In addition to atrophy measurements, reliable MTR measurements can be obtained from the optic nerve and spinal cord, which shows the feasibility of the application of MT MRI for the assessment of the involvement of these critical structures in the course of MS.
Two ROI-based studies (203,204) reported abnormal MTR values in the optic nerve after an acute ON, independently of the presence of T2-visible abnormalities (204). Inglese et al. (91) demonstrated a correlation between MTR changes and the degree of visual function recovery after an acute episode of ON in 30 MS patients, showing that MTR reduction was more pronounced in the optic nerves of MS patients with no recovery than in those with clinical recovery, and that similar reductions were seen in patients with Leber's hereditary optic neuropathy, indicating that axonal loss is likely to be an important contributor to MTR decrease in MS. In a serial MTR study of patients with acute ON, Hickman et al. (92) showed that the MTR of the affected optic nerves was not different from that of optic nerves from normal controls during the acute phase, but it declined over time significantly with a nadir at about eight months after disease onset, despite the rapid initial visual recovery. The MTR decline is consistent with demyelination and axonal damage; the late nadir may have been due to slow clearance of myelin debris. Subsequently, diseased optic nerve MTR appeared to rise, possibly due to remyelination. Although more technically demanding, successful DW MRI of the optic nerve (205,206) has also been obtained in healthy individuals (205,206) and MS patients (205). Iwasawa et al. (205) assessed water diffusion in the optic nerves of patients with ON, demonstrating significant different optic nerve ADC values between controls and patients. In addition, this study demonstrated that ADC values are decreased in the acute (inflammatory) stage of ON and increased in the chronic phase.
Using ROI analysis, Silver et al. (207) found reduced MTR values in the cervical cord of 12 MS patients in comparison with healthy volunteers; however, no correlation was found between cord MTR and disability, probably due to the small number of subjects enrolled and the limited portion of cord studied. These results have been partially confirmed by a subsequent study performed on 65 MS patients (208), where a weak correlation between the reduction of MTR values and the increase of clinical disability has been found. More recently, the use of histogram analysis has allowed to obtain a more global picture of cord pathology in patients with MS. Histogram analysis has demonstrated that cord MTR histogram metrics in CIS (98), RRMS (209), and early-onset MS (158) patients are similar to those of healthy individuals. On the contrary, cord MTR metrics are markedly reduced in patients with SPMS and PPMS (110,210). Average cervical cord MTR is lower in MS patients with locomotor disability than in those without (209). In PPMS, a model including cord area and cord MTR histogram peak height was significantly, albeit modestly, associated with the degree of disability (110). In patients with MS, cord MTR is only partially correlated with brain MTR (210), suggesting that MS pathology in the cord is not amere reflection of brain pathology and, as a consequence, measuring cord pathology might be a rewarding exercise in terms of understanding MS pathophysiology.
With increasing technical advances, it has also become possible to study cord MS pathology using DW MRI (211-216). A preliminary study, which assessed water diffusion in seven cord lesions of three MS patients with locomotor disability (213), found increased MD values in MS cord lesions in comparison to the cord tissue from healthy volunteers. More recently, Filippi et al. (215) used histogram analysis to assess water molecular diffusivity of the cervical cord from 44 patients with either RRMS or SPMS and found reduced average cord FA in MS patients compared with controls (Fig. 15). In MS, the reduction of cord FA was correlated with the degree of disability. Altered MD and FA cord histogram derived metrics have also been found in patients with PPMS (216).
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