Diffusion magnetic resonance imaging in preterm brain injury

Inroduction

White matter injury and abnormal maturation are thought to be major contributors to the neurodevelopmental disabilities observed in children and adolescents who were born preterm. Early detection of abnormal white matter maturation is important in the design of preventive, protective, and rehabilitative strategies for the management of the preterm infant. Diffusion-weighted magnetic resonance imaging (d-MRI) has become a valuable tool in assessing white matter maturation and injury in survivors of preterm birth. In this review, we aim to (1) describe the basic concepts of d-MRI; (2) evaluate the methods that are currently used to analyse d-MRI; (3) discuss neuroimaging correlates of preterm brain injury observed at term corrected age; during infancy, adolescence and in early adulthood; and (4) explore the relationship between d-MRI measures and subsequent neurodevelopmental performance.

Methods

References for this review were identified through searches of PubMed and Google Scholar before March 2013.

Results

The impact of premature birth on cerebral white matter can be observed from term-equivalent age through to adulthood. Disruptions to white matter development, identified by d-MRI, are related to diminished performance in functional domains including motor performance, cognition and behaviour in early childhood and in later life.

Conclusion

d-MRI is an effective tool for investigating preterm white matter injury. With advances in image acquisition and analysis approaches, d-MRI has the potential to be a biomarker of subsequent outcome and to evaluate efficacy of clinical interventions in this population.

     

Quantification of diffusion tensor imaging in normal white matter maturation of early childhood using an automated processing pipeline

Objectives

The degree and status of white matter myelination can be sensitively monitored using diffusion tensor imaging (DTI). This study looks at the measurement of fractional anistropy (FA) and mean diffusivity (MD) using an automated ROI with an existing DTI atlas.

Methods

Anatomical MRI and structural DTI were performed cross-sectionally on 26 normal children (newborn to 48?months old), using 1.5-T MRI. The automated processing pipeline was implemented to convert diffusion-weighted images into the NIfTI format. DTI-TK software was used to register the processed images to the ICBM DTI-81 atlas, while AFNI software was used for automated atlas-based volumes of interest (VOIs) and statistical value extraction.

Results

DTI exhibited consistent grey–white matter contrast. Triphasic temporal variation of the FA and MD values was noted, with FA increasing and MD decreasing rapidly early in the first 12?months. The second phase lasted 12–24?months during which the rate of FA and MD changes was reduced. After 24?months, the FA and MD values plateaued.

Conclusion

DTI is a superior technique to conventional MR imaging in depicting WM maturation. The use of the automated processing pipeline provides a reliable environment for quantitative analysis of high-throughput DTI data.

Key Points

? Diffusion tensor imaging outperforms conventional MRI in depicting white matter maturation. ? DTI will become an important clinical tool for diagnosing paediatric neurological diseases. ? DTI appears especially helpful for developmental abnormalities, tumours and white matter disease. ? An automated processing pipeline assists quantitative analysis of high throughput DTI data.     

Amide Proton Transfer (APT) MR imaging and Magnetization Transfer (MT) MR imaging of pediatric brain development

Objectives

To quantify the brain maturation process during childhood using combined amide proton transfer (APT) and conventional magnetization transfer (MT) imaging at 3 Tesla.

Methods

Eighty-two neurodevelopmentally normal children (44 males and 38 females; age range, 2?190 months) were imaged using an APT/MT imaging protocol with multiple saturation frequency offsets. The APT-weighted (APTW) and MT ratio (MTR) signals were quantitatively analyzed in multiple brain areas. Age-related changes in MTR and APTW were evaluated with a non-linear regression analysis.

Results

The APTW signals followed a decreasing exponential curve with age in all brain regions measured (R²?=?0.7?0.8 for the corpus callosum, frontal and occipital white matter, and centrum semiovale). The most significant changes appeared within the first year. At maturation, larger decreases in APTW and lower APTW values were found in the white matter. On the contrary, the MTR signals followed an increasing exponential curve with age in the same brain regions measured, with the most significant changes appearing within the initial 2 years. There was an inverse correlation between the MTR and APTW signal intensities during brain maturation.

Conclusions

Together with MT imaging, protein-based APT imaging can provide additional information in assessing brain myelination in the paediatric population.

Key Points

? APTW signals followed a decreasing exponential curve with age. ? The most significant APTW changes appeared within the first year ? At maturation, larger APTW decreases and lower APTW appeared in white matter ? MTR signals followed an increasing exponential curve with age

     

Diffusion tensor and tensor metrics imaging in intracranial epidermoid cysts

Purpose

To explore the utility of diffusion tensor imaging (DTI) and diffusion tensor metrics (DTM) in characterizing the structural pathology of epidermoid cysts. DTI gives information about the tissue structure; a high fractional anisotropy (FA) indicates a highly structured orientation of the tissue, fibers, or white matter tracts. Based on the tensor rank, a set of three metrics has been described that can be used to measure the directional dependence of diffusion: linear anisotropy (CL), planar anisotropy (CP), and spherical anisotropy (CS). DTM takes into account the shape of diffusion anisotropy and hence may provide better insight into the orientation of structures than FA.

Materials and Methods

DTI was performed in three patients with epidermoid cysts. FA, directionally‐averaged mean diffusivity (Dav), exponential apparent diffusion coefficient (eADC), and DTM, such as CL, CP, and CS, were measured from the tumor core as well as from the normal‐appearing white matter. Histopathological correlation was obtained.

Results

Epidermoid cysts showed high FA with Dav values similar to that of normal white matter. eADC maps did not show any restriction of diffusion. FA values were high, but not as high as that for the white matter. CP values were higher and CL values were lower than those obtained for the white matter in various regions.

Conclusion

High CP values suggest preferential diffusion of water molecules along a two‐dimensional geometry, which could be attributed to the well‐structured orientation of keratin filaments and flakes within the tumor as demonstrated by histopathology. Advanced imaging modalities like DTI with DTM can provide information regarding the microstructural anatomy of the epidermoid cysts. J. Magn. Reson. Imaging 2009;29:967–970. © 2009 Wiley‐Liss, Inc.     

Diffusional kurtosis imaging analysis in patients with hypertension

Purpose

Hypertension is associated with substantial morbidity in Japan. The aim of this work was to evaluate whether hypertension is associated with white matter microstructural changes by using diffusional kurtosis imaging (DKI).

Methods

We explored the regional patterns of white matter alteration in 15 hypertensive middle-aged male participants and 11 normotensive controls by using DKI-based whole-brain analysis. In addition, we investigated whether the observed white matter microstructural changes were related to systolic or diastolic blood pressure by using Pearson’s correlation coefficient analysis.

Results

Mean diffusional kurtosis (MDK) values were significantly higher in hypertensive participants than in normotensive participants (P < 0.05; family-wise error correction for multiple comparisons), indicating widespread microstructural changes in white matter. Moreover, we noted a statistically significant positive correlation between systolic and diastolic blood pressure and MDK values of the whole brain.

Conclusion

Our study suggests that microstructural white matter changes occur in middle-aged men with hypertension, even before the onset of cerebrovascular disease. Thus, DKI might be used as a screening tool for risk of cerebrovascular disease. This highlights the need to further elucidate the relationship between hypertension and DKI of the brain.     

A preliminary diffusional kurtosis imaging study of Parkinson disease: comparison with conventional diffusion tensor imaging

Introduction

Diffusional kurtosis imaging (DKI) is a more sensitive technique than conventional diffusion tensor imaging (DTI) for assessing tissue microstructure. In particular, it quantifies the microstructural integrity of white matter, even in the presence of crossing fibers. The aim of this preliminary study was to compare how DKI and DTI show white matter alterations in Parkinson disease (PD).

Methods

DKI scans were obtained with a 3-T magnetic resonance imager from 12 patients with PD and 10 healthy controls matched by age and sex. Tract-based spatial statistics were used to compare the mean kurtosis (MK), mean diffusivity (MD), and fractional anisotropy (FA) maps of the PD patient group and the control group. In addition, a region-of-interest analysis was performed for the area of the posterior corona radiata and superior longitudinal fasciculus (SLF) fiber crossing.

Results

FA values in the frontal white matter were significantly lower in PD patients than in healthy controls. Reductions in MK occurred more extensively throughout the brain: in addition to frontal white matter, MK was lower in the parietal, occipital, and right temporal white matter. The MK value of the area of the posterior corona radiata and SLF fiber crossing was also lower in the PD group.

Conclusion

DKI detects changes in the cerebral white matter of PD patients more sensitively than conventional DTI. In addition, DKI is useful for evaluating crossing fibers. By providing a sensitive index of brain pathology in PD, DKI may enable improved monitoring of disease progression.     

MR imaging of hypoglycemic encephalopathy: lesion distribution and prognosis prediction by diffusion-weighted imaging

Introduction

The aim of this study was to evaluate the patterns of hypoglycemic encephalopathy on diffusion-weighted imaging (DWI) and the relationship between the imaging patterns and clinical outcomes.

Methods

This retrospective study included 17 consecutive patients that had hypoglycemic encephalopathy with DWI abnormalities. The topographic distributions of the DWI abnormalities of the cortex, deep gray matter, and white matter structures were assessed. In addition, possible correlation between the patterns of brain injury on DWI and clinical outcomes was investigated.

Results

There were three patterns of DWI abnormalities: involvement of both gray and white matter (n?=?8), selective involvement of gray matter (n?=?4), and selective involvement of white matter (n?=?5). There was no significant difference in the initial blood glucose levels among patients for each of the imaging patterns. Most patients (16/17) had bilateral symmetrical abnormalities. Among patients with bilateral symmetrical gray and/or white matter injuries, one had moderate to severe disability and 14 remained in a persistent vegetative state. The two patients with a focal unilateral white matter abnormality and a localized splenial abnormality recovered without neurological deficits.

Conclusion

The results of this study showed that white matter was more sensitive to hypoglycemia than previously thought and there was no specific association between the patterns of injury and clinical outcomes whether the cerebral cortex, deep gray matter, and/or white matter were affected. Diffuse and extensive injury observed on the DWI predicts a poor neurologic outcome in patients with hypoglycemic injuries.     

Changes of brain metabolite concentrations during maturation in different brain regions measured by chemical shift imaging

Introduction

We examined the effect of maturation on the regional distribution of brain metabolite concentrations using multivoxel chemical shift imaging.

Methods

From our pool of pediatric MRI examinations, we retrospectively selected patients showing a normal cerebral MRI scan or no pathologic signal abnormalities at the level of the two-dimensional 1H MRS-CSI sequence and an age-appropriate global neurological development, except for focal neurological deficits. Seventy-one patients (4.5 months–20 years) were identified. Using LC Model, spectra were evaluated from voxels in the white matter, caudate head, and corpus callosum.

Results

The concentration of total N-acetylaspartate increased in all regions during infancy and childhood except in the right caudate head where it remained constant. The concentration of total creatine decreased in the caudate nucleus and splenium and minimally in the frontal white matter and genu. It remained largely constant in the parietal white matter. The concentration of choline-containing compounds had the tendency to decrease in all regions except in the parietal white matter where it remained constant. The concentration of myoinositol decreased slightly in the splenium and right frontal white matter, remained constant on the left side and in the caudate nucleus, and rose slightly in the parietal white matter and genu.

Conclusion

CSI determined metabolite concentrations in multiple cerebral regions during routine MRI. The obtained data will be helpful in future pediatric CSI measurements deciding whether the ratios of the main metabolites are within the range of normal values or have to be considered as probably pathologic.

     

Brain MRI diffusion-weighted imaging in patients with classical phenylketonuria

Introduction  

The aim of this study was to grade magnetic resonance white matter abnormalities (WMAs) of classical phenylketonuria (cPKU) patients treated from birth and to compare sensitivity and specificity of T2-weighted and diffusion-weighted images (DWI).     

Age-related white matter changes in high b-value q-space diffusion-weighted imaging

Introduction

To assess and compare age-related diffusion changes in the white matter in different cerebral lobes, as quantified by diffusion-weighted imaging (DWI) and high b-value q-space imaging (QSI).

Methods

Seventy-three cases without neurological symptoms or imaging abnormalities were grouped by age as young (<30 years, n?=?20), middle-aged (30–49 years, n?=?19), old (50–69 years, n?=?18), and very old (>70 years, n?=?16) and imaged by a 1.5-T MR scanner for DWI and QSI. Apparent diffusion coefficient (ADC) and mean displacement (MDP) values were calculated in the white matter of frontal, parietal, and temporal lobes and compared using Dunnett’s test, with the young group as a control.

Results

MDP values in frontal and parietal lobes were significantly higher in old and very old age groups than in the young, while those in the temporal lobes were significantly higher only in the very old group. ADC values were significantly higher in all three lobes in the very old group.

Conclusion

QSI is more sensitive than DWI to age-related myelin loss in white matter.     

Punctate white matter lesions in infants: new insights using susceptibility-weighted imaging

Introduction  

Punctate white matter lesions (PWML) are recognized with magnetic resonance imaging (MRI) as hypersignal on T1-weighted imaging and hyposignal on T2-weighted imaging. Our aim was to assess how often a hemorrhagic component was present in PWML using susceptibility-weighted imaging (SWI).     

Diffusion tensor imaging and brain volumetry in Fabry disease patients

Introduction

Fabry disease is a rare lysosomal storage disorder leading to cellular accumulation of globotriaosylceramide, especially in blood vessels. It is associated with severe early onset cerebrovascular disease and kidney and heart failure. The purpose of this study was to reveal possible disturbances in white matter integrity in Fabry disease patients using voxelwise diffusion-tensor imaging (DTI) analysis.

Methods

Twelve Fabry disease patients, along with 13 healthy controls, underwent DTI and structural MRI. Voxel-based analysis of the DTI data was performed to assess possible differences in DTI parameters between Fabry disease patients and healthy controls. A selective region of interest analysis was performed for healthy volunteers and Fabry disease patients having a mild burden of T2-hyperintense lesions. We also measured normalised brain tissue volumes and performed a voxel-based volume analysis for grey matter.

Results

Voxel-based analysis of DTI data showed areas of significantly reduced fractional anisotropy and increased mean diffusivity in patients with Fabry disease. Eight patients had a mild burden of white matter lesions on their T2 scans. Region of interest analysis on areas showing reduced fractional anisotropy in voxelwise analysis also revealed reduced fractional anisotropy values in this patient group compared to eight healthy volunteers. The brain volume analyses did not reveal significant differences between the Fabry disease patients and the controls.

Conclusion

These findings suggest a microstructural damage in brain white matter of Fabry disease patients, which can be revealed before excessive white matter lesions load is visible on conventional MR scans.     

Diffusion-weighted imaging improves prediction in cognitive outcome and clinical phases in patients with carbon monoxide intoxication

Introduction

Changes in apparent diffusion coefficient (ADC) values often reflect tissue injury. Use of ADC as a surrogate marker to assess clinical phases has not been systemically applied in patients with carbon monoxide (CO) intoxication.

Methods

Fifty-nine magnetic resonance imaging scans and cognitive evaluations were performed in 47 patients with CO intoxication and compared with 22 sex- and age-matched controls. The patients were further classified into three groups based on the clinical phases, namely, acute (within 2 weeks), delayed neuropsychiatric (2 weeks to 6 months), and chronic (>1 year) groups. The ADC values were measured in 16 regions of interests (ROIs) and correlated with cognitive test scores.

Results

Among the 59 evaluations, 15 were in the acute, 26 in the delayed neuropsychiatric, and 18 in the chronic groups. Among the ROIs, significant elevations of ADC values were found in the corpus callosum and globus pallidus in all three CO phases compared with the controls, and the ADC values were highest in the chronic phases. In contrast, the ADC values in peripheral gray matter and white matter were highest in the delayed neuropsychiatric group. Both globus pallidus and corpus callosum ADC values correlated with multiple cognitive test scores.

Conclusion

Using ADC as a surrogate marker, the globus pallidus and corpus callosum can be considered to be two vulnerable structures in the gray and white matter. Significant differences between ADC values correlated well with clinical phase and cognitive performance.     

Unraveling pathology in juvenile Alexander disease: serial quantitative MR imaging and spectroscopy of white matter

Introduction

Alexander disease is a rare disorder of the central nervous system with characteristic symmetric white matter abnormalities with frontal predominance on magnetic resonance (MR) images. Histopathology shows a lack of myelin in the affected white matter, variably interpreted as hypomyelination or demyelination. To increase our insight into the nature of the pathology leading to the MR imaging findings in Alexander disease, we applied serial MR imaging, spectroscopy, magnetization transfer (MT) imaging (MTI), and diffusion tensor imaging (DTI) in six patients with juvenile Alexander disease.

Methods

The MR imaging protocol comprised T1- and T2-weighted spin echo images and fluid-attenuated inversion recovery images. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), and MT ratio (MTR) maps were generated, and MR spectroscopy concentrations were quantified for several metabolites.

Results

MR imaging showed similar cerebral white matter abnormalities in all patients, with only minor increase on prolonged follow-up, despite sometimes serious clinical progression. MR spectroscopy showed highly elevated levels of myo-inositol, lactate, and choline-containing compounds and decreased total N-acetyl-aspartate and N-acetyl-aspartyl-glutamate levels in the abnormal white matter. High values of ADC were observed, and both FA and MTR were attenuated.

Conclusion

The sequential MR imaging findings in Alexander disease provide strong evidence against active demyelination as sole explanation for the underlying pathology. An alternative explanation for our spectroscopic, DTI, and MTI findings—which would suggest demyelination—could be hyperplasia and hypertrophy of astrocytes, as seen in low grade gliomas.     

Presence of a central vein within white matter lesions on susceptibility weighted imaging: a specific finding for multiple sclerosis?

Introduction  

Susceptibility weighted imaging depicts the perivenous extent of multiple sclerosis white matter lesions (MS-WML) in vivo by directly visualizing their centrally running vein. The aim of this study was to investigate the specificity of this finding for MS.     

Using diffusion tensor imaging and immunofluorescent assay to evaluate the pathology of multiple sclerosis

Purpose:

To determine the ability of the principal diffusion tensor imaging (DTI) indices to predict the underlying histopathology evaluated with immunofluorescent assay (IFA).

Materials and Methods:

Conventional T2 and 3D multishot‐diffusion weighted echoplanar imaging (3D ms‐DWEPI) was performed on a fixed, ex vivo human cervical spinal cord (CSC) from a patient with a history of multiple sclerosis (MS). In all, 170 regions of interest (ROIs) were selected within the white matter and categorized as a high intensity lesion (HIL), low intensity lesion (LIL), and normal‐appearing white matter (NAWM). The longitudinal diffusivity (λl), radial diffusivity (λr), and fractional anisotropy (FA) were obtained from each ROI. The underlying histopathology was then evaluated using immunofluorescent assay with antibodies directed to myelin and neurofilament staining.

Results:

The mean values for λl and λr were significantly elevated within HIL relative to NAWM and LIL. IFA analysis of HIL demonstrated significant demyelination, without significant if any axon loss. The FA values were significantly reduced in HIL and LILs. FA values were also reduced in lesions with increased λl and λr values relative to normal.

Conclusion:

Aberrant λl, λr, and FA relative to normal values are strong indicators of demyelination. DTI indices are not specific for axon loss. IFA analysis is a reliable method to demonstrate myelin and axon pathology within the ex vivo setting. J. Magn. Reson. Imaging 2011;33:557–564. © 2011 Wiley‐Liss, Inc.     

Assessment of brain maturation in the preterm infants using diffusion tensor imaging (DTI) and enhanced T2 star weighted angiography (ESWAN)

Purpose

To assess the brain maturation of preterm infants using diffusion tensor imaging (DTI) and enhanced T2 star weighted angiography (ESWAN).

Materials and methods

Conventional magnetic resonance imaging (MRI), DTI and ESWAN were performed in 60 preterm infants and 21 term controls. 60 preterm infants were subgrouped to two groups according to the age at imaging: before and at term-equivalent age (TEA). Fractional anisotropy (FA), apparent diffusion coefficient (ADC) map from DTI, T₂* and R₂* maps from ESWAN were post-processed at an off-line workstation. The values of FA, ADC, T₂* and R₂* from the posterior limb of internal capsule (PLIC), frontal white matter (FWM), occipital white matter (OWM) and lentiform nuclei (LN) were determined. These parameters were compared between preterm and term infants. Correlations of DTI and ESWAN parameters with the gestational age, postmenstrual age and postnatal age were analyzed.

Results

ADCs of FWM, OWM and LN, and T₂* values of the PLIC and LN were higher in the preterm infants at TEA compared with the term controls.The correlations were existed between the postmenstrual age and the values of FA, ADC, T₂*, R₂* from the PLIC, values of ADC, T₂*, R₂* from the LN, T₂* value from the OWM. The correlations were also found between the postnatal age and the values of FA, ADC, T₂* from the PLIC, and T₂* value from the LN.

Conclusion

The maturity of preterm brain around TEA was different from that of term controls and appeared to be independent of the prematurity at birth. T₂* was one of valuable indices to evaluate brain maturation in preterm infants.     

Sporadic meningioangiomatosis: imaging findings with histopathologic correlations in seven patients

Introduction

Meningioangiomatosis (MA) is a rare benign cerebral lesion. We aimed to evaluate the CT and MR features of sporadic MA, with a focus on the correlation between imaging and histopathologic findings.

Methods

CT (n?=?7) and MR (n?=?8) images of eight patients (6 men and 2 women; mean age, 12.8 years; range, 4–22 years) with pathologically proven MA were retrospectively reviewed. After dividing the MA lesions according to their distribution into cortical and subcortical white matter components, the morphologic characteristics were analyzed and correlated with histopathologic findings in seven patients.

Results

CT and MR images showed cortical (n?=?4, 50 %) and subcortical white matter (n?=?7, 88 %) components of MA. All four cortical components revealed hyperattenuation on CT scan and T1 isointensity/T2 hypointensity on MR images, whereas subcortical white matter components showed hypoattenuation on CT scan and T1 hypointensity/T2 hyperintensity on MR images. Two cortical components (25 %) demonstrated enhancement and one subcortical white matter component demonstrated cystic change. Seven cases were available for imaging-histopathologic correlation. In all seven cases, the cortex was involved by MA and six patients (86 %) showed subcortical white matter involvement by MA. There were excellent correlations between the imaging and histopathologic findings in subcortical white matter components, and the accuracy was 100 % (seven of seven); whereas there were poor correlations in cortical components, and the accuracy was 43 % (three of seven).

Conclusions

The cerebral cortex and subcortical white matter were concomitantly involved by MA. Subcortical white matter components of MA were more apparent than cortical components on CT and MR imaging.     

The neuroanatomical phenotype of tuberous sclerosis complex: focus on radial migration lines

Introduction

The contribution of radial migration lines (RMLs) to the neuroanatomical and neurocognitive phenotype of tuberous sclerosis complex (TSC) is unclear. The aim of this study was to perform a comprehensive evaluation of the neuroradiological phenotype of TSC, distinguishing RMLs from normal-appearing white matter (NAWM) using diffusion tensor imaging (DTI) and volumetric fluid-attenuated inversion recovery imaging.

Methods

Magnetic resonance images of 30 patients with TSC were evaluated. The frequencies of RMLs, tubers, and subependymal nodules (SENs) were determined for every hemispheric lobe. Cerebellar lesions and subependymal giant cell tumors were counted. DTI metrics were obtained from the NAWM of every hemispheric lobe and from the largest RML and tuber. Analyses of variance and correlations were performed to investigate the associations between neuroanatomical characteristics and relationships between RML frequency and neurocognitive outcomes. NAWM DTI metrics were compared with measurements of 16 control patients.

Results

A mean of 47 RMLs, 27 tubers, and 10 SENs were found per patient, and the frequencies of these lesions were strongly correlated (p?<?0.001). RML fractional anisotropy and mean diffusivity were strongly inversely correlated (p?=?0.003). NAWM DTI metrics were similar to the controls (p?=?0.26). RML frequency was strongly associated with age of seizure onset (p?=?0.003), intelligence outcomes (p?=?0.01), and level of autistic features (p?=?0.007).

Conclusion

A detailed neuroradiological phenotype is presented, showing that RMLs are the most frequent neuroanatomical lesion, are responsible for white matter DTI abnormalities, and are strongly associated with age of seizure onset, intelligence outcomes, and level of autistic features.     

Assessment of damage to cerebral white matter fiber in the subacute phase after carbon monoxide poisoning using fractional anisotropy in diffusion tensor imaging

Introduction  

Chronic neuropsychiatric symptoms after carbon monoxide (CO) poisoning are caused by demyelination of cerebral white matter fibers. We examined whether diffusion tensor imaging can sensitively represent damage to fibers of the centrum semiovale in the subacute phase after CO intoxication.