Partial volume effects in MRI studies of multiple sclerosis

We have estimated the accuracy of volume measurements of multiple sclerosis (MS) lesions made using magnetic resonance imaging (MRI) for lesions of comparable diameter to the image slice thickness. We used a phantom containing objects of known volume and obtained images using a range of slice thicknesses. Measurements on the phantom were used to assess a theoretical model, which was then employed to investigate the effects of image dimensions and geometry upon volume measurement accuracy. We observed measured volume to be dependent upon slice thickness. Thin slices gave the most accurate estimate of volume. As slice thickness increased relative to object diameter, the error in the volume measurement increased (to as much as 100%), the volume measured being dependent on the position of the object relative to the slice center. Using a signal intensity threshold value of 50% to outline objects gave results closest to the actual volume. As expected, a lower threshold value tended to give higher volume estimates (up to 100% larger), as did a semi-automated local edge detection technique. For accurate volume measurement, the slice thickness should be no more than a fifth of anticipated object diameter. For typical MS lesions (7 mm in diameter), this implies using a 1.5-mm slice thickness. For serial studies, a repositioning error of 1 mm could lead to differences in the volume measurement of individual lesions of up to 12% between studies for lesions of typical MS size and 5-mm slice thickness. These results emphasize the need for accurate patient repositioning, relatively thin slices, for regular quality assurance checks to ensure that pixel size and slice position are correct and stable over time, and that lesion outlining is performed in a consistent fashion. We would recommend the use of a 3D sequence with 1 mm cubic voxels for accurate measurements of MS lesions.     

Quantitative MRI texture analysis in chronic active multiple sclerosis lesions

ObjectiveRecently, there has been an increasing interest in “chronic enlarging” or “chronic active” multiple sclerosis (MS) lesions that are associated with clinical disability. However, investigation of dynamic lesion volume changes requires longitudinal MRI data from two or more time points. The aim of this study was to investigate the application of texture analysis (TA) on baseline T1-weighted 3D magnetization-prepared rapid acquisition gradient-echo (MPRAGE) images to differentiate chronic active from chronic stable MS lesions.Material and methodsTo identify chronic active lesions as compared to non-enhancing stable lesions, two MPRAGE datasets acquired on a 3 T MRI at baseline and after 12 months follow-up were applied to the Voxel-Guided Morphometry (VGM) algorithm. TA was performed on the baseline MPRAGE images, 36 texture features were extracted for each lesion.ResultsOverall, 374 chronic MS lesions (155 chronic active and 219 chronic stable lesions) from 60 MS patients were included in the final analysis. Multiple texture features including “DISCRETIZED_HISTO_Energy”, “GLCM_Energy”, “GLCM_Contrast” and “GLCM_Dissimilarity” were significantly higher in chronic active as compared to chronic stable lesions. Partial least squares regression yielded an area under the curve of 0.7 to differentiate both lesion types.ConclusionOur results suggest that multiple texture features extracted from MPRAGE images indicate higher intralesional heterogeneity, however they demonstrate only a fair accuracy to differentiate chronic active from chronic stable MS lesions.     

On NUFFT-based gridding for non-Cartesian MRI

For MRI with non-Cartesian sampling, the conventional approach to reconstructing images is to use the gridding method with a Kaiser-Bessel (KB) interpolation kernel. Recently, Sha et al. [L. Sha, H. Guo, A.W. Song, An improved gridding method for spiral MRI using nonuniform fast Fourier transform, J. Magn. Reson. 162(2) (2003) 250-258] proposed an alternative method based on a nonuniform FFT (NUFFT) with least-squares (LS) design of the interpolation coefficients. They described this LS_NUFFT method as shift variant and reported that it yielded smaller reconstruction approximation errors than the conventional shift-invariant KB approach. This paper analyzes the LS_NUFFT approach in detail. We show that when one accounts for a certain linear phase factor, the core of the LS_NUFFT interpolator is in fact real and shift invariant. Furthermore, we find that the KB approach yields smaller errors than the original LS_NUFFT approach. We show that optimizing certain scaling factors can lead to a somewhat improved LS_NUFFT approach, but the high computation cost seems to outweigh the modest reduction in reconstruction error. We conclude that the standard KB approach, with appropriate parameters as described in the literature, remains the practical method of choice for gridding reconstruction in MRI.     

