Maarten J. Versluis

Assessment of middle cerebral artery diameter during hypocapnia and hypercapnia in humans using ultra-high-field MRI

In the evaluation of cerebrovascular CO2 reactivity measurements, it is often assumed that the diameter of the large intracranial arteries insonated by transcranial Doppler remains unaffected by changes in arterial CO2 partial pressure. However, the strong cerebral vasodilatory capacity of CO2 challenges this assumption, suggesting that there should be some changes in diameter, even if very small. Data from previous studies on effects of CO2 on cerebral artery diameter [middle cerebral artery (MCA)] have been inconsistent. In this study, we examined 10 healthy subjects (5 women, 5 men, age 21-30 yr). High-resolution (0.2 mm in-plane) MRI scans at 7 Tesla were used for direct observation of the MCA diameter during hypocapnia, -1 kPa (-7.5 mmHg), normocapnia, 0 kPa (0 mmHg), and two levels of hypercapnia, +1 and +2 kPa (7.5 and 15 mmHg), with respect to baseline. The vessel lumen was manually delineated by two independent observers. The results showed that the MCA diameter increased by 6.8 ± 2.9% in response to 2 kPa end-tidal P(CO2) (PET(CO2)) above baseline. However, no significant changes in diameter were observed at the -1 kPa (-1.2 ± 2.4%), and +1 kPa (+1.4 ± 3.2%) levels relative to normocapnia. The nonlinear response of the MCA diameter to CO2 was fitted as a continuous calibration curve. Cerebral blood flow changes measured by transcranial Doppler could be corrected by this calibration curve using concomitant PET(CO2) measurements. In conclusion, the MCA diameter remains constant during small deviations of the PET(CO2) from normocapnia, but increases at higher PET(CO2) values.

Origin and reduction of motion and f0 artifacts in high resolution T2*-weighted magnetic resonance imaging: application in Alzheimer's disease patients.

The altered iron concentration in many neurodegenerative diseases such as Alzheimers disease (AD) has led to the development of MRI sequences that are sensitive to the accompanying changes in the transverse relaxation rate. Heavily T(2)*-weighted imaging sequences at high magnetic field strength (7T and above), in particular, show potential for detecting small changes in iron concentration. However, these sequences require a long echo time in combination with a long scanning time for high resolution and are therefore prone to image artifacts caused by physiological fluctuations, patient motion or system instabilities. Many groups have found that the high image quality that was obtained using high resolution T(2)*-weighted sequences at 7T in healthy volunteers, could not be obtained in AD patients. In this study the source of the image artifacts was investigated in phantom and in healthy volunteer experiments by incorporating movement parameters and resonance frequency (f0) variations which were measured in AD patients. It was found that image degradation caused by typical f0 variations was a factor-of-four times larger than artifacts caused by movement characteristic of AD patients in the scanner. In addition to respiratory induced f0 variations, large jumps in the f0 were observed in AD patients. By implementing a navigator echo technique to correct for f0 variations, the image quality of high resolution T(2)*-weighted images increased considerably. This technique was successfully applied in five AD patients and in five subjective memory complainers. Visual scoring showed improvements in image quality in 9 out of 10 subjects. Ghosting levels were reduced by 24+/-13%.

Increased Number of Microinfarcts in Alzheimer Disease at 7-T MR Imaging

PURPOSE To assess the prevalence and number of cortical microinfarcts in patients with Alzheimer disease (AD) by using a 7-T magnetic resonance (MR) imaging system, to assess the independent association of cortical microinfarcts with cognitive dysfunction, and to investigate potential confounding effects of the coexisting presence of cerebral amyloid angiopathy (CAA). MATERIALS AND METHODS The local institutional review board approved this study. In all cases, informed consent was obtained. High-spatial-resolution fluid-attenuated inversion recovery and T2*-weighted images were acquired in 14 AD patients and 18 control subjects to assess the presence of microinfarcts and microbleeds. Presence of CAA was assessed according to the Boston criteria. Image analysis was performed independently by two reviewers. Mann-Whitney U test was performed to assess differences in number of microinfarcts between groups. Negative binomial regression models were used to assess the association between diagnosis of AD and diagnosis of CAA and number of microinfarcts, between diagnosis of AD and number of microbleeds and number of microinfarcts, and between cognitive function and number of microinfarcts, all corrected for age and sex. RESULTS Interobserver agreement was excellent for detecting microinfarcts (κ = 0.91) (P < .001). Patients with AD demonstrated higher number (P = .005) of microinfarcts (mean, 7.2) compared with control subjects (mean, 1.8). Negative binomial regression models showed an independent association between AD and number of microinfarcts (P = .006) and a trend for CAA and microinfarcts (P = .052). A negative correlation was found between cognitive function and the number of microinfarcts (P = .009). CONCLUSION Patients with AD show more microinfarcts than do control subjects, the number of microinfarcts correlates with global cognitive performance, and the presence of microinfarcts was mainly AD rather than CAA related.

