Reproducibility of myelin content-based human habenula segmentation at 3 Tesla.

In vivo morphological study of the human habenula, a pair of small epithalamic nuclei adjacent to the dorsomedial thalamus, has recently gained significant interest for its role in reward and aversion processing. However, segmenting the habenula from in vivo magnetic resonance imaging (MRI) is challenging due to the habenula's small size and low anatomical contrast. Although manual and semi-automated habenula segmentation methods have been reported, the test-retest reproducibility of the segmented habenula volume and the consistency of the boundaries of habenula segmentation have not been investigated. In this study, we evaluated the intra- and inter-site reproducibility of in vivo human habenula segmentation from 3T MRI (0.7-0.8 mm isotropic resolution) using our previously proposed semi-automated myelin contrast-based method and its fully-automated version, as well as a previously published manual geometry-based method. The habenula segmentation using our semi-automated method showed consistent boundary definition (high Dice coefficient, low mean distance, and moderate Hausdorff distance) and reproducible volume measurement (low coefficient of variation). Furthermore, the habenula boundary in our semi-automated segmentation from 3T MRI agreed well with that in the manual segmentation from 7T MRI (0.5 mm isotropic resolution) of the same subjects. Overall, our proposed semi-automated habenula segmentation showed reliable and reproducible habenula localization, while its fully-automated version offers an efficient way for large sample analysis.

Visible-light-mediated Diels-Alder reactions under single-chain polymer confinement: investigating the role of the crosslinking moiety on catalyst activity.

Macromolecular scaffolds are rapidly emerging in catalysis owing to the ability to control catalyst placement at precise locations. This spatial proximity allows for enhanced catalyst activity that may not be observed using small molecules. Herein, we describe a triphenylpyrylium (TPT)-based visible-light active single-chain polymer nanoparticle (SCNP) that facilitates the radical cation [4 + 2]-cycloaddition. We find that the catalytic activity is highly dependent on the styrylarene comonomer used, wherein it can act as a redox mediator under confinement, increasing the catalytic turnover (TON) by up to 30 times in comparison to free TPT in solution. Mechanistic studies indicate that TPT excited states are quenched by the acene, with the resultant radical cation formed from naphthalene-based SCNPs able to proceed in oxidizing the dienophile in the elementary step of the reaction, while leading to near quantitative yields of the cycloadduct. The TPT-SCNP demonstrates enhanced photocatalyst efficiency compared to molecular TPT, and is able to be recycled and reused in three iterations of the reaction prior to decreased performance from photobleaching. Our results overall suggest that the confined nature of the SCNP and spatial proximity of acene-based pendants enforces their participation as cocatalytic redox mediators that impart enhanced photoredox catalysis under confinement.

Imaging Habenula Volume in Schizophrenia and Bipolar Disorder.

The habenula (Hb), a bilateral nucleus located next to the dorsomedial thalamus, is of particular relevance to psychiatric disorders based on preclinical evidence linking the Hb to depressive and amotivational states. However, studies in clinical samples are scant because segmentation of the Hb in neuroimaging data is challenging due to its small size and low contrast from the surrounding tissues. Negative affective states dominate the clinical course of schizophrenia and bipolar disorder and represent a major cause of disability. Diagnosis-related alterations in the volume of Hb in these disorders have therefore been hypothesized but remain largely untested. To probe this question, we used a recently developed objective and reliable semi-automated Hb segmentation method based on myelin-sensitive magnetic resonance imaging (MRI) data. We ascertained case-control differences in Hb volume from high resolution structural MRI data obtained from patients with schizophrenia (n = 95), bipolar disorder (n = 44) and demographically matched healthy individuals (n = 52). Following strict quality control of the MRI data, the final sample comprised 68 patients with schizophrenia, 32 with bipolar disorder and 40 healthy individuals. Regardless of diagnosis, age, sex, and IQ were not correlated with Hb volume. This was also the case for age of illness onset and medication (i.e., antipsychotic dose and lithium-treatment status). Case-control differences in Hb volume did not reach statistical significance; their effect size (Cohen's d) was negligible on the left (schizophrenia: 0.14; bipolar disorder: -0.03) and small on the right (schizophrenia: 0.34; bipolar disorder: 0.26). Nevertheless, variability in the volume of the right Hb was associated with suicidality in the entire patient sample (ρ = 0.29, p = 0.004) as well as in each patient group (bipolar disorder: ρ = 0.34, p = 0.04; schizophrenia: ρ = 0.25, p = 0.04). These findings warrant replication in larger samples and longitudinal designs and encourage more comprehensive characterization of Hb connectivity and function in clinical populations.