Uptake of dextran-coated monocrystalline iron oxides in tumor cells and macrophages

Although several dextran-coated iron oxide preparations are in preclinical and clinical use, little is known about the mechanism of uptake into cells. As these particles have been shown to accumulate in macrophages and tumor cells, we performed cellular uptake and inhibition studies with a prototypical monocrystalline iron oxide nanoparticle (MION). MION particles were labeled with fluorescein isothiocyanate or radioiodinated and purified by gel permeation chromatography. Two preparations of MION particles were used in cell experiments: nontreated MION and plasma-opsonized MION purified by gradient density purification. As determined by immunoblotting, opsonization resulted in C3, vitro-nectin, and fibronectin association with MION. Incubation of cells with fluorescent MION showed active uptake of particles in macrophages both before and after opsonization. In C6 tumor cells, however, intracellular MION was only detectable in dividing cells. Quantitatively, ¹²⁵I-labeled MION was internalized into cells with uptake values ranging from 17 ng (in 9L gliosarcoma) to 970 ng iron per million cells for peritoneal macrophages. Opsonization increased MION uptake into macrophages sixfold, whereas it increased the uptake in C6 tumor cells only twofold. Results from uptake inhibition assay suggest that cellular uptake of nonopsonized (dextran-coated) MION particles is mediated by fluid-phase endocytosis, whereas receptor-mediated endocytosis is presumably responsible for the uptake of opsonized (protein-coated) particles.     

FDG-MicroPET and Diffusion-Weighted MR Image Evaluation of Early Changes After Radiofrequency Ablation in Implanted VX2 Tumors in Rabbits

The objective of this study was to evaluate the early changes after radiofrequency ablation (RFA) in VX2 rabbit tumors implanted into the back muscles by diffusion-weighted magnetic resonance (MR) imaging and ¹⁸F-2-fluoro-2-deoxy-D-glucose positron emission tomography (¹⁸F-FDG PET). Percutaneous CT-guided RFA was conducted in seven rabbits with implanted VX2 tumors. VX2 tumors on the other side were untreated and served as the control. MR imaging was performed with a clinical 1.5-T instrument 2 days after RFA, and FDG-PET, using a high-resolution PET scanner for small animals, was obtained 3 days after the procedure. The mean apparent diffusion coefficient (ADC) values and radioactivity count of untreated and ablated tumors were calculated. Untreated VX2 tumors showed hyperintensity on T1-, T2-, and diffusion-weighted MR images, ring-enhanced on contrast-enhanced T1-weighted imaging, and ring-shaped FDG accumulation on FDG-PET. Ablated VX2 tumors showed slight hyperintensity on T1-, T2-, and diffusion-weighed images, slight enhancement on contrast-enhanced T1-weighted images, and low accumulation on FDG-PET. The ADC value of ablated VX2 tumors (1.52 ± 0.24 × 10⁻³ mm²/s) was significantly higher than that of untreated tumors (1.09 ± 0.12 × 10⁻³; p < 0.05). The tumor/muscle ratio of ablated tumors (0.5 ± 0.3) was significantly lower than that of untreated tumors (11.6 ± 3.2; p < 0.05). Histopathological examination confirmed the lack of viable tumor cells in the ablated lesions. The results indicate that both ADC value and FDG-PET are potentially useful markers for monitoring the early effects of RFA.     

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.     

T1 and T2 relaxivity of intracellular and extracellular USPIO at 1.5T and 3T clinical MR scanning

