Primary cardiac lymphoma demonstrated by delayed contrast-enhanced magnetic resonance imaging

Delayed contrast-enhanced magnetic resonance (MR) imaging that nullifies the signal of normal myocardium produces great differences in myocardial signal intensity between normal and infarcted myocardium. A case of primary cardiac lymphoma is presented in which delayed contrast-enhanced MR imaging clearly identified the localization and extension of a lymphoma infiltrating the myocardium.     

Polyclonal human immunoglobulin G labeled with polymeric iron oxide: antibody MR imaging

Human polyclonal immunoglobulin (Ig) G was attached to a monocrystalline iron oxide nanocompound (MION), a small superparamagnetic probe developed for receptor and antibody magnetic resonance (MR) imaging. The resulting complex, MION-IgG, had a slightly negative surface charge, a molecular weight of 150-180 kDa, and 0.36 microgram of IgG attached per milligram of iron. After intravenous administration of MION-IgG to normal rats, most of the compound localized in liver, spleen, and bone marrow. In an animal model of myositis, MION-IgG caused reduced signal intensity (most apparent on T2-weighted spin-echo and gradient-echo images) at the site of inflammation. No change in signal intensity existed after an injection of unlabeled MION. Site-specific localization of MION-IgG was corroborated with scintigraphic imaging with indium-111 IgG and MION-In-111-IgG and was confirmed histologically with iron staining. These results indicate that antibody MR imaging is feasible in vivo. Target-specific and antibody MR imaging could be easily extended to other applications, including detection of cancer, infarction, and degenerative diseases.     

Occlusive myocardial infarction: investigation of bis-gadolinium mesoporphyrins-enhanced T1-weighted MR imaging in a cat model

PURPOSE: To test whether bis-gadolinium mesoporphyrins-enhanced magnetic resonance (MR) imaging can accurately depict irreversibly damaged myocardium in occlusive myocardial infarction. MATERIALS AND METHODS: Ten cats were subjected to 90 minutes of occlusion of the left anterior descending coronary artery. Bis-gadolinium mesoporphyrins-enhanced T1-weighted MR imaging was performed in the cats for 6 hours. Histopathologic examinations with 2'3'5-triphenyl tetrazolium chloride (TTC) staining and electron microscopy were performed on the resected specimens. The time course and pattern of signal intensity enhancement were evaluated. The size of the infarcted myocardium was estimated on the MR images by measuring the size of the signal intensity-enhanced area. RESULTS: In eight of 10 cats, it was impossible to distinguish infarcted myocardium from normal myocardium at visual inspection of T1-weighted MR images. The contrast ratio between infarcted and normal myocardium did not increase significantly over time. In one of the two remaining cats, a doughnut pattern of signal intensity enhancement was noted. The other cat showed intensely homogeneous enhancement of infarcted myocardium at MR imaging. The size of the area of signal intensity enhancement at MR imaging in these two cats was accurately mapped to that of the infarction on the TTC-stained specimens. CONCLUSION: Occlusive myocardial infarction cannot be accurately detected at bis-gadolinium mesoporphyrins-enhanced MR imaging.     

Magnetically labeled cells can be detected by MR imaging

To determine the feasibility of MR imaging of magnetically labeled cells, different cell lines were labeled with monocrystalline iron oxide (MION) particles. Phantoms containing MION labeled cells were then assembled and imaged by MR at 1.5 T using T1-weighted and T2-weighted pulse sequences. MION uptake ranged from 8.5 × 10⁴ to 2.9 × 10⁵ particles/cell for tumor cells (9L and LX1, respectively) to 1.5 × 10⁶ to 4.8 × 10⁸ particles/cell for “professional phagocytes” (J774 and peritoneal macrophages, respectively). On the T1-weighted images, cell-internalized MION appeared hyperintense relative to agar and similar to MION in aqueous solution. On T2-weighted images, signal intensity varied according to concentration of MION within cells. Cell-internalized MION caused similar MR signal changes of cells as did free MION; however, at a dose that was an order of magnitude lower, depending on the pulse sequence used. The detectability of MION within cells was approximately 2 ng Fe, which corresponded to 10⁵ tumor cells/well or 5 × 10³ macrophages/well. We conclude that a variety of cells can be efficiently labeled with MION by simple incubation. Intracellular labeling may be used for MR imaging of in vivo cell tracking.     

