A majority rule approach for region-of-interest-guided streamline fiber tractography.

Hand-drawn gray matter regions of interest (ROI) are often used to guide the estimation of white matter tractography, obtained from diffusion-weighted magnetic resonance imaging (DWI), in healthy and in patient populations. However, such ROIs are vulnerable to rater bias of the individual segmenting the ROIs, scan variability, and individual differences in neuroanatomy. In this report, a "majority rule" approach is introduced for ROI segmentation used to guide streamline tractography in white matter structures. DWI of one healthy participant was acquired in ten separate sessions using a 3 T scanner over the course of a month. Four raters identified ROIs within the left hemisphere [Cerebral Peduncle (CPED); Internal Capsule (IC); Hand Portion of the Motor Cortex, or Hand Bump, (HB)] using a group-established standard operating procedure for ROI definition to guide the estimation of streamline tracts within the corticospinal tract (CST). Each rater traced the ROIs twice for each scan session. The overlap of each rater's two ROIs was used to define a representative ROI for each rater. These ROIs were combined to create a "majority rules" ROI, in which the rule requires that each voxel is selected by at least three of four raters. Reproducibility for ROIs and CST segmentations were analyzed with the Dice Similarity Coefficient (DSC). Intra-rater reliability for each ROI was high (DSCs ≥ 0.83). Inter-rater reliability was moderate to adequate (DSC range 0.54-0.75; lowest for IC). Using intersected majority rules ROIs, the resulting CST showed improved overlap (DSC = 0.82) in the estimated streamline tracks for the ten sessions. Despite high intra-rater reliability, there was lower inter-rater reliability consistent with the expectation of rater bias. Employing the majority rules method improved reliability in the overlap of the CST.

Immune response induced by three Mycobacterium bovis BCG substrains with diverse regions of deletion in a C57BL/6 mouse model.

This study was performed to examine the adaptive immune response generated by three Mycobacterium bovis bacillus Calmette-Guérin (BCG) substrains to determine if the number of genomic regions of deletion played a significant role in determining the magnitude of the immune response or affected their ability to reduce the bacterial burden following low-dose aerosol challenge with a virulent M. tuberculosis strain. BCG Connaught, Pasteur, and Sweden were chosen as representative substrains, as they possessed many, intermediate, and few regions of deletion, respectively, as a result of changes in the genome in various regions. Mice were vaccinated subcutaneously and were then examined at 14, 21, and 42 days postvaccination. BCG was observed in the spleen, lung, and lymph nodes. BCG Connaught induced a greater pulmonary T-cell response than the other two substrains at day 14 postvaccination, although by 42 days postvaccination activated T-cell levels dropped to the levels observed in control mice for all three substrains. Among the three substrains, BCG Connaught induced significantly greater levels of interleukin-12 in bone marrow-derived macrophage cultures. Mice challenged at days 14, 21, and 42 postvaccination displayed an equal capacity to reduce the bacterial burden in the lungs and spleen. The data provide evidence that although the BCG substrains generated qualitatively and quantitatively different immune responses, they induced similar reductions in the bacterial burden against challenge with a virulent M. tuberculosis strain in the mouse model of tuberculosis. The data raise questions about the assessment of vaccine immune responses and the relationship to a vaccine's ability to reduce the bacterial burden.