Fibre orientation atlas guided rapid segmentation of white matter tracts.

Fibre tract delineation from diffusion magnetic resonance imaging (MRI) is a valuable clinical tool for neurosurgical planning and navigation, as well as in research neuroimaging pipelines. Several popular methods are used for this task, each with different strengths and weaknesses making them more or less suited to different contexts. For neurosurgical imaging, priorities include ease of use, computational efficiency, robustness to pathology and ability to generalise to new tracts of interest. Many existing methods use streamline tractography, which may require expert neuroimaging operators for setting parameters and delineating anatomical regions of interest, or suffer from as a lack of generalisability to clinical scans involving deforming tumours and other pathologies. More recently, data-driven approaches including deep-learning segmentation models and streamline clustering methods have improved reproducibility and automation, although they can require large amounts of training data and/or computationally intensive image processing at the point of application. We describe an atlas-based direct tract mapping technique called 'tractfinder', utilising tract-specific location and orientation priors. Our aim was to develop a clinically practical method avoiding streamline tractography at the point of application while utilising prior anatomical knowledge derived from only 10-20 training samples. Requiring few training samples allows emphasis to be placed on producing high quality, neuro-anatomically accurate training data, and enables rapid adaptation to new tracts of interest. Avoiding streamline tractography at the point of application reduces computational time, false positives and vulnerabilities to pathology such as tumour deformations or oedema. Carefully filtered training streamlines and track orientation distribution mapping are used to construct tract specific orientation and spatial probability atlases in standard space. Atlases are then transformed to target subject space using affine registration and compared with the subject's voxel-wise fibre orientation distribution data using a mathematical measure of distribution overlap, resulting in a map of the tract's likely spatial distribution. This work includes extensive performance evaluation and comparison with benchmark techniques, including streamline tractography and the deep-learning method TractSeg, in two publicly available healthy diffusion MRI datasets (from TractoInferno and the Human Connectome Project) in addition to a clinical dataset comprising paediatric and adult brain tumour scans. Tract segmentation results display high agreement with established techniques while requiring less than 3 min on average when applied to a new subject. Results also display higher robustness than compared methods when faced with clinical scans featuring brain tumours and resections. As well as describing and evaluating a novel proposed tract delineation technique, this work continues the discussion on the challenges surrounding the white matter segmentation task, including issues of anatomical definitions and the use of quantitative segmentation comparison metrics.

The feasibility of an adapted virtual mindfulness intervention for Special Olympics athletes and their caregivers.

BACKGROUND: Virtual mindfulness may be helpful for individuals with intellectual disabilities in the context of COVID-related disruptions of in-person programming, such as Special Olympics (SO). This study examined the feasibility of a virtual mindfulness intervention for SO athletes and their caregivers. METHOD: SO athletes (n = 44) and their caregivers (n = 29) participated in a 6-week adapted virtual mindfulness intervention. Athletes completed mindfulness and well-being questionnaires prior to, immediately following, and 3-months post-intervention. Caregivers completed questionnaires assessing their own stress, mindfulness, and well-being, as well as athlete mental health. Exit interviews were conducted immediately following the intervention. RESULTS: The intervention was feasible in terms of demand, implementation, acceptability, and limited testing efficacy. There were significant improvements in athlete well-being and mental health, and caregiver stress and mindfulness post-intervention. CONCLUSIONS: Adapted virtual mindfulness groups may be an effective intervention in improving the well-being of adults with intellectual disabilities and their caregivers.

Brain volume in Tanzanian children with sickle cell anaemia: A neuroimaging study.

