scholarly journals Potential Pitfalls of Using Fractional Anisotropy, Axial Diffusivity, and Radial Diffusivity as Biomarkers of Cerebral White Matter Microstructure

2022 ◽  
Vol 15 ◽  
Author(s):  
Chase R. Figley ◽  
Md Nasir Uddin ◽  
Kaihim Wong ◽  
Jennifer Kornelsen ◽  
Josep Puig ◽  
...  
Keyword(s):  
White Matter ◽  
Fractional Anisotropy ◽  
Brain Aging ◽  
Common Knowledge ◽  
Diffusion Imaging ◽  
Cerebral White Matter ◽  
Radial Diffusivity ◽  
Axial Diffusivity ◽  
White Matter Microstructure ◽  
Or Groups

Fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) are commonly used as MRI biomarkers of white matter microstructure in diffusion MRI studies of neurodevelopment, brain aging, and neurologic injury/disease. Some of the more frequent practices include performing voxel-wise or region-based analyses of these measures to cross-sectionally compare individuals or groups, longitudinally assess individuals or groups, and/or correlate with demographic, behavioral or clinical variables. However, it is now widely recognized that the majority of cerebral white matter voxels contain multiple fiber populations with different trajectories, which renders these metrics highly sensitive to the relative volume fractions of the various fiber populations, the microstructural integrity of each constituent fiber population, and the interaction between these factors. Many diffusion imaging experts are aware of these limitations and now generally avoid using FA, AD or RD (at least in isolation) to draw strong reverse inferences about white matter microstructure, but based on the continued application and interpretation of these metrics in the broader biomedical/neuroscience literature, it appears that this has perhaps not yet become common knowledge among diffusion imaging end-users. Therefore, this paper will briefly discuss the complex biophysical underpinnings of these measures in the context of crossing fibers, provide some intuitive “thought experiments” to highlight how conventional interpretations can lead to incorrect conclusions, and suggest that future studies refrain from using (over-interpreting) FA, AD, and RD values as standalone biomarkers of cerebral white matter microstructure.

scholarly journals Infratentorial pathology in frontotemporal dementia: cerebellar grey and white matter alterations in FTD phenotypes

2021 ◽  
Author(s):  
Mary Clare McKenna ◽  
Rangariroyashe H. Chipika ◽  
Stacey Li Hi Shing ◽  
Foteini Christidi ◽  
Jasmin Lope ◽  
...  
Keyword(s):  
White Matter ◽  
Fractional Anisotropy ◽  
Cortical Thickness ◽  
Cerebellar Atrophy ◽  
Primary Progressive Aphasia ◽  
Radial Diffusivity ◽  
Axial Diffusivity ◽  
Progressive Aphasia ◽  
Primary Progressive ◽  
Crus I

AbstractThe contribution of cerebellar pathology to cognitive and behavioural manifestations is increasingly recognised, but the cerebellar profiles of FTD phenotypes are relatively poorly characterised. A prospective, single-centre imaging study has been undertaken with a high-resolution structural and diffusion tensor protocol to systematically evaluate cerebellar grey and white matter alterations in behavioural-variant FTD(bvFTD), non-fluent variant primary progressive aphasia(nfvPPA), semantic-variant primary progressive aphasia(svPPA), C9orf72-positive ALS-FTD(C9 + ALSFTD) and C9orf72-negative ALS-FTD(C9-ALSFTD). Cerebellar cortical thickness and complementary morphometric analyses were carried out to appraise atrophy patterns controlling for demographic variables. White matter integrity was assessed in a study-specific white matter skeleton, evaluating three diffusivity metrics: fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD). Significant cortical thickness reductions were identified in: lobule VII and crus I in bvFTD; lobule VI VII, crus I and II in nfvPPA; and lobule VII, crus I and II in svPPA; lobule IV, VI, VII and Crus I and II in C9 + ALSFTD. Morphometry revealed volume reductions in lobule V in all groups; in addition to lobule VIII in C9 + ALSFTD; lobule VI, VIII and vermis in C9-ALSFTD; lobule V, VII and vermis in bvFTD; and lobule V, VI, VIII and vermis in nfvPPA. Widespread white matter alterations were demonstrated by significant fractional anisotropy, axial diffusivity and radial diffusivity changes in each FTD phenotype that were more focal in those with C9 + ALSFTD and svPPA. Our findings indicate that FTD subtypes are associated with phenotype-specific cerebellar signatures with the selective involvement of specific lobules instead of global cerebellar atrophy.

