DTI Metrics Research Articles

Assessing changes in brain structure in new-onset children with acute lymphoblastic leukemia.

Brain structure injury was presented in acute lymphoblastic leukemia (ALL) after treatment; however, its alterations in new-onset stage are still unclear. We aim to explore white matter (WM) and grey matter (GM) alterations using surface-based morphometry (SBM) and tract-based spatial statistics (TBSS) in new-onset pediatric ALL. Thirty-five ALL and 33 typically developing (TD) children were prospectively recruited and underwent three-dimensional T1-weighted and diffusion tensor (DTI) imaging. DTI metrics, cortical GM features, anddeep GM nuclei volume were compared between groups differences. In ALL, the only increased FA in the body of corpus callosum (PFWE-corrected = 0.023) and left superior corona radiata (PFWE-corrected = 0.045) were presented. Relative to TDs, pediatric ALL presented a significant decrease in cortical surface area (CSA), thickness (CT), and volume in orbital gyri, supramarginal gyrus, middle temporal gyrus, and superior temporal gyrus (all CWP = 0.01). Additionally, increased CT and CSA were found in lingual gyrus and left sulcus intermedius primus, respectively (all CWP = 0.01). Smaller volumes in pediatric ALL were observed in bilateral thalamus, caudate, hippocampus, and right putamen (PFDR-corrected < 0.05). Widespread brain structural abnormalities were found in new-onset pediatric ALL, which suggest disease itself can cause brain structural injury. This study revealed the altered white matter integrity and gray matter morphology characteristics in childhood acute lymphoblastic leukemia on new-onset stage. It is suggested that there may be structural impairment before chemotherapy. MRI is a sensitive way for early detection on brain structural damage in childhood acute lymphoblastic leukemia.

DTI fiber-tracking parameters adjacent to gliomas: the role of tract irregularity value in operative planning, resection, and outcome.

The goal of glioma surgery is maximal tumor resection associated with minimal post-operative morbidity. Diffusion tensor imaging-tractography/fiber tracking (DTI-FT) is a valuable white-matter (WM) visualization tool for diagnosis and surgical planning. Still, it assumes a descriptive role since the main DTI metrics and parameters showed several limitations in clinical use. New applications and quantitative measurements were recently applied to describe WM architecture that surround the tumor area. The brain adjacent tumor area (BAT) is defined as the region adjacent to the gross tumor volume, which contains signal abnormalities on T2-weighted or FLAIR sequences. The DTI-FT analysis of the BAT can be adopted as predictive values and a guide for safe tumor resection. This is an observational prospective study on an extensive series of glioma patients who performed magnetic resonance imaging (MRI) with pre-operative DTI-FT analyzed on the BAT by two different software. We examined DTI parameters of Fractional anisotropy (FA mean, min-max), Mean diffusivity (MD), and the shape-metric "tract irregularity" (TI) grade, comparing it with the surgical series' clinical, radiological, and outcome data. The population consisted of 118 patients, with a mean age of 60.6 years. 82 patients suffering from high-grade gliomas (69.5%), and 36 from low-grade gliomas (30.5%). A significant inverse relationship exists between the FA mean value and grading (p = 0.001). The relationship appears directly proportional regarding MD values (p = 0.003) and TI values (p = 0.005). FA mean and MD values are susceptible to significant variations with tumor and edema volume (p = 0.05). TI showed an independent relationship with grading regardless of tumor radiological features and dimensions, with a direct relationship with grading, ki67% (p = 0,05), PFS (p < 0.001), and EOR (p < 0.01). FA, MD, and TI are useful predictive measures of the clinical behavior of glioma, and TI could be helpful for tumor grading identification and surgical planning.

Effect of metacognitive interpersonal therapy on brain structural connectivity in borderline personality disorder: Results from the CLIMAMITHE randomized clinical trial