Brain injury is a common complication of sickle cell anaemia (SCA). White matter (WM) and cortical and subcortical grey matter (GM), structures may have reduced volume in patients with SCA. This study focuses on whether silent cerebral infarction (SCI), vasculopathy or anaemia affects WM and regional GM volumes in children living in Africa. Children with SCA (n = 144; aged 5-20 years; 74 male) and sibling controls (n = 53; aged 5-17 years; 29 male) underwent magnetic resonance imaging. Effects of SCI (n = 37), vasculopathy (n = 15), and haemoglobin were assessed. Compared with controls, after adjusting for age, sex and intracranial volume, patients with SCA had smaller volumes for WM and cortical, subcortical and total GM, as well as bilateral cerebellar cortex, globus pallidus, amygdala and right thalamus. Left globus pallidus volume was further reduced in patients with vasculopathy. Putamen and hippocampus volumes were larger in patients with SCA without SCI or vasculopathy than in controls. Significant positive effects of haemoglobin on regional GM volumes were confined to the controls. Patients with SCA generally have reduced GM volumes compared with controls, although some subcortical regions may be spared. SCI and vasculopathy may affect the trajectory of change in subcortical GM and WM volume. Brain volume in non-SCA children may be vulnerable to contemporaneous anaemia.

Evaluation of dual-energy X-ray absorptiometry compared to magnetic resonance imaging for collecting measurements of the human bony pelvis.

OBJECTIVES: Imaging methods to measure the human pelvis in vivo provide opportunities to better understand pelvic variation and adaptation. Magnetic resonance imaging (MRI) provides high-resolution images, but is more expensive than dual-energy X-ray absorptiometry (DXA). We sought to compare pelvic breadth measurements collected from the same individuals using both methods, to investigate if there are systematic differences in pelvic measurement between these imaging methods. METHODS: Three pelvic breadth dimensions (bi-iliac breadth, bi-acetabular breadth, medio-lateral inlet breadth) were collected from MRI and DXA scans of a cross-sectional sample of healthy, nulliparous adult women of South Asian ancestry (n = 63). Measurements of MRI and DXA pelvic dimensions were collected four times in total, with one baseline data collection session and three replications. Data collected from these sessions were averaged, used to calculate technical error of measurement and entered into a Bland-Altman analysis. Linear regression models were fitted with a given MRI pelvic measurement regressed on the same measurement collected from DXA scans, as well as MRI mean bias regressed on DXA mean bias. RESULTS: Technical error of measurement was higher in DXA measurements of bi-iliac breadth and medio-lateral pelvic inlet breadth and higher for MRI measurements of bi-acetabular breadth. Bland Altman analyses showed no statistically significant relationship between the mean bias of MRI and DXA, and the differences between MRI and DXA pelvic measurements. CONCLUSIONS: DXA measurements of pelvic breadth are comparable to MRI measurements of pelvic breadth. DXA is a less costly imaging technique than MRI and can be used to collect measurements of skeletal elements in living people.

Mutations in thyroid hormone receptor α1 cause premature neurogenesis and progenitor cell depletion in human cortical development.

Mutations in the thyroid hormone receptor α 1 gene (THRA) have recently been identified as a cause of intellectual deficit in humans. Patients present with structural abnormalities including microencephaly, reduced cerebellar volume and decreased axonal density. Here, we show that directed differentiation of THRA mutant patient-derived induced pluripotent stem cells to forebrain neural progenitors is markedly reduced, but mutant progenitor cells can generate deep and upper cortical layer neurons and form functional neuronal networks. Quantitative lineage tracing shows that THRA mutation-containing progenitor cells exit the cell cycle prematurely, resulting in reduced clonal output. Using a micropatterned chip assay, we find that spatial self-organization of mutation-containing progenitor cells in vitro is impaired, consistent with down-regulated expression of cell-cell adhesion genes. These results reveal that thyroid hormone receptor α1 is required for normal neural progenitor cell proliferation in human cerebral cortical development. They also exemplify quantitative approaches for studying neurodevelopmental disorders using patient-derived cells in vitro.

Comparative analysis of signal models for microscopic fractional anisotropy estimation using q-space trajectory encoding.

