Relaxation effects of clustered particles.

Relations between spatial distribution of superparamagnetic iron oxide (SPIO) particles and the image contrast caused by SPIO were investigated. Actual clustering pattern of particles was measured in the liver and spleen of animals using intravital laser confocal microscopy. SPIO-doped phantoms with and without Sephadex beads were made to simulate these patterns, and relaxation parameters were measured using a 1.5-T clinical scanner. Finally, these results were compared to clinical image data using SPIO particulate agent. Intravital microscopy indicated that the clustering of latex beads was more predominant in hepatic Kupffer cells than in splenic macrophages (P < 0.001). Phantoms without Sephadex beads showed an approximately linear increase of 1/T1 (R1), 1/T2 (R2) and 1/T2* (R2*) values with increasing SPIO concentration. However, with Sephadex beads, R1 and R2 showed little change with increasing SPIO concentration, while R2* showed the same linear increase with SPIO. Also, the R2* values were higher with Sephadex beads. These results were consistent with the clinical imaging data, where signal reduction was significantly smaller in the spleen (-0.4% +/- 27.4%) than in the liver (50.4% +/- 16.8%, P < 0.00001) on T2*-weighted images, but the reduction in the spleen (47.2% +/- 16.1%) was equivalent to the liver (38.8% +/- 26.0%) on T2-weighted images.

Hepatic iron concentration: noninvasive estimation by means of MR imaging techniques.

PURPOSE: To identify a magnetic resonance (MR) imaging method sufficiently sensitive and specific in the estimation of hepatic iron content to obviate liver biopsy. MATERIALS AND METHODS: Thirty-eight patients underwent percutaneous needle biopsy of the liver with chemical measurement of the hepatic iron concentration and hepatic MR imaging with several spin-echo and gradient-recalled-echo (GRE) techniques. Correlations between MR imaging parameters and the hepatic iron concentration were determined. RESULTS: Inverse curvilinear relationships were noted between several MR parameters and hepatic iron concentrations. GRE sequences with short repetition and echo times were more accurate and precise than spin-echo sequences for the estimation of hepatic iron concentration. A GRE sequence with a repetition time of 18 msec, an echo time of 5 msec, and a flip angle of 10 degrees showed close correlation between the hepatic iron concentration and the natural logarithm of the ratio of the signal intensity of liver to the SD of background noise (r = -0.94) and low coefficient of variation (12%). CONCLUSION: MR imaging with these parameters is a rapid, noninvasive, and accurate modality for estimation of hepatic iron concentration; it is sufficiently accurate and precise to obviate liver biopsy for the purpose of measuring hepatic iron concentration.

Teleradiology: experiences with magnetic resonance imaging using this new technology.

Teleradiology, a term encompassing electronic transmission of images for interpretation, is becoming an important part of telemedicine. Telemedicine is an exciting new electronic means of distributing specific medical knowledge by computer network. Teleradiology allows healthcare providers in locations that previously might not have had this service to access the use of radiology specialists and subspecialists. The combination of more efficiency in interpretation and the availability of high-quality imaging equipment to rural areas will be even more important in the future. The current concepts of teleradiology are discussed, as well as the findings of the authors' investigation of accuracy and agreement of interpretations of magnetic resonance imaging examinations.

Time after excision and temperature alter ex vivo tissue relaxation time measurements.

Previously unreported effects of tissue storage were recently observed in the authors' experimental magnetic resonance (MR) studies. To evaluate the effect of elapsed time after excision and storage temperature on tissue relaxation time measurements, tissue samples from the liver, pancreas, kidney, testis, spleen, and brain were obtained in rats. T1 and T2 were first measured within 5 minutes of excision, and between subsequent measurements, tubes were kept in a water bath at 40 degrees C, at room temperature (28 degrees C), or in an ice bath (4 degrees C). Cellular and organellar integrity was assessed with electron microscopy and correlated with the MR findings. At 40 degrees C (20-MHz spectrometer), the T1 of liver decreased from 280 msec +/- 8 to 212 msec +/- 10 during the first 60 minutes; the T1 of pancreas decreased from 276 msec +/- 3 to 208 msec +/- 2. Other tissues showed less than a 5% decrease in T1. T2 changes were smaller than T1 changes in all tissues. Electron microscopy of pancreatic acinar cells showed postmortem changes in mitochondria evolving over the first 60 minutes after death. Manganese loading experiments implicated mitochondrial manganese stores in the observed enhanced postmortem decrease in T1. This study calls into question reported relaxation time data for liver and pancreas. MR studies of excised tissues must account for time and temperature to prevent systematic experimental errors.

Effects of spatial distribution on proton relaxation enhancement by particulate iron oxide.