BackgroundRecently, we showed that Metacognitive Interpersonal Therapy (MIT) is effective in improving clinical symptoms in borderline personality disorder (BPD). Here, we investigated whether the effect of MIT on clinical features is associated to microstructural changes in brain circuits supporting core BPD symptoms. MethodsForty-seven BPD were randomized to MIT or structured clinical management, and underwent a clinical assessment and diffusion-weighted imaging before and after the intervention. Fractional anisotropy (FA), mean, radial, and axial diffusivities maps were computed using FSL toolbox. Microstructural changes were assessed (i) voxel-wise, with tract based spatial statistics (TBSS) and (ii) ROI-wise, in the triple network system (default mode, salience, and executive control networks). The effect of MIT on brain microstructure was assessed with paired tests using FSL PALM (voxel-wise), Linear Mixed-Effect Models or Generalized Linear Mixed Models (ROI-wise). Associations between microstructural and clinical changes were explored with linear regression (voxel-wise) and correlations (ROI-wise). ResultsThe voxel-wise analysis showed that MIT was associated with increased FA in the bilateral thalamic radiation and left associative tracts (p < .050, family-wise error rate corrected). At network system level, MIT increased FA and both interventions reduced AD in the executive control network (p = .05, uncorrected). LimitationsThe DTI metrics can't clarify the nature of axonal changes. ConclusionsOur results indicate that MIT modulates brain structural connectivity in circuits related to associative and executive control functions. These microstructural changes may denote activity-dependent plasticity, possibly representing a neurobiological mechanism underlying MIT effects. Trial registrationClinicalTrials.govNCT02370316 (https://clinicaltrials.gov/study/NCT02370316).

Effects of Mixed Metal Exposure on MRI Metrics in Basal Ganglia.

Welding fumes contain various metals. Past studies, however, mainly focused on Manganese (Mn)-related neurotoxicity. This study investigated welding-related mixed metal exposure effects on MRI metrics in the basal ganglia (BG) and their dose-response relationship. Subjects with (N = 23) and without (N = 24) a welding exposure history were examined. Metal exposure was estimated with exposure history questionnaire and whole blood metal levels. T1 (weighted-intensity and relaxation time; estimates of brain Mn accumulation), diffusion tensor imaging [Axial (AD), mean (MD), radial diffusivity (RD), and fractional anisotropy (FA); estimates of microstructural differences] metrics in BG [caudate nucleus, putamen, and globus pallidus (GP)] and voxel-based morphometry (for volume) were examined and related with metal exposure measures. Compared to controls, welders showed higher GP R1 (1/T1; p = 0.034) but no differences in blood metal and T1-weighted (T1W) values in any ROIs (p's > 0.120). They also had higher AD and MD values in the GP (p's < 0.033) but lower FA values in the putamen (p = 0.039) with no morphologic differences. In welders, higher blood Mn and Vanadium (V) levels predicted higher BG R1 and T1W values (p's < 0.015). There also were significant overall metal mixture effects on GP T1W and R1 values. Moreover, GP AD and MD values showed non-linear associations with BG T1W values: They increased with increasing T1W values only above certain threshold of T1 values. The current findings suggest that Mn and V individually but also metal mixtures jointly predict GP T1 signals that may in turn contribute to altered DTI metrics in the BG after certain exposure threshold levels.

In vivo cardiac diffusion tensor imaging on an MR system featuring ultrahigh performance gradients with 200 mT/m maximum gradient strength.

Our aim is to assess the potential of an MR system with ultrahigh performance gradients (200 mT/m maximum gradient strength) to address two interrelated challenges in cardiac DTI: low SNR and sensitivity to bulk motion. Imaging was performed in 20 healthy volunteers, two patients, and one swine post-myocardial infarction. The impact of maximum gradient strength was assessed with spin echo cardiac DTI featuring second-order motion compensation and varying maximum system gradient strengths (40, 80, 200 mT/m). Motion compensation requirements at 200 mT/m were assessed with sequences featuring zeroth-, first-, and second-order motion compensation. SNR, mean diffusivity, fractional anisotropy, helix angle transmurality, and secondary eigenvector angle in the left ventricle were compared. Increasing maximum system gradient strength from 40 and 80 mT/m to 200 mT/m increased SNR of b = 500 s/mm2 images by 150% and 40% due to reductions in TE. Observed improvements in DTI metrics included reduction in variance in mean diffusivity and helix angle transmurality across healthy volunteers, improved visualization of myocardial borders and delineation of suspected scar. Whereas second-order motion compensation acquisitions were robust to motion-induced signal dropout, zeroth- and first-order motion compensation acquisitions suffered from severe signal loss and localized signal voids, respectively. Ultrahigh performance gradients (200 mT/m) enable high SNR DWIs of the heart and resultant improvements in diffusion tensor metrics. Despite reduced diffusion-encoding duration, second-order motion compensation is required to overcome sensitivity to cardiac motion.