Microscopic diffusion anisotropy imaging using diffusion-weighted MRI and multidimensional diffusion encoding is a promising method for quantifying clinically and scientifically relevant microstructural properties of neural tissue. Several methods for estimating microscopic fractional anisotropy (µFA), a normalized measure of microscopic diffusion anisotropy, have been introduced but the differences between the methods have received little attention thus far. In this study, the accuracy and precision of µFA estimation using q-space trajectory encoding and different signal models were assessed using imaging experiments and simulations. Three healthy volunteers and a microfibre phantom were imaged with five non-zero b-values and gradient waveforms encoding linear and spherical b-tensors. Since the ground-truth µFA was unknown in the imaging experiments, Monte Carlo random walk simulations were performed using axon-mimicking fibres for which the ground truth was known. Furthermore, parameter bias due to time-dependent diffusion was quantified by repeating the simulations with tuned waveforms, which have similar power spectra, and with triple diffusion encoding, which, unlike q-space trajectory encoding, is not based on the assumption of time-independent diffusion. The truncated cumulant expansion of the powder-averaged signal, gamma-distributed diffusivities assumption, and q-space trajectory imaging, a generalization of the truncated cumulant expansion to individual signals, were used to estimate µFA. The gamma-distributed diffusivities assumption consistently resulted in greater µFA values than the second order cumulant expansion, 0.1 greater when averaged over the whole brain. In the simulations, the generalized cumulant expansion provided the most accurate estimates. Importantly, although time-dependent diffusion caused significant overestimation of µFA using all the studied methods, the simulations suggest that the resulting bias in µFA is less than 0.1 in human white matter.

Clinically feasible diffusion MRI in muscle: Time dependence and initial findings in Duchenne muscular dystrophy.

PURPOSE: To characterize the diffusion time-dependence in muscle in healthy adult volunteers, boys with Duchenne's muscular dystrophy (DMD), and age-matched controls in a clinically feasible acquisition time for pediatric applications. METHODS: Diffusion data were acquired using a pulsed gradient stimulated echo diffusion preparation at 5 different diffusion times (70, 130, 190, 250, and 330 ms), at 4 different b-values (0, 200, 400, 600, and 800 s/mm2 ) and 6 directions (orthogonal x, y, and z and diagonal xy, xz, and yz) and processed to obtain standard diffusion indices (mean diffusivity [MD] and fractional anisotropy [FA]) at each diffusion time. RESULTS: Time-dependent diffusion was seen in muscle in healthy adult volunteers, boys with DMD, and age-matched controls. Boys with DMD showed reduced MD and increased FA values in comparison to age matched controls across a range of diffusion times. A diffusion time of Δ = 190 ms had the largest effect size. CONCLUSIONS: These results could be used to optimize diffusion imaging in this disease further and imply that these diffusion indices may become an important biomarker in monitoring progression in DMD in the future.

Comparison of models of diffusion in Wilms' tumours and normal contralateral renal tissue.

OBJECTIVE: ADC (Apparent Diffusion Coefficient) derived from Diffusion-Weighted Imaging (DWI) has shown promise as a non-invasive quantitative imaging biomarker in Wilms' tumours. However, many non-Gaussian models could be applied to DWI. This study aimed to compare the suitability of four diffusion models (mono exponential, IVIM [Intravoxel Incoherent Motion], stretched exponential, and kurtosis) in Wilms' tumours and the unaffected contralateral kidneys. MATERIALS AND METHODS: DWI data were retrospectively reviewed (110 Wilms' tumours and 75 normal kidney datasets). The goodness of fit for each model was measured voxel-wise using Akaike Information Criteria (AIC). Mean AIC was calculated for each tumour volume (or contralateral normal kidney tissue). One-way ANOVAs with Greenhouse-Geisser correction and post hoc tests using the Bonferroni correction evaluated significant differences between AIC values; the lowest AIC indicating the optimum model. RESULTS: IVIM and stretched exponential provided the best fits to the Wilms' tumour DWI data. IVIM provided the best fit for the normal kidney data. Mono exponential was the least appropriate fitting method for both Wilms' tumour and normal kidney data. DISCUSSION: The diffusion weighted signal in Wilms' tumours and normal kidney tissue does not exhibit a mono-exponential decay and is better described by non-Gaussian models of diffusion.

White Matter Integrity in Tanzanian Children With Sickle Cell Anemia: A Diffusion Tensor Imaging Study.

