Role of diffusion tensor imaging metrics and in vivo proton magnetic resonance spectroscopy in the differential diagnosis of cystic intracranial mass lesions

The purpose of this study was to determine whether proton magnetic resonance spectroscopy (PMRS) and diffusion tensor imaging (DTI) indices, fractional anisotropy (FA) and mean diffusivity (MD) can be used to distinguish brain abscess from cystic brain tumors, which are difficult to distinguish by conventional magnetic resonance imaging (MRI). Fifty-three patients with intracranial cystic mass lesions and 10 normal controls were studied. Conventional MRI, PMRS and DTI of all the patients were performed on a 1.5-T GE scanner. Forty patients were with brain abscess and 13 with cystic tumors. Cytosolic amino acids (AAs) were present in 32 of 40 brain abscess patients. Out of 13 patients with cystic tumors, lactate and choline were seen in 3 and only lactate was present in 10 patients on PMRS. All 40 cases of abscess had high FA, while all 13 cases of tumor cysts had high MD values. We conclude that FA measurements are more sensitive in predicting the abscess, while PMRS and MD are more specific in differentiating abscess from cystic tumors. We suggest that PMRS should be combined with DTI rather than with diffusion-weighted imaging as FA can be used as an additional parameter for separation of abscess from other cystic intracranial mass lesions.     

Understanding changes in DTI metrics in patients with different stages of neurocysticercosis

Diffusion tensor imaging (DTI) was performed on 25 patients with neurocysticercosis (NCC). The aim of this study was to investigate the changes in DTI measures during the evolutionary course of NCC lesions from vesicular to calcified stage in the brain. DTI measures were quantified from the NCC lesions of all patients. On the basis of conventional imaging findings, NCC lesions were classified into vesicular, vesicular colloidal, granular nodular and calcified stages. Significant inverse correlation was observed between the evolutionary stage of NCC lesion and mean diffusivity (MD; r=−0.748, P<0.001) and spherical anisotropy (CS; r=−0.585, P<.001) values. Significant direct correlations were observed between evolutionary stages of NCC lesion and mean fractional anisotropy (FA; r=0.575, P<0.001), linear anisotropy (CL; r=0.478, p<0.001) and planar anisotropy (CP; r=0.561, p<0.001) values. Successive decrease in MD values calculated from NCC lesions was observed, moving from vesicular to granular nodular stage. On FA, CL and CP maps, a significant increase in signal intensity value was observed in calcified as compared to other stages. We conclude that DTI measures may indicate the evolutionary changes in NCC from vesicular to calcified stage.     

Analyzing diffusion tensor images with ghosting artifacts: the effects of direct and indirect normalization

The current study aims to assess the applicability of direct or indirect normalization for the analysis of fractional anisotropy (FA) maps in the context of diffusion-weighted images (DWIs) contaminated by ghosting artifacts. We found that FA maps acquired by direct normalization showed generally higher anisotropy than indirect normalization, and the disparities were aggravated by the presence of ghosting artifacts in DWIs. The voxel-wise statistical comparisons demonstrated that indirect normalization reduced the influence of artifacts and enhanced the sensitivity of detecting anisotropy differences between groups. This suggested that images contaminated with ghosting artifacts can be sensibly analyzed using indirect normalization.     

Intersubject variability in the analysis of diffusion tensor images at the group level: fractional anisotropy mapping and fiber tracking techniques

Introduction

Diffusion tensor imaging (DTI) provides comprehensive information about quantitative diffusion and connectivity in the human brain. Transformation into stereotactic standard space is a prerequisite for group studies and requires thorough data processing to preserve directional inter-dependencies. The objective of the present study was to optimize technical approaches for this preservation of quantitative and directional information during spatial normalization in data analyses at the group level.

Methods

Different averaging methods for mean diffusion-weighted images containing DTI information were compared, i.e., region of interest-based fractional anisotropy (FA) mapping, fiber tracking (FT) and corresponding tractwise FA statistics (TFAS). The novel technique of intersubject FT that takes into account directional information of single data sets during the FT process was compared to standard FT techniques. Application of the methods was shown in the comparison of normal subjects and subjects with defined white matter pathology (alterations of the corpus callosum).