Anisotropy component of DTI reveals long-term neuroinflammation following repetitive mild traumatic brain injury in rats

BackgroundThis study aimed to investigate the long-term effects of repetitive mild traumatic brain injury (rmTBI) with varying inter-injury intervals by measuring diffusion tensor metrics, including mean diffusivity (MD), fractional anisotropy (FA), and diffusion magnitude (L) and pure anisotropy (q).MethodsEighteen rats were randomly divided into three groups: short-interval rmTBI (n = 6), long-interval rmTBI (n = 6), and sham controls (n = 6). MD, FA, L, and q values were analyzed from longitudinal diffusion tensor imaging at days 50 and 90 after rmTBI. Immunohistochemical staining against neurons, astrocytes, microglia, and myelin was performed. Analysis of variance, Pearson correlation coefficient, and simple linear regression model were used.ResultsAt day 50 post-rmTBI, lower cortical FA and q values were shown in the short-interval group (p ≤ 0.038). In contrast, higher FA and q values were shown for the long-interval group (p ≤ 0.039) in the corpus callosum. In the ipsilesional external capsule and internal capsule, no significant changes were found in FA, while lower L and q values were shown in the short-interval group (p ≤ 0.028) at day 90. The q values in the external capsule and internal capsule were negatively correlated with the number of microglial cells and the total number of astroglial cells (p ≤ 0.035).ConclusionTensor scalar measurements, such as L and q values, are sensitive to exacerbated chronic injury induced by rmTBI with shorter inter-injury intervals and reflect long-term astrogliosis induced by the cumulative injury.Relevance statementTensor scalar measurements, including L and q values, are potential DTI metrics for detecting long-term and subtle injury following rmTBI; in particular, q values may be used for quantifying remote white matter (WM) changes following rmTBI.Key PointsThe alteration of L and q values was demonstrated after chronic repetitive mild traumatic brain injury.Changing q values were observed in the impact site and remote WM.The lower q values in the remote WM were associated with astrogliosis.Graphical

White matter substrates underlying morphological awareness deficit in Chinese children with developmental dyslexia

BackgroundMorphological awareness (MA) deficit is strongly associated with Chinese developmental dyslexia (DD). However, little is known about the white matter substrates underlying the MA deficit in Chinese children with DD. MethodsIn the current study, 34 Chinese children with DD and 42 typical developmental (TD) children were recruited to complete a diffusion magnetic resonance imaging scan and cognitive tests for MA. We conducted linear regression to test the correlation between MA and DTI metrics, the structural abnormalities of the tracts related to MA, and the interaction effect of DTI metrics by group on MA. ResultsFirst, MA was significant related to the right inferior occipito-frontal fascicle (IFO) and inferior longitudinal fsciculus (ILF), the bilateral thalamo-occipital (T_OCC) and the left arcuate fasciculus (AF); second, compared to TD children, Chinese children with DD had lower axial diffusivity (AD) in the right IFO and T_OCC; third, there were significant interactions between metrics (fractional anisotropy (FA) and radial diffusivity (RD)) of the right IFO and MA in groups. The FA and RD of the right IFO were significantly associated with MA in children with DD but not in TD children. ConclusionIn conclusion, compared to TD children, Chinese children with DD had axonal degeneration not only in the ventral tract (the right IFO) but also the visuospatial tract (the right T_OCC) which were associated with their MA deficit. And Chinese MA involved not only the ventral tracts, but also the visuospatial pathway and dorsal tracts.

Locus coeruleus contrast and diffusivity metrics differentially relate to age and memory performance

Neurocognitive aging researchers are increasingly focused on the locus coeruleus, a neuromodulatory brainstem structure that degrades with age. With this rapid growth, the field will benefit from consensus regarding which magnetic resonance imaging (MRI) metrics of locus coeruleus structure are most sensitive to age and cognition. To address this need, the current study acquired magnetization transfer- and diffusion-weighted MRI images in younger and older adults who also completed a free recall memory task. Results revealed significantly larger differences between younger and older adults for maximum than average magnetization transfer-weighted contrast (MTC), axial than mean or radial single-tensor diffusivity (DTI), and free than restricted multi-compartment diffusion (NODDI) metrics in the locus coeruleus; with maximum MTC being the best predictor of age group. Age effects for all imaging modalities interacted with sex, with larger age group differences in males than females for MTC and NODDI metrics. Age group differences also varied across locus coeruleus subdivision for DTI and NODDI metrics, and across locus coeruleus hemispheres for MTC. Within older adults, however, there were no significant effects of age on MTC or DTI metrics, only an interaction between age and sex for free diffusion. Finally, independent of age and sex, higher restricted diffusion in the locus coeruleus was significantly related to better (lower) recall variability, but not mean recall. Whereas MTC has been widely used in the literature, our comparison between the average and maximum MTC metrics, inclusion of DTI and NODDI metrics, and breakdowns by locus coeruleus subdivision and hemisphere make important and novel contributions to our understanding of the aging of locus coeruleus structure.