Background and Purpose- Widespread reductions in white matter integrity are associated with cognitive dysfunction in sickle cell anemia. Silent cerebral infarction (SCI), vasculopathy (VSC), and low hemoglobin concentration (Hb) are implicated; we aimed to determine independent contributions to microstructural white matter injury and whether white matter integrity differs across arterial territories. Methods- Sixty two children with sickle cell anemia aged 6 to 19 years were prospectively studied at Muhimbili National Hospital, Tanzania. SCI± and VSC± were identified on magnetic resonance imaging (MRI)/magnetic resonance angiography (MRA) scans by 2 neuroradiologists. Tract-based spatial statistics tested for voxel-wise differences in diffusion tensor imaging metrics (ie, fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity) between SCI± and VSC± groups, with correlations between diffusion tensor imaging metrics and Hb. In tract-based spatial statistics analyses, potentially mediating factors (ie, age, sex, as well as Hb, SCI, and/or vasculopathy) were covariates. Differences in mean diffusion tensor imaging metrics across regions of interest in arterial territories were explored. Results- Compared with SCI- patients (n=45), SCI+ patients (n=17) exhibited increased radial diffusivity in multiple regions; negative relationships were observed between mean diffusivity, axial diffusivity, and Hb (P<0.005). Compared with VSC- patients (n=49), mild (n=6) or moderate (n=7) VSC+ patients exhibited reduced fractional anisotropy in widespread regions (P<0.05) including the anterior longitudinal fasciculi, corpus callosum, internal capsule, corona radiata, and corticospinal tracts. Overall, the posterior cerebral arterial territory had higher mean mean diffusivity and mean radial diffusivity than the anterior and middle cerebral arterial territories, although no patient had vasculopathy in this area. There was an interaction between territory and vasculopathy. Conclusions- SCI, vasculopathy, and Hb are independent risk factors, and thus treatment targets, for diffuse white matter injury in patients with sickle cell anemia. Exacerbation of hemodynamic stress may play a role.

Validation and noise robustness assessment of microscopic anisotropy estimation with clinically feasible double diffusion encoding MRI.

PURPOSE: Double diffusion encoding (DDE) MRI enables the estimation of microscopic diffusion anisotropy, yielding valuable information on tissue microstructure. A recent study proposed that the acquisition of rotationally invariant DDE metrics, typically obtained using a spherical "5-design," could be greatly simplified by assuming Gaussian diffusion, facilitating reduced acquisition times that are more compatible with clinical settings. Here, we aim to validate the new minimal acquisition scheme against the standard DDE 5-design, and to quantify the proposed method's noise robustness to facilitate future clinical use. THEORY AND METHODS: DDE MRI experiments were performed on both ex vivo and in vivo rat brains at 9.4 T using the 5-design and the proposed minimal design and taking into account the difference in the number of acquisitions. The ensuing microscopic fractional anisotropy (µFA) maps were compared over a range of b-values up to 5000 s/mm2 . Noise robustness was studied using analytical calculations and numerical simulations. RESULTS: The minimal protocol quantified µFA at an accuracy comparable to the estimates obtained by means of the more theoretically robust DDE 5-design. µFA's sensitivity to noise was found to strongly depend on compartment anisotropy and tensor magnitude in a nonlinear manner. When µFA < 0.75 or when mean diffusivity is particularly low, very high signal-to-noise ratio is required for precise quantification of µFA. CONCLUSION: Our work supports using DDE for quantifying microscopic diffusion anisotropy in clinical settings but raises hitherto overlooked precision issues when measuring µFA with DDE and typical clinical signal-to-noise ratio.

Microscopic susceptibility anisotropy imaging.

