T1 and proton density at 7 T in patients with multiple sclerosis: an initial study

Magnetic resonance imaging of cortical lesions due to multiple sclerosis (MS) has been hampered by the lesions' small size and low contrast to adjacent, normal-appearing tissue. Knowing cortical lesion T1 and proton density (PD) would be highly beneficial for the process of developing and optimizing dedicated magnetic resonance (MR) sequences through computer modeling of MR tissue responses. Eight patients and seven healthy control subjects were scanned at 7 T using a series of inversion recovery turbo field echo scans with varying inversion times. Regions of interest were drawn in white matter, gray matter, cortical lesions, white matter lesions and cerebrospinal fluid. White matter and gray matter T1s were significantly higher in MS patients than in controls. Cortical and white matter lesion T1 and PD are also presented for the first time. The advantages of ultrahigh field MR imaging will be important for future investigations in MS research and sequence optimization for the detection of cortical lesions.     

MR spectroscopic imaging of glutathione in the white and gray matter at 7 T with an application to multiple sclerosis

Detection of glutathione (GSH) is technically challenging at clinical field strengths of 1.5 or 3 T due to its low concentration in the human brain coupled with the fact that conventional single-echo acquisitions, typically used for magnetic resonance (MR) spectroscopy acquisitions, cannot be used to resolve GSH given its overlap with other resonances. In this study, an MR spectral editing scheme was used to generate an unobstructed detection of GSH at 7 T. This technique was used to obtain normative white (WM) and gray matter (GM) GSH concentrations over a two-dimensional region. Results indicated that GSH was significantly higher (P<.001) in GM relative to WM in normal subjects. This finding is consistent with previous radionuclide experiments and histochemical staining and validates this 7 T MR spectroscopy technique. To our knowledge, this is the first study to report normative differences in WM and GM glutathione concentrations in the human brain. Glutathione is a biomarker for oxidative status and this non-invasive in vivo measurement of GSH was used to explore its sensitivity to oxidative state in multiple sclerosis (MS) patients. There was a significant reduction (P<.001) of GSH between the GM in MS patients and normal controls. No statistically significant GSH differences were found between the WM in controls and MS patients. Reduced GSH was also observed in a MS WM lesion. This preliminary investigation demonstrates the potential of this marker to probe oxidative state in MS.     

Automatic white matter lesion segmentation using an adaptive outlier detection method

White matter (WM) lesions are diffuse WM abnormalities that appear as hyperintense (bright) regions in cranial magnetic resonance imaging (MRI). WM lesions are often observed in older populations and are important indicators of stroke, multiple sclerosis, dementia and other brain-related disorders. In this paper, a new automated method for WM lesions segmentation is presented. In the proposed method, the presence of WM lesions is detected as outliers in the intensity distribution of the fluid-attenuated inversion recovery (FLAIR) MR images using an adaptive outlier detection approach. Outliers are detected using a novel adaptive trimmed mean algorithm and box-whisker plot. In addition, pre- and postprocessing steps are implemented to reduce false positives attributed to MRI artifacts commonly observed in FLAIR sequences. The approach is validated using the cranial MRI sequences of 38 subjects. A significant correlation (R=0.9641, P value=3.12×10(-3)) is observed between the automated approach and manual segmentation by radiologist. The accuracy of the proposed approach was further validated by comparing the lesion volumes computed using the automated approach and lesions manually segmented by an expert radiologist. Finally, the proposed approach is compared against leading lesion segmentation algorithms using a benchmark dataset.     

Automatic segmentation of brain white matter and white matter lesions in normal aging: comparison of five multispectral techniques

White matter loss, ventricular enlargement and white matter lesions are common findings on brain scans of older subjects. Accurate assessment of these different features is therefore essential for normal aging research. Recently, we developed a novel unsupervised classification method, named ‘Multispectral Coloring Modulation and Variance Identification’ (MCMxxxVI), that fuses two different structural magnetic resonance imaging (MRI) sequences in red/green color space and uses Minimum Variance Quantization (MVQ) as the clustering technique to segment different tissue types. Here we investigate how this method performs compared with several commonly used supervised image classifiers in segmenting normal-appearing white matter, white matter lesions and cerebrospinal fluid in the brains of 20 older subjects with a wide range of white matter lesion load and brain atrophy. The three tissue classes were segmented from T₁-, T₂-, T₂?- and fluid attenuation inversion recovery (FLAIR)-weighted structural MRI data using MCMxxxVI and the four supervised multispectral classifiers available in the Analyze package, namely, Back-Propagated Neural Networks, Gaussian classifier, Nearest Neighbor and Parzen Windows. Bland–Altman analysis and Jaccard index values indicated that, in general, MCMxxxVI performed better than the supervised multispectral classifiers in identifying the three tissue classes, although final manual editing was still required to deliver radiologically acceptable results. These analyses show that MVQ, as implemented in MCMxxxVI, has the potential to provide quick and accurate white matter segmentations in the aging brain, although further methodological developments are still required to automate fully this technique.     

