Measurement of bioreactor perfusion using dynamic contrast agent-enhanced magnetic resonance imaging.

Dynamic magnetic resonance imaging was used to monitor solute diffusion through aggregates of Chinese hamster ovary cells growing on macroporous carriers in a fixed-bed bioreactor. Diffusion-weighted (1)H magnetic resonance imaging (MRI) and scanning electron microscopy demonstrated that cell growth in the bioreactor was heterogeneous, with the highest cell densities being found at the periphery of the carriers. T(1)-weighted magnetic resonance imaging measurements of the inflow of a commonly used magnetic resonance contrast agent, gadolinium-diethylenetriaminopentaacetic acid (Gd-DTPA), showed that migration of the agent through the peripheral cell masses could be explained by diffusion. However, appearance of the contrast agent in the center of the carriers was too fast to be explained by simple diffusion and indicated that these regions were perfused by convective flow. The average diffusivity of Gd-DTPA through the cell mass was found to be (2.4 +/- 0.2) x 10(-10) m(2) sec(-) (mean +/- SEM). This technique will be useful in the characterization and development of high-cell-density bioreactor systems, in which solute transport plays a critical role in cell growth and physiology.     

Hollow fiber bioreactor: new development for the study of contrast agent transport into hepatocytes by magnetic resonance imaging

The aim of our study was to develop a magnetic resonance (MR)-compatible in vitro model containing freshly isolated rat hepatocytes to study the transport of hepatobiliary contrast agents (CA) by MR imaging (MRI). We set up a perfusion system including a perfusion circuit, a heating device, an oxygenator, and a hollow fiber bioreactor (HFB). The role of the porosity and surface of the hollow fiber (HF) as well as the perfusate flow rate applied on the diffusion of CAs and O2 was determined. Hepatocytes were isolated and injected in the extracapillary space of the HFB (4 x 10(7) cells/mL). The hepatocyte HFB was perfused with an extracellular CA, gadopentetate dimeglumine (Gd-DTPA), and gadobenate dimeglumine (Gd-BOPTA), which also enters into hepatocytes. The HFB was imaged in the MR room using a dynamic T1-weighed sequence. No adsorption of CAs was detected in the perfusion system without hepatocytes. The use of a membrane with a high porosity (0.5 microm) and surface (420 cm2), and a high flow rate perfusion (100 mL/min) resulted in a rapid filling of the HFB with CAs. The cellular viability of hepatocytes in the HFB was greater than 85% and the O2 consumption was maintained over the experimental period. The kinetics of MR signal intensity (SI) clearly showed the different behavior of Gd-BOPTA that enters into hepatocytes and Gd-DTPA that remains extracellular. Thus, these results show that our newly developed in vitro model is an interesting tool to investigate the transport kinetics of hepatobiliary CAs by measuring the MR SI over time.     

Application of cell penetrating peptide in magnetic resonance imaging of bone marrow mesenchymal stem cells

Tracking the distribution and differentiation of stem cells by high-resolution imaging techniqueswould have significant clinical and research implications.In this study,a model cell-penetrating peptide wasused to carry gadolinium particles for magnetic resonance imaging (MRI) of mesenchymal stem cells (MSCs).MSCs were isolated from rat bone marrow and identified by osteogenic differentiation in vitro.The cell-penetrating peptide labeled with fluorescein-5-isothiocyanate (FITC) and gadolinium was synthesized by asolid-phase peptide synthesis method.Fluorescein imaging analysis confirmed that this new peptide couldinternalize into the cytoplasm and nucleus at room temperature,4℃ and 37℃.Gadolinium were efficientlyinternalized into mesenchymal stem cells by the peptide in a time or concentration-dependent manner,resulting in intercellular shortening of longitudinal relaxation enhancements,which were obviously detectedby 1.5 Tesla Magnetic Resonance Imaging.Cytotoxicity assay and flow cytometric analysis showed thatthe intercellular contrast medium incorporation did not affect cell viability at the tested concentrations.Thein vitro experiment results suggested that the new constructed peptides could be a vector for trackingMSCs.     

