Ulrike Nöth

BOLD and perfusion changes during epileptic generalised spike wave activity

It is unclear whether neurovascular coupling is maintained during epileptic discharges. Knowing this is important to allow appropriate inferences from functional imaging studies of epileptic activity. Recent blood oxygen level-dependent (BOLD) functional MRI (fMRI) studies have demonstrated negative BOLD responses (NBR) in frontal, parietal and posterior cingulate cortices during generalised spike wave activity (GSW). We hypothesized that GSW-related NBR commonly reflect decreased cerebral blood flow (CBF). We measured BOLD and cerebral blood flow responses using simultaneous EEG with BOLD and arterial spin label (ASL) fMRI at 3 T. Four patients with epilepsy were studied; two with idiopathic generalized epilepsy (IGE) and two with secondary generalized epilepsy (SGE). We found GSW-related NBR in frontal, parietal and posterior cingulate cortices. We measured the coupling between BOLD and CBF changes during GSW and normal background EEG and found a positive correlation between the simultaneously measured BOLD and CBF throughout the imaged volume. Frontal and thalamic activation were seen in two patients with SGE, concordant with the electro-clinical features of their epilepsy. There was striking reproducibility of the GSW-associated BOLD response in subjects previously studied at 1.5 T. Our results show a preserved relationship between BOLD and CBF changes during rest and GSW activity consistent with normal neurovascular coupling in patients with generalized epilepsy and in particular during GSW activity. Cortical activations appear to reflect areas of discharge generation whilst deactivations reflect changes in conscious resting state activity.

A fast B1-mapping method for the correction and normalization of magnetization transfer ratio maps at 3 T

In neuroimaging, there is increasing interest in magnetization transfer (MT) techniques which yield information about bound water protons. One of the main applications is the investigation of the myelin integrity in the central nervous system (CNS). However, several problems may arise, in particular at high magnetic field strengths: B1 inhomogeneities may yield deviations of the MT saturation angle and thus non-uniformities of the measured MT ratio (MTR). This effect can be corrected for but requires in general additional time consuming B1 mapping. Furthermore, increased values of the specific absorption rate (SAR) may require a reduction of the saturation angle for individual subjects, impairing comparability of results. In this work, a B1 mapping method based on magnetization-prepared FLASH with slice selective preparation and excitation pulses and correction for relaxation effects is presented, yielding B1 maps with whole brain coverage, an in-plane resolution of 4 mm, a slice thickness of 3 mm, and a clinically acceptable duration of 46 s. The method is tested both in vitro and in vivo and applied in a subsequent in vivo study to show that MTR values in human brain tissue depend approximately linearly on the preparation angle, with a slope similar to values reported for 1.5 T. Calibration data and B1 maps are applied to B1 inhomogeneity corrections of MTR maps. Subsequently, it is shown that B1-corrected MTR maps acquired at reduced preparation angles due to individual SAR restrictions can be normalized, allowing for a direct comparison with maps acquired at the full angle.

Correction of systematic errors in quantitative proton density mapping

Interest in techniques yielding quantitative information about brain tissue proton densities is increasing. In general, all parameters influencing the signal amplitude are mapped in several acquisitions and then eliminated from the image data to obtain pure proton density weighting. Particularly, the measurement of the receiver coil sensitivity profile is problematic. Several methods published so far are based on the reciprocity theorem, assuming that receive and transmit sensitivities are identical. Goals of this study were (1) to determine quantitative proton density maps using an optimized variable flip angle method for T1 mapping at 3 T, (2) to investigate if systematic errors can arise from insufficient spoiling of transverse magnetization, and (3) to compare two methods for mapping the receiver coil sensitivity, based on either the reciprocity theorem or bias field correction. Results show that insufficient spoiling yields systematic errors in absolute proton density of about 3–4 pu. A correction algorithm is proposed. It is shown that receiver coil sensitivity mapping based on the reciprocity theorem yields erroneous proton density values, whereas reliable data are obtained with bias field correction. Absolute proton density values in different brain areas, evaluated on six healthy subjects, are in excellent agreement with recent literature results. Magn Reson Med, 2012.

