Multitask Learning Based Three-Dimensional Striatal Segmentation of MRI: fMRI and PET Objective Assessments.

BACKGROUND: Recent studies have established a clear topographical and functional organization of projections to and from complex subdivisions of the striatum. Manual segmentation of these functional subdivisions is labor-intensive and time-consuming, and automated methods are not as reliable as manual segmentation. PURPOSE: To utilize multitask learning (MTL) as a method to segment subregions of the striatum consisting of pre-commissural putamen (prePU), pre-commissural caudate (preCA), post-commissural putamen (postPU), post-commissural caudate (postCA), and ventral striatum (VST). STUDY TYPE: Retrospective. POPULATION: Eighty-seven total data sets from patients with schizophrenia and matched controls. FIELD STRENGTH/SEQUENCE: 1.5 T and 3.0 T, T1 -weighted (SPGR SENSE, 3D BRAVO). ASSESSMENT: MTL-generated segmentations were compared to the Imperial College London Clinical Imaging Center (CIC) atlas. Dice similarity coefficient (DSC) was used to compare the automated methods to manual segmentations. Positron emission tomography (PET) imaging: 60 minutes of emission data were acquired using [11 C]raclopride. Data were reconstructed by filtered back projection (FBP) with computed tomography (CT) used for attenuation correction. Binding potential values, BPND , and region of interest (ROI) time series and whole-brain connectivity using functional magnetic resonance imaging (fMRI) images were compared between manual and both automated segmentations. STATISTICAL TESTS: Pearson correlation and paired t-test. RESULTS: MTL-generated segmentations showed excellent spatial agreement with manual (DSC ≥0.72 across all striatal subregions). BPND values from MTL-generated segmentations were shown to correlate well with manual segmentations with R2 ≥ 0.91 in all caudate and putamen subregions, and R2  = 0.69 in VST. Mean Pearson correlation coefficients of the fMRI data between MTL-generated and manual segmentations were also high in time series (≥0.86) and whole-brain connectivity (≥0.89) across all subregions. DATA CONCLUSION: Across both PET and fMRI task-based assessments, results from MTL-generated segmentations more closely corresponded to results from manually drawn ROIs than CIC-generated segmentations did. Therefore, the proposed MTL approach is a fast and reliable method for three-dimensional striatal subregion segmentation with results comparable to manually segmented ROIs. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 1.

Imaging the Vesicular Acetylcholine Transporter in Schizophrenia: A Positron Emission Tomography Study Using [18F]-VAT.

BACKGROUND: Despite longstanding interest in the central cholinergic system in schizophrenia (SCZ), cholinergic imaging studies with patients have been limited to receptors. Here, we conducted a proof-of-concept positron emission tomography study using [18F]-VAT, a new radiotracer that targets the vesicular acetylcholine transporter as a proxy measure of acetylcholine transmission capacity, in patients with SCZ and explored relationships of vesicular acetylcholine transporter with clinical symptoms and cognition. METHODS: A total of 18 adult patients with SCZ or schizoaffective disorder (the SCZ group) and 14 healthy control participants underwent a positron emission tomography scan with [18F]-VAT. Distribution volume (VT) for [18F]-VAT was derived for each region of interest, and group differences in VT were assessed with 2-sample t tests. Functional significance was explored through correlations between VT and scores on the Positive and Negative Syndrome Scale and a computerized neurocognitive battery (PennCNB). RESULTS: No group differences in [18F]-VAT VT were observed. However, within the SCZ group, psychosis symptom severity was positively associated with VT in multiple regions of interest, with the strongest effects in the hippocampus, thalamus, midbrain, cerebellum, and cortex. In addition, in the SCZ group, working memory performance was negatively associated with VT in the substantia innominata and several cortical regions of interest including the dorsolateral prefrontal cortex. CONCLUSIONS: In this initial study, the severity of 2 important features of SCZ-psychosis and working memory deficit-was strongly associated with [18F]-VAT VT in several cortical and subcortical regions. These correlations provide preliminary evidence of cholinergic activity involvement in SCZ and, if replicated in larger samples, could lead to a more complete mechanistic understanding of psychosis and cognitive deficits in SCZ and the development of therapeutic targets.