Proton magnetic resonance studies of triethyltin-induced edema during perinatal brain development in rabbits.

To better understand the role of myelin-associated water in the differentiation of white and gray matter in magnetic resonance (MR) imaging, changes in MR relaxation processes were studied in rabbits during myelination and after induction of cytotoxic edema with triethyltin (TET). Normal rabbits were killed at various age intervals ranging from premature (28 days' gestation) to adult, and changes in MR relaxation times (T1 and T2) and in water and electrolyte content were determined for various areas of brain and muscle. Similar measurements were made in rabbits of comparable age exposed to TET. Light and electron microscopy and MR imaging were used to follow myelin development and morphological changes induced by TET. During the first 30 postnatal days, both T1 and T2 declined by 50% in normal rabbits, a fall that paralleled the loss in brain water and sodium that occurred during the same period. Exposure to TET prolonged T1 and T2 in white but not gray matter, reflecting the accumulation of sodium and water (edema fluid) in white matter areas. Multiexponential analysis revealed a second, longer component in T2 magnetization decay of TET-exposed white matter, presumably attributable to accumulation of non-ordered water within intramyelinic vacuoles, a supposition consistent with electron microscopic and MR imaging findings. In contrast to reports by others, changes in T1 (but not T2) closely correlated with alterations in brain water (r = 0.93, df = 39). The absence of tissue disruption in the animals in the present study may account for these differences, but further studies will be required both to resolve this question and to fully understand MR images of white matter edema in mature and immature brain.

MR imaging of laser-tissue interactions.

A new application of magnetic resonance (MR) imaging to map the spatial and temporal distribution of the effects of Nd:YAG lasers on tissues was studied. The temperature dependence of MR relaxation mechanisms and the high sensitivity of MR to changes in the mobility and distribution of tissue water make it particularly suitable for the demonstration and control of thermal energy deposition in tissues. In heterogeneous tissues, MR imaging does not follow changing temperatures directly because even in the case of reversible thermal interactions, there is a hysteresis in the dynamic relationship between MR signal intensity and temperature. Appropriate matching of the laser and MR pulse sequences can, however, optimize the detection of relatively small laser energy deposition, and reversible and irreversible tissue changes can be distinguished. There is a potential for the integration of MR imaging and lasers for three-dimensional control and monitoring of laser-tissue interactions.

Application of the maximum likelihood principle to separate exponential terms in T2 relaxation of nuclear magnetic resonance.

The method of maximum likelihood has been implemented for the estimation of multiple exponential components of T2 decay curves in spin echo NMR measurements on biologic tissues. Each Each component contributes an exponential term described by two parameters (initial amplitude and T2) to the T2 decay curve. The maximum likelihood method estimates the parameters and their standard errors for all terms simultaneously, avoiding the subjectivity inherent in methods such as graphical peeling. In the model used, it was assumed that water protons are compartmentalized and that the measured spin echo signals from the protons undergoing relaxation obey the Poisson distribution. A system of non-linear equations was derived and solved iteratively for the values of the exponential parameters which maximize the likelihood of obtaining the observed data under these assumptions. The approach was implemented for bi- and tri-exponential models on a MicroVAX II computer (Digital Equipment Corporation, Maynard, MA). Simulations of bi- and tri-exponential data, with and without system noise, were analyzed to assess the accuracy and reproducibility of the method. A subset of the simulations was repeated with non-linear least squares techniques and was compared to the results obtained with maximum likelihood. Rabbit muscle and gerbil brain samples were measured and analyzed with the maximum likelihood method. The simulations showed that within specific limits on relative sizes and relaxation rates of components, these parameters can be estimated with errors less than 5%. The comparison to non-linear least squares analysis showed that the maximum likelihood method is generally superior in estimating the parameters in difficult cases. The results from tissue measurements demonstrate that the method is effective even in cases where graphical peeling would clearly not yield reliable results.

Reflex inhibition of urethral sphincters to permit voiding in paraplegia.