scholarly journals A Correlational Study between Microstructural White Matter Properties and Macrostructural Gray Matter Volume Across Normal Ageing: Conjoint DTI and VBM Analysis

2018 ◽  
Vol 11 ◽  
pp. 1178623X1879992 ◽  
Author(s):  
Vikas Pareek ◽  
VP Subramanyam Rallabandi ◽  
Prasun K Roy
Keyword(s):  
White Matter ◽  
Life Span ◽  
Fractional Anisotropy ◽  
Gray Matter ◽  
Healthy Aging ◽  
Gray Matter Volume ◽  
Mean Diffusivity ◽  
Radial Diffusivity ◽  
Axial Diffusivity ◽  
Matter Volume

We investigate the relationship between Gray matter’s volume vis-a-vis White matter’s integrity indices, such Axial diffusivity, Radial diffusivity, Mean diffusivity, and Fractional anisotropy, in individuals undergoing healthy aging. We investigated MRI scans of 177 adults across 20 to 85 years. We used Voxel-based morphometry, and FDT-FSL analysis for estimation of Gray matter volume and White matter’s diffusion indices respectively. Across the life span, we observed an inter-relationship between the Gray matter and White matter, namely that both Axial diffusivity and Mean Diffusivity show strong correlation with Gray matter volume, along the aging process. Furthermore, across all ages the Fractional anisotropy and Mean diffusivity are found to be significantly reduced in females when compared to males, but there are no significant gender differences in Axial Diffusivity and Radial diffusivity. We conclude that for both genders across all ages, the Gray matter’s Volume is strongly correlated with White matter’s Axial Diffusivity and Mean Diffusivity, while being weakly correlated with Fractional Anisotropy. Our study clarifies the multi-scale relationship in brain tissue, by elucidating how the White matter’s micro-structural parameters influences the Gray matter’s macro-structural characteristics, during healthy aging across the life-span.

scholarly journals Greater Loss of White Matter Integrity in Postural Instability and Gait Difficulty Subtype of Parkinson's Disease

2014 ◽  
Vol 41 (6) ◽  
pp. 763-768 ◽  
Author(s):  
Quanquan Gu ◽  
Peiyu Huang ◽  
Min Xuan ◽  
Xiaojun Xu ◽  
Dan Li ◽  
...  
Keyword(s):  
White Matter ◽  
Fractional Anisotropy ◽  
Diffusion Tensor ◽  
Critical Role ◽  
Postural Instability ◽  
White Matter Integrity ◽  
Radial Diffusivity ◽  
Superior Longitudinal Fasciculus ◽  
Axial Diffusivity ◽  
White Matter Abnormalities

ABSTRACTBackground: Patients with the postural instability and gait difficulty (PIGD) subtype of Parkinson disease (PD) are at a higher risk of dysfunction and are less responsive to dopamine replacement therapy. The PIGD subtype was found to largely associate with white matter lesions, but details of the diffusion changes within these lesions have not been fully investigated. Voxel-based analysis for diffusion tensor imaging data is one of the preferred measures to compare diffusion changes in each voxel in any part of the brain. Methods: PD patients with the PIGD (n=12) and non-PIGD subtypes (n=12) were recruited to compare diffusion differences in fractional anisotropy, axial diffusivity, and radial diffusivity with voxel-based analysis. Results: Significantly reduced fractional anisotropy in bilateral superior longitudinal fasciculus, bilateral anterior corona radiata, and the left genu of the corpus callosum were shown in the PIGD subtype compared with the non-PIGD subtype. Increased radial diffusivity in the left superior longitudinal fasciculus was found in the PIGD subtype with no statistical differences in axial diffusivity found. Conclusions: Our study confirms previous findings that white matter abnormalities were greater in the PIGD subtype than in the non-PIGD subtype. Additionally, our findings suggested: (1) compared with the non-PIGD subtype, loss of white matter integrity was greater in the PIGD subtype; (2) bilateral superior longitudinal fasciculus may play a critical role in microstructural white matter abnormalities in the PIGD subtype; and (3) reduced white matter integrity in the PIGD subtype could be mainly attributed to demyelination rather than axonal loss.

scholarly journals Genetic relatedness of axial and radial diffusivity indices of cerebral white matter microstructure in late middle age

2018 ◽  
Vol 39 (5) ◽  
pp. 2235-2245 ◽  
Author(s):  
Sean N. Hatton ◽  
Matthew S. Panizzon ◽  
Eero Vuoksimaa ◽  
Donald J. Hagler ◽  
Christine Fennema-Notestine ◽  
...  
Keyword(s):  
White Matter ◽  
Genetic Relatedness ◽  
Middle Age ◽  
Cerebral White Matter ◽  
Radial Diffusivity ◽  
White Matter Microstructure

scholarly journals Advanced MR diffusion imaging and chemotherapy-related changes in cerebral white matter microstructure of survivors of childhood bone and soft tissue sarcoma?