Three-dimensional cardiac cine magnetic resonance imaging with an ultrasmall superparamagnetic iron oxide blood pool agent (NC100150)

The purpose of this study was to assess image quality of three-dimensional (3D) cardiac cine magnetic resonance (MR) imaging before and after administration of a T1-shortening ultrasmall superparamagnetic iron oxide blood pool agent (NC100150). 3D cardiac cine MR imaging was performed in 13 volunteers using a radiofrequency-spoiled cardiac-gated 3D cine gradient-echo sequence with short repetition and echo times. Compared with precontrast images, postcontrast images showed no enhancement in fat and skeletal muscle, moderate enhancement in myocardium, and significant enhancement in ventricular cavity. After contrast injection, the signal ratio of the ventricular chamber to the myocardium significantly increased, and dramatic improvements were seen in the quality of the cineangiographic images and the depiction of cardiac valves. This quantitative study has shown that 3D cardiac cine MR imaging using a blood pool agent provided MR ventriculography and cineangiography with excellent image quality.     

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.     

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

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

Gd—DTPA增强MRI诊断心肌梗塞

15例心脏作Gd-DTPA增强前后MRI检查,增强后为连续动态观察。其中7例为正常对照;7例为心肌梗塞(包括5例亚急性和2例慢性心肌梗塞);1例为陈旧性心肌梗塞。结果显示:增强前正常心肌信号率与梗塞心肌信号率无差别。增强后梗塞心肌信号率既高于增强前也明显高于其周围的正常心肌。无论肉眼观察还是信号测量均发现Gd-DTPA增强MRI能诊断心肌梗塞,改善心肌梗塞的显示。作者对增强后心肌信号率的系列变化作了描述。     

MR imaging of intrarenal macrophage infiltration in an experimental model of nephrotic syndrome.

The objective of this study was to use MR imaging to detect macrophage infiltration of the kidney after injection of ultrasmall superparamagnetic iron oxide (USPIO) particles in a rat model of experimental nephropathy. Ninety micromol of USPIO were injected intravenously in 10 rats with nephropathy secondary to intravenous injection of 5 mg of puromycin aminonucleoside (PAN), and in 10 control rats. The signal intensity was measured in each kidney compartment before and 24 h after injection of the contrast agent. FLASH sequences were performed on a spectrometer operating at 4.7 T. MR findings were compared with histological data. Twenty-four hours after injection of USPIO, a significant decrease (P < 0.0001) was observed in signal intensity in each kidney compartment in the PAN group. There was no variation in the control group. In the diseased kidneys, histological data revealed the presence of macrophages with iron oxide particles within their cytoplasm and lysosomes. Using USPIO, MR imaging can evidence infiltration of the rat kidney by macrophages.     

An improved MR imaging technique for the visualization of myocardial infarction

PURPOSE: To design a segmented inversion-recovery turbo fast low-angle shot (turboFLASH) magnetic resonance (MR) imaging pulse sequence for the visualization of myocardial infarction, compare this technique with other MR imaging approaches in a canine model of ischemic injury, and evaluate its utility in patients with coronary artery disease. MATERIALS AND METHODS: Six dogs and 18 patients were examined. In dogs, infarction was produced and images were acquired by using 10 different pulse sequences. In patients, the segmented turboFLASH technique was used to acquire contrast material-enhanced images 19 days +/- 7 (SD) after myocardial infarction. RESULTS: Myocardial regions of increased signal intensity were observed in all animals and patients at imaging. With the postcontrast segmented turboFLASH sequence, the signal intensity of the infarcted myocardium was 1,080% +/- 214 higher than that of the normal myocardium in dogs-nearly twice that of the next best sequence tested and approximately 10-fold greater than that in previous reports. All 18 patients with myocardial infarction demonstrated high signal intensity at imaging. On average, the signal intensity of the high-signal-intensity regions in patients was 485% +/- 43 higher than that of the normal myocardium. CONCLUSION: The segmented inversion-recovery turboFLASH sequence produced the greatest differences in regional myocardial signal intensity in animals. Application of this technique in patients with infarction substantially improved differentiation between injured and normal regions.     