Dendrimer functionalized magnetic nanoparticles as a promising platform for localized hyperthermia and magnetic resonance imaging diagnosis

Magnetic iron oxide nanoparticles are a well-explored class of nanomaterials known for their high magnetization and biocompatibility. They have been used in various biomedical applications such as drug delivery, biosensors, hyperthermia, and magnetic resonance imaging (MRI) contrast agent. It is necessary to surface modify the nanoparticles with a biocompatible moiety to prevent their agglomeration and enable them to target to the defined area. Dendrimers have attracted considerable attention due to their small size, monodispersed, well-defined globular shape, and a relative ease incorporation of targeting ligands. In this study, superparamagnetic iron oxide nanoparticles were synthesized via a coprecipitation method. The magnetic nanoparticles (MNPs) had been modified with (3-aminopropyl) triethoxysilane, and then polyamidoamine functionalized MNPs had been synthesized cycling. Various characterization techniques had been used to reveal the morphology, size, and structure of the nanoparticles such as scanning electron microscopy, transmission electron microscope, X-ray diffraction analysis, and vibrating sample magnetometer, Fourier-transform infrared spectroscopy and zeta potential measurements. In addition, the cytotoxicity property of G3–dendrimer functionalized MNPs were evaluated using 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide assay which confirmed the biocompatibility of the nanocomposites. Dendrimer functionalized MNPs are able to act as contrast agents for MRI and magnetic fluid hyperthermia mediators. A superior heat generation was achieved for the given concentration according to the hyperthermia results. MRI results show that the synthesized nanocomposites are a favorable option for MRI contrast agent. We believe that these dendrimer functionalized MNPs have the potential of integrating therapeutic and diagnostic functions in a single carrier.     

Nuclear magnetic resonance imaging of mummified corpses

Clinical applications of nuclear magnetic resonance (NMR) imaging have demonstrated its great potential for noninvasive examinations of soft tissues. Here preliminary experiments are reported on mummified human tissue by means of NMR cross-sectional and transmission imaging. For this purpose the natural viscosity of the tissues has been lowered by rehydration with an aqueous solution of 20% acetone.     

Analysis of CHO-K1 cell growth in a fixed bed bioreactor using magnetic resonance spectroscopy and imaging

Non-invasive magnetic resonance imaging and spectroscopy techniques have been used to monitor the growth and distribution of Chinese hamster ovary K1 cells growing in a fixed bed bioreactor composed of macroporous carriers. Diffusion-weighted 1H magnetic resonance spectroscopy was used to monitor the volume fraction of the bioreactor occupied by the cells and diffusion-weighted 1H magnetic resonance imaging was used to map cell distribution. The imaging measurements demonstrated that cell growth in the bioreactor was heterogeneous, with the highest cell densities being found at the surface of the carriers. The increase in the volume fraction occupied by the cells during cell growth showed a close correlation with bioreactor ATP content measured using 31P magnetic resonance spectroscopy. These magnetic resonance measurements, in conjunction with measurements of bioreactor glucose consumption, allowed estimation of the specific glucose consumption rate. This declined during the culture, in parallel with medium glucose concentration. This revised version was published online in July 2006 with corrections to the Cover Date.     

Haemodynamic effects of macrocyclic and linear gadolinium chelates in rats: role of calcium and transmetallation

Several studies were undertaken to compare four magnetic resonance imaging (MRI) contrast media (CM) as regards acute haemodynamic effects in rats and to investigate the mechanisms involved. (1) Normotensive rats received a rapid bolus intravenous injection of 0.5 mmol kg of each CM. The effects of Gd-DOTA, Gd-HP-DO3A, Gd-DTPA and Gd-DTPA-BMA on blood pressure (BP) were compared. (2) The haemo-dynamic effects of Gd-DTPA (0.5 mmol kg ) were compared to those of isovolumic and isoosmolar Zn-DTPA and glucose solutions. (3) The haemodynamic profiles of Gd-DTPA and Gd-DTPA-BMA were recorded with and without addition of ionized calcium. (4) The mechanism of Gd-HP-DO3A-induced tran-sient rise in BP was investigated by evaluating the effects of phentolamine or diltiazem pretreatment. For (1) the greatest drop in BP occurred following Gd-DTPA (a linear chelate) injection (–18 ± 2% vs base-line, P < 0.01). Gd-DTPA-BMA, another lineate chelate, also induced a slight but significant reduction in BP (–8 ± 2% at 45 s, P < 0.05). Gd-DOTA, a macrocyclic CM, had virtually no haemodynamic effects. For (2) the Gd-DTPA-induced drop in BP was greater than that of the osmolality-matched glucose control and lower than that of osmolality-matched Zn-DTPA. For (3) a transmetallation phenomenon versus free ionized calcium is possible in the case of both linear CM (Gd-DTPA and Gd-DTPA-BMA) since Ca significantly reduced the CM-induced decrease in BP. For (4) a transient rise in BP was observed following Gd-HP-DO3A, another macrocyclic chelate, associated with a concomitant increase in stroke volume. This effect was antagonized neither by phentolamine nor by diltiazem. The decrease in BP following injection of Gd-DTPA or Gd-DTPA-BMA may not only be osmolality-related since (a) Gd-DOTA solution, whose osmo-lality is greater than that of Gd-DTPA-BMA, had a lesser effect, and (b) this hypotensive effect was corrected by addition of ionized calcium. The transient Gd-HP-DO3A-induced rise in BP is probably the consequence of a positive inotropic effect. © Rapid Science 1998     