In this study we evaluated the effects of intracellular compartmentalization of the ultrasmall superparamagnetic iron oxide (USPIO) ferumoxtran-10 on its proton T1 and T2 relaxivities at 1.5 and 3T. Monocytes were labeled with ferumoxtran-10 by simple incubation. Decreasing quantities of ferumoxtran-10-labeled cells (2.5×10⁷-0.3×10⁷ cells/ml) and decreasing concentrations of free ferumoxtran-10 (without cells) in Ficoll solution were evaluated with 1.5 and 3T clinical magnetic resonance (MR) scanners. Pulse sequences comprised axial spin echo (SE) sequences with multiple TRs and fixed TE and SE sequences with fixed TR and increasing TEs. Signal intensity measurements were used to calculate T1 and T2 relaxation times of all samples, assuming a monoexponential signal decay. The iron content in all samples was determined by inductively coupled plasma atomic emission spectrometry and used for calculating relaxivities. Measurements at 1.5T and 3T showed higher T1 and T2 relaxivity values of free extracellular ferumoxtran-10 as opposed to intracellularly compartmentalized ferumoxtran-10, under the evaluated conditions of homogeneously dispersed contrast agents/cells in Ficoll solution and a cell density of up to 2.5×10⁷ cells/ml. At 3T, differences in T1-relaxivities between intra- and extracellular USPIO were smaller, while differences in USPIO T2-relaxivities were similar compared with 1.5T. In conclusion, cellular compartmentalization of ferumoxtran-10 changes proton relaxivity. This work was supported by a seed grant from the Department of Radiology, University of California of San Francisco.     

Diffusion-weighted MR imaging of abdominopelvic abscesses

This study was conducted to determine the incremental value of diffusion-weighted MR imaging (DW-MRI) over T2-weighted imaging diagnosing abdominopelvic abscesses and compare apparent diffusion coefficient (ADC) values of abscesses and non-infected ascites. In this IRB-approved, HIPAA-compliant study, two radiologists retrospectively compared T2-weighted, T2-weighted + DW-MRI and T2-weighted + contrast enhanced MR images of 58 patients (29 with abscess, 29 with ascites) who underwent abdominal MRI for abscess detection. Confidence and sensitivity was compared using McNemar’s test. ADC of abscesses and ascites was compared by t test, and a receiver operating characteristic (ROC) curve was constructed. Detection of abscesses and confidence improved significantly when T2-weighted images were combined with DW-MRI (sensitivity: observer 1—100%, observer 2—96.6%) or contrast enhanced images (sensitivity: both observers—100%) compared to T2-weighted images alone (sensitivity: observer 1—65.5%, observer 2—72.4%). All abscesses showed restricted diffusion. Mean ADC of abscesses (observer 1—1.17 ± 0.42 × 10⁻3 mm2/s, observer 2—1.43 ± 0.48 × 10⁻³ mm2/s) was lower than ascites (observer 1—3.57 ± 0.68 × 10⁻³ mm2/s, observer 2—3.42 ± 0.67 × 10⁻³ mm2/s) (p < 0.01). ROC analysis showed perfect discrimination of abscess from ascites with threshold ADC of 2.0 × 10⁻³ mm2/s (Az value 1.0). DW-MRI is a valuable adjunct to T2-weighted images diagnosing abdominopelvic abscesses. ADC measurements may have the potential to differentiate abdominal abscesses from ascites.     

MR Imaging–Based In Vivo Macrophage Imaging to Monitor Immune Response after Radiofrequency Ablation of the Liver

PurposeTo establish molecular magnetic resonance (MR) imaging instruments for in vivo characterization of the immune response to hepatic radiofrequency (RF) ablation using cell-specific immunoprobes.Materials and MethodsSeventy-two C57BL/6 wild-type mice underwent standardized hepatic RF ablation (70 °C for 5 minutes) to generate a coagulation area measuring 6–7 mm in diameter. CD68⁺ macrophage periablational infiltration was characterized with immunohistochemistry 24 hours, 72 hours, 7 days, and 14 days after ablation (n = 24). Twenty-one mice were subjected to a dose-escalation study with either 10, 15, 30, or 60 mg/kg of rhodamine-labeled superparamagnetic iron oxide nanoparticles (SPIONs) or 2.4, 1.2, or 0.6 mg/kg of gadolinium-160 (¹⁶⁰Gd)-labeled CD68 antibody for assessment of the optimal in vivo dose of contrast agent. MR imaging experiments included 9 mice, each receiving 10-mg/kg SPIONs to visualize phagocytes using T2¹-weighted imaging in a horizontal-bore 9.4-T MR imaging scanner, ¹⁶⁰Gd-CD68 for T1-weighted MR imaging of macrophages, or 0.1-mmol/kg intravenous gadoterate (control group). Radiological-pathological correlation included Prussian blue staining, rhodamine immunofluorescence, imaging mass cytometry, and immunohistochemistry.ResultsRF ablation–induced periablational infiltration (206.92 μm ± 12.2) of CD68⁺ macrophages peaked at 7 days after ablation (P < .01) compared with the untreated lobe. T2¹-weighted MR imaging with SPION contrast demonstrated curvilinear T2¹ signal in the transitional zone (TZ) (186 μm ± 16.9), corresponsing to Iron Prussian blue staining. T1-weighted MR imaging with ¹⁶⁰Gd-CD68 antibody showed curvilinear signal in the TZ (164 μm ± 3.6) corresponding to imaging mass cytometry.ConclusionsBoth SPION-enhanced T2¹-weighted and ¹⁶⁰Gd-enhanced T1-weighted MR imaging allow for in vivo monitoring of macrophages after RF ablation, demonstrating the feasibility of this model to investigate local immune responses.     

