Detection of silicone migration and biodegradation with NMR.
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Breast Implants↗
Biomedical subjects
J L Ackerman
Publications and source records attributed to J L Ackerman.
Study of aging of silicone rubber biomaterials with NMR.
Multinuclear nuclear magnetic resonance (NMR) spectroscopy (29Si, 13C, 1H) is used to characterize the aging process of silicone rubber-based biomaterials in a rat model. 1H NMR relaxation measurements (spin-lattice, T1, and spin-spin, T2, relaxation times) were performed to better understand the molecular dynamics of polysiloxane chains in implants. After 1 year of implantation in animals, changes in the 1H T2 relaxation times and the NMR spectra were observed in polydimethylsiloxane, Silastic sheets and chin implants, while these measurements remain unchanged in finger joints. Very small amounts of fat were detected in all types of silicone rubber implants at the end of the implantation period. This work shows that free silicone migrates from the implants to adjacent tissues and distant sites, such as spleen or liver, and is chemically modified.
Animals↗
Solid state phosphorus-31 magnetic resonance imaging of bone mineral.
Chemically selective solid state phosphorus-31 nuclear magnetic resonance (NMR) imaging of the mineral phase of bone and synthetic calcium phosphate models for bone mineral is demonstrated with microscopy-scale (about 5 mm field of view) apparatus at 6.0 T magnetic field strength. Pixel-by-pixel linear combination of image data from multiple radio frequency (RF) pulse sequences, chosen to develop contrast between chemical constituents of interest in the mineral, generates derived images showing the distribution of individual constituents. The technique combines the noninvasive character of magnetic resonance imaging (MRI) with the ability of solid state NMR spectroscopy to characterize subtle chemical variations in bone mineral, as well as to measure the amount of mineral. These methods are, in principle, extensible to larger dimensional scales suitable for live animal subjects or human limbs.
Animals↗
Communication in orthodontic treatment planning: bioethical and informed consent issues.
Orthodontic treatment planning is an interactive process in which the patient or parent and the orthodontist serve as co-decision makers. As in most partnerships, there is a natural tension between the orthodontist and the patient because of differences in their frames of reference. The orthodontist generally is influenced more by the objective findings (the problem list), whereas patients are guided more by subjective issues related to their perceived needs, desires, and values. The art of careful probing and listening to the patient as part of the treatment planning process is an essential skill. One of the most difficult situations in contemporary orthodontics is presented by the patient with a jaw discrepancy for which the alternative treatments are orthodontic camouflage through dental compensation or surgical-orthodontic correction. Computer imaging to simulate the probable treatment outcomes can facilitate communication about these alternatives by eliminating misconceptions. Full disclosure and the consideration of all viable treatment alternatives have great benefits from a risk management standpoint, in addition to their bioethical merits.
Adolescent↗
Re: Do patients with silicone-gel breast implants have elevated levels of blood silicon compared with control patients?
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Breast Implants↗
A unique protonated phosphate group in bone mineral not present in synthetic calcium phosphates. Identification by phosphorus-31 solid state NMR spectroscopy.
The detailed chemical composition and microstructure of freshly deposited bone mineral, and how these properties change with maturation of the mineral, have been studied intensively and still remain controversial. For example, current analytical technology is inadequate for the unambiguous characterization of the monohydrogen phosphate ions in bone mineral. Using a differential cross polarization/magic angle spinning solid state nuclear magnetic resonance spectroscopy technique, we suppress the dominant orthophosphate (PO4-3) signal to reveal the spectra of the minor phosphate constituents. This method depends upon differences in the cross polarization time constants for phosphorus-31 nuclei in protonated and non-protonated phosphate ions. It is now possible for the first time to directly measure both the proportion of acid phosphate (HPO4-2) as well as the parameters which characterize its isotropic and anisotropic chemical shift. In bone from three species at several developmental stages, we have found a single type of acid phosphate species, identical in all of the specimens examined. The phosphorus-31 isotropic chemical shift of this acid phosphate group in bone mineral corresponds precisely with that of acid phosphate in octacalcium phosphate, and not with that of brushite. In contrast, the bone acid phosphate anisotropic chemical shift parameters are close to those of brushite, and differ significantly from those of octacalcium phosphate. The orthophosphate resonances of bone mineral, synthetic hydroxyapatite and synthetic octacalcium phosphate share identical chemical isotropic shifts, and similar chemical shift anisotropies. The implication of these results is that the intimate structure of the acid phosphate group in bone mineral is unique, and that none of the common synthetic calcium phosphates accounts well for all of the observed solid state phosphorus-31 NMR properties of bone mineral.
Animals↗
In vivo 1H chemical shift imaging of silicone implants.
