Caroline Micallef

Imaging language networks before and after anterior temporal lobe resection: Results of a longitudinal fMRI study

Purpose:  Anterior temporal lobe resection (ATLR) controls seizures in up to 70% of patients with intractable temporal lobe epilepsy (TLE) but, in the language dominant hemisphere, may impair language function, particularly naming. Functional reorganization can occur within the ipsilateral and contralateral hemispheres. We investigated reorganization of language in left‐hemisphere–dominant patients before and after ATLR; whether preoperative functional magnetic resonance imaging (fMRI) predicts postoperative naming decline; and efficiency of postoperative language networks.

Conventional magnetic resonance imaging in confirmed progressive supranuclear palsy and multiple system atrophy

Conventional magnetic resonance imaging (cMRI) is often used to aid the diagnosis of progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), but its ability to predict the histopathological diagnosis has not been systematically studied. cMRI from 48 neuropathologically confirmed cases, including PSP (n = 22), MSA (n = 13), Parkinsons disease (PD) (n = 7), and corticobasal degeneration (n = 6), and controls (n = 9) were assessed blinded to clinical details and systematically rated for reported abnormalities. Clinical diagnosis and macroscopic postmortem findings were retrospectively assessed. Radiological assessment of MRI was correct in 16 of 22 (72.7%) PSP cases and 10 of 13 (76.9%) MSA cases with substantial interrater agreement (Cohens kappa 0.708; P < .001); no PSP case was misclassified as MSA or vice versa. MRI was less sensitive but more specific than clinical diagnosis in PSP and both more sensitive and specific than clinical diagnosis in MSA. The “hummingbird” and “morning glory” signs were highly specific for PSP, and “the middle cerebellar peduncle sign” and “hot cross bun” for MSA, but sensitivity was lower (up to 68.4%) and characteristic findings may not be present even at autopsy. cMRI, clinical diagnosis, and macroscopic examination at postmortem have similar sensitivity and specificity in predicting a neuropathological diagnosis. We have validated specific radiological signs in pathologically confirmed PSP and MSA. However, the low sensitivity of these and macroscopic findings at autopsy suggest a need for imaging techniques sensitive to microstructural abnormalities without regional atrophy.

Advanced diffusion imaging sequences could aid assessing patients with focal cortical dysplasia and epilepsy

Highlights • Malformations of cortical development are a common cause of refractory epilepsy.• They are often invisible on structural imaging and only detected following surgery.• We assess a novel diffusion imaging technique (NODDI) in patients with dysplasia.• This shows more conspicuous changes than other clinical or diffusion scans.• This technique may assist the identification of FCD in patients with epilepsy.

The midbrain to pons ratio A simple and specific MRI sign of progressive supranuclear palsy

Objectives: MRI-based measurements used to diagnose progressive supranuclear palsy (PSP) typically lack pathologic verification and are not easy to use routinely. We aimed to develop in histologically proven disease a simple measure of the midbrain and pons on sagittal MRI to identify PSP. Methods: Measurements of the midbrain and pontine base on midsagittal T1-weighted MRI were performed in confirmed PSP (n = 12), Parkinson disease (n = 2), and multiple system atrophy (MSA) (n = 7), and in controls (n = 8). Using receiver operating characteristic curve analysis, cutoff values were applied to a clinically diagnosed cohort of 62 subjects that included PSP (n = 21), Parkinson disease (n = 10), MSA (n = 10), and controls (n = 21). Results: The mean midbrain measurement of 8.1 mm was reduced in PSP (p < 0.001) with reduction in the midbrain to pons ratio (PSP smaller than MSA; p < 0.001). In controls, the mean midbrain ratio was approximately two-thirds of the pontine base, in PSP it was <52%, and in MSA the ratio was greater than two-thirds. A midbrain measurement of <9.35 mm and ratio of 0.52 had 100% specificity for PSP. In the clinically defined group, 19 of 21 PSP cases (90.5%) had a midbrain measurement of <9.35 mm. Conclusions: We have developed a simple and reliable measurement in pathologically confirmed disease based on the topography of atrophy in PSP with high sensitivity and specificity that may be a useful tool in the clinic.

Diffusion tensor imaging tractography to visualize the relationship of the optic radiation to epileptogenic lesions prior to neurosurgery

Purpose:  About one‐third of patients with epilepsy are refractory to medical treatment and may be amenable to surgery. However, in patients with lesions on or near the presumed course of the optic radiation, the potential benefits of resection must be balanced against the risk of a visual field deficit. This study demonstrates the utility of diffusion tensor imaging (DTI) tractography in delineating the course of the optic radiation and its relationship to the epileptogenic lesion prior to epilepsy surgery.

