions; P less than .05), whereas nonenhanced MR imaging permitted detection of splenic lesions in only two of 18 patients (four individual lesions). Maximum tumor-spleen contrast was achieved within 60 minutes after intravenous administration. These initial clinical results indicate that MR imaging with superparamagnetic iron oxide may offer improved accuracy in the diagnosis of splenic tumors.

Adenocarcinoma↗

Pyogenic liver abscess: contrast-enhanced MR imaging in rats.

MR imaging was used to evaluate experimentally induced pyogenic liver abscesses in an animal model. Rats were examined before and after IV administration of either gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA), ferrite particles, or both contrast agents together. Pyogenic liver abscesses appeared hypointense on T1-weighted images and hyperintense on T2-weighted images. Bolus administration of Gd-DTPA using a fast spin-echo sequence with repetition time of 250 msec and echo time of 20 msec (SE 250/20) showed transient selective enhancement of normal hepatic tissue and increased lesion conspicuity, quantitatively assessed by the contrast-to-noise ratio, which increased from -35.7 to -59.0. Delayed leakage of Gd-DTPA into the abscess center partially obscured small lesions at 30-60 min. Ferrite particles reduced the signal intensity of normal liver, and the abscess then appeared homogenously hyperintense. Applying the SE 500/32 sequence, the contrast-to-noise ratio increased from -1.2 to +74.0. Coordinated administration of both contrast agents showed a further increase in contrast to +94.0, with a hyperintense abscess rim surrounded by hypointense liver. Gd-DTPA increases abscess-liver contrast by rim enhancement of the abscess wall, and ferrite increases the abscess-liver contrast by selectively decreasing the signal intensity of surrounding normal liver. As a result of increased contrast-to-noise ratio, both contrast agents, alone or in combination, increase the conspicuity of hepatic abscesses.

Animals↗

Dual-contrast MR imaging of liver cancer in rats.

MR contrast agents increase hepatic tumor conspicuity, as measured in terms of contrast-to-noise (C/N) ratios. With an animal model of hepatic metastases from breast cancer, IV administration of Gd-DTPA (0.2 mmol/kg) shows a biphasic time response, transiently increasing the signal intensity of liver relative to tumor, with C/N ratio magnitudes increasing from -5.7 to -16.3 (SE 250/20); after a delay, the signal intensity of tumor increases relative to liver with a reversal of the C/N sign from negative to positive and an increase in the C/N magnitude to +25.0. IV administration of ferrite particles (0.05 mmol Fe/kg) shows a monophasic time response, increasing signal intensity of tumor relative to liver from +1.5 to +49.5 (SE 500/30). When both contrast agents were administered together (dual-contrast technique), the tumor-liver C/N magnitude reached a maximum of +67.8 (SE 500/30) 12 min after drug infusion. Analysis of individual contrast and noise factors contributing to this technique revealed a strong correlation between the signal intensity of liver and the signal intensity of ghost artifacts, which increase after administration of Gd-DTPA (r = .89) and decrease after administration of ferrite (r = 1.0). Dual-contrast imaging shows a synergistic addition of contrast and suppression of noise from ghost artifacts, maximizing the C/N and increasing the conspicuity of focal liver lesions.

Animals↗

Differentiation of hepatic metastases from hepatic hemangiomas and cysts by using MR imaging.

T1-weighted and T2-weighted pulse sequences were employed for MR imaging of hepatic metastatic tumors (98 patients), hemangiomas (24 patients), and cysts (seven patients); a 0.6-T superconducting magnet was used. In a retrospective study, signal intensity and morphology were used to establish criteria for differentiating metastases from hemangiomas and cysts. The signal intensity of the lesion alone failed to be an etiologic discriminator because over 96% of all masses had a signal intensity less than that of liver on T1-weighted sequences, and at least 90% had a signal intensity greater than that of liver on T2-weighted sequences. Morphologic features depicted on T2-weighted images were more specific than those depicted on T1-weighted images in differential diagnosis. Amorphous, target, and halo signs and a change in morphology were present only in metastatic disease, with a frequency of 45%, 27%, 13%, and 12%, respectively. Two other morphologic patterns--doughnut and lightbulb signs--were found to have overlapping causes. Overall, at least one of the specific signs was observed in 92% of patients with metastatic disease. These data suggest that T2-weighted pulse sequences are essential for discriminating between hepatic metastases and hepatic hemangiomas and cysts. MR imaging is a promising technique for distinguishing these lesions.

