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R Weissleder

Publications and source records attributed to R Weissleder.

At least 145 records · Page 8Linked to original sources
PubMed1990

Receptor imaging: application to MR imaging of liver cancer.

A new contrast agent for magnetic resonance (MR) imaging, directed to asialoglycoprotein (ASG) receptors on hepatocytes, was used for detection of liver cancer in rats. Ultrasmall superparamagnetic (mean size, 12 nm) particles of iron oxide (USPIOs) were targeted to ASG receptors by coating particles with arabinogalactan (AG). Liver T2 relaxation times decreased more effectively after a single intravenous administration of AG-USPIO than after an equal dose of a conventional superparamagnetic liver MR contrast agent (AMI-25; mean size, 72 nm). Receptor affinity studies demonstrated that receptor-mediated attachment and subsequent cellular endocytosis do not occur in primary malignant (hepatocellular carcinoma) or metastatic (adenocarcinoma) tumors, because the surface ASG receptors are lost during malignant dedifferentiation. In vitro relaxation and in vivo MR imaging experiments of liver tumors show that targeting USPIO to hepatocytes rather than to the mononuclear phagocytic system allows a considerable dose reduction, increases tumor-liver contrast, and potentially allows distinction of ASG-positive (benign hepatocellular) and ASG-negative (malignant hepatocellular) tumors.

Animals↗
PubMed1990

Detection of hepatic metastases: comparison of contrast-enhanced CT, unenhanced MR imaging, and iron oxide-enhanced MR imaging.

Diagnostic accuracy of contrast-enhanced CT, unenhanced MR imaging, and MR images enhanced with superparamagnetic iron oxide was evaluated in 10 patients with histologically proved hepatic metastases. First, diagnostic performance of the imaging technique with respect to the ability of radiologists to recognize the presence or absence of a metastasis was measured by using receiver-operating-characteristic (ROC) analysis of single images. Second, the total number of lesions (N = 108) detected by "complete" CT and MR examinations was counted. Finally, lesion-liver contrast-to-noise ratios (CNR) were measured in all MR sequences. The area under the ROC curve was .67 +/- .03 for contrast-enhanced CT, .81 +/- .07 for the unenhanced SE 260/14 sequence, and .92 +/- .01 for the iron oxide-enhanced SE 1500/40 sequence. The enhanced SE 1500/40 sequence yielded significantly (p less than .005) greater accuracy than did contrast-enhanced CT. The same sequence detected significantly (p less than .05) more lesions than all other imaging techniques (19% more than the best unenhanced MR sequence and 36% more than contrast-enhanced CT). The enhanced SE 1500/40 sequence also yielded the highest CNR value (19.5 +/- 10.2) of all MR sequences. These results indicate that iron oxide-enhanced MR imaging is a superior imaging technique for the detection of hepatic lesions.

Adult↗
PubMed1990

MR receptor imaging: ultrasmall iron oxide particles targeted to asialoglycoprotein receptors.

Previously we have reported that ultrasmall superparamagnetic iron oxide (USPIO) particles migrate across capillary endothelium, a prerequisite for the design of particulate pharmaceuticals for MR receptor imaging. In the current study, USPIO particles are directed specifically to asialoglycoprotein (ASG) receptors by coupling galactose terminals in the form of arabinogalactan (AG) to these particles. Biodistribution data showed that ASG-directed, AG-coated USPIO (AG-USPIO) particles selectively accumulate in the liver but not in other organs. Electron microscopy of liver showed electron-dense iron oxide particles bound to hepatocyte cell-surface membranes and in large numbers within intracellular lysosomes. The specificity of AG-USPIO for asialoglycoprotein receptors was confirmed by incubation experiments with and without ASG-blocking agents such as D(+)galactose and asialofetuin. In vivo MR imaging in rats showed a significant decrease in liver signal intensity at low doses (2 mumol Fe/kg); no significant changes were observed in the spleen. This decrease in signal intensity is larger than that observed with conventional iron oxides at equal doses. These initial data suggest that, for the first time, superparamagnetic agents can be directed to specific sites for MR imaging by strategies such as receptor targeting.

Animals↗
PubMed1989

Interstitial lymphangiography: initial clinical experience with a dimeric nonionic contrast agent.

Interstitial lymphangiography performed with intradermal injection of a new nonionic dimeric contrast agent was used to examine 34 normal lower extremities and 35 lower extremities with proved lymphedema. An infusion pump was used to inject 2 mL of the contrast agent into the intradermal interdigital space at a rate of 0.1 mL/min. In all normal extremities, the injection deposit appeared homogeneous, and one to five lymph vessels could be identified. Diffusion of contrast agent into perilymphatic tissue occurred 30-40 cm proximal to the injection site; inguinal lymph nodes were, therefore, not routinely visualized. The findings at interstitial lymphangiography were abnormal in all extremities with advanced lymphedema. The results indicate that interstitial lymphangiography with the use of a nonionic dimeric contrast agent allows morphologic assessment of lymphatic vessels and facilitates the diagnosis of lymphatic obstructive disease.

Adolescent↗
PubMed1989

Central scars in primary liver tumors: MR features, specificity, and pathologic correlation.

Tumor scars were identified at pathologic study and magnetic resonance (MR) imaging in ten of 17 (59%) primary liver tumors (nine hepatocellular carcinomas, four giant hemangiomas, two hepatic adenomas, and two cases of focal nodular hyperplasia). Histopathologic examination revealed three types of scar tissue. Inflammatory scars (n = 4), with edema, necrosis, hypercellularity, and loose fibrous tissue, appeared hypointense relative to liver on T1-weighted images and hyperintense on T2-weighted images. Vascular scars (n = 3), predominantly composed of vascular channels traversing collagenous tissue, showed MR features similar to those of inflammatory scars. Collagenous scars (n = 3) appeared hypointense relative to liver on both T1-weighted and T2-weighted images. Central tumor scars are a frequent but nonspecific feature of both benign and malignant primary liver tumors.

Adult↗
PubMed1989

Short TI inversion-recovery imaging of the liver: pulse-sequence optimization and comparison with spin-echo imaging.

Magnitude-reconstructed short inversion-time (TI) inversion-recovery (IR) sequences have the advantage of reducing the signal of fat while providing additive T1 and T2 contrast. A double-echo short TI IR sequence was implemented to offer different degrees of T1- and T2-dependent image contrast. In 50 consecutive patients with proved liver tumors (30 metastases, 13 hemangiomas, seven other primary liver tumors), images obtained with a double-echo IR sequence at a repetition time (TR) of 1,500 msec, echo time (TE) of 30 and 60 msec, and TI of 80 msec (TR/TE/TI = 1,500/30, 60/80) were compared with those obtained with spin-echo (SE) sequences at a TR of 275 msec and a TE of 14 msec (TR/TE = 275/14) and 2,350/60, 120, 180. Metastases-liver contrast-to-noise ratios were highest at SE 275/14, followed by IR 1,500/30/80 and SE 2,350/180. IR 1,500/30/80 and SE 275/14 sequences consistently showed higher sensitivity for the detection of metastases than T2-weighted SE sequences. Differential diagnosis of benign and malignant lesions was more reliable with T2-weighted SE sequences than T2-weighted short TI IR sequences.

Adult↗
PubMed1989

Experimental lymph node metastases: enhanced detection with MR lymphography.

Magnetic resonance (MR) lymphography with superparamagnetic iron oxide (AMI-25) as a contrast agent was developed in an animal model with tumor-bearing lymph nodes. After interstitial administration of 20 mumol of iron per kilogram of body weight into the footpads of rats, the T2 of popliteal and paraaortic lymph nodes decreased from 67 msec +/- 8.2 to 9.5 msec +/- 0.9 and 9.3 msec +/- 0.9, respectively. T2 relaxation times of lymph nodes containing metastases showed a significantly higher value (61 msec +/- 6.2, P less than .005) after interstitial administration of the contrast agent. Intravenous administration of AMI-25 did not produce enhancement of normal or metastatic lymph node relaxation times. The signal intensity of normal lymph nodes decreased profoundly on spin-echo MR images (repetition time of 500 msec, echo time of 30 msec) after interstitial administration, whereas lymph nodes with metastases showed no significant change in signal intensity. Experimental results indicate that MR lymphography may potentially increase the sensitivity of MR imaging the detection of lymphatic malignancy.

Animals↗
PubMed1989

Superparamagnetic iron oxide-enhanced MR imaging: pulse sequence optimization for detection of liver cancer.

