Enhancement effects and relaxivities of gadolinium-DTPA at 1.5 versus 3 Tesla: a phantom study.

PURPOse: To investigate the difference in enhancement effects and relaxivities of the gadolinium chelate at 1.5 and 3 Tesla (T) and to elucidate the contribution of the high magnetic field to contrast enhancement in spin-echo (SE) and gradient-echo (GRE) images. METHODS: Phantoms containing water with or without gadopentetate dimeglumine (Gd-DTPA) at different concentrations were scanned using 1.5T and 3T MRI scanners of the same manufacturer and under the same temperature conditions and scanning parameters. Relaxivities of gadolinium, R1 and R2, were estimated from serial T1 and T2 values of the phantoms using linear regression. Contrast enhancement ratios in SE and GRE T1-weighted images were compared at 1.5 and 3T. RESULTS: The R1 and R2 of Gd-DTPA at 1.5 and 3T were 4.79 and 5.14, and 4.50 and 5.09, respectively. Although the relaxivities at 3T were slightly lower than those at 1.5T, the contrast enhancement ratio improved in both SE and GRE images as a result of T1 prolongation of the water at 3T. CONCLUSION: The decrease in relaxivities of the Gd-DTPA at 3T appears to be so small that T1 prolongation of the water improves contrast enhancement, suggesting a potential clinical advantage in administration of Gd-DTPA at high field strength.     

High-relaxivity contrast-enhanced magnetic resonance neuroimaging: a review

Evaluation of brain lesions using magnetic resonance imaging (MRI) provides information that is critical for accurate diagnosis, prognosis, therapeutic intervention and monitoring response. Conventional contrast-enhanced MR neuroimaging using gadolinium (Gd) contrast agents primarily depicts disruption of the blood-brain barrier, demonstrating location and extent of disease, and also the morphological details at the lesion site. However, conventional imaging results do not always accurately predict tumour aggressiveness. Advanced functional MRI techniques such as dynamic contrast-enhanced perfusion-weighted imaging utilise contrast agents to convey physiological information regarding the haemodynamics and neoangiogenic status of the lesion that is often complementary to anatomical information obtained through conventional imaging. Most of the Gd contrast agents available have similar T1 and T2 relaxivities, and thus their contrast-enhancing capabilities are comparable. Exceptions are gadobenate-dimeglumine, Gd-EOB-DTPA, Gadobutrol and gadofosveset, which, owing to their transient-protein-binding capability, possess almost twice (and more) the T1 and T2 relaxivities as other agents at all magnetic field strengths. Numerous comparative studies have demonstrated the advantages of the increased relaxivity in terms of enhanced image contrast, image quality and diagnostic confidence. Here we summarise the benefits of higher relaxivity for the most common neuroimaging applications including MRI, perfusion-weighted imaging and MRA for evaluation of brain tumours, cerebrovascular disease and other CNS lesions.     

Nanotemplate-engineered nanoparticles containing gadolinium for magnetic resonance imaging of tumors

PURPOSE: To design nanoparticles containing accessible gadolinium atoms (Gd-NPs) as a contrast agent for magnetic resonance imaging of tumors. METHODS: Nanoparticles containing phospholipid-chelates (phosphoethanolamine diethylenetriaminepentaacetate) and DSPE-PEG (MW5000) were prepared from Brij 78 and stearyl alcohol using the nanotemplate engineering approach. After addition of GdCl3, the presence of gadolinium on the surface of nanoparticles was quantified using inductively coupled plasma atomic emission spectroscopy. The in vitro relaxivities of the Gd-NPs in phosphate buffered saline were assessed at 4.7 T. The conditional binding constants of nanoparticle formulations were determined spectrophotometrically by competitive titration. Transmetallation kinetics of Gd from nanoparticles with Cu2+ and Zn2+ as the competing ions was measured in acetate buffer. The biodistribution profiles, pharmacokinetics, and contrast enhancement in tumor region was studied after administration of Gd-NPs to nude mice bearing A549 lung carcinoma xenografts. RESULTS: Gd-NPs with an average diameter of 138 nm possessing surface chelating functions were prepared from GRAS (generally regarded as safe) materials. The longitudinal relaxivity (r1) and transverse relaxivity (r2) of Gd-NPs in 10% fetal bovine serum at 4.7 T were 7.1 (+/-0.2) and 13.0 (+/-0.7) 1/mM/s, respectively. These pegylated Gd-NPs had enhanced relaxivities and exhibited particle size stability, sufficient binding affinity, and kinetic inertness under physiologic conditions. The contrast enhancement in tumors was demonstrated 40, 120, and 360 minutes after intravenous injection of Gd-NPs at a dose of 0.1 mmol Gd/kg. The Gd plasma concentration of Gd-NPs over a period of 24 hours fit a two-compartmental model with Cl sys = 0.89 mL/h and MRT = 5.93 h. The amount of Gd that accumulated in the tumor region was consistent with the estimated value obtained by T1 measurements using MR imaging. CONCLUSION: Pegylated nanoparticles composed of biocompatible, biodegradable materials and possessing accessible Gd ions on their surface induce relaxivities in the bulk water signal and accumulated sufficiently in tumors, demonstrating their utility as potential magnetic resonance imaging tumor contrast enhancement agents.     