Automatic segmentation of white matter lesions on magnetic resonance images of the brain by using an outlier detection strategy

White matter lesions (WMLs) are commonly observed on the magnetic resonance (MR) images of normal elderly in association with vascular risk factors, such as hypertension or stroke. An accurate WML detection provides significant information for disease tracking, therapy evaluation, and normal aging research. In this article, we present an unsupervised WML segmentation method that uses Gaussian mixture model to describe the intensity distribution of the normal brain tissues and detects the WMLs as outliers to the normal brain tissue model based on extreme value theory. The detection of WMLs is performed by comparing the probability distribution function of a one-sided normal distribution and a Gumbel distribution, which is a specific extreme value distribution. The performance of the automatic segmentation is validated on synthetic and clinical MR images with regard to different imaging sequences and lesion loads. Results indicate that the segmentation method has a favorable accuracy competitive with other state-of-the-art WML segmentation methods.     

Quantitative estimation of brain white matter abnormalities in elderly subjects using magnetic resonance imaging

Twenty-five elderly subjects were examined with brain magnetic resonance imaging (MRI). The subjects were divided into two groups: those with Mini-Mental State Examination (MMSE) scores above 25, and those subjects with MMSE scores between 18 and 24. The degree of white matter abnormalities (WMA) (expressed as relative volumes) as well as the presence of cerebrovascular risk factors were evaluated in the two groups. We found that a) subjects with low MMSE scores had significantly larger relative volumes of WMA than the subjects with higher scores, b) a significant correlation (r_s = 0.53, p < 0.009) between MMSE scores and the relative volume of WMA was also established, and c) a weak significant correlation (r_s = −0.51, p < 0.05) between arterial blood pressure and WMA was found in the subjects with high MMSE scores. Besides these findings no other correlations between the presence of cerebrovascular risk factors and WMA were found in any of the groups.     

Biexponential analysis of diffusion-related signal decay in normal human cortical and deep gray matter

Diffusion imaging with high-b factors, high spatial resolution and cerebrospinal fluid signal suppression was performed in order to characterize the biexponential nature of the diffusion-related signal decay with b-factor in normal cortical gray and deep gray matter (GM). Integration of inversion pulses with a line scan diffusion imaging sequence resulted in 91% cerebrospinal fluid signal suppression, permitting accurate measurement of the fast diffusion coefficient in cortical GM (1.142+/-0.106 microm2/ms) and revealing a marked similarity with that found in frontal white matter (WM) (1.155+/-0.046 microm2/ms). The reversal of contrast between GM and WM at low vs high b-factors is shown to be due to a significantly faster slow diffusion coefficient in cortical GM (0.338+/-0.027 microm2/ms) than in frontal WM (0.125+/-0.014 microm2/ms). The same characteristic diffusion differences between GM and WM are observed in other brain tissue structures. The relative component size showed nonsignificant differences among all tissues investigated. Cellular architecture in GM and WM are fundamentally different and may explain the two- to threefold higher slow diffusion coefficient in GM.     

Bi-exponential diffusion signal decay in normal appearing white matter of multiple sclerosis

Purpose

Our aim was to characterize bi-exponential diffusion signal changes in normal appearing white matter of multiple sclerosis (MS) patients.

Methods

Diffusion parameters were measured using mono-exponential (0–1000 s/mm²) and bi-exponential (0–5000 s/mm²) approaches from 14 relapsing-remitting subtype of MS patients and 14 age- and sex-matched controls after acquiring diffusion-weighted images on a 3T MRI system. The results were analyzed using parametric or nonparametric tests and multiple linear regression models.

Results

Mono-exponential apparent diffusion coefficient (ADC) slightly increased in controls (P=.09), but decreased significantly in MS as a function of age, nonetheless an elevated ADC was observed with increasing lesion number in patients. Bi-exponential analyses showed that the increased ADC is the result of decreased relative volume fraction of slow diffusing component (f_s). However, the fast and slow diffusion components (ADC_f, ADC_s) did not change as a function of either age in controls or lesion number and age in MS patients.

