Differentiating T2 hyperintensity in neonatal white matter by two-compartment model of diffusional kurtosis imaging.
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ABSTRACT:
SUBMITTER: Gao J
PROVIDER: S-EPMC4830988 | biostudies-other | 2016 Apr
REPOSITORIES: biostudies-other
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Project description:Glaucoma is an optic neuropathy characterized by death of retinal ganglion cells and loss of their axons, progressively leading to blindness. Recently, glaucoma has been conceptualized as a more diffuse neurodegenerative disorder involving the optic nerve and also the entire brain. Consistently, previous studies have used a variety of magnetic resonance imaging (MRI) techniques and described widespread changes in the grey and white matter of patients. Diffusion kurtosis imaging (DKI) provides additional information as compared with diffusion tensor imaging (DTI), and consistently provides higher sensitivity to early microstructural white matter modification. In this study, we employ DKI to evaluate differences among healthy controls and a mixed population of primary open angle glaucoma patients ranging from stage I to V according to Hodapp-Parrish-Anderson visual field impairment classification. To this end, a cohort of patients affected by primary open angle glaucoma (n = 23) and a group of healthy volunteers (n = 15) were prospectively enrolled and underwent an ophthalmological evaluation followed by magnetic resonance imaging (MRI) using a 3T MR scanner. After estimating both DTI indices, whole-brain, voxel-wise statistical comparisons were performed in white matter using Tract-Based Spatial Statistics (TBSS). We found widespread differences in several white matter tracts in patients with glaucoma relative to controls in several metrics (mean kurtosis, kurtosis anisotropy, radial kurtosis, and fractional anisotropy) which involved localization well beyond the visual pathways, and involved cognitive, motor, face recognition, and orientation functions amongst others. Our findings lend further support to a causal brain involvement in glaucoma and offer alternative explanations for a number of multidomain impairments often observed in glaucoma patients.
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Project description:Myelin breakdown and neural fiber loss occur in aging. This study used white matter tract integrity metrics derived from biophysical modeling using Diffusional Kurtosis Imaging to assess loss of myelin (i.e., extraaxonal diffusivity, radial direction, De,?) and axonal density (i.e., axonal water fraction) in cognitively unimpaired older adults. Tract-based spatial statistics and region of interest analyses sought to identify ontogenic differences and age-related changes in white matter tracts using cross-sectional and longitudinal data analyzed with general linear and mixed-effects models. In addition to pure diffusion parameters (i.e., fractional anisotropy, mean diffusivity, mean kurtosis), we found that white matter tract integrity metrics significantly differentiated early- from late-myelinating tracts, correlated with age in spatially distinct regions, and identified primarily extraaxonal changes over time. Percent metric changes were |0.3-0.9|% and |0.0-1.9|% per year using cross-sectional data and longitudinal data, respectively. There was accelerated decline in some late- versus early-myelinating tracts in older age. These results demonstrate that these metrics may inform further study of the transition from age-related changes to neurodegenerative decline.
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Project description:Background and purposeIncreasing DTI studies have demonstrated that white matter microstructural abnormalities play an important role in type 2 diabetes mellitus-related cognitive impairment. In this study, the diffusional kurtosis imaging method was used to investigate WM microstructural alterations in patients with type 2 diabetes mellitus and to detect associations between diffusional kurtosis imaging metrics and clinical/cognitive measurements.Materials and methodsDiffusional kurtosis imaging and cognitive assessments were performed on 58 patients with type 2 diabetes mellitus and 58 controls. Voxel-based intergroup comparisons of diffusional kurtosis imaging metrics were conducted, and ROI-based intergroup comparisons were further performed. Correlations between the diffusional kurtosis imaging metrics and cognitive/clinical measurements were assessed after controlling for age, sex, and education in both patients and controls.ResultsAltered diffusion metrics were observed in the corpus callosum, the bilateral frontal WM, the right superior temporal WM, the left external capsule, and the pons in patients with type 2 diabetes mellitus compared with controls. The splenium of the corpus callosum and the pons had abnormal kurtosis metrics in patients with type 2 diabetes mellitus. Additionally, altered diffusion metrics in the right prefrontal WM were significantly correlated with disease duration and attention task performance in patients with type 2 diabetes mellitus.ConclusionsWith both conventional diffusion and additional kurtosis metrics, diffusional kurtosis imaging can provide additional information on WM microstructural abnormalities in patients with type 2 diabetes mellitus. Our results indicate that WM microstructural abnormalities occur before cognitive decline and may be used as neuroimaging markers for predicting the early cognitive impairment in patients with type 2 diabetes mellitus.