The effects of magnetic resonance (MR) pulse sequences and timing parameters on tumor-liver contrast were studied in an animal model of metastatic liver cancer. Six spin-echo (SE), three inversion-recovery (IR), and four gradient-echo (GRE) sequences were evaluated at 0.6 T before and after injection of super-paramagnetic iron oxide. GRE techniques, irrespective of echo time and flip angle, showed the greatest change in signal intensity (enhancement) of the liver after administration of iron oxide. Single-acquisition GRE sequences (16 seconds) matched the contrast-to-noise ratio (C/N) performance of the most effective 6.4-minute SE sequences. Multiexcitation GRE sequences showed tumor-liver C/Ns per unit time that were significantly (P less than .05) higher than those achieved with SE and IR sequences. GRE sequences, which recruit intravoxel dephasing as an additional source of transverse relaxation enhancement (T2*), show a higher C/N per unit time and in this respect seem superior to SE and IR sequences for MR imaging with superparamagnetic iron oxide.

Animals↗
PubMed1989

Superparamagnetic iron oxide: pharmacokinetics and toxicity.

The pharmacokinetics (distribution, metabolism, bioavailability, excretion) and toxicity (acute and subacute toxicity, mutagenicity) of a superparamagnetic iron oxide preparation (AMI-25), currently used in clinical trials, were evaluated by 59Fe radiotracer studies, measurements of relaxation times, the ability to reverse iron deficiency anemia, histologic examination, and laboratory parameters. One hour after administration of AMI-25 to rats (18 mumol Fe/kg; 1 mg Fe/kg), 82.6 +/- 0.3% of the administered dose was sequestered in the liver and 6.2 +/- 7.6% in the spleen. Peak concentrations of 59Fe were found in liver after 2 hr and in the spleen after 4 hr. 59Fe slowly cleared from liver (half-life, 3 days) and spleen (half-life, 4 days) and was incorporated into hemoglobin of erythrocytes in a time-dependent fashion. The half-time of the T2 effect on liver and spleen (24-48 hr) was shorter than the 59Fe clearance, indicating metabolism of AMI-25 into other forms of iron. IV administration of AMI-25 (30 mg Fe/kg) corrected iron-deficiency anemia and showed bioavailability similar to that of commercially available IV iron preparations within 7 days. No acute or subacute toxic effects were detected by histologic or serologic studies in rats or beagle dogs who received a total of 3000 mumol Fe/kg, 150 times the dose proposed for MR imaging of the liver. Our results indicate that AMI-25 is a fully biocompatible potential contrast agent for MR.

Animals↗
PubMed1989

The diagnosis of splenic lymphoma by MR imaging: value of superparamagnetic iron oxide.

This study was designed to evaluate superparamagnetic iron oxide (AMI-25) as a contrast agent for MR to distinguish normal spleens from those diffusely infiltrated by lymphoma. As diffuse splenic involvement lacks visible tumor-tissue boundaries, signal-intensity measurements of spleens were used as a diagnostic criterion in 33 patients (lymphoma, n = 8; benign splenomegaly, n = 5; normal subjects, n = 20). Unenhanced MR images were insensitive (four of eight patients) and nonspecific (20 of 25 patients) in the diagnosis of lymphoma. After injection of superparamagnetic iron oxide (40 mumol Fe/kg), lymphomatous spleens showed a significantly higher signal intensity (p less than .05) than did normal spleens or spleens enlarged by benign disease (hepatic cirrhosis, n = 4; spherocytosis, n = 1). Changes in splenic MR signal intensity unambiguously identified eight of eight lymphomatous spleens and 25 of 25 normal or enlarged spleens that did not contain lymphoma. Phagocytosis of superparamagnetic iron oxide in lymphomatous spleens is reduced because of diffuse displacement of splenic macrophages by lymphoma cells and/or by immunologic suppression of macrophage activity. Our results suggest that superparamagnetic iron oxide (AMI-25) can improve the accuracy of MR imaging in the diagnosis of splenic lymphoma. With further development, this noninvasive technique may reduce the need for diagnostic splenectomy in lymphoma patients.

Contrast Media↗
PubMed1989

Primary liver tumors: diagnosis by MR imaging.