Initial Evaluation of 18F-GE-179, a Putative PET Tracer for Activated N-Methyl d-Aspartate Receptors

N-methyl d-aspartate (NMDA) ion channels play a key role in a wide range of physiologic (e.g., memory and learning tasks) and pathologic processes (e.g., excitotoxicity). To date, suitable PET markers of NMDA ion channel activity have not been available. 18F-GE-179 is a novel radioligand that selectively binds to the open/active state of the NMDA receptor ion channel, displacing the binding of 3H-tenocyclidine from the intrachannel binding site with an affinity of 2.4 nM. No significant binding was observed with 10 nM GE-179 at 60 other neuroreceptors, channels, or transporters. We describe the kinetic behavior of the radioligand in vivo in humans. Methods: Nine healthy participants (6 men, 3 women; median age, 37 y) each underwent a 90-min PET scan after an intravenous injection of 18F-GE-179. Continuous arterial blood sampling over the first 15 min was followed by discrete blood sampling over the duration of the scan. Brain radioactivity (KBq/mL) was measured in summation images created from the attenuation- and motion-corrected dynamic images. Metabolite-corrected parent plasma input functions were generated. We assessed the abilities of 1-, 2-, and 3-compartment models to kinetically describe cerebral time–activity curves using 6 bilateral regions of interest. Parametric volume-of-distribution (VT) images were generated by voxelwise rank-shaping regularization of exponential spectral analysis (RS-ESA). Results: A 2-brain-compartment, 4-rate-constant model best described the radioligand’s kinetics in normal gray matter of subjects at rest. At 30 min after injection, 37% of plasma radioactivity represented unmetabolized 18F-GE-179. The highest mean levels of gray matter radioactivity were seen in the putamina and peaked at 7.5 min. A significant positive correlation was observed between K1 and VT (Spearman ρ = 0.398; P = 0.003). Between-subject coefficients of variation of VT ranged between 12% and 16%. Voxelwise RS-ESA yielded similar VTs and coefficients of variation. Conclusion: 18F-GE-179 exhibits high and rapid brain extraction, with a relatively homogeneous distribution in gray matter and acceptable between-subject variability. Despite its rapid peripheral metabolism, quantification of 18F-GE-179 VT is feasible both within regions of interest and at the voxel level. The specificity of 18F-GE-179 binding, however, requires further characterization with in vivo studies using activation and disease models.

Accurate Localization of Optic Radiation During Neurosurgery in an Interventional MRI Suite

Accurate localization of the optic radiation is key to improving the surgical outcome for patients undergoing anterior temporal lobe resection for the treatment of refractory focal epilepsy. Current commercial interventional magnetic resonance imaging (MRI) scanners are capable of performing anatomical and diffusion weighted imaging and are used for guidance during various neurosurgical procedures. We present an interventional imaging workflow that can accurately localize the optic radiation during surgery. The workflow is driven by a near real-time multichannel nonrigid image registration algorithm that uses both anatomical and fractional anisotropy pre- and intra-operative images. The proposed workflow is implemented on graphical processing units and we perform a warping of the pre-operatively parcellated optic radiation to the intra-operative space in under 3 min making the proposed algorithm suitable for use under the stringent time constraints of neurosurgical procedures. The method was validated using both a numerical phantom and clinical data using pre- and post-operative images from patients who had undergone surgery for treatment of refractory focal epilepsy and shows strong correlation between the observed post-operative visual field deficit and the predicted damage to the optic radiation. We also validate the algorithm using interventional MRI datasets from a small cohort of patients. This work could be of significant utility in image guided interventions and facilitate effective surgical treatments.

Feasibility of multimodal 3D neuroimaging to guide implantation of intracranial EEG electrodes.

Highlights • Developed pipeline for multimodal image integration to guide epilepsy surgery.• Reported the key principles of the pipeline and its detailed description.• Demonstrated feasibility of the developed pipeline for multimodal image integration.• Illustrated potential benefits of intraoperative use of the pipeline.

Structural imaging biomarkers of sudden unexpected death in epilepsy

The mechanisms underlying sudden unexpected death in epilepsy (SUDEP) remain unclear. Wandschneider et al. reveal increased amygdalo-hippocampal volume in cases of SUDEP and in individuals at high risk, compared to individuals at low risk and people without epilepsy. Findings are consistent with histopathological reports in sudden infant death syndrome.

Auditory tracts identified with combined fMRI and diffusion tractography.

The auditory tracts in the human brain connect the inferior colliculus (IC) and medial geniculate body (MGB) to various components of the auditory cortex (AC). While in non-human primates and in humans, the auditory system is differentiated in core, belt and parabelt areas, the correspondence between these areas and anatomical landmarks on the human superior temporal gyri is not straightforward, and at present not completely understood. However it is not controversial that there is a hierarchical organization of auditory stimuli processing in the auditory system. The aims of this study were to demonstrate that it is possible to non-invasively and robustly identify auditory projections between the auditory thalamus/brainstem and different functional levels of auditory analysis in the cortex of human subjects in vivo combining functional magnetic resonance imaging (fMRI) with diffusion MRI, and to investigate the possibility of differentiating between different components of the auditory pathways (e.g. projections to areas responsible for sound, pitch and melody processing). We hypothesized that the major limitation in the identification of the auditory pathways is the known problem of crossing fibres and addressed this issue acquiring DTI with b-values higher than commonly used and adopting a multi-fibre ball-and-stick analysis model combined with probabilistic tractography. Fourteen healthy subjects were studied. Auditory areas were localized functionally using an established hierarchical pitch processing fMRI paradigm. Together fMRI and diffusion MRI allowed the successful identification of tracts connecting IC with AC in 64 to 86% of hemispheres and left sound areas with homologous areas in the right hemisphere in 86% of hemispheres. The identified tracts corresponded closely with a three-dimensional stereotaxic atlas based on postmortem data. The findings have both neuroscientific and clinical implications for delineation of the human auditory system in vivo.