Agarose Gel Phantoms Research Articles

Optimization and validation of a fully‐integrated pulse sequence for modified look‐locker inversion‐recovery (MOLLI) T1 mapping of the heart

To optimize and validate a fully-integrated version of modified Look-Locker inversion-recovery (MOLLI) for clinical single-breathhold cardiac T1 mapping. A MOLLI variant allowing direct access to all pulse sequence parameters was implemented on a 1.5T MR system. Varying four critical sequence parameters, MOLLI was performed in eight gadolinium-doped agarose gel phantoms at different simulated heart rates. T1 values were derived for each variant and compared to nominal T1 values. Based on the results, MOLLI was performed in midcavity short-axis views of 20 healthy volunteers pre- and post-Gd-DTPA. In phantoms, a readout flip angle of 35 degrees , minimum TI of 100 msec, TI increment of 80 msec, and use of three pausing heart cycles allowed for most accurate and least heart rate-dependent T1 measurements. Using this pulse sequence scheme in humans, T1 relaxation times in normal myocardium were comparable to data from previous studies, and showed narrow ranges both pre- and postcontrast without heart rate dependency. We present an optimized implementation of MOLLI for fast T1 mapping with high spatial resolution, which can be integrated into routine imaging protocols. T1 accuracy is superior to the original set of pulse sequence parameters and heart rate dependency is avoided.

Prediction of convection-enhanced drug delivery to the human brain

The treatment for many neurodegenerative diseases of the central nervous system (CNS) involves the delivery of large molecular weight drugs to the brain. The blood brain barrier, however, prevents many therapeutic molecules from entering the CNS. Despite much effort in studying drug dispersion with animal models, accurate drug targeting in humans remains a challenge. This article proposes an engineering approach for the systematic design of targeted drug delivery into the human brain. The proposed method predicts achievable volumes of distribution for therapeutic agents based on first principles transport and chemical kinetics models as well as accurate reconstruction of the brain geometry from patient-specific diffusion tensor magnetic resonance imaging. The predictive capabilities of the methodology will be demonstrated for invasive intraparenchymal drug administration. A systematic procedure to determine the optimal infusion and catheter design parameters to maximize penetration depth and volumes of distribution in the target area will be discussed. The computational results are validated with agarose gel phantom experiments. The methodology integrates interdisciplinary expertise from medical imaging and engineering. This approach will allow physicians and scientists to design and optimize drug administration in a systematic fashion.

Preliminary assessment of one-dimensional MR elastography for use in monitoring focused ultrasound therapy

The purpose of this work is to assess a fast technique that measures tissue stiffness and temperature during focused ultrasound thermal therapy (FUS). A one-dimensional (1D) MR elastography (MRE) pulse sequence was evaluated for the purpose of obtaining rapid measurements of thermally induced changes in tissue stiffness and temperature for monitoring FUS treatments. The accuracy of the 1D measurement was studied by comparing tissue displacements measured by 1D MRE with those measured by the well-established 2D MRE pulse sequence. The reproducibility of the 1D MRE measurement was assessed, in gel phantoms and ex vivo porcine tissue, for varied FUS intensity levels (31.5–199.9 W cm−2) and over a range of displacements at the focus (0.1–1 µm). Temperature elevations in agarose gel phantoms were measured using 1D MRE and calibrated using fiberoptic-thermometer-based measurements. The 1D MRE displacement measurements are highly correlated with those obtained with the 2D technique (R2 = 0.88–0.93), indicating that 1D MRE can successfully measure tissue displacement. Ten repeated trials at each FUS power level yielded a minimum detectable displacement change of 0.2 µm in phantoms and 0.4 µm in tissue (at 95% confidence level). The 1D MRE temperature measurements correlated well with temperature changes measured simultaneously with fiberoptic thermometers (R2 = 0.97). The 1D MRE technique is capable of detecting tissue displacements as low as 0.4 µm, which is an order of magnitude smaller than 5 µm displacements expected during FUS therapy (Le et al 2005 AIP Conf. Proc.: Ther. Ultrasound 829 186–90). Additionally, 1D MRE was shown to provide adequate measurements of temperature elevations in tissue. These findings indicate that 1D MRE may be an effective tool for monitoring FUS treatments.