Results

Fiber tracking was applied to averaged data sets and showed similar results compared with FT on single subject data. The application of TFAS to averaged data showed averaged FA values around 0.4 for normal controls. The values were in the range of the standard deviation for averaged FA values for TFAS applied to single subject data. These results were independent of the applied averaging technique. A significant reduction of the averaged FA values was found in comparison to TFAS applied to data from subjects with defined white matter pathology (FA around 0.2).

Conclusion

The applicability of FT techniques in the analysis of different subjects at the group level was demonstrated. Group comparisons as well as FT on group averaged data were shown to be feasible. The objective of this work was to identify the most appropriate method for intersubject averaging and group comparison which incorporates intersubject variability of the directional information.     

Diffusion properties of cortical and pericortical tissue: regional variations, reliability and methodological issues

Characterizing the diffusion properties of cortical tissue is complicated by intersubject variability in the relative locations of gyri and sulci. Here we extend methods of measuring the average diffusion properties of gyral and sulcal structures after they have been aligned to a common template of cortical surface anatomy. Diffusion tensor image (DTI) data were gathered from 82 young subjects and co-registered with high-resolution T1 images that had been inflated and co-registered to a hemispherically unified spherical coordinate system based on FreeSurfer. We analyzed fractional anisotropy (FA), mean diffusivity (MD) and the novel quantity of cortical primary diffusion direction (cPDD) at five surfaces parallel to the white/gray junction, spanning approximately 5 mm from the pial surface into white matter. FA increased with increasing depth, whereas MD and cPDD were reduced. There were highly significant and reliable regional differences in FA, MD and cPDD as well as systematic differences between cortical lobes and between the two hemispheres. The influence of nearby cortical spinal fluid (CSF), local cortical curvature and thickness, and sulcal depth was also investigated. We found that FA correlated significantly with cortical curvature and sulcal depth, while MD was strongly influenced by nearby CSF. The measurement of FA, MD and cPDD near the cortical surface clarifies the organization of fiber projections to and from the cortex.     

Validation of the anisotropy index ellipsoidal area ratio in diffusion tensor imaging

A new diffusion anisotropy index, ellipsoidal area ratio (EAR), was described recently and proved to be less noise-sensitive than fractional anisotropy (FA) by theory and simulation. Here we show that EAR has higher signal-to-noise ratios than FA in average diffusion tensor imaging data from 40 normal subjects. EAR was also more sensitive than FA in detecting white matter abnormalities in a patient with widespread diffuse axonal injury. Monte Carlo simulation showed that EAR's mean values are more biased by noise than FA when anisotropy is small, both for single fiber tracts and when fiber tracts cross. However, the improved signal-to-noise ratio of EAR relative to FA suggests that EAR may be a superior measure of anisotropy both in quantifying both deep white matter with relatively uniform fiber tracts and pericortical white matter structure with relatively low anisotropy and fiber crossings.     

Alterations in diffusion properties of white matter in Williams syndrome

Diffusion tensor imaging (DTI) was used to investigate the involvement of brain white matter in Williams syndrome (WS), a genetic neurodevelopmental disorder. Whole-brain DTIs were obtained from 16 young adults with WS and 16 normal controls. A voxel-based analysis was performed to compare fractional anisotropy (FA) values between the two groups. A tract-based analysis was also performed to compare FA values between the two groups along two major white matter tracts that pass through the external capsule: the uncinate and inferior fronto-occipital fasciculi. Several regions of both increased and decreased FA were found within major white matter tracts that connect functional regions that have previously been implicated in the cognitive and neurological symptoms of the syndrome. The tract-based analysis provided additional insight into the involvement of specific white matter tracts implicated in the voxel-based analysis within the external capsule. The results from this study support previously reported changes in white matter diffusion properties in WS and demonstrate the potential usefulness for tract-based analysis in future studies of the disorder.     

Removal of partial volume averaging with free water in MR diffusion tensor imaging using inversion recovery for b0 image

Purpose

To remove the partial volume averaging effect of free water in MR diffusion imaging of neural tissues by use of the fluid attenuated inversion recovery (FLAIR) without the penalty of an extended scan time.