Focal nodular hyperplasia of the liver on ferumoxides-enhanced MR imaging: features on conventional spin-echo, fast spin-echo and gradient-echo pulse sequences

The aim of this study was to assess the efficacy of a superparamagnetic iron oxide, ferumoxides, in the detection and characterization of focal nodular hyperplasia (FNH) on MR conventional spin-echo (SE), fast spin-echo (FSE) and gradient-echo (GRE) images. Fourteen adults with 27 FNHs were evaluated at 1.5 T before and after injection of ferumoxides. T1-weighted and T2-weighted SE, T2-weighted FSE and T2^*-weighted GRE sequences were used and analysed qualitatively and quantitatively. One hundred percent of FNHs showed a significant postcontrast decrease in signal intensity on T2- and T2*-weighted images. Heavily T2-weighted SE images showed the maximum decrease in FNH signal-to-noise ratio (S/N). Postcontrast GRE T2^*-weighted images improved the detection of the central scar and the delineation of FNHs and demonstrated the best lesion-to-liver contrast-to-noise ratio (C/N). Postcontrast T1-weighted SE images showed the least lesion-to-liver C/N. Ferumoxides-enhanced MR imaging can help detect and characterize FNH. Conventional pre- and postcontrast T2-weighted SE images and postcontrast GRE T2*-weighted images should be used preferentially. Received: 30 November 1998; Revised: 5 April 1999; Accepted: 6 April 1999     

Optimal imaging protocol after intraocular silicone oil tamponade.

PURPOSEOur purpose was to define the optimal protocol for imaging of the orbits after vitreous humor replacement with silicone oil.METHODSEleven eyes in 10 patients with tractional and/or rhegmatogenous retinal detachment were studied. Five CT scans and 18 high-field (1.5 T) MR images were obtained. Standard T1-weighted, T1-weighted with fat and silicone saturation, fast spin density-weighted, and T2-weighted orbital MR sequences were performed. Unique pulse sequences included fast spin density-weighted and T2-weighted imaging with and without fat saturation or silicone saturation, gradient-echo imaging, and short-tau inversion recovery imaging.RESULTSThe T1-weighted MR and CT studies were comparable in displaying the silicone. However, the fat- or silicone-saturated fast T2-weighted sequences always showed the fibrous bands and subretinal fluid to best advantage. In one case, the eye also contained inadvertently retained perfluorocarbon liquid, which blended with silicone oil on both saturated images, requiring companion T1-weighted sequences without saturation to demonstrate its presence.CONCLUSIONSimple, commonly available fat-saturated fast T2-weighted MR images supplemented by standard T1-weighted images are all that are needed to evaluate the eye efficiently after vitrectomy and tamponade.     

High-resolution variable flip angle 3D MR imaging of trabecular microstructure in vivo

Two conceptually related variable-flip-angle 3D spin-echo pulse sequences were designed for imaging at voxel sizes of 2–5 × 10^?3 mm³ corresponding to pixel areas of less than 100 × 100 μm² and section thicknesses on the order of 300–400 μm on a conventional 1.5 T MR imaging system equipped with 1 G/cm imaging field gradients, providing 12 sections in 10 min imaging time. The pulse sequences make use of the concept of restoring longitudinal magnetization inverted by the 180° phase reversal pulse and are derivatives of pulse sequences previously dubbed “FATE” and “RASEE.” It is shown that even in the small-voxel regime (< 10^?2 mm³ voxel size) and at echo times on the order of 10 ms, gradient echo images are sensitive to intrinsic fields causing artifactual boundary effects, including signal loss from intravoxel phase scrambling and spatial mismapping. At this resolution the variable flipangle spin-echo pulse sequences are demonstrated to be better suited for imaging magnetically heterogeneous systems such as trabecular bone microstructure in vivo. These pulse sequences are found to be substantially less sensitive to distortions from magnetic dipole fields occurring at the boundaries of two phases of different magnetic permeability.     

