Timo Krings

Clinical application of proton magnetic resonance spectroscopy in the diagnosis of intracranial mass lesions

Diagnosis of primary and secondary brain tumours and other focal intracranial mass lesions based on imaging procedures alone is still a challenging problem. Proton magnetic resonance spectroscopy (1H-MRS) gives completely different information related to cell membrane proliferation, neuronal damage, energy metabolism and necrotic transformation of brain or tumour tissues. Our purpose was to evaluate the clinical utility of 1H-MRS added to MRI for the differentiation of intracranial neoplastic and non-neoplastic mass lesions. 176 mostly histologically verified lesions were studied with a constant clinically available single volume 1H-MRS protocol following routine MRI. 12 spectra (6.8%) were not of satisfactory diagnostic quality; 164 spectroscopic data sets were therefore available for definitive evaluation. Our study shows that spectroscopy added to MRI helps in tissue characterization of intracranial mass lesions, thereby leading to an improved diagnosis of focal brain disease. Non-neoplastic lesions such as cerebral infarctions and brain abscesses are marked by decreases in choline (Cho), creatine (Cr) and N-acetyl-aspartate (NAA), while tumours generally have elevated Cho and decreased levels of Cr and NAA. Gliomas exhibit significantly increased Cho and lipid formation with higher WHO tumour grading. Metastases have elevated Cho similar to anaplastic astrocytomas, but can be differentiated from high-grade gliomas by their higher lipid levels. Extra-axial tumours, i.e. meningiomas and neurinomas, are characterized by a nearly complete absence of the neuronal marker NAA. The additive information of 1H-MRS led to a 15.4%-higher number of correct diagnoses, to 6.2% fewer incorrect and 16% fewer equivocal diagnoses than with structural MRI data alone.

Safety and efficacy of NA-1 in patients with iatrogenic stroke after endovascular aneurysm repair (ENACT): a phase 2, randomised, double-blind, placebo-controlled trial

BACKGROUND Neuroprotection with NA-1 (Tat-NR2B9c), an inhibitor of postsynaptic density-95 protein, has been shown in a primate model of stroke. We assessed whether NA-1 could reduce ischaemic brain damage in human beings. METHODS For this double-blind, randomised, controlled study, we enrolled patients aged 18 years or older who had a ruptured or unruptured intracranial aneurysm amenable to endovascular repair from 14 hospitals in Canada and the USA. We used a computer-generated randomisation sequence to allocate patients to receive an intravenous infusion of either NA-1 or saline control at the end of their endovascular procedure (1:1; stratified by site, age, and aneurysm status). Both patients and investigators were masked to treatment allocation. The primary outcome was safety and primary clinical outcomes were the number and volume of new ischaemic strokes defined by MRI at 12-95 h after infusion. We used a modified intention-to-treat (mITT) analysis. This trial is registered with ClinicalTrials.gov, number NCT00728182. FINDINGS Between Sept 16, 2008, and March 30, 2011, we randomly allocated 197 patients to treatment-12 individuals did not receive treatment because they were found to be ineligible after randomisation, so the mITT population consisted of 185 individuals, 92 in the NA-1 group and 93 in the placebo group. Two minor adverse events were adjudged to be associated with NA-1; no serious adverse events were attributable to NA-1. We recorded no difference between groups in the volume of lesions by either diffusion-weighted MRI (adjusted p value=0·120) or fluid-attenuated inversion recovery MRI (adjusted p value=0·236). Patients in the NA-1 group sustained fewer ischaemic infarcts than did patients in the placebo group, as gauged by diffusion-weighted MRI (adjusted incidence rate ratio 0·53, 95% CI 0·38-0·74) and fluid-attenuated inversion recovery MRI (0·59, 0·42-0·83). INTERPRETATION Our findings suggest that neuroprotection in human ischaemic stroke is possible and that it should be investigated in larger trials. FUNDING NoNO Inc and Arbor Vita Corp.

Cortical activation patterns during complex motor tasks in piano players and control subjects. A functional magnetic resonance imaging study

We performed functional magnetic resonance imaging (MRI) in professional piano players and control subjects during an overtrained complex finger movement task using a blood oxygenation level dependent echo-planar gradient echo sequence. Activation clusters were seen in primary motor cortex, supplementary motor area, premotor cortex and superior parietal lobule. We found significant differences in the extent of cerebral activation between both groups with piano players having a smaller number of activated voxels. We conclude that, due to long-term motor practice a different cortical activation pattern can be visualized in piano players. For the same movements lesser neurons need to be recruited. The different volume of the activated ortical areas might therefore reflect the different effort necessary for motor performance in both groups.

Effects of Blood Estrogen Level on Cortical Activation Patterns during Cognitive Activation as Measured by Functional MRI

Modulation of the blood estrogen level as it occurs during the menstrual cycle has a strong influence on both neuropsychological and neurophysiological parameters. One of currently preferred hypotheses is that the menstrual cycle hormones modulate functional hemispheric lateralization. We examined six male and six female subjects by functional magnetic resonance imaging (fMRI) to image cortical activation patterns associated with cognitive and motor activation to determine whether these changes during the menstrual cycle can be visualized. Female subjects, who did not use oral contraceptives, were scanned twice, once during the menses and once on the 11/12 day of the menstrual cycle. A word-stem-completion task, a mental rotation task and a simple motor task were performed by all subjects. Our data provide evidence that the menstrual cycle hormones influence the overall level of cerebral hemodynamics to a much stronger degree than they influence the activation pattern itself. No differences were seen between male subjects and female subjects during the low estrogen phase. During both neuropsychological tasks blood estrogen level had a profound effect on the size but not on the lateralization or the localization of cortical activation patterns. The female brain under estrogen showed a marked increase in perfusion in cortical areas involved in both cognitive tasks, whereas the hemodynamic effects during the motor tasks were less pronounced. This might be due to differences in neuronal or endothelian receptor concentration, differences in synaptic function, or, most likely, changes in the cerebrovascular anatomy in different cortical regions.

Localization of the motor hand area using transcranial magnetic stimulation and functional magnetic resonance imaging

OBJECTIVE The anatomical location of the motor area of the hand may be revealed using functional magnetic resonance imaging (fMRI). The motor cortex representation of the intrinsic hand muscles consists of a knob-like structure. This is omega- or epsilon-shaped in the axial plane and hook-shaