Reversibility of experimental acute renal failure in rats: assessment with USPIO-enhanced MR imaging

The purpose of this study was to evaluate the potential reversibility of kidney lesions in an experimental model of acute renal failure using ultra-small particles of iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging. This study was conducted in 21 uninephrectomized rats using a model of iodinated contrast media-induced renal failure. Thirteen rats received selective intraarterial renal administration of diatrizoate (370 mg/ml) and were compared with two control groups, including six animals injected with saline and two noninjected animals. MR imaging was performed 28 hours, 8 days, and 22 days after the procedure. Each MR session included axial and coronal T1- and coronal T2-weighted images before and after intravenous administration of 60 micromol Fe/kg of USPIO. The rats were sacrificed immediately after the last MR session for pathologic evaluation. MR images were qualitatively and quantitatively interpreted with respect to pathologic data, and differences were statistically studied. At day 22, histology showed 4 severely diseased kidneys with focal areas of necrosis, 5 mildly diseased kidneys with tubular vacuolization, and 12 normal kidneys. On quantitative data, a high correlation between the percentage of negative enhancement and histologic data was observed (P < 0.05). Qualitative interpretation showed a sensitivity and specificity of USPIO-enhanced T2-weighted MR images of 88% and 91%, respectively. Follow-up enhancement curves showed a constant increase of intrarenal USPIO negative enhancement in normal kidneys between day 1 and day 22, whereas all severely involved kidneys displayed higher USPIO negative enhancement at day 1 without significant changes over time until day 22. USPIO may be useful for in vivo follow-up of the reversibility of experimentally induced iodinated contrast media renal impairment in animals.     

USPIO-enhanced MR imaging of macrophage infiltration in native and transplanted kidneys: initial results in humans

The purpose of this study was to evaluate the detection and characterization of macrophage infiltration in native and transplanted kidneys using ultrasmall superparamagnetic iron oxide particles (USPIO). Among 21 patients initially enrolled, 12 scheduled for renal biopsy for acute or rapidly progressive renal failure (n = 7) or renal graft rejection (n = 5) completed the study. Three magnetic resonance (MR) sessions were performed with a 1.5-T system, before, immediately after and 72 h after i.v. injection of USPIO at doses of 1.7–2.6 mg of iron/kg. Signal intensity change was evaluated visually and calculated based on a region of interest (ROI) positioned on the kidney compartments. Histological examination showed cortical macrophage infiltration in four patients (>5 macrophages/mm²), two in native kidneys (proliferative extracapillary glomerulonephritis) and two in transplants (acute rejection). These patients showed a 33 ± 18% mean cortical signal loss on T2*-weighted images. In the remaining eight patients, with <5 macrophages/mm², there was no cortical signal loss. However, in three of these, presenting with ischemic acute tubular necrosis, a strong (42 ± 18%) signal drop was found in the medulla exclusively. USPIO-enhanced MR imaging can demonstrate infiltration of the kidneys by macrophages both in native and transplanted kidneys and may help to differentiate between kidney diseases.     

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 μmol/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.     

Mn-DPDP–enhanced MR imaging of malignant liver lesions: Efficacy and safety in 20 patients

Twenty patients with malignant liver lesions underwent magnetic resonance (MR) imaging with manganese (II) DPDP [N,N′-dipyridoxylethylenediamine-N,N′-diacetate 5,5′-bis(phosphate)] to evaluate the safety and efficacy of the contrast agent. In two groups of 10 patients each, 5 μmol/kg Mn-DPDP was administered intravenously (3 mL/min) at a concentration of either 50 or 10 μmol/mL. T1- and T2-weighted images were obtained with a 1.5-T imager. Six patients reported a total of eight instances of side effects (flush, feeling of warmth, metallic taste) of which seven occured at the 50 μmol/mL concentration. A significant decrease in alkaline phosphatase levels 2 hours after injection was recorded. On T1-weighted images, the 10 μmol/mL formulation yielded significantly greater increases in contrast-to-noise ratio (79.8%–137.5%) than the 50 μmol/mL formulation (46.2%–86.6%). In a blinded reader study of 10 patients with one to five lesions each, no lesion was missed on Mn-DPDP–enhanced T1-weighted images; however, four false-positive foci were identified. The authors conclude that slow administration of 5 μmol/kg Mn-DPDP at a concentration of 10 μmol/mL is safe and efficient enough to proceed to further clinical trials.     