Initial experience of 3 tesla endorectal coil magnetic resonance imaging and 1H-spectroscopic imaging of the prostate

RATIONALE AND OBJECTIVES: We sought to explore the feasibility of magnetic resonance imaging (MRI) of the prostate at 3T, with the knowledge of potential drawbacks of MRI at high field strengths. MATERIAL AND METHOD: MRI, dynamic MRI, and 1H-MR spectroscopic imaging were performed in 10 patients with prostate cancer on 1.5T and 3T whole-body scanners. Comparable scan protocols were used, and additional high-resolution measurements at 3T were acquired. For both field strengths the signal-to-noise ratio was calculated and image quality was assessed. RESULT: At 3T the signal-to-noise ratio improved. This resulted in increased spatial MRI resolution, which significantly improved anatomic detail. The increased spectral resolution improved the separation of individual resonances in MRSI. Contrast-enhanced time-concentration curves could be obtained with a doubled temporal resolution. CONCLUSIONS: Initial results of endorectal 3T 1H-MR spectroscopic imaging in prostate cancer patients showed potential advantages: the increase in spatial, temporal, and spectral resolution at higher field strength may result in an improved accuracy in delineating and staging prostate cancer.     

Magnetic resonance imaging of the pancreas at 3.0 tesla: qualitative and quantitative comparison with 1.5 tesla

OBJECTIVES: We sought to perform a preliminary comparison of signal-to-noise ratio (SNR) and image quality for magnetic resonance imaging (MRI) of the pancreas at 1.5 and 3 T. MATERIALS AND METHODS: Two imaging cohorts were studied using a T2-weighted, single-shot fast spin-echo pulse sequence and a T1-weighted, fat-suppressed 3D gradient-echo pulse sequence. In the first cohort, 4 subjects were imaged using identical imaging parameters before and after contrast administration at 1.5 and 3.0 T. The SNR was quantified for the pancreas as well as for the liver, spleen, and muscle. In a second cohort of 12 subjects in whom the receiver bandwidth was adjusted for field strength, SNR measurements and qualitative rankings of image quality were performed. RESULTS: In the study cohort using identical imaging parameters at both magnetic field strengths, the mean (SD) ratios of SNR at 3.0 to 1.5 T of the single-shot fast spin-echo images for the pancreas, liver, spleen, and muscle were 1.63 (0.39), 1.82 (0.39), 1.45 (0.18), 2.01 (0.16), respectively. For the precontrast fat-suppressed 3D gradient-echo sequence, the corresponding ratios were 1.28 (0.29), 1.26 (0.30), 1.16 (0.27), and 1.76 (0.45), respectively; for the arterial phase, the corresponding ratios were 2.02 (0.28), 1.60 (0.42), 1.47 (0.26), and 1.94 (0.32), respectively; and for the delayed postcontrast phase, the corresponding ratios were 1.63 (0.51), 2.01 (0.25), 1.66 (0.06), and 2.31 (0.47), respectively. The SNR benefit of 3.0 T was significantly greater on contrast-enhanced as compared with noncontrast T1-weighted 3D gradient-echo images. In the second study cohort, SNR was superior at 3.0 T, although the use of a reduced readout bandwidth at 1.5 T substantially diminished the advantage of the higher field system. With qualitative comparison of images obtained at the 2 magnetic field strengths, the fat-suppressed 3D gradient-echo images obtained at 3.0 T were preferred, whereas the single shot fast spin-echo images obtained at 1.5 T were preferred because of better signal homogeneity. CONCLUSIONS: Our results in a small cohort of volunteers and patients demonstrate a marked improvement in SNR at 3.0 T compared with 1.5 T (by a factor of 2 in some cases) when identical imaging parameters were used. The SNR advantage at 3.0 T is diminished but persists when the receiver bandwidth is adjusted for magnetic field strength. The results suggest that 3.0 T may offer promise for improved body MRI, although further technical development to optimize SNR and improve signal homogeneity will be needed before its full potential can be achieved.     