2018 ◽  
Vol 39 (8) ◽  
pp. 3375-3387 ◽  
Author(s):  
Charlotte Sleurs ◽  
Jurgen Lemiere ◽  
Daan Christiaens ◽  
Thibo Billiet ◽  
Ronald Peeters ◽  
...  
Keyword(s):  
White Matter ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Diffusion Imaging ◽  
Cerebral White Matter ◽  
White Matter Microstructure ◽  
Mr Diffusion

scholarly journals Myelin Water Fraction in Relation To Fractional Anisotropy and Reading in 10-Year-Old Children

2021 ◽  
Author(s):  
Maria Economou ◽  
Thibo Billiet ◽  
Jan Wouters ◽  
Pol Ghesquière ◽  
Jolijn Vanderauwera ◽  
...  
Keyword(s):  
White Matter ◽  
Fractional Anisotropy ◽  
Reading Ability ◽  
Word Reading ◽  
Diffusion Imaging ◽  
Water Fraction ◽  
Diffusion Weighted ◽  
White Matter Microstructure ◽  
Myelin Water Fraction

Abstract Diffusion-weighted imaging studies have repeatedly shown that white matter correlates with reading throughout development. However, the neurobiological interpretation of this relationship is constrained by the limited microstructural specificity of diffusion imaging. A critical component of white matter microstructure is myelin, which can be investigated noninvasively using MRI. Here, diffusion-weighted as well as myelin water imaging were applied to examine the links of myelin water fraction (MWF) with fractional anisotropy (FA; a common diffusion index) and reading ability in 10-year-old children (n = 69). The results replicate previous reports on a positive relationship between FA and MWF, which is significant in dorsal but not ventral tracts. Moreover, our findings revealed a negative correlation between word reading and MWF in left reading-related white matter tracts. Altogether, this study contributes important insights into the role of myelin-related processes in the relationship between reading and white matter structure.

scholarly journals Quantitative diffusion tensor imaging analysis does not distinguish pediatric canines with mucopolysaccharidosis I from control canines

2017 ◽  
Vol 30 (5) ◽  
pp. 454-460
Author(s):  
Dana M Middleton ◽  
Jonathan Y Li ◽  
Steven D Chen ◽  
Leonard E White ◽  
Patricia I Dickson ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Fractional Anisotropy ◽  
Imaging System ◽  
Diffusion Tensor ◽  
Brain Regions ◽  
Magnetic Resonance Imaging System ◽  
Radial Diffusivity ◽  
Mucopolysaccharidosis I ◽  
Diffusivity Measurements

Purpose We compared fractional anisotropy and radial diffusivity measurements between pediatric canines affected with mucopolysaccharidosis I and pediatric control canines. We hypothesized that lower fractional anisotropy and higher radial diffusivity values, consistent with dysmyelination, would be present in the mucopolysaccharidosis I cohort. Methods Six canine brains, three affected with mucopolysaccharidosis I and three unaffected, were euthanized at 7 weeks and imaged using a 7T small-animal magnetic resonance imaging system. Average fractional anisotropy and radial diffusivity values were calculated for four white-matter regions based on 100 regions of interest per region per specimen. A 95% confidence interval was calculated for each mean value. Results No difference was seen in fractional anisotropy or radial diffusivity values between mucopolysaccharidosis affected and unaffected brains in any region. In particular, the 95% confidence intervals for mucopolysaccharidosis affected and unaffected canines frequently overlapped for both fractional anisotropy and radial diffusivity measurements. In addition, in some brain regions a large range of fractional anisotropy and radial diffusivity values were seen within the same cohort. Conclusion The fractional anisotropy and radial diffusivity values of white matter did not differ between pediatric mucopolysaccharidosis affected canines and pediatric control canines. Possible explanations include: (a) a lack of white matter tissue differences between mucopolysaccharidosis affected and unaffected brains at early disease stages; (b) diffusion tensor imaging does not detect any existing differences; (c) inflammatory processes such as astrogliosis produce changes that offset the decreased fractional anisotropy values and increased radial diffusivity values that are expected in dysmyelination; and (d) our sample size was insufficient to detect differences. Further studies correlating diffusion tensor imaging findings to histology are warranted.

