Engineering Enhanced Pore Sizes Using FhuA Δ1-160 from E. coli Outer Membrane as Template

<p>Mean AD for ten major white matter tracts in healthy term controls (blue bars) and ELBW infants (red bars).</p

Reliability and Repeatability of Quantitative Tractography Methods for Mapping Structural White Matter Connectivity in Preterm and Term Infants at Term-Equivalent Age

<div><p>Premature infants exhibit widespread insults and delays in white matter maturation that can be sensitively detected early using diffusion tensor imaging. Diffusion tensor tractography facilitates in vivo visualization of white matter tracts and has the potential to be more sensitive than simpler two-dimensional DTI-based measures. However, the reliability and reproducibility of performing tractography for major white matter tracts in preterm infants is not known. The main objective of our study was to develop highly reliable and repeatable methods for ten white matter tracts in extremely low birth weight infants (birth weight ≤1000 g) at term-equivalent age. To demonstrate clinical utility, we also compared fiber microstructural and macrostructural parameters between preterm and healthy term controls. Twenty-nine ELBW infants and a control group of 15 healthy term newborns were studied. A team of researchers experienced in neuroanatomy/neuroimaging established the manual segmentation protocol based on a priori anatomical knowledge and an extensive training period to identify sources of variability. Intra- and inter-rater reliability and repeatability was tested using intra-class correlation coefficient, within-subject standard deviation (SD), repeatability, and Dice similarity index. Our results support our primary goal of developing highly reliable and reproducible comprehensive methods for manual segmentation of 10 white matter tracts in ELBW infants. The within-subject SD was within 1–2% and repeatability within 3–7% of the mean values for all 10 tracts. The intra-rater Dice index was excellent with a range of 0.97 to 0.99, and as expected, the inter-rater Dice index was lower (range: 0.80 to 0.91), but still within a very good reliability range. ELBW infants exhibited fewer fiber numbers and/or abnormal microstructure in a majority of the ten quantified tracts, consistent with injury/delayed development. This protocol could serve as a valuable tool for prompt evaluation of the impact of neuroprotective therapies and as a prognostic biomarker for neurodevelopmental impairments.</p></div

Mean number of voxels for ten major white matter tracts in healthy term controls (blue bars) and ELBW infants (red bars).

<p>Mean number of voxels for ten major white matter tracts in healthy term controls (blue bars) and ELBW infants (red bars).</p

<i>Intra</i>-rater and <i>inter</i>-rater Dice similarity index for total number of voxels of ten white matter tracts in preterm and term infants.

<p><i>Intra</i>-rater and <i>inter</i>-rater Dice similarity index for total number of voxels of ten white matter tracts in preterm and term infants.</p

Location of ROIs on DTI color maps for the uncinate (UNC) tract in a preterm infant.

<p>(A) First polygonal shaped ROI drawn for segmenting the UCN in coronal view; (B) Fiber bundle after the first ROI was drawn in sagittal view; (C) The second ROI drawn anterior to the first ROI on the same coronal image; (D) Final trajectory of the UNC in sagittal view.</p

Mean total number of fibers with corresponding <i>intra</i>-rater measurement error, repeatability coefficient, and reliability data for ten white matter tracts in preterm and term infants.

<p>Mean total number of fibers with corresponding <i>intra</i>-rater measurement error, repeatability coefficient, and reliability data for ten white matter tracts in preterm and term infants.</p

<i>Inter</i>-rater measurement error, repeatability coefficient, and reliability data for total number of fibers of ten white matter tracts in preterm and term infants.

<p><i>Inter</i>-rater measurement error, repeatability coefficient, and reliability data for total number of fibers of ten white matter tracts in preterm and term infants.</p

Location of ROIs on DTI color maps for the fornix (FX) in a preterm infant.

<p>(A) First polygonal shaped seed point of the first ROI around the FX in axial view; (B) Location of the fornix after the first ROI was drawn in sagittal orientation; (C) Second polygonal shaped ROI in axial view; (D) FX after the second ROI was drawn in sagittal view; (E) Third oval shaped ROI placement in axial view; (F) Final FX trajectory in sagittal view.</p

Location of ROIs on DTI color maps for the inferior fronto-occipital (IFO) tract in a preterm infant.

<p>(A) First polygonal shaped ROI in coronal view; (B) Fiber trajectory after the first ROI was drawn in sagittal view; (C) Final trajectory of the IFO tract in axial view; (D) Polygonal shaped second ROI in coronal view; (E) Final trajectory of the IFO tract and the starting and the ending ROI points of the tract in sagittal view.</p

<i>Inter</i>-rater measurement error, repeatability coefficient, and reliability data for total number of voxels of ten white matter tracts in preterm and term infants.

<p><i>Inter</i>-rater measurement error, repeatability coefficient, and reliability data for total number of voxels of ten white matter tracts in preterm and term infants.</p