Dy-DTPA derivatives as relaxation agents for very high field MRI: the beneficial effect of slow water exchange on the transverse relaxivities.

Proton longitudinal and transverse relaxivities of Dy(DTPA)(2-) and Dy-DTPA bisamide derivatives (Dy(DTPA-BA): Dy-DTPA bisamide, Dy(DTPA-BEA): Dy-DTPA bisethylamide, Dy(DTPA-BnBA): Dy-DTPA bis-n-butylamide, and Dy(DTPA-BBMA): Dy-DTPA bisbismethylamide) were analyzed between 0.47 T and 18.8 T. Curie longitudinal relaxation was clearly observed at magnetic fields larger than 2.4 T, but the longitudinal relaxivities are limited by the fast rotation of the complexes. Rotational correlation times were separately assessed by deuterium relaxometry of the diamagnetic deuterated lanthanum analogs. Transverse relaxivity, which depends on the square of the magnetic field and on the residence time of the coordinated water molecule (tau(M)), was more than 7.5 times larger at 18.8 T and 310 K for Dy(DTPA-BA) and Dy(DTPA-BEA) as compared to Dy(DTPA)(2-). This difference is mainly related to the slower water exchange of the bisamide complexes, as confirmed by the values of tau(M) measured by oxygen-17 relaxometry. Such Dy-complexes, characterized by relatively long tau(M) values (tauM310 larger than 100 ns but smaller than 1 micros), thus appear to be useful as negative T(2) (or transverse) contrast agents for high-field imaging. This was demonstrated by the spin-echo images of phantoms obtained at 4.7 T on samples containing Dy(DTPA)(2-) and Dy(DTPA-BEA).     

Improved preoperative evaluation of cerebral cavernomas by high-field, high-resolution susceptibility-weighted magnetic resonance imaging at 3 Tesla: comparison with standard (1.5 T) magnetic resonance imaging and correlation with histopathological findings--preliminary results

OBJECTIVES: To compare high-field, high-resolution, susceptibility-weighted magnetic resonance imaging (3 Tesla [T] HR-SW-MRI) and standard (1.5 Tesla [T]) MRI for the detection of cerebral cavernomas. To evaluate the ability of 3 T HR-SW-MRI to visualize intralesional structures compared with standard (1.5 T) MRI, in correlation with histopathologic findings. MATERIALS AND METHODS: Seventeen patients with cerebral cavernomas underwent both standard (1.5 T) MRI (T1-SE, T2-TSE, T2*-GRE) and 3 T HR-SW-MRI (TR/TE 43.3/9.1 millisecond; 512 x 384 x 48 matrix; FOV 250 mm; SI 72 mm) at our institution. All MR images were evaluated by 3 radiologists in consensus for detectability, size (1 cm), and conspicuity (good, acceptable, poor) of the lesions at both field strengths, and for the presence of hypointense intralesional tubular structures. In 7 patients, MR findings were correlated with histopathologic findings. RESULTS: Both 3 T HR-SW-MRI and standard (1.5 T) MRI detected 22 lesions in 17 patients; 3 T HR-SW-MRI detected an additional 7 lesions in 6 patients. On average, 3 T HR-SW-MRI detected 1.706 +/- 0.92 (median = 1) lesions per patient, whereas standard (1.5 T) MRI detected 1.235 +/- 0.664 lesions per patient (P = 0.016). Lesion conspicuity was good in all 3 T HR-SW-MR images and good in 68.2% and acceptable in 31.8% of standard (1.5 T) MR images (P = 0.016). In 22 lesions detected at both field strengths, 3 T HR-SW-MRI demonstrated intralesional tubular structures in 72.7% and standard (1.5 T) MRI demonstrated these structures in 31.8% (P = 0.001). Intralesional tubular structure correlated to conglomerates of cavernous vessel, as verified by histopathology. CONCLUSION: Compared with standard (1.5 T) MRI, 3 T HR-SW-MRI allows superior detection and characterization of cerebral cavernomas. Despite increased susceptibility effects, ie, signal loss at higher magnetic field strengths, the visualization of intralesional tubular structures is feasible. This may be helpful in the diagnosis, presurgical planning, and noninvasive follow-up after gamma-knife radiosurgery.     