Materials and methods

The magnetic resonance images were obtained from a normal volunteer in a coronal slice orientation at 3 T with the 20-channel rf coil. In diffusion imaging only the b0 images were obtained with the FLAIR contrast while the diffusion weighted images were obtained without the FLAIR contrast. A composition of FLAIR b0 and non-FLAIR diffusion weighted images was used in calculating the diffusion tensor and fractional anisotropy after compensating the reduced signal amplitude due to the inversion recovery in the FLAIR b0 images. The fractional anisotropy of the non-FLAIR, FLAIR, and the composite methods were analyzed for the mean and histogram in the corpus callosum, cervical spine, and the fornix tracts.

Results

The partial volume averaging effect was observed in the corpus callosum, the cervical spine, and the fornix tracts in the non-FLAIR b0 and diffusion images. The partial volume averaging effect was removed in the FLAIR diffusion images which took more than twice the scan time than the non-FLAIR diffusion imaging. The proposed composite FLAIR diffusion imaging removed the partial volume averaging effect as in the FLAIR diffusion imaging. The distribution of the FA histogram was very different between the non-FLAIR and FLAIR diffusion images, while it was very similar between the FLAIR and the composite FLAIR after correcting the white matter signal in the FLAIR b0 images.

Conclusions

The proposed composite FLAIR diffusion imaging method was equally effective in removing the partial volume averaging effect as the FLAIR diffusion imaging at a limited increase of the scan time since only a small number of b0 images needed to be obtained with the FLAIR contrast.     

Dependence of the fractional anisotropy in cervical spine from the number of diffusion gradients,repeated acquisition and voxel size

The aim of this study is to investigate the consequences of using different gradient schemes, number of repeated measurements and voxel size on the fractional anisotropy (FA) value in a diffusion tensor imaging (DTI) sequence on the cervical tract of the spinal cord. Twenty healthy volunteers underwent a total of 86 DTI axial acquisitions performed by using different voxel size and number of diffusion gradient directions (NDGDs). Three different diffusion gradient schemes were applied, named 6, 15 and 32 according to the NDGD. Furthermore, some acquisitions were repeated to investigate the effects of image averaging on FA value.     

Comparison of diffusion tensor,dynamic susceptibility contrast MRI and Tc-Tetrofosmin brain SPECT for the detection of recurrent high-grade glioma

Introduction

Treatment induced necrosis is a relatively frequent finding in patients treated for high-grade glioma. Differentiation by imaging modalities between glioma recurrence and treatment induced necrosis is not always straightforward. This is a comparative study of diffusion tensor imaging (DTI), dynamic susceptibility contrast MRI and ^99mTc-Tetrofosmin brain single-photon emission computed tomography (SPECT) for differentiation of recurrent glioma from treatment induced necrosis.

Methods

A prospective study was made of 30 patients treated for high-grade glioma who had suspected recurrent tumor on follow-up MRI. All had been treated by surgical resection of the tumor followed by standard postoperative radiotherapy with chemotherapy. No residual tumor had been found on brain imaging immediately after the initial treatment. All the patients were studied with dynamic susceptibility contrast brain MRI and, within a week, ^99mTc-Tetrofosmin brain SPECT.

Results

Both ^99mTc-Tetrofosmin brain SPECT and dynamic susceptibility contrast MRI could discriminate between tumor recurrence and treatment induced necrosis with 100% sensitivity and 100% specificity. An apparent diffusion coefficient (ADC) ratio cut-off value of 1.27 could differentiate recurrence from treatment induced necrosis with 65% sensitivity and 100% specificity and a fractional anisotropy (FA) ratio cut-off value of 0.47 could differentiate recurrence from treatment induced necrosis with 57% sensitivity and 100% specificity. A significant correlation was demonstrated between ^99mTc-Tetrofosmin uptake ratio and rCBV (P = 0.003).

Conclusions

Dynamic susceptibility contrast MRI and brain SPECT with ^99mTc-Tetrofosmin had the same accuracy and may be used to detect recurrent tumor following treatment for glioma. DTI also showed promise for the detection of recurrent tumor, but was inferior to both dynamic susceptibility contrast MRI and brain SPECT.     