When the spinal motoneurons innervating the external sphincter of the urethra cannot be inhibited voluntarily due to lesions of the spinal cord, the normal capacity to relax this physiologic valve during micturition is lost. Even if contractions of the bladder occur, urinary outflow may be completely blocked at the sphincter, leading to distention of the bladder and the risk of urinary infection. A method is described for controllably relaxing the sphincter, which permits free outflow of urine in paraplegic cats. One pudendal nerve is sectioned, paralyzing half of the sphincter, but leaving the experimental animals entirely continent. The motoneurons supplying the other half of the sphincter are inhibited by means of spinal reflexes, eliminating active resistance to urethral flow. The simplicity of this approach suggests that it may prove equally effective in human paraplegia.

Myelinated and nonmyelinated nerves: comparison of proton MR properties.

The magnetic resonance (MR) relaxation rates of protons were compared in the myelinated and nonmyelinated nerves of the garfish. The long, large olfactory nerve of the garfish, as an easily accessible source of nonmyelinated axons, is uniquely suited for such a comparison. The T1 and T2 measurements revealed distinct and consistent differences between nonmyelinated olfactory nerves and myelinated optic and oculomotor nerves. Comparisons between water content, lipid content, and relaxation rates indicated that the differences in MR properties represent complex differences in the distribution and physical environment of the constituent lipid and water protons.

Wallerian degeneration demonstrated by magnetic resonance: spectroscopic measurements on peripheral nerve.

Wallerian degeneration of rat sciatic nerves was induced by nerve section. Fifteen days later the degenerated nerves were compared with the intact contralateral nerves from the same animal. Histological sections showed the changes typical of wallerian degeneration: axonal degeneration and secondary demyelination. The freshly dissected nerves were analyzed by magnetic resonance (MR) spectroscopy at 10 MHz, and the water content was determined by dehydration. In the degenerated nerves there was a marked prolongation of both T1 and T2 relaxation times, accompanied by an increase of water content. The results demonstrate the sensitivity of MR for detection of secondary demyelination and disintegration of nerve structures. These results suggest that it should be possible to detect wallerian degeneration in MR images; this will have an important impact on neuropathological diagnosis of central and peripheral nervous system lesions.

Effects of impulse frequency, PTP, and temperature on responses elicited in large populations of motoneurons by impulses in single Ia-fibers.

Excitatory postsynaptic potentials (EPSPs) were evoked in large populations of motoneurons by impulses in single Ia- and group II fibers and recorded from L7 and S1 ventral roots by means of a sucrose-gap technique and spike-triggered averaging, as previously described (33, 34). Factors known to influence conduction at branch points in peripheral nerves or transmission in the Ia projection to motoneurons were studied to determine their effects on these postsynaptic population potentials (PSPPs). When impulse frequency was plotted against the amplitude of these PSPPs, a sequence of low-frequency depression, higher frequency facilitation, and still higher frequency depression was regularly observed. Similar plots of PSPP amplitude versus impulse frequency in a small sample of group II spindle fibers did not reveal any low-frequency depression. Higher frequency facilitation and depression followed the same pattern as that produced by Ia-fibers. Early potentiation of the PSPPs was produced by applying 20 stimulating pulses at 500/s to branches of the medial gastrocnemius nerves containing single Ia-fibers. Single, posttetanic PSPPs were recorded at fixed intervals following each tetanus and averaged. A brief, initial depression followed by a rapidly declining potentiation of PSPPs was regularly observed. When the core temperature was reduced from 41 to 35 degrees C, there was an approximately linear increase in the amplitude of PSPPs. At each temperature a combination of cooling and posttetanic potentiation (PTP) elicited larger PSPPs than cooling alone. The effects of impulse frequency, PTP, and temperature on PSPPs may all be interpreted in terms of their known effects on action potentials or on conduction at branch points in peripheral nerves. Similar effects on transmission or transmission failure in the terminal arborizations of Ia-fibers would account for the influence of these factors on PSPPs. Alternatively, these same three factors might cause similar effects on PSPPs through influences they might exert on the transmitter release mechanism.

Flexor reflex control of the external sphincter of the urethra in paraplegia.

In paraplegics and quadriplegics a profound paralysis of skeletal muscles occurs below the level of the spinal lesion. Unexplained in this state is the development of an overactive external urethral sphincter, which interferes with emptying of the bladder and may lead to infection of the urinary tract. Studies of cats show that the discharge of motoneurons causing this contraction has all the characteristics of a flexor reflex.