Fat-suppressed fast spin-echo mid-TE (TE[effective]=34) MR images: comparison with fast spin-echo T2-weighted images for the diagnosis of tears and anatomic variants of the glenoid labrum

Objective. To compare the sensitivity, specificity, and accuracy of fat-suppressed fast spin-echo (FSE) mid-TE (TE[effective]=34) images with fat-suppressed FSE T2-weighted images for the diagnosis of labral abnormalities. Design and patients. The study included 27 consecutive patients who had axial fat-suppressed FSE T2-weighted and fat-suppressed FSE mid-TE MR images, and had labral abnormalities diagnosed at arthroscopy. The acquisition time was about 5 min for each sequence, but the mid-TE sequence allowed a higher spatial resolution than the T2-weighted images (256×256 versus 256×192). Twenty-eight age-matched patients with arthroscopically normal labra were included as a control group. The labrum was graded on the MR images as normal or abnormal separately by two musculoskeletal radiologists who were masked to the history and arthroscopic results. The surgical findings were used as the gold standard for calculating the sensitivity, specificity, and accuracy for interpreting the correct location of a labral abnormality. The sensitivity, specificity, and accuracy for the two sequences were compared with a McNemar test, and significance defined as P<0.05. Results. For observer 1, the sensitivity for labral abnormalities was 0.59 on the T2-weighted images, and 0.78 on the mid-TE images (P=0.12). The specificity was 0.54 for the T2-weighted, and 0.64 for the mid-TE images (P=0.51). The accuracy was 0.56 for the T2-weighted, and 0.71 for the mid-TE images (P=0.08). For observer 2, the sensitivity/specificity/accuracy was 0.67/0.93/0.80 for the T2-weighted, and 0.70/0.86/0.78 for the mid-TE images (all P>0.5). Conclusion. In this small study there is no statistically significant difference for demonstrating labral abnormalities between FSE T2-weighted images, and higher-resolution fat-suppressed FSE mid-TE (TE[effective]=34) images obtained with a similar acquisition time. Although there was a general trend toward higher sensitivity and accuracy with the mid-TE sequence, particularly for one of the two observers, a larger study is needed to determine whether this is the preferred single axial pulse sequence for conventional MR imaging of the labrum. Received: 28 June 1999 Revision requested: 9 September 1999 Revision received: 20 September 1999 Accepted: 28 September 1999     

The value of b required to avoid T2 shine-through from old lucunar infarcts in diffusion-weighted imaging

Multiple small infarcts of different ages are common in small-vessel disease. Diffusion-weighted imaging (DWI) is a powerful method for discriminating new from chronic lesions. This can be done on the diffusion-weighted images provided that b is sufficiently high. Our purpose was to determine that critical value of b. We reviewed DWI from a previous study of acute, mainly lacunar strokes, and selected 18 old lacunar infarcts, well defined on uncoded images with b 0 s/m² (i. e., T2-weighted images) but invisible on DWI with b 1200 × 10⁶ s/m². We used a 1.5 tesla imager and single-shot echo-planar technique. We had seven separate acquisitions with echo time 123 ms and b in steps between 0 and 1200 × 10⁶ s/m². Two neuroradiologists blinded to the selection of lesions carried out two different lesion-detection procedures, thereby testing each lesion four times, giving a total of 72 tests of b values. The results were consistent, indicating a level for detection of 800 × 10⁶ s/m² in two tests, 400–600 × 10⁶ s/m² in 65 tests and at lower values in the remainder. For imagers up to 1.5 tesla, at long repetition times and an echo time up to 120 ms T2-shine through of old lacunar infarcts can be avoided using b of 1000 × 10⁶ s/m². Received: 5 July 2000 Accepted: 6 December 2000     

