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D D Stark

Publications and source records attributed to D D Stark.

At least 37 records · Page 2Linked to original sources

Hepatic cirrhosis and hepatitis: MR imaging enhanced with superparamagnetic iron oxide.

Superparamagnetic iron oxide was applied as a reticuloendothelial contrast agent in the diagnosis of cirrhosis and hepatitis in seven patients. Three patients had compensated cirrhosis, and four had active hepatitis. T1- and T2-weighted spin-echo magnetic resonance images were obtained before and 1 hour after the administration of iron oxide. Eight patients without diffuse liver disease served as a control group. Normal liver tissue showed a 75% +/- 9% reduction in signal intensity after the administration of iron oxide, and the liver appeared homogeneously hypointense. Cirrhotic liver tissue showed a smaller response (P less than .05) to iron oxide, with a 52% +/- 13% reduction in liver signal intensity. Inhomogeneous structures could be observed in enhanced images and are thought to represent fibrous bands or regenerating nodules. Liver tissue with active hepatitis showed a markedly reduced response to iron oxide (11% +/- 2%) (P less than .05), and the parenchyma appeared homogeneous. The authors conclude that the uptake of iron oxide particles is inhomogeneously altered in cirrhosis because of structural changes and homogeneously decreased in hepatitis because of functional changes of hepatic parenchyma.

Contrast Media↗

First clinical trial of a new superparamagnetic iron oxide for use as an oral gastrointestinal contrast agent in MR imaging.

The authors report the results of preclinical testing and initial clinical application of a superparamagnetic iron oxide specifically prepared as a contrast agent for magnetic resonance (MR) imaging of the gastrointestinal tract. MR imaging was performed at 0.6 and 1.5 T in 15 volunteers. Images of the upper abdomen and pelvis were obtained before and after ingestion of the contrast material at doses of 22.5-225.0 mg of iron in 600-900 L. Two readers scored the images. Delivery of contrast material into the proximal and distal small bowel, with obvious loss of signal intensity (T2 enhancement), was achieved in all subjects. Enhanced images showed improved delineation of the head and tail of the pancreas, anterior margins of the kidneys, and paraaortic region. The contrast agent did not generate artifacts, an improvement over prototype formulations evaluated previously in animals. Except for a brief episode of diarrhea in five subjects, the agent was well tolerated. Use of this contrast agent improved the diagnostic quality of abdominal MR images by enabling the distinction of the bowel from nonbowel structures at concentrations that did not produce image distortion.

Adult↗

Hepatic tumors: quantitative tissue characterization with MR imaging.

To determine which quantitative methods of image analysis are most suitable for the differential diagnosis of benign and malignant hepatic lesions, the authors analyzed magnetic resonance images obtained at 0.6 T in 42 patients with proved hepatic cavernous hemangioma and 63 patients with various hepatic malignancies. The lesion-liver signal-intensity ratio for images obtained with a repetition time of 2,350 msec and echo time of 180 msec was most helpful in distinguishing hemangiomas from cancer (area under the receiving operator characteristic curve [ROC] = 0.99 +/- 0.005). All 38 lesions with lesion-liver signal-intensity ratios greater than 3.5 were hemangiomas, whereas all 57 hepatic tumors with a ratio less than 2.5 were malignant neoplasms. A specificity of 93% and sensitivity of 89% can be achieved with use of quantitative signal-intensity data only. The authors conclude that in conjunction with heavily T2-weighted pulse sequences, signal-intensity ratios are an important adjunct to morphologic analysis in the differential diagnosis of hepatic neoplasms.

Adult↗

Localization of P-31 MR signal with use of superparamagnetic iron oxide particles.

Volume localization of magnetic resonance signals was achieved by using the regional susceptibility differences produced by superparamagnetic iron oxide particles. In vitro experiments demonstrated a direct linear relationship between the concentration of particulate iron and phosphorus-31 chemical shift or line broadening. In vivo experiments indicated that an intravenous dose of 5-10 mg of iron per kilogram of body weight suppressed P-31 signal from normal liver in healthy rats. In rats with hepatic implants of mammary adenocarcinoma, superparamagnetic iron oxide particles suppressed detectable P-31 or hydrogen-1 signal arising from healthy liver tissue, but not that from tumor. Signal due to surface tissues, which affect surface-coil spectra, could be selectively suppressed with a film-based application of particles to the abdominal wall. Thus, P-31 spectra from simulated or actual lesions could be selectively detected after chemically suppressing signals from neighboring or surrounding tissue.

Adenosine Triphosphate↗

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↗

Iron oxide-enhanced MR imaging of the liver and spleen: review of the first 5 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 phagocytic Kupffer cells of the reticuloendothelial system (RES) but are not retained in tumor tissue. Consequently, there is a fivefold 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 detectability in the liver and spleen on 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 mumols Fe/kg body weight. In the United States, SPIO compounds evaluated to date are still approved for use in investigational studies only. Newer commercial formulations currently being evaluated may extend clinical safety margins.

Animals↗

Clinical use of a nonferromagnetic needle for magnetic resonance-guided biopsy.

Five patients who had liver lesions detected by magnetic resonance (MR) and/or computed tomography (CT) were biopsied using MR guidance with a specially designed nonferromagnetic needle. The 20-gauge needle was constructed from Type 316 stainless steel in order to maximize needle visibility and minimize needle-tip artifact. In all cases adequate tissue was obtained for diagnosis and no side effects were observed during the biopsy or on clinical follow-up despite the fact that the needle was within the patient in MR for an average of 30 min.

Biopsy, Needle↗

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↗

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↗

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↗

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↗

Forty-millisecond MR imaging of the abdomen at 2.0 T.

The ability of an ultrafast magnetic resonance (MR) imaging technique to provide abdominal MR images free of motion artifacts was studied. Individual T2-weighted transverse MR images were acquired in as little as 40 msec on a whole-body system operating at 2.0 T. Clinical evaluation was undertaken with fat-suppressed images in which only protons of water molecules contributed to image signal intensity. The ultrafast MR images were compared with conventional MR images obtained at 0.6 T. In 22 patients and two healthy volunteers, ultrafast MR images were of diagnostic quality and free of motion artifacts. Images obtained at an echo time (TE) of 30 msec (imaging time, 40 msec) had liver signal-to-noise ratios of 56.3 +/- 22.6 (n = 19). Because of a smaller data matrix, ultrafast MR images had soft-tissue interfaces that were less sharp than those of the highest-quality conventional MR images in which no motion artifacts were present. However, ultrafast MR images demonstrated high T2-dependent soft-tissue contrast, and pathologic and normal anatomies were readily detected with both imaging techniques. This ultrafast imaging technique has significant promise in whole-body MR imaging, in which motion artifacts often degrade image quality.

Abdomen↗

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↗

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↗

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↗

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↗