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

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0255711
Author(s):  
Naila Rahman ◽  
Kathy Xu ◽  
Mohammad Omer ◽  
Matthew D. Budde ◽  
Arthur Brown ◽  
...  
Keyword(s):  
Diffusion Mri ◽  
Spin Echo ◽  
Spatial Scales ◽  
Mean Diffusivity ◽  
Sample Sizes ◽  
High Reproducibility ◽  
Linear Diffusion ◽  
Microstructural Changes ◽  
Diffusion Kurtosis

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.

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 ◽  
...  
Keyword(s):  
Diffusion Mri ◽  
Spin Echo ◽  
Spatial Scales ◽  
Mean Diffusivity ◽  
Region Of Interest ◽  
Sample Sizes ◽  
High Reproducibility ◽  
Microstructural Changes ◽  
Increased Sensitivity

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).

The effect of microvascular obstruction on the myocardial microstructure: a diffusion tensor imaging study

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
A Das ◽  
K Kelly ◽  
M Aldred ◽  
I Teh ◽  
CK Stoeck ◽  
...  
Keyword(s):  
Microvascular Obstruction ◽  
Diffusion Tensor ◽  
Spin Echo ◽  
Mean Diffusivity ◽  
Imaging Study ◽  
Free Breathing ◽  
Helix Angle ◽  
Acquisition Time ◽  
Heart Research

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

scholarly journals Diffusion MRI Changes in the Healthy Aging Canine Brain

2020 ◽  
Author(s):  
Erica F. Barry ◽  
John P. Loftus ◽  
Wen-Ming Luh ◽  
Mony J. de Leon ◽  
Sumit N. Niogi ◽  
...  
Keyword(s):  
White Matter ◽  
Diffusion Mri ◽  
Healthy Aging ◽  
Parietal Lobe ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Human Aging ◽  
Age Related ◽  
Age Related Changes

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.

scholarly journals Oscillating-gradient diffusion magnetic resonance imaging detects acute subcellular structural changes in the mouse forebrain after neonatal hypoxia-ischemia

2018 ◽  
Vol 39 (7) ◽  
pp. 1336-1348 ◽  
Author(s):  
Dan Wu ◽  
Lee J Martin ◽  
Frances J Northington ◽  
Jiangyang Zhang
Keyword(s):  
Diffusion Mri ◽  
Structural Changes ◽  
Spatial Scales ◽  
Brain Structures ◽  
Contralateral Side ◽  
Neonatal Hypoxia ◽  
Gradient Diffusion ◽  
Hypoxia Ischemia ◽  
Apparent Diffusion

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.

scholarly journals Neurobiological underpinnings of rapid white matter plasticity during intensive reading instruction

2020 ◽  
Author(s):  
Elizabeth Huber ◽  
Aviv Mezer ◽  
Jason D. Yeatman
Keyword(s):  
White Matter ◽  
Reading Instruction ◽  
Diffusion Mri ◽  
Large Scale ◽  
Mean Diffusivity ◽  
Quantitative Mri ◽  
Diffusion Kurtosis Imaging ◽  
Control Group ◽  
Intensive Reading ◽  
Diffusion Kurtosis

AbstractHuman white matter is remarkably plastic. Yet it is challenging to infer the biological underpinnings of this plasticity using non-invasive measurements like diffusion MRI. Here we capitalize on metrics derived from diffusion kurtosis imaging (DKI) to interpret previously reported changes in mean diffusivity throughout the white matter during an 8-week, intensive reading intervention. We then use an independent quantitative MRI measurement of R1 (1/T1 relaxation time) in the same white matter regions; since R1 closely tracks variation in myelin content, it provides complementary information about white matter microstructure. Behavioral measures, multi-shell diffusion MRI data, and quantitative T1 data were collected at regular intervals during the intervention in a group of 33 children with reading difficulties (7-12 years old), and over the same period in an age-matched non-intervention control group. Changes in DKI parameters modeled over the intervention were consistent with increased hindrance in the extra-axonal space, rather than a large-scale change in axon density and/or myelination. Supporting this interpretation, analysis of R1 values did not suggest a change in myelin, although R1 estimates were correlated with individual differences in reading skill. Together, these results suggest that large-scale changes in diffusivity observed over a short timescale during an intensive educational experience are most likely to reflect changes occurring in the extra-axonal space, in line with recent work highlighting the role of glial cells in experience-dependent plasticity and learning.

scholarly journals Microstructural characteristics of chronic infarct segments assessed using diffusion tensor imaging