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Project description:Major depressive disorder (MDD) is a globally prevalent psychiatric disorder that results from disruption of multiple neural circuits involved in emotional regulation. Although previous studies using diffusion tensor imaging (DTI) found smaller values of fractional anisotropy (FA) in the white matter, predominantly in the frontal lobe, of patients with MDD, studies using diffusion kurtosis imaging (DKI) are scarce. Here, we used DKI whole-brain analysis with tract-based spatial statistics (TBSS) to investigate the brain microstructural abnormalities in MDD. Twenty-six patients with MDD and 42 age- and sex-matched control subjects were enrolled. To investigate the microstructural pathology underlying the observations in DKI, a compartment model analysis was conducted focusing on the corpus callosum. In TBSS, the patients with MDD showed significantly smaller values of FA in the genu and frontal portion of the body of the corpus callosum. The patients also had smaller values of mean kurtosis (MK) and radial kurtosis (RK), but MK and RK abnormalities were distributed more widely compared with FA, predominantly in the frontal lobe but also in the parietal, occipital, and temporal lobes. Within the callosum, the regions with smaller MK and RK were located more posteriorly than the region with smaller FA. Model analysis suggested significantly smaller values of intra-neurite signal fraction in the body of the callosum and greater fiber dispersion in the genu, which were compatible with the existing literature of white matter pathology in MDD. Our results show that DKI is capable of demonstrating microstructural alterations in the brains of patients with MDD that cannot be fully depicted by conventional DTI. Though the issues of model validation and parameter estimation still remain, it is suggested that diffusion MRI combined with a biophysical model is a promising approach for investigation of the pathophysiology of MDD.
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Project description:ObjectiveIntraventricular hemorrhage (IVH) is a serious neurological complication in premature infants. This study aimed to investigate the white matter impairments and neurodevelopmental outcomes of severe IVH in extremely preterm infants with gestation age less than 28 weeks.MethodsWe retrospectively evaluated the extremely preterm infants between 2017 and 2020. Neurodevelopmental outcomes were evaluated with the Bayley Scales of Infant and Toddler Development-III at 2 years of corrected age. Diffusional kurtosis imaging (DKI) was employed to evaluate the microstructural changes in white matter tracts. Mean kurtosis (MK) and fractional anisotropy (FA) values of DKI were measured in the brain regions including posterior limbs of the internal capsule (PLIC) and the corpus callosum at term equivalent age.ResultsOf 32 extremely preterm infants with severe IVH during the follow-up period, 18 cases were identified as neurodevelopmental impairments. The delay rates of motor and language were 58.4% and 52.7%. The cases with neurodevelopmental impairments had lower MK and FA values in both bilateral PLIC and the corpus callosum. The analysis of multivariable regression models predicting motor and language outcomes at 2 years of corrected age, showed that the decreases of MK values in both PLIC and the corpus callosum at the term equivalent age contributed to a significantly increased risk of neurodevelopmental impairments (all p < 0.05). During follow-up period, obvious loss of nerve fiber bundles was observed with DKI tractography.ConclusionMotor and language abilities at age 2 years were associated with MK values of DKI at the term equivalent age in both PLIC and the corpus callosum of extremely preterm infants with severe IVH. The evaluation of white matter microstructural changes with MK values might provide feasible indicators of neurodevelopmental outcomes of extremely preterm infants with severe intraventricular hemorrhage.
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Project description:Background and purposeWhite matter fiber tractography relies on fiber bundle orientation estimates from diffusion MR imaging. However, clinically feasible techniques such as DTI and diffusional kurtosis imaging use assumptions, which may introduce error into in vivo orientation estimates. In this study, fiber bundle orientations from DTI and diffusional kurtosis imaging are compared with diffusion spectrum imaging as a criterion standard to assess the performance of each technique.Materials and methodsFor each subject, full DTI, diffusional kurtosis imaging, and diffusion spectrum imaging datasets were acquired during 2 independent sessions, and fiber bundle orientations were estimated by using the specific theoretic assumptions of each technique. Angular variability and angular error measures were assessed by comparing the orientation estimates. Tractography generated with each of the 3 reconstructions was also examined and contrasted.ResultsOrientation estimates from all 3 techniques had comparable angular reproducibility, but diffusional kurtosis imaging decreased angular error throughout the white matter compared with DTI. Diffusion spectrum imaging and diffusional kurtosis imaging enabled the detection of crossing-fiber bundles, which had pronounced effects on tractography relative to DTI. Diffusion spectrum imaging had the highest sensitivity for detecting crossing fibers; however, the diffusion spectrum imaging and diffusional kurtosis imaging tracts were qualitatively similar.ConclusionsFiber bundle orientation estimates from diffusional kurtosis imaging have less systematic error than those from DTI, which can noticeably affect tractography. Moreover, tractography obtained with diffusional kurtosis imaging is qualitatively comparable with that of diffusion spectrum imaging. Because diffusional kurtosis imaging has a shorter typical scan time than diffusion spectrum imaging, diffusional kurtosis imaging is potentially more suitable for a variety of clinical and research applications.