A comparison of white matter microstructure and correlates with neuropsychological measures in younger and older adults.

With a globally aging population, there is a need to better understand how brain structure relates to function in healthy older and younger adults. 34 healthy participants divided into older (17; Mean = 70.9, SD = 5.4) and younger adults (17; Mean = 28.1, SD = 2.8) underwent diffusion-weighted imaging and neuropsychological assessment, including the California Verbal Learning Test 2nd Edition and the Trail Making Test (TMT-A and TMT-B). Differences in white matter microstructure for older and younger adults and the association between DTI metrics (fractional anisotropy, FA; mean diffusivity, MD) and cognitive performance were analyzed using tract-based spatial statistics (p < 0.05, corrected). Older adults had significantly lower FA and higher MD than younger adults in widespread brain regions. There was a significant negative correlation between executive function (TMT-B) and MD for older adults in the right superior/anterior corona radiata and the corpus callosum. No significant relationship was detected between DTI metrics and executive function in younger adults or with memory performance in either group. The findings underscore the need to examine brain-behaviour relationships as a function of age. Future studies should include comprehensive assessments in larger lifespan samples to better understand the aging brain.

Diffusion tensor imaging in anisotropic tissues: application of reduced gradient vector schemes in peripheral nerves

BackgroundIn contrast to the brain, fibers within peripheral nerves have distinct monodirectional structure questioning the necessity of complex multidirectional gradient vector schemes for DTI. This proof-of-concept study investigated the diagnostic utility of reduced gradient vector schemes in peripheral nerve DTI.MethodsThree-Tesla magnetic resonance neurography of the tibial nerve using 20-vector DTI (DTI20) was performed in 10 healthy volunteers, 12 patients with type 2 diabetes, and 12 age-matched healthy controls. From the full DTI20 dataset, three reduced datasets including only two or three vectors along the x- and/or y- and z-axes were built to calculate major parameters. The influence of nerve angulation and intraneural connective tissue was assessed. The area under the receiver operating characteristics curve (ROC-AUC) was used for analysis.ResultsSimplified datasets achieved excellent diagnostic accuracy equal to DTI20 (ROC-AUC 0.847–0.868, p ≤ 0.005), but compared to DTI20, the reduced models yielded mostly lower absolute values of DTI scalars: median fractional anisotropy (FA) ≤ 0.12; apparent diffusion coefficient (ADC) ≤ 0.25; axial diffusivity ≤ 0.96, radial diffusivity ≤ 0.07). The precision of FA and ADC with the three-vector model was closest to DTI20. Intraneural connective tissue was negatively correlated with FA and ADC (r ≥ -0.49, p < 0.001). Small deviations of nerve angulation had little effect on FA accuracy.ConclusionsIn peripheral nerves, bulk tissue DTI metrics can be approximated with only three predefined gradient vectors along the scanner’s main axes, yielding similar diagnostic accuracy as a 20-vector DTI, resulting in substantial scan time reduction.Relevance statementDTI bulk tissue parameters of peripheral nerves can be calculated with only three predefined gradient vectors at similar diagnostic performance as a standard DTI but providing a substantial scan time reduction.Key points• In peripheral nerves, DTI parameters can be approximated using only three gradient vectors.• The simplified model achieves a similar diagnostic performance as a standard DTI.• The simplified model allows for a significant acceleration of image acquisition.• This can help to introduce multi-b-value DTI techniques into clinical practice.Graphical

Macro- and microvascular contributions to cerebral structural alterations in patients with asymptomatic carotid artery stenosis

