Wouter M. Teeuwisse

Can Arterial Spin Labeling Detect White Matter Perfusion Signal

Since the invention of arterial spin labeling (ASL) it has been acknowledged that ASL does not allow reliable detection of a white matter (WM) perfusion signal. However, recent developments such as pseudo‐continuous labeling and background suppression have improved the quality. The goal of this research was to study the ability of these newer ASL sequences to detect WM perfusion signal. Background suppressed pseudo‐continuous ASL was implemented at 3T with multislice 2D readout after 1525 ms. In five volunteers it was shown that 10 min scanning resulted in significant perfusion signal in 70% of WM voxels. Increasing the labeling and delay time did not lead to a higher percentage. In 27 normal volunteers it was found that 35 averages are necessary to detect significant WM signal, but 150 averages are needed to detect signal in the deep WM. Finally, it was shown in a patient with a cerebral arteriovenous malformation that pseudo‐continuous ASL enabled the depiction of hypointense WM perfusion signal, although dynamic susceptibility contrast MRI showed that this region was merely showing delayed arrival of contrast agent than hypoperfusion. It can be concluded that, except within the deep WM, ASL is sensitive enough to detect WM perfusion signal and perfusion deficits. Magn Reson Med, 2009.

Intra- and Multicenter Reproducibility of Pulsed, Continuous and Pseudo-Continuous Arterial Spin Labeling Methods for Measuring Cerebral Perfusion

Intra- and multicenter reproducibility of currently used arterial spin labeling (ASL) methods were assessed at three imaging centers in the Netherlands, equipped with Philips 3TMR scanners. Six healthy participants were scanned twice at each site. The imaging protocol consisted of continuous ASL (CASL), pseudo-continuous ASL (p-CASL) with and without background suppression, pulsed ASL (PASL) with single and multiple inversion times (TIs), and selective ASL for segmentation. Reproducibility was expressed in terms of the coefficient of repeatability and the repeatability index. Voxelwise analysis of variance was performed, yielding brain maps that reflected regional variability. Intra- and multicenter reproducibility were comparable for all methods, except for single TI PASL, with better intracenter reproducibility (F-test of equality of two variances, P < 0.05). Pseudo-continuous ASL and multi TI PASL varied least between sites. Variability maps of all methods showed most variability near brain-feeding arteries within sessions and in gray matter between sessions. On the basis of the results of this study, one could consider the use of reference values in clinical routine, with whole-brain p-CASL perfusion varying < 20% over repeated measurements within the same individuals considered to be normal. Knowledge on regional variability allows for the use of perfusion-weighted images in the assessment of local cerebral pathology.

Quantitative assessment of the effects of high‐permittivity pads in 7 Tesla MRI of the brain

The use of high‐permittivity materials has been shown to be an effective method for increasing transmit and receive sensitivity in areas of low‐signal intensity in the brain at high field. Results in this article show that the use of these materials does not increase the intercoil coupling for a phased array receive coil, does not have any detrimental effects on the B0 homogeneity within the brain, and does not affect the specific absorption rate distribution within the head. Areas of the brain close to the pads exhibit significant increases (>100%) in transmit field efficiency, but areas further away show a less pronounced (∼10%) decrease due to the homogenization of the transmit field and the loss introduced by the dielectric pads. Magn Reson Med, 2012.

A central role for venom in predation by Varanus komodoensis (Komodo Dragon) and the extinct giant Varanus (Megalania) priscus

The predatory ecology of Varanus komodoensis (Komodo Dragon) has been a subject of long-standing interest and considerable conjecture. Here, we investigate the roles and potential interplay between cranial mechanics, toxic bacteria, and venom. Our analyses point to the presence of a sophisticated combined-arsenal killing apparatus. We find that the lightweight skull is relatively poorly adapted to generate high bite forces but better adapted to resist high pulling loads. We reject the popular notion regarding toxic bacteria utilization. Instead, we demonstrate that the effects of deep wounds inflicted are potentiated through venom with toxic activities including anticoagulation and shock induction. Anatomical comparisons of V. komodoensis with V. (Megalania) priscus fossils suggest that the closely related extinct giant was the largest venomous animal to have ever lived.

Simulations of high permittivity materials for 7 T neuroimaging and evaluation of a new barium titanate-based dielectric

High permittivity “dielectric pads” have been shown to increase image quality at high magnetic fields in regions of low radiofrequency transmit efficiency. This article presents a series of electromagnetic simulations to determine the effects of pad size and geometry, relative permittivity value, as well as thickness on the transmit radiofrequency fields for neuroimaging at 7 T. For a 5‐mm thick pad, there is virtually no effect on the transmit field for relative permittivity values lower than ∼90. Significant improvements are found for values between 90 and ∼180. If the relative permittivity is increased above ∼180 then areas of very low transmit efficiency are produced. For a 1‐cm thick pad, the corresponding numbers are ∼60 and ∼120, respectively. Based upon the findings, a new material (barium titanate, relative permittivity ∼150) is used to produce thin (∼5 mm) dielectric pads which can easily be placed within a standard receive head array. Experimental measurements of transmit sensitivities, as well as acquisition of T2‐ and T  2* ‐weighted images show the promise of this approach. Magn Reson Med, 2012.