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Project description:Background and purposeConventional MR imaging typically yields normal images of the brain or indicates lesions in areas of high aquaporin expression in patients with neuromyelitis optica. Diffusional kurtosis imaging was applied in patients with neuromyelitis optica to determine whether this technique could detect alterations in diffusion and diffusional kurtosis parameters in normal-appearing white matter and to explore the relationship between diffusional kurtosis imaging and DTI parameters.Materials and methodsThirteen patients with neuromyelitis optica and 13 healthy controls underwent MR imaging of the brain with conventional and diffusional kurtosis imaging sequences. Tract-based spatial statistics and region-of-interest-based analyses were conducted to identify differences between patients with neuromyelitis optica and controls through conventional DTI and diffusional kurtosis imaging parameters. The parameters were correlated to determine the potential relationship between them.ResultsCompared with healthy controls, several diffusional kurtosis imaging and DTI parameters were altered in various fiber tracts of patients with neuromyelitis optica (P < .05). A significant decrease (P < .05) in radial kurtosis was observed in the corpus callosum and anterior corona radiata and left optic radiation. Differences (P < .1) in mean kurtosis were found in patients with neuromyelitis optica. We found a negative correlation between diffusional kurtosis imaging (radial kurtosis, axial kurtosis, mean kurtosis) and the corresponding DTI parameters (radial diffusivity, axial diffusivity, mean diffusivity). Positive correlations were found for radial kurtosis and mean kurtosis with fractional anisotropy.ConclusionsThis study demonstrated differences in conventional diffusion and diffusional kurtosis parameters, especially radial kurtosis, in the normal-appearing white matter of patients with neuromyelitis optica compared with healthy controls. Larger studies of patients with neuromyelitis optica should be performed to assess the potential clinical impact of these findings.
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Project description:ObjectivePhenylketonuria (PKU) is an autosomal recessive disorder whereby deficiencies in phenylalanine metabolism cause progressive neurological dysfunction. Managing PKU is challenging, with disease monitoring focussed on short-term phenylalanine control rather than measures of neuronal damage. Conventional imaging lacks sensitivity, however diffusion kurtosis imaging (DKI), a new MRI method may reveal subclinical white matter structural changes in PKU.MethodsThis cohort study involved adults with PKU recruited during routine clinical care. MRI, neurocognitive assessment and historical phenylalanine (Phe) levels were collected. A hypothesis-generating case study comparing diet-compliant and non-compliant siblings confirmed that DKI metrics are sensitive to dietary adherence and prompted a candidate metric (Krad/KFA ratio). We then tested this metric in a Replication cohort (PKU = 20; controls = 43).ResultsBoth siblings scored outside the range of controls for all DKI-based metrics, with severe changes in the periventricular white matter and a gradient of severity toward the cortex. Krad/KFA provided clear separation by diagnosis in the Replication cohort (p < 0.001 in periventricular, deep and pericortical compartments). The ratio also correlated negatively with attention (r = -0.51 & -0.50, p < 0.05) and positively with 3-year mean Phe (r = 0.45 & 0.58, p < 0.01).ConclusionDKI reveals regionally-specific, progressive abnormalities of brain diffusion characteristics in PKU, even in the absence of conspicuous clinical signs or abnormalities on conventional MRI. A DKI-based marker derived from these scores (Krad/KFA ratio) was sensitive to cognitive impairment and PKU control over the medium term and may provide a meaningful subclinical biomarker of end-organ damage.
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Project description:Background:The corpus callosum is implicated in the pathophysiology of autism spectrum disorder (ASD). However, specific structural deficits and underlying mechanisms are yet to be well defined. Methods:We employed diffusional kurtosis imaging (DKI) metrics to characterize white matter properties within five discrete segments of the corpus callosum in 17 typically developing (TD) adults and 16 age-matched participants with ASD without co-occurring intellectual disability (ID). The DKI metrics included axonal water fraction (f axon) and intra-axonal diffusivity (D axon), which reflect axonal density and caliber, and extra-axonal radial (RDextra) and axial (ADextra) diffusivities, which reflect myelination and microstructural organization of the extracellular space. The relationships between DKI metrics and processing speed, a cognitive feature known to be impaired in ASD, were also examined. Results:ASD group had significantly decreased callosal f axon and D axon (p?=?.01 and p?=?.045), particularly in the midbody, isthmus, and splenium. Regression analysis showed that variation in DKI metrics, primarily in the mid and posterior callosal regions explained up to 70.7% of the variance in processing speed scores for TD (p?=?.001) but not for ASD (p?>?.05). Conclusion:Decreased DKI metrics suggested that ASD may be associated with axonal deficits such as reduced axonal caliber and density in the corpus callosum, especially in the mid and posterior callosal areas. These data suggest that impaired interhemispheric connectivity may contribute to decreased processing speed in ASD participants.
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