In order to study the aging process (i.e., silicone migration, fat infiltration) of silicone (polydimethylsiloxane, PDMS) based biomaterials in living subjects by NMR imaging, a hybrid 1H selective excitation and saturation chemical shift imaging technique (IR/CHESS-CSSE) has been developed. This sequence allows selective mapping of the distribution of silicone protons in vivo, while suppressing the contributions of fat and water. Our results indicate that a combined inversion recovery and CHESS pulse, followed by a spoiler gradient, must be applied to suppress all contributions of fat protons to the NMR signal. The sensitivity of our experiments allows the detection of a chemically unchanged silicone concentration of 5% in a voxel of 0.9 mm3 at a signal/noise ratio of 2.
Adipose Tissue↗
In vivo degradation of silicones.
29Si nuclear magnetic resonance (NMR) spectroscopy is applied to study the degradation of polysiloxanes (silicones) in vivo. Our results with animal models show that silicone migrates from the implant to the liver (29Si resonance at -20 ppm) and new silicon containing compounds form after the silicones are introduced into the rats. The new 29Si resonances in the chemical shift range of -40 to -85 ppm are related to hydrolyzed silicone, those at -90 to -115 ppm are indicative of the presence of silica (SiO2), and the peaks observed at -120 to -150 are related to high coordinated silicon complexes. These resonances are not present in the 29Si spectra of the silicones before implantation. Our findings demonstrate that silicones are not metabolically inert.
Animals↗
In vivo localized proton NMR spectroscopy of silicone.
1H NMR localized spectroscopy (STEAM) can assess unambiguously the presence of free chemically unchanged silicone in animal tissue after injection of silicone oil. Although the signal-to-noise ratio obtained in 1H imaging is sufficient to detect the distribution of relatively large amounts of silicone in vivo, the specificity of silicone detection can be improved by using 1H localized spectroscopy techniques. The sensitivity of the STEAM experiments is sufficient to detect silicone at a concentration of 0.5% in a voxel of 27 mm3. Preliminary results from rats with silicone gel-filled implants show no detectable amounts of silicone in sites such as lymph nodes, the liver or the spleen, 3 or 6 months after implantation.
Animals↗
Migration and biodegradation of free silicone from silicone gel-filled implants after long-term implantation.
In vivo 1H NMR chemical shift imaging (CSI), 1H NMR localized spectroscopy (STEAM) and multinuclear NMR spectroscopy (29Si, 13C, 1H) were used to characterize the aging process of silicone gel-filled implants in a rat model after long-term implantation. Although no significant changes could be observed in the implants or surrounding tissue by in vivo 1H chemical shift imaging, in vivo 1H localized spectroscopy of the livers from the longer term population revealed the presence of silicone. Ex vivo 29Si spectroscopy of the liver, spleen, and the capsule formed around the 9 and 12 month implants clearly demonstrated and confirmed for the first time that a significant amount of free silicone migrates from silicone gel-filled implants. Also, these results show that silicones are not metabolically inert, and their biodegradation in tissue and within the implant can be monitored after 9 and 12 months by changes in the 29Si chemical shifts seen in corresponding ex vivo spectra. The NMR findings are supported by those obtained by atomic absorption spectroscopy. Silicone aging changes not only the chemical composition of the gel, but also its proton T2 relaxation times, which increase with long implantation times. The three dimensional structure of the gel disintegrates (i.e., polymer chain rupture), increasing the molecular mobility of the polymer and, consequently, its protons T2 values. The relaxation data we obtained reflect this in vivo degradation, especially in the case of implant rupture. Additionally, small concentrations of fat in the silicone gel were found within the implants. The presence of these lipophilic substances also might increase the T2 values (plasticizer effect). These findings may assist in evaluating the implant integrity and disease symptoms related to their presence in humans.
Animals↗
Phosphorus-31 magnetic resonance imaging of hydroxyapatite: a model for bone imaging.
One-dimensional 31P nuclear magnetic resonance images (projections) of synthetic calcium hydroxyapatite, Ca10(OH)2(PO4)6, have been obtained for samples on the order of 0.5 to 1.0 cm in linear extent at 7.4 T magnetic field strength. Because of the solid state nature of these samples, short 31P spin-spin relaxation times under 1 ms occur, necessitating echo times of 1 ms and phase-encoding magnetic field gradient pulses shorter than 500 microseconds. Optimal projection quality and shortest acquisition times result from pulsed gradient phase-encoding of the spatial dimension, using a compensating gradient pulse to cancel the distorting effects of gradient waveform transients. The exceedingly long 31P spin-lattice relaxation times could lead to potentially intolerable image acquisition times; these have been reduced with a flipback pulse technique. In addition to holding great potential as a novel research tool in the study of biomineralization of those organisms containing calcium phosphate solid phases, these methods should be of general utility in the multinuclear imaging of a wide variety of solids of interest in biophysics and materials science.