On the down-sampling of diffusion MRI data along the angular dimension

BackgroundIt has been established that the diffusion gradient directions in diffusion MRI should be uniformly distributed in 3D spherical space, so that orientation-dependent diffusion properties (e.g., fractional anisotropy or FA) can be properly quantified. Sometimes the acquired data need to be down-sampled along the angular dimension before computing diffusion properties (e.g., to exclude data points corrupted by motion artifact; to harmonize data obtained with different protocols). It is important to quantitatively assess the impact of data down-sampling on measurement of diffusion properties.Materials and methodsHere we report 1) a numerical procedure for down-sampling diffusion MRI (e.g., for data harmonization), and 2) a spatial uniformity index of diffusion directions, aiming to predict the quality of the chosen down-sampling schemes (e.g., from data harmonization; or rejection of motion corrupted data points). We quantitatively evaluated human diffusion MRI data, which were down-sampled from 64 or 60 diffusion gradient directions to 30 directions, in terms of their 1) FA value accuracy (using fully-sampled data as the ground truth), 2) FA fitting residuals, and 3) spatial uniformity indices.ResultsOur experimental data show that the proposed spatial uniformity index is correlated with errors in FA obtained from down-sampled diffusion MRI data. The FA fitting residuals that are typically used to assess diffusion MRI quality are not correlated with either FA errors or spatial uniformity index.ConclusionsThese results suggest that the spatial uniformity index could be more valuable in assessing quality of down-sampled diffusion MRI data, as compared with FA fitting residual measures. We expect that our implemented software procedure should prove valuable for 1) guiding data harmonization for multi-site diffusion MRI studies, and 2) assessing the impact of rejecting motion corrupted data points on the accuracy of diffusion measures.     

Dynamics of lasers with two-dimensional distributed feedback

A model of a laser exploiting two-dimensional (2D) distributed feedback is developed. A new feedback mechanism can be realized using a dielectric structure with the width having double-periodical sinusoidal or chessboard modulation. It is shown that 2D Bragg resonator possesses high selectivity over both the longitudinal and the transverse indices. Within semi-classical approach nonlinear dynamics of 2D distributed feedback laser (DFL) is studied and spatial synchronization of radiation from extended active medium is demonstrated.     

Measuring extraocular muscle volume using dynamic contours

The effect of medical treatment on extraocular muscle enlargement in thyroid associated ophthalmopathy (TAO) may be monitored by measuring the change in volume of the extraocular muscles on serial orbital MRI examinations. In theory, 3D image sets offer the opportunity to minimise errors due to poor repositioning and partial volume effects. This study describes an automated technique for estimating extraocular muscle volumes from 3D datasets. Operator input is minimal and the technique is robust. Verification of the technique on both simulated and real datasets is described. For simulated image sets, both automated segmentation and manual outlining produced estimates of volume which were on average 4% less than "true" volume. For real patient data, extraocular muscle volumes measured by the automated technique were 1.6% (SD 13%) less than volumes measured by manual outlining. Coefficient of variation for repeat outlining of the same image dataset for the automated technique was 1.0%, compared with 4% for manual outlining. The manual technique took an experienced operator approximately 20 min to perform, compared to 7 min for the automated technique. The automated method is therefore rapid, reproducible and at least as accurate as other available methods.     

Correlation between enhancing lesion number and volume on standard and triple dose gadolinium-enhanced brain MRI scans from patients with multiple sclerosis.