Atherosclerosis can underly internal carotid artery stenosis (ICAS), a major risk factor for ischemic stroke, as well as small vessel disease (SVD). This study aimed to investigate hemodynamics and structural alterations associated with SVD in ICAS patients. 28 patients with unilateral asymptomatic ICAS and 30 age-matched controls underwent structural (T1-/T2-weighted and diffusion tensor imaging [DTI]) and hemodynamic (pseudo-continuous arterial spin labeling and dynamic susceptibility contrast) magnetic resonance imaging. SVD-related alterations were assessed using free water (FW), FW-corrected DTI, and peak-width of skeletonized mean diffusivity (PSMD). Furthermore, cortical thickness, cerebral blood flow (CBF), and capillary transit time heterogeneity (CTH) were analyzed. Ipsilateral to the stenosis, cortical thickness was significantly decreased in the posterior dorsal cingulate cortex (p = 0.024) and temporal pole (p = 0.028). ICAS patients exhibited elevated PSMD (p = 0.005), FW (p < 0.001), and contralateral alterations in FW-corrected DTI metrics. We found significantly lateralized CBF (p = 0.011) and a tendency for lateralized CTH (p = 0.067) in the white matter (WM) related to ICAS. Elevated PSMD and FW may indicate a link between SVD and WM changes. Contralateral alterations were seen in FW-corrected DTI, whereas hemodynamic and cortical changes were mainly ipsilateral, suggesting SVD might influence global brain changes concurrent with ICAS-related hemodynamic alterations.

Reduced cross-scanner variability using vendor-agnostic sequences for single-shell diffusion MRI.

To reduce the inter-scanner variability of diffusion MRI (dMRI) measures between scanners from different vendors by developing a vendor-neutral dMRI pulse sequence using the open-source vendor-agnostic Pulseq platform. We implemented a standard EPI based dMRI sequence in Pulseq. We tested it on two clinical scanners from different vendors (Siemens Prisma and GE Premier), systematically evaluating and comparing the within- and inter-scanner variability across the vendors, using both the vendor-provided and Pulseq dMRI sequences. Assessments covered both a diffusion phantom and three human subjects, using standard error (SE) and Lin's concordance correlation to measure the repeatability and reproducibility of standard DTI metrics including fractional anisotropy (FA) and mean diffusivity (MD). Identical dMRI sequences were executed on both scanners using Pulseq. On the phantom, the Pulseq sequence showed more than a 2.5× reduction in SE (variability) across Siemens and GE scanners. Furthermore, Pulseq sequences exhibited markedly reduced SE in-vivo, maintaining scan-rescan repeatability while delivering lower variability in FA and MD (more than 50% reduction in cortical/subcortical regions) compared to vendor-provided sequences. The Pulseq diffusion sequence reduces the cross-scanner variability for both phantom and in-vivo data, which will benefit multi-center neuroimaging studies and improve the reproducibility of neuroimaging studies.

Diffusion tensor imaging metrics as natural markers of multiple sclerosis-induced brain disorders with a low Expanded Disability Status Scale score

Non-invasive and effective differentiation along with determining the degree of deviations compared to the healthy cohort is important in the case of various brain disorders, including multiple sclerosis (MS). Evaluation of the effectiveness of diffusion tensor metrics (DTM) in 3T DTI for recording MS-related deviations was performed using a time-acceptable MRI protocol with unique comprehensive detection of systematic errors related to spatial heterogeneity of magnetic field gradients. In a clinical study, DTMs were acquired in segmented regions of interest (ROIs) for 50 randomly selected healthy controls (HC) and 50 multiple sclerosis patients. Identical phantom imaging was performed for each clinical measurement to estimate and remove the influence of systematic errors using the b-matrix spatial distribution in the DTI (BSD-DTI) technique. In the absence of statistically significant differences due to age in healthy volunteers and patients with multiple sclerosis, the existence of significant differences between groups was proven using DTM. Moreover, a statistically significant impact of spatial systematic errors occurs for all ROIs and DTMs in the phantom and for approximately 90 % in the HC and MS groups. In the case of a single patient measurement, this appears for all the examined ROIs and DTMs. The obtained DTMs effectively discriminate healthy volunteers from multiple sclerosis patients with a low mean score on the Expanded Disability Status Scale. The magnitude of the group differences is typically significant, with an effect size of approximately 0.5, and similar in both the standard approach and after elimination of systematic errors. Differences were also observed between metrics obtained using these two approaches. Despite a small alterations in mean DTMs values for groups and ROIs (1–3 %), these differences were characterized by a huge effect (effect size ∼0.8 or more). These findings indicate the importance of determining the spatial distribution of systematic errors specific to each MR scanner and DTI acquisition protocol in order to assess their impact on DTM in the ROIs examined. This is crucial to establish accurate DTM values for both individual patients and mean values for a healthy population as a reference. This approach allows for an initial reliable diagnosis based on DTI metrics.