Contrast agents for nuclear magnetic resonance imaging

Nuclear magnetic resonance imaging relies upon differences in relaxation times for much of its ability to resolve anatomical structures and to detect changes in tissue. The natural differences can be changed by the administration of paramagnetic substances, such as metal complexes and stable organic free radicals, and ferromagnetic materials, such as small particles of magnetite. Detailed studies of the chemistry and biophysics of such substances in the body are required if they are to become safe and effective contrast agents for use in medical NMR imaging.     

Development of concurrent magnetic resonance imaging and volumetric optoacoustic tomography: A phantom feasibility study

Optoacoustic tomography (OAT) and magnetic resonance imaging (MRI) provide highly complementary capabilities for anatomical and functional imaging of living organisms. Herein, we investigate on the feasibility of combining both modalities to render concurrent images. This was achieved by introducing a specifically-designed copper-shielded spherical ultrasound array into a preclinical MRI scanner. Phantom experiments revealed that the OAT probe caused minimal distortion in the MRI images, while synchronization of the laser and the MRI pulse sequence enabled defining artifact-free acquisition windows for OAT. Good dynamic OAT contrast from superparamagnetic iron oxide nanoparticles, a commonly used agent for MRI contrast enhancement, was also observed. The hybrid OAT-MRI system thus provides an excellent platform for cross-validating functional readings of both modalities. Overall, this initial study serves to establish the technical feasibility of developing a hybrid OAT-MRI system for biomedical research.     

Electron microscopy study of intrahepatic ultrasmall superparamagnetic iron oxide kinetics in the rat. Relation with magnetic resonance imaging.

Ultrasmall superparamagnetic iron oxide (USPIO) contrast agents for use in magnetic resonance imaging (MRI) are currently undergoing clinical evaluation. However, the images observed and the kinetic profiles obtained differ from one agent to another. In this study, BD IX rats received an intravenous penis injection of the USPIO contrast agents AMI-HS and AMI-227. A cytologic study of the liver was performed, and the data obtained were compared with those of MRI. Images acquired in light microscopy, transmission electron microscopy, microanalysis and electron diffraction provided data on the cell categories involved in the processing of these contrast agents, the importance and modalities of each category relative to this processing, and the modalities of agent elimination. AMI-HS was rapidly removed from the bloodstream by Kupffer's cells and hepatocytes and then eliminated through bile ducts. AMI-227 remained much longer in the blood compartment since it was processed very slowly by endothelial and Kuppfer's cells in the near absence of hepatocytic participation and thus of elimination by the bile ducts. These results allowed us to base our interpretation of MRI sequences on cytologic observations.     

In vivo phenotyping of the ob/ob mouse by magnetic resonance imaging and 1H-magnetic resonance spectroscopy

Objective: We studied ob/ob and wild‐type (WT) mice to characterize the adipose tissues depots and other visceral organs and to establish an experimental paradigm for in vivo phenotyping. Research Methods and Procedures: An in vivo evaluation was conducted using magnetic resonance imaging and ¹H‐magnetic resonance spectroscopy (¹H‐MRS). We used T1‐weighted images and three‐dimensional spin echo T1‐weighted images for the morphological analysis and ¹H‐MRS spectra on all body mass, as well as ¹H‐MRS spectra focalized on specific lipid depots [triglyceride (TG) depots] for a molecular analysis. Results: In ob/ob mice, three‐dimensional evaluation of the trunk revealed that ～64% of the volume consists of white adipose tissue, which is 72% subcutaneous and 28% visceral. In vivo ¹H‐MRS showed that 20.00 ± 6.92% in the WT group and 58.67 ± 6.65% in the ob/ob group of the total proton content is composed of TG protons. In in vivo‐localized spectra of ob/ob mice, we found a polyunsaturation degree of 0.5247 in subcutaneous depots. In the liver, we observed that 48.7% of the proton signal is due to water, whereas in the WT group, the water signal amounted to 82.8% of the total proton signal. With the sequences used, the TG amount was not detectable in the brain or kidneys. Discussion: The present study shows that several parameters can be obtained by in vivo examination of ob/ob mice by magnetic resonance imaging and ¹H‐MRS and that the accumulated white adipose tissue displays low polyunsaturation degree and low hydrolipidic ratio. Relevant anatomical alterations observed in urinary and digestive apparatuses should be considered when ob/ob mice are used in experimental paradigms.     