We investigated the correlations between numbers and volumes of multiple sclerosis (MS) lesions enhancing on standard dose (SD) and triple dose (TD) gadolinium (Gd)-enhanced brain magnetic resonance imaging (MRI) scans, to clarify whether the measurement of enhancing lesion volumes or the use of TD MRI give additional information which can not be obtained by counting enhancing lesions on SD scans. SD and TD Gd-enhanced brain MRI scans were obtained every month for three months from 40 MS patients. The numbers of total and new enhancing lesions were counted, and the total volumes of enhancing lesions were measured from each of the four scans obtained with the two techniques. Univariate correlations between enhancing lesion numbers and volumes were assessed. The numbers of total and new enhancing lesions seen either on SD or TD scans were significantly correlated (r = 0.91 and 0.93, respectively). The numbers and volumes of total enhancing lesions were significantly correlated on both SD (r = 0.90), and TD (r = 0.89) scans. Moderate correlations were found between the total number of enhancing lesions on SD scans and the average difference between TD and SD scans for total enhancing lesion number (r = 0.66), and between the number of new enhancing lesions on SD scans and the average difference between TD and SD scans for new enhancing lesion number (r = 0.50). Our findings indicate that, both on SD and TD MRI, the counts and the volumes of total and new enhancing lesions are highly correlated, and that lesion counting may suffice to monitor MS activity. On the contrary, this study confirms the usefulness of TD MRI for a more complete assessment of the acute changes occurring in MS patients.     

Increased differentiation of intracranial white matter lesions by multispectral 3D-tissue segmentation: preliminary results

MRI is a very sensitive imaging modality, however with relatively low specificity. The aim of this work was to determine the potential of image post-processing using 3D-tissue segmentation technique for identification and quantitative characterization of intracranial lesions primarily in the white matter. Forty subjects participated in this study: 28 patients with brain multiple sclerosis (MS), 6 patients with subcortical ischemic vascular dementia (SIVD), and 6 patients with lacunar white matter infarcts (LI). In routine MR imaging these pathologies may be almost indistinguishable. The 3D-tissue segmentation technique used in this study was based on three input MR images (T(1), T(2)-weighted, and proton density). A modified k-Nearest-Neighbor (k-NN) algorithm optimized for maximum computation speed and high quality segmentation was utilized. In MS lesions, two very distinct subsets were classified using this procedure. Based on the results of segmentation one subset probably represent gliosis, and the other edema and demyelination. In SIVD, the segmented images demonstrated homogeneity, which differentiates SIVD from the heterogeneity observed in MS. This homogeneity was in agreement with the general histological findings. The LI changes pathophysiologically from subacute to chronic. The segmented images closely correlated with these changes, showing a central area of necrosis with cyst formation surrounded by an area that appears like reactive gliosis. In the chronic state, the cyst intensity was similar to that of CSF, while in the subacute stage, the peripheral rim was more prominent. Regional brain lesion load were also obtained on one MS patient to demonstrate the potential use of this technique for lesion load measurements. The majority of lesions were identified in the parietal and occipital lobes. The follow-up study showed qualitatively and quantitatively that the calculated MS load increase was associated with brain atrophy represented by an increase in CSF volume as well as decrease in "normal" brain tissue volumes. Importantly, these results were consistent with the patient's clinical evolution of the disease after a six-month period. In conclusion, these results show there is a potential application for a 3D tissue segmentation technique to characterize white matter lesions with similar intensities on T(2)-weighted MR images. The proposed methodology warrants further clinical investigation and evaluation in a large patient population.     

Serial gadolinium-DTPA of spinal cord MRI in multiple sclerosis: triple vs. single dose

We compared the sensitivity of single and triple dose Gd-DTPA magnetic resonance imaging (MRI) in detecting enhancing lesions in the spinal cord (SC) from 15 patients with multiple sclerosis (MS). The patients were examined monthly on four occasions. We detected two enhancing lesions in two of 15 (13%) patients when a single dose of Gd-DTPA was used. No additional lesions were detected when a triple dose of Gd-DTPA was used. These results 1) confirm that enhanced spinal cord imaging does not significantly increase the detection of active lesions in MS, 2) they do not support the general application of triple dose Gd-DTPA when examining the SC but 3) suggest that further studies taking into account SC symptoms are necessary.     

