Arash Kamali

Development and Aging of the Healthy Human Brain Uncinate Fasciculus across the Lifespan using Diffusion Tensor Tractography

The human brain uncinate fasciculus (UF) is an important cortico-cortical white matter pathway that directly connects the frontal and temporal lobes, although there is a lack of conclusive support for its exact functional role. Using diffusion tensor tractography, we extracted the UF, calculated its volume and normalized it with respect to each subjects intracranial volume (ICV) and analyzed its corresponding DTI metrics bilaterally on a cohort of 108 right-handed children and adults aged 7-68 years. Results showed inverted U-shaped curves for fractional anisotropy (FA) with advancing age and U-shaped curves for radial and axial diffusivities reflecting white matter progressive and regressive myelination and coherence dynamics that continue into young adulthood. The mean FA values of the UF were significantly larger on the left side in children (p=0.05), adults (p=0.0012) and the entire sample (p=0.0002). The FA leftward asymmetry (Left>Right) is shown to be due to increased leftward asymmetry in the axial diffusivity (p<0.0001) and a lack of asymmetry (p>0.23) for the radial diffusivity. This is the first study to provide baseline normative macro and microstructural age trajectories of the human UF across the lifespan. Results of this study may lend themselves to better understanding of UF role in future behavioral and clinical studies.

Diffusion tensor tractography quantification of the human corpus callosum fiber pathways across the lifespan

Several anatomical attributes of the human corpus callosum (CC) including the midsagittal cross-sectional area, thickness, and volume, have been used to assess CC integrity. We extended our previous lifespan quantitative diffusion tensor imaging (DTI) study of the regional CC midsagittal areas to include the CC volumes obtained from DTI fiber tracking. In addition to the entire CC tracked subvolumes we normalized volume with respect to each subjects intracranial volume (ICV) and the corresponding DTI metrics of the different specialized fiber pathways of the CC on a cohort of 99 right-handed children and adults aged 7-59 years. Results indicated that the CC absolute volume, the normalized volume fraction, and the fractional anisotropy followed inverted U-shaped curves, while the radial diffusivities followed a U-shaped curve reflecting white matter progressive and regressive myelination dynamics that continue into young adulthood. Our study provides for the first time normative baseline macro- and microstructural age trajectories of the human CC subvolumes across the lifespan that can be helpful for normative behavioral and clinical studies.

Diffusion tensor quantification of the human midsagittal corpus callosum subdivisions across the lifespan

The midsagittal corpus callosum (CC) cross-sectional area subdivisions have been used as early and sensitive markers of human brain white matter connectivity, development, natural aging and disease. Despite the simplicity and conspicuity of the appearance of the CC on anatomical magnetic resonance imaging (MRI), the published quantitative MRI literature on its regional sex and age trajectories are contradictory. The availability of noninvasive quantitative methods to assess the CC regions across the human lifespan would help clarify its contribution to behavior and cognition. In this report, we extended the utility of a recently described semi-automated diffusion tensor imaging (DTI) tissue segmentation method to utilize the high orientation contrast of the CC on DTI. Using optimized DTI methods on a cohort of 121 right-handed children and adults aged 6-68 years, we examined the CC areas and corresponding DTI metrics of the different functionally specialized sectors of the CC. Both the area and fractional anisotropy metrics followed inverted U-shaped curves, while the mean and radial diffusivities followed U-curves reflecting white matter progressive and regressive myelination dynamics that continue into young adulthood.

Tracing superior longitudinal fasciculus connectivity in the human brain using high resolution diffusion tensor tractography

The major language pathways such as superior longitudinal fasciculus (SLF) pathways have been outlined by experimental and diffusion tensor imaging (DTI) studies. The SLF I and some of the superior parietal lobule connections of the SLF pathways have not been depicted by prior DTI studies due to the lack of imaging sensitivity and adequate spatial resolution. In the current study, the trajectory of the SLF fibers has been delineated on five healthy human subjects using diffusion tensor tractography on a 3.0-T scanner at high spatial resolution. We also demonstrate for the first time the trajectory and connectivity of the SLF fibers in relation to other language pathways as well as the superior parietal lobule connections of the language circuit using high spatial resolution DTI in the healthy adult human brain.

Caudate nuclei volume, diffusion tensor metrics, and T(2) relaxation in healthy adults and relapsing-remitting multiple sclerosis patients: implications for understanding gray matter degeneration.

To investigate the utility of caudate nuclei (CN) macro‐ and microstructural metrics as markers of gray matter degeneration in healthy adults and relapsing‐remitting multiple sclerosis (RRMS) patients.

Diffusion tensor tractography of the human brain cortico-ponto-cerebellar pathways: a quantitative preliminary study.

To investigate the utility of diffusion tensor tractography at 1mm slice thickness to map and quantify the whole trajectory of different cortico‐ponto‐cerebellar pathways of the healthy adult human brain.

Feasibility of prefronto-caudate pathway tractography using high resolution diffusion tensor tractography data at 3T.

