In vivo 7 Tesla imaging of the dentate granule cell layer in schizophrenia.

Purpose: The hippocampus is central to the pathophysiology of schizophrenia. Histology shows abnormalities in the dentate granule cell layer (DGCL), but its small size (~100 μm thickness) has precluded in vivo human studies. We used ultra high field magnetic resonance imaging (MRI) to compare DGCL morphology of schizophrenic patients to matched controls.

Method: Bilateral hippocampi of 16 schizophrenia patients (10 male) 40.7 ± 10.6 years old (mean ± standard deviation) were imaged at 7 Tesla MRI with heavily T₂*-weighted gradient-echo sequence at 232 μm in-plane resolution (0.08 μL image voxels). Fifteen matched controls (8 male, 35.6 ± 9.4 years old) and one ex vivo post mortem hippocampus (that also underwent histopathology) were scanned with same protocol. Three blinded neuroradiologists rated each DGCL on a qualitative scale of 1 to 6 (from "not discernible" to "easily visible, appearing dark gray or black") and mean left and right DGCL scores were compared using a non-parametric Mann-Whitney test.

Results: MRI identification of the DGCL was validated with histopathology. Mean right and left DGCL ratings in patients (3.2 ± 1.0 and 3.5 ± 1.2) were not statistically different from those of controls (3.9 ± 1.1 and 3.8 ± 0.8), but patients had a trend for lower right DGCL score (p = 0.07), which was significantly associated with patient diagnosis (p = 0.05). The optimal 48% sensitivity and 80% specificity for schizophrenia were achieved with a DGCL rating of ≤2.

Conclusion: Decreased contrast in the right DGCL in schizophrenia was predictive of schizophrenia diagnosis. Better utility of this metric as a schizophrenia biomarker may be achieved in future studies of patients with homogeneous disease subtypes and progression rates.