Differential tractography

Introduction

Figure: conventional tractography compared with differential tractography. Conventional tractography tracks "existence", whereas differential tractography tracks "differences".






















Tracking differences instead of tracking existence
Differential tractography is a new type of tractography that compares repeat scans of the same individuals to capture neuronal injury reflected by a decrease of anisotropy. It is realized by adding a criterion to track along trajectories only if a decrease of anisotropy is found between repeat scans. Integrating this “tracking-the-difference” paradigm into the fiber tracking process results in a new tractography modality called differential tractography. It will track the exact portion of pathways exhibiting substantial differences in anisotropy. The additional criterion ignores unaffected regions and enhances meaningful findings related to neuronal injury. 

Conventional fiber tracking, in comparison, is based on a “tracking-the-existence” paradigm. It only considers anisotropy from one MRI scan and thus will include all existing pathways regardless of whether they have an injury. 

The following are steps to reproduce the result published in the differential tractography paper. 

*This feature is only available after 8/23/2019 version. Please update DSI Studio before you start.

Step 1: Experiment design


You will need to have "longitudinal data" (one baseline scan and one follow-up scan) of the same subject to run differential tractography. The scanning interval has to be more than one month. The optimal is more than 3 months because structural change needs time to build up. For estimating FDR, the optimal experiment setting include additional "sham" scan, which is an additional baseline scan one or two days after the baseline scan. This additional baseline scan will be used in estimating the false discovery rate. If there is no sham scan, then an "alternative sham" approach can be used.


Step 2: Diffusion MRI acquisition


Differential tractography can be applied to any diffusion data set, including DTI data, multi-shell data, and DSI data. But, we found that higher b-value signals will be more specific for early-stage neuronal changes, whereas low b-value signal may include a lot of physiological fluctuations. If your data are acquired at low b-value (e.g., < 3000), then you can expect to have a higher false discovery rate (FDR). In the original study, we used 256-direction grid sampling with b-max=7000 to get excellent FDR values lower than 0.05. Using DTI data may increase FDR to 0.2

The recommend b-table and acquisition setting can be found here. The setting in the link has b-max=4000. For differential tractography, you may need to increase both the voxel size to 2.5 mm cubic and b-value to 7000.

Step 3: Quality Control


Quality control is critical for differential tractography because the signal dropout will also be captured by differential tractography. After you collected the data, first convert DICOM/NIFTI to SRC file. The webpage also has a quality check section. Make sure that all your SRC data are created and pass the quality control.

Step 4: Compare differences 


Open the baseline SRC file in [Step T2 Reconstruction], make sure that the mask at Step T2(a) is okay, and in Step T2b(1) select [GQI] and click the [Compare SRC...] button in T2b(2) to assign the SRC file of the follow-up scan. The other setting follows the figure:


Then click [Run reconstruction]. 

DSI Studio will generate a fib.gz file with a file name like: baseline.src.gz.odf8.f5.df.follow_up.R96.rdi.gqi.1.25.fib.gz

Here R96 means the R squared value is 0.96, which is very good. If the value is lower than R80, then you will need to check the data quality or email Frank to see if there is any problem in the data registration. 

Step 5: Tracking differences as the differential tractography


a. Open the generated FIB file in [Step T3 Fiber Tracking] 
b. In the right upper corner [Step T3c Option] window, expand the [Tracking Parameters]
c. At [Tracking Parameters][Terminate If], assign 50,000 "seed"
d. At [Tracking Parameters][Differential Tracking Index], assign "dec_qa" to track decrease of "qa". You may use "dec_fa" to track decrease of "fa". The increase anisotropy can be tracked by "inc_qa" or "inc_fa". 
e. At [Tracking Parameters][Differential Tracking Threshold], assign 0.2 to track anisotropy decrease larger than 20%. The recommended value for [Differential Tracking Threshold] is 0.2~0.5, depending on the condition. 20% is good for early demyelination. 50%is good for axonal loss.
f. (Optional) The sensitivity and specificity can be adjusted by [Tracking Parameters][Min Length (mm)]. Lower value like 20 mm is more sensitive, whereas 40 mm is more specific. See figure below for an example.
g. (Optional) You can add ROI from an atlas to limit the findings to a specific region or use automatic fiber tracking to limit one specific pathway (see Diffusion MRI Fiber Tracking in DSI Studio)




Step 6: Estimating FDR 

A sham setting is needed to estimate the FDR, and the procedure is shown as follows:


The paradigm is to replace the follow-up scan by a sham scan and repeat the analysis. The FDR is calculated as (number of tracks in the sham scan) by (number tracks in the follow-up scans). If there is no sham scan, you can change [Differential Tracking Index] to "inc_qa" (or "inc_fa" for DTI data) in the previous step as the "alternative sham".

If the FDR value is lower than 0.2, then it is worth reporting. FDR < 0.05 is confirmative of the findings.

FAQ


























1. Can I apply differential tractography to DTI dataset?
Ans: Yes, the exact procedure can be applied to DTI data, but the FDR will not be as good as the recommended acquisition (e.g., Diffusion MRI acqusition)

2. Can I apply differential tractography to study increased connectivity? 
Ans: Yes, but you may need a control subject or a sham scan to estimate FDR. You cannot use "alternative sham" approach (see the original paper for details).

3. Can I combine differential tractography with ROI?
Ans: Yes, differential tractography can be combined with an ROI to limit the findings to a region.


Reference

Yeh FC, Zaydan IM, Suski VR, Lacomis D, Richardson RM, Maroon J, Barrios-Martinez J. Differential Tractography as a Track-Based Biomarker for Neuronal Injury. Neuroimage. 2019.

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