PURPOSE: The gradient-echo MR signal in brain white matter depends on the orientation of the fibers with respect to the external magnetic field. To map microstructure-specific magnetic susceptibility in orientationally heterogeneous material, it is thus imperative to regress out unwanted orientation effects. METHODS: This work introduces a novel framework, referred to as microscopic susceptibility anisotropy imaging, that disentangles the 2 principal effects conflated in gradient-echo measurements, (a) the susceptibility properties of tissue microenvironments, especially the myelin microstructure, and (b) the axon orientation distribution relative to the magnetic field. Specifically, we utilize information about the orientational tissue structure inferred from diffusion MRI data to factor out the B0 -direction dependence of the frequency difference signal. RESULTS: A human pilot study at 3 T demonstrates proxy maps of microscopic susceptibility anisotropy unconfounded by fiber crossings and orientation dispersion as well as magnetic field direction. The developed technique requires only a dual-echo gradient-echo scan acquired at 1 or 2 head orientations with respect to the magnetic field and a 2-shell diffusion protocol achievable on standard scanners within practical scan times. CONCLUSIONS: The quantitative recovery of microscopic susceptibility features in the presence of orientational heterogeneity potentially improves the assessment of microstructural tissue integrity.

Time-dependent diffusion MRI as a probe of microstructural changes in a mouse model of Duchenne muscular dystrophy.

Dystrophic muscles show a high variability of fibre sizes and altered sarcolemmal integrity, which are typically assessed by histology. Time-dependent diffusion MRI is sensitive to tissue microstructure and its investigation through age-related changes in dystrophic and healthy muscles may help the understanding of the onset and progression of Duchenne muscular dystrophy (DMD). We investigated the capability of time-dependent diffusion MRI to quantify age and disease-related changes in hind-limb muscle microstructure between dystrophic (mdx) and wild-type (WT) mice of three age groups (7.5, 22 and 44 weeks). Diffusion time-dependent apparent diffusion coefficients (ADCs) of the gastrocnemius and tibialis anterior muscles were determined versus age and diffusion-gradient orientation at six diffusion times (Δ; range: 25-350 ms). Mean muscle ADCs were compared between groups and ages, and correlated with T2 , using Student's t test, one-way analysis of variance and Pearson correlation, respectively. Muscle fibre sizes and sarcolemmal integrity were evaluated by histology and compared with diffusion measurements. Hind-limb muscle ADC showed characteristic restricted diffusion behaviour in both mdx and WT animals with decreasing ADC values at longer Δ. Significant differences in ADC were observed at long Δ values (≥ 250 ms; p < 0.05, comparison between groups; p < 0.01, comparison between ages) with ADC increased by 5-15% in dystrophic muscles, indicative of reduced diffusion restriction. No significant correlation was found between T2 and ADC. Additionally, muscle fibre size distributions showed higher variability and lower mean fibre size in mdx than WT animals (p < 0.001). The extensive Evans Blue Dye uptake shown in dystrophic muscles revealed substantial sarcolemmal damage, suggesting diffusion measurements as more consistent with altered permeability rather than changes in muscle fibre sizes. This study shows the potential of diffusion MRI to non-invasively discriminate between dystrophic and healthy muscles with enhanced sensitivity when using long Δ.

MRI profiling of focal cortical dysplasia using multi-compartment diffusion models.

OBJECTIVE: Focal cortical dysplasia (FCD) lesion detection and subtyping remain challenging on conventional MRI. New diffusion models such as the spherical mean technique (SMT) and neurite orientation dispersion and density imaging (NODDI) provide measurements that potentially produce more specific maps of abnormal tissue microstructure. This study aims to assess the SMT and NODDI maps for computational and radiological lesion characterization compared to standard fractional anisotropy (FA) and mean diffusivity (MD). METHODS: SMT, NODDI, FA, and MD maps were calculated for 33 pediatric patients with suspected FCD (18 histologically confirmed). Two neuroradiologists scored lesion visibility on clinical images and diffusion maps. Signal profile changes within lesions and homologous regions were quantified using a surface-based approach. Diffusion parameter changes at multiple cortical depths were statistically compared between FCD type IIa and type IIb. RESULTS: Compared to fluid-attenuated inversion recovery (FLAIR) or T1-weighted imaging, lesions conspicuity on NODDI intracellular volume fraction (ICVF) maps was better/equal/worse in 5/14/14 patients, respectively, while on SMT intra-neurite volume fraction (INVF) in 3/3/27. Compared to FA or MD, lesion conspicuity on the ICVF was better/equal/worse in 27/4/2, while on the INVF in 20/7/6. Quantitative signal profiling demonstrated significant ICVF and INVF reductions in the lesions, whereas SMT microscopic mean, radial, and axial diffusivities were significantly increased. FCD type IIb exhibited greater changes than FCD type IIa. No changes were detected on FA or MD profiles. SIGNIFICANCE: FCD lesion-specific signal changes were found in ICVF and INVF but not in FA and MD maps. ICVF and INVF showed greater contrast than FLAIR in some cases and had consistent signal changes specific to FCD, suggesting that they could improve current presurgical pediatric epilepsy imaging protocols and can provide features useful for automated lesion detection.