Multicentre dose-ranging study on the efficacy of USPIO ferumoxtran-10 for liver MR imaging

AIM: A dose ranging multicentre phase-II clinical trial was conducted to evaluate the efficacy of ultrasmall superparamagnetic iron oxide (USPIO) ferumoxtran-10 for magnetic resonance (MR) imaging of focal hepatic lesions. MATERIAL AND METHODS: Ninety-nine patients with focal liver lesions received USPIO at a dose of 0.8 (n = 35), 1.1 (n = 32), or 1.7 (n = 32) mg Fe/kg. Liver MR imaging was performed before and after USPIO with T1-weighted and T2-weighted pulse sequences. Images were analysed by two independent readers for additional information (lesion detection, exclusion, characterization and patient management). Signal intensity (SI) based quantitative measurements were also taken. RESULTS: Post-contrast medium MR imaging showed additional information in 71/97 patients (73%) for reader one and 83/96 patients (86%) for reader two. The results with all three doses were statistically significant (P < 0.05). Signal intensity analysis revealed that all three doses increased liver SI on T1-weighted images and decreased liver SI on T2-weighted images. On T2-weighted images metastases increased in contrast relative to normal hepatic parenchyma whereas haemangiomas decreased in contrast. On T2-weighted images there was statistically improved efficacy at the intermediate dose, which did not improve at the highest dose. CONCLUSION: Ultrasmall superparamagnetic iron oxide was an effective contrast agent for liver MR imaging at all doses and a dose of 1.1 mg Fe/kg was recommended for future clinical trials.     

MRI in focal liver disease: A comparison of small and ultra-small superparamagnetic iron oxide as hepatic contrast agents

The purpose of this study was to compare small and ultrasmall superparamagnetic iron oxide particles (SPIO and USPIO, respectively) as MR contrast agents for the evaluation of focal hepatic disease. In two different patient groups (SPIO [n = 53], USPIO [n = 27]), with focal liver disease (metastases, hepatocellular carcinoma [HCC], hepatocellular adenoma [HCA], and focal nodular hyperplasia [FNH]), spin-echo T1- and T2-weighted images (T1WI, T2WI) were obtained at 1.0T, before and after intravenous contrast administration. The percentage signal-to-noise ratio (SNR) change and lesion-to-liver contrast (LLC) were measured and statistically compared. The liver decreased in signal intensity (SI) after SPIO administration (?28%) and increased after USPIO administration (+16%) on T1WI. On T2WI, the liver decreased in SI on postcontrast images with both agents (?78% SPIO, ?73% USPIO). This difference was not statistically significantly different (P ? .07). Both SPIO and USPIO provided >500% improvement in LLC on T2WI. On T1WI, LLC was increased in metastases (120%) and HCC (325%) with SPIO. Post-USPIO, LLC was increased on T1WI only in metastases (>500%). Both SPIO and USPIO show excellent hepatic uptake, presumed secondary to reticuloendothelial activity, based on the degree of %SI change seen in the liver after administration of contrast on T2WI. However, USPIO preparations exhibit blood pool activity that may aid in further characterization of focal liver lesions, as is evidenced by their greater T1 effect in the liver and in some focal liver lesions.     

Nephrotoxicity of high-dose gadolinium compared with iodinated contrast

To determine if high-dose gadolinium chelates are less nephrotoxic than iodinated contrast. Records of 342 patients who had received high-dose gadolinium (.2 to .4 mmol/kg) for magnetic resonance imaging were reviewed to identify patients who had also received iodinated contrast for radiographic examinations. Their clinical course and laboratory data were reviewed to identify changes in serum creatinine attributable to the contrast agents. In 64 patients, serum creatinine data were available pre and post both gadolinium and iodinated contrast. The mean change in serum creatinine after gadolinium in these 64 patients was ?.07 mg/dL (?6 μmol/L). By comparison, the mean change in serum creatinine in the same patients after iodinated contrast was .35 mg/dL (+31 μmol/L) from 2.0 ± 1.4 to 2.3 ± 1.8 (P=.002). Eleven of the 64 patients had iodinated contrast-induced renal failure (.5 mg/dL or greater rise in serum creatinine); none had gadolinium contrast-induced renal failure despite the high gadolinium dose and high prevalence of underlying renal insufficiency. High-dose gadolinium chelates are significantly less nephrotoxic than iodinated contrast.     

