scholarly journals Test-retest reproducibility of in vivo oscillating gradient and microscopic anisotropy diffusion MRI in mice at 9.4 Tesla

2021 ◽  
Author(s):  
Naila Rahman ◽  
Kathy Xu ◽  
Mohammad Omer ◽  
Matthew Budde ◽  
Arthur Brown ◽  
...  

Background and Purpose: Microstructure imaging with advanced diffusion MRI (dMRI) techniques have shown increased sensitivity and specificity to microstructural changes in various disease and injury models. Oscillating gradient spin echo (OGSE) dMRI, implemented by varying the oscillating gradient frequency, and microscopic anisotropy (µA) dMRI, implemented via tensor valued diffusion encoding, may provide additional insight by increasing sensitivity to smaller spatial scales and disentangling fiber orientation dispersion from true microstructural changes, respectively. The aims of this study were to characterize the test-retest reproducibility of in vivo OGSE and µA dMRI metrics in the mouse brain at 9.4 Tesla and provide estimates of required sample sizes for future investigations. Methods: Eight adult C57Bl/6 mice were scanned twice (5 days apart). Each imaging session consisted of multifrequency OGSE and µA dMRI protocols. Metrics investigated included µA, isotropic and anisotropic kurtosis, and the diffusion dispersion rate (Λ), which explores the power-law frequency dependence of mean diffusivity. The dMRI metric maps were analyzed with mean region-of-interest (ROI) and whole brain voxel-wise analysis. Bland-Altman plots and coefficients of variation (CV) were used to assess the reproducibility of OGSE and µA metrics. Furthermore, we estimated sample sizes required to detect a variety of effect sizes. Results: Bland-Altman plots showed negligible biases between test and retest sessions. ROI-based CVs revealed high reproducibility for both µA (CVs < 8 %) and Λ (CVs < 15 %). Voxel-wise CV maps revealed high reproducibility for µA (CVs ~ 10 %), but low reproducibility for OGSE metrics (CVs ~ 50 %). Conclusion: Most of the µA dMRI metrics are reproducible in both ROI-based and voxel-wise analysis, while the OGSE dMRI metrics are only reproducible in ROI-based analysis. µA and Λ may provide sensitivity to subtle microstructural changes (4 - 8 %) with feasible sample sizes (10 – 15).

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0255711
Author(s):  
Naila Rahman ◽  
Kathy Xu ◽  
Mohammad Omer ◽  
Matthew D. Budde ◽  
Arthur Brown ◽  
...  

Background and purpose Microstructure imaging with advanced diffusion MRI (dMRI) techniques have shown increased sensitivity and specificity to microstructural changes in various disease and injury models. Oscillating gradient spin echo (OGSE) dMRI, implemented by varying the oscillating gradient frequency, and microscopic anisotropy (μA) dMRI, implemented via tensor valued diffusion encoding, may provide additional insight by increasing sensitivity to smaller spatial scales and disentangling fiber orientation dispersion from true microstructural changes, respectively. The aims of this study were to characterize the test-retest reproducibility of in vivo OGSE and μA dMRI metrics in the mouse brain at 9.4 Tesla and provide estimates of required sample sizes for future investigations. Methods Twelve adult C57Bl/6 mice were scanned twice (5 days apart). Each imaging session consisted of multifrequency OGSE and μA dMRI protocols. Metrics investigated included μA, linear diffusion kurtosis, isotropic diffusion kurtosis, and the diffusion dispersion rate (Λ), which explores the power-law frequency dependence of mean diffusivity. The dMRI metric maps were analyzed with mean region-of-interest (ROI) and whole brain voxel-wise analysis. Bland-Altman plots and coefficients of variation (CV) were used to assess the reproducibility of OGSE and μA metrics. Furthermore, we estimated sample sizes required to detect a variety of effect sizes. Results Bland-Altman plots showed negligible biases between test and retest sessions. ROI-based CVs revealed high reproducibility for most metrics (CVs < 15%). Voxel-wise CV maps revealed high reproducibility for μA (CVs ~ 10%), but low reproducibility for OGSE metrics (CVs ~ 50%). Conclusion Most of the μA dMRI metrics are reproducible in both ROI-based and voxel-wise analysis, while the OGSE dMRI metrics are only reproducible in ROI-based analysis. Given feasible sample sizes (10–15), μA metrics and OGSE metrics may provide sensitivity to subtle microstructural changes (4–8%) and moderate changes (> 6%), respectively.