2021 ◽  
Vol 22 (Supplement_2) ◽  
Author(s):  
A Das ◽  
C Kelly ◽  
I Teh ◽  
C Stoeck ◽  
S Kozerke ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
Diffusion Tensor ◽  
Spin Echo ◽  
Mean Diffusivity ◽  
Free Breathing ◽  
Helix Angle ◽  
Acquisition Time ◽  
Transmural Infarct ◽  
Subendocardial Mi

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.

scholarly journals Multimodal Hippocampal Subfield Grading For Alzheimer’s Disease Classification

2018 ◽  
Author(s):  
Kilian Hett ◽  
Vinh-Thong Ta ◽  
Gwenaëlle Catheline ◽  
Thomas Tourdias ◽  
José V. Manjón ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Diffusion Mri ◽  
Mean Diffusivity ◽  
Disease Classification ◽  
Structural Alterations ◽  
Hippocampal Subfields ◽  
Microstructural Alterations ◽  
Diffusivity Measurements

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.

scholarly journals Diffusion tensor cardiovascular magnetic resonance detects altered myocardial microstructure in patients with acute st-elevation myocardial infarction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Rajakulasingam ◽  
S Nielles-Vallespin ◽  
P.F Ferreira ◽  
A.D Scott ◽  
Z Khalique ◽  
...  
Keyword(s):  
Cardiovascular Magnetic Resonance ◽  
Magnetic Resonance ◽  
Diffusion Tensor ◽  
Research Training ◽  
Mean Diffusivity ◽  
Funding Source ◽  
Microstructural Changes ◽  
Acute Stemi ◽  
Training Fellowship

Abstract Background Diffusion Tensor Cardiovascular Magnetic Resonance (DT-CMR) can quantify metrics of tissue integrity (mean diffusivity [MD] and fractional anisotropy [FA]) and changes in laminar microstructures (sheetlets), which reorientate from more wall-parallel in diastole (DIA) towards wall-perpendicular in systole (SYS) as the myocardium thickens, quantified by E2 angle [E2A]. Microstructural changes after STEMI may provide new insights into adverse LV remodelling and risk stratification. Methods In vivo DT-CMR was performed 3–5 days after PPCI for first presentation STEMI (N=19, mean age 57±9, 79% male). DT-CMR was acquired in 2 short-axes (SYS & DIA) using a STEAM-EPI sequence. 12 segment analysis of MD, FA, E2A and E2A mobility (ΔE2A = E2ASYS − E2ADIA) was performed. Infarct (INF) segments were defined as &gt;25% LGE, adjacent (ADJ, located contiguous to INF) and remote (REM, all other segments). Wilcoxon signed rank tests were used with threshold P&lt;0.017 (Bonferroni corrected). Results See Table. MD in both SYS and DIA was significantly higher in INF and ADJ regions compared to REM. FA in both SYS and DIA was lower in the INF and ADJ compared to REM. E2ADIA was higher in INF, indicating a more wall-perpendicular orientation of sheetlets, compared to ADJ and REM zones. E2ASYS in INF was significantly reduced, indicating a more wall-parallel orientation of sheetlets, compared to ADJ and REM regions, resulting in significantly reduced sheetlet mobility (ΔE2A). Conclusions Microstructural changes can be detected after acute STEMI by in vivo DT-CMR. Zonal changes in MD and FA may suggest loss of barriers to water diffusion and altered cardiomyocyte organisation, respectively. We provide the first report of reduced sheetlet mobility after acute STEMI in INF. Ongoing work is evaluating the mechanisms and prognostic importance of altered sheetlet mobility after STEMI. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation Clinical Research Training Fellowship

The neurophysiology of ketamine: an integrative review

2020 ◽  
Vol 31 (5) ◽  
pp. 457-503
Author(s):  
Rebecca McMillan ◽  
Suresh D. Muthukumaraswamy
Keyword(s):  
Spatial Scales ◽  
Integrative Review ◽  
Acute Effects ◽  
Future Work

AbstractThe drug ketamine has been extensively studied due to its use in anaesthesia, as a model of psychosis and, most recently, its antidepressant properties. Understanding the physiology of ketamine is complex due to its rich pharmacology with multiple potential sites at clinically relevant doses. In this review of the neurophysiology of ketamine, we focus on the acute effects of ketamine in the resting brain. We ascend through spatial scales starting with a complete review of the pharmacology of ketamine and then cover its effects on in vitro and in vivo electrophysiology. We then summarise and critically evaluate studies using EEG/MEG and neuroimaging measures (MRI and PET), integrating across scales where possible. While a complicated and, at times, confusing picture of ketamine’s effects are revealed, we stress that much of this might be caused by use of different species, doses, and analytical methodologies and suggest strategies that future work could use to answer these problems.

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