R2 and R2* Mapping for Sensing Cell-bound Superparamagnetic Nanoparticles: In Vitro and Murine in Vivo Testing

To prospectively determine the cellular iron uptake by using R2 and R2* mapping with multiecho readout gradient-echo and spin-echo sequences. All experiments were approved by the institutional animal care committee. Lung carcinoma cells were lipofected with superparamagnetic iron oxides (SPIOs). Agarose gel phantoms containing (a) 1 x 10(5) CCL-185 cells per milliliter of agarose gel with increasing SPIO load (0.01-5.00 mg of iron per milliliter in the medium), (b) different amounts (5.0 x 10(3) to 2.5 x 10(5) cells per milliliter of agarose gel) of identically loaded cells, and (c) free (non-cell-bound) SPIOs at the iron concentrations described for (b) were analyzed with 3.0-T R2 and R2* relaxometry. Iron uptake was analyzed with light microscopy, quantified with atomic emission spectroscopy (AES), and compared with MR data. For in vivo relaxometry, agarose gel pellets containing SPIO-labeled cells, free SPIO, unlabeled control cells, and pure agarose gel were injected into three nude mice each. Linear and nonlinear regression analyses were performed. Light microscopy and AES revealed efficient SPIO particle uptake (mean uptake: 0.22 pg of iron per cell +/- 0.1 [standard deviation] for unlabeled cells, 31.17 pg of iron per cell +/- 4.63 for cells incubated with 0.5 mg/mL iron). R2 and R2* values were linearly correlated with cellular iron load, number of iron-loaded cells, and content of freely dissolved iron (r(2) range, 0.92-0.99; P < .001). For cell-bound SPIO, R2* effects were significantly greater than R2 effects (P < .01); for free SPIO, R2 and R2* effects were similar. In vivo relaxometry enabled accurate prediction of the number of labeled cells. R2' (R2* - R2) mapping enabled differentiation between cell-bound and free iron in vitro and in vivo. Quantitative R2 and R2* mapping enables noninvasive estimations of cellular iron load and number of iron-labeled cells. Cell-bound SPIOs can be differentiated from free SPIOs with R2' imaging.

STEAM-Sequenz mit Multi-Echo-Auslese für die statische Magnetresonanz-Elastographie

In static magnetic resonance elastography, the elasticity of an object is determined by measuring the internal displacement between two compression states. To reduce signal loss during the long time delay between application of external deformation and the static compression state, a STEAM sequence with a long mixing time is used. This results in long scan times. The aim of this work was the development of a STEAM sequence with a multi-echo-readout, which allows the reduction of scan time and number of necessary external deformations. This new sequence was compared to the standard STEAM sequence on an agarose gel phantom with a hard inclusion. In addition, the elasticity of thermal tissue lesions was investigated, which were induced using high-intensity focused ultrasound (HIFU). During a given measurement time, more acquisitions per image can be taken using the multi-echo-readout. As a result the signal-to-noise ratio is increased and errors in the data become clearly smaller. Drawbacks of the new sequence are its higher signal loss due to T 2-decay and its greater sensitivity against ghosting artefacts caused by k-space segmentation. During the investigation of the thermally-induced lesions, a clear contrast in elasticity between normal tissue and the treated region was observed. Taking advantage of the greater accuracy of the new STEAM sequence, it was shown, that this contrast is significantly larger than the one in conventional MR parameters.

Compensation for spin‐lock artifacts using an off‐resonance rotary echo in T1ρoff‐weighted imaging

The origin of image artifacts in an off-resonance spin-locking experiment is shown to be imperfections in the excitation flip angle. A pulse sequence for off-resonance spin locking is implemented that compensates for imperfections in the excitation flip angle through an off-resonance rotary echo. The off-resonance rotary echo alternates the frequency offset and phase of the RF transmitter during two spin-locking pulses of equal duration. The underlying theory is detailed, and MR images demonstrate the effectiveness of the technique in agarose gel phantoms and in in vivo human brain at 3T.

Contrast and spatial resolution in MREIT using low amplitude current

Magnetic resonance–electrical impedance tomography employs low amplitude currents injected or induced inside an object. The additional magnetic field due to these currents results in a phase in the MR images. In this study, a modified fast spin–echo sequence was used to measure this magnetic field, which is obtained by scaling the MR phase image. A finite element method with first order triangular elements was used for the solution of the forward problem. An iterated sensitivity matrix-based algorithm was developed for the inverse problem. The resulting ill-conditioned matrix equation was regularized using the Tikhonov method and solved using a conjugate gradient solver. The spatial and contrast resolution of the technique was tested using agarose gel phantoms. A circular phantom with 7 cm diameter and 1 cm thickness is used in the phantom experiments. The amplitude of the injected current was 1 mA. 3, 5 and 8 mm diameter insulators and high conductor objects are used for the spatial resolution study and an average full-width half-maximum value of 4.7 mm is achieved for the 3 mm insulator case. For the contrast analysis, the conductivity of a 15 mm object is varied between 44% and 500% with respect to the background and results are compared to the ideal reconstruction.

