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Article: Neuroimaging Advances in Diagnosis and Differentiation of HIV, Comorbidities, and Aging in the cART Era.

Nir, Talia M / Haddad, Elizabeth / Thompson, Paul M / Jahanshad, Neda

Current topics in behavioral neurosciences

2021 Volume 50, Page(s) 105–143

Abstract: In the "cART era" of more widely available and accessible treatment, aging and HIV-related comorbidities, including symptoms of brain dysfunction, remain common among HIV-infected individuals on suppressive treatment. A better understanding of the ... ...

Abstract	In the "cART era" of more widely available and accessible treatment, aging and HIV-related comorbidities, including symptoms of brain dysfunction, remain common among HIV-infected individuals on suppressive treatment. A better understanding of the neurobiological consequences of HIV infection is essential for developing thorough treatment guidelines and for optimizing long-term neuropsychological outcomes and overall brain health. In this chapter, we first summarize magnetic resonance imaging (MRI) methods used in over two decades of neuroHIV research. These methods evaluate brain volumetric differences and circuitry disruptions in adults living with HIV, and help map clinical correlations with brain function and tissue microstructure. We then introduce and discuss aging and associated neurological complications in people living with HIV, and processes by which infection may contribute to the risk for late-onset dementias. We describe how new technologies and large-scale international collaborations are helping to disentangle the effect of genetic and environmental risk factors on brain aging and neurodegenerative diseases. We provide insights into how these advances, which are now at the forefront of Alzheimer's disease research, may advance the field of neuroHIV. We conclude with a summary of how we see the field of neuroHIV research advancing in the decades to come and highlight potential clinical implications.
MeSH term(s)	Adult ; Aging ; Brain/diagnostic imaging ; HIV Infections/complications ; HIV Infections/epidemiology ; Humans ; Neurodegenerative Diseases ; Neuroimaging
Language	English
Publishing date	2021-03-30
Publishing country	Germany
Document type	Journal Article
ISSN	1866-3370
ISSN	1866-3370
DOI	10.1007/7854_2021_221
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Article ; Online: Evaluating Fiber Orientation Dispersion Measures Computed From Single-Shell Diffusion MRI.

Villalon-Reina, Julio E / Nir, Talia M / Nourollahimoghadam, Elnaz / Dhinagar, Nikhil / Jahanshad, Neda / Thompson, Paul M / Henriques, Rafael Neto

Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference

2023 Volume 2023, Page(s) 1–6

Abstract: Fiber orientation dispersion is one of the fundamental features that can be estimated from diffusion magnetic resonance imaging (dMRI) of the brain. Several approaches have been proposed to estimate dispersion from single- and multi-shell dMRI ... ...

Abstract	Fiber orientation dispersion is one of the fundamental features that can be estimated from diffusion magnetic resonance imaging (dMRI) of the brain. Several approaches have been proposed to estimate dispersion from single- and multi-shell dMRI acquisitions. Here, we derive solutions to bring these proposed methods to a standard orientation dispersion index (ODI) with the goal of making them comparable across different dMRI acquisitions. To illustrate the utility of the measures in studying brain aging, we further examined the age-dependent trajectory of the different single- and multi-shell ODI estimates in the white matter across the lifespan.Clinical Relevance- This work computes metrics of brain microstructure that can be adapted for large neuroimaging initiatives that aim to study the brain's development and aging, and to identify deviations that may serve as biomarkers of brain disease.
MeSH term(s)	Diffusion Magnetic Resonance Imaging/methods ; Brain/diagnostic imaging ; Brain/pathology ; White Matter/diagnostic imaging ; Neuroimaging/methods
Language	English
Publishing date	2023-12-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2694-0604
ISSN (online)	2694-0604
DOI	10.1109/EMBC40787.2023.10340067
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Article: Gradient Patterns of Age-Related Diffusivity Changes in Cerebral White Matter.

Boban, Jasmina / Thurnher, Majda M / Boban, Nikola / Law, Meng / Jahanshad, Neda / Nir, Talia M / Lendak, Dajana F / Kozic, Dusko

Frontiers in neurology

2022 Volume 13, Page(s) 870909

Abstract: The current concept of brain aging proposes three gradient patterns of changes in white matter that occur during healthy brain aging: antero-posterior, supero-inferior, and the myelodegeneration-retrogenesis (or the "last-in-first-out") concept. The aim ... ...