Cysts↗

Severe acute pancreatitis after percutaneous biopsy of the pancreas.

A retrospective review of 184 pancreatic biopsies in 178 patients was performed to assess the prevalence of severe postbiopsy pancreatitis. The size, contour, and pathology of the lesions biopsied; the course of the needle (i.e., through bowel or other viscera); the size of the needle; the number of needle passes made; and the guidance technique used were analyzed. Severe pancreatitis developed in five cases (five patients) 5/184 or 3% of the biopsies), usually within 24-48 hr. Three of the five patients who developed pancreatitis had true-negative biopsies (normal pancreas) proved either at surgery (two) or at clinical follow-up (one). The diagnoses for the two remaining patients were adenocarcinomas. In four of the five patients, the diagnosis of severe pancreatitis was made by inspection at surgery. The fifth case was diagnosed by CT. Three patients who underwent surgery and one patient who had percutaneous drainage recovered from the pancreatitis. The fifth patient died despite surgical intervention. All five patients with pancreatitis had masses 3 cm or smaller as compared with the overall group, in which 71 (39%) of the 184 biopsies performed had masses smaller than 3 cm. Overall, 18% of the biopsies were true negative, compared with the 60% true-negative rate in the pancreatitis group. The bowel was transgressed in 21% of all 178 patients, including three of the five pancreatitis patients. We conclude that although the risk of pancreatitis is exceedingly small in percutaneous needle biopsies, it may occur, and at a higher rate than previously reported.

Acute Disease↗

Ferrite particles: a superparamagnetic MR contrast agent for the reticuloendothelial system.

The potential of superparamagnetic ferrite particles as a contrast agent for magnetic resonance (MR) imaging was studied by in vitro MR spectroscopy and in vivo MR imaging in laboratory animals. After aqueous preparations of ferrite particles were administered intravenously, MR spectroscopy showed greatly decreased T2 relaxation times of liver and spleen, with only minimally altered T1, and no changes in lung, kidney, or muscle. Effects occurred within 30 minutes of injection and persisted for more than 6 months. MR imaging with pulse sequences that provide T2-dependent contrast demonstrated that ferrite produced profound signal loss from liver, spleen, and bone marrow. Sequestration of ferrite particles in hepatic reticuloendothelial cells was confirmed by means of light and electron microscopy. Because ferrite has a potent effect on MR signal and exhibits tissue-specific localization, it warrants further study as a contrast agent for MR imaging of the reticuloendothelial system (i.e., liver, spleen, and bone marrow).

Animals↗

Ferrite particles: a superparamagnetic MR contrast agent for enhanced detection of liver carcinoma.

The potential of superparamagnetic ferrite particles to enhance detection of liver carcinoma at magnetic resonance (MR) imaging was studied with in vitro MR spectroscopy and in vivo MR imaging in animal models. After intravenous administration of ferrite, MR spectroscopy showed selective shortening of T2 relaxation times in normal liver but not in tumor. MR imaging showed that ferrite produced profound signal loss only from normal liver and not tumor; thus, differences in signal intensity between liver and tumor were greatly enhanced, especially on pulse sequences with T2-dependent contrast. Motion artifacts were reduced as well because of less signal from liver. Microscopic analysis showed sequestration of ferrite particles in hepatic reticuloendothelial cells but not in hepatocytes or tumor tissue, and there was no evidence of cellular injury. Ferrite particles efficiently and predictably enhance signal differences between normal liver and tumor and permit considerable latitude in selection of pulse sequence and timing parameters. Thus, they have considerable promise as a tissue-specific MR contrast agent for improved detection of liver carcinoma.

Adenocarcinoma↗

Ferrite particles for bowel contrast in MR imaging: design issues and feasibility studies.