High field magnetic resonance imaging evaluation of superparamagnetic iron oxide nanoparticles in a permanent rat myocardial infarction

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate superparamagnetic iron oxide (SPIO) nanoparticles to discriminate infarcted from normal tissue after myocardial infarction using high field MR imaging (7 tesla).MATERIALS AND METHODS: Permanent myocardial infarction was induced in rats. SPIO nanoparticles (1 mg Fe/kg) were assessed with T1-weighted gradient echo sequence to visualize the myocardial infarction 48 hours after ligature (n = 6). Furthermore, MR Imaging was performed using a T2-weighted RARE sequence and nanoparticles were injected (5 or 10 mg Fe/kg) on 36 rats 5, 24 or 48 hours after infarction. RESULTS: No changes in contrast between normal and infarcted myocardium was observed after nanoparticle injection on T1-weighted images. However, nanoparticles induced a significant contrast increase between normal and infarcted myocardium on T2-weighted images whatever the delay between infarction and imaging (2.99 +/- 1.66 preinjection vs. 7.82 +/- 1.96 after SPIO injection at a dose of 5 mg Fe/kg 5 hours postinfarction, P = 0.0001). CONCLUSIONS: Nanoparticle injection made it possible to discriminate normal from infarcted myocardium on T2-weighted images. However, the high magnetic field prevented the visualization of the T1 effect of SPIO nanoparticles.     

Mapping cyclic change of regional myocardial blood volume using steady-state susceptibility effect of iron oxide nanoparticles

PURPOSE: To demonstrate an in vivo magnetic resonance imaging (MRI) technique that maps the cyclic change of regional myocardial blood volume (MBV) during the cardiac cycle. MATERIALS AND METHODS: The method is based on the dominant T(2)* shortening effect of iron oxide nanoparticle-induced magnetic susceptibility perturbation in myocardium in the steady state. The technique was demonstrated in vivo with normal mouse hearts at 9.4 T. The regional MBV maps in left ventricular myocardium were computed from the steady-state pre- and post-monocrystalline iron oxide nanoparticle (MION) gradient echo (GE) cine images. Cyclic changes of MBV in normal mice were analyzed quantitatively in different transmural and angular locations. RESULTS: High-resolution MBV maps at various cardiac points were obtained. The study showed a general regional MBV decrease from end-diastole (ED) to end-systole (ES). Percentage reductions were 18.2 +/- 6.6%, P < 0.03 in the lateral wall and 24.7 +/- 3.1%, P < 0.0002 in the interventricular septum. The heterogeneous characteristics of MBV transmural distribution were also reported. CONCLUSION: The steady-state susceptibility effect of intravascular superparamagnetic contrast agent (CA) can be used to map the cyclic change of regional MBV. This imaging approach is relatively simple and may provide a new perspective for functional assessment of the microvasculature in myocardium.     

A physiological barrier distal to the anatomic blood-brain barrier in a model of transvascular delivery

BACKGROUND AND PURPOSE: Osmotic disruption of the blood-brain barrier (BBB) provides a method for transvascular delivery of therapeutic agents to the brain. The apparent global delivery of viral-sized iron oxide particles to the rat brain after BBB opening as seen on MR images was compared with the cellular and subcellular location and distribution of the particles. METHODS: Two dextran-coated superparamagnetic monocrystalline iron oxide nanoparticle contrast agents, MION and Feridex, were administered intraarterially in rats at 10 mg Fe/kg immediately after osmotic opening of the BBB with hyperosmolar mannitol. After 2 to 24 hours, iron distribution in the brain was evaluated first with MR imaging then by histochemical analysis and electron microscopy to assess perivascular and intracellular distribution. RESULTS: After BBB opening, MR images showed enhancement throughout the disrupted hemisphere for both Feridex and MION. Feridex histochemical staining was found in capillaries of the disrupted hemisphere. Electron microscopy showed that the Feridex particles passed the capillary endothelial cells but did not cross beyond the basement membrane. In contrast, after MION delivery, iron histochemistry was detected within cell bodies in the disrupted hemisphere, and the electron-dense MION core was detected intracellularly and extracellularly in the neuropil. CONCLUSION: MR images showing homogeneous delivery to the brain at the macroscopic level did not indicate delivery at the microscopic level. These data support the presence of a physiological barrier at the basal lamina, analogous to the podocyte in the kidney, distal to the anatomic (tight junction) BBB, which may limit the distribution of some proteins and viral particles after transvascular delivery to the brain.     