Targeting of hematopoietic progenitor cells with MR contrast agents

PURPOSE: To label human hematopoietic progenitor cells with various magnetic resonance (MR) imaging contrast agents and to obtain 1.5-T MR images of them. MATERIALS AND METHODS: Hematopoietic progenitor cells, labeled with ferumoxides, ferumoxtran, magnetic polysaccharide nanoparticles-transferrin, P7228 liposomes, and gadopentetate dimeglumine liposomes underwent MR imaging with T1- and T2-weighted spin-echo and fast field-echo sequences. Data were analyzed by measuring MR signal intensities and R1 and R2* relaxation rates of labeled cells and nonlabeled control cells. Mean quantitative data for the various contrast agent groups were assessed for significant differences compared with control cells by means of the Scheffe test. As a standard of reference, MR imaging data were compared with electron microscopic and spectrometric data. RESULTS: For all contrast agents, intracellular cytoplasm uptake was demonstrated with electron microscopy and was quantified with spectrometry. When compared with nonlabeled control cells, progenitor cells labeled with iron oxides showed significantly (P <.05) increased R2*. Cells labeled with gadopentetate dimeglumine liposomes showed significantly increased R1. Detection thresholds were 5 x 10(5) cells for gadopentetate dimeglumine liposomes and ferumoxtran, 2.5 x 10(5) cells for ferumoxides and P7228 liposomes, and 1 x 10(5) cells for magnetic polysaccharide nanoparticles-transferrin. CONCLUSION: Hematopoietic progenitor cells can be labeled with MR contrast agents and can be depicted with a standard 1.5-T MR imager.     

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.     

磁性标记的小胶质细胞在大鼠脑内的MR示踪

目的 探讨超顺磁性氧化铁颗粒(SPIO)标记的小胶质细胞在正常大鼠及阿尔茨海默病(AD)大鼠体内移植后,MR活体示踪的可行性.方法 以日本血液凝集病毒包膜(HVJ-E)为标记载体,将SPIO标记的小胶质细胞经颈内动脉注入正常大鼠(5只)及AD大鼠动物模型(5只)体内,3 d后应用7.0 T MR行T2*序列扫描,并与脑组织切片组织化学染色结果对照.结果 在正常大鼠脑内,MRI可见数个点状的信号改变区,这些信号改变区散在地分布在脑内各处,脑组织切片显示铁颗粒标记细胞位置与信号改变部位一致.MRI能够检测到由数个标记细胞引起的信号强度的改变.在AD大鼠模型脑内,MRI可见β-淀粉样蛋白42(Aβ42)注射区信号强度明显下降,信号改变区面积较大.与之相比,生理盐水注射区信号改变的强度及面积均不如Aβ42注射区改变明显.Aβ42注射区的标记细胞数为(454±47)个/mm2,明显高于生理盐水注射区的标记细胞数(83±13)个/mm2(P<0.05).结论 MRI可作为一种非侵入性检测手段在活的动物体内追踪标记细胞,在AD细胞水平的治疗中具有一定临床应用前景.     

Early identification of aortic valve sclerosis using iron oxide enhanced MRI

Purpose:

To test the ability of MION‐47 enhanced MRI to identify tissue macrophage infiltration in a rabbit model of aortic valve sclerosis (AVS).

Materials and Methods:

The aortic valves of control and cholesterol‐fed New Zealand White rabbits were imaged in vivo pre‐ and 48 h post‐intravenous administration of MION‐47 using a 1.5 Tesla (T) MR clinical scanner and a CINE fSPGR sequence. MION‐47 aortic valve cusps were imaged ex vivo on a 3.0T whole‐body MR system with a custom gradient insert coil and a three‐dimensional (3D) FIESTA sequence and compared with aortic valve cusps from control and cholesterol‐fed contrast‐free rabbits. Histopathological analysis was performed to determine the site of iron oxide uptake.

Results:

MION‐47 enhanced the visibility of both control and cholesterol‐fed rabbit valves in in vivo images. Ex vivo image analysis confirmed the presence of significant signal voids in contrast‐administered aortic valves. Signal voids were not observed in contrast‐free valve cusps. In MION‐47 administered rabbits, histopathological analysis revealed iron staining not only in fibrosal macrophages of cholesterol‐fed valves but also in myofibroblasts from control and cholesterol‐fed valves.