The proton relaxation effect of superparamagnetic iron oxide (SPIO) particles under varying conditions of spatial distribution was investigated with use of phantoms. Agar phantoms containing various concentrations of SPIO or gadopentetate dimeglumine, with and without Sephadex beads, were studied. Phantoms with Sephadex had a heterogeneous spatial distribution of iron oxide, comparable to liver tissue in vivo. Relaxometry at 0.47 T showed decreased T2 relaxivity of SPIO in Sephadex phantoms compared with that in agar phantoms without Sephadex. On T2-weighted images obtained at 1.5 T, the signal intensity of Sephadex phantoms showed less SPIO relaxation effect than that of plain agar phantoms. Unlike SPIO, gadopentetate dimeglumine showed the same relaxivities and signal intensity in plain agar and Sephadex phantoms. The results show that the T2 relaxation effect of iron oxide depends on its spatial distribution. A heterogeneous spatial distribution, as in intact liver tissue, diminishes the T2 relaxivity of iron oxide particles.

Contrast-enhanced MR imaging of the liver.

Postcontrast images with a 0.1 mmol/kg dose of a gadolinium chelate with extracellular distribution, when acquired dynamically during breath holding, can improve both differential diagnosis and lesion recognition in liver MR imaging. Initial results at 0.3 mmol/kg, compared with 0.1 mmol/kg, suggest a substantial improvement in lesion identification at the high dose, as assessed by using signal intensity difference divided by noise. Of the gadolinium chelates with predominantly renal excretion, only gadoteridol is presently approved in the United States at the high dose, with limited clinical evaluation for liver imaging performed to date. For linear chelates, such as gadopentetate dimeglumine and gadodiamide injection, the degree to which release of free gadolinium ion occurs is a possible issue because of lower in vivo stability (42,43). Preliminary results with hepatobiliary gadolinium chelates and iron particulate agents are favorable with regard to efficacy, although these agents remain in clinical trials.

Enhanced tumor detection in the presence of fatty liver disease: cell-specific contrast agents.

It is assumed that hepatobiliary, cell-specific contrast agents will be adversely affected by the presence of diffuse liver disease. The diagnostic efficacy for tumor detection in the presence of fatty liver disease was experimentally studied at contrast-enhanced magnetic resonance (MR) imaging with manganese-DPDP (N,N'-dipyridoxylethylenediamine-N,N'-diacetate 5,5'-bis[phosphate]) and gadobenate dimeglumine (Gd-BOPTA/dimeg) and compared with conventional and chemical shift imaging. Carcinosarcoma was implanted into the liver of rats, and fatty liver was induced with L-ethionine. Without contrast agents, the tumor-fatty liver contrast-to-noise ratio (C/N) was increased on T1-weighted and decreased on T2-weighted MR images relative to tumor-bearing control rats without fatty liver. Chemical shift imaging (phase-contrast method) increased the tumor-fatty liver C/N from 2.3 +/- 1.0 to 6.1 +/- 1.7 (P < .001). Mn-DPDP and Gd-BOPTA/dimeg increased the tumor-fatty liver C/N from -5.4 +/- 1.6 to -11.0 +/- 1.9 and -9.8 +/- 3.4, respectively (P < .001). The hepatobiliary, cell-specific contrast agents were equally effective in both fatty and non-fatty liver and outperformed both chemical shift and conventional MR imaging in detecting liver tumors.

Contrast-enhanced MR imaging of diffuse and focal splenic disease with use of magnetic starch microspheres.

The diagnostic value of magnetic starch microspheres (MSM), a new superparamagnetic contrast agent, was studied in experimental models of diffuse and focal splenic disease in rats by means of ex vivo relaxometry and in vivo magnetic resonance (MR) imaging. Owing to small differences in unenhanced T1 and T2 values between diffuse lymphoma and normal spleen, MR imaging failed to distinguish tumor-bearing animals from control animals by signal-to-noise ratios (SNRs) obtained with T1- and T2-weighted spin-echo sequences. One hour after injection of 20 mumol/kg MSM, lymphomatous spleen showed significantly (P < .001) reduced enhancement relative to normal splenic tissue. As a result, animals with diffuse lymphoma (SNR: 10.3 +/- 1.7) could be easily differentiated from control animals (SNR: 5.5 +/- 0.6) on T2-weighted (TR msec/TE msec = 2,000/45) images. In focal splenic disease, MSM produced normal enhancement of nontumorous splenic tissue, whereas relaxation times of tumors were not different before and after contrast agent injection. On T2-weighted images (2,000/45), the tumor-spleen contrast-to-noise ratio increased from 4.8 +/- 1.6 to 21.8 +/- 1.9 (+354%), improving conspicuity of splenic tumors. The results show that MSM-enhanced MR imaging improves the detection of diffuse and focal splenic disease.

Evaluation of hepatocyte-specific paramagnetic contrast media for MR imaging of hepatitis.