Brain structure in children with congenital visual disorders and visual impairment.

AIM: To examine if congenital visual impairment is associated with differences in brain anatomy in children. METHOD: Ten children (8-12y) with congenital disorders of the peripheral visual system with severe visual impairment (SVI; >0.8 logMAR) or mild-to-moderate visual impairment (MVI; 0.6-0.8 logMAR) were compared to 21 typically sighted comparison (TSC) children. Thalamus volume, grey matter density, white matter microstructure, and integrity of visual tracts were investigated in SVI, MVI, and TSC groups with anatomical and diffusion-weighted magnetic resonance imaging. RESULTS: Compared to the TSC group, the SVI group had lower white matter integrity in tracts of the visual system (optic radiations: SVI 0.35±0.015, TSC 0.39±0.007 [p=0.022]; posterior corpus callosum: SVI 0.37±0.019; TSC 0.42±0.009 [p=0.033]) and lower left thalamus volume (SVI 4.37±0.087; TSC 4.99±0.339 [p=0.015]). Neuroanatomical differences were greater in the SVI group, while no consistent differences between the MVI and TSC group were observed. INTERPRETATION: Posterior tracts of the visual system are compromised in children with congenital visual impairment versus those who are typically sighted. The severity of visual input appears to have affected neuroanatomical development as significant reductions were only found in the SVI group. WHAT THIS PAPER ADDS: Severe visual impairment in mid-childhood is associated with reduced integrity of visual pathways and reduced thalamus volume.

Developmental origins of variability in pelvic dimensions: Evidence from nulliparous South Asian women in the United Kingdom.

OBJECTIVES: Pelvic growth may be sensitive to early-life nutrition, with implications for maternal risk of obstructed labor. However, the "developmental origins" of adult pelvic variability require further investigation. We tested whether adult pelvic dimensions are associated with two components of height, indexing different periods of linear growth: tibia length, a proxy for early postnatal growth, and height-residual (height regressed on tibia length), a proxy for later growth. We also tested whether adult pelvic dimensions are associated with birth weight, a marker of nutritional investment in utero. METHODS: In this cross-sectional study, data were obtained on 68 nulliparous young women of South Asian ancestry. Pelvic dimensions (bi-iliac and bi-acetabular breadth, anteroposterior pelvic inlet and outlet, interspinous and intertuberous diameter) were measured using magnetic resonance imaging. Height and tibia length were measured manually. Birth weight and gestational age were obtained by recall. Multivariable regression models were fitted with a given pelvic dimension regressed on height-residual, tibia, and birth weight, with the latter adjusted for gestational age. RESULTS: Controlling for birth weight, height-residual was predictive of bi-acetabular breadth, bi-iliac breadth, and the pelvic inlet, while tibia length significantly predicted all dimensions except interspinous diameter. Controlling for the linear growth variables, birth weight was predictive of bi-iliac breadth only. CONCLUSIONS: Markers of linear growth during both early and later development were associated with adult pelvic dimensions, whereas size at birth was poorly predictive. Efforts to reduce stunting in early life may facilitate the attainment of maximum potential growth for both height and the pelvis.

Robust kidney perfusion mapping in pediatric chronic kidney disease using single-shot 3D-GRASE ASL with optimized retrospective motion correction.