Contrast-enhanced MR imaging of the liver: Comparison between Gd-BOPTA and mangafodipir

The purpose of the study was to evaluate the MR contrast agents gadolinium benzyloxypropionictetro-acetate (Gd-BOPTA) and Mangafodipir for liver enhancement and the lesion-liver contrast on T1W spin-echo (SE) and gradient-recalled-echo (GRE) images. Fifty-one patients (three groups of 17 patients each) with known or suspected liver lesions were evaluated with T1W SE (300/12) and GRE (77-80/2.3-2.5/80°) images before and after intravenous (IV) Gd-BOPTA (0.1 or 0.05 mmol/kg) or Mangafodipir (5 μmol/kg) in phase II to III clinical trials. Quantitative analysis by calculating liver signal-to-noise ratio (SNR), lesion-liver contrast-to-noise ratio (CNR), and spleen-liver CNR was performed. Liver SNR and spleen-liver CNR were always significantly increased postcontrast. SNR was highest after application of 0.1 mmol/kg Gd-BOPTA (51.3 ± 3.6, P < .05). CNR was highest after Mangafodipir (?22.6 ± 2.7), but this was not significantly different from others (P = .07). Overall, GRE images were superior to SE images for SNR and CNR. Mangafodipir and Gd-BOPTA (0.1 mmol/kg) provide equal liver enhancement and lesion conspicuity postcontrast. By all criteria, contrast-enhanced T1-weighted GRE were comparable to SE images.     

Imaging of macrophages in soft-tissue infection in rats: relationship between ultrasmall superparamagnetic iron oxide dose and MR signal characteristics

PURPOSE: To describe dose-dependent signal intensity (SI) characteristics of experimentally induced soft-tissue abscesses on 1.5-T T1- and T2*-weighted magnetic resonance (MR) images obtained 24 hours after administration of ultrasmall superparamagnetic iron oxide (USPIO) and to describe the relationship between SI and amount of USPIO uptake and macrophage iron content. MATERIALS AND METHODS: Local institutional review committee on animal care approved the experiments, which were performed according to the guidelines of the National Institutes of Health and the committee on animal research at our institution. Unilateral calf muscle abscesses were induced in 21 rats with an injection of a Staphylococcus aureus suspension. The rats were divided into three groups of seven animals each: low USPIO dose (50 micromol of iron per kilogram of body weight), high USPIO dose (150 micromol Fe/kg), and control (saline solution). All rats were imaged before and 24 hours after USPIO administration at 1.5 T (transverse T1-weighted spin-echo, T2*-weighted fast gradient-echo, and short inversion time inversion-recovery sequences). Images were analyzed quantitatively and qualitatively with regard to SI and signal pattern. Temporal variation of calculated contrast-to-noise ratios was analyzed with the Wilcoxon signed rank test. MR findings were correlated with histopathologic findings, including those of electron microscopy. RESULTS: Twenty-four hours after USPIO administration in the high-dose group, susceptibility effects were present in abscess periphery on postcontrast T2*-weighted images (P=.04), and SI enhancement was noted on postcontrast T1-weighted images within both abscess wall and abscess center (P=.04 for both). In the low-dose group, SI enhancement was noted in entire abscess on T1-weighted postcontrast images (P=.03). Neither significant SI loss (P=.09) nor susceptibility effects were detected in periphery or center of any abscess on postcontrast T2*-weighted images. There was no obvious difference in total amount of macrophages among the groups, but there was a clear difference with regard to individual iron content of iron-positive macrophages between the USPIO dose groups. CONCLUSION: At 1.5 T, SI characteristics of abscesses on T1- and T2*-weighted images obtained 24 hours after USPIO injection strongly depend on administered dose of the contrast agent. At low doses, T1 effects were stronger than T2* effects.     