2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
A Das ◽  
K Kelly ◽  
M Aldred ◽  
I Teh ◽  
CK Stoeck ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Heart Research UK Background Diffusion tensor cardiac magnetic resonance (DT-CMR) imaging allows for characterising myocardial microstructure in-vivo using mean diffusivity (MD), fractional anisotropy (FA), secondary eigenvector angle (E2A) and helix angle (HA) maps. Following myocardial infarction (MI), alterations in MD, FA and HA proportions have previously been reported. E2A depicts the contractile state of myocardial sheetlets, however the behaviour of E2A in infarct segments, and all DTI markers in areas of microvascular obstruction (MVO) is also not fully understood.  Purpose We performed spin echo DTI in patients following ST-elevation MI (STEMI) in order to investigate acute changes in DTI parameters in remote and infarct segments both with and without MVO. Method Twenty STEMI patients (16 men, 4 women, mean age 59) had acute (5 ± 2d) 3T CMR scans. CMR protocol included: second order motion compensated (M012) free-breathing spin echo DTI (3 slices, 18 diffusion directions at b-values 100s/mm2[3], 200s/mm2[3] and 500s/mm2[12], reconstructed resolution was 1.66x1.66x8mm); cine and late gadolinium enhancement (LGE) imaging. Average MD, FA, E2A HA parameters were calculated on a  16 AHA segmental level. HA maps were described by dividing values into left-handed HA (LHM, -90° &lt; HA &lt; -30°), circumferential HA (CM, -30° &lt; HA &lt; 30°), and right-handed HA (RHM, 30° &lt; HA &lt; 90°) and reported as relative proportions. Segments were defined as infarct (positive for LGE) and remote (opposite to the infarct).  Results DTI acquisition was successful in all patients (acquisition time 13 ± 5mins). Ten patients had evidence of MVO on LGE images. MD was significantly higher in infarct regions in comparison to remote; MVO-ve infarct segments had significantly higher MD than MVO + ve infarct segments (MD remote= 1.46 ± 0.12x10-3mm2/s, MD MVO + ve = 1.59 ± 0.12x10-3mm2/s, MD MVO-ve  = 1.75 ± 0.12x10-3mm2/s, ANOVA p &lt; 0.01). FA was reduced in infarct segments in comparison to remote; MVO-ve infarct segments had significantly lower FA than MVO + ve infarct segments (FAremote= 0.37 ± 0.02, FA MVO + ve = 0.31 ± 0.02 x 10-3mm2/s, MD MVO-ve =0.25 ± 0.02, ANOVA p &lt; 0.01). E2A values were significantly lower in infarct segments compared to remote; MVO + ve infarct segments had significantly lower values than MVO-ve. (E2A remote= 57.4 ± 5.2°, E2A MVO-ve = 46.8 ± 2.5°, E2A MVO + ve = 36.8 ± 3.1°, ANOVA p &lt; 0.001). RHM% (corresponding to subendocardium) was significantly lower in infarct segments compared to remote; MVO + ve infarct segments had significantly lower RHM% than MVO-ve. (RHM remote= 37 ± 3%, RHM RHM MVO-ve= 28 ± 7%, MVO + ve= 8 ± 5%, ANOVA p &lt; 0.001). Conclusion The presence of MVO results in a decrease in MD and increase in FA in comparison to surrounding infarct segments. However, the reduction in E2A and right-handed myocytes on HA in infarct segments is further exacerbated by the presence of MVO. Further study is required to investigate the underlying mechanisms for such alterations in signal intensity. Abstract Figure. A case of transmural septal MI with MVO


2021 ◽  
Author(s):  
Chiara Maffei ◽  
Christine Lee ◽  
Michael Planich ◽  
Manisha Ramprasad ◽  
Nivedita Ravi ◽  
...  