Quantitative proton density mapping: correcting the receiver sensitivity bias via pseudo proton densities

Most methods for mapping proton densities (PD) in brain tissue are based on measuring all parameters influencing the signal intensity with subsequent elimination of any weighting not related to PD. This requires knowledge of the receiver coil sensitivity profile (RP), the measurement of which can be problematic. Recently, a method for compensating the influence of RP non-uniformities on PD data at a field strength of 3T was proposed, based on bias field correction of spoiled gradient echo image data to remove the low spatial frequency bias imposed by RP variations from uncorrected PD maps. The purpose of the current study was to present and test an independent method, based on the well-known linear relationship between the longitudinal relaxation rate R1 and 1/PD in brain tissue. For healthy subjects, RP maps obtained with this method and the resulting PD maps are very similar to maps based on bias field correction, and quantitative PD values acquired with the new independent method are in very good agreement with literature values. Furthermore, both methods for PD mapping are compared in the presence of several pathologies (multiple sclerosis, stroke, meningioma, recurrent glioblastoma).

The Human Operculo-Insular Cortex Is Pain-Preferentially but Not Pain-Exclusively Activated by Trigeminal and Olfactory Stimuli

Increasing evidence about the central nervous representation of pain in the brain suggests that the operculo-insular cortex is a crucial part of the pain matrix. The pain-specificity of a brain region may be tested by administering nociceptive stimuli while controlling for unspecific activations by administering non-nociceptive stimuli. We applied this paradigm to nasal chemosensation, delivering trigeminal or olfactory stimuli, to verify the pain-specificity of the operculo-insular cortex. In detail, brain activations due to intranasal stimulation induced by non-nociceptive olfactory stimuli of hydrogen sulfide (5 ppm) or vanillin (0.8 ppm) were used to mask brain activations due to somatosensory, clearly nociceptive trigeminal stimulations with gaseous carbon dioxide (75% v/v). Functional magnetic resonance (fMRI) images were recorded from 12 healthy volunteers in a 3T head scanner during stimulus administration using an event-related design. We found that significantly more activations following nociceptive than non-nociceptive stimuli were localized bilaterally in two restricted clusters in the brain containing the primary and secondary somatosensory areas and the insular cortices consistent with the operculo-insular cortex. However, these activations completely disappeared when eliminating activations associated with the administration of olfactory stimuli, which were small but measurable. While the present experiments verify that the operculo-insular cortex plays a role in the processing of nociceptive input, they also show that it is not a pain-exclusive brain region and allow, in the experimental context, for the interpretation that the operculo-insular cortex splay a major role in the detection of and responding to salient events, whether or not these events are nociceptive or painful.

Simultaneous electroencephalography-functional MRI at 3 T: An analysis of safety risks imposed by performing anatomical reference scans with the EEG equipment in place

To describe heating effects to be expected in simultaneous electroencephalography (EEG) and magnetic resonance imaging (MRI) when deviating from the EEG manufacturers instructions; to test which anatomical MRI sequences have a sufficiently low specific absorption rate (SAR) to be performed with the EEG equipment in place; and to suggest precautions to reduce the risk of heating.

Improved visibility of brain tumors in synthetic MP-RAGE anatomies with pure T1 weighting

Conventional MRI for brain tumor diagnosis employs T2‐weighted and contrast‐enhanced T1‐weighted sequences. Non‐enhanced T1‐weighted images provide improved anatomical details for precise tumor location, but reduced tumor‐to‐background contrast as elevated T1 and proton density (PD) values in tumor tissue affect the signal inversely. Radiofrequency (RF) coil inhomogeneities may further mask tumor and edema outlines. To overcome this problem, the aims of this work were to employ quantitative MRI techniques to create purely T1‐weighted synthetic anatomies which can be expected to yield improved tissue and tumor‐to‐background contrasts, to compare the quality of conventional and synthetic anatomies, and to investigate optical contrast and visibility of brain tumors and edema in synthetic anatomies. Conventional magnetization‐prepared rapid acquisition of gradient echoes (MP‐RAGE) anatomies and maps of T1, PD and RF coil profiles were acquired in comparable and clinically feasible times. Three synthetic MP‐RAGE anatomies (PD T1 weighting both with and without RF bias; pure T1 weighting) were calculated for healthy subjects and 32 patients with brain tumors. In healthy subjects, the PD T1‐weighted synthetic anatomies with RF bias precisely matched the conventional anatomies, yielding high signal‐to‐noise (SNR) and contrast‐to‐noise (CNR) ratios. Pure T1 weighting yielded lower SNR, but high CNR, because of increased optical contrasts. In patients with brain tumors, synthetic anatomies with pure T1 weighting yielded significant increases in optical contrast and improved visibility of tumor and edema in comparison with anatomies reflecting conventional T1 contrasts. In summary, the optimized purely T1‐weighted synthetic anatomy with an isotropic resolution of 1 mm, as proposed in this work, considerably enhances optical contrast and visibility of brain tumors and edema. Copyright