Conclusions

These data demonstrated that the myelin content of the white matter affects diffusion in relapsing-remitting subtype of multiple sclerosis that is possibly a consequence of the shift between different water fractions.     

RF-related heating assessment of extracranial neurosurgical implants at 7 T

Purpose

The purpose was to evaluate radiofrequency (RF)-related heating of commonly used extracranial neurosurgical implants in 7-T magnetic resonance imaging (MRI).

Materials and methods

Experiments were performed using a 7-T MR system equipped with a transmit/receive RF head coil. Four commonly used titanium neurosurgical implants were studied using a test procedure adapted from the American Society for Testing and Materials Standard F2182-11a. Implants (n = 4) were tested with an MRI turbo spin echo pulse sequence designed to achieve maximum RF exposure [specific absorption rate (SAR) level = 9.9 W/kg], which was further validated by performing calorimetry. Maximum temperature increases near each implant's surface were measured using fiberoptic temperature probes in a gelled-saline-filled phantom that mimicked the conductive properties of soft tissue. Measurement results were compared to literature data for patient safety.

Results

The highest achievable phantom averaged SAR was determined by calorimetry to be 2.0 ± 0.1 W/kg due to the highly conservative SAR estimation model used by this 7-T MR system. The maximum temperature increase at this SAR level was below 1.0 °C for all extracranial neurosurgical implants that underwent testing.

Conclusion

The findings indicated that RF-related heating under the conditions used in this investigation is not a significant safety concern for patients with the particular extracranial neurosurgical implants evaluated in this study.     

Automatic segmentation of cerebral white matter hyperintensities using only 3D FLAIR images

Magnetic Resonance (MR) white matter hyperintensities have been shown to predict an increased risk of developing cognitive decline. However, their actual role in the conversion to dementia is still not fully understood. Automatic segmentation methods can help in the screening and monitoring of Mild Cognitive Impairment patients who take part in large population-based studies. Most existing segmentation approaches use multimodal MR images. However, multiple acquisitions represent a limitation in terms of both patient comfort and computational complexity of the algorithms. In this work, we propose an automatic lesion segmentation method that uses only three-dimensional fluid-attenuation inversion recovery (FLAIR) images. We use a modified context-sensitive Gaussian mixture model to determine voxel class probabilities, followed by correction of FLAIR artifacts. We evaluate the method against the manual segmentation performed by an experienced neuroradiologist and compare the results with other unimodal segmentation approaches. Finally, we apply our method to the segmentation of multiple sclerosis lesions by using a publicly available benchmark dataset. Results show a similar performance to other state-of-the-art multimodal methods, as well as to the human rater.     

Exploring the feasibility of simultaneous electroencephalography/functional magnetic resonance imaging at 7 T

The increased blood oxygenation level-dependent contrast available at high field makes the implementation of combined EEG/fMRI experiments at 7 T highly worthwhile from the point of view of fMRI data quality, but the higher field poses greater technical challenges for achieving good quality EEG data. A study of the feasibility of recording EEG signals from human subjects at 7 T using a commercially available, MR-compatible EEG system has therefore been carried out. This involved systematic measurement of the sources of noise in EEG recordings made in the 7 T scanner and measurement of RF heating effects on a gel phantom in the presence of a 32-electrode EEG cap. Having found no significant safety concerns and identified a set-up (involving switching off the magnet's cryo-cooler pumps and mounting the EEG amplifier on a cantilever) that limited scanner-induced noise, combined EEG/fMRI experiments employing visual stimulation were then successfully carried out on two human subjects. With the use of beamformer-based analysis of the EEG data, driven responses and alpha-band, event-related desynchronisation were identified in both subjects.     

Intracranial microvascular imaging at 7 T MRI with transceiver RF coils

Purpose

To investigate intracranial microvascular images with transceiver radio-frequency (RF) coils at ultra-high field 7 T magnetic resonance imaging (MRI).

Materials and methods

We designed several types of RF coils for the study of 7 T magnetic resonance angiography and analyzed quantitatively each coil's performance in terms of the signal-to-noise ratio (SNR) profiles to evaluate the usefulness of RF coils for microvascular imaging applications. We also obtained the microvascular images with different resolutions and parallel imaging technique.

