Shadi F. Othman

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 μm × 34 μm × 500 μm). Microscopic MRE (μMRE) 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. μMRE experiments were conducted at 11.74 T in a 56‐mm vertical bore magnet with a 10 mm diameter × 75 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 μMRE 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. Magn Reson Med, 2005.

Magnetic resonance microscopy for monitoring osteogenesis in tissue-engineered construct in vitro

Magnetic resonance microscopy (MRM) is used to monitor osteogenesis in tissue-engineered constructs. Measurements of the developing tissues MR relaxation times (T(1) and T(2)), apparent diffusion coefficient (ADC) and elastic shear modulus were conducted over a 4-week growth period using an 11.74 T Bruker spectrometer with an imaging probe adapted for MR elastography (MRE). Both the relaxation times and the ADC show a statistically significant decrease after only one week of tissue development while the tissue stiffness increases progressively during the first two weeks of in vitro growth. The measured MR parameters are correlated with histologically monitored osteogenic tissue development. This study shows that MRM can provide quantitative data with which to characterize the growth and development of tissue-engineered bone.

High-resolution/high-contrast MRI of human articular cartilage lesions.

Background Magnetic resonance microscopy (MRM) is an important experimental tool in the identification of early cartilage lesions. Methods Normal and degenerated cartilage samples were imaged at 11.74 T using a standard spin echo sequence. Quantitative MR measurements for T1, T2, and ADC were obtained and mapping for T2 and ADC was performed. The bi-exponential model for T2 relaxation was also explored. Histology was carried out for comparison with MR images. Results MR images of cartilage samples displaying early stages of degeneration were positively correlated to their histological appearance in 23-μm high-resolu-tion images and also with much shorter imaging times at 47-μm resolution. T2 maps enable delineation of the actual cartilage zones, distinguishing the super?cial zone in particular. The bi-exponential model can reflect cartilage components at different stages of degeneration. Interpretation At 11.74 T, with 23-μm resolution or with 47-μm resolution and shorter imaging times, MRM provides images that allow visualization of early stages of cartilage degeneration, including super?cial ?brillation. This has not been shown previously. The images also allow quantitative measurements (T1, T2, and ADC) in each cartilage region, which can be indicative of different stages of cartilage degeneration.

Ultrasound Accelerated Bone Tissue Engineering Monitored with Magnetic Resonance Microscopy

Tissue engineering has the potential to treat bone loss, but current bone restoration methods, including osteogenesis from mesenchymal stem cells (MSCs), require three to four weeks for bone formation to occur. In this study, we stimulated the formation of engineered bone tissue with low-intensity ultrasound, which has been proven to accelerate bone healing in vivo. One group of engineered bone constructs received ultrasound stimulation 20 minutes per day over a 3-week growth period. We monitored the growth of all the engineered constructs quantitatively and noninvasively using magnetic resonance microscopy (MRM), where the T2 relaxation times of all the constructs were measured, on a weekly basis, using an 11.74 T Bruker spectrometer. Histological and immunocytochemical sections were obtained for all constructs and correlated with the MR results. This study shows that ultrasound can accelerate osteogenesis in vitro for tissue engineered bone, the growth and development of which can be monitored using MRM

Underwater sound transmission through arrays of disk cavities in a soft elastic medium.

Scattering from a cavity in a soft elastic medium, such as silicone rubber, resembles scattering from an underwater bubble in that low-frequency monopole resonance is obtainable in both cases. Arrays of cavities can therefore be used to reduce underwater sound transmission using thin layers and low void fractions. This article examines the role of cavity shape by microfabricating arrays of disk-shaped air cavities into single and multiple layers of polydimethylsiloxane. Comparison is made with the case of equivalent volume cylinders which approximate spheres. Measurements of ultrasonic underwater sound transmission are compared with finite element modeling predictions. The disks provide a deeper transmission minimum at a lower frequency owing to the drum-type breathing resonance. The resonance of a single disk cavity in an unbounded medium is also calculated and compared with a derived estimate of the natural frequency of the drum mode. Variation of transmission is determined as a function of disk tilt angle, lattice constant, and layer thickness. A modeled transmission loss of 18 dB can be obtained at a wavelength about 20 times the three-layer thickness, and thinner results (wavelength/thickness ∼ 240) are possible for the same loss with a single layer depending on allowable hydrostatic pressure.

Microscopic magnetic resonance elastography (μMRE) applications

Microscopic magnetic resonance elastography (μMRE) is a phase contrast based imaging technique that is capable of mapping the acoustic shear waves resulting from low amplitude cyclic displacement in tissue-like materials. This new technique has proven successful in imaging gel phantoms mimicking soft biological tissues with shear moduli ranging from 0.7 to 40 kPa. The 4-dimensional (4D) spatial-temporal shear wave vector can be measured, which in turn can be used to identify material properties with high spatial resolution. Experiments were conducted using 5 and 10 mm RF saddle coils in the 10 mm vertical imaging bore of an 11.74 Tesla magnet. The field-of-view ranged from 4 to 14 mm, with in plane resolution up to 34 μm x 34 μm and slice thickness up to 100 μm using shear wave excitation of 550 to 580 Hz. In this study, the capability and constraints of μMRE are investigated. The constraints include the range of measured shear moduli, excitation frequency, and minimum physical sample volume. Applications investigated include: 1) late-stage frog oocytes with typical diameter from 1 to 1.5 mm; and 2) tissue engineered constructs at different growth stages. Mesenchymal stem cells (MSCs) extracted from bone marrow can serve as progenitor cells that differentiate into specific types of tissues such as bone, adipose tissue, cartilage and muscle. μMRE can monitor the growth of such tissues and evaluate their mechanical properties. Also, a silicon-based tissue phantom material (CF-11-2188, Nusil Technologies) is tested in order to address challenges associated with excitation frequency and the dispersive nature of the media.

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 verti...

Radiation force of ultrasound as shear wave source in microscopic magnetic resonance elastography

Microscopic magnetic resonance elastography (micro‐MRE) is a high‐resolution imaging technique for measuring the viscoelastic properties of small synthetic and biological samples. Taking MRE to the microscopic scale requires stronger static fields, stronger magnetic field gradients, higher performance RF coils, and more compact, higher frequency shear wave actuators. Prior work by our group has been conducted at 11.74 T. A needle attached to a vibrating cantilever beam was placed in contact with the surface of the sample to generate shear waves up to 800 Hz. At higher frequencies, the excited shear waves attenuate within an extremely short distance such that only a very small region in the vicinity of the actuator can be studied due to inherent dynamic range limitations. In principle, modulated focused radiation force of US should be able to create a localized shear wave source within the test sample at a distance from the US transducer, thereby enabling micro‐MRE probing of the sample at very high frequencies (up to 5 kHz). A confocal US transducer was fabricated to create such a source within the working constraints of the micro‐MRE system. Initial feasibility studies are reviewed in this presentation. [Research supported by NIH Grant No. EB004885‐01.]