Conclusion:

Although iron oxide labeling of macrophage infiltration in AVS has the potential to detect the disease process early, a macrophage‐specific iron compound rather than passive targeting may be required. J. Magn. Reson. Imaging 2010;31:110–116. © 2009 Wiley‐Liss, Inc.     

Dextran-coated superparamagnetic iron oxide,an MR contrast agent for assessing lymph nodes in the head and neck.

PURPOSETo investigate dextran-coated superparamagnetic iron oxide particles (BMS 180549) as an MR contrast agent for assessing lymph nodes.METHODSFive different doses ranging from 0.3 to 1.7 mg Fe/kg were evaluated in five healthy human male subjects as part of a phase 1 clinical study. T1-, T2-, and proton density-weighted spin-echo images as well as multiplanar gradient-echo and spoiled gradient-echo images were acquired before and 1 hour, 4 hours, and 24 hours after contrast administration. Image analysis was performed with visually selected regions of interest. Signal intensities were measured for neck lymph nodes and the adjacent muscle. Enhancement effects were evaluated as a function of dose, imaging time after contrast administration, and MR pulse sequence.RESULTSThe iron oxide particles were phagocytized by macrophages within the normal functioning lymph nodes, resulting in a dramatic decrease in signal intensity because of magnetic susceptibility effects. T2*-weighted gradient echo and T2-weighted spin echo showed significant decrease in the signal intensity of normal lymph nodes at 24 hours after contrast injection at a dose of 1.7 mg Fe/kg. No significant changes in lymph node signal intensity on T1-weighted spin-echo images were noted at any dose or imaging time point.CONCLUSIONSThis preliminary clinical evaluation demonstrates intravenous delivery of an iron-based contrast agent, resulting in negative enhancement of normal lymph nodes.     

Superparamagnetic Iron Oxide Hepatic MR Imaging: Efficacy and Safety Using Conventional and Fast Spin-Echo Pulse Sequences

The purpose of this study was to evaluate the technical efficacy and safety of iv ferumozldes (Feridex^a), a superparamagnetic iron oxide contrast agent for detection of hepatic lesions using conventional spin-echo and fast spin-echo MR images. Precontract and postcontrast MR studies were performed on 25 patients with suspected focal hepatic lesions. Conventional Tl-and T2-weighted MR images, as well as fast spin-echo and fat suppressed fast spin-echo MR images, were evaluated. Quantitative assessment of the contrast agent was performed obtaining region of interest measurements of the liver, spleen, and selected hepatic lesions. The pulse sequences were also evaluated subjectively for overall image quality and a subjective assessment of lesion detection. The use of a superparamagnetic iron oxide contrast agent led to a decrease in hepatic signal intensity on all pulse sequences. Lesion-to-liver contrast increased 41.1%, 36.5%, and 32.0% on the conventional T2, fast spin-echo, and fat suppressed fast spin echo pulse sequences, respectively. Lesion-to-liver contrast decreased on the T1-weighted postcontrast pulse sequence by 23.8%. Despite Improvement in lesion-to-liver contrast, radiologists subjectively preferred the precontract sequences because of overall better image quality. At a dose of 10 μmol/kg, fenunoxides favorably impacts lesion-to-liver contrast, and may be useful in hepatic imaging, more with conventional T2-weighted spin-echo pulse sequences than with T2-weighted fast spin-echo pulse sequences.     

Labeling efficacy of superparamagnetic iron oxide nanoparticles to human neural stem cells: comparison of ferumoxides, monocrystalline iron oxide, cross-linked iron oxide (CLIO)-NH2 and tat-CLIO.