Diffusion tensor imaging within the healthy cervical spinal cord: Within- participants reliability and measurement error

BackgroundDiffusion tensor imaging (DTI) is a promising technique for the visualization of the cervical spinal cord (CSC) in vivo. It provides information about the tissue structure of axonal white matter, and it is thought to be more sensitive than other MR imaging techniques for the evaluation of damage to tracts in the spinal cord. AimThe purpose of this study was to determine the within-participants reliability and error magnitude of measurements of DTI metrics in healthy human CSC. MethodsA total of twenty healthy controls (10 male, mean age: 33.9 ± 3.5 years, 10 females, mean age: 47.5 ± 14.4 years), with no family history of any neurological disorders or a contraindication to MRI scanning were recruited over a period of two months. Each participant was scanned twice with an MRI 3 T scanner using standard DTI sequences. Spinal Cord Toolbox (SCT) software was used for image post-processing. Data were first corrected for motion artefact, then segmented, registered to a template, and then the DTI metrics were computed. The within-participants coefficients of variation (CV%), the single and average within-participants intraclass correlation coefficients (ICC) and Bland-Altman plots for WM, VC, DC and LC fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were determined for the cervical spinal cord (between the 2nd and 5th cervical vertebrae). ResultsDTI metrics showed poor to excellent within-participants reliability for both single and average ICC and moderate to high reproducibility for CV%, all variation dependent on the location of the ROI. The BA plots showed good within-participants agreement between the scan-rescan values. ConclusionResults from this reliability study demonstrate that clinical trials using the DTI technique are feasible and that DTI, in particular regions of the cord is suitable for use for the monitoring of degenerative WM changes.

The impact of subjective cognitive decline on aging effects in the brain as measured by diffusion tensor imaging

AbstractBackgroundDiffusion tensor imaging (DTI) can separate subjective cognitive decline (SCD) participants who progress to mild cognitive impairment and those who do not 1. We explored the effect age and memory performance has on DTI measures in SCD and controls in the hippocampal cingulum bundle, which is typically affected early in the course of Alzheimer’s disease2.Method325 participants Cam‐CAN 3 (127 SCD) older than 55 were included in the analysis. Diffusion imaging data was collected on a 3T Siemens TIM Trio scanner with a 32‐channel head coil for 0, 1000 and 2000 s/mm2 b‐values and 30 gradient directions. Preprocessing and calculation of the DTI metrics fractional anisotropy (FA, mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AxD) were completed using MRTrix3, FSL and MATLAB. The hippocampal cingulum bundle regions of interest (ROIs) were extracted from the ICBM‐DTI‐81 atlas. Memory was assessed using the delayed story recall (DSR) task from WMS‐III. Linear regression models were completed in R. Gender was included as a nuisance variable.ResultThere were no differences in gender or age distribution between cohorts, however participants with SCD had a 14% lower DSR score (Table 1). There was a significant interaction effect between age and cohort in MD, AxD, and RD (Figure 1), as well as between memory and age in AxD (Figure 2). In post‐hoc analyses, compared to controls, the SCD group showed a stronger correlation with age in MD, AxD, and RD (Figure 1) while participants with worse memory showed a stronger correlation with age in MD (Figure 2), indicating an accelerated aging effect.ConclusionParticipants with SCD and worse memory present with an accelerated aging effect, showing steeper variations in diffusion microstructure with age. Since SCD is likely to be a preclinical stage of Alzheimer’s disease, future work will analyze this effect with more advanced diffusion microstructure models to further elucidate the underlying pathophysiology. • Selnes P, Aarsland D, Bjornerud A, et al. J Alzheimers Dis. 2013;33(3):723‐36. • Jack Jr CR, Knopman DS, Jagust WJ, et al. The Lancet Neurology. 2013;12(2):207‐16. • Shafto MA, Tyler LK, Dixon M, et al. BMC neurology. 2014;14(1):1‐25.