Diverse materials with varying physical and magnetic properties have been evaluated as gastrointestinal contrast agents for magnetic resonance (MR) imaging. Uniform marking of the small bowel remains the greatest challenge. Ferrites are magnetically active iron oxide particles that are miscible with water and cause loss of signal on MR images. The decrease in MR signal intensity produced by ferrites occurs with a wide range of iron concentrations (0.1-10 mM) and with both T1- and T2-weighted pulse sequences. These effects of ferrites are explained by predominant T2 shortening with negligible T1 effects. The ferrite preparation used in this study was stable in vitro, with little iron solubilized by acid. Intragastric administration of ferrite (5 mg of iron per kg in 6 ml) routinely marked the small bowel of rats. The authors conclude that ferrites represent a promising new class of contrast agents for gastrointestinal MR imaging.

Animals↗

Hepatic metastases: randomized, controlled comparison of detection with MR imaging and CT.

To determine the accuracy of magnetic resonance (MR) imaging relative to computed tomography (CT) in the diagnosis of liver metastases, a randomized, controlled study was conducted of 135 subjects, including 57 with cancer metastatic to the liver, 27 with benign cysts or hemangiomas, and 51 without focal liver disease. The sensitivity of MR imaging for detecting individual metastatic deposits was 64%, significantly greater than 51% for CT (P less than .001); the difference in sensitivity for identifying patients with one or more hepatic metastases was less (82% for MR imaging vs. 80% for CT). In patients without hepatic metastases, the specificity of MR imaging was 99% versus 94% for CT. Significant differences were found between individual MR pulse sequences in detection of individual lesions. The sensitivity of both T1-weighted spin-echo (SE) (64%) and inversion-recovery (IR) (65%) pulse sequences was significantly (P less than .001) greater than either the TE (echo time) 60 msec (43%) or TE 120 msec (43%) T2-weighted pulse sequences. Overall, the accuracy of a single T1-weighted (10-minute) pulse sequence was superior to that of contrast-enhanced CT.

Adrenal Gland Neoplasms↗

Amebic liver abscess: diagnosis and treatment evaluation with MR imaging.

Magnetic resonance images were obtained before and after treatment in 17 patients with 29 amebic liver abscesses. Pretreatment T1-weighted images showed a sharply circumscribed, heterogeneous, low-signal-intensity mass, devoid of normal hepatic tissue and corresponding to the abscess cavity as measured sonographically. T2-weighted images showed the abscess cavity as a hyperintense region and also showed a larger region of hyperintensity extending from the cavity margins to the liver surface, corresponding to edematous but morphologically normal liver tissue. After treatment, the abscess cavity became homogeneously hypointense on T1-weighted images, corresponding to liquefaction of the abscess center. With successful treatment, concentric rings corresponding to (a) an inner margin of inflamed granulation tissue, (b) bands of type I collagen, and (c) the outer margin of atrophic and/or mildly inflamed liver tissue became prominent on T1- and T2-weighted images. T2-weighted images showed rapid resolution of the perifocal hepatic edema.

Adolescent↗

MR imaging of splenic metastases: ferrite-enhanced detection in rats.

Detection of intrasplenic neoplasms using sonography, CT, and scintigraphy is limited by poor inherent tumor-spleen contrast relative to image noise. Despite the wide range of contrast parameters available for MR imaging, similar limitations have been found with this technique. Magnetopharmaceuticals have the ability to enhance tumor-spleen contrast and improve lesion detectability. In this study, a rodent model of cancer metastasized to the spleen was used to evaluate the potential of superparamagnetic ferrite particles as a tissue-specific reticuloendothelial contrast agent. Other studies have shown ferrite to have little or no toxicity. Without contrast material, metastatic adenocarcinoma of the spleen could not be distinguished from normal splenic parenchyma on in vivo MR images. At a dose of 50 mumol Fe/kg, the T2 relaxation time of spleen decreased by 77%, while tumor T2 was essentially unchanged (p less than .005). Intrasplenic tumors 4-6 mm in size became readily detectable on in vivo MR images after the administration of ferrite particles. Lesion conspicuity, quantitated by the tumor-spleen contrast-to-noise ratio, showed a 43-fold increase. Ferrite particles show great promise as a contrast agent to enhance the detection of focal splenic lesions.

Adenocarcinoma↗