In vivo blood T1 measurements at 1.5 T, 3 T, and 7 T

The longitudinal relaxation time of blood is a crucial parameter for quantification of cerebral blood flow by arterial spin labeling and is one of the main determinants of the signal‐to‐noise ratio of the resulting perfusion maps. Whereas at low and medium magnetic field strengths (B0), its in vivo value is well established; at ultra‐high field, this is still uncertain. In this study, longitudinal relaxation time of blood in the sagittal sinus was measured at 1.5 T, 3 T, and 7 T. A nonselective inversion pulse preceding a Look‐Locker echo planar imaging sequence was performed to obtain the inversion recovery curve of venous blood. The results showed that longitudinal relaxation time of blood at 7 T was ∼ 2.1 s which translates to an anticipated 33% gain in the signal‐to‐noise ratio in arterial spin labeling experiments due to T1 relaxation alone compared with 3 T. In addition, the linear relationship between longitudinal relaxation time of blood and B0 was confirmed. Magn Reson Med, 70:1082–1086, 2013.

Functional and Structural Diversification of the Anguimorpha Lizard Venom System

Venom has only been recently discovered to be a basal trait of the Anguimorpha lizards. Consequently, very little is known about the timings of toxin recruitment events, venom protein molecular evolution, or even the relative physical diversifications of the venom system itself. A multidisciplinary approach was used to examine the evolution across the full taxonomical range of this ∼130 million-year-old clade. Analysis of cDNA libraries revealed complex venom transcriptomes. Most notably, three new cardioactive peptide toxin types were discovered (celestoxin, cholecystokinin, and YY peptides). The latter two represent additional examples of convergent use of genes in toxic arsenals, both having previously been documented as components of frog skin defensive chemical secretions. Two other novel venom gland-overexpressed modified versions of other protein frameworks were also recovered from the libraries (epididymal secretory protein and ribonuclease). Lectin, hyaluronidase, and veficolin toxin types were sequenced for the first time from lizard venoms and shown to be homologous to the snake venom forms. In contrast, phylogenetic analyses demonstrated that the lizard natriuretic peptide toxins were recruited independently of the form in snake venoms. The de novo evolution of helokinestatin peptide toxin encoding domains within the lizard venom natriuretic gene was revealed to be exclusive to the helodermatid/anguid subclade. New isoforms were sequenced for cysteine-rich secretory protein, kallikrein, and phospholipase A2 toxins. Venom gland morphological analysis revealed extensive evolutionary tinkering. Anguid glands are characterized by thin capsules and mixed glands, serous at the bottom of the lobule and mucous toward the apex. Twice, independently this arrangement was segregated into specialized serous protein-secreting glands with thick capsules with the mucous lobules now distinct (Heloderma and the Lanthanotus/Varanus clade). The results obtained highlight the importance of utilizing evolution-based search strategies for biodiscovery and emphasize the largely untapped drug design and development potential of lizard venoms.

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

Sources of variation in multi-centre brain MTR histogram studies: body-coil transmission eliminates inter-centre differences

AbstractObject: 1. Identify sources of variation affecting Magnetisation Transfer Ratio (MTR) histogram reproducibility between-centres. 2. Demonstrate complete elimination of inter-centre difference. Materials and methods: Six principle sources of variation were summarised and analysed. These are:the imager coil used for radiofrequency (RF) transmission, imager stability, the shape and other parameters describing the Magnetisation Transfer (MT) pulse, the MT sequence used (including its parameters), the image segmentation methodology, and the histogram generation technique. Transmit field nonuniformity and B1 errors are often the largest factors. PLUMB (Peak Location Uniformity in MTR histograms of the Brain) plots are a convenient way of visualising differences. Five multi-centres studies were undertaken to investigate and minimise differences. Results: Transmission using a body coil, with a close-fitting array of surface coils for reception, gave the best uniformity. Differences between two centres, having MR imagers from different manufacturers, were completely eliminated by using body coil excitation, making a small adjustment to the MT pulse flip angle, and carrying out segmentation at a single centre. Histograms and their peak location and height values were indistinguishable. Conclusions: Body coil excitation is preferred for multi-centre studies. Analysis (segmentation and histogram generation) should ideally be carried out at a single site.

Robustness and reproducibility of flow territories defined by planning-free vessel-encoded pseudocontinuous arterial spin-labeling.

SUMMARY: Flow-territory mapping by MR imaging ASL noninvasively provides a unique insight into the distribution of cerebral perfusion. The introduction of planning-free vessel-encoded pCASL made flow-territory mapping feasible for clinical use, though lack of individual planning could impede reproducibility of this technique. We assessed the reproducibility of planning-free vessel-encoded pCASL in patients and controls. Results indicated that planning-free vessel-encoded pCASL is a reproducible method that could assist in clinical decision-making.