MR imaging with ultrasmall superparamagnetic iron oxide particles in experimental soft-tissue infections in rats

PURPOSE: To investigate the feasibility of macrophage magnetic resonance (MR) imaging in rats by using an experimental soft-tissue infection model. MATERIALS AND METHODS: Thirteen rats with unilateral calf-muscle infection were imaged with a 4.7-T MR imager at an early chronic stage of infection (day 4 before contrast material injection, days 4-7 after injection). Eleven animals were imaged before and 3 and 24 hours after intravenous application of ultrasmall superparamagnetic iron oxide (USPIO), and eight animals were additionally imaged 48 hours and three animals 72 hours after USPIO application. Two infected rats served as controls. T1- and T2-weighted spin-echo and T2*-weighted gradient-echo sequences were applied. All animals were sacrificed, and histopathologic findings were correlated with findings on MR images. Electron microscopy was performed in two rats. For quantitative analysis, signal intensities on T2*-weighted images and T2 values on T2 maps were measured within regions of interest, and the temporal variation was analyzed by using the signed rank test. RESULTS: Visualization of USPIO-loaded macrophages was most sensitive with a T2*-weighted sequence. USPIO distribution pattern and quantitative analysis of T2 and T2* effects 3 hours after USPIO application were significantly different (P <.05) from those at 24 and 48 hours, reflecting the dynamic transit of the particle accumulation from the intravascular to the intracellular compartment by means of macrophage phagocytosis. Local signal intensity alterations could be correlated with iron-loaded macrophages at histopathologic examination. CONCLUSION: Activated macrophages in acute soft-tissue infection can be labeled with USPIOs and detected with MR imaging because of susceptibility effects.     

Performance of Gd-EOB-DTPA and superparamagnetic iron oxide particles in the detection of primary liver cancer: A comparative study by alternative free-response receiver operating characteristic analysis

The performance of gadolinium-ethoxybenzyl-dieth-ylenetriaminepentaacetic acid (Gd-EOB-DTPA) and superparamagnetic iron oxide (SPIO) particles in detecting liver cancer was compared using alternative free-response receiver operating characteristic (AFROC) analysis, which allowed observers to indicate both the confidence level and the locations of all perceived abnormalities. Axial T1-weighted MR images (1.5 T) pre/post Gd-EOB-DTPA (25 μmol/kg) injection were obtained for 12 rats with chemically induced liver tumors (64 tumors). T2-weighted images (T2WI) were obtained pre/post SPIO (10 μmol/kg) injection for the same animal. Liver signal-to-noise ratio (SNR), tumor-liver contrast-to-noise ratio (CNR), and histopathologic sections corresponding to MR images were obtained. In AFROC, the location and the confidence level for each tumor were indicated independently on MR images by four radiologists. By plotting true-positive fraction and probability of false-positive per image, the area under the AFROC curve (A1) was estimated and statistically analyzed between each sequence. Either drug significantly improved tumor-liver CNR (P < .001) and tumor detection (diameter ≤ 6 mm; P < .05). Gd-EOB-DTPA significantly (P < .05) improved the A1 in T1WI. There was no A1 difference between T2WI + SPIO and T1WI + Gd-EOB-DTPA. Gd-EOB-DTPA-enhanced T1WI showed the same performance as SPIO-enhanced T2WI in detecting liver tumors.     

Enhancement efficacy of magnetic starch microspheres (MSM) in conventional spin-echo and turbo spin-echo sequences at 0.5 T and 1.5 T

The efficacy of the superparamagnetic contrast agent magnetic starch microspheres (MSM) was evaluated in vitro by NMR relaxometry and in vivo by MR imaging using T2-weighted spin-echo (SE) and turbo spin-echo (TSE) sequences at 0.5 T and 1.5 T in 60 normal rats who received MSM in doses of 10–50 μmol/kg. MR imaging was performed using T2-weighted SE and TSE sequences. The relaxation rates 1/T1 and 1/T2 for liver and spleen increased linearly with MSM concentrations up to 30 μmol/kg body weight, and approached almost constant levels for higher doses. The slopes in the linear part of the 1/T2 diagram were 0.62 Hz ± 0.03 for the liver and 0.51 Hz ± 0.06 × kg/μmol for the spleen. On all T2-weighted sequences at 0.5 T and 1.5 T, liver signal-to-noise ratio (SNR) decreased by a factor of 2-3 already at the lowest dose of 10 μmol/kg. SNR values of TSE sequences exceeded values for SE sequences by 50–80%. The SNR decrease was not significantly different between SE and TSE sequences. Our results show that MSM is well suited as a T2 contrast agent at both magnetic field strengths when using conventional SE and fast TSE sequences.     