A systematic approach to magnetic resonance imaging evaluation of epiphyseal lesions

Magnetic Resonance Imaging (MRI) is the preferred modality of choice to image epiphyseal lesions. It provides excellent soft tissue resolution and extent of disease. A wide spectrum of tumor and tumor like lesions can involve the epiphysis. Early and accurate diagnosis as well as appropriate management of epiphyseal lesions is critical as these conditions may lead to disabling complications such as, limb length discrepancy, angular or joint surface deformities and secondary osteoarthritis. In this article, we discuss the role of conventional sequences, such as T1W, fluid sensitive T2W and intravenous (IV) Gadolinium enhanced sequences as well as the additional value of problem solving MRI sequences such as, chemical shift and diffusion weighted imaging. Based on the imaging findings on various MRI sequences and lesion characteristics, a systematic approach directed to the diagnoses of epiphyseal lesions is presented and discussed. MRI features of clinically and biopsy proven examples of the epiphyseal lesions, such as osteomyelitis, intra-osseous abscess, infiltrative malignancy, metastases, transient osteoporosis, subchondral insufficiency fracture, avascular necrosis, osteochondral fracture, osteochondritis dissecans, eosinophilic granuloma and geode are demonstrated. Using this systematic approach, the reader will be able to better characterize epiphyseal lesions with a potential to positively affect patient management.     

Optimization and numerical evaluation of multi-compartment diffusion MRI using the spherical mean technique for practical multiple sclerosis imaging

BackgroundThe multi-compartment diffusion MRI using the spherical mean technique (SMT) has been suggested to enhance the pathological specificity to tissue injury in multiple sclerosis (MS) imaging, but its accuracy and precision have not been comprehensively evaluated.MethodsA Cramer-Rao Lower Bound method was used to optimize an SMT protocol for MS imaging. Finite difference computer simulations of spins in packed cylinders were then performed to evaluate the influences of five realistic pathological features in MS lesions: axon diameter, axon density, free water fraction, axonal crossing, dispersion, and undulation.ResultsSMT derived metrics can be biased by some confounds of pathological variations, such as axon size and free water fraction. However, SMT in general provides valuable information to characterize pathological features in MS lesions with a clinically feasible protocol.ConclusionSMT may be used as a practical MS imaging method and should be further improved in clinical MS imaging.     

White matter changes in multiple sclerosis: correlation of q-space diffusion MRI and 1H MRS

OBJECTIVE: To explore the diagnostic usefulness of high b-value diffusion magnetic resonance brain imaging ("q-space" imaging) in multiple sclerosis (MS). More specifically, we aimed at evaluating the ability of this methodology to identify tissue damage in the so-called normal-appearing white matter (NAWM). DESIGN: In this study we examined the correlation between q-space diffusion imaging and magnetic resonance spectroscopy (MRS)-based two-dimensional 1H chemical shift imaging. Eight MS patients with different degree of disease severity and seven healthy subjects were scanned in a 1.5-T magnetic resonance imaging (MRI) scanner. The MRI protocol included diffusion tensor imaging (DTI) (with bmax of 1000 s/mm2), high b-value diffusion-weighted imaging (with bmax of 14,000 s/mm2) and 2D chemical shift imaging. The high b-value data set was analyzed using the q-space methodology to produce apparent displacement and probability maps. RESULTS: We found that the q-space diffusion displacement and probability image intensities correlated well with N-acetylaspartate levels (r=.61 and .54, respectively). Furthermore, NAWM that was abnormal on MRS was also found to be abnormal using q-space diffusion imaging. In these areas, the q-space displacement values increased from 3.8+/-0.2 to 4.6+/-0.6 microm (P<.02), the q-space probability values decreased from 7.4+/-0.3 to 6.8+/-0.3 (P<.002), while DTI revealed only a small, but still significant, reduction in fractional anisotropy values from 0.40+/-0.02 to 0.37+/-0.02 (P<.05). CONCLUSION: High b-value diffusion imaging can detect tissue damage in the NAWM of MS patients. Despite the theoretical limitation of this method, in practice it provides additional information which is clinically relevant for detection of tissue damage not seen in conventional imaging techniques.     