Hippocampus‐associated tract degradation follows differential DTI patterns and is influenced by amyloid in MCI patients

AbstractBackgroundDiffusion tensor imaging (DTI) has been leveraged to understand microstructural alterations to limbic and cortico‐cortical tracts in Alzheimer’s disease (AD). However, investigation into the key changes and patterns of fractional anisotropy (FA) and mean diffusivity (MD) metrics in the early stages of MCI has not been widely investigated. This study aimed to establish whether the early DTI white matter tract changes in MCI patients are decoupled and whether amyloid positivity (Aβ+/Aβ‐) is associated with early tract degradation.Method171 participants (103 MCI &amp; 73 CN) were recruited from the AD Neuroimaging Initiative (ADNI; adni.loni.usc.edu) database. For each participant, FA and MD maps were obtained at their baseline scan and voxel wise analysis was carried out using FSL (https://fsl.fmrib.ox.ac.uk/fsl/) and Tract‐Based Spatial Statistics (https://fsl.fmrib.ox.ac.uk/fsl/fslwiki/TBSS). Students t‐tests were conducted on the FA and MD changes in hippocampal WM tracts, previously identified as areas of potential early degradation. Comparisons between CN and MCI groups were made along Aβ+ and Aβ‐ groups.ResultWe found evidence for WM degradation, indicated by lower FA scores in MCI participants compared with controls, in the specific regions of interest of the fornix (p = 0.004) and tapetum (p = 0.012). Mean diffusivity was increased in the MCI group compared to CN in areas of the fornix (p &lt; 0.001), consistent with FA alterations, yet differed from areas identified in FA changes owing to changes in the uncinate fasciculus (p = 0.022) and cingulum (p = 0.003). Comparison of DTI metrics in the fornix between amyloid status groups revealed that Aβ+ participants had significantly lower FA compared to Aβ‐ participants (p = 0.047), but MD did not significantly differ.ConclusionThese results confirm the notion that WM tract integrity degradation in the tract apparatus surrounding the hippocampus occur early in the AD trajectory. However, results indicate that FA alterations occur in different patterns to that of MD and that amyloid may influence these patterns. This supports the idea that efforts to develop therapeutics which maintain WM tract integrity early may be key to slowing AD progression.

The impact of subjective cognitive decline on aging effects in the brain as measured by diffusion tensor imaging

AbstractBackgroundDiffusion tensor imaging (DTI) can separate subjective cognitive decline (SCD) participants who progress to mild cognitive impairment and those who do not 1. We explored the effect age and memory performance has on DTI measures in SCD and controls in the hippocampal cingulum bundle, which is typically affected early in the course of Alzheimer’s disease2.Method325 participants Cam‐CAN 3 (127 SCD) older than 55 were included in the analysis. Diffusion imaging data was collected on a 3T Siemens TIM Trio scanner with a 32‐channel head coil for 0, 1000 and 2000 s/mm2 b‐values and 30 gradient directions. Preprocessing and calculation of the DTI metrics fractional anisotropy (FA, mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AxD) were completed using MRTrix3, FSL and MATLAB. The hippocampal cingulum bundle regions of interest (ROIs) were extracted from the ICBM‐DTI‐81 atlas. Memory was assessed using the delayed story recall (DSR) task from WMS‐III. Linear regression models were completed in R. Gender was included as a nuisance variable.ResultThere were no differences in gender or age distribution between cohorts, however participants with SCD had a 14% lower DSR score (Table 1). There was a significant interaction effect between age and cohort in MD, AxD, and RD (Figure 1), as well as between memory and age in AxD (Figure 2). In post‐hoc analyses, compared to controls, the SCD group showed a stronger correlation with age in MD, AxD, and RD (Figure 1) while participants with worse memory showed a stronger correlation with age in MD (Figure 2), indicating an accelerated aging effect.ConclusionParticipants with SCD and worse memory present with an accelerated aging effect, showing steeper variations in diffusion microstructure with age. Since SCD is likely to be a preclinical stage of Alzheimer’s disease, future work will analyze this effect with more advanced diffusion microstructure models to further elucidate the underlying pathophysiology.1. Selnes P, Aarsland D, Bjornerud A, et al. J Alzheimers Dis. 2013;33(3):723‐36.2. Jack Jr CR, Knopman DS, Jagust WJ, et al. The Lancet Neurology. 2013;12(2):207‐16.3. Shafto MA, Tyler LK, Dixon M, et al. BMC neurology. 2014;14(1):1‐25.

Harmonization of multi-site diffusion tensor imaging data for cervical and thoracic spinal cord at 1.5T and 3T using longitudinal ComBat.