Comparison of ultrasmall particles of iron oxide (USPIO)-enhanced T2-weighted, conventional T2-weighted, and gadolinium-enhanced T1-weighted MR images in rats with experimental autoimmune encephalomyelitis

BACKGROUND AND PURPOSE: Ultrasmall particles of iron oxide (USPIO) constitute a contrast agent that accumulates in cells from the mononuclear phagocytic system. In the CNS they may accumulate in phagocytic cells such as macrophages. The goal of this study was to compare USPIO-enhanced MR images with conventional T2-weighted images and gadolinium-enhanced T1-weighted images in a model of experimental autoimmune encephalomyelitis (EAE). METHODS: Nine rats with EAE and four control rats were imaged at 4.7 T and 1.5 T with conventional T1- and T2-weighted sequences, gadolinium-enhanced T1-weighted sequences, and T2-weighted sequences obtained 24 hours after intravenous injection of a USPIO contrast agent, AMI-227. Histologic examination was performed with hematoxylin-eosin stain, Perls' stain for iron, and ED1 immunohistochemistry for macrophages. RESULTS: USPIO-enhanced images showed a high sensitivity (8/9) for detecting EAE lesions, whereas poor sensitivity was obtained with T2-weighted images (1/9) and gadolinium-enhanced T1-weighted images (0/9). All the MR findings in the control rats were negative. Histologic examination revealed the presence of macrophages at the site where abnormalities were seen on USPIO-enhanced images. CONCLUSION: The high sensitivity of USPIO for macrophage activity relative to other imaging techniques is explained by the histologic findings of numerous perivascular cell infiltrates, including macrophages, in EAE. This work supports the possibility of intracellular USPIO transport to the CNS by monocytes/macrophages, which may have future implications for imaging of human inflammatory diseases.     

Effects of iodinated contrast and field strength on gadolinium enhancement: implications for direct MR arthrography

PURPOSE: To optimize direct magnetic resonance (MR) arthrography by determining the effect of dilution of gadolinium in iodinated contrast, saline, or albumin on T1-weighted, T2-weighted, and gradient-recalled echo (GRE) images, and the effect of scanner field strength. MATERIALS AND METHODS: Gadopentetate dimeglumine was diluted into normal saline, albumin, or iodinated contrast (0.625 mmol/liter to 40 mmol/liter). Samples were scanned at 1.5T and 0.2T. Signal intensity was measured using T1-weighted spin-echo (SE), T2-weighted SE, and two- and three-dimensional GRE (20 degrees-75 degrees flip angle) sequences. Graphical analysis of signal intensity vs. gadolinium concentration was performed. RESULTS: Albumin had no effect on gadolinium contrast. Dilution of gadolinium in iodinated contrast decreased signal intensity on all sequences compared to samples of identical concentration diluted in saline at both 1.5T and 0.2T: with a 2 mmol/liter gadolinium solution at 1.5T, signal was decreased by 26.1% on T1-weighted images, 31.7% on GRE20 images, and 28.9% on GRE45 images, and the T2 value decreased by 71.1%; at 0.2T, signal was decreased by 23.5% on T1-weighted images. On all sequences, the peak signal shifted to the left (lower gadolinium concentration) when diluted in iodinated contrast. Peak signal was also seen at different gadolinium concentrations on different sequences and field strength: at 1.5T, peak in saline/iodine was 2.5/0.625 mmol/liter on T1-weighted images, and 2.5/1.25 mmol/liter on GRE20 and GRE45 sequences. At 0.2T, peak in saline/iodine was 0.625-2.5/1.25 mmol/liter on T1-weighted images, 0.625-2.5/1.25 on GRE45 images, 2.5-10.0/1.25-5.0 mmol/liter on GRE65 images, and 1.25-5.0/0.625-1.25 mmol/liter on GRE75 images. CONCLUSION: Dilution of gadolinium in iodinated contrast results in decreased signal on T1-weighted, T2-weighted, and GRE images compared to dilution in saline or albuminfor both 1.5-T and 0.2-T scanners; if gadolinium is diluted in iodinated contrast for MR arthrography, a lower concentration should be used because the peak is shifted to the left. The use of iodinated contrast should be minimized, as it may diminish enhancement and lower the sensitivity and specificity of MR arthrography. Optimal gadolinium concentration for MR arthrography is dependent on scanner field strength and a broader range of gadolinium concentration can be used to provide maximal signal at low field strength.     