The development of scanners with ultra-high gradients, spearheaded by the Human Connectome Project, has led to dramatic improvements in the spatial, angular, and diffusion resolution that is feasible for in vivo diffusion MRI acquisitions. The improved quality of the data can be exploited to achieve higher accuracy in the inference of both microstructural and macrostructural anatomy. However, such high-quality data can only be acquired on a handful of Connectom MRI scanners worldwide, while remaining prohibitive in clinical settings because of the constraints imposed by hardware and scanning time. In this study, we first update the classical protocols for tractography-based, manual annotation of major white-matter pathways, to adapt them to the much greater volume and variability of the streamlines that can be produced from today's state-of-the-art diffusion MRI data. We then use these protocols to annotate 42 major pathways manually in data from a Connectom scanner. Finally, we show that, when we use these manually annotated pathways as training data for global probabilistic tractography with anatomical neighborhood priors, we can perform highly accurate, automated reconstruction of the same pathways in much lower-quality, more widely available diffusion MRI data. The outcomes of this work include both a new, comprehensive atlas of WM pathways from Connectom data, and an updated version of our tractography toolbox, TRActs Constrained by UnderLying Anatomy (TRACULA), which is trained on data from this atlas. Both the atlas and TRACULA are distributed publicly as part of FreeSurfer. We present the first comprehensive comparison of TRACULA to the more conventional, multi-region-of-interest approach to automated tractography, and the first demonstration of training TRACULA on high-quality, Connectom data to benefit studies that use more modest acquisition protocols.


2020 ◽  
Author(s):  
Fardin Nabizadeh ◽  
Seyed Behnamedin Jameie ◽  
Saghar Khani ◽  
Aida Rezaei ◽  
Fatemeh Ranjbaran ◽  
...  

Abstract Alzheimer’s Disease (AD) is characterized by cognitive impairments and memory difficulties, which hinder daily activities and lead to personal and behavioral problems. In recent years, blood-based biomarkers like plasma phosphorylated tau protein at threonine 181 (p tau 181) emerged as new tools and showed sufficient power in detecting AD patients from healthy people. Here we investigate the correlation between p tau 181 and white matter microstructural changes in AD. We add 41 patients diagnosed with Alzheimer’s, 119 patients with mild cognitive impairments and 43 healthy controls with baseline plasma p tau 181 level and DTI values for each region of interest from the ADNI database. The analysis revealed that the plasma level of p tau 181 could predict changes of MD (Mean Diffusivity), RD (Radial Diffusivity), DA (Axial Diffusivity) and FA (Fractional Anisotropy) parameters in widespread regions and there is a significant association between white matter pathway alteration in different regions and p tau 181 plasma measurements within each group. In conclusion, our findings showed that plasma p tau 181 levels are associated with cellular and molecular changes in AD, which enhance the biomarkers for diagnostic procedures and support the application of plasma p tau 181 as a biomarker for white matter changes and neurodegeneration. Longitudinal studies are also necessary for proving the efficacy of these biomarkers and predicting the role in structural changes.


2020 ◽  
Author(s):  
Fardin Nabizadeh ◽  
Seyed Behnamedin Jameie ◽  
Saghar Khani ◽  
Aida Rezaei ◽  
Niloofar Deravi

Abstract Alzheimer’s Disease (AD) is characterized by cognitive impairments and memory difficulties, which cause daily activities, personal and behavioural problems. In recent years blood-based biomarkers like plasma phosphorylated tau protein at threonine 181 (p tau 181) emerged as new tools and showed a sufficient power in detecting AD patients from healthy people. Here we investigate the correlation between p tau 181 and white matter microstructural changes in AD. We add 41 Alzheimer diagnosed patients, 155 participants with mild cognitive impairments and 43 healthy controls with baseline plasma p tau 181 level and DTI values for each region of interest from the ADNI database. The analysis revealed that the plasma level of p tau 181 could predict changes of MD( Mean Diffusivity), RD(Radial Diffusivity), DA(Axial Diffusivity) and FA(Fractional Anisotropy) parameters in widespread regions and there is a significant association between white matter pathways alteration in different regions and p tau 181 plasma measurement within each group. In conclusion, our findings showed that plasma p tau 181 levels are associated with cellular and molecular changes in AD, which enhance this biomarker's for diagnostic procedures and support the application of plasma p tau 181 as a biomarker for white matter changes and neurodegeneration. Longitudinal studies are also necessary to prove the efficacy of these biomarkers and predicting role in structural changes.