Quantitative T2′-Mapping in Acute Ischemic Stroke

Background and Purpose— Quantitative T2′-mapping detects regional changes in the relation of oxygenated and deoxygenated haemoglobine and might reflect areas with increased oxygen extraction. T2′-mapping in conjunction with an elaborate algorithm for motion correction was performed in patients with acute large-vessel stroke, and quantitative T2′-values were determined within the diffusion-weighted imaging lesion and perfusion-restricted tissue. Methods— Eleven patients (median age, 71 years) with acute middle cerebral or internal carotid artery occlusion underwent MRI before scheduled endovascular treatment. MR-examination included diffusion- and perfusion-weighted imaging and quantitative, motion-corrected mapping of T2′. Time-to-peak maps were thresholded for different degrees of perfusion delays (eg, ≥0 s, ≥ 2s) when compared with a reference time-to-peak value from healthy contralateral tissue. Mean T2′-values in areas with reduced apparent diffusion coefficient and in areas with impaired perfusion were compared with T2′-values in corresponding contralateral areas. Results— Median time between symptom onset and MRI was 238 minutes. T2′-values were significantly reduced within the apparent diffusion coefficient -lesion when compared with contralateral healthy tissue (83 ms [67, 97] versus 97 ms [91, 111]; P<0.003). In perfusion-restricted tissue, T2′-values were also significantly lower when compared with contralateral healthy tissue (ie, for time to peak, ≥0 s 93 ms [86, 102] versus 104 [90, 110]; P=0.008) but were significantly higher than within the apparent diffusion coefficient lesion. The severity of the perfusion impairment had no influence on median T2′-values. Conclusions— Motion-corrected T2′-mapping reveals significant and gradually declining values from healthy to perfusion-disturbed to apparent diffusion coefficient-restricted tissue. Current T2′-mapping can differentiate between the ischemic core and the perfusion-impaired areas but not on its own between penumbral and oligemic tissue.

Brain Mapping-Based Model of Δ 9 -Tetrahydrocannabinol Effects on Connectivity in the Pain Matrix

Cannabinoids receive increasing interest as analgesic treatments. However, the clinical use of Δ9-tetrahydrocannabinol (Δ9-THC) has progressed with justified caution, which also owes to the incomplete mechanistic understanding of its analgesic effects, in particular its interference with the processing of sensory or affective components of pain. The present placebo-controlled crossover study therefore focused on the effects of 20 mg oral THC on the connectivity between brain areas of the pain matrix following experimental stimulation of trigeminal nocisensors in 15 non-addicted healthy volunteers. A general linear model (GLM) analysis identified reduced activations in the hippocampus and the anterior insula following THC administration. However, assessment of psychophysiological interaction (PPI) revealed that the effects of THC first consisted in a weakening of the interaction between the thalamus and the secondary somatosensory cortex (S2). From there, dynamic causal modeling (DCM) was employed to infer that THC attenuated the connections to the hippocampus and to the anterior insula, suggesting that the reduced activations in these regions are secondary to a reduction of the connectivity from somatosensory regions by THC. These findings may have consequences for the way THC effects are currently interpreted: as cannabinoids are increasingly considered in pain treatment, present results provide relevant information about how THC interferes with the affective component of pain. Specifically, the present experiment suggests that THC does not selectively affect limbic regions, but rather interferes with sensory processing which in turn reduces sensory-limbic connectivity, leading to deactivation of affective regions.

An improved method for retrospective motion correction in quantitative T2* mapping

A new method for motion correction of T2*-weighted data and resulting quantitative T2* maps is presented. For this method, additional data sets with a reduced number of phase encoding steps covering the k-space centre are acquired. Motion correction is based on a 3-step procedure: (1) calculation of improved input data sets with reduced artefact levels from the original data, (2) creation of a target data set free of movement artefacts on the basis of the improved input data sets, and (3) fitting of original data to the target data set, yielding an optimum combination of acquired k-space data which suppresses lines affected by movement. The method was tested on healthy subjects performing pre-trained movement. Motion correction was successful unless the same k-space line was affected by movement in all data sets acquired on a specific subject. The method was applied to patients suffering from subarachnoid haemorrhage (group 1) or tumours (group 2) with accompanying edema in the brain. Motion correction improved the interpretability of T2*-weighted patient data and resulting quantitative T2* maps considerably by allowing a clear delineation between ventricle and edema and a clear localisation of haemorrhage (group 1) or a clear delineation of tumour accompanying edema (group 2) which was not possible in data affected by movement.