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.     

Myocardial infarction: optimization of inversion times at delayed contrast-enhanced MR imaging

Seventeen patients underwent magnetic resonance (MR) imaging for myocardial viability with a protocol approved by the institutional review board and gave written informed consent. Breath-hold cine inversion-recovery segmented k-space true fast imaging with steady-state precession sequence, referred to as inversion time (TI) mapping, was performed to determine optimal TI for myocardial infarction inversion-recovery imaging. From TI mapping, optimal TI was 180-315 msec 10-15 minutes after administration of 0.15 mmol/kg of gadolinium-based contrast material. At that optimal TI, relative signal intensity of infarcted myocardium compared with uninfarcted myocardium was maximal (mean +/- standard deviation, 297.8% +/- 86.5), whereas signal-to-noise ratio of uninfarcted myocardium was minimal (4.5 +/- 1.2). When applied to conventional myocardial infarction inversion-recovery imaging, optimal TI resulted in nulling of signal intensity of uninfarcted myocardium in all patients and in excellent conspicuity of infarcted myocardium in all nine patients with visible infarction.     

Histologic confirmation of microvascular hyperpermeability to macromolecular MR contrast medium in reperfused myocardial infarction

A macromolecular MR contrast medium (MMCM) designed to permit histochemical staining and specific tissue localization, albumin-(biotin)10-(Gd-DTPA)25 (Bio-Alb-Gd), was used in a rat model of reperfused myocardial infarction to confirm the presence and distribution of microvascular hyperpermeability. T1-weighted spin-echo images were acquired before and after administration of Bio-Alb-Gd. An avidin-biotin-complex (ABC) stain, specific for the biotinylated MR contrast medium, was used to define the MMCM distribution and to detect any regional change in micro-vascular permeability related to infarction. Immediately after Bio-Alb-Gd administration, the infarcted region was enhanced, with greatest signal intensity noted at the rim and less at the center. There was a gradual increase in signal intensity of the initially hypointense central region. The steady increase in signal intensity of the central region suggested convection transport of MMCM through the interstitial space and its influx into cellular compartment after leakage from the vascular compartment. Histologic findings confirmed regional microvascular hyperpermeability corresponding to the site of infarction and a predominant rim distribution of the MMCM. Bio-Alb-Gd was identified at high microscopic power in the intravascular, interstitial, and intracellular spaces at the periphery of reperfused infarcted myocardium. Bio-Alb-Gd can be used as an MR contrast medium in reperfused infarcted myocardium to confirm the existence and to localize altered microvascular permeability to macromolecules. Bio-Alb-Gd contrast technique removes all the ambiguity between the distribution of the MR or other imaging contrast agent and the distribution of the substrate for histochemical staining.     

Iron oxide nanoparticle-labeled rat smooth muscle cells: cardiac MR imaging for cell graft monitoring and quantitation

PURPOSE: To perform a quantitative analysis of anionic maghemite nanoparticle-labeled cells in vitro and determine the effect of labeling on signal intensity at magnetic resonance (MR) imaging. MATERIALS AND METHODS: The study was approved by the institutional animal care and use committee at H?pital Bichat. In vitro cell proliferation, iron content per cell, and MR signal intensity of cells were measured in agarose phantoms for 0-14 days of culture after labeling of rat smooth muscle cells with anionic maghemite nanoparticles. Next, iron oxide-labeled smooth muscle cells were injected into healthy hearts and hearts with ischemic injury in seven live Fisher rats. Ex vivo MR imaging experiments in excised hearts 2 and 48 hours after injection were performed with a 1.5-T medical imaging system by using T2-weighted gradient-echo and spin-echo sequences. Histologic sections were obtained after MR imaging. Correlation analyses between division factor of iron load and cell amplification factor and between 1/T2 and number of labeled cells or number of days in culture were performed by using linear regression. RESULTS: Viability of smooth muscle cells was not affected by magnetic labeling. Transmission electron micrographs of cells revealed the presence of iron oxide nanoparticles in vesicles up to day 14 of culture. Intracellular iron concentration decreased in parallel with cell division (r2 = 0.99) and was correlated with MR signal intensity (r2 = 0.95). T2*-weighted MR images of excised rat hearts showed hypointense signal in myocardium at 2 and 48 hours after local injection of labeled cells. Subsequent histologic staining evidenced iron oxide nanoparticles within cells and confirmed the presence of the original cells at 2 and 48 hours after implantation. CONCLUSION: Magnetic labeling of smooth muscle cells with anionic maghemite nanoparticles allows detection of cells with MR imaging after local transplantation in the heart.     

