IAM Study Publications

IAM Study logo

Below is a list of IAM study-related papers. All papers were written using IAM data and/or laid the groundwork for IAM data analysis. Full texts of all these papers are available using the links embedded into each paper title.

Published Manuscripts

Annals of Neurology June 2022 Cover

Greater Diffusion Restriction in White Matter in Preclinical Alzheimer's Disease.
Alzheimer's disease (AD) involves many co-occurring changes in the brain. Beta-amyloid builds up and, likely at the same time, white matter degeneration also occurs. This study examined white matter degeneration in the earliest stages of AD. It was shown that other factors may be influencing white matter degeneration in AD rather than just beta-amyloid buildup.

Modeling white matter tract integrity in aging with diffusional kurtosis imaging.

Certain physical changes occur in the brain as we age. This study attempted to see if a certain set of measures called White Matter Tract Integrity could be used to track these changes. According to the results, the measures examined were useful for seeing age-related changes in the brain.

Diffusion MRI detects early brain microstructure abnormalities in 2-month-old 3×Tg-AD mice.
This study focused on a breed of mice that develop characteristics of Alzheimer’s disease (AD) similar to those in humans. This team found that certain diffusion MRI measures were able to detect very early AD-related brain changes in certain brain regions in AD-prone mice.

Diffusion MRI detects basal forebrain cholinergic abnormalities in the 3xTg-AD mouse model of Alzheimer’s disease.
Like the above study, this study also looked at diffusion MRI measures in Alzheimer’s disease (AD)-prone mice. This team examined a wider range of measures and brain regions; the results showed that these measures were useful for monitoring the progress of AD in mice.

Comparison of conventional and actuarial neuropsychological criteria for mild cognitive impairment in a clinical setting.
Cognitive testing is crucial to evidence-based practice in neuropsychology. This study centered on a new type of cognitive testing called ANP. This team found that ANP is more specific and yielded fewer false positives than the current conventional type of cognitive testing (CNP).

Characterizing intra-axonal water diffusion with direction-averaged triple diffusion encoding MRI.
Triple diffusion encoding (TDE) is a method of using diffusion MRI to examine brain cells in finer detail. Using TDE, this team was able to look at water movement both inside and outside of the axon (the part of a nerve cell that carries electrical impulses from one end of the cell to the other). The results showed that the method in question gave greater information about the microstructure of the brain than previous methods.

A Bayesian hierarchical change point model with parameter constraints.
A change point in Alzheimer’s disease (AD) describes the point at which cognitive decline accelerates. A new model for characterizing the onset of AD based on change points was discussed in this study. The results showed that this new model was able to predict AD progression and the personalized risk of dementia from AD.

Modeling white matter microstructure with fiber ball imaging.
Similar to paper #5 above, this study also looked at a method of using diffusion MRI data to examine brain microstructures more closely. The method in question is called fiber ball imaging (FBI). The result of this study showed that this set of new FBI measures can be applied to future data.

Measuring intra-axonal T2 in white matter with direction-averaged diffusion MRI.
Relaxation time is a parameter of diffusion MRI that can be examined to look at brain microstructure. Like the paper above, this study focused on improving diffusion MRI techniques to look at finer details in brain microstructure, this time relating to relaxation time. The results showed a way use relaxation time to look at water movement specifically inside of axons.

Comparison of cumulant expansion and q-space imaging estimates for diffusional kurtosis in brain.
Diffusional kurtosis, a measure of water diffusion in the brain, can be calculated with a process called cumulant expansion (CE) or q-space (QS) imaging. Both methods of were found to be strongly correlated and contained agreeable information on brain microstructure.

Optimization of data acquisition and analysis for fiber ball imaging.
Fiber ball imaging (FBI) is a diffusion MRI technique that uses a specific mathematical function called a Funk transform to look at connections in the brain using fiber orientation density function (fODF). Examining connections in the brain this way requires that diffusion MRI parameters are optimized for best results. This study reports that FBI predictions are valid within certain MRI parameters.

Optimized rectification of fiber orientation density function.
Similar to the paper above, this study looks at fiber orientation density functions (fODFs). These measures are sensitive to signal noise, imaging artifacts, and other signal deteriorating factors. These types of artifacts can skew the analysis of fODFs. This paper proposes a method for correcting for the above issues.

High fidelity fiber orientation density functions from fiber ball imaging.
Fiber orientation density functions (fODFs) contain information about white matter axon arrangements. Typically, fODFs are used with other types of analysis such as tractography, not analyzed by themselves. However, high fidelity fODFs, which can be used to study the effects of diseases on the structure of axons, can be obtained using certain diffusion MRI parameters.

Diffusion MRI detects longitudinal white matter changes in the 3xTg-AD mouse model of Alzheimer’s disease.
Similar to papers #2 and #3, this study focused on Alzheimer’s disease (AD) prone mice. Results show that diffusion MRI can show changes in white matter in both normal aging brains and brains with AD.

Triple diffusion encoding MRI predicts intra-axonal and extra-axonal diffusion tensors in white matter.
Biological interpretations of diffusion MRI metrics can be challenging because it is unclear which type of brain tissue they affect. We can get past this by using models that look at specific tissue types and their diffusion characteristics. A diffusion MRI technique called triple diffusion encoding (TDE) uses information that is specific to different tissue compartments.

Psychometric Properties of the NIH Toolbox Cognition Battery in Healthy Older Adults: Reliability, Validity, and Agreement with Standard Neuropsychological Tests.
A type of cognitive testing called the NIHTB-CB is becoming more commonly used in neuropsychology. This study compared NIHTB-CB to older types of cognitive testing. The results showed that the NIHTB-CB test was both valid and reliable in older adults.

Brain Reserve in a Case of Cognitive Resilience to Severe Leukoaraiosis.
Brain reserve is the idea that brain integrity influences how a brain responds to disease or injury. This study profiles a single case of a type of white matter disease called Leukoaraiosis. Results showed the usefulness of a diffusion MRI technique called fiber ball imaging (FBI) to identify brain reserve in a case of severe white matter disease.Accepted Manuscripts

Fiber Ball white matter modeling reveals microstructural alterations in healthy brain aging.
Similar to and building upon many of the above papers, this study looked at both improved diffusion MRI data acquisition and analysis – specifically a technique called fiber ball white matter modeling (FBWM). Results showed that FBWM gave more detailed information about healthy brain aging than previous diffusion MRI techniques..

Interim Research Products

A Pythonic Implementation of the DESIGNER Pipeline for Diffusion Tensor and Diffusional Kurtosis Imaging [Preprint].
In diffusion MRI (dMRI) analysis, preprocessing describes cleaning up MRI images by removing image artifacts and other errors. Tensor calculation is the process of mathematically extrapolating different types of measures from a set of dMRI data. This paper details a new type of software called PyDesigner which performs preprocessing and tensor calculation. This software is integral to all the analysis done using IAM Study data.· Dhiman S, Teves JB, Thorn KE, McKinnon ET, Moss HG, Adisetiyo V, Ades-Aron B, Veraart J, Chen J, Fieremans E, Benitez A, Helpern JA, Jensen JH. PyDesigner: A Pythonic Implementation of the DESIGNER Pipeline for Diffusion Tensor and Diffusional Kurtosis Imaging [Preprint]. Neuroscience; 2021 Oct. Available from: http://biorxiv.org/lookup/doi/10.1101/2021.10.20.465189