Abstract	The current concept of brain aging proposes three gradient patterns of changes in white matter that occur during healthy brain aging: antero-posterior, supero-inferior, and the myelodegeneration-retrogenesis (or the "last-in-first-out") concept. The aim of this study was to correlate white matter diffusivity measures (fractional anisotropy-FA, mean diffusivity-MD, radial diffusivity-RD, and axial diffusivity-AD) in healthy volunteers with chronological age and education level, in order to potentially incorporate the findings with proposed patterns of physiological brain aging. The study was performed on 75 healthy participants of both sexes, with an average age of 37.32 ± 11.91 years underwent brain magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI). DTI was performed using tract-based spatial statistics (TBSS), with the analysis of four parameters: FA, MD, RD, and AD. Skeletonized measures were averaged in 29 regions of interest in white matter. Correlations between age and DTI measures and between education-level and DTI measures were performed using Pearson's correlation test. To correct for multiple comparisons, we applied a Bonferroni correction to the
Language	English
Publishing date	2022-06-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2022.870909
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Article: Lifespan reference curves for harmonizing multi-site regional brain white matter metrics from diffusion MRI.

Zhu, Alyssa H / Nir, Talia M / Javid, Shayan / Villalon-Reina, Julio E / Rodrigue, Amanda L / Strike, Lachlan T / de Zubicaray, Greig I / McMahon, Katie L / Wright, Margaret J / Medland, Sarah E / Blangero, John / Glahn, David C / Kochunov, Peter / Håberg, Asta K / Thompson, Paul M / Jahanshad, Neda

bioRxiv : the preprint server for biology

2024

Abstract: Age-related white matter (WM) microstructure maturation and decline occur throughout the human lifespan, complementing the process of gray matter development and degeneration. Here, we create normative lifespan reference curves for global and regional WM ...

Abstract	Age-related white matter (WM) microstructure maturation and decline occur throughout the human lifespan, complementing the process of gray matter development and degeneration. Here, we create normative lifespan reference curves for global and regional WM microstructure by harmonizing diffusion MRI (dMRI)-derived data from ten public datasets (N = 40,898 subjects; age: 3-95 years; 47.6% male). We tested three harmonization methods on regional diffusion tensor imaging (DTI) based fractional anisotropy (FA), a metric of WM microstructure, extracted using the ENIGMA-DTI pipeline. ComBat-GAM harmonization provided multi-study trajectories most consistent with known WM maturation peaks. Lifespan FA reference curves were validated with test-retest data and used to assess the effect of the ApoE4 risk factor for dementia in WM across the lifespan. We found significant associations between ApoE4 and FA in WM regions associated with neurodegenerative disease even in healthy individuals across the lifespan, with regional age-by-genotype interactions. Our lifespan reference curves and tools to harmonize new dMRI data to the curves are publicly available as eHarmonize (https://github.com/ahzhu/eharmonize).
Language	English
Publishing date	2024-03-01
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.02.22.581646
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Article: Microstructural Mapping of Neural Pathways in Alzheimer's Disease using Macrostructure-Informed Normative Tractometry.

Feng, Yixue / Chandio, Bramsh Q / Villalon-Reina, Julio E / Thomopoulos, Sophia I / Nir, Talia M / Benavidez, Sebastian / Laltoo, Emily / Chattopadhyay, Tamoghna / Joshi, Himanshu / Venkatasubramanian, Ganesan / John, John P / Jahanshad, Neda / Reid, Robert I / Jack, Clifford R / Weiner, Michael W / Thompson, Paul M

bioRxiv : the preprint server for biology

2024

Abstract: Introduction: Diffusion MRI is sensitive to the microstructural properties of brain tissues, and shows great promise in detecting the effects of degenerative diseases. However, many approaches analyze single measures averaged over regions of interest, ... ...

Abstract	Introduction: Diffusion MRI is sensitive to the microstructural properties of brain tissues, and shows great promise in detecting the effects of degenerative diseases. However, many approaches analyze single measures averaged over regions of interest, without considering the underlying fiber geometry. Methods: Here, we propose a novel Macrostructure-Informed Normative Tractometry (MINT) framework, to investigate how white matter microstructure and macrostructure are jointly altered in mild cognitive impairment (MCI) and dementia. We compare MINT-derived metrics with univariate metrics from diffusion tensor imaging (DTI), to examine how fiber geometry may impact interpretation of microstructure. Results: In two multi-site cohorts from North America and India, we find consistent patterns of microstructural and macrostructural anomalies implicated in MCI and dementia; we also rank diffusion metrics' sensitivity to dementia. Discussion: We show that MINT, by jointly modeling tract shape and microstructure, has potential to disentangle and better interpret the effects of degenerative disease on the brain's neural pathways.
Language	English
Publishing date	2024-04-28
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.04.25.591183
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Article: Cortical microstructural associations with CSF amyloid and pTau.

