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Biomedical subjects

R Weissleder

Publications and source records attributed to R Weissleder.

At least 163 records · Page 9Linked to original sources
PubMed1988

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↗
PubMed1988

Lymphedema: evaluation of qualitative and quantitative lymphoscintigraphy in 238 patients.

Lymphoscintigraphy was performed in 128 patients with primary lymphedema, in 91 patients with secondary lymphedema, and in 19 healthy volunteers. A total of 457 extremities were examined. Technetium-99m-labeled human serum albumin was injected subcutaneously, and passive muscular exercise was standardized to reduce the variability of lymphatic function. The scintigrams were analyzed for visualization of lymph vessels and lymph nodes, dilatation of lymphatic vessels, existence of collateral vessels, and dermal backflow. With this qualitative interpretation alone, the diagnosis of lymphedema was established in 216 of 308 extremities (70.1%). Quantitative parameters derived from clearance data showed abnormal lymphatic function in all 308 extremities. Whereas qualitative lymphoscintigraphy allows the characterization of lymphatic morphology, quantitative lymphoscintigraphy is very accurate in detection of incipient lymphedema.

Adolescent↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

MR imaging of focal splenic tumors.

This study was undertaken to define the MR appearance of splenic tumors in 16 cancer patients with focal splenic lesions; 50 volunteers and liver cancer patients without splenic abnormalities served as controls. In 14 patients with focal splenic lesions, differences between splenic and lesion signal intensities permitted detection of splenic lesions on MR images, either because of cystic or necrotic areas lengthening T2 within the tumor, because of T1 shortening from tumor-associated hemorrhage, or because of T2 shortening of surrounding spleen in two cases of suspected transfusional iron overload. In one spleen, a lesion appeared isointense on both T1- and T2-weighted pulse sequences and was detected only by gross splenic deformity. In one other case, CT defined splenic metastases not visible on MR images. Measurements of signal intensity of normal spleens and tumor are so similar that spin-echo MR imaging can underestimate the size and extent of focal splenic disease or may miss lesions entirely. We conclude that MR imaging is a less sensitive technique for detecting focal lesions of the spleen than for detecting focal hepatic lesions.

Adult↗
PubMed1988

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↗
PubMed1988

[Magnetic resonance tomography of focal liver and spleen lesions. Experiences using ferrite, a new RES-specific MR contrast medium].

Superparamagnetic iron oxide (ferrite), a novel, reticuloendothelial cell-specific contrast agent used for magnetic resonance imaging (MRI), was evaluated in the detection of liver and spleen tumors in animal models and in phase I and II clinical trials in 33 patients. The initial results obtained in experimental cancer models showed a dramatic improvement in tumor detection. Our first clinical trials confirmed the experimental results and showed that ferrite-enhanced MRI significantly (p less than 0.05) increases the detection of individual lesions. Furthermore, the threshold of detectable tumor size decreased significantly, to 3 mm, when standard MR spin echo imaging techniques were used.

Animals↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

Ferrite-enhanced MR imaging of hepatic lymphoma: an experimental study in rats.

The purpose of this investigation was to define the potential of unenhanced and ferrite-enhanced MR to detect hepatic lymphoma. Rats were implanted with diffuse and focal hepatic lymphoma. Both in vitro measurements of relaxation times and in vivo MR imaging of normal liver and of diffuse and focal hepatic lymphoma were compared. Diffuse infiltrative hepatic lymphoma showed increased T1 (45%) and T2 (41%) relaxation times in vitro, but could not be distinguished from normal control livers on in vivo spin echo (SE) images with a repetition time of 500 msec and an echo time of 30 msec (SE 500/30) or SE 1500/60 images. Focal hepatic lymphoma showed increased T1 (185%) and T2 (115%) relaxation times relative to normal liver tissue. Focal hepatic lymphoma was undetectable on unenhanced SE 500/30 MR images (contrast-to-noise ratio, C/N = 0.4) and was slightly hyperintense on SE 1500/60 images (C/N = 1.1). Ferrite (50 mumol Fe/kg) was administered to improve tissue contrast. In normal control animals, T2 of liver in vitro decreased from 29.3 +/- 3.3 msec to 11.1 +/- 1.2 msec, and image signal-to-noise ratio (S/N) of liver in vivo decreased from 16.1 +/- 2.4 to 2.8 +/- 0.3 (p less than .005). Ferrite-enhanced diffuse hepatic lymphoma showed in vitro T2 values and in vivo MR image S/N values indistinguishable from those of normal control animals. The T2 of focal hepatic lymphoma was essentially unaltered by ferrite. On SE 500/30 images, focal hepatic lymphoma became readily detectable, quantitated by a 35-fold increase in tumor-liver C/N. We conclude that clinical studies are warranted to determine the value of ferrite enhanced MR as a technique for the enhanced detection of focal hepatic lymphoma.