IDQC MRI weighted by longitudinal relaxation in the rotating frame

A long-duration, low-power, off-resonance spin-locking pulse was incorporated into the COSY revamped by asymmetric z gradient-echo detection (CRAZED) pulse sequence in order to evaluate the effects of intermolecular double-quantum longitudinal relaxation in the tilted rotating frame (T1rho,DQ(eff)). This modified CRAZED sequence was followed by a standard fast spin-echo imaging sequence to form images with T1rho,DQ(eff)-weighted contrast. Imaging experiments were performed on an agarose-gel phantom and mouse-tail tissue at 600 MHz. Experimental results demonstrated the feasibility of imaging applications based on T1rho,DQ(eff) as a novel contrast mechanism, and showed that iDQC off-resonance longitudinal relaxation in the rotating frame T1rho,DQ(eff) is sensitive to the tilt angle theta and the effective spin-locking field omegae. Imaging based on T1rho,DQ(eff)) has reduced RF power deposition compared to on-resonance spin-locking, which is advantageous for human applications.

Measurement of ion diffusion using magnetic resonance electrical impedance tomography

In magnetic resonance electrical impedance tomography (MREIT), currents are applied to an object, the resulting magnetic flux density measured using MRI and the conductivity distribution reconstructed using these MRI data. In this study, we assess the ability of MREIT to monitor changes in the conductivity distribution of an agarose gel phantom, using injected current pulses of 900 µA. The phantom initially contained a distinct region of high sodium chloride concentration which diffused into the background over time. MREIT data were collected over a 12 h span, and conductivity images were reconstructed using the iterative sensitivity matrix method with Tikhonov regularization. The results indicate that MREIT was able to monitor the changing conductivity and concentration distributions resulting from the diffusion of ions within the agarose gel phantom.

Balanced alternating steady‐state elastography

A conventional balanced steady-state free precession (b-SSFP) sequence scheme was modified such that the dynamic equilibrium becomes very sensitive to small cyclic displacements, generating two distinct and alternating steady states. This novel technique is proposed for the visualization of propagating transverse acoustic shear waves, as used in MR elastography (MRE) to determine the mechanical properties of materials or in vivo soft tissue. Experiments with tissue-like agarose gel phantoms and simulations demonstrate that the novel sequence offers an increase in phase sensitivity by about one order in magnitude compared to standard motion-encoding methods. In addition, the new method benefits from the very short acquisition times achieved by b-SSFP protocols.

Microscopic magnetic resonance elastography (μMRE)

Magnetic resonance elastography (MRE) was extended to the microscopic scale to image low-frequency acoustic shear waves (typically less than 1 kHz) in soft gels and soft biological tissues with high spatial resolution (34 micromx34 micromx500 microm). Microscopic MRE (microMRE) was applied to agarose gel phantoms, frog oocytes, and tissue-engineered adipogenic and osteogenic constructs. Analysis of the low-amplitude shear wave pattern in the samples allowed the material stiffness and viscous loss properties (complex shear stiffness) to be identified with high spatial resolution. microMRE experiments were conducted at 11.74 T in a 56-mm vertical bore magnet with a 10 mm diameterx75 mm length cylindrical space available for the elastography imaging system. The acoustic signals were generated at 550-585 Hz using a piezoelectric transducer and high capacitive loading amplifier. Shear wave motion was applied in synchrony with the MR pulse sequence. The field of view (FOV) ranged from 4 to 14 mm for a typical slice thickness of 0.5 mm. Increasing the agarose gel concentration resulted in an increase in shear elasticity and shear viscosity. Shear wave motion propagated through the frog oocyte nucleus, enabling the measurement of its shear stiffness, and in vitro shear wave images displayed contrast between adipogenic and osteogenic tissue-engineered constructs. Further development of microMRE should enable its use in characterizing stiffer materials (e.g., polymers, composites, articular cartilage) and assessing with high resolution the mechanical properties of developing tissues.