The hepatocyte-specific paramagnetic magnetic resonance (MR) contrast agents manganese-DPDP [N,N'-dipyridoxylethylenediamine-N,N'-diacetate 5,5'bis-(phosphate)] and gadobenate dimeglumine were used for diagnosing chemically induced hepatitis in rats. Ex vivo liver tissue relaxation times and in vivo MR image signal-to-noise ratios were compared before and after contrast agent administration. Ex vivo relaxometry and in vivo MR imaging showed that Mn-DPDP enhanced normal and diseased livers to the same degree at all time points from 5 to 120 minutes. Gadobenate dimeglumine showed reduced T1 and T2 enhancements in hepatitis relative to those of normal liver, in the early phase (5-30 minutes). However, these effects are offsetting, and as a result, MR imaging failed to allow distinction of diseased from normal livers. This surprising result observed in vivo was in fact predicted by applying the Bloch equation to our ex vivo data. Our results show that detection and quantitation of hepatitis with MR imaging enhanced with paramagnetic cell-specific contrast agents will be more difficult than anticipated.

Orally administered manganese chloride: enhanced detection of hepatic tumors in rats.

To evaluate its potential as a tissue-specific hepatobiliary magnetic resonance (MR) contrast agent, manganese chloride was orally administered to rats in increasing doses of 100-1,500 mumol/kg MnCl2, and the relaxation times of liver, pancreas, kidney, and heart were measured with ex vivo relaxometry and in vivo MR imaging. Two hours after ingestion of 200 mumol/kg MnCl2, liver T1 was decreased by 48%, whereas tumor T1 decreased by only 9%. On spin-echo MR images, the signal-to-noise ratio in liver increased by 54%; the contrast-to-noise ratio in tumor, by 375%. The T1 of pancreas, kidney, and heart decreased by 8%, 23%, and 13%, respectively. At subjective assessment, the signal intensity of the upper gastrointestinal tract was reduced, likely because of the high concentration of manganese in the lumen, and delineation of the intestine from other abdominal structures was improved. These results indicate that orally administered MnCl2 causes substantial, reproducible, and tissue-specific enhancement of liver. Because enhancement of tumor was minimal, orally administered MnCl2 may potentially be used to improve detection of hepatic tumors.

Enhancement of tumor-liver contrast-to-noise ratio with gadobenate dimeglumine in MR imaging of rats.

The efficacy for tumor detection of the hepatocyte-specific contrast agent gadobenate dimeglumine (gadolinium-BOPTA/Dimeg) was evaluated in four different experimental tumor models in rats. Histologic findings were correlated with quantitative data derived from ex vivo relaxometry and in vivo magnetic resonance (MR) imaging. Noninfiltrating tumors showed maximal enhancement of liver parenchyma 5-10 minutes after contrast agent administration, with a plateau over the next 30 minutes. In contrast, infiltrating tumors, which caused hepatocellular injury and inflammatory changes, delayed maximal enhancement of tumor-free parenchyma by 15-20 minutes. Nonspecific tumor enhancement depended on tumor vascularity and occurred in the early phase after contrast agent administration. Despite differences in specific enhancement of tumor-free parenchyma and nonspecific tumor enhancement, tumor-liver contrast-to-noise ratios increased 96%-248% in all tumor models 30 minutes after intravenous administration of 75 mmol/kg Gd-BOPTA/Dimeg. Gd-BOPTA/Dimeg enhanced tumor conspicuity independently of the histologic characteristics of the tumor.

Diagnosis of fatty liver with MR imaging.

The diagnosis of fatty liver with magnetic resonance (MR) imaging was evaluated in experimental rat models of simple fatty infiltration and fatty liver with hepatocellular injury. T1 and T2 were measured ex vivo and correlated with the histologic degree of fatty infiltration. Enhancement of fatty liver with four different cells-specific contrast agents was studied with ex vivo relaxometry and in vivo MR imaging. Quantitative analysis of conventional and chemical shift MR images was correlated with biochemically determined fat content of the liver. Diet-induced simple fatty infiltration of the liver caused a decrease in T1 of 15%, whereas the T1 of L-ethionine-induced fatty liver with hepatocellular injury increased by 12%. T2 showed a positive correlation with the degree of fatty infiltration in both models. Cell-specific hepatobiliary contrast agents showed the same liver uptake and relaxation enhancement in fatty livers as in normal livers. Conventional T1-weighted images and chemical shift images showed good correlation (r = .83 and .80, respectively) between signal intensity and the degree of fatty infiltration. However, only chemical shift imaging was reliable in the diagnosis of fatty liver.

Clinical indications for MRI.

Safety considerations for MRI will continue to require careful attention and detailed scientific investigation. As new insights are gained into the hazards of time-varying electromagnetic and static magnetic fields, more sophisticated assessment of the true risk will be possible. At the present time, for established clinical indications, the risk of a mismanagement of disease appears to outweigh the minimal or unknown risks of MRI. Other than the mechanical hazards of implanted or external metallic or electrical devices, MRI seems to be an extraordinarily safe and compatible environment for patients undergoing evaluation of suspected diseases.