Improved signal to noise in proton spectroscopy of the human calf muscle at 7 T using localized B1 calibration

Large variations of tip angle within a slice can lead to suboptimal pulse power optimization using standard techniques, which measure the average tip angle over a slice; this effect is especially pronounced at fields of 7 T and above. A technique was introduced that performed a volume‐selective power optimization in less than 10 sec and automatically calibrates the radiofrequency pulses for subsequent spectroscopy scans. Using this technique, MR spectra were acquired in the human calf of seven healthy volunteers with a partial volume Tx/Rx coil. Increases in signal‐to‐noise ratio based upon the unsuppressed water signal between 22 ± 5% and 166 ± 42%, compared to spectra obtained with the conventional power calibration technique, were measured in different regions of the calf muscle. This new technique was able to measure the inhomogeneous radiofrequency field at 7 T and its use resulted in a considerable signal‐to‐noise ratio increase. Magn Reson Med, 2010.

Fast high resolution whole brain T2* weighted imaging using echo planar imaging at 7 T

Magnetic susceptibility based (T(2)* weighted) contrast in MRI at high magnetic field strength is of great value in research on brain structure and cortical architecture, but its use is hampered by the low signal-to-noise ratio (SNR) efficiency of the conventional spoiled gradient echo sequence (GRE) leading to long scan times even for a limited number of slices. In this work, we show that high resolution (0.5mm isotropic) T(2)* weighted images of the whole brain can be obtained in 6min by utilizing the high SNR efficiency of echo-planar imaging (EPI). A volumetric (3D) EPI protocol is presented and compared to conventional 3D GRE images acquired with the same resolution, amount of T(2)* weighting, and imaging duration. Spatial coverage in 3D EPI was increased by a factor of 4.5 compared to 3D GRE, while also the SNR was increased by a factor of 2. Image contrast for both magnitude and phase between gray and white matter was similar for both sequences, with enhanced conspicuity of anatomic details in the 3D EPI images due to the increased SNR. Even at 7T, image blurring and distortion is limited if the EPI train length remains short (not longer than the T(2)* of the imaged tissue). 3D EPI provides steps (speed, whole brain coverage, and high isotropic resolution) that are necessary to utilize the benefits of high field MRI in research that employs T(2)* weighted imaging.

Initial results on in vivo human coronary MR angiography at 7 T

Seven tesla (T) MR imaging is potentially promising for the morphologic evaluation of coronary arteries because of the increased signal‐to‐noise ratio compared to lower field strengths, in turn allowing improved spatial resolution, improved temporal resolution, or reduced scanning times. However, there are a large number of technical challenges, including the commercial 7 T systems not being equipped with homogeneous body radiofrequency coils, conservative specific absorption rate constraints, and magnified sample‐induced amplitude of radiofrequency field inhomogeneity. In the present study, an initial attempt was made to address these challenges and to implement coronary MR angiography at 7 T. A single‐element radiofrequency transmit and receive coil was designed and a 7 T specific imaging protocol was implemented, including significant changes in scout scanning, contrast generation, and navigator geometry compared to current protocols at 3 T. With this methodology, the first human coronary MR images were successfully obtained at 7 T, with both qualitative and quantitative findings being presented. Magn Reson Med, 2009.