Results

The overlapped 6-channel (ch) transceiver coil exhibited the highest performance for angiographic imaging. Although other multi-channel coils, such as 4- or 8-ch, were also suitable for fast imaging, these coils performed poorly in homogeneity or SNR for angiographic imaging. Furthermore, the 8-ch coil was poor in SNR at the center of the brain, while it had the highest SNR at the periphery.

Conclusion

The present study has demonstrated that the overlapped 6-ch coil with large-size loop coils provided the best performance for microvascular imaging or angiography with the ultra-high-field 7 T MRI, mainly because of its long penetration depth together with high SNR.     

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.     

High-resolution intracranial MRA at 7T using autocalibrating parallel imaging: initial experience in vascular disease patients

Purpose

Greater spatial resolution in intracranial three-dimensional time-of-flight (TOF) magnetic resonance angiography (MRA) is possible at higher field strengths, due to the increased contrast-to-noise ratio (CNR) from the higher signal-to-noise ratio and the improved background suppression. However, at very high fields, spatial resolution is limited in practice by the acquisition time required for sequential phase encoding. In this study, we applied parallel imaging to 7T TOF MRA studies of normal volunteers and patients with vascular disease, in order to obtain very high resolution (0.12 mm³) images within a reasonable scan time.

Materials and Methods

Custom parallel imaging acquisition and reconstruction methods were developed for 7T MRA, based on generalized autocalibrating partially parallel acquisition (GRAPPA). The techniques were compared and applied to studies of seven normal volunteers and three patients with cerebrovascular disease.

Results

The technique produced high resolution studies free from discernible reconstruction artifacts in all subjects and provided excellent depiction of vascular pathology in patients.

Conclusions

7T TOF MRA with parallel imaging is a valuable noninvasive angiographic technique that can attain very high spatial resolution.     

Longitudinal brain imaging of five malignant glioma patients treated with bevacizumab using susceptibility-weighted magnetic resonance imaging at 7 T

Malignant glioma is a rare tumor type characterized by prominent vascular proliferation. Antiangiogenic therapy with the monoclonal antibody bevacizumab is considered as a promising therapeutic strategy, although the effect on tumor vascularization is unclear. High-field susceptibility-weighted imaging (SWI) visualizes the microvasculature and may contribute to the investigation of antiangiogenic therapy responses in gliomas. We prospectively studied five adult malignant glioma patients treated with bevacizumab-containing regimens. In each patient, we performed three 7-T SWI and T1-weighted imaging investigations (baseline and 2 and 4 weeks after the start of bevacizumab treatment). In addition, we imaged a postmortem brain of a patient with glioblastoma using 7-T SWI and performed detailed histopathological analysis. We observed almost total resolution of brain edema in three of five patients after initiation of bevacizumab therapy. In one case with rapid increase of the lesion size despite bevacizumab therapy, SWI showed progressive increase of irregular hypointense structures, most likely corresponding to increasing amounts of pathological microvasculature. In one case with progressive neurological decline, 7-T images showed multiple intratumoral microhemorrhages after the first bevacizumab application. Correlation of postmortem neuroimaging with histopathology confirmed that SWI-positive structures correspond to tumor vasculature. The experience from our case series indicates that longitudinal 7-T SWI seems to be an appropriate method for investigation of changes in brain tumor vascularization over time under antiangiogenic therapy.     

Real-time color-flow MRI at 3 T using variable-density spiral phase contrast

The purpose of this study was to demonstrate and evaluate the performance of real-time color-flow MRI at 3 T using variable-density spiral (VDS) phase contrast. Spiral phase contrast imaging was implemented within a flexible real-time interactive MRI system that provided continuous image reconstruction and an intuitive user interface. The pulse sequence consisted of a spectral-spatial excitation, bipolar gradient, spiral readout and gradient spoiler. VDSs were utilized to increase spatial and/or temporal resolution relative to uniform-density spirals (UDSs). Parameter choices were guided by specific applications. Sliding window reconstruction was used to achieve a maximum display rate of 40 frames/s. No breath-holding or gating was used. Our results demonstrated that real-time color-flow movies using UDS and VDS provided adequate visualization of intracardiac flow, carotid flow and proximal coronary flow in healthy volunteers. Average aortic outflow velocity measured at the aortic valve plane using VDS was 29.4% higher than that using UDS. Peak velocity measured in the common carotid artery using VDS was 9.8% higher than that using UDS.     

