# Advancing and calibrating anisotropic diffusion MR imaging brain connectome with Taxon brain network diffusion phantoms

> **NIH NIH R44** · PSYCHOLOGY SOFTWARE TOOLS, INC. · 2020 · $621,536

## Abstract

There is a critical gap in the reliability of anisotropic diffusion magnetic resonance imaging (AdMRI). This gap can be
filled by using a ground truth measurement capability that allows for the necessary parametric control of water filled
geometries of tubes at the micron scale that can produce paths representative of the millions of axons across centimeters in
brain tract trajectories. Diffusion Tensor Imaging (DTI) publications report clinically significant systematic error that
confounds accurate quantitative assessments across instruments and time. Reference phantoms that provide exact error
metrics will advance MRI biophysics science and clinical quantitative accuracy. Correction algorithms using reference data
can reduce systematic measurement error, enabling accurate reproducible measurement and provide cross scanner norms
for AdMRI pathology. This project will deliver the first viable AdMRI phantom “ground truth” using ‘Taxons™’ (textile
axon shaped nanotubes), invented by this team, and apply advanced bi-component polymer nanoscale production methods
to create structures matched to human tissue histology. In doing this we will deliver axon scale taxons at 800 nanometer
diameter, with a packing density of one million taxons per mm2, matched to actual human corpus callosum axon
measurements. In Phase I we proposed and delivered taxons with 12 micron inner diameter tubes with a packing density of
1241 per mm2 that could be filled with water and produce FA measurement in the human tissue range. We actually “over-
delivered”, exceeding a packing density of 1,000,000 per mm2 covering the human axonal tissue range. We can now
precisely parametrically control the diameters, packing density, restricted/hindered, and isotropic water fractions to test and
improve leading compartmental models of diffusion. We created a fasciculus routing machine that can, at viable cost, create
human scale fasciculus routes matched to human tissue, such as the optic system eye to LGN, of 20 million routed taxons.
The 1 to 1 scale taxonal network phantoms quantify dMRI measurement accuracy for each taxon path with 100 micron path
precision along the trajectory. We scanned the phase I phantoms at ten sites. We established in empirical studies that there
is substantial systematic, cross instrument and measurement error (e.g., 5x the TBI effect size), that the error is stable, and
can be corrected for (removed 94% of systematic error). Phase II of this project will: 1) provide the first AdMRI phantom
for ground truth measurement to quantify dMRI biophysics, spatial homogeneity, and routing precision; 2) provide fully
automated quantification of accuracy and repeatability of measurement; 3) assess AdMRI precision of 20+ sites, quantifying
measurement error at 1.5, 3, 7, 9.4 and 14T field strength; and4) develop a set of routing phantoms (Eye>LGN> V1, spinal
cord and cortical tracts). These phantoms and/or subcomponents will be measured with non-MRI methods (confocal &
el...

## Key facts

- **NIH application ID:** 9893037
- **Project number:** 5R44NS103729-03
- **Recipient organization:** PSYCHOLOGY SOFTWARE TOOLS, INC.
- **Principal Investigator:** Anthony P Zuccolotto
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $621,536
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893037

## Citation

> US National Institutes of Health, RePORTER application 9893037, Advancing and calibrating anisotropic diffusion MR imaging brain connectome with Taxon brain network diffusion phantoms (5R44NS103729-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9893037. Licensed CC0.

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