Liver-lesion tissue contrast on MR images: effect of iron oxide concentration and magnetic field strength

This study assessed the enhancement of liver-lesion contrast by using low levels of iron oxide contrast agent at four common magnetic resonance (MR) imaging field strengths: 0.15, 0.35, 0.5, and 1.5 T. Adenocarcinomas were percutaneously inserted into the livers of 15 rats. Iron oxide was given intravenously in concentrations of 0 (control group), 2.5, 5, 10, and 20 mumol/kg to three rats in each concentration group. All images were acquired between 1 and 24 hours after injection. Liver-lesion contrast ratios and contrast-to-noise ratios (C/Ns) were calculated. Results showed increased liver-lesion contrast and C/Ns with increased iron oxide concentration up to 10-20 mumol/kg at all four magnetic field strengths. At 0.15 T, iron oxide produced lower gains in tumor-liver contrast. At middle and high magnetic field strengths, liver-lesion contrast was similar for each level of iron oxide concentration, but C/Ns were markedly higher at 1.5 T than at middle field strength. Low levels of iron oxide contrast agent are effective at magnetic field strengths of 0.35 T and above, producing the greatest increase in C/N at middle field strengths.     

T1 measurements in cell cultures: a new tool for characterizing contrast agents at 1.5T.

The objective of this work was to assess the feasibility and accuracy of T1 and relaxivity measurements in cell cultures using 1.5T magnetic resonance imaging (MRI) with the long-term goal to develop a tool for evaluation of novel paramagnetic agents in a realistic macromolecular environment. This initial study was carried out using MCF-7 cells treated with independently determined concentrations of Gd-DTPA. Two cell culture systems were evaluated: cell pellets and single layers of cells grown on microporous inserts. High-resolution T1 measurements of cell cultures were acquired with two dimensional Inversion Recovery Fast Spin Echo (2D-IR-FSE), three dimensional Inversion Recovery Fast Spin Echo (3D-IR-FSE), and 3D-SPGR sequences. The T1 and relaxivity accuracy of these sequences was confirmed with aqueous Gd-DTPA samples of known concentration. Relaxivities of 1.71 +/- 0.15 [mM(-1)second(-1)] and 1.55 +/- 0.50 [mM(-1)second(-1)] were measured in the cell pellets and cell monolayers, respectively, and were different from the value of 4.3 [mM(-1)second(-1)] for Gd-DTPA in water. Both cell pellets and monolayers are suitable for initial assessment of novel MR contrast agents.     

Time-to-echo optimization for spin echo magnetic resonance imaging of liver metastasis using superparamagnetic iron oxide particles.

Superparamagnetic iron oxide (SPIO) particles are used as a contrast agent in liver magnetic resonance imaging (MRI). SPIO particles exert their greatest influence on T2-weighted MR signal intensity. The time-to-echo (TE) value that provides optimal contrast has not been systematically studied over the range of clinically relevant field strengths. The purpose of this study was to quantitatively evaluate the TE dependence of the post-SPIO tumor to liver contrast-to-noise ratio (CNR). The hypothesis was that there is a TE that provides an optimal CNR. Subjects having probable metastatic hepatic lesions secondary to colorectal carcinoma were studied. Pre- and post-SPIO images were acquired at TE-effective (TE(eff)) equal to 46, 76, and 106 msec by using a turbo spin echo pulse sequence at 0.2 T and 1.5 T. The CNR for all lesions greater than 1 cm in diameter was determined in pre- and post-SPIO images. A paired statistical design was used to identify TE-related CNR dependencies. The primary findings were as follows. (1) CNR differences attributable to TE(eff) variation over the range of 46-106 msec were less than 34%. For 0.2 T, TE(eff) = 46 msec yielded a statistically significantly greater CNR than did TE(eff) = 76 or 106 msec. The same was true at the higher field strength, but differences were not significant. (2) Signal-to-noise measures suggested that SPIO reduced the lesion signal. (3) Post-SPIO CNR was significantly greater at 1.5 T than at 0.2 T. The observations indicate that over the field strength range of 0.2-1.5 T, CNR differences attributable to the TE(eff) variation, while being statistically significant in some cases, are small relative to those resulting from the SPIO administration.     

