Correlating quantitative MR imaging with histopathology in X-linked adrenoleukodystrophy

BACKGROUND AND PURPOSE:Quantitative MR imaging techniques may improve the pathologic specificity of MR imaging regarding white matter abnormalities. Our purposes were to determine whether ADC, FA, MTR, and MRS metabolites correlate with the degree of white matter damage in patients with X-ALD; whether differences in ADC, FA, and MTR observed in vivo are retained in fresh and formalin-fixed postmortem brain tissue; and whether the differences predict histopathology.MATERIALS AND METHODS:MRS metabolites, MTR, ADC, and FA, were determined in 7 patients with X-ALD in 3 white matter areas (NAWM, active demyelination, and complete demyelination) and were compared with values obtained in 14 controls. MTR, ADC, and FA were assessed in postmortem brains from 15 patients with X-ALD and 5 controls. Values were correlated with the degree of astrogliosis and density of myelin, axons, and cells. Equations to estimate histopathology from MR imaging parameters were calculated by linear regression analysis.RESULTS:MRS showed increased mIns, Lac, and Cho and decreased tNAA in living patients with X-ALD; the values depended on the degree of demyelination. MTR, ADC, and FA values were different in postmortem than in vivo white matter, but differences related to degrees of white matter damage were retained. ADC was high and FA and MTR were low in abnormal white matter. Correlations between histopathologic findings and MR imaging parameters were strong. A combination of ADC and FA predicted pathologic parameters best.CONCLUSIONS:Changes in quantitative MR imaging parameters, present in living patients and related to the severity of white matter pathology, are retained in postmortem brain tissue. MR imaging parameters predict white matter histopathologic parameters.

Conventional MR imaging has a high sensitivity for the detection of white matter abnormalities. However, it cannot distinguish among different pathologic substrates of white matter lesions. Pathologic findings associated with T2 hyperintensity and T1 hypointensity of the white matter are highly variable and include hypomyelination, demyelination, axonal loss, gliosis, interstitial edema, and cystic white matter degeneration.¹ Application of additional quantitative MR imaging techniques, such as DTI, MTI, and proton MRS, may improve the pathologic specificity of MR imaging findings and, in this way, add to the understanding of white matter disease processes. Quantitative MR imaging parameters may also provide reliable measures of the degree of white matter abnormality and may be applicable in the monitoring of treatment of white matter disorders.X-ALD is one of the most common leukodystrophies. In 80% of the patients with cerebral involvement, MR imaging shows a large bilateral white matter lesion involving the periventricular and deep white matter of the posterior parietal and occipital lobes.² Histopathologically, the center of the lesion is characterized by almost complete loss of axons and myelin, accompanied by attenuated astrogliosis. Active demyelination occurs at the edge of the lesion, accompanied by axonal damage and loss and inflammation.^2,3 Outside the lesion, the white matter is apparently normal. We decided to study the possible contribution of quantitative MR imaging parameters to the prediction of histologic parameters and chose X-ALD as the study subject because this disease allows comparison of large white matter areas with different degrees of myelin loss, axonal loss, and gliosis within the same brain section.A few studies have investigated the pathologic specificity of quantitative MR imaging parameters in the white matter of postmortem MS brains by comparing them with histopathologic parameters in MS lesions. In a study by Schmierer et al⁴ significant correlations were found between myelin content and MTR and between myelin content and axonal count. In an earlier study by van Waesberghe et al,⁵ T1 signal intensity and MTR were strongly correlated with axonal attenuation. Comparison of MRS and stereotactic brain biopsy findings in patients with MS revealed a parallel decrease of tNAA and reduction of axonal attenuation in demyelinating plaques.⁶ Concomitant increases of Cho and mIns were found to correspond to glial proliferation; elevation of Lac was associated with inflammation.⁷ A postmortem study correlating diffusion parameters with histopathology in patients with MS showed associations between myelin content and FA and ADC.⁶ A correlative in vivo MR imaging−postmortem histopathology study of the diffusely abnormal white matter in chronic MS showed that decreased FA values were associated with extensive axonal loss and reduced myelin density.⁸In our present study, we obtained quantitative MR imaging parameters, including MTR, diffusion parameters, and MRS metabolite concentrations, from living patients with the cerebral form of X-ALD and healthy control subjects. We also studied fresh and formalin-fixed postmortem brain sections of patients with X-ALD and controls with both MR imaging and histopathology.The aims of this study were the following: 1) to determine whether the degree of change in ADC, FA, MTR, and MRS metabolites correlates with the degree of white matter damage in vivo and in postmortem brain tissue in patients with X-ALD; 2) to determine whether the differences in ADC, FA, and MTR observed in vivo are retained in fresh and fixed postmortem brain tissue and, thus, whether application of quantitative MR imaging parameters in studies of postmortem tissue would be justified; and 3) to assess whether ADC, FA, and MTR predict histologic changes with regard to amounts of myelin, axons, gliosis, and cell density.     

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.     

Diffusion tensor imaging and tractography of the kidneys: assessment of chronic parenchymal diseases

Objective

To assess renal dysfunction in chronic kidney diseases using diffusion tensor imaging (DTI).

Methods

Forty-seven patients with impaired renal function (study group) and 17 patients without renal diseases (control group) were examined using DTI sequences. Cortical and medullary regions of interest (ROIs) were located to obtain the corresponding values of the apparent diffusion coefficient (ADC) and the fractional anisotropy (FA). The mean values of the ADC and FA, for each ROI site, were obtained in each group and were compared. Furthermore, the correlations between the diffusion parameters and the estimated glomerular filtration rate (eGFR) were determined.

Results

In both the normal and affected kidneys, we obtained the cortico-medullary difference of the ADC and the FA values. The FA value in the medulla was significantly lower (P?=?0.0149) in patients with renal function impairment as compared to patients with normal renal function. A direct correlation between DTI parameters and the eGFR was not found. Tractography visualised disruption of the regular arrangement of the tracts in patient with renal function alteration.

Conclusion

DTI could be a useful tool in the evaluation of chronic kidney disease and, in particular, the medullary FA value seems to be the main parameter for assessing renal damage.

Key Points

? Magnetic resonance diffusion tensor imaging (MRDTI) provides new information about renal problems. ? DTI allows non-invasive repeatable evaluation of the renal parenchyma, without contrast media. ? DTI could become useful in the management of chronic parenchymal disease. ? DTI seems more appropriate for renal evaluation than diffusion-weighted imaging.     

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.     

Patterns in early diffusion-weighted MRI in children with haemolytic uraemic syndrome and CNS involvement

Objectives

Diffusion-weighted imaging (DWI) in children with diarrhoea associated haemolytic uraemic syndrome (D+HUS) and cerebral involvement was evaluated retrospectively.

Methods

DWI within 24?h of onset of neurological symptoms. The apparent diffusion coefficient (ADC) was measured in grey/white matter and correlated with clinical and laboratory findings.

Results

DWI was abnormal in all. Abnormal ADC was detected in the supratentorial white matter (6/12) and cortex (1/12), the basal ganglia (5/12), the thalami (4/12), and the cerebellum (1/12). ADC was reduced in 5/12, increased in 4/12, and both in 3/12. Mean serum sodium was lower in patients with DWI abnormalities affecting the white matter (6/12), than in those with basal ganglia/thalamic involvement (6/12). Neurological outcome was normal in 4/11 and abnormal in 7/11, and 1 patient died, outcome did not correlate to either localisation or type of DWI abnormality.

Conclusions

In D+HUS with neurological symptoms, early DWI may reveal abnormal ADC not only in the basal ganglia/thalami, but also in the white matter/cortex. Besides thrombotic microangiopathy, toxic effects of shiga toxin, azotaemia and hyponatraemia / hypoosmolality may be involved in cerebral involvement in children with D+HUS. Findings on early MRI seem not to predict clinical course or outcome.

Key Points

? DWI MR imaging may detect early CNS involvement in haemolytic uraemic syndrome ? Different pathogenetical mechanisms may contribute to the CNS disease in HUS ? Early MRI findings do not seem to allow prediction of clinical outcome     

Assessment of reduced field of view in diffusion tensor imaging of the lumbar nerve roots at 3 T

Objectives

To assess the value of reduced field of view (rFOV) imaging in diffusion tensor imaging (DTI) and tractography of the lumbar nerve roots at 3 T from the perspective of future clinical trials.

Methods

DTI images of the lumbar nerves were obtained in eight healthy volunteers, with and without the rFOV technique. Non-coplanar excitation and refocusing pulses associated with outer volume suppression (OVS) were used to achieve rFOV imaging. Tractography was performed. A visual evaluation of image quality was made by two observers, both senior musculoskeletal radiologists. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured in L5 and S1 roots.

Results

rFOV images of the L5 and S1 roots were assessed as being superior to full FOV (fFOV) images. Image quality was rated as good to excellent by both observers. Interobserver agreement was good. No significant difference was found in FA and ADC measurements of the L5 or S1 roots. On the contrary, only poor-quality images could be obtained with fFOV imaging as major artefacts were present.

Conclusion

The rFOV approach was essential to achieve high-quality DTI imaging of lumbar nerve roots on 3-T MRI.

Key Points

? Diffusion tensor 3-T MR imaging of lumbar nerve roots creates severe artefacts. ? A reduced field of view drastically reduces artefacts, thereby improving image quality. ? Good-quality tractography images can even be obtained with rFOV imaging. ? rFOV DTI is better than fFOV DTI for clinical studies.     

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.     

Aortic stiffness is associated with white matter integrity in patients with type 1 diabetes

Objective

To assess the association between aortic pulse wave velocity (PWV) as a marker of arterial stiffness and diffusion tensor imaging of brain white matter integrity in patients with type 1 diabetes using advanced magnetic resonance imaging (MRI) technology.

Methods

Forty-one patients with type 1 diabetes (23 men, mean age 44?±?12 years, mean diabetes duration 24?±?13 years) were included. Aortic PWV was assessed using through-plane velocity-encoded MRI. Brain diffusion tensor imaging (DTI) measurements were performed on 3-T MRI. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were calculated for white and grey matter integrity. Pearson correlation and multivariable linear regression analyses including cardiovascular risk factors as covariates were assessed.

Results

Multivariable linear regression analyses revealed that aortic PWV is independently associated with white matter integrity FA (β?=??0.777, p?=?0.008) in patients with type 1 diabetes. This effect was independent of age, gender, mean arterial pressure, body mass index, smoking, duration of diabetes and glycated haemoglobin levels. Aortic PWV was not significantly related to grey matter integrity.

Conclusions

Our data suggest that aortic stiffness is independently associated with reduced white matter integrity in patients with type 1 diabetes.

Key Points

? Aortic stiffness is associated with brain injury. ? Aortic stiffness exposes small vessels to high pressure fluctuations and flow. ? Aortic stiffness is associated with microvascular brain injury in diabetes. ? This suggests a vascular contribution to early subtle microstructural deficits.     

Evaluation of white matter damage in patients with Alzheimer’s disease and in patients with mild cognitive impairment by using diffusion tensor imaging

Purpose

The objective of this study was to evaluate white matter tissue damage in patients with Alzheimer’s disease (AD) and in patients with mild cognitive impairment (MCI) using diffusion tensor imaging (DTI).

Materials and methods

Forty-seven subjects were evaluated: 14 patients with AD, 15 with MCI and 18 healthy volunteers. All subjects were studied using conventional magnetic resonance imaging (MRI) and DTI (32 directions) with a 1.5 T magnet. Fractional anisotropy (FA) was measured in the following regions: frontal, occipital, parietal and temporal white matter and in the genu and splenium of the corpus callosum. The results were compared between the different groups and correlated with the Mini-Mental State Evaluation (MMSE) scores.

Results

A statistically significant difference was obtained between controls and MCI patients (p<0.007) and between controls and AD patients (p<0.05) with regard to FA of the white matter in the splenium. A statistically significant difference was obtained between controls and AD patients with regard to FA in the genu (p<0.016). Moreover, there was a statistically significant difference between controls and AD patients considering the genu (p<0.016) and the frontal white matter on the right side (p<0.024). The MMSE scores correlated with the FA values measured in the genu, the splenium and frontal white matter on the right side. No significant differences were identified between patients with AD and those with MCI.

Conclusions

DTI could be of value in the early detection of white-matter damage in patients with MCI and AD. The DTI values correlate with the neuropsychological tests.     

Diffusion abnormality in posterior cingulate fiber tracts in Alzheimer’s disease: tract-specific analysis

Purpose

The aim of this study was to determine diffusion abnormalities in the posterior cingulate fiber tracts (PCFTs) in patients with Alzheimer’s disease (AD) by diffusion tensor tractography (DTT).

Materials and methods

We studied 23 AD patients and 18 age-matched normal controls who underwent magnetic resonance imaging using diffusion tensor imaging (DTI). DTT of PCFTs was generated from DTI. Mean diffusivity (MD) and fractional anisotropy (FA) were measured in co-registered voxels along with DTT of PCFTs. Student’s t-test was used to compare results between the AD patients and normal controls.

Results

The MD in PCFTs was significantly higher in AD patients than in normal controls (P = 0.019). The FA in PCFTs was significantly lower in AD patients than in normal controls (P = 0.007).

Conclusion

The abnormal MD increase and FA decrease, which is considered to indicate a net loss of barriers that restrict water molecular motion and tissue anisotropy of white matter, is consistent with neuropathological data that demonstrate partial loss of myelin, axons, and oligodendrial cells in white matter of AD brains. Our results suggest that MD and FA reflect progression of AD-related histopathological changes in the PCFTs and may represent a useful biological index for monitoring AD.     

Quantitation of brain tissue changes associated with white matter hyperintensities by diffusion‐weighted and magnetization transfer imaging: The LADIS (leukoaraiosis and disability in the elderly) study

Purpose

To explore the value of diffusion‐weighted imaging (DWI) and magnetization transfer imaging (MTI) for the improved detection and quantification of cerebral tissue changes associated with ageing and white matter hyperintensities (WMH).

Materials and Methods

DWI (n = 340) and MTI (n = 177) were performed in nine centers of the multinational Leukoaraiosis And DISability (LADIS) study investigating the impact of WMH on 65‐ to 85‐year‐old individuals without prior disability. We assessed the apparent diffusion coefficient (ADC) and magnetization transfer ratio (MTR) of normal appearing brain tissue (NABT) and within WMH and related them to subjects' age and WHM severity according to the Fazekas score.

Results

ADC and MTR values showed a significant inter‐site variation, which was stronger for the MTR. After z‐transformation multiple regression analysis revealed WMH severity and age as significant predictors of global ADC and MTR changes. Only lesional ADC, but not MTR was related to WMH severity.

Conclusion

ADC and MTR are both sensitive for age and WMH related changes in NABT. The ADC is more sensitive for tissue changes within WMH and appears to be more robust for multicenter settings. J. Magn. Reson. Imaging 2009;29:268–274. © 2009 Wiley‐Liss, Inc.     

Diagnostic evaluation of magnetization transfer and diffusion kurtosis imaging for prostate cancer detection in a re-biopsy population

Objective

To evaluate diffusion kurtosis imaging (DKI) and magnetisation transfer imaging (MTI) compared to standard MRI for prostate cancer assessment in a re-biopsy population.

Methods

Thirty-patients were imaged at 3 T including DKI (K_app and D_app) with b-values 150/450/800/1150/1500 s/mm² and MTI performed with and without MT saturation. Patients underwent transperineal biopsy based on prospectively defined MRI targets. Receiver-operating characteristic (ROC) analyses assessed the parameters and Wilcoxon-signed ranked test assessed relationships between metrics.

Results

Twenty patients had ≥ 1 core positive for cancer in a total of 26 MRI targets (Gleason 3+3 in 8, 3+4 in 12, ≥ 4+3 in 6): 13 peripheral (PZ) and 13 transition zone (TZ). The apparent diffusion coefficient (ADC) and D_app were significantly lower and the K_app and MT ratio (MTR) significantly higher in tumour versus benign tissue (all p ≤ 0.005); ROC values 0.767-1.000. Normal TZ had: lower ADC and D_app and higher K_app and MTR compared to normal PZ. MTR showed a moderate correlation to K_app (r = 0.570) and D_app (r = -0.537) in normal tissue but a poor correlation in tumours. No parameter separated low-grade (Gleason 3+3) from high-grade (≥ 3+4) disease for either PZ (p = 0.414-0.825) or TZ (p = 0.148-0.825).

Conclusion

ADC, D_app, K_app and MTR all distinguished benign tissue from tumour, but none reliably differentiated low- from high-grade disease.

Key Points

? MTR was significantly higher in PZ and TZ tumours versus normal tissue ? K _app was significantly lower and D _app higher for PZ and TZ tumours ? There was no incremental value for DKI/MTI over mono-exponential ADC parameters ? No parameter could consistently differentiate low-grade (Gleason 3+3) from high-grade (≥ 3+4) disease ? Divergent MTR/DKI values in TZ tumours suggests they offer different functional information

     

Diffusion tensor imaging to guide surgical planning in intramedullary spinal cord tumors in children

Introduction

Intramedullary spinal cord neoplasms (ISCN) in children provide diagnostic, treatment and management dilemmas. Resection results in the best chance for disease control, but the greatest risk of neurologic deficit. We hypothesize that diffusion tensor imaging (DTI) and diffusion tensor-fiber tracking (DT-FT) can help characterize margins of pediatric ISCN to aid in surgical planning.

Methods

This HIPAA compliant retrospective study was performed after Institutional Review Board approval. Patients with ISCN from a single tertiary care pediatric institution were identified, and patients with preoperative DTI were evaluated.

Results

Ten patients (eight males and two females) with ISCN with preoperative DTI were identified. The mean age was 11.1?±?6.2 years (range, 2–18 years). Eight tumors demonstrated DTI and DT-FT evidence of splayed cord tracts, and two demonstrated evidence of infiltration of cord tracts. The eight patients with splayed tracts underwent resection, with seven achieving gross-total resection and one subtotal resection. The two patients with infiltration of white matter tracts underwent biopsy of their lesion.

Conclusions

DTI of pediatric ISCN can aid in defining the margins of the tumor and relationship to the intrinsic white matter structures of the spinal cord. Splaying and displacement of fiber tracts appears to predict a discrete margin to the tumor and resectability, whereas infiltration of the white matter tracts suggests biopsy may be more advisable.     

Diffusion tensor imaging of the median nerve in recurrent carpal tunnel syndrome - initial experience

Objectives

To investigate median nerve structure in patients with recurrent carpal tunnel syndrome (CTS) using diffusion tensor imaging (DTI) and to relate DTI changes to anatomical MRI and to measures of median nerve function.

Methods

Median nerve structure was quantified according to DTI in patients with recurrent CTS and in healthy controls of similar age. Anatomical MRI was used to identify the presence of nerve compression and fibrosis. Median nerve function was measured using electromyography, a force-tracking task (accuracy of precision grip control) and clinical measures.

Results

Patients showed reduced apparent diffusion coefficient (ADC), reduced axial diffusivity (AD) and radial diffusivity (RD) along the median nerve compared with controls (P?<?0.001). Patients with endoneural fibrosis had the greatest reductions in ADC and in RD. ADC and AD correlated positively with nerve conduction velocity (R?=?0.54 and R?=?0.68, respectively) and fractional anisotropy correlated negatively with error during force-tracking (R?=?-0.58).

Conclusions

A specific pattern of DTI changes in the median nerve was identified in patients with recurrent CTS. Fibrosis may be underlying these structural changes. The correlations with nerve conduction velocity and accuracy of force control suggest that DTI is a promising technique in the study of median nerve structure in recurrent CTS.

Key Points

? Diffusion tensor imaging (DTI) offers further possibilities in musculoskeletal magnetic resonance imaging. ? DTI reveals median nerve changes in recurrent carpal tunnel syndrome. ? DTI changes were greater with signs of median nerve fibrosis. ? DTI parameters correlated with nerve conduction and force control measures. ? DTI is a promising technique in recurrent carpal tunnel syndrome.     

Relationship between cognitive impairment and white-matter alteration in Parkinson’s disease with dementia: tract-based spatial statistics and tract-specific analysis

Objectives

We investigated the relationship between white-matter alteration and cognitive status in Parkinson’s disease (PD) with and without dementia by using diffusion tensor imaging.

Methods

Twenty PD patients, 20 PDD (Parkinson’s disease with dementia) patients and 20 age-matched healthy controls underwent diffusion tensor imaging. The mean diffusivity and fractional anisotropy (FA) map of each patient group were compared with those of the control group by using tract-based spatial statistics. Tractography images of the genu of the corpus callosum fibre tracts were generated, and mean diffusivity and FA were measured.

Results

FA values in many major tracts were significantly lower in PDD patients than in control subjects; in the prefrontal white matter and the genu of the corpus callosum they were significantly lower in PDD patients than in PD patients. There was a significant correlation between the Mini-Mental State Examination (MMSE) scores and the FA values of the prefrontal white matter and the genu of the corpus callosum in patients with PD.

Conclusions

Our study shows a relationship between cognitive impairment and alteration of the prefrontal white matter and genu of the corpus callosum. These changes may be useful in assessing the onset of dementia in PD patients.

Key Points

? Dementia is a common and important non-motor sign of Parkinson’s disease (PD). ? The neuropathological basis of dementia in PD is not clear. ? DTI shows abnormalities in the prefrontal white matter in PD with dementia. ? Prefrontal white matter alteration may be useful biomarker of dementia in PD.     

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.     

Diffusion-weighted MR imaging in assessing cervical tumour response to nonsurgical therapy

Purpose

This study was undertaken to assess whether there is a correlation between the response of cervical tumours to nonsurgical therapy (chemo- and/or radiotherapy) and apparent diffusion coefficient (ADC) values.

Patients and methods

Seventeen consecutive patients prospectively underwent pelvic magnetic resonance (MR) imaging including diffusion-weighted imaging (DWI) sequences before and after nonsurgical therapy for cervical cancer. A control group of 17 patients without cervical pathology was matched to the study group. Differences in baseline ADC maps between the two groups and within the study group before and after therapy were assessed by nonparametric tests.

Results

The diameter and volume of cervical cancers decreased after therapy in 14/17 lesions (responders) and increased in 3/17 lesions (nonresponders). The ADC values of responders increased significantly (p=0.0009). Percent changes in ADC values before and after therapy were higher in responders than nonresponders (p=0.04). There was no significant difference in ADC values between responders and nonresponders at the staging MR examination (p=0.09) and no significant correlation between pretreatment ADC values and percentage of tumour reduction. Tumours with higher percent ADC value increase showed higher tumour reduction volume, but this was not significant (p=0.12).

Conclusions

ADC values of cervical cancer after therapy showed significant differences compared with pretherapy values, particularly for responders.     

Detection of early neuronal damage in CADASIL patients by q-space MR imaging

Introduction

q-Space imaging is a novel magnetic resonance (MR) technique that enables the assessment of ultrastructural changes of white matter. We hypothesized that this technique would facilitate the assessment of the progressive nature of neuronal damage seen in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

Methods

This study was approved by the institutional review board. Seven consecutive adult patients (five men and two women) with the CADASIL gene mutation were studied. Two patients were preclinical cases without overt episodes of stroke. The control group consisted of five normal volunteers. All MR examinations were performed using a 1.5-T whole-body imager. q-Space imaging was performed using a single-shot, echo-planar imaging technique and Δ/δ?=?142/17 ms. Gradient magnitudes were increased in nine steps to reach a maximal b value of 10,000 s/mm². Total acquisition time of q-space imaging was 25 min. The ADC maps calculated from the b?=?1,000 images were used for comparisons.

Results

Both q-space imaging and ADC maps depicted progressive neuronal damage. Early neuronal damage was especially well depicted using q-space imaging, with preferential involvement of the frontal lobes and central gray matters. Later progression was better depicted by b?=?1,000 ADC maps at the temporal lobes. Visual assessment of images revealed a trend for occipital lobe sparing, especially on q-space imaging.

Conclusion

q-Space imaging demonstrated early neuronal damage in a characteristic distribution. Since this method appears to be sensitive to early neuronal damage, it could conceivably aid in monitoring patients in the preclinical stage and may help in assessing the effects of future medical interventions.     

Does the use of hormonal contraceptives cause microstructural changes in cerebral white matter? Preliminary results of a DTI and tractography study

Objective

To evaluate the effect of monophasic combined oral contraceptive pill (COCP) and menstrual cycle phase in healthy young women on white matter (WM) organization using diffusion tensor imaging (DTI).

Methods

Thirty young women were included in the study; 15 women used COCP and 15 women had a natural cycle. All subjects underwent DTI magnetic resonance imaging during the follicular and luteal phase of their cycle, or in different COCP cycle phases. DTI parameters were obtained in different WM structures by performing diffusion tensor fibre tractography. Fractional anisotropy and mean diffusivity were calculated for different WM structures. Hormonal plasma concentrations were measured in peripheral venous blood samples and correlated with the DTI findings.

Results

We found a significant difference in mean diffusivity in the fornix between the COCP and the natural cycle group. Mean diffusivity values in the fornix were negatively correlated with luteinizing hormone and estradiol blood concentrations.

Conclusion

An important part in the limbic system, the fornix, regulates emotional processes. Differences in diffusion parameters in the fornix may contribute to behavioural alternations related to COCP use. This finding also suggests that the use of oral contraceptives needs to be taken into account when designing DTI group studies.

Key Points

? Diffusion tensor MRI offers new insights into brain white matter microstructure. ? The effects of oral hormonal contraception were examined in young women. ? Diffusion tensor images and hormone blood concentrations were evaluated. ? Women using hormonal contraception demonstrated higher mean diffusivity in the fornix. ? These changes may contribute to behavioural alternations related to contraception use.     

Regional apparent diffusion coefficient values in 3rd trimester fetal brain

Introduction

Apparent diffusion coefficient (ADC) values in the developing fetus can be used in the diagnosis and prognosis of prenatal brain pathologies. To this end, we measured regional ADC in a relatively large cohort of normal fetal brains in utero.

Methods

Diffusion-weighted imaging (DWI) was performed in 48 non-sedated 3rd trimester fetuses with normal structural MR imaging results. ADC was measured in white matter (frontal, parietal, temporal, and occipital lobes), basal ganglia, thalamus, pons, and cerebellum. Regional ADC values were compared by one-way ANOVA with gestational age as covariate. Regression analysis was used to examine gestational age-related changes in regional ADC. Four other cases of CMV infection were also examined.

Results

Median gestational age was 32 weeks (range, 26–33 weeks). There was a highly significant effect of region on ADC, whereby ADC values were highest in white matter, with significantly lower values in basal ganglia and cerebellum and the lowest values in thalamus and pons. ADC did not significantly change with gestational age in any of the regions tested. In the four cases with fetal CMV infection, ADC value was associated with a global decrease.

Conclusion

ADC values in normal fetal brain are relatively stable during the third trimester, show consistent regional variation, and can make an important contribution to the early diagnosis and possibly prognosis of fetal brain pathologies.