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

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.

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.

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.

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.