Mn(II)-monosubstituted polyoxometalates as candidates for contrast agents in magnetic resonance imaging

Two mono-substituted manganese polyoxometalates, K(6)MnSiW(11)O(39) (MnSiW(11)) and K(8)MnP(2)W(17)O(61) (MnP(2)W(17)), have been evaluated by in vivo and in vitro experiments as the candidates of potential tissue-specific contrast agents for magnetic resonance imaging (MRI). T1-relaxivities of 12.1mM(-1)s(-1) for MnSiW(11) and 4.7 mM(-1)s(-1) for MnP(2)W(17) (400 MHz, 25 degrees C) were higher than or similar to that of the commercial MRI contrast agent (GdDTPA). Their relaxivities in BSA and hTf solutions were also reported. After administration of MnSiW(11) and MnP(2)W(17) to Wistar rats, MR imaging showed longer and remarkable enhancement in rat liver and favorable renal excretion capability. The signal intensity increased by 74.0+/-4.9% for the liver during the whole imaging period (90 min) and by 67.2+/-5.3% for kidney within 20-70 min after injection at 40+/-3 micromol kg(-1) dose for MnSiW(11). MnP(2)W(17) induced 71.5+/-15.1% enhancement for the liver in 10-45 min range and 73.1+/-3.2% enhancement for kidney within 5-40 min after injection at 39+/-3 micromol kg(-1) dose. In vitro and in vivo study showed MnSiW(11) and MnP(2)W(17) being favorable candidates as the tissue-specific contrast agents for MRI.     

Effect of transplantation route on stem cell migration to fibrotic liver of rats via cellular magnetic resonance imaging

Background aimsAssessing mesenchymal stromal cells (MSCs) after grafting is essential for understanding their migration and differentiation processes. The present study sought to evaluate via cellular magnetic resonance imaging (MRI) if transplantation route may have an effect on MSCs engrafting to fibrotic liver of rats.MethodsRat MSCs were prepared, labeled with superparamagnetic iron oxide and scanned with MRI. Labeled MSCs were transplanted via the portal vein or vena caudalis to rats with hepatic fibrosis. MRI was performed in vitro before and after transplantation. Histologic examination was performed. MRI scan and imaging parameter optimization in vitro and migration under in vivo conditions were demonstrated.ResultsStrong MRI susceptibility effects could be found on gradient echo-weighted, or T21-weighted, imaging sequences from 24 h after labeling to passage 4 of labeled MSCs in vitro. In vivo, MRI findings of the portal vein group indicated lower signal in liver on single shot fast spin echo-weighted, or T2-weighted, imaging and T21-weighted imaging sequences. The low liver MRI signal increased gradually from 0–3 h and decreased gradually from 3 h to 14 days post-transplantation. The distribution pattern of labeled MSCs in liver histologic sections was identical to that of MRI signal. It was difficult to find MSCs in tissues near the portal area on day 14 after transplantation; labeled MSCs appeared in fibrous tuberculum at the edge of the liver. No MRI signal change and a positive histologic examination were observed in the vena caudalis group.ConclusionsThe portal vein route seemed to be more beneficial than the vena caudalis on MSC migration to fibrotic liver of rats via MRI.     

Study of temporomandibular joint disorder in older patients by magnetic resonance imaging

doi: 10.1111/j.1741‐2358.2011.00552.x Study of temporomandibular joint disorder in older patients by magnetic resonance imaging (MRI) Objectives: To compare characteristics in older patients in a sample of the general population of those with temporomandibular joint disorder (TMJD). Materials and methods: A prospective study was carried out between 2001 and 2008 in patients with TMJD. The whole sample consisted of 141 patients divided in two groups: 31 patients aged over 60 (median age 67.9, ranging from 60 to 82) and the remaining 110 patients (median age 36.3, ranging from 12 to 59) who were seeking treatment. Clinical diagnostics was confirmed by MRI. Pain intensity was rated on a visual analogue scale (VAS 0‐10). Results: There was no statistical difference between average pain in older patients (6.2) and patients aged up to 59 (5.7) evaluated by VAS. There was a statistically significant difference (p = 0.002) in pain duration: older patients reported shorter duration of experienced pain (7.8 months) than patients aged up to 59 (12.2 months). Conclusion: In this study, it was found that 22% were older patients with TMJD. A higher level of anxiety was shown in both patients’ groups, regardless of shorter pain experience in the older patients.     