MR features of 153 proved primary liver tumors (95 malignant, 58 benign) in 55 patients with hepatocellular carcinoma (21), cholangiocarcinoma (seven), carcinosarcoma (one), hepatoblastoma (one), hemangioma (16), hepatic adenoma (four), focal nodular hyperplasia (three), leiomyoma (one), and hemangioendothelioma (one) were studied retrospectively to determine which techniques are most reliable for lesion detection and which criteria are most useful for differential diagnosis. MR data were correlated with histologic features such as fatty degeneration, fibrosis, and peritumoral edema. Unlike metastatic cancer, hepatocellular carcinoma was best detected (p less than .01) with T2-weighted pulse sequences. The mean tumor-liver T2 difference was 34.4%, while the mean T1 difference was only 21.8%. A tissue-specific diagnosis of hepatocellular carcinoma was possible in 14 of 21 patients by identification of fatty degeneration of the tumor (eight of 17), tumor capsule (five of 21), and/or vascular invasion (six of 21). MR features of peritumoral edema, present in six of 21 patients with hepatocellular carcinoma and in seven of 25 patients with metastases, were exclusively associated with malignant tumors. The large variation in tissue characteristics (relaxation times and proton density) seen in primary liver tumors necessitates the use of multiple pulse sequences to maximize lesion detection. However, the combined use of T1- and T2-weighted spin-echo and T2-weighted phase-contrast images had the advantage of distinguishing benign from malignant primary liver tumors in 48 of 55 patients in this series.

Adenoma↗
PubMed1989

Detection of hepatic metastases with MR imaging: spin-echo vs phase-contrast pulse sequences at 0.6 T.

The purpose of this study was to compare the sensitivity of T1-weighted and T2-weighted spin-echo (SE) pulse sequences with T2-weighted phase-contrast (PC) imaging techniques for the detection of hepatic metastases. Pulse-sequences performance was evaluated in 52 consecutive patients with 88 hepatic metastases who underwent MR imaging at 0.6 T. Lesion-liver contrast-to-noise ratios (CNR) on SE 260/14 (-12.4 +/- 6.7) and PC 2350/60 (+10.8 +/- 4.2) images were significantly (p less than .05) greater than on SE 2350/60 (+ 7.8 +/- 3.9), SE 2350/120 (+8.1 +/- 4.8), SE 2350/180 (+7.9 +/- 4.5), and PC 2350/30 (+4.6 +/- 2.9) images. Sensitivity for detection of 88 individual metastases was comparable on SE 260/14 (78 of 88 patients) and PC 2350/60 (81 of 88 patients) images and was significantly (p less than .05) greater than on in-phase T2-weighted SE images (TE = 60, 70 of 88 patients; TE = 120, 69 of 88 patients; TE = 180, 65 of 88 patients). Histologic analysis of tumor-free liver showed fatty change in 11 of 13 specimens available for pathologic evaluation. In all 11 of those patients, PC images increased tumor-liver contrast in comparison with the in-phase SE images. This analysis suggests that for detection of hepatic metastases at midfield strengths, the T1-weighted, short TR/short TE (SE 260/14) and the T2-weighted, phase-contrast (PC 2350/60) pulse sequences offer comparable performance.

Adult↗
PubMed1989

Magnetic resonance imaging of liver tumors.

Careful optimization of scanning techniques, particularly motion artifact suppression, has been essential to achieve reproducible results in abdominal MRI. The investigators experience indicates that MRI can be more accurate than other imaging methods for the detection of focal liver lesions. Furthermore, MRI is able to solve the major clinical problems in differential diagnosis of benign and malignant liver lesions: cancer v cavernous hemangioma or focal fat. MRI has reduced the dependence on liver biopsy and angiography to diagnose and stage focal liver lesions. Unfortunately, both imaging techniques, especially motion artifact suppression methods, vary widely among machines operating at different field strengths. Therefore, as hardware and software evolve, it is necessary to retrace the steps of pulse sequence optimization and clinical testing. Hopefully, in the future, standardized imaging techniques will become available for body MRI.

Adenoma, Bile Duct↗
PubMed1988

Splenic lymphoma: ferrite-enhanced MR imaging in rats.

Ferrite, a new magnetic resonance (MR) contrast agent, was evaluated in the detection and diagnosis of splenic lymphoma. Before administration of ferrite, normal rat spleens and spleens with diffuse lymphoma showed similar in vitro relaxation times and in vivo MR imaging signal-to-noise ratios (S/N). After the administration of ferrite (50 mumol Fe/kg), the T2 time of lymphomatous spleen was 27.0 msec +/- 2.9 (mean +/- standard deviation), which was significantly greater than that of normal spleen (10.7 msec +/- 1.5, P less than .005). The S/N of ferrite-enhanced in vivo MR images of lymphomatous spleen was 12.4 +/- 0.9, which was significantly greater than normal (5.7 +/- 0.2, P less than .005). Similar experiments with animal models of micronodular lymphoma also demonstrated that ferrite-enhanced MR imaging can distinguish micronodular lymphoma from normal spleen. Benign splenomegaly, studied with an animal model of erythroid hyperplasia, showed ferrite-enhanced MR tissue characteristics that were indistinguishable from those of normal spleen.

Animals↗