Moderating registration misalignment in voxelwise comparisons of DTI data: a performance evaluation of skeleton projection

An evaluative methodology and five accompanying performance measures were developed to quantitatively assess the performance of the skeleton projection algorithm constituting the heart of tract-based spatial statistics (TBSS). The performance measures were designed to quantify the accuracy of skeleton projection in its indented task of alleviating any residual misalignment that may remain after image registration. A ground truth fractional anisotropy (FA) image was slightly warped using a realistic warp field that served to model post-registration residual misalignment of varying magnitudes. Skeleton projection was then used to register the warped FA image to the ground truth. Performing skeleton projection was found to yield up to 50% better correspondence between the values of FA compared to smoothing, despite the fact that less than 10% of post-registration misalignment was corrected. The align-max-with-max strategy underlying TBSS was posited as a potential explanation for this high correspondence in the values of FA, at the expense of lesser alignment between anatomically concordant voxels.     

Geometric analysis of the b-dependent effects of Rician signal noise on diffusion tensor imaging estimates and determining an optimal b value

The optimal diffusion weighting (DW) factor, b, for use in diffusion tensor imaging (DTI) studies remains uncertain. In this study, the geometric relations of DW quantities are examined, in particular, the effects of Rician noise in the measured magnetic resonance signal. This geometric analysis is used to make theoretical predictions for selecting a b value to reduce the influence of noise. It is shown that the optimal b value for DTI studies in healthy human parenchyma is approximately b=1200 s mm⁻², with a simple relation given as well for a given expected apparent diffusion coefficient. Monte-Carlo simulations on sets of realistic DTI measures are then performed, verifying the optimal DW for minimizing estimate errors. The effects of noise on various DTI parameters such as anisotropy indices (fractional anisotropy and scaled relative anisotropy), mean diffusivity, radial diffusivity, eigenvalues and the direction of the first eigenvector are investigated as well.     

Aging effects on cerebral asymmetry: a voxel-based morphometry and diffusion tensor imaging study

The hemispheres of the human brain are functionally and structurally asymmetric. The purpose of this study was to evaluate the effects of aging on gray and white matter asymmetry. Two hundred twenty-six right-handed normal volunteers aged 21–71 years were included in this study. The effects of aging on gray matter volume asymmetry and white matter fractional anisotropy asymmetry were evaluated with use of voxel-based morphometry and voxel-based analysis of fractional anisotropy maps derived from diffusion tensor imaging (DTI), respectively. The voxel-based morphometry showed no significant correlation between age and gray matter volume asymmetry. The voxel-based analysis of DTI also showed no significant correlation between age and white matter fractional anisotropy asymmetry. Our results showed no significant effects of aging on either gray matter volume asymmetry or white matter fractional anisotropy asymmetry.     

Exploratory voxel-based analysis of diffusion indices and hemispheric asymmetry in normal aging

Age-related microstructural changes in brain white matter can be studied by utilizing indices derived from diffusion tensor imaging (DTI): apparent diffusion coefficient (ADC) and fractional anisotropy (FA). The objective of this study is to examine alterations in FA and ADC by employing exploratory voxel-based analysis (VBA) and region(s) of interest (ROI)-based analysis. A highly nonlinear registration algorithm was used to align the ADC and FA image volumes of different subjects to perform accurate voxel-level statistics for two age groups, as well as for hemispheric asymmetry for both age groups. VBA shows significant age-related decline in FA with frontal predominance (frontal white matter, and genu and anterior body of the corpus callosum), superior portions of a splenium and highly oriented fibers of the posterior limb of the internal capsule and the anterior and posterior limbs of the external capsule. Hemispheric asymmetry of FA, as assessed by VBA, showed that for the young-age group, significant right-greater-than-left asymmetry exists in the genu, splenium and body of the corpus callosum and that left-greater-than-right asymmetry exists in the anterior limb of the external capsule and in the posterior limb of the internal capsule, thalamus, cerebral peduncle and temporal-parietal regions. VBA of the hemispheric asymmetry of the middle-age group revealed much less asymmetry. Regions showing age-related changes and hemispheric asymmetry from VBA were, for a majority of the findings, in conformance with ROI analysis and with the known pattern of development and age-related degradation of fiber tracks. The study shows the feasibility of the VBA of DTI indices for exploratory investigations of subtle differences in population cohorts, especially when findings are not localized and/or known a priori.     

