Neuromelanin-Sensitive MRI as Candidate Marker for Treatment Resistance in First-Episode Schizophrenia.

OBJECTIVE: Markers for treatment resistance in schizophrenia are needed to reduce delays in effective treatment. Nigrostriatal hyperdopaminergic function plays a critical role in the pathology of schizophrenia, yet antipsychotic nonresponders do not show increased dopamine function. Neuromelanin-sensitive MRI (NM-MRI), which indirectly measures dopamine function in the substantia nigra, has potential as a noninvasive marker for nonresponders. Increased NM-MRI signal has been shown in psychosis, but has not yet been assessed in nonresponders. In this study, the authors investigated whether nonresponders show lower NM-MRI signal than responders. METHODS: NM-MRI scans were acquired in 79 patients with first-episode psychosis and 20 matched healthy control subjects. Treatment response was assessed at a 6-month follow-up. An a priori voxel-wise analysis within the substantia nigra tested the relation between NM-MRI signal and treatment response in patients. RESULTS: Fifteen patients were classified as nonresponders and 47 patients as responders. Seventeen patients were excluded, primarily because of medication nonadherence or change in diagnosis. Voxel-wise analysis revealed 297 significant voxels in the ventral tier of the substantia nigra that were negatively associated with treatment response. Nonresponders and healthy control subjects had significantly lower NM-MRI signal than responders. Receiver operating characteristic curve analysis showed that NM-MRI signal separated nonresponders with areas under the curve between 0.62 and 0.85. In addition, NM-MRI signal in patients did not change over 6 months. CONCLUSIONS: These findings provide further evidence for dopaminergic differences between medication responders and nonresponders and support the potential of NM-MRI as a clinically applicable marker for treatment resistance in schizophrenia.

Acceleration of neuromelanin-sensitive MRI sequences in the substantia nigra using standard MRI options.

PURPOSE: Neuromelanin MRI (NM-MRI) is applied as a proxy measurement of dopaminergic functioning of the substantia nigra pars compacta (SN). To increase its clinical applicability, a fast and easily applicable NM-MRI sequence is needed. This study therefore compared accelerated NM-MRI sequences using standard available MRI options with a validated 2D gradient recalled echo NM-MRI sequence with off-resonance magnetization transfer (MT) pulse (2D-MToffRes). METHODS: We used different combinations of compressed sense (CS) acceleration, repetition times (TR), and MT pulse to accelerate the validated 2D-MToffRes. In addition, we compared a recently introduced 3D sequence with the 2D-MToffRes. RESULTS: Our results show that the 2D sequences perform best with good to excellent reliability. Only excellent intraclass correlation coefficients were found for the CS factor 2 sequences. CONCLUSION: We conclude that there are several reliable approaches to accelerate NM-MRI, in particular by using CS.