3T-diffusion tensor tractography and 1H-MR-spectroscopy in motor neuron disease

Purpose: To assess the diagnostic accuracy of combined 3T 1H-MR-Spectroscopy (MRS) and Diffusion Tensor Imaging (DTI) in patients with suspected motor neuron disease versus EMG, Transcranial Magnetic Stimulation (TMS) and the El-Escorial scale as a gold standard.

Methods: 18 patients (11 male, mean age 59 (45 to 73) years) with suspected motor neuron disease were studied with MRS and DTI. For MRS, absolute NAA and relative NAA/Cho ratios of corresponding 30×25×20mm cubic volumes of interest (VOIs) within the primary motor cortex were calculated. For DTI, the corticospinal tracts (CST) were tracked using a 3 point seed technique. Fractional anisotropy (FA) and Mean Diffusivity (MD) were measured bilaterally at the level of the precentral gyrus, corona radiata, internal capsule, cerebral peduncles, pons and pyramid and compared to a control group of 34 age- and sex-matched volunteers. FA and MD statistics were additionally averaged on the CSTs as a whole. Patients were clinically assessed and grouped (1=controls, 2–4=patients) according to the El-Escorial and ALSFRS scales. Observers were blinded to results of clinical ratings and TMS. DTI and MRS were evaluated independently by different investigators.

Results: Clinically, there were 4 „definite“, 4 „probable“, and 6 „possible“ ALS patients according to the El-Escorial score. Three patients had different diagnoses (Kennedy Syndrome 1, cervical myelopathy 1, polyneuropathy 1). Mean FA of participants with „probable“ and „definite“ assessments were below double standard deviation of healthy controls for the corona radiata and precentral gyrus. Overall, mean FA of groups 3 and 4 was significantly lower in the upper three regions (p <0.05). In the brainstem regions, DTI results were close together. MRS indicated NAA reduction beyond double standard deviation in six of eight patients with clinical evidence for upper motor neuron involvement. MRS and DTI were congruent at the level of the precentral gyrus and corona radiata in all but three cases, one belonged to the „definite“ El-Escorial category (DTI indicated first motor neuron degeneration, MRS did not), one was correctly excluded from motor neuron disease by DTI (Kennedy syndrome was proven by genetic analysis) whereas MRS indicated CST involvement. DTI tended to be false-positive for CST affection in a case with lower motor neuron involvement only.

Conclusion: Combined MRS and DTI at 3T effectively adds to classical more invasive procedures to detect and to exclude motor neuron disease.