Mapping the human brain white matter tracts relative to cortical and deep gray matter using diffusion tensor imaging at high spatial resolution

The mapping of the human brain white matter fiber networks relative to deep subcortical and cortical gray matter requires high spatial resolution which is challenged by the low signal-to-noise ratio. The purpose of this short report was to introduce a whole brain high spatial resolution diffusion tensor imaging (DTI) protocol that enabled for the first time the mapping of corticopontocerebellar, frontostriatal and thalamofrontal fiber pathways in addition to other limbic, commissural, association and projection white matter pathways relative to the segmented deep gray (e.g., caudate nuclei) and the cortical lobes. Our DTI acquisition protocol and analysis strategy provide important template for brain-behavior research and for teaching brain mapping and are clinically affordable for patient comfort.     

High-resolution in vivo diffusion tensor imaging of the injured cat spinal cord using self-navigated,interleaved, variable-density spiral acquisition (SNAILS-DTI)

Diffusion tensor magnetic resonance imaging (DTI) is useful for studying the microstructural changes in the spinal cord following traumatic injury; however, image quality is generally poor due to the small size of the spinal cord, physiological motion and susceptibility artifacts. Self-navigated, interleaved, variable-density spiral diffusion tensor imaging (SNAILS-DTI) is a distinctive pulse sequence that bypasses many of the challenges associated with DTI of the spinal cord, particularly if imaging gradient hardware is of conventional quality. In the current study, we have demonstrated the feasibility of implementing SNAILS-DTI on a clinical 3.0-T MR scanner and examined the effect of navigator filter parameters on image quality and reconstruction time. Results demonstrate high-quality, high-resolution (546 μm×546 μm) in vivo DTI images of the cat spinal cord after traumatic spinal cord injury.     

On high b diffusion imaging in the human brain: ruminations and experimental insights

Interest in the manner in which brain tissue signal decays with b factor in diffusion imaging schemes has grown in recent years following the observation that the decay curves depart from purely monoexponential decay behavior. Regardless of the model or fitting function proposed for characterizing sufficiently sampled decay curves (vide infra), the departure from monoexponentiality spells increased tissue characterization potential. The degree to which this potential can be harnessed to improve specificity, sensitivity and spatial localization of diseases in brain, and other tissues, largely remains to be explored. Furthermore, the degree to which currently popular diffusion tensor imaging methods, including visually impressive white matter fiber “tractography” results, have almost completely ignored the nonmonoexponential nature of the basic signal decay with b factor is worthy of communal introspection. Here we limit our attention to a review of the basic experimental features associated with brain water signal diffusion decay curves as measured over extended b-factor ranges, the simple few parameter fitting functions that have been proposed to characterize these decays and the more involved models, e.g.,“ruminations,” which have been proposed to account for the nonmonoexponentiality to date.     

Assessment of hepatocellular carcinoma using apparent diffusion coefficient and diffusion kurtosis indices: preliminary experience in fresh liver explants

Objectives

The objective was to perform ex vivo evaluation of non-Gaussian diffusion kurtosis imaging (DKI) for assessment of hepatocellular carcinoma (HCC), including presence of treatment-related necrosis, using fresh liver explants.

Methods

Twelve liver explants underwent 1.5-T magnetic resonance imaging using a DKI sequence with maximal b-value of 2000 s/mm². A standard monoexponential fit was used to calculate apparent diffusion coefficient (ADC), and a non-Gaussian kurtosis fit was used to calculate K, a measure of excess kurtosis of diffusion, and D, a corrected diffusion coefficient accounting for this non-Gaussian behavior. The mean value of these parameters was measured for 16 HCCs based upon histologic findings. For each metric, HCC-to-liver contrast was calculated, and coefficient of variation (CV) was computed for voxels within the lesion as an indicator of heterogeneity. A single hepatopathologist determined HCC necrosis and cellularity.

Results

The 16 HCCs demonstrated intermediate-to-substantial excess diffusional kurtosis, and mean corrected diffusion coefficient D was 23% greater than mean ADC (P=.002). HCC-to-liver contrast and CV of HCC were greater for K than ADC or D, although these differences were significant only for CV of HCCs (P≤.046). ADC, D and K all showed significant differences between non-, partially and completely necrotic HCCs (P≤.004). Among seven nonnecrotic HCCs, cellularity showed a strong inverse correlation with ADC (r=−0.80), a weaker inverse correlation with D (− 0.24) and a direct correlation with K (r= 0.48).

Conclusions

We observed non-Gaussian diffusion behavior for HCCs ex vivo; this DKI model may have added value in HCC characterization in comparison with a standard monoexponential model of diffusion-weighted imaging.     

Non-Gaussian diffusion MRI assessment of brain microstructure in mild cognitive impairment and Alzheimer’s disease

We report the first application of a novel diffusion-based MRI method, called diffusional kurtosis imaging (DKI), to investigate changes in brain tissue microstructure in patients with mild cognitive impairment (MCI) and AD and in cognitively intact controls. The subject groups were characterized and compared in terms of DKI-derived metrics for selected brain regions using analysis of covariance with a Tukey multiple comparison correction. Receiver operating characteristic (ROC) and binary logistic regression analyses were used to assess the utility of regional diffusion measures, alone and in combination, to discriminate each pair of subject groups. ROC analyses identified mean and radial kurtoses in the anterior corona radiata as the best individual discriminators of MCI from controls, with the measures having an area under the ROC curve (AUC) of 0.80 and 0.82, respectively. The next best discriminators of MCI from controls were diffusivity and kurtosis (both mean and radial) in the prefrontal white matter (WM), with each measure having an AUC between 0.77 and 0.79. Finally, the axial diffusivity in the hippocampus was the best overall discriminator of MCI from AD, having an AUC of 0.90. These preliminary results suggest that non-Gaussian diffusion MRI may be beneficial in the assessment of microstructural tissue damage at the early stage of MCI and may be useful in developing biomarkers for the clinical staging of AD.     

Development and initial evaluation of 7-T q-ball imaging of the human brain

Diffusion tensor imaging (DTI) noninvasively depicts white matter connectivity in regions where the Gaussian model of diffusion is valid but yields inaccurate results in those where diffusion has a more complex distribution, such as fiber crossings. q-ball imaging (QBI) overcomes this limitation of DTI by more fully characterizing the angular dependence of intravoxel diffusion with larger numbers of diffusion-encoding directional measurements at higher diffusion-weighting factors (b values). However, the former technique results in longer acquisition times and the latter technique results in a lower signal-to-noise ratio (SNR). In this project, we developed specialized 7-T acquisition methods utilizing novel radiofrequency pulses, eight-channel parallel imaging EPI and high-order shimming with a phase-sensitive multichannel B0 field map reconstruction. These methods were applied in initial healthy adult volunteer studies, which demonstrated the feasibility of performing 7-T QBI. Preliminary comparisons of 3 T with 7 T within supratentorial crossing white matter tracts documented a 79.5% SNR increase for b=3000 s/mm2 (P=.0001) and a 38.6% SNR increase for b=6000 s/mm2 (P=.015). With spherical harmonic reconstruction of the q-ball orientation distribution function at b=3000 s/mm2, 7-T QBI allowed for accurate visualization of crossing fiber tracts with fewer diffusion-encoding acquisitions as compared with 3-T QBI. The improvement of 7-T QBI at b factors as high as 6000 s/mm2 resulted in better angular resolution as compared with 3-T QBI for depicting fibers crossing at shallow angles. Although the increased susceptibility effects at 7 T caused problematic distortions near brain-air interfaces at the skull base and posterior fossa, these initial 7-T QBI studies demonstrated excellent quality in much of the supratentorial brain, with significant improvements as compared with 3-T acquisitions in the same individuals.