Contribution of Sinerem® used as blood-pool contrast agent: Detection of cerebral blood volume changes during apnea in the rabbit

The authors suggest that ultra-small paramagnetic iron oxide (USPIO) particles used as blood pool contrast agents may increase the sensitivity of midfield MRI (i.e., less than 1.5 Tesla) to physiological variations in cerebral blood volume. This hypothesis was tested on a rabbit model of apnea which increases pCO₂ and cerebral blood volume. Using Sinerem® as the USPIO at a blood concentration of 60 μmol iron/kg body weight, an 8% T₂*-weighted signal decrease could be observed at 1.0 T with 25–33% increase in pCO₂. Comparatively, in the absence of USPIO, T₂*-weighted signal dropped only 4% during apnea and after mild hyperoxygenation beforehand, due to increased deoxyhemoglobin content. These preliminary data suggest that USPIOs could play an important role in functional MRI at midfield strength, by sensitizing the signal to cerebral blood volume changes.     

Ultrasmall supraparamagnetic iron oxide-enhanced magnetic resonance imaging of antigen-induced arthritis: a comparative study between SHU 555 C, ferumoxtran-10, and ferumoxytol

OBJECTIVES: We sought to compare the ability of 3 ultrasmall superparamagnetic iron oxides (USPIOs) to detect and characterize antigen-induced arthritis with MR imaging. MATERIALS AND METHODS: A monoarthritis was induced in the right knee of 18 rats. The left knee served as a normal control. Knees underwent magnetic resonance (MR) imaging before, up to 2 hours, and 24 hours after injection (p.i.) of 200 mumol Fe/kg SHU 555 C (n= 6), ferumoxtran-10 (n = 6), or ferumoxytol (n = 6), using T2-2D-SE 100/20,40,60,80/90 (TR/TE/flipangle), T2*-3D-spoiled gradient recalled (SPGR) 100/15/38, and T1-3D-SPGR 50/1,7/60 sequences. RESULTS: Quantitative signal to noise ratio and DeltaSI data of arthritic knees on T1- and T2*-weighted MR images showed no significant differences between the 3 USPIOs (P > 0.05). At 2 hours p.i., SNR and DeltaSI data were significantly increased from baseline on T1-weighted images and significantly decreased on T2*-weighted images (P < 0.001). At 24 hours p.i., the T1-enhancement returned to baseline, whereas the T2*-enhancement remained significantly elevated (P < 0.001). Immunostains demonstrated an USPIO compartmentalization in macrophages in the arthritic synovium. CONCLUSIONS: Based on the relatively small number of animals in our study group, inflammation in antigen-induced arthritis can be equally detected and characterized with any of the three USPIOs evaluated.     

Imaging end-stage kidney disease in adults. Low-field MR imaging with magnetization transfer vs. ultrasonography

Purpose: To 1) assess the potential of magnetization transfer (MT)-weighted MR imaging to improve the often poor visibility of native kidneys in patients with a renal transplant; and 2) compare low-field MR imaging and ultrasonography (US) for imaging these fibrotic kidney remnants.Material and Methods: Seventy-two native kidneys of 36 patients were prospectively evaluated with US and MR. In low-field (0.1 T) MR imaging, T1-, T2- and MT-weighted sequences were used. MT-weighted images were compared with T2-weighted images in their ability to delineate the kidneys from their surroundings whereas US and MR were compared for detection of renal cysts and possible solid tumors.Results: MT-weighted images proved superior to conventional T2-weighted images in producing contrast between the kidney remnants and their fatty surroundings. Although US revealed a few small renal cysts that were not seen at MR images, no statistical difference was found between the two modalities in this respect.Conclusion: MT imaging, due to its unique protein-specific signal depression, offers significantly improved visualization and delineation of end-stage kidneys. US, because its better availability and cost-benefit ratio, remains the method-of-choice compared to low-field MR imaging in detecting cysts in multicystic kidneys. MR investigation is helpful in selected patients and may be used as an alternative.     