Animals↗
PubMed1987

Sonographic diagnosis of subclavian and internal jugular vein thrombosis.

Seven patients with internal jugular and/or subclavian vein thrombosis were studied with real-time sonography and venography. High-resolution real-time sonography was used to tabulate morphologic parameters (venous size, shape, intraluminal echoes, and presence of collateral veins), as well as physiologic parameters (mobile venous valves, distention, compressibility, pulsation). Chronic venous thrombosis was characterized by the presence of collateral veins, spread of the thrombus to other major veins, and loss of normal vascular landmarks with poor visualization of the actual thrombus, the "cut-off sign." Acute catheter-induced thrombosis was confined to one vessel, and the thrombus was seen clearly in all cases. Two new signs of thrombosis, the absence of the beating venous valve and the "cut-off sign," are particularly useful in the sonographic diagnosis of internal jugular vein thrombosis.

Humans↗
PubMedDate not supplied

Dynamic signal intensity changes in liver with superparamagnetic MR contrast agents.

The dynamic effects of three different superparamagnetic magnetic resonance (MR) contrast agents on liver signal were evaluated with an echo-planar imaging technique. The contrast agents were (a) USPIO (ultrasmall superparamagnetic iron oxide), which has a long blood half-life and was developed for MR imaging of lymph nodes and bone marrow; (b) AG (arabinogalactan)-USPIO, an asialoglycoprotein receptor--directed iron oxide with hepatocyte uptake; and (c) AMI-25, a conventional reticuloendothelial iron oxide agent. Dynamic liver signal intensity (SI) curves reflect different uptake mechanisms for the different agents. Receptor blocking experiments indicate that intracellular redistribution or clustering of the AG-USPIO (known to occur from electron microscopy studies) does not contribute to the decrease in liver SI. Monitoring liver SI over time with echo-planar imaging may provide a better understanding of the kinetics of the growing number of MR contrast agents and allow optimization of imaging protocols to exploit peak enhancement.

Animals↗
PubMedDate not supplied

Polymeric contrast agents for MR imaging of adrenal glands.

A variety of adrenal imaging agents have been used in nuclear medicine, but no agent has been developed for magnetic resonance (MR) imaging. The authors have previously observed accumulation of aminated macromolecules in adrenal glands. They now report the synthesis of a model polymeric aminated contrast agent for enhanced MR imaging of the adrenal glands. The model agent consisted of a poly-L-lysine conjugate (molecular weight, 245 kd) that had 70% free epsilon amino groups and 30% diethylenetriaminepentaacetic acid (DTPA)-derivatized amino groups to bind indium-111 or gadolinium. One hour after intravenous administration of this compound, adrenal uptake was 10.1% +/- 0.7 of injected dose per gram of tissue. When all free epsilon amino groups of the polylysine were completely substituted with DTPA, adrenal uptake was 3.4 times lower, indicating the importance of free amino groups for adrenal uptake. MR imaging in rats showed that a dose of 0.08 mmol of gadolinium per kilogram of the agent was sufficient to enhance the signal intensity of adrenal glands. There hours after intravenous administration of the agent, signal intensity of the adrenal glands was 186% of precontrast values (liver, 165%; kidney, 91%). Fluorescence microscopy showed that the agent accumulated primarily in the cortical zona glomerulosa and in the adrenal medulla. These initial studies demonstrate the feasibility of designing contrast agents for MR imaging of the adrenal glands.

Adrenal Glands↗
PubMedDate not supplied

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.

Animals↗