Cell internalization of anionic maghemite nanoparticles: quantitative effect on magnetic resonance imaging.

Anionic iron oxide nanoparticles are efficiently internalized into macrophages where they concentrate within micrometric endosomes, conferring on them a high magnetic susceptibility. The uptake of anionic maghemite nanoparticles by macrophages was quantified by an electron spin resonance (ESR) experiment. MR spin-echo sequences were performed with various TEs and TRs. The contrast enhancement was compared between two types of agarose phantoms with the same equivalent ferrite concentrations but containing either dispersed isolated nanoparticles or magnetically labeled macrophages. It is shown that the intracellular confinement of maghemite nanoparticles within micrometric endosomes results in a significant decrease of the longitudinal relaxivity and a moderate decrease of the transverse relaxivity compared to the relaxivities of the dispersed isolated nanoparticles. As a consequence, the signature of endosomal magnetic labeling consists of a negative contrast on T(1)-weighted images in the whole ferrite concentration range, whereas the presence of extracellular isolated nanoparticles can result in a positive enhancement.     

Cardiac magnetic resonance parallel imaging at 3.0 Tesla: technical feasibility and advantages

PURPOSE: To quantify changes in signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), specific absorption rate (SAR), RF power deposition, and imaging time in cardiac magnetic resonance imaging with and without the application of parallel imaging at 1.5 T and 3.0 T. MATERIALS AND METHODS: Phantom and volunteer data were acquired at 1.5 T and 3.0 T with and without parallel imaging. RESULTS: Doubling field strength increased phantom SNR by a factor of 1.83. In volunteer data, SNR and CNR values increased by factors of 1.86 and 1.35, respectively. Parallel imaging (reduction factor = 2) decreased phantom SNR by a factor of 1.84 and 2.07 when compared to the full acquisition at 1.5 T and 3.0 T, respectively. In volunteers, SNR and CNR decreased by factors of 2.65 and 2.05 at 1.5 T and 1.99 and 1.75 at 3.0 T, respectively. Doubling the field strength produces a nine-fold increase in SAR (0.0751 to 0.674 W/kg). Parallel imaging reduced the total RF power deposition by a factor of two at both field strengths. CONCLUSIONS: Parallel imaging decreases total scan time at the expense of SNR and CNR. These losses are compensated at higher field strengths. Parallel imaging is effective at reducing total power deposition by reducing total scan time.     

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.     

Multicontrast-weighted magnetic resonance imaging of atherosclerotic plaques at 3.0 and 1.5 Tesla: ex-vivo comparison with histopathologic correlation

The purpose was to analyze magnetic resonance (MR) plaque imaging at 3.0 Tesla and 1.5 Tesla in correlation with histopathology. MR imaging (MRI) of the abdominal aorta and femoral artery was performed on seven corpses using T1-weighted, T2-weighted, and PD-weighted sequences at 3.0 and 1.5 Tesla. Cross-sectional images at the branching of the inferior mesenteric artery and the profunda femoris were rated with respect to image quality. Corresponding cross sections of the imaged vessels were obtained at autopsy. The atherosclerotic plaques in the histological slides and MR images were classified according to the American Heart Association (AHA) and analyzed for differences. MRI at 3.0 Tesla offered superior depiction of arterial wall composition in all contrast weightings, rated best for T2-weighted images. Comparing for field strength, the highest differences were observed in T1-weighted and T2-weighted techniques (both P< or =0.001), with still significant differences in PD-weighted sequence (P< or =0.005). The majority of plaques were histologically classified as calcified plaques. In up to 21% of the cases, MRI at both field strengths detected signal loss characteristic of calcification although calcified plaque was absent in histology. MRI at 3.0 Tesla offers superior plaque imaging quality compared with 1.5 Tesla, but further work is necessary to determine whether this translates in superior diagnostic accuracy.     