PURPOSE: To develop a robust renal arterial spin labeling (ASL) acquisition and processing strategy for mapping renal blood flow (RBF) in a pediatric cohort with severe kidney disease. METHODS: A single-shot background-suppressed 3D gradient and spin-echo (GRASE) flow-sensitive alternating inversion recovery (FAIR) ASL acquisition method was used to perform 2 studies. First, an evaluation of the feasibility of single-shot 3D-GRASE and retrospective noise reduction methods was performed in healthy volunteers. Second, a pediatric cohort with severe chronic kidney disease underwent single-shot 3D-GRASE FAIR ASL and RBF was quantified following several retrospective motion correction pipelines, including image registration and threshold-free weighted averaging. The effect of motion correction on the fit errors of saturation recovery (SR) images (required for RBF quantification) and on the perfusion-weighted image (PWI) temporal signal-to-noise ratio (tSNR) was evaluated, as well as the intra- and inter-session repeatability of renal longitudinal relaxation time (T1 ) and RBF. RESULTS: The mean cortical and/or functional renal parenchyma RBF in healthy volunteers and CKD patients was 295 ± 97 and 95 ± 47 mL/100 g/min, respectively. Motion-correction reduced image artefacts in both T1 and RBF maps, significantly reduced SR fit errors, significantly increased the PWI tSNR and improved the improved the repeatability of T1 and RBF in the pediatric patient cohort. CONCLUSION: Single-shot 3D-GRASE ASL combined with retrospective motion correction enabled repeatable non-invasive RBF mapping in the first pediatric cohort with severe kidney disease undergoing ASL scans.

In vivo demonstration of microscopic anisotropy in the human kidney using multidimensional diffusion MRI.

PURPOSE: To demonstrate the feasibility of multidimensional diffusion MRI to probe and quantify microscopic fractional anisotropy (µFA) in human kidneys in vivo. METHODS: Linear tensor encoded (LTE) and spherical tensor encoded (STE) renal diffusion MRI scans were performed in 10 healthy volunteers. Respiratory triggering and image registration were used to minimize motion artefacts during the acquisition. Kidney cortex-medulla were semi-automatically segmented based on fractional anisotropy (FA) values. A model-free analysis of LTE and STE signal dependence on b-value in the renal cortex and medulla was performed. Subsequently, µFA was estimated using a single-shell approach. Finally, a comparison of conventional FA and µFA is shown. RESULTS: The hallmark effect of µFA (divergence of LTE and STE signal with increasing b-value) was observed in all subjects. A statistically significant difference between LTE and STE signal was found in the cortex and medulla, starting from b = 750 s/mm2 and b = 500 s/mm2 , respectively. This difference was maximal at the highest b-value sampled (b = 1000 s/mm2 ) which suggests that relatively high b-values are required for µFA mapping in the kidney compared to conventional FA. Cortical and medullary µFA were, respectively, 0.53 ± 0.09 and 0.65 ± 0.05, both respectively higher than conventional FA (0.19 ± 0.02 and 0.40 ± 0.02). CONCLUSION: The feasibility of combining LTE and STE diffusion MRI to probe and quantify µFA in human kidneys is demonstrated for the first time. By doing so, we show that novel microstructure information-not accessible by conventional diffusion encoding-can be probed by multidimensional diffusion MRI. We also identify relevant technical limitations that warrant further development of the technique for body MRI.

Structural connectivity of the amygdala in young adults with autism spectrum disorder.

Autism spectrum disorder (ASD) is characterized by impairments in social cognition, a function associated with the amygdala. Subdivisions of the amygdala have been identified which show specificity of structure, connectivity, and function. Little is known about amygdala connectivity in ASD. The aim of this study was to investigate the microstructural properties of amygdala-cortical connections and their association with ASD behaviours, and whether connectivity of specific amygdala subregions is associated with particular ASD traits. The brains of 51 high-functioning young adults (25 with ASD; 26 controls) were scanned using MRI. Amygdala volume was measured, and amygdala-cortical connectivity estimated using probabilistic tractography. An iterative 'winner takes all' algorithm was used to parcellate the amygdala based on its primary cortical connections. Measures of amygdala connectivity were correlated with clinical scores. In comparison with controls, amygdala volume was greater in ASD (F(1,94) = 4.19; p = .04). In white matter (WM) tracts connecting the right amygdala to the right cortex, ASD subjects showed increased mean diffusivity (t = 2.35; p = .05), which correlated with the severity of emotion recognition deficits (rho = -0.53; p = .01). Following amygdala parcellation, in ASD subjects reduced fractional anisotropy in WM connecting the left amygdala to the temporal cortex was associated with with greater attention switching impairment (rho = -0.61; p = .02). This study demonstrates that both amygdala volume and the microstructure of connections between the amygdala and the cortex are altered in ASD. Findings indicate that the microstructure of right amygdala WM tracts are associated with overall ASD severity, but that investigation of amygdala subregions can identify more specific associations.

