Peter J. Koopmans

Three dimensional echo-planar imaging at 7 Tesla.

Functional MRI (fMRI) most commonly employs 2D echo-planar imaging (EPI). The advantages for fMRI brought about by the increasingly popular ultra-high field strengths are best exploited in high-resolution acquisitions, but here 2D EPI becomes impractical for several reasons, including the very long volume acquisitions times. In this study at 7 T, a 3D EPI sequence with full parallel and partial Fourier imaging capability along both phase encoding axes was implemented and used to evaluate the sensitivity of 3D and corresponding 2D EPI acquisitions at four different spatial resolutions ranging from small to typical voxel sizes (1.5-3.0 mm isotropic). Whole-brain resting state measurements (N=4) revealed a better, or at least comparable sensitivity of the 3D method for gray and white matter. The larger vulnerability of 3D to physiological effects was outweighed by the much shorter volume TR, which moreover allows whole-brain coverage at high resolution within fully acceptable limits for event-related fMRI: TR was only 3.07 s for 1.5 mm, 1.88 s for 2.0 mm, 1.38 s for 2.5 mm and 1.07 s for 3.0 mm isotropic resolution. In order to investigate the ability to detect and spatially resolve BOLD activation in the visual cortex, functional 3D EPI experiments (N=8) were performed at 1 mm isotropic resolution with parallel imaging acceleration of 3x3, resulting in a TR of only 3.2 s for whole-brain coverage. From our results, and several other practical advantages of 3D over 2D EPI found in the present study, we conclude that 3D EPI provides a useful alternative for whole-brain fMRI at 7 T, not only when high-resolution data are required.

Simultaneous multislice (SMS) imaging techniques

Simultaneous multislice imaging (SMS) using parallel image reconstruction has rapidly advanced to become a major imaging technique. The primary benefit is an acceleration in data acquisition that is equal to the number of simultaneously excited slices. Unlike in‐plane parallel imaging this can have only a marginal intrinsic signal‐to‐noise ratio penalty, and the full acceleration is attainable at fixed echo time, as is required for many echo planar imaging applications. Furthermore, for some implementations SMS techniques can reduce radiofrequency (RF) power deposition. In this review the current state of the art of SMS imaging is presented. In the Introduction, a historical overview is given of the history of SMS excitation in MRI. The following section on RF pulses gives both the theoretical background and practical application. The section on encoding and reconstruction shows how the collapsed multislice images can be disentangled by means of the transmitter pulse phase, gradient pulses, and most importantly using multichannel receiver coils. The relationship between classic parallel imaging techniques and SMS reconstruction methods is explored. The subsequent section describes the practical implementation, including the acquisition of reference data, and slice cross‐talk. Published applications of SMS imaging are then reviewed, and the article concludes with an outlook and perspective of SMS imaging. Magn Reson Med 75:63–81, 2016.

Layer-specific BOLD activation in human V1

The neocortex is known to have a distinct laminar structure which has previously been probed in animals using high‐resolution fMRI. Detection of layer‐specific activation in humans has however to date proven elusive. In this study we demonstrate for the first time such layer‐specific activation, specifically at a depth corresponding to layer IV of human primary visual cortex (V1). We used a gradient‐echo (GE) sequence at 3T with an isotropic resolution of 0.75 mm, in which a stria at the depth of layer IV was visible in the averaged time series, and could be used as an anatomical landmark. Upon visual stimulation (7.5 Hz flickering checkerboard) the signal increase of 3% in layer IV was significantly higher than in the neighboring laminae. The width of this activation peak was 0.8–1 mm. Based on this result and known laminar organization of the intracortical vasculature we conclude that in the direction perpendicular to the cortical surface the intrinsic spatial resolution of the GE‐BOLD fMRI signal is in the submillimetre range. Human laminar fMRI is a significant development which may improve our understanding of intracortical activation patterns and of the way in which different cortical regions interact. Hum Brain Mapp, 2010.

Power Independent of Number of Slices (PINS) radiofrequency pulses for low-power simultaneous multislice excitation.

This communication describes radiofrequency pulses capable of performing spatially periodic excitation, inversion, and refocusing. The generation of such pulses either by multiplication of existing radiofrequency pulses by a Dirac comb function or by means of Fourier series expansion is described. Practical schemes for the implementation of such pulses are given, and strategies for optimizing the pulse profile at fixed pulse duration are outlined. The pulses are implemented using a spin‐echo sequence. The power deposition is independent of the number of slices acquired, and hence the power deposition per slice is considerably reduced compared to multislice imaging. Excellent image quality is obtained both in phantoms and in images of the human head. These pulses should find widespread application for multiplexed imaging, in particular at high static magnetic field strengths and for pulse sequences that have a high radiofrequency power deposition and could lead to dramatic increases in scanning efficiency. Magn Reson Med, 2011.

Multi-echo fMRI of the cortical laminae in humans at 7 T.