Effect of contrast dose and field strength in the magnetic resonance detection of brain metastases

PURPOSE: To compare the diagnostic efficacy of a standard and cumulative triple dose of magnetic resonance (MR) imaging contrast agent in the evaluation of brain metastases using a high-field 3.0 T MR unit versus a standard field 1.5 T MR unit. METHODS: Twenty-two patients with suspected brain metastases were examined at both field strengths using identical postcontrast coronal 3D gradient echo with magnetization preparation, which was adjusted separately for each field strength. In both groups initially, iv injection of 0.1 mmol/kg body weight gadolinium chelate (gadodiamide) and thereafter, 0.2 mmol/kg body weight gadodiamide were administered. Subjective assessment of the images was performed independently by 3 neuroradiologists. Objective measurement of signal-to-noise and contrast-to-noise ratios was obtained. RESULTS: The subjective assessment of cumulative triple-dose 3.0 T images obtained the best results compared with other sequences, detecting 84 metastases, followed by 1.5 T cumulative triple-dose enhanced images with 81 brain metastases. The objective assessment confirmed those results, showing significantly higher signal-to-noise and contrast-to-noise ratios with 3.0 T than with 1.5 T. CONCLUSIONS: Cumulative triple-dose images of both field strengths were superior to standard field strengths. However, administration of gadodiamide contrast agent produces higher contrast between tumor and normal brain on 3.0 T than on 1.5 T, resulting in better detection of brain metastases and leptomeningeal involvement.     

Comparison between functional magnetic resonance imaging at 1.5 and 3 Tesla: effect of increased field strength on 4 paradigms used during presurgical work-up

OBJECTIVES: We sought to evaluate the benefit of 3 T compared with 1.5 T during presurgical functional magnetic resonance imaging. MATERIALS AND METHODS: Six participants performed a motor, a visual, and 2 language paradigms both at 1.5 and 3 T. The number of activated voxels, mean t-value, and assessment of language dominancy were compared between both field strengths. Group analysis was performed to evaluate the influence of field strength on the cortical language activation patterns. RESULTS: The number of activated voxels and mean t-values were significantly higher at 3 T for all paradigms. Using the same statistical threshold, language activation was significantly less lateralized, and more activation zones were depicted at 3 T compared with 1.5 T. CONCLUSIONS: Sensitivity associated with visual, motor and language functional magnetic resonance imaging increased significantly at 3 T. Additional cortical areas were depicted during language processing at 3 T. For assessment of language dominancy, usage of more stringent statistical thresholds at 3 T is suggested.     

Fluorescent bacterial magnetic nanoparticles as bimodal contrast agents

OBJECTIVES: The purpose of this study was to assess whether fluorochrome-coupled bacterial magnetic nanoparticles can be used as bimodal contrast agent for both magnetic resonance imaging (MRI) and near-infrared fluorescence optical (NIRF) imaging of cultured macrophages. MATERIALS AND METHODS: Bacterial magnetic nanoparticles (magnetosomes, particle diameter: 42 nm) were harvested from Magnetospirillum gryphiswaldense and characterized by using MRI. After covalent coupling to the fluorescent dye DY-676 (lambdaabs./lambdaem.= 676 nm/701 nm, Dyomics, Jena, Germany), the fluorescent magnetosomes were analyzed by fluorescence-activated cell sorting. Subsequently, murine macrophages J774 were incubated with the bimodal contrast agent (3 hours) and examined by a whole-body near infrared small animal imaging system as well as by using a 1.5 T clinical MR system. Moreover, labeled cells were characterized using confocal laser scanning microscopy (CLSM) and ultrathin section transmission electron microscopy. RESULTS: Characterization of the nanoparticles by MRI revealed R1 and R2 relaxivities of 3.2 mMs and 526 mMs, respectively. Fluorochrome-coupled magnetosomes exhibited increased fluorescence intensities at wavelengths >670 nm. Macrophages that were incubated with the contrast agent showed a significant fluorescence emission in the near infrared range as imaged with a whole body NIR imaging system, FACS analysis and CLSM. Moreover, CLSM data showed the greatest fluorescence intensities within intracellular compartments and colocalized with the magnetosomes. With MRI, both T1 and T2 relaxation times were substantially shortened at concentrations greater than 600 cells/microL. DISCUSSION AND CONCLUSION: Macrophages could be labeled with fluorescent magnetosomes, and they were successfully imaged using both a 1.5 T MR scanner as well as with NIRF optical methods. The use of this bimodal contrast agent for diagnostic purposes may benefit from the excellent spatial resolution of the MRI and the high sensitivity of the fluorescence imaging.     