scholarly journals White matter differences between essential tremor and Parkinson disease

Neurology ◽  
2018 ◽  
Vol 92 (1) ◽  
pp. e30-e39 ◽  
Author(s):  
Meher R. Juttukonda ◽  
Giulia Franco ◽  
Dario J. Englot ◽  
Ya-Chen Lin ◽  
Kalen J. Petersen ◽  
...  
Keyword(s):  
White Matter ◽  
Parkinson Disease ◽  
Essential Tremor ◽  
Fractional Anisotropy ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Superior Cerebellar Peduncle ◽  
Radial Diffusivity ◽  
Cerebellar Peduncles ◽  
Cerebellar Peduncle

ObjectiveTo assess white matter integrity in patients with essential tremor (ET) and Parkinson disease (PD) with moderate to severe motor impairment.MethodsSedated participants with ET (n = 57) or PD (n = 99) underwent diffusion tensor imaging (DTI) and fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity values were computed. White matter tracts were defined using 3 well-described atlases. To determine candidate white matter regions that differ between ET and PD groups, a bootstrapping analysis was applied using the least absolute shrinkage and selection operator. Linear regression was applied to assess magnitude and direction of differences in DTI metrics between ET and PD populations in the candidate regions.ResultsFractional anisotropy values that differentiate ET from PD localize primarily to thalamic and visual-related pathways, while diffusivity differences localized to the cerebellar peduncles. Patients with ET exhibited lower fractional anisotropy values than patients with PD in the lateral geniculate body (p < 0.01), sagittal stratum (p = 0.01), forceps major (p = 0.02), pontine crossing tract (p = 0.03), and retrolenticular internal capsule (p = 0.04). Patients with ET exhibited greater radial diffusivity values than patients with PD in the superior cerebellar peduncle (p < 0.01), middle cerebellar peduncle (p = 0.05), and inferior cerebellar peduncle (p = 0.05).ConclusionsRegionally, distinctive white matter microstructural values in patients with ET localize to the cerebellar peduncles and thalamo-cortical visual pathways. These findings complement recent functional imaging studies in ET but also extend our understanding of putative physiologic features that account for distinctions between ET and PD.

scholarly journals Discrimination of epileptogenic lesions and perilesional white matter using diffusion tensor magnetic resonance imaging

2018 ◽  
Vol 32 (1) ◽  
pp. 10-16
Author(s):  
Alexander Rau ◽  
Elias Kellner ◽  
Niels A Foit ◽  
Niklas Lützen ◽  
Dieter H Heiland ◽  
...  
Keyword(s):  
White Matter ◽  
Fractional Anisotropy ◽  
Diffusion Tensor ◽  
Focal Cortical Dysplasia ◽  
Mean Diffusivity ◽  
Area Under The Curve ◽  
P Value ◽  
Radial Diffusivity ◽  
Normal Appearing White Matter ◽  
Diffusion Parameters

The aim of this study was to evaluate whether ganglioglioma (GGL), dysembryoplastic neuroepithelial tumour (DNET) and FCD (focal cortical dysplasia) are distinguishable through diffusion tensor imaging. Additionally, it was investigated whether the diffusion measures differed in the perilesional (pNAWM) and in the contralateral normal appearing white matter (cNAWM). Six GGLs, eight DNETs and seven FCDs were included in this study. Quantitative diffusion measures, that is, axial, radial and mean diffusivity and fractional anisotropy, were determined in the lesion identified on isotropic T2 or FLAIR-weighted images and in pNAWM and cNAWM, respectively. DNET differed from FCD in mean diffusivity, and GGL from FCD in radial diffusivity. Both types of glioneuronal tumours were different from pNAWM in fractional anisotropy and radial diffusivity. For identifying the tumour edges, threshold values for tumour-free tissue were investigated with receiver operating characteristic analyses: tumour could be separated from pNAWM at a threshold ≤ 0.32 (fractional anisotropy) or ≥ 0.56 (radial diffusivity) *10–3 mm2/s (area under the curve 0.995 and 0.990 respectively). While diffusion parameters of FCDs differed from cNAWM (radial diffusivity (*10–3 mm/s2): 0.74 ± 0.19 vs. 0.43 ± 0.05; corrected p-value < 0.001), the pNAWM could not be differentiated from the FCD.

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