Encoding Textual Information in Magnetic Resonance Imaging

The data of magnetic resonance imaging (MRI) studies include not only grayscale images, but also textual information associated with them —personal data about the patient, parameters of scanning and data processing, etc. This information is stored separately from graphic images. Therefore, the possibility for its correction and loss cannot be excluded. In this paper, the method of generation of marker information on diagnostic images is described. The marker information, as a textual analogue, is entered on the image during an MRI scan and becomes an integral part of the diagnostic material along with the images of anatomical structures. The method is realized by using the selective radiofrequency presaturation of non-scanable slices oriented perpendicularly to the scanned slices. It leads to the formation of bands of reduced signal in the areas of intersections of these slices on images. In this case, the band thicknesses are equal to the thicknesses of non-scanable slices. Different combinations of these bands (marker lines) are formed directly on images and can contain information about MRI studies. This information is determined not only by positions and angle orientations of bands, but also by their thickness, total brightness and brightness distribution in the transverse direction of these bands. The examples of introducing and positioning the marker information in conventional MRI studies are presented.     

Lesion load measurements in multiple sclerosis: the effect of incorporating magnetization transfer contrast in fast-FLAIR sequence

We compared the ability and reproducibility of a fast fluid-attenuated inversion recovery (fast-FLAIR) sequence with and without a magnetization transfer (MT) pulse for detecting and measuring multiple sclerosis (MS)-related abnormalities on magnetic resonance imaging (MRI) scans from 20 patients. The Contrast-to-Noise ratios between lesions and normal-appearing white matter, lesion numbers, lesion volumes and the variability of such measurements were similar for the two sequences. This suggests that the addition of MT to FLAIR sequences as currently implemented on standard MRI scanners does not improve the detection of MS lesions.     

Relativisitic longitudinal non-Abelian oscillations in quark-antiquark plasma

We study the relativistic version of the non-Abelian, longitudinal wave in quark-antiquark plasma reported earlier by Bhat et al [Phys. Rev. D39, 649 (1989)]. We have also relaxed various approximations they made in their analysis. Both the quark and antiquark dynamics are taken in our analysis. The non-linearity arising from non-Abelian field as well as from plasma are included. Hence it is an exact longitudinal mode in relativistic quark-antiquark plasma, relevant to the study of quark gluon plasma. We find that earlier results are reproduced for non-relativistic and low amplitude oscillations, but are modified for relativistic or large amplitude waves. Further more, the above results are based on just four first-order equations for gauge invariant quantities derived from gauge covariant twelve first-order equations.     

Activity revealed in MRI of multiple sclerosis without contrast agent. A preliminary report

Disease activity in multiple sclerosis is usually accompanied by blood-brain barrier disruption, which can be assessed with contrast-enhanced magnetic resonance imaging (MRI). This paper describes a technique that gives information about disease activity using magnetization transfer MRI. Image combination methods using follow-up scans, like the one presented here, have the potential to show MS lesions that correlate with enhancement.     

Reproducibility of the gadolinium concentration measurements and of the fitting parameters of the vascular input function in the superior sagittal sinus in a patient population

It is widely recognised that the measurement of the arterial input function (AIF) is a key issue and a major source of errors in the pharmacokinetic modelling of dynamic, contrast-enhanced magnetic resonance imaging (DCE-MRI) data, and the modality of the AIF determination is still a matter of debate. In this study we addressed the problem of the intrinsic variability of the AIF within the imaged volume of a DCE-MRI scan by systematically investigating the change in the concentration of contrast agent over time and the fit parameters of the derived vascular input function (VIF) obtained from the superior sagittal sinus (SSS) of a patient population that was scanned longitudinally during treatment for high grade glioma. From a total of 82 scanning sessions, we compared the results obtained with three different DCE-MRI protocols and between two different fitting functions. We applied a correction algorithm to the measured concentration-time curves to minimize the effect of the low temporal resolution on the VIF, and investigated the effect of this algorithm on the reproducibility. Finally, where possible, we compared the signal obtained in the SSS to the signal obtained in the middle cerebral artery. We found a good intrapatient reproducibility of both the measured gadolinium concentrations and VIF parameters, and that the variation of the parameters due to slice location within a patient was significantly lower than the intra patient variation. Intrapatient, interscan differences were significantly less marked than inter-patient differences showing a good intraclass correlation coefficient. We did encounter a MRI protocol dependence of the VIF fitting parameters. The correction algorithm significantly improved the reproducibility of the fitting parameters. These results support the idea that the use of a patient specific measured AIF, not necessarily averaged over a large volume, offers a significant benefit with respect to an external AIF or a measured cohort average AIF.     