Mapping the human brain frontostriatal pathways using noninvasive diffusion tensor imaging (DTI) has been hampered by the inadequate imaging sensitivity, poor spatial resolution, lower tensor anisotropy within gray matter, increased partial volume averaging effects and poor signal-to-noise ratio. We investigated for the first time the utility of high spatial resolution DTI-based fiber-tractography using the fiber assignment by continuous tracking (FACT) to reconstruct and quantify bilaterally the prefronto-caudo-thalamic connections within the human brain at 3T. Five healthy right-handed men (age range 24-37 years) were studied. We traced the anterior thalamic radiation and prefronto-caudo-thalamic pathways bilaterally and measured the volume of each tract and the corresponding diffusion tensor metrics in all subjects. The anterior thalamic radiation tract volume and corresponding fractional anisotropy (FA) were significantly larger bilaterally than prefronto-caudate pathway, whereas the mean diffusivity (D(av)) values were similar (p>0.7). For both anterior thalamic radiation and prefronto-caudate pathway the tract volume and corresponding DTI metrics (FA, D(av)) were not significantly different between the two hemispheres (p>0.2). Our DTI acquisition protocol and analysis permitted the reconstruction of the connectivity of the caudate with the thalamus as well as with the prefrontal cortex and allowed tracking of the whole trajectory of the prefronto-caudo-thalamic pathway.

Decoding the superior parietal lobule connections of the superior longitudinal fasciculus/arcuate fasciculus in the human brain

The temporo-parietal (TP) white matter connections between the inferior parietal lobule and superior temporal gyrus as part of the superior longitudinal fasciculus/arcuate fasciculus (SLF/AF) or middle longitudinal fasciculus (MdLF) have been studied in prior diffusion tensor tractography (DTT) studies. However, few studies have been focusing on the higher TP connections of the superior parietal lobule with the temporal lobe. These higher TP connections have been shown to have a role in core processes such as attention, memory, emotions, and language. Our most recent study, for the first time, hinted to the possibility of a long white matter connection interconnecting the superior parietal lobule (SPL) with the posterior temporal lobe in human brain which we call the SLF/AF TP-SPL and for a shorter abbreviation, the TP-SPL. We decided to further investigate this white matter connection using fiber assignment by continuous tracking deterministic tractography and high spatial resolution diffusion tensor imaging on 3T. Five healthy right-handed men (age range 24-37 years) were studied. We delineated the SPL connections of the SLF/AF TP bilaterally in five normal adult human brains. Using a high resolution DTT technique, we demonstrate for the first time, the trajectory of a long fiber bundle connectivity between the SPL and posterior temporal lobe, called the SLF/AF TP-SPL (or the TP-SPL), bilaterally in five healthy adult human brains. We also demonstrate the trajectory of the vertically oriented posterior TP connections, interconnecting the inferior parietal lobule (IPL) with the posterior temporal lobe (TP-IPL) in relation to the TP-SPL, arcuate fasciculus and other major language pathways. In the current study, for the first time, we categorized the TP connections into the anterior and posterior connectivity groups and subcategorized each one into the SPL or IPL connections.

Mapping the human brain white matter tracts relative to cortical and deep gray matter using diffusion tensor imaging at high spatial resolution

The mapping of the human brain white matter fiber networks relative to deep subcortical and cortical gray matter requires high spatial resolution which is challenged by the low signal-to-noise ratio. The purpose of this short report was to introduce a whole brain high spatial resolution diffusion tensor imaging (DTI) protocol that enabled for the first time the mapping of corticopontocerebellar, frontostriatal and thalamofrontal fiber pathways in addition to other limbic, commissural, association and projection white matter pathways relative to the segmented deep gray (e.g., caudate nuclei) and the cortical lobes. Our DTI acquisition protocol and analysis strategy provide important template for brain-behavior research and for teaching brain mapping and are clinically affordable for patient comfort.

Diffusion tensor imaging of the human cerebellar pathways and their interplay with cerebral macrostructure

Cerebellar white matter (WM) connections to the central nervous system are classified functionally into the Spinocerebellar (SC), vestibulocerebellar (VC), and cerebrocerebellar subdivisions. The SC pathways project from spinal cord to cerebellum, whereas the VC pathways project from vestibular organs of the inner ear. Cerebrocerebellar connections are composed of feed forward and feedback connections between cerebrum and cerebellum including the cortico-ponto-cerebellar (CPC) pathways being of cortical origin and the dentate-rubro-thalamo-cortical (DRTC) pathway being of cerebellar origin. In this study we systematically quantified the whole cerebellar system connections using diffusion tensor magnetic resonance imaging (DT-MRI). Ten right-handed healthy subjects (7 males and 3 females, age range 20–51 years) were studied. DT-MRI data were acquired with a voxel size = 2 mm × 2 mm × 2 mm at a 3.0 Tesla clinical MRI scanner. The DT-MRI data were prepared and analyzed using anatomically-guided deterministic tractography methods to reconstruct the SC, DRTC, fronto-ponto-cerebellar (FPC), parieto-ponto-cerebellar (PPC), temporo-ponto-cerebellar (TPC) and occipito-ponto-cerebellar (OPC). The DTI-attributes or the cerebellar tracts along with their cortical representation (Brodmann areas) were presented in standard Montréal Neurological Institute space. All cerebellar tract volumes were quantified and correlated with volumes of cerebral cortical, subcortical gray matter (GM), cerebral WM and cerebellar GM, and cerebellar WM. On our healthy cohort, the ratio of total cerebellar GM-to-WM was ~3.29 ± 0.24, whereas the ratio of cerebral GM-to-WM was approximately 1.10 ± 0.11. The sum of all cerebellar tract volumes is ~25.8 ± 7.3 mL, or a percentage of 1.6 ± 0.45 of the total intracranial volume (ICV).