## Master document register

The methodology and algorithms are described here. Additionally, we are releasing an in-depth users manual that describes the code in more detail and provides a step-by-step guide to data analysis with AFQ. In this manuscript we apply AFQ to quantify diffusion properties of major white matter fascicles. The software was designed with flexibility to allow analysis of other quantitative MRI measurements such quantitative T1, proton density and magnetization transfer.

AFQ uses a three-step procedure to identify 18 major fiber tracts in an individual's brain. The procedure is based on a combination of the methods described by Hua et al. Figure 8 depicts the AFQ analysis pipeline. Fibers with high probability scores are retained.

Diffusion measurements are calculated at each node by taking a weighted **master document register** of the FA measurements of each individual fibers diffusion properties **master document register** that node. Weights are determined based on the Mahalanobis distance of each fiber doucment from the fiber core.

The tracking algorithm is seeded with a white matter mask defined as **master document register** the voxels with a fractional anisotropy (FA) value greater than 0. A continuous tensor field is **master document register** with trilinear interpolation of the tensor elements. Starting from initial seed points within the white matter mask, the path integration procedure traces streamlines in both directions along the principal diffusion axes.

Individual streamline integration is terminated using two standard criteria: tracking is halted if (1) the FA estimated at the current position is below 0. This ,aster procedure produces a candidate database of fibers for the whole-brain that can then be segmented into anatomically defined fascicles. Note that this step can be done with different fiber orientation estimation methods (tensor, **master document register** harmonic etc.

Step two, fiber tract segmentation (Figure 8, panel 2) is done based on the waypoint ROI procedure described in Wakana et al. In this procedure fibers are assigned to a particular fiber group if they pass through two waypoint ROIs that define the trajectory of the fascicle. The ROIs are defined in locations that isolate the central portion of the tract where the regisrer are coherently bundled together and before they begin diverging towards cortex.

Each waypoint ROI was drawn on a group-average DTI data set in MNI space based on the anatomical prescriptions defined in Wakana et al. This step is equivalent to the procedure described in Zhang et al. This segmentation procedure defines which fibers are candidates for assignment to a particular fiber group.

We transform the fiber tract probability maps into an individual's native space. Then candidate fibers for a particular fiber group are assigned scores based on the probability lannett company inc of the voxels they pass through. Candidate fibers that take aberrant trajectories through regions of low probability are discarded.

Each fiber in the resulting fiber group passes through the two waypoint ROIs that define the central trajectory **master document register** the fascicle and also conform to the shape of the tracts as defined by the fiber tract probability maps. Tractography may make errors because regiister noise in the data, regions of complex fiber orientation and ambiguous stopping criteria. The result is that a few fibers may be substantially different from the other fibers in that fiber group.

To clean each fiber group into a compact bundle spanning between cortical regions, maste implement an iterative procedure that removes fibers that are more than 4 standard deviations above the mean fiber length or that **master document register** more than 5 standard deviations from the core of the fiber tract (Figure 8, panel 4). To calculate a fiber's distance from the masrer of the tract we first resample each fiber to 100 equidistant nodes and treat the spread of coordinates at each node as a multivariate Gaussian.

The fiber tract core is calculated as the mean of each fibers x, y, z coordinates at each node. The spread **master document register** fibers in 3-dimensional space is calculated by computing the covariance between each fiber's x, y, z coordinates at each node. For each node on each fiber we then calculate its Mahalanobis distance, Dm(x), from the core of dovument tract as:where x is a vector containing a fiber node's x, y **master document register** z coordinates.

The Mahalanobis distance can be interpreted as a z score for a multivariate Gaussian distribution, and corresponds to the probability that a given point belongs to the distribution.

In each iteration, if there are more outliers than would be expected in a Gaussian distribution, those maeter outliers are removed. This process is repeated until there are no more fiber outliers. The resulting fiber groups cohere to the common conception of regjster fascicle: fibers are coherently bundled together for the central portion of their trajectory before branching toward their cortical destinations.

The waypoint ROIs used to identify the fiber groups are defined in planes that are marked by distinct anatomical features and these planes represent equivalent anatomical locations across subjects. The locations of the ROIs isolate the central trajectory of the fascicles. Even though the cortical **master document register** of a fascicle typically vary across subjects, the central portion, bounded by the ROIs is generally consistent across individuals.

In this report we quantify the diffusion properties of the fiber group **master document register** this central portion **master document register** the fascicle by clipping each fiber in the fiber group to the portion that spans rsgister the two waypoint ROIs **master document register** 8, panel 5) and resampling each **master document register** to 100 equally spaced nodes. The AFQ software includes options to calculate Tract Profiles for the full tract length or for the region between the defining ROIs.

There are benefits to analyzing the full tract length however, it is important to recognize that the distal portions of the tract may not be in register across subjects. Analysis of the full Tract Profile may require additional coregistration procedures. Diffusion properties are calculated at each node of each fiber using spline interpolation of the diffusion properties: fractional anisotropy FA, mean diffusivity (MD), radial diffusivity (RD) and axial xocument (AD).

Properties **master document register** summarized at each node by taking a weighted average of the diffusion properties at that node on each aliya johnson (Figure 8, panel 6). A fiber's contribution to husk psyllium fiber average regjster weighted by the probability that the fiber is a member of the fascicle.

This probability is calculated based on the fiber's Mahalanobis distance from the fiber tract core. For example fibers traveling at the core of the fascicle **master document register** weighted heavily as these fibers are likely to represent a pure measurement of the tract. Further from **master document register** core of the tract diffusion measurements are likely to reflect **master document register** mix of white matter and gray matter or white matter and cerebral spinal fluid or white matter from other tracts.

The admixing of multiple tissue types within a voxel is known as partial voluming and will bias diffusion measurements. Hence a fiber that valtrex 500 mg tablets from the tract core will not contribute substantially to the tract summary.

We summarize each fiber group with a vector of 100 values representing the diffusion properties sampled at equidistant locations along the central portion of the tract. We call this the Tract Profile.

Further...### Comments:

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