Improvements in high-field localized MRS of the medial temporal lobe in humans using new deformable high-dielectric materials

The intrinsic nonuniformities in the transmit radiofrequency field from standard quadrature volume resonators at high field are particularly problematic for localized MRS in areas such as the temporal lobe, where a low signal‐to‐noise ratio and poor metabolite quantification result from destructive B  1+ field interference, in addition to line broadening and signal loss from strong susceptibility gradients. MRS of the temporal lobe has been performed in a number of neurodegenerative diseases at clinical fields, but a relatively low signal‐to‐noise ratio has prevented the reliable quantification of, for example, glutamate and glutamine, which are thought to play a key role in disease progression. Using a recently developed high‐dielectric‐constant material placed around the head, localized MRS of the medial temporal lobe using the stimulated echo acquisition mode sequence was acquired at 7 T. The presence of the material increased the signal‐to‐noise ratio of MRS by a factor of two without significantly reducing the sensitivity in other areas of the brain, as shown by the measured B  1+ maps. An increase in the receive sensitivity B  1− was also measured close to the pads. The spectral linewidth of the unsuppressed water peak within the voxel of interest was reduced slightly by the introduction of the dielectric pads (although not to a statistically significant degree), a result confirmed by using a pad composed of lipid. Using LCmodel for quantitative analysis of metabolite concentrations, the increase in signal‐to‐noise ratio and the slight decrease in spectral linewidth contributed to statistically significant reductions in the Cramer–Rao lower bounds (CRLBs), also allowing the levels of glutamate and glutamine to be quantified with CRLBs below 20%. Copyright

Elevated brain iron is independent from atrophy in Huntington's Disease

Increased iron in subcortical structures in patients with Huntingtons Disease (HD) has been suggested as a causal factor of neuronal degeneration. The present study examines iron accumulation, measured using magnetic resonance imaging (MRI), in premanifest gene carriers and in early HD patients as compared to healthy controls. In total 27 early HD patients, 22 premanifest gene carriers and 25 healthy controls, from the Leiden site of the TRACK-HD study, underwent 3T MRI including high resolution 3D T(1)- and T(2)-weighted and asymmetric spin echo (ASE) sequences. Magnetic Field Correlation (MFC) maps of iron levels were constructed to assess magnetic field inhomogeneities and compared between groups in the caudate nucleus, putamen, globus pallidus, hippocampus, amygdala, accumbens nucleus, and thalamus. Subsequently the relationship of MFC value to volumetric data and disease state was examined. Higher MFC values were found in the caudate nucleus (p<0.05) and putamen (p<0.005) of early HD compared to controls and premanifest gene carriers. No differences in MFC were found between premanifest gene carriers and controls. MFC in the caudate nucleus and putamen is a predictor of disease state in HD. No correlation was found between the MFC value and volume of these subcortical structures. We conclude that Huntingtons disease patients in the early stages of the disease, but not premanifest gene carriers, have higher iron concentrations in the caudate nucleus and putamen. We have demonstrated that the iron content of these structures relates to disease state in gene carriers, independently of the measured volume of these structures.

Differences in apparent diffusion coefficients of brain metabolites between grey and white matter in the human brain measured at 7 T.

Diffusion weighted spectroscopy can provide microstructural information that is specific to compartmental geometry. So far, in human brain, apparent diffusion coefficients (ADCs) of only the metabolites N‐acetyl aspartate, creatine (tCr) and choline (tCho) have been assessed. High field MR at 7 T allows the collection and analysis of diffusion weighted spectroscopy data of additional metabolites of interest such as glutamate (Glu), N‐acetyl aspartyl glutamate, and glutamine (Gln), which are of interest due to their different compartmentalization and role in brain physiology. In this study, we performed 1H diffusion weighted spectroscopy at 7 T using a diffusion‐weighted PRESS sequence in parietal white matter (n = 6) and occipital grey matter (n = 7). Data were analyzed using the LCmodel. ADCs could reliably be obtained of N‐acetyl aspartate, tCr, tCho, Glu, Gln in grey and white matter, and N‐acetyl aspartyl glutamate in white matter. Significant differences in ADC values were observed between grey and white matter for all metabolites. ADCs in grey matter were consistently lower than in white matter. These differences can probably be attributed to different compartmentalization as well as to the differential impact of diffusion time on ADC of different molecules under conditions of restricted diffusion. Magn Reson Med, 2012.

Volumetric B1 (+) mapping of the brain at 7T using DREAM.

To tailor and optimize the Dual Refocusing Echo Acquisition Mode (DREAM) approach for volumetric B1+ mapping of the brain at 7T.