The effects of ageing on mouse muscle microstructure: a comparative study of time-dependent diffusion MRI and histological assessment.

The investigation of age-related changes in muscle microstructure between developmental and healthy adult mice may help us to understand the clinical features of early-onset muscle diseases, such as Duchenne muscular dystrophy. We investigated the evolution of mouse hind-limb muscle microstructure using diffusion imaging of in vivo and in vitro samples from both actively growing and mature mice. Mean apparent diffusion coefficients (ADCs) of the gastrocnemius and tibialis anterior muscles were determined as a function of diffusion time (Δ), age (7.5, 22 and 44 weeks) and diffusion gradient direction, applied parallel or transverse to the principal axis of the muscle fibres. We investigated a wide range of diffusion times with the goal of probing a range of diffusion lengths characteristic of muscle microstructure. We compared the diffusion time-dependent ADC of hind-limb muscles with histology. ADC was found to vary as a function of diffusion time in muscles at all stages of maturation. Muscle water diffusivity was higher in younger (7.5 weeks) than in adult (22 and 44 weeks) mice, whereas no differences were observed between the older ages. In vitro data showed the same diffusivity pattern as in vivo data. The highlighted differences in diffusion properties between young and mature muscles suggested differences in underlying muscle microstructure, which were confirmed by histological assessment. In particular, although diffusion was more restricted in older muscle, muscle fibre size increased significantly from young to adult age. The extracellular space decreased with age by only ~1%. This suggests that the observed diffusivity differences between young and adult muscles may be caused by increased membrane permeability in younger muscle associated with properties of the sarcolemma.

Cerebral perfusion characteristics show differences in younger versus older children with sickle cell anaemia: Results from a multiple-inflow-time arterial spin labelling study.

Sickle cell anaemia (SCA) is associated with chronic anaemia and oxygen desaturation, which elevate cerebral blood flow (CBF) and increase the risk of neurocognitive complications. Arterial spin labelling (ASL) provides a methodology for measuring CBF non-invasively; however, ASL techniques using only a single inflow time are not sufficient to fully characterize abnormal haemodynamic behaviour in SCA. This study investigated haemodynamic parameters from a multi-inflow-time ASL acquisition in younger (8-12 years) and older (13-18 years) children with SCA with and without silent cerebral infarction (SCI+/-) (n = 20 and 19 respectively, 6 and 4 SCI+ respectively) and healthy controls (n = 9 and 7 respectively). Compared with controls, CBF was elevated globally in both groups of patients. In the younger SCA patients, blood oxygen content was negatively correlated with CBF in the middle and posterior cerebral artery territories and significantly positively correlated with bolus arrival time (BAT) in the anterior and middle cerebral artery territories. In older children, SCA patients had significantly shorter BAT than healthy controls and there was a significant negative correlation between CBF and oxygen content only in the territory of the posterior cerebral artery, with a trend for a correlation in the anterior cerebral artery but no relationship for the middle cerebral artery territory. In the younger group, SCI+ patients had significantly higher CBF in the posterior cerebral artery territory (SCI+ mean = 92.78 ml/100 g/min; SCI- mean = 72.71 ml/100 g/min; F = 4.28, p = 0.04), but this no longer reached significance when two children with abnormal transcranial Doppler and one with haemoglobin SC disease were excluded, and there were no significant differences between patients with and without SCI in the older children. With age, there appears to be increasing disparity between patients and controls in terms of the relationship between CBF and oxygen content in the anterior circulation, potentially predicting the risk of acute and chronic compromise of brain tissue.