Species dependence on plasma protein binding and relaxivity of the gadolinium-based MRI contrast agent MS-325

RATIONALE AND OBJECTIVES: We sought to determine whether there is a species dependence on plasma protein and serum album binding and/or relaxivity of the MR contrast agent MS-325. METHODS: Equilibrium binding of MS-325 to plasma proteins or purified serum albumin was determined as a function of chelate concentration. T1 and T2 values were determined at 0.47 and 1.41 T, and NMRD profiles were measured to determine the changes in relaxivity over varying field strengths from 0.002 to 1.2 T. RESULTS: The binding of MS-325 to either animal plasma or serum albumin plateaus at chelate concentrations less than 0.1 mM with human, pig, and rabbit plasmas showing maximum binding. Human and pig plasmas show the greatest observed relaxivity enhancement in the presence of MS-325. CONCLUSIONS: MS-325 exhibits increased relaxivity in blood plasma as the result of plasma protein binding. Binding ranged from 64% to 91% and was species dependent: human > pig approximately rabbit > dog approximately rat approximately mouse.     

Exogenous contrast agent improves sensitivity of gradient-echo functional magnetic resonance imaging at 9.4 T.

Relative to common clinical magnetic field strengths, higher fields benefit functional brain imaging both by providing additional signal for high-resolution applications and by improving the sensitivity of endogenous contrast due to the blood oxygen level dependent (BOLD) mechanism, which has limited detection power at low magnetic fields relative to the use of exogenous contrast agent. This study evaluates the utility of iron oxide contrast agent for gradient echo functional MRI at 9.4 T in rodents using cocaine and methylphenidate as stimuli. Relative to the BOLD method, the use of high iron doses and short echo times provided a roughly twofold global increase in functional sensitivity, while also suppressing large vessel signal and reducing susceptibility artifacts. Furthermore, MRI measurements of the functional percentage change in cerebral blood volume (CBV) showed excellent agreement with results obtained at much lower magnetic field strengths, demonstrating that MRI estimates of this quantity are roughly independent of magnetic field when appropriate techniques are employed. The derived field dependencies for relative sensitivity and MRI estimates of the percentage change in CBV suggest that the benefits provided by exogenous agents will persist even at much higher magnetic fields than 9.4 T.     

NMRD investigation of DyDTPA- and GdDTPA-labeled starch particles. Selection of a suitable suspension medium and influence of the starch matrix on relaxivity

RATIONALE AND OBJECTIVES: The primary aim was to investigate the influence of the starch matrix on the T1 relaxivities of starch particles labeled with gadolinium and dysprosium diethylenetriamine pentaacetic acid (GdDTPA-SP and DyDTPA-SP). Achieving this required the selection of a medium that was suitable for suspending the particles and that had field-independent T1 relaxation rates, thereby eliminating errors in relaxivity determinations resulting from a field-dependent background. METHODS: GdDTPA-SP with low and high gadolinium content, DyDTPA-SP, and empty DTPA-SP were suspended in an aqueous medium containing 5% (w/w) of a polyethylene glycol-based block copolymer. 1/T1 NMRD profiles were obtained in the temperature range of 5 degrees to 35 degrees C. RESULTS: Using the block copolymer, particles did not settle, and samples could be prepared at a low temperature to avoid particle degradation, the intrinsic T1 relaxation rate of the suspension medium was field-independent and identical to that of water from 25 degrees to 35 degrees C. The T1 relaxivities of DyDTPA-SP were higher than those of dysprosium diethylenetriamine pentaacetate-bis(methylamide) (DyDTPA-BMA) and decreased with increasing magnetic field strength. The T1 relaxivity of GdDTPA-SP was higher than that of GdDTPA at all fields, and decreased with decreasing temperature and increasing gadolinium content. CONCLUSIONS: The GdDTPA-SP results showed that the particulate starch matrix served a dual role, with opposing influences on relaxivity. It provided a means for increasing the rotational correlation time (tau R), which resulted in higher relaxivities. However, it also retarded radial diffusion of water molecules within the particle interior, which significantly counteracted the enhancing effect of tau R. For DyDTPA-SP, the starch matrix provided an additional diamagnetic contribution, resulting in relaxivities higher than those of DyDTPA-BMA. The block copolymer was suitable as a suspension medium for DyDTPA-SP and GdDTPA-SP and should also be applicable for other particulates.