Acute myocardial infarction: MR evaluation in 29 patients

This study evaluated the ability of MR to identify and characterize the region of myocardial infarction in humans. Twenty-nine patients, all with ECG and enzyme rises consistent with an acute myocardial infarction, were studied by MR 3-17 days from the onset of acute chest pain. Four patients were excluded because of inability to acquire adequate MR studies. For comparison, 20 normal subjects were studied who also had gated MR examinations. The site of infarction was visualized in 23 patients as an area of high signal intensity in relation to the normal myocardium, a contrast that increased on the second-echo image. The regions of abnormal signal intensity corresponded to the anatomic site of infarction as defined by the ECG changes. The mean T2 relaxation time of the infarcted myocardium (79 +/- 22 msec) was significantly prolonged in comparison with the mean T2 (43.9 +/- 9 msec) of normal myocardium (p less than .01). The mean percentage of contrast (intensity difference) between normal and infarcted myocardium was much greater on the second-echo images (65.6 +/- 34.0%) than the first-echo images (27.5 +/- 18.7%). In the normal subjects there was no difference in T2 between the anterolateral (40.3 +/- 5.7 msec) and septal (39.5 +/- 7.4 msec) regions, and percentages of contrast between these two regions of myocardium on the first-echo (9.1 +/- 7.4%) and second-echo (15.0 +/- 13.3%) images were similar. Thus, MR can be used to directly visualize acute infarcts. However, it has several pitfalls, including the necessity to differentiate signal from slowly flowing blood in the ventricle, from increased signal from a region of infarction and artifactual variation of signal intensity in the myocardium due to respiratory motion or residual cardiac motion.     

MR imaging of cardiac thrombi

This retrospective study of 10 magnetic resonance (MR) examinations in patients with cardiac thrombi (eight in left ventricle and two in right atrium) was performed to assess the ability of MR for demonstrating cardiac thrombi and describe the appearance of cardiac thrombi using the spin echo technique. Cardiac thrombi usually had higher signal intensity than the normal myocardium on MR imaging, especially on the second echo (TE of 56 or 60 ms) image. Differentiation between cardiac thrombus and intracardiac signal resulting from slowly flowing blood was possible based on different signal intensity changes using various techniques. In conclusion, MI imaging constitutes another noninvasive modality for the detection of cardiac thrombus. Further work is needed to determine its accuracy compared with that of two-dimensional echocardiography.     

Superparamegnetic iron oxides for MRI

Pharmaceutical iron oxide preparations have been used as MRI contrast agents for a variety of purposes. These agents predominantly decrease T2 relaxation times and therefore cause a decrease in signal intensity of tissues that contain the agent. After intravenous adminstration, dextran-coated iron oxides typically accumulate in phagocytic cells in liver and spleen. Clinical trials have shown that iron oxide increases lesion/liver and lesion/spleen contrast, that more lesions can be depicted than on plain MRI or CT, and that the size threshold for lesion detection decreases. Decreased uptake of iron oxides in liver has been observed in hepatitis and cirrhosis, potentially allowing the assessment of organ function. More recently a variety of novel, target-specific monocrydtalline iron oxides compounds have been used for receptor and immunospecific images. Future development of targeted MRI contrast agents is critical for organ- or tissue-specific quantitative and functional MRI. Correspondence to: R. Weissleder