Changes in the MR parameters of inflamed neural tissue were measured in vitro. Tumor necrosis factor-alpha (TNF-␣) was injected into rat sciatic nerves to induce inflammation with negligible axonal loss and demyelination. The MR parameters, such as T 1 /T 2 relaxation and magnetization transfer (MT), were measured 2 days after TNF-␣ injection and were found to be substantially different from those of normal nerves. The average T 1 /T 2 relaxation times increased, whereas the MT ratio (MTR) and the quantitative MT parameter M 0B (which describes the semisolid pool of protons) decreased. The MR parameters correlated very well with the extracellular volume fraction (EM) of neural tissue evaluated by quantitative histopathology. The multicomponent T 2 relaxation was shown to provide the best quantitative assessment of changes in neural tissue microstructure, and allowed us to distinguish between the processes of inflammation and demyelination. In comparison, the MT measurements were less successful due to competing contributions of demyelination and pH-sensitive changes in the MT effect. Inflammation commonly occurs in a wide spectrum of nervous system diseases, including multiple sclerosis (MS) (1), stroke (2), dementia (3), and traumatic brain injury (4). It is difficult to distinguish the processes of inflammation from those of neural tissue degeneration, such as axonal loss and demyelination, because similar qualitative changes occur in the MR signal intensities of T 1 -, T 2 -, or magnetization transfer (MT)-weighted images. MRI evaluations of tissue pathology are further complicated by the fact that inflammation, axonal loss, and demyelination often occur concurrently. The precise identification of the pathophysiological processes that occur in nervous system disorders is of considerable importance in our ability to accurately diagnose disease, understand the mechanisms and dynamics of neural tissue degeneration, and evaluate treatment efficacy. There is, therefore, a great need to establish MRI protocols that are capable of differentiating and quantitatively assessing these pathologies.Quantitative MR measures are thought to provide more specific information about changes in tissue microstructure. For example, the multicomponent T 2 relaxation is sensitive to white matter (WM) demyelination in multiple sclerosis (MS). The observed short T 2 component, which occurs at approximately 10 -20 ms, has been associated with water in the myelin sheath (5), and thus provides a measure of the processes of demyelination and remyelination. We recently demonstrated that the magnitude of the short T 2 component correlates very well with the amount of myelin in nerves undergoing degeneration and spontaneous regeneration following traumatic injury of the peripheral nervous system (PNS) (6). Conversely, the MT effect is thought to be mainly mediated by the processes of MT exchange between water and lipid protons within the myelin sheath (7,8). It has been shown (9) that the observed changes in the MT ratio (MTR) and the decrea...

Changes in the magnetic resonance (MR) parameters of demyelinated neural tissue were measured in vitro using an experimental animal model. A tellurium (Te) diet was applied to weanling rats to induce the demyelination process in the sciatic nerve. The quantitative MR parameters, such as T(1), T(2) relaxation time constants and magnetization transfer (MT) were measured each day after applying the Te diet (up to 7 days) and were found to be substantially different from those of normal nerves. An increase in the average T(1) and T(2) was observed along with a decrease in the MT ratio (MTR) and the quantitative MT parameter M(0B), which describes the semisolid pool of protons. Most of the MR parameters correlated very well with the myelin fraction of neural tissue evaluated by quantitative histopathology. The T(2) relaxation spectrum provided the most efficient quantitative assessment of changes in neural tissue microstructure and its analysis resulted in a powerful tool to distinguish the processes of demyelination and inflammation. In comparison, the MT measurements were less successful.

Ingestion of tellurium (Te), a toxic element, produces paralysis of the hind limbs in weanling rats that is due to temporary, segmental demyelination of the sciatic nerves bilaterally. Weanling rats were fed a 1.1% elemental Te diet and sacrificed at various time points for histological and magnetic resonance (MR) analysis of the sciatic nerves. No controls exhibited impairments of the hind limbs, whereas Te-treated animals became progressively impaired with increased Te exposure. Toluidine blue-stained nerve sections of Te-treated animals showed widened endoneurial spaces, disrupted myelin sheaths, swollen Schwann cells, and a few instances of axonal degeneration. Te decreased healthy myelin by 68% and increased percent extracellular matrix by 45% on day 7. MR experiments showed a decrease in the area of the short T2 component, an increase in average T1, and an increase in the position of the intermediate T2 component in Te-treated nerves. The correlation coefficient for healthy myelin and average T1 was 0.88 and that for healthy myelin and the area underneath the short T2 component was 0.77. The area of the short T2 component has been postulated as the best measure of the process of demyelination.