Characteristics of ultrasmall superparamagnetic iron oxides in patients with brain tumors

OBJECTIVE: The aim of this study was to evaluate the characteristics of an ultrasmall superparamagnetic iron oxides (USPIO) agent in patients with brain tumors and to correlate changes on MRI with histopathologic data collected systematically in all patients. SUBJECTS AND METHODS: Nine patients with brain tumors were imaged before and 24 hr after administration of a USPIO at a dose of 2.6 mg Fe/kg. Analysis of MR images included qualitative and quantitative comparison of the USPIO and gadolinium enhancement of brain tumors. Brain surgery was performed 25-112 hr after administration of the USPIO. The histopathologic workup included iron histochemistry with diaminobenzidine (DAB)-enhanced Perls stain. RESULTS: In seven of nine patients, USPIO-related changes of signal intensity were observed in gadolinium-enhancing brain tumors on T1- and T2*-weighted sequences. The difference in signal intensity on T1-weighted USPIO series was 40.1% +/- 26.7% (mean +/- SD). On T2*-weighted USPIO series, the difference in signal intensity was -33.1% +/- 18.4% in solid tumor parts. Areas of suspected radiation necrosis did not enhance in three patients with prior radiation therapy. Iron histochemistry revealed the presence of iron deposits in macrophages in two patients. CONCLUSION: USPIO agents will not replace gadolinium in the workup of patients with brain tumors. Our findings suggest that USPIO agents seem to offer complementary information and may help to differentiate between brain tumors and areas of radiation necrosis. Signal intensity changes on T2*-weighted images might be related to the blood pool properties of the agent, possibly reflecting steady-state susceptibility effects.     

Lymph nodes: microstructural anatomy at MR imaging

High-resolution microscopic magnetic resonance (MR) images of rodent lymph nodes were directly correlated with sections obtained for histologic study to determine the microstructural anatomy of lymph nodes seen at MR imaging and to evaluate signal intensity changes induced by a novel intravenous lymphotropic MR contrast agent (ultrasmall superparamagnetic iron oxide [USPIO]). High-resolution T2-weighted images of unenhanced lymph nodes demonstrated medullary sinus as regions of low signal intensity and follicles as high-intensity structures. After a single intravenous administration of USPIO (160 mumol/kg), both T1-weighted and T2-weighted images showed areas of focal signal intensity loss in medullary sinuses corresponding to the distribution of uptake by macrophages. Lymph follicles appeared unchanged in signal intensity, as they are largely devoid of macrophages. This model of microscopic MR imaging should provide the basis for (a) understanding differences between patterns of contrast-enhanced normal lymph nodes and those of diseased ones and (b) guiding the development of targeting strategies for novel pharmaceuticals at the cellular level.     

MR angiography with an ultrasmall superparamagnetic iron oxide blood pool agent

The purpose of the study was to investigate the use of a dextran-coated ultrasmall superparamagnetic iron oxide (USPIO) as a blood pool contrast agent for thoracic and abdominal MR angiography. Abdominal and thoracic MR angiography was performed in six healthy volunteers using two-dimensional and three-dimensional spoiled gradient echo (SPGR) sequences before and after intravenous administration of USPIO. Doses ranged from 1.1 to 2.6 mg Fe/kg. Flip angle was varied from 20 to 60°. Subjective image quality, analysis of signal-to-noise ratio (SNR), and blood T1 relaxation times were measured. USPIO significantly lowered the T1 of blood (from 1,210 ms precontrast to 159 ms postcontrast at a dose of 2.6 mg Fe/kg) (P < .01). Image quality on coronal fast three-dimensional breath-hold SPGR images of the abdomen increased with increasing dose and was maximum at the highest dose, producing an aortic SNR of 9.6 compared to 1.8 precontrast. Axial two-dimensional time-of-flight (TOF) aortic SNR was reduced significantly from 13 on precontrast to 6 on the postcontrast images at the highest dose (P < .05) due to T2* shortening effects. There was little flip angle dependence on image quality. Due to the T1 shortening effect and long intravascular half-life, USPIO improved visualization of vascular anatomy using three-dimensional fast SPGR imaging. The echo time must be minimized to minimize signal loss from T2* shortening effects. The blood pool distribution of USPIO is useful for equilibriumphase MR angiography.