OBJECTIVE: We wanted to compare the human neural stem cell (hNSC) labeling efficacy of different superparamagnetic iron oxide nanoparticles (SPIONs), namely, ferumoxides, monocrystalline iron oxide (MION), cross-linked iron oxide (CLIO)-NH(2) and tat-CLIO. MATERIALS AND METHODS: The hNSCs (5 x 10(5) HB1F3 cells/ml) were incubated for 24 hr in cell culture media that contained 25 microg/ml of ferumoxides, MION or CLIO-NH(2), and with or without poly-L-lysine (PLL) and tat-CLIO. The cellular iron uptake was analyzed qualitatively with using a light microscope and this was quantified via atomic absorption spectrophotometry. The visibility of the labeled cells was assessed with MR imaging. RESULTS: The incorporation of SPIONs into the hNSCs did not affect the cellular proliferations and viabilities. The hNSCs labeled with tat-CLIO showed the longest retention, up to 72 hr, and they contained 2.15+/-0.3 pg iron/cell, which are 59 fold, 430 fold and six fold more incorporated iron than that of the hNSCs labeled with ferumoxides, MION or CLIO-NH(2), respectively. However, when PLL was added, the incorporation of ferumoxides, MION or CLIO-NH(2) into the hNSCs was comparable to that of tat-CLIO. CONCLUSION: For MR imaging, hNSCs can be efficiently labeled with tat-CLIO alone or with a combination of ferumoxides, MION, CLIO-NH(2) and the transfection agent PLL.     

Detection of hepatic metastases by superparamagnetic iron oxide-enhanced MR imaging: prospective comparison between 1.5-T and 3.0-T images in the same patients

Objective:

To prospectively compare the diagnostic performance of superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging at 3.0 T and 1.5 T for detection of hepatic metastases.

Methods:

A total of 28 patients (18 men, 10 women; mean age, 61 years) with 80 hepatic metastases were prospectively examined by SPIO-enhanced MR imaging at 3.0 T and 1.5 T. T1-weighted gradient-recalled-echo (GRE) images, T2*-weighted GRE images and T2-weighted fast spin-echo (SE) images were acquired. The tumour-to-liver contrast-to-noise ratio (CNR) of the lesions was calculated. Three observers independently reviewed each image. Image artefacts and overall image quality were analysed, sensitivity and positive predictive value for the detection of hepatic metastases were calculated, and diagnostic accuracy using the receiver-operating characteristics (ROC) method was evaluated.

Results:

The tumour-to-liver CNRs were significantly higher at 3.0 T. Chemical shift and motion artefact were more severe, and overall image quality was worse on T2-weighted fast SE images at 3.0 T. Overall image quality of the two systems was similar on T1-weighted GRE images and T2*-weighted GRE images. Sensitivity and area under the ROC curve for the 3.0-T image sets were significantly higher.

Conclusion:

SPIO-enhanced MR imaging at 3.0 T provided better diagnostic performance for detection of hepatic metastases than 1.5 T.     

Transmission imaging for registration of ictal and interictal single-photon emission tomography, magnetic resonance imaging and electroencephalography

A method developed for registration of ictal and interictal single-photon emission tomography (SPET), magnetic resonance imaging (MRI) and electroencephalography (EEG) is described. For SPET studies, technetium-99m ethyl cysteinate dimer (ECD) was injected intravenously while the patient was monitored on video-EEG to document the ictal or interictal state. Imaging was performed using a triple-head gamma camera equipped with a transmission imaging device using a gadolinium-153 source. The images (128×128 pixels, voxel size 3.7×3.7×3.6 mm³) were reconstructed using an iterative algorithm and postfiltered with a Wiener filter. The gold-plated silver electrodes on the patient’s scalp were utilized as markers for registration of the ictal and interictal SPET images, as these metallic markers were clearly seen on the transmission images. Fitting of the marker sets was based on a non-iterative least squares method. The interictal SPET image was subtracted from the ictal image after scaling. The T1-weighted MPRAGE MR images with voxel size of 1.0×1.0×1.0 mm³ were obtained with a 1.5-T scanner. For registration of MR and subtraction SPET images, the external marker set of the ictal SPET study was fitted to the surface of the head segmented from MR images. The SPET registration was tested with a phantom experiment. Registration of ictal and interictal SPET in five patient studies resulted in a 2-mm RMS residual of the marker sets. The estimated RMS error of registration in the final result combining locations of the electrodes, subtraction SPET and MR images was 3–5 mm. In conclusion, transmission imaging can be utilized for an accurate and easily implemented registration procedure for ictal and interictal SPET, MRI and EEG. Received 20 September and in revised form 16 October 1999