To the best of our knowledge, this is the first prospective study using DTI and MRS to observe secondary changes in the thalamus, remote from a single subcortical cerebral infarction within the territory of the MCA. A significantly increased MD at W12 and a significantly decreased NAA at W4 and W12 were observed in the thalamus ipsilateral to the infarction. This suggests that both DTI and MRS detect certain aspects of early secondary thalamic damage in patients with acute infarction of the corona radiata, and MRS might be more sensitive than DTI in detecting secondary thalamic damage in the early stages of a stroke. Moreover, a significant negative correlation between MD and NAA at W1, W4, and W12 in the ipsilateral thalamus was found, suggesting that the structural loss in neurons is consistent with the dysfunction.
In this study, asymmetry indices comparing MD, FA, and peak areas of NAA, Cho, and Cr in thalamus were evaluated to reduce inter-patient and inter-exam variability. Analysis of MD, FA, and peak areas of NAA, Cho, and Cr, together with asymmetry indices of those parameters, showed that NAA was significantly decreased at W4 and W12, while MD was increased at W12 compared to W1 and controls. However, there were no significant differences in MD and NAA at W1 compared to controls by analysis of asymmetry indices. DTI and MRS parameter values in the contralateral thalamus were stable during the observation period, and thus can be regarded as an internal reference for calculating asymmetry indices. By using this method, effects of hypertension or other factors on MRI data may be ruled out; furthermore, the consistency of trends in MD and NAA changes shown by asymmetry indices and absolute values suggests that asymmetry indices might be a more reliable and reasonable method.
Increased MD in the ipsilateral thalamus may be a reflection of secondary degeneration due to disruption of white matter tracts linking the thalamus to other structures, specifically degeneration of cortico-thalamic or thalamocortical pathways [12, 24]. A significant increase of MD in the ipsilateral thalamus was found between W1 and W12, and between W4 and W12, but there were no significant changes between W1 and W4. Such increases in MD in the thalamus have also been described in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) [24, 25]. Similarly, in a study on patients with MCA infarcts, an increase in MD was observed between the first and the sixth month in the ipsilateral thalamus in patients with cerebral cortex involvement . The difference in our study is that the infarction was located in the corona radiata, without cortical involvement, thus excluding the effects of cortical damage on the thalamus. The abnormal diffusion observed in the thalamus in our study suggest that the secondary damage is cumulative from W1 to W12, and it is more obvious at later stages after infarction. FA is a measure of the directionality of diffusion, and is greater in white matter tracts than in grey matter. In our study, there was no significant FA difference observed in thalami between patients and controls, between thalami ipsilateral and contralateral to the infarction, which may be due to fewer oriented fiber bundles, and more nuclei in parallel within the thalamus. It was noteworthy that, in a study on CADASIL, significant reductions in anisotropy were found in thalami on both sides in patients compared to the controls . It is probable that longer follow-up and more sophisticated image analysis techniques are required for determining FA changes in the thalamus ipsilateral to a remote infarction. Accordingly, these results provide evidence that DTI may detect early damage to the thalamus ipsilateral to the infarction, and increased MD in the ipsilateral thalamus might have diagnostic value in demonstrating and evaluating secondary damage, although it may not show the changes of dynamic process within 4 weeks after stroke onset.
Animal and autopsy studies have shown that neuronal degeneration and a reduction in the number of nerve cells occur in the ipsilateral thalamus after MCA infarction [3–6, 8]. Our analysis of spectroscopic images acquired with proton MRS show a significantly progressive decrease in the ipsilateral thalamic NAA in patients from W1 to W4, and W4 to W12, indicating neuronal and/or axonal loss and dysfunction. Such changes in thalamus are in line with previously-reported findings in the ipsilateral thalamus after infarction [3–6, 8]. It is presumable that after corona radiata infarction, thalamic neuronal anterograde and retrograde degeneration induces neuronal and/or axonal loss and dysfunction in the ipsilateral thalamus, which results in damage to cortico-thalamic or thalamocortical fibers. Cho/Cr increases in the thalami of depressive patients have been associated with membrane phospholipids related to metabolism abnormality . In our study, there were no significant changes of Cho during the observation period. This suggests that the pathological alterations in membrane turnover in the thalamus with secondary damage might be a chronic process. Moreover, NAA decreased obviously within 4 weeks, but no significant changes in MD were found during this stage. These results indicate that MRS can also detect early damage in the ipsilateral thalamus after infarction MRS is more sensitive in revealing the dynamic process of secondary damage in the ipsilateral thalamus in the early stages of stroke.
Correlations between DTI and MRS parameters have been reported in healthy volunteers and primary progressive multiple sclerosis (ppMS) patients. A negative correlation between NAA and ADC was found in ppMS patients and controls [26, 27]. In our study, we also found a significant negative correlation between MD and NAA at W1, W4, and W12, suggesting that neuronal structure damage indicated by increased MD was approximately coincident with neuronal metabolism damage indicated by decreased NAA. This consistency of neuronal structure loss and dysfunction suggests a phenomenon of neuronal degeneration in the ipsilateral thalamus. In addition, FA correlates positively with NAA at W1, but showed no correlations at W4 and W12, suggesting that FA cannot reflect secondary damage process indicated by increased MD and decreased NAA in the ipsilateral thalamus. Cho showed negative correlations with MD, suggesting a constructive role of Cho in the preservation of neuron structures . It is in agreement with a previous study on healthy controls in which a negative correlation of MD with Cho was shown . Moreover, MD showed negative correlations to Cr suggests integrity of structure indicated by MD was associated with neuronal energy use and storage indicated by Cr in thalamus .