MRI scanner hardware, field strengths, and sequence parameters are major variables in diffusion studies of the spinal cord. Reliability between scanners is not well known, particularly for the thoracic cord. DTI data was collected for the entire cervical and thoracic spinal cord in thirty healthy adult subjects with different MR vendors and field strengths. DTI metrics were extracted and averaged for all slices within each vertebral level. Metrics were examined for variability and then harmonized using longitudinal ComBat (longComBat). Four scanners were used: Siemens 3T Prisma, Siemens 1.5T Avanto, Philips 3T Ingenia, Philips 1.5T Achieva. Average full cord diffusion values/standard deviation for all subjects and scanners were FA: 0.63, σ = 0.10, MD: 1.11, σ = 0.12 × 10-3 mm2/s, AD: 1.98, σ = 0.55 × 10-3 mm2/s, RD: 0.67, σ = 0.31 × 10-3 mm2/s. FA metrics averaged for all subjects by level were relatively consistent across scanners, but large variability was found in diffusivity measures. Coefficients of variation were lowest in the cervical region, and relatively lower for FA than diffusivity measures. Harmonized metrics showed greatly improved agreement between scanners. Variability in DTI of the spinal cord arises from scanner hardware differences, pulse sequence differences, physiological motion, and subject compliance. The use of longComBat resulted in large improvement in agreement of all DTI metrics between scanners. This study shows the importance of harmonization of diffusion data in the spinal cord and potential for longitudinal and multisite clinical research and clinical trials.

Comparison of distortion correction preprocessing pipelines for DTI in the upper limb.

DTI characterizes tissue microstructure and provides proxy measures of nerve health. Echo-planar imaging is a popular method of acquiring DTI but is susceptible to various artifacts (e.g., susceptibility, motion, and eddy currents), which may be ameliorated via preprocessing. There are many pipelines available but limited data comparing their performance, which provides the rationale for this study. DTI was acquired from the upper limb of heathy volunteers at 3T in blip-up and blip-down directions. Data were independently corrected using (i) FSL's TOPUP & eddy, (ii) FSL's TOPUP, (iii) DSI Studio, and (iv) TORTOISE. DTI metrics were extracted from the median, radial, and ulnar nerves and compared (between pipelines) using mixed-effects linear regression. The geometric similarity of corrected b = 0 images and the slice matched T1-weighted (T1w) images were computed using the Sörenson-Dice coefficient. Without preprocessing, the similarity coefficient of the blip-up and blip-down datasets to the T1w was 0·80 and 0·79, respectively. Preprocessing improved the geometric similarity by 1% with no difference between pipelines. Compared to TOPUP & eddy, DSI Studio and TORTOISE generated 2% and 6% lower estimates of fractional anisotropy, and 6% and 13% higher estimates of radial diffusivity, respectively. Estimates of anisotropy from TOPUP & eddy versus TOPUP were not different but TOPUP reduced radial diffusivity by 3%. The agreement of DTI metrics between pipelines was poor. Preprocessing DTI from the upper limb improves geometric similarity but the choice of the pipeline introduces clinically important variability in diffusion parameter estimates from peripheral nerves.

The Challenge of Diffusion Magnetic Resonance Imaging in Cerebral Palsy: A Proposed Method to Identify White Matter Pathways.

Cerebral palsy (CP), a neuromotor disorder characterized by prenatal brain lesions, leads to white matter alterations and sensorimotor deficits. However, the CP-related diffusion neuroimaging literature lacks rigorous and consensual methodology for preprocessing and analyzing data due to methodological challenges caused by the lesion extent. Advanced methods are available to reconstruct diffusion signals and can update current advances in CP. Our study demonstrates the feasibility of analyzing diffusion CP data using a standardized and open-source pipeline. Eight children with CP (8-12 years old) underwent a single diffusion magnetic resonance imaging (MRI) session on a 3T scanner (Achieva 3.0T (TX), Philips Healthcare Medical Systems, Best, The Netherlands). Exclusion criteria were contraindication to MRI and claustrophobia. Anatomical and diffusion images were acquired. Data were corrected and analyzed using Tractoflow 2.3.0 version, an open-source and robust tool. The tracts were extracted with customized procedures based on existing atlases and freely accessed standardized libraries (ANTs, Scilpy). DTI, CSD, and NODDI metrics were computed for each tract. Despite lesion heterogeneity and size, we successfully reconstructed major pathways, except for a participant with a larger lesion. Our results highlight the feasibility of identifying and quantifying subtle white matter pathways. Ultimately, this will increase our understanding of the clinical symptoms to provide precision medicine and optimize rehabilitation.