Static magnetic field effects on human subjects related to magnetic resonance imaging systems

Goal: This paper reviews recent studies evaluating human subjects for physiologic or neuro-cognitive function adverse effects resulting from exposure to static magnetic fields of magnetic resonance imaging systems.

Materials and Methods: The results of three studies are summarized. Two studies evaluated exposure to a maximum of 8 Tesla (T). The first series studied 25 normal human subjects’ sequential vital signs (heart rate, blood pressure, blood oxygenation, core temperature, ECG, respiratory rate) measured at different magnetic field strengths to a maximum of 8 T. A second series of 25 subjects were studied at 0.05 and 8 T (out and in the bore of the magnet), performing 12 different standardized neuro-psychological tests and auditory–motor reaction times. The subjects’ comments were recorded immediately following the study and after a three-month interval. The third study contained 17 subjects, placed near the bore of a 1.5 T magnet, and it used six different cognitive, cognitive–motor, or sensory tests.

Results: There were no clinically significant changes in the subjects’ physiologic measurements at 8 T. There was a slight increase in the systolic blood pressure with increasing magnetic field strength. There did not appear to be any adverse effect on the cognitive performance of the subjects at 8 T. A few subjects commented at the time of initial exposure on dizziness, metallic taste in the mouth, or discomfort related to the measurement instruments or the head coil. There were no adverse comments at 3 months. The 1.5 T study had two of the four neuro-behavioral domains exhibiting adverse effects (sensory and cognitive–motor).

Conclusions: These studies did not demonstrate any clinically relevant adverse effects on neuro-cognitive testing or vital sign changes. One short-term memory, one sensory, and one cognitive–motor test demonstrated adverse effects, but the significance is not clear.     

Revisiting excitation pattern design for magnetic resonance imaging through optimisation of the signal contrast efficiency

The design of excitation signals for Magnetic Resonance Imaging (MRI) is cast as an optimal control problem. Here, we demonstrate that signals other than pulse excitations, which are ubiquitous in MRI, can provide adequate excitation, thus challenging the optimality and ubiquity of pulsed signals. A class of on-resonance piecewise continuous amplitude modulated signals is introduced. It is shown that despite the bilinear nature of the Bloch equations, the spins system response is largely analytically tractable for this class of signals, using Galerkin approximation methods. To challenge the optimality of the pulse excitation, an appropriate cost criterion, the Signal Contrast Efficiency (SCE), is developed. It is to be optimised subject to dynamics expressed by the Bloch equations. To solve the problem the Bloch equation is transferred to the excitation dependent rotating frame of reference. The numerical solutions to the problem for different tissue types show that for a short period of time, pulse excitations provide the maximum signal contrast. However, the problem should be solved for longer periods of time which may result in a different answer than a pulse. For this purpose, the approximate analytic solution which is derived based on averaging the Bloch equation in the excitation dependent rotating frame of reference will be used to find the optimal excitation pattern. The solution to the optimisation problem is potentially useful for all forms of MRI including structural and functional imaging. The objective of this paper is to show that while classically transient response of pulses have been monitored so far, the optimal excitation pattern may be the steady state response of a non-pulse excitation.     

Yield stress of pretreated corn stover suspensions using magnetic resonance imaging

Cellulose fibers in water form networks that give rise to an apparent yield stress, especially at high solids contents. Measuring the yield stress and correlating it with fiber concentration is important for the biomass and pulp industries. Understanding how the yield stress behaves at high solids concentrations is critical to optimize enzymatic hydrolysis of biomass in the production of biofuels. Rheological studies on pretreated corn stover and various pulp fibers have shown that yield stress values correlate with fiber mass concentration through a power‐law relationship. We use magnetic resonance imaging (MRI) as an in‐line rheometer to measure velocity profiles during pipe flow. If coupled with pressure drop measurements, these allow yield stress values to be determined. We compare our results with literature values and discuss the accuracy and precision of the rheo‐MRI measurement, along with the effects of fiber characteristics on the power‐law coefficients. Biotechnol. Bioeng. 2011;108: 2312–2319. © 2011 Wiley Periodicals, Inc.     

Contrast-enhancement cardiac magnetic resonance imaging beyond the scope of viability

The clinical applications of cardiovascular magnetic resonance imaging with contrast enhancement are expanding. Besides the direct visualisation of viable and non-viable myocardium, this technique is increasingly used in a variety of cardiac disorders to determine the exact aetiology, guide proper treatment, and predict outcome and prognosis. In this review, we discuss the value of cardiovascular magnetic resonance imaging with contrast enhancement in a range of cardiac disorders, in which this technique may provide insights beyond the scope of myocardial viability.