2016 ◽  
Author(s):  
Lee B Reid ◽  
Martin V Sale ◽  
Ross Cunnington ◽  
Jason B Mattingley ◽  
Stephen E Rose

AbstractWe have reported reliable changes in behaviour, brain structure and function in 24 healthy right-handed adults who practiced a finger-thumb opposition sequence task with their left hand for 10 mins daily, over four weeks. Here we extend these findings by employing diffusion MRI to investigate white-matter changes in the corticospinal tract, basal-ganglia, and connections of the dorsolateral prefrontal cortex. Twenty-three participant datasets were available with pre-training and post-training scans. Task performance improved in all participants (mean: 52.8%, SD: 20.0%; group p<0.01 FWE) and widespread microstructural changes were detected across the motor system of the ‘trained’ hemisphere. Specifically, region-of-interest based analyses of diffusion MRI (n=21) revealed significantly increased fractional anisotropy in the right caudate nucleus (4.9%; p<0.05 FWE), and decreased mean diffusivity in the left nucleus accumbens (-1.3%; p<0.05 FWE). Diffusion MRI tractography (n=22), seeded by sensorimotor cortex fMRI activation, also revealed increased fractional anisotropy in the right corticomotor tract (mean 3.28%; p<0.05 FWE) predominantly reflecting decreased radial diffusivity. These changes were consistent throughout the entire length of the tract. The left corticomotor tract did not show any changes. FA also increased in white matter connections between the right middle frontal gyrus and both right caudate nucleus (17/22 participants; p<0.05 FWE) and right supplementary motor area (18/22 participants; p<0.05 FWE). Equivalent changes in FA were not seen in the left (‘non-trained’) hemisphere. In combination with our functional and structural findings, this study provides detailed, multifocal evidence for widespread neuroplastic changes in the human brain resulting from motor training.


2020 ◽  
Author(s):  
Erica F. Barry ◽  
John P. Loftus ◽  
Wen-Ming Luh ◽  
Mony J. de Leon ◽  
Sumit N. Niogi ◽  
...  

AbstractWhite matter dysfunction and degeneration have been a topic of great interest in healthy and pathological aging. While ex vivo studies have investigated age-related changes in canines, little in vivo canine aging research exists. Quantitative diffusion MRI such as diffusion tensor imaging (DTI) has demonstrated aging and neurodegenerative white matter changes in humans. However, this method has not been applied and adapted in vivo to canine populations. This study aimed to test the hypothesis that white matter diffusion changes frequently reported in human aging are also found in aged canines. The study used Tract Based Spatial Statistics (TBSS) and a region of interest (ROI) approach to investigate age related changes in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AxD) and radial diffusivity (RD). The results show that, compared to younger animals, aged canines have significant decreases in FA in parietal and temporal regions as well as the corpus callosum and fornix. Additionally, AxD decreases were observed in parietal, frontal and midbrain regions. Similarly, an age-related increase in RD was observed in the right parietal lobe while MD decreases were found in the midbrain. These findings suggest that canine samples offer a model for healthy human aging as they exhibit similar white matter diffusion tensor changes with age.


2018 ◽  
Vol 39 (7) ◽  
pp. 1336-1348 ◽  
Author(s):  
Dan Wu ◽  
Lee J Martin ◽  
Frances J Northington ◽  
Jiangyang Zhang

The recently developed oscillating-gradient diffusion MRI (OG-dMRI) technique extends our ability to examine brain structures at different spatial scales. In this study, we investigated the sensitivity of OG-dMRI in detecting cellular and subcellular structural changes in a mouse model of neonatal hypoxia ischemia (HI). Neonatal mice received unilateral HI injury or sham injury at postnatal day 10, followed by in vivo T2-weighted and diffusion MRI of the brains at 3–6 h and 24 h after HI. Apparent diffusion coefficient (ADC) maps were acquired using conventional pulsed-gradient dMRI (PG-dMRI) and OG-dMRI with oscillating frequencies from 50 to 200 Hz. Pathology at cellular and subcellular levels was evaluated using neuronal, glial, and mitochondrial markers. We found significantly higher rates of ADC increase with oscillating frequencies (Δ fADC) in the ipsilateral edema region, compared to the contralateral side, starting as early as 3 h after HI. Even in injured regions that showed no apparent change in PG-ADC or pseudo-normalized PG-ADC measurements, Δ fADC remained significantly elevated. Histopathology showed swelling of sub-cellular structures in these regions with no apparent whole-cell level change. These results suggest that OG-dMRI is sensitive to subcellular structural changes in the brain after HI and is less susceptible to pseudo-normalization than PG-dMRI.