Phased array 3D MR spectroscopic imaging of the brain at 7 T

Ultra-high-field 7 T magnetic resonance (MR) scanners offer the potential for greatly improved MR spectroscopic imaging due to increased sensitivity and spectral resolution. Prior 7 T human single-voxel MR Spectroscopy (MRS) studies have shown significant increases in signal-to-noise ratio (SNR) and spectral resolution as compared to lower magnetic fields but have not demonstrated the increase in spatial resolution and multivoxel coverage possible with 7 T MR spectroscopic imaging. The goal of this study was to develop specialized radiofrequency (RF) pulses and sequences for three-dimensional (3D) MR spectroscopic imaging (MRSI) at 7 T to address the challenges of increased chemical shift misregistration, B1 power limitations, and increased spectral bandwidth. The new 7 T MRSI sequence was tested in volunteer studies and demonstrated the feasibility of obtaining high-SNR phased-array 3D MRSI from the human brain.     

Principal component and linear discriminant analysis of T1 histograms of white and grey matter in multiple sclerosis

Twenty-three relapsing remitting multiple sclerosis (RRMS) patients and 14 controls were imaged to produce normal-appearing white and grey matter T1 histograms. These were used to assess whether histogram measures from principal component analysis (PCA) and linear discriminant analysis (LDA) out-perform traditional histogram metrics in classification of T1 histograms into control and RRMS subject groups and in correlation with the expanded disability status score (EDSS). The histograms were classified into one of two groups using a leave-one-out analysis. In addition, the patients were scanned serially, and the calculated parameters correlated with the EDSS. The classification results showed that the more complex techniques were at least as good at classifying the subjects as histogram mean, peak height and peak location, with PCA/LDA having success rates of 76% for white matter and 68%/65% for grey matter. No significant correlations were found with EDSS for any histogram parameter. These results indicate that there is much information contained within the grey matter as well as the white matter histograms. Although in these histograms PCA and LDA did not add greatly to the discriminatory power of traditional histogram parameters, they provide marginally better performance, while relying only on data-driven feature selection.     

Multiple sclerosis: Benefits of q-space imaging in evaluation of normal-appearing and periplaque white matter

Introduction

Diffusion tensor imaging (DTI) reveals white matter pathology in patients with multiple sclerosis (MS). A recent non-Gaussian diffusion imaging technique, q-space imaging (QSI), may provide several advantages over conventional MRI techniques in regard to in vivo evaluation of the disease process in patients with MS. The purpose of this study is to investigate the use of root mean square displacement (RMSD) derived from QSI data to characterize plaques, periplaque white matter (PWM), and normal-appearing white matter (NAWM) in patients with MS.

Methods

We generated apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps by using conventional DTI data from 21 MS patients; we generated RMSD maps by using QSI data from these patients. We used the Steel–Dwass test to compare the diffusion metrics of regions of interest in plaques, PWM, and NAWM.

Results

ADC differed (P < 0.05) between plaques and PWM and between plaques and NAWM. FA differed (P < 0.05) between plaques and NAWM. RMSD differed (P < 0.05) between plaques and PWM, plaques and NAWM, and PWM and NAWM.

Conclusion

RMSD values from QSI may reflect microstructural changes and white-matter damage in patients with MS with higher sensitivity than do conventional ADC and FA values.     

Measurement of T1 of human arterial and venous blood at 7 T

Techniques for measuring cerebral perfusion require accurate longitudinal relaxation (T1) of blood, an MRI parameter that is field dependent. T1 of arterial and venous human blood was measured at 7 T using three different sources — pathology laboratory, blood bank and in vivo. The T1 of venous blood was measured from sealed samples from a pathology lab and in vivo. Samples from a blood bank were oxygenated and mixed to obtain different physiological concentrations of hematocrit and oxygenation. T1 relaxation times were estimated using a three-point fit to a simple inversion recovery equation. At 37 °C, the T1 of blood at arterial pO₂ was 2.29 ± 0.1 s and 2.07 ± 0.12 at venous pO₂. The in vivo T1 of venous blood, in three subjects, was slightly longer at 2.45 ± 0.11 s. T1 of arterial and venous blood at 7 T was measured and found to be significantly different. The T1 values were longer in vivo than in vitro. While the exact cause for the discrepancy is unknown, the additives in the blood samples, degradation during experiment, oxygenation differences, and the non-stagnant nature of blood in vivo could be potential contributors to the lower values of T1 in the venous samples.