Nir, Talia M / Villalón-Reina, Julio E / Salminen, Lauren / Haddad, Elizabeth / Zheng, Hong / Thomopoulos, Sophia I / Jack, Clifford R / Weiner, Michael W / Thompson, Paul M / Jahanshad, Neda

medRxiv : the preprint server for health sciences

2023

Abstract: Diffusion MRI (dMRI) can be used to probe microstructural properties of brain tissue and holds great promise as a means to non-invasively map Alzheimer's disease (AD) pathology. Few studies have evaluated multi-shell dMRI models, such as neurite ... ...

Abstract	Diffusion MRI (dMRI) can be used to probe microstructural properties of brain tissue and holds great promise as a means to non-invasively map Alzheimer's disease (AD) pathology. Few studies have evaluated multi-shell dMRI models, such as neurite orientation dispersion and density imaging (NODDI) and mean apparent propagator (MAP)-MRI, in cortical gray matter where many of the earliest histopathological changes occur in AD. Here, we investigated the relationship between CSF pTau
Language	English
Publishing date	2023-04-11
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.04.10.23288366
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Article ; Online: Cortical microstructural associations with CSF amyloid and pTau.

Nir, Talia M / Villalón-Reina, Julio E / Salminen, Lauren E / Haddad, Elizabeth / Zheng, Hong / Thomopoulos, Sophia I / Jack, Clifford R / Weiner, Michael W / Thompson, Paul M / Jahanshad, Neda

Molecular psychiatry

2023

Abstract	Diffusion MRI (dMRI) can be used to probe microstructural properties of brain tissue and holds great promise as a means to non-invasively map Alzheimer's disease (AD) pathology. Few studies have evaluated multi-shell dMRI models such as neurite orientation dispersion and density imaging (NODDI) and mean apparent propagator (MAP)-MRI in cortical gray matter where many of the earliest histopathological changes occur in AD. Here, we investigated the relationship between CSF pTau
Language	English
Publishing date	2023-12-13
Publishing country	England
Document type	Journal Article
ZDB-ID	1330655-8
ISSN	1476-5578 ; 1359-4184
ISSN (online)	1476-5578
ISSN	1359-4184
DOI	10.1038/s41380-023-02321-7
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Article ; Online: Planum temporale surface area and grey matter asymmetries in chimpanzees (Pan troglodytes): the effect of handedness and comparison with findings in humans.

Hopkins, William D / Nir, Talia M

Behavioural brain research

2009 Volume 208, Issue 2, Page(s) 436–443

Abstract: The planum temporale (PT) is the bank of tissue that lies posterior to Heschl's gyrus and is considered a key brain region involved in language and speech in the human brain. In the human brain, both the surface area and grey matter volume of the PT is ... ...

Abstract	The planum temporale (PT) is the bank of tissue that lies posterior to Heschl's gyrus and is considered a key brain region involved in language and speech in the human brain. In the human brain, both the surface area and grey matter volume of the PT is larger in the left compared to right hemisphere in approximately 2/3rds of individuals, particularly among right-handed individuals. Here we examined whether chimpanzees show asymmetries in the PT for grey matter volume and surface area in a sample of 103 chimpanzees from magnetic resonance images. The results indicated that, overall, the chimpanzees showed population-level leftward asymmetries for both surface area and grey matter volumes. Furthermore, chimpanzees that prefer to gesture with their right-handed had significantly greater leftward grey matter asymmetries compared to ambiguously- and left-handed apes. When compared to previously published data in humans, the direction and magnitude of PT grey matter asymmetries were similar between humans and apes; however, for the surface area measures, the human showed more pronounced leftward asymmetries. These results suggest that leftward asymmetries in the PT were present in the common ancestor of chimpanzees and humans.
MeSH term(s)	Animals ; Brain Mapping ; Cephalometry/methods ; Female ; Functional Laterality ; Gestures ; Humans ; Image Processing, Computer-Assisted/methods ; Magnetic Resonance Imaging/methods ; Male ; Pan troglodytes/anatomy & histology ; Psychomotor Performance/physiology ; Sex Factors ; Temporal Lobe/anatomy & histology
Language	English
Publishing date	2009-12-24
Publishing country	Netherlands
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	449927-x
ISSN	1872-7549 ; 0166-4328
ISSN (online)	1872-7549
ISSN	0166-4328
DOI	10.1016/j.bbr.2009.12.012
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Article ; Online: Age and sex effects on advanced white matter microstructure measures in 15,628 older adults: A UK biobank study.