2021 ◽  
Vol 22 (Supplement_2) ◽  
Author(s):  
A Das ◽  
C Kelly ◽  
I Teh ◽  
C Stoeck ◽  
S Kozerke ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Background The microstructural changes following myocardial infarction (MI) can be characterised in-vivo with cardiac diffusion tensor imaging (cDTI) imaging, using mean diffusivity (MD), fractional anisotropy (FA), secondary eigenvector angle (E2A) and helix angle (HA) maps. In this study, we use cDTI to explore the microstructural differences between subendocardial and transmural chronic infarct segments. Method Twenty STEMI patients (15 men, 5 women, mean age 59) underwent 3T CMR scan at 3 months following presentation (mean interval 107 ± 18 days). Scan protocol included: second order motion compensated (M012) free-breathing spin echo DTI (3 slices, 18 diffusion directions at b-values 100s/mm2[3], 200s/mm2[3] and 500s/mm2[12], acquired resolution was 2.20x2.27x8mm3; cine gradient echo and LGE imaging. Average MD, FA, E2A and HA parameters were calculated on a 16-AHA-segmental level. HA maps were described by dividing values into left-handed HA (LHM, -90° &lt; HA &lt; -30°), circumferential HA (CM, -30° &lt; HA &lt; 30°), and right-handed HA (RHM, 30° &lt; HA &lt; 90°) and reported as relative proportions. Infarct segments were identified using LGE; patients were categorised according to the maximal transmurality of their infarct segments, into subendocardial (&lt;50% LGE) or transmural (&gt;50% LGE) MI. Results DTI acquisition was successful in all patients (acquisition time 13 ± 5mins). Ten patients had transmural MI. The results are shown in table 1. Transmurally infarcted segments had significantly lower FA (FA subendocardial MI = 0.27 ± 0.04, FA transmural MI = 0.23 ± 0.02, p &lt; 0.01), lower E2A (E2A subendocardial MI = 47 ± 7°, E2A transmural MI = 38 ± 6°, p &lt; 0.01) and lower proportions of right-handed cardiomyocytes (RHM subendocardial MI = 21 ± 5%, RHM transmural MI = 14 ± 5%, p &lt; 0.01) than subendocardial infarct segments.  Conclusion Compared to subendocardial MI segments, the diffusion of water molecules is more isotropic in transmurally infarcted myocardium as evidenced by lower FA values, signifying increased structural disarray. The significantly lower E2A values suggest that laminar sheetlets of transmural infarct segments remain fixed at shallower angles during systole and are unable to reach their usual contractile configuration. The lower proportions of RHM on HA maps highlight the significantly greater loss of subendocardial cardiomyocytes in transmural infarct segments. Further studies are required to assess if these segmental changes can be predictive of long-term LV remodelling.


2018 ◽  
Author(s):  
Kilian Hett ◽  
Vinh-Thong Ta ◽  
Gwenaëlle Catheline ◽  
Thomas Tourdias ◽  
José V. Manjón ◽  
...  

ABSTRACTNumerous studies have proposed biomarkers based on magnetic resonance imaging (MRI) to detect and predict the risk of evolution toward Alzheimer’s disease (AD). While anatomical MRI captures structural alterations, studies demonstrated the ability of diffusion MRI to capture microstructural modifications at an earlier stage. Several methods have focused on hippocampus structure to detect AD. To date, the patch-based grading framework provides the best biomarker based on the hippocampus. However, this structure is complex since the hippocampus is divided into several heterogeneous subfields not equally impacted by AD. Former in-vivo imaging studies only investigated structural alterations of these subfields using volumetric measurements and microstructural modifications with mean diffusivity measurements. The aim of our work is to study the efficiency of hippocampal subfields compared to the whole hippocampus structure with a multimodal patch-based framework that enables to capture subtler structural and microstructural alterations. To this end, we analyze the significance of the different hippocampal subfields for AD diagnosis and prognosis with volumetric, diffusivity measurements and a novel multimodal patch-based grading framework that combines structural and diffusion MRI. The experiments conducted in this work showed that the whole hippocampus provides the most discriminant biomarkers for advanced AD detection while biomarkers applied into subiculum obtain the best results for AD prediction, improving by 2% the accuracy compared to the whole hippocampus.


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