Recent developments in ultra high field MRI and receiver coil technology have opened up the possibility of laminar fMRI in humans. This could offer greater insight into human brain function by elucidating both the interaction between brain regions on the basis of laminar activation patterns associated with input and output, and the interactions between laminae in a specific region. We used very high isotropic spatial resolution (0.75 mm voxel size), multi-echo acquisition (gradient-echo) in a 7 T fMRI study of human primary visual cortex (V1) and novel data analysis techniques to quantitatively investigate the echo time dependence of laminar profiles, laminar activation, and physiological noise distributions over an extended region of cortex. We found T(2)* profiles to be explicable in terms of variations in myelin content. Laminar activation profiles vary with echo time (TE): at short TE the highest signal changes are measured at the pial surface; this maximum shifts into grey matter at longer TEs. The top layers peak latest as these have the longest transverse relaxation time. Theoretical simulations and experiment suggest that the intravascular contribution to functional signal changes is significant even at long TE. Based on a temporal noise analysis we argue that the (physiological) noise contributions will ameliorate differences in sensitivity between the layers in a statistical analysis, and correlates with laminar blood volume distribution. We also show that even at this high spatial resolution the physiological noise limit to sensitivity is reached within V1, implying that cortical sub-regions can be examined with this technique.

Whole brain, high resolution spin-echo resting state fMRI using PINS multiplexing at 7 T.

This article demonstrates the application of spin-echo EPI for resting state fMRI at 7 T. A short repetition time of 1860 ms was made possible by the use of slice multiplexing which permitted whole brain coverage at high spatial resolution (84 slices of 1.6 mm thickness). Radiofrequency power deposition was kept within regulatory limits by use of the power independent of number of slices (PINS) technique. A high in-plane spatial resolution of 1.5 mm was obtained, while image distortion was ameliorated by the use of in-plane parallel imaging techniques. Data from six subjects were obtained with a measurement time of just over 15 min per subject. A group level independent component (IC) analysis revealed 24 non-artefactual resting state networks, including those commonly found in standard acquisitions, as well as plausible networks for a broad range of regions. Signal was measured from regions commonly rendered inaccessible due to signal voids in gradient echo acquisitions. Dual regression was used to obtain spatial IC maps at the single subject level revealing exquisite localisation to grey matter that is consistent with a high degree of T(2)-weighting in the acquisition sequence. This technique hence holds great promise for both resting state and activation studies at 7 T.

Low cerebrospinal fluid concentrations of the nucleotide HIV reverse transcriptase inhibitor, Tenofovir

Background:Tenofovir is a nucleotide HIV reverse transcriptase inhibitor whose chemical properties suggest that it may not penetrate into the central nervous system in therapeutic concentrations. The studys objective was to determine tenofovirs penetration into cerebrospinal fluid (CSF). Methods:CNS HIV Antiretroviral Therapy Effects Research is a multicenter observational study to determine the effects of antiretroviral therapy on HIV-associated neurological disease. Single random plasma and CSF samples were drawn within an hour of each other from subjects taking tenofovir between October 2003 and March 2007. All samples were assayed by mass spectrometry with a detection limit of 0.9 ng/mL. Results:One hundred eighty-three participants (age 44 ± 8 years; 83 ± 32 kg; 33 females; CSF protein 44 ± 16 mg/dL) had plasma and CSF samples drawn 12.2 ± 6.9 and 11 ± 7.8 hours post dose, respectively. Median plasma and CSF tenofovir concentrations were 96 ng/mL [interquartile range (IQR) 47–153 ng/mL] and 5.5 ng/mL (IQR 2.7–11.3 ng/mL), respectively. Thirty-four of 231 plasma (14.7%) and 9 of 77 CSF samples (11.7%) were below detection. CSF to plasma concentration ratio from paired samples was 0.057 (IQR 0.03–0.1; n = 38). Median CSF to wild-type 50% inhibitory concentration ratio was 0.48 (IQR 0.24–0.98). Seventy-seven percent of CSF concentrations were below the tenofovir wild-type 50% inhibitory concentration. More subjects had detectable CSF HIV with lower (⩽7 ng/mL) versus higher (>7ng/mL) CSF tenofovir concentrations (29% versus 9%; P = 0.05). Conclusions:Tenofovir concentrations in the CSF are only 5% of plasma concentrations, suggesting limited transfer into the CSF, and possibly active transport out of the CSF. CSF tenofovir concentrations may not effectively inhibit viral replication in the CSF.

Accelerated human cardiac diffusion tensor imaging using simultaneous multislice imaging

To demonstrate the feasibility of accelerating measurements of cardiac fiber structure using simultaneous multislice (SMS) imaging.

Slice accelerated diffusion‐weighted imaging at ultra‐high field strength

Diffusion magnetic resonance imaging (dMRI) data with very high isotropic resolution can be obtained at 7T. However, for extensive brain coverage, a large number of slices is required, resulting in long acquisition times (TAs). Recording multiple slices simultaneously (SMS) promises to reduce the TA.

Application of PINS radiofrequency pulses to reduce power deposition in RARE/turbo spin echo imaging of the human head

To explore the use of PINS radiofrequency (RF) pulses to reduce RF power deposition in multiband/simultaneous multislice imaging with the RARE/turbo spin echo (TSE) sequence at 3T and 7T.