A longitudinal study comparing the sensitivity of CSE and RARE sequences in detecting new multiple sclerosis lesions

In this longitudinal study, we evaluated the sensitivities of dual-echo, conventional spin-echo (CSE), and rapid-acquisition relaxation-enhanced (RARE) scans for detecting the appearance of new lesions in multiple sclerosis (MS). Dual echo, CSE, and RARE scans were obtained on four occasions each separated by 28 days from five patients with relapsing-remitting MS using a 1.5-Tesla machine. A total of 44 new lesions were detected by the two sequences. Thirty-five lesions were seen on both sequences, three only on CSE and six only on FSE. This study indicates that CSE may be substituted by RARE when monitoring short-term disease activity in MS.     

Choice of contrast enhancement index for dynamic magnetic resonance mammography

Indices are often used in dynamic MRI of the breast to quantitate signal enhancement within suspicious lesions. Two indices are commonly used: one calculates the difference in pre- and postcontrast signal intensity, normalised to a base-line signal intensity such as that of fat (which does not enhance) whilst the other calculates the ratio of pre- to postcontrast signal intensity. The results of a computational simulation are presented which demonstrate the superiority of the normalised signal difference index, based on the criterion that the best index is that which is least influenced by initial tissue T₁. This hypothesis was tested by comparing the two indices in a group of patients with clinical or mammographic suspicion of recurrent breast carcinoma. Of 37 patient examinations using Gadolinium enhanced MRI of the breast, 11 patients showed 13 lesions with some degree of enhancement, which were subsequently diagnosed histologically as either benign or malignant. The normalised signal difference index showed no overlap between the benign and malignant groups, whereas some overlap was observed with the signal ratio index. The clinical findings are therefore consistent with the results of the computational simulation.     

Correcting saturation effects of the arterial input function in dynamic susceptibility contrast-enhanced MRI: a Monte Carlo simulation

To prevent systematic errors in quantitative brain perfusion studies using dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI), a reliable determination of the arterial input function (AIF) is essential. We propose a novel algorithm for correcting distortions of the AIF caused by saturation of the peak amplitude and discuss its relevance for longitudinal studies. The algorithm is based on the assumption that the AIF can be separated into a reliable part at low contrast agent concentrations and an unreliable part at high concentrations. This unreliable part is reconstructed, applying a theoretical framework based on a transport-diffusion theory and using the bolus-shape in the tissue. A validation of the correction scheme is tested by a Monte Carlo simulation. The input of the simulation was a wide range of perfusion, and the main aim was to compare this input to the determined perfusion parameters. Another input of the simulation was an AIF template derived from in vivo measurements. The distortions of this template was modeled via a Rician distribution for image intensities. As for a real DSC-MRI experiment, the simulation returned the AIF and the tracer concentration-dependent signal in the tissue. The novel correction scheme was tested by deriving perfusion parameters from the simulated data for the corrected and the uncorrected case. For this analysis, a common truncated singular value decomposition approach was applied. We find that the saturation effect caused by Rician-distributed noise leads to an overestimation of regional cerebral blood flow and regional cerebral blood volume, as compared to the input parameter. The aberration can be amplified by a decreasing signal-to-noise ratio (SNR) or an increasing tracer concentration. We also find that the overestimation can be successfully eliminated by the proposed saturation-correction scheme. In summary, the correction scheme will allow DSC-MRI to be expanded towards higher tracer concentrations and lower SNR and will help to increase the measurement to measurement reproducibility for longitudinal studies.