Microscopic dynamic magnetic resonance elastography

Microscopic magnetic resonance elastography (uMRE) is a high resolution imaging technique for measuring the viscoelastic properties of small synthetic and biological samples. Mechanical shear waves, typically with amplitudes of less than 100 μm and frequencies of 500–600 Hz, are induced using a piezoelectric oscillator directly coupled to the region of interest. By using multiple phase offsets and motion encoding gradients we acquire data that allows the generation of images that depict shear wave motion and the calculation of local values of the tissue viscoelastic properties. Recent MRE investigations are increasingly being conducted at higher spatial resolution to establish histological correlations between elasticity maps and tissue structures; such microscopic MRE studies require stronger static fields, stronger magnetic field gradients, higher performance RF coils, and more compact, higher frequency mechanical actuators. Microscopic MRE experiments were conducted at 11.74 T in a 54 mm diameter vertical bore magnet with a 10 mm diameter×25 mm length cylindrical space available for imaging. The field-of-view ranged from 4 to 14 mm. The study was conducted on agarose gel phantoms of different concentrations ranging from 025%–1% w. Different biological samples, including frog oocytes and tissue engineered constructs, were also tested.

A finite element model for analyzing shear wave propagation observed in magnetic resonance elastography

Magnetic resonance elastography (MRE) is a novel non-invasive approach to determine material stiffness by using a conventional magnetic resonance imaging (MRI) system incorporated with an oscillating motion-sensitizing gradient to detect nodal displacements produced by a shear excitation wave. The effects of material properties, excitation frequency, boundary conditions, and applied tension on shear wavelength measurement must be examined before MRE can become a useful diagnostic tool. We propose finite element (FE) modeling as a robust method to systematically study the effects of these parameters. An axisymmetric FE model was generated with ABAQUS to simulate agarose gel phantoms. The effects of material stiffness, density, and excitation frequency on propagating shear wavelength were examined individually. The effect of the boundary conditions on shear wavelength was also demonstrated. Results of shear wavelength from MRE measurement were compared with the results of FE model, which showed good agreement between the methods.

Observation of nonlinear shear wave propagation using magnetic resonance elastography.

MR elastography (MRE) is an MRI modality that is increasingly being used to image tissue elasticity throughout the body. One MRE technique that has received a great deal of attention is based on visualizing shear waves, which reveal stiffness by virtue of their local wavelength. However, the shape of propagating shear waves can also provide valuable information about the nonlinear stress-strain behavior of tissue. Here an experiment is proposed that allows the observation of nonlinear wave propagation based on spatial-temporal phase contrast images. A theoretical description of the wave propagation was developed that reflects typical MRE excitation, which involves excitation modes both parallel and perpendicular to B0. Based on this model, it is shown that both odd and even higher harmonics are produced with their amplitudes dependent on the details of the actuator, imaging geometry, and the nonlinear tissue properties. With appropriate motion encoding, harmonic vibrations arising from nonlinear tissue response can be detected. The effect is demonstrated on an agarose gel phantom using a sinusoidal shear vibration of 150 Hz, and clearly shows the presence of harmonics at 600 and 750 Hz. Using an estimate of the strain energy of the phantom, we were able to determine the nonlinear tissue properties.

In vivo fate of superparamagnetic iron oxides during sepsis

The enzymatic generation of nitric oxide (NO) in vivo has been reported to be modulated by ions, such as copper and iron. Superparamagnetic iron oxide (SPIO) or ferumoxides is a liver-specific magnetic resonance contrast agent that is taken up by the Kupffer cells, where NO is generated by inducible nitric oxide synthase (iNOS). Thus, it is important to evaluate SPIO in vivo under conditions, such as infectious disease, where significant amounts of NO are generated by iNOS. In this study, we monitored the pharmacokinetics of SPIO in the liver of septic-shock mice and rats. A significant decrease in the ferric iron EPR signal was observed during NO generation in septic-shock mice compared with control mice doped with only SPIO. These results were also confirmed in a model reaction system consisting of SPIO and the NO donor, S-nitroso-N-acetyl DL penicillamine (SNAP). We compared NO generation quantitatively in the liver of the septic-shock rats, either in the presence or absence of SPIO, and found that the presence of SPIO did not affect the NO-generating activity of NOS expressed in the liver. T 2-weighted MR images of an agarose gel phantom containing different SPIO to NO donor (SNAP) ratios clearly demonstrated that the contrast enhancement by SPIO decreased with increasing NO at constant SPIO levels. The reduced contrast is most probably due to the reduction of ferric to ferrous irons, resulting in a decrease in paramagnetic relaxation of water protons. These results show that SPIO can be a versatile NO-sensitive indicator, especially employing MRI as a powerful tool to ‘visualize’ sites of NO generation.

Quantification and minimization of magnetic susceptibility artifacts on GRE images.

The purpose of this work was to determine the optimal imaging parameters for minimization of metallic susceptibility artifacts during gradient echo (GRE) imaging. We performed GRE imaging of titanium screws in a nickel-doped agarose gel phantom, systematically varying several parameters to characterize and quantify susceptibility artifacts. The greatest reduction in artifact size came from using a short TE; increasing the frequency matrix and decreasing the slice thickness also contributed substantially to reducing the artifact size. Whenever possible, implanted prostheses should be aligned with the main magnetic field to minimize artifact size. Parameters with negligible effect on artifact size included bandwidth, phase encode matrix, and field of view. Radiologists can easily adjust the above parameters in their imaging protocols to improve GRE image quality in patients with implanted metallic devices.

MRI thermometry in phantoms by use of the proton resonance frequency shift method: application to interstitial laser thermotherapy

In this work the temperature dependence of the proton resonance frequency was assessed in agarose gel with a high melting temperature (95C) and in porcine liver in vitro at temperatures relevant to thermotherapy (25-80C). Furthermore, an optically tissue-like agarose gel phantom was developed and evaluated for use in MRI. The phantom was used to visualize temperature distributions from a diffusing laser fibre by means of the proton resonance frequency shift mehod. An approximately linear relationship (0.0085 ppm ) between proton resonance frequency shift and temperature change was found for agarose gel, whereas deviations from a linear relationship were observed for porcine liver. The optically tissue-like agarose gel allowed reliable MRI temperature monitoring, and the MR relaxation times ( and ) and the optical properties were found to be independently alterable. Temperature distributions around a diffusing laser fibre, during irradiation and subsequent cooling, were assessed with high spatial resolution (voxel size=4.3 mm) and with random uncertainties ranging from 0.3C to 1.4C (1 SD) with a 40 s scan time.

Practical design of a high-strength breast gradient coil.

A high-strength three-axis local gradient coil set was constructed for MRI of the breast. Gradient fields with good uniformity (<10% deviation from the desired gradient) over most of the volume required for breast imaging were generated with efficiencies of up to 3.3 mT/m/A. The coils will allow diffusion breast imaging in clinically acceptable examination times. The electrical design, water cooling system, and fabrication techniques are described. Preliminary tests of the coil included images of a grid phantom and diffusion measurements in a short-T2 agarose gel phantom.

Magnetic resonance imaging of transverse acoustic strain waves.

We describe a phase contrast based MRI technique with high sensitivity to cyclic displacement that is capable of quantitatively imaging acoustic strain waves in tissue-like materials. A formalism for considering gradient waveforms as basis functions to measure arbitrary cyclic motion waveforms is introduced. Experiments with tissue-like agarose gel phantoms show that it is possible to measure small cyclic displacements at a submicron level by an appropriate choice of the applied gradient basis function and to use this capability to observe the spatial and temporal pattern of displacements caused by acoustic strain waves. The propagation characteristics of strain waves are determined by the mechanical properties of the media. It is therefore possible to use this technique to noninvasively estimate material properties such as elastic modulus.

Reliability and exactness of MRI-based volumetry: a phantom study.

This study investigated the influence of slice thickness, section orientation, contrast, shape, and sequence type on the exactness of MRI-based volumetry. Ni-doped agarose gel phantoms (4 to 46 ml) were scanned with a T1-weighted three-dimensional Fourier transform (FT) fast low-angle shot (FLASH) and a multiecho two-dimensional FT-Turbo spin-echo (SE) sequence. After segmentation with a three-dimensional region-growing algorithm, the geometric volume was measured considering the partial volume effect. The variability coefficient (Pearson) was .7%. The volumetric error increased with slice thickness, depending on the size and form of the object. Cross sections resulted in smaller error than longitudinal sections (finger-shaped phantoms, nonisotropic image data). Three-dimensional FT imaging. Results of slice thickness and section orientation experiments can be explained by the partial volume effect Higher errors in two-dimensional FT imaging were caused by object movements between two interleaved acquisitions. The study shows a considerable influence of the imaging parameters on the exactness, which depends on size and form of the structure of interest.