Lawrence, Katherine E / Nabulsi, Leila / Santhalingam, Vigneshwaran / Abaryan, Zvart / Villalon-Reina, Julio E / Nir, Talia M / Ba Gari, Iyad / Zhu, Alyssa H / Haddad, Elizabeth / Muir, Alexandra M / Laltoo, Emily / Jahanshad, Neda / Thompson, Paul M

Brain imaging and behavior

2021 Volume 15, Issue 6, Page(s) 2813–2823

Abstract: A comprehensive characterization of the brain's white matter is critical for improving our understanding of healthy and diseased aging. Here we used diffusion-weighted magnetic resonance imaging (dMRI) to estimate age and sex effects on white matter ... ...

Abstract	A comprehensive characterization of the brain's white matter is critical for improving our understanding of healthy and diseased aging. Here we used diffusion-weighted magnetic resonance imaging (dMRI) to estimate age and sex effects on white matter microstructure in a cross-sectional sample of 15,628 adults aged 45-80 years old (47.6% male, 52.4% female). Microstructure was assessed using the following four models: a conventional single-shell model, diffusion tensor imaging (DTI); a more advanced single-shell model, the tensor distribution function (TDF); an advanced multi-shell model, neurite orientation dispersion and density imaging (NODDI); and another advanced multi-shell model, mean apparent propagator MRI (MAPMRI). Age was modeled using a data-driven statistical approach, and normative centile curves were created to provide sex-stratified white matter reference charts. Participant age and sex substantially impacted many aspects of white matter microstructure across the brain, with the advanced dMRI models TDF and NODDI detecting such effects the most sensitively. These findings and the normative reference curves provide an important foundation for the study of healthy and diseased brain aging.
MeSH term(s)	Aged ; Aged, 80 and over ; Biological Specimen Banks ; Brain/diagnostic imaging ; Cross-Sectional Studies ; Diffusion Magnetic Resonance Imaging ; Diffusion Tensor Imaging ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; United Kingdom ; White Matter/diagnostic imaging
Language	English
Publishing date	2021-09-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2377165-3
ISSN	1931-7565 ; 1931-7557
ISSN (online)	1931-7565
ISSN	1931-7557
DOI	10.1007/s11682-021-00548-y
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Article ; Online: Effects of ApoE4 and ApoE2 genotypes on subcortical magnetic susceptibility and microstructure in 27,535 participants from the UK Biobank.

Nir, Talia M / Zhu, Alyssa H / Gari, Iyad Ba / Dixon, Daniel / Islam, Tasfiya / Villalon-Reina, Julio E / Medland, Sarah E / Thompson, Paul M / Jahanshad, Neda

Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing

2021 Volume 27, Page(s) 121–132

Abstract: Disrupted iron homeostasis is associated with several neurodegenerative diseases, including Alzheimer's disease (AD), and may be partially modulated by genetic risk factors. Here we evaluated whether subcortical iron deposition is associated with ApoE ... ...

Abstract	Disrupted iron homeostasis is associated with several neurodegenerative diseases, including Alzheimer's disease (AD), and may be partially modulated by genetic risk factors. Here we evaluated whether subcortical iron deposition is associated with ApoE genotype, which substantially affects risk for late-onset AD. We evaluated differences in subcortical quantitative susceptibility mapping (QSM), a type of MRI sensitive to cerebral iron deposition, between either ApoE4 (E3E4+E4E4) or ApoE2 (E2E3+E2E2) carriers and E3 homozygotes (E3E3) in 27,535 participants from the UK Biobank (age: 45-82 years). We found that ApoE4 carriers had higher hippocampal (d=0.036; p=0.012) and amygdalar (d=0.035; p=0.013) magnetic susceptibility, particularly individuals aged 65 years or older, while those carrying ApoE2 (which protects against AD) had higher QSM only in the hippocampus (d=0.05; p=0.006), particularly those under age 65. Secondary diffusion MRI microstructural associations in these regions revealed greater diffusivity and less diffusion restriction in E4 carriers, however no differences were detected in E2 carriers. Disease risk conferred by ApoE4 may be linked with higher subcortical iron burden in conjunction with inflammation or neuronal loss in aging individuals, while ApoE2 associations may not necessarily reflect unhealthy iron deposits earlier in life.
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/genetics ; Apolipoprotein E2/genetics ; Apolipoprotein E4/genetics ; Apolipoproteins E/genetics ; Biological Specimen Banks ; Computational Biology ; Genotype ; Humans ; Middle Aged ; United Kingdom
Chemical Substances	Apolipoprotein E2 ; Apolipoprotein E4 ; Apolipoproteins E
Language	English
Publishing date	2021-12-13
Publishing country	United States
Document type	Journal Article
ISSN	2335-6936
ISSN (online)	2335-6936
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