Bone and Bones↗
MR contrast due to microscopically heterogeneous magnetic susceptibility: numerical simulations and applications to cerebral physiology.
We calculate the effects of subvoxel variations in magnetic susceptibility on MR image intensity for spin-echo (SE) and gradient-echo (GE) experiments for a range of microscopic physical parameters. The model used neglects the overlap of gradients from one magnetic inclusion to the next, and so is valid for low volume fractions and weak perturbations of the magnetic field. Transverse relaxation is predicted to deviate significantly from linear exponential decay in both SE and GE at a particle radius of 2.5 microns. Calculated changes in transverse relaxation rates for SE and GE increase linearly with volume fraction of high-susceptibility regions of 5 microns diameter, but increase with about the 3/2 power of volume fraction of regions with 15 micron spacing between centers. This sensitivity to the actual size and spacing of magnetized regions may allow them to be measured on the basis of contrast. without being resolved in images. GE and SE decay rates are approximately twice as sensitive to long cylinders of 5 microns diameter than to spheres of the same size, for diffusion constants of 2.5 micron 2/ms. Calculated changes in transverse decay rates increase with approximately the square of field and susceptibility variation for 5-microns spheres and a diffusion constant of 2.5 microns 2/ms. This exponent is smaller for cylindrical magnetized regions of the same size, and also depends on the diffusion constant. We discuss possible applications of our theoretical results to the analysis of the effects of high-susceptibility contrast agents in brain. Experimental data from the literature are compared with calculated signal changes according to the model. The monotonic dependence of decay rates on the volume of distribution of the contrast agent suggests that cerebral blood volume and flow could be measured using MR contrast.
Brain↗
Porous block hydroxyapatite in orthognathic surgery.
Seventy-six nonconsecutive patients undergoing orthognathic surgery, in whom blocks of porous hydroxyapatite were implanted into osteotomy gaps in lieu of autogenous bone grafts, are the subjects of this report. Surgical procedures include inferior maxillary repositioning (10 patients), maxillary advancement (24 patients), transverse maxillary expansions (17 patients) and inferior repositioning of the chin (25 patients). A total of 140 anatomic sites were implanted. Eleven patients later consented to open biopsy of the implant material at a mean 10.2 months following implantation. At the time of follow-up, mean 16.3 months, excellent osseous stability was observed. Three patients developed complications relative to the presence of the implant. Twenty-one of 24 biopsy specimens demonstrated an osseous union of implant to bone with osseous deposition within the implant pores. Radiographic follow-up revealed implant blocks to maintain their volume with no change in density or discreteness. The biological behavior and biomechanical properties of porous block hydroxyapatite are discussed. These implant characteristics make it a feasible bone graft substitute in orthognathic surgery and justify its continued use in this context.
Adolescent↗
Nuclear magnetic resonance microscopy of atheroma in human coronary arteries.
The purpose of this study was to use direct nuclear magnetic resonance (NMR) microscopy to quantitate and image accumulations of atheroma lipids in human coronary arteries and to validate the results by comparison with histologic preparations. NMR microscopy was performed on a superconducting experimental NMR imaging system operating at 2 Tesla with a probe designed for short echo time (TE), strong B1 field strength, and small samples. Data acquisition used multiple-offset chemical encoding with offsets based on the thermotropic spectral signature of atheroma lipids within the human arterial vessel wall. Three separate channels of image data yielded color axis display of atheroma within the vessel walls. Atheroma location by histology was identified by rarefaction of stroma, as the lipids are extracted in the process of embedding in paraffin. Perimeters, areas, and a shape index (perimeter2:4 pi area) of lumen, atheroma, and outer wall were determined and compared for NMR vs histology. There was no significant difference in the measurements with the exception of luminal shape indices, which were uniformly larger by histology, attributable to flattening of the vessels during histologic preparation. NMR measurement of atheroma content of coronary artery walls agreed well with histology (r = 0.996). NMR microscopy with color axis display proved able to quantitate and image atheroma in coronary arteries, obviating the distortions and lipid removal associated with fixation, embedding, and sectioning for histology.
Adult↗
Dynamic imaging with lanthanide chelates in normal brain: contrast due to magnetic susceptibility effects.
Using a one-dimensional rapid imaging technique, we have found that injection of lanthanide chelates such as Gd(DTPA)2- leads to a significant decrease (50%) in rat brain signal intensity at 1.45 T using T2-weighted pulse sequences; however, no effect of comparable size is observed with T1-weighted pulse sequences. The transient effect and its kinetics were followed with a temporal resolution of between 1 and 8 s. Experiments with different lanthanide chelates show that the observed decrease in signal intensity correlates with the magnetic moment of each agent but not with their longitudinal relaxivity. Three-dimensional chemical-shift resolved experiments demonstrate significant line broadening in brain during infusion with Dy(DTPA)2-. Our results show that the cause of this effect is the difference in susceptibility between the capillaries, containing the contrast agent, and the surrounding tissue. As a result of these susceptibility differences, field gradients are produced in the tissue and diffusion of water through these gradients leads to a loss of spin phase coherence and thus a decrease in signal intensity. We propose this as a new type of contrast agent mechanism in NMR. The effect and its kinetics are likely to be related to important physiological parameters such as cerebral blood volume and cerebral blood flow, and do not depend on a breakdown of the blood-brain barrier as do conventional contrast agent techniques.
Animals↗
Dynamic range compression in MRI by means of a nonlinear gradient pulse.
In current magnetic resonance imaging (MRI), valuable information must often be discarded because the NMR signal has greater dynamic range than the analog-to-digital converter (ADC) hardware. Typically, a small set of high-intensity data points near the center of the spin echo is responsible for most of the MRI data dynamic range. We predict that it is possible to reduce the dynamic range of the MRI spin echo by incorporating an identical nonlinear gradient pulse into each repetition of the imaging pulse sequence, prior to data sampling. This pulse converts the phase distribution of the subject, ordinarily a linear function of image coordinates, into a nonlinear function. A nonlinear phase distribution can have a negligible impact on image magnitude and yet a profound impact on spin-echo magnitude. Given a nonlinear phase distribution, there will no longer be a single data point at which all of the protons have an identical phase (the echo center). Instead, the protons become phase coherent on a piecemeal basis, the echo peak is smoothed out, and its maximum amplitude and dynamic range are greatly diminished. Using gradient pulses of quadratic spatial variation, we estimate that maximum echo amplitude and dynamic range can be reduced in most cases by an order of magnitude.
Analog-Digital Conversion↗
Perfluorinated organic liquids and emulsions as biocompatible NMR imaging agents for 19F and dissolved oxygen.
Emulsions of fluorocarbons are finding considerable use in physiology for intravascular oxygen transport. Their wide clinical application as blood substitutes, anti-shock, and anti-ischemic agents seems imminent. Whole body NMR imaging is rapidly gaining clinical application and may one day almost completely supplant X-ray imaging. All of the 19F compounds used in biocompatible fluorocarbon emulsions give 19F signals identical to those in the corresponding neat liquid. In concentrations of 10% w/v they are readily imaged. The paramagnetic oxygen molecule reduces T1 in such a way as to make possible whole body imaging of oxygen. T1 typically decreases from 1-4 to 0.3-0.5 seconds and is an inverse linear function of oxygen tension. Spin-lattice relaxation times versus oxygen tensions from 0 to 600 torr have been obtained for F-decalin, F-tributylamine, and F-44E. The usefulness of these 19F effects in clinical NMR imaging depends upon the sensitivity of the method and the tolerable dose. The 19F signal may find use in monitoring 19F compounds as vapors or gases dissolved in plasma or in perfluorocarbons in neat liquid or particle form.
Animals↗
Practical aspects involved in the design and set up of a 0.15 T, 6-coil resistive magnet, whole body NMR imaging facility.
Many technical and logistical questions must be addressed when planning the installation of an NMR imaging system. These considerations become particularly significant when the facility is being established within an existing medical center complex. This paper presents a report on the practical aspects and experience obtained in siting a 6-coil 0.15 T resistive magnet system. The topics discussed include: floor loading; ferromagnetic environment; the effect of iron on the magnet field strength and homogeneity characteristics; shimming procedures; temperature stability requirements; rf shielding; and effects of the magnetic field on common medical instrumentation and magnetic media. It was found that the field shift as a function of the distance of a steel mass from the center of the magnet exhibited an (1/r)5.2 +/- 0.5 to (1/r) 4.2 +/- 0.3 dependence for axial and radial positions respectively which, as expected, is somewhat weaker than the (1/r)6 dependence expected by point dipole approximations. Field distortions caused by the presence of ferromagnetic material in radial positions may be essentially fully compensated with first order transverse shim coils (most conveniently, the x and y imaging gradient coils could be used). Axially distributed material requires, in addition to first order z-gradient correction, higher order axial shim compensation. The temperature stability of the magnet system over the scan period must be better than 0.2 degrees C to insure that temperature-induced field fluctuations are less than the intrinsic static inhomogeneity: and, ideally, below 0.01 degrees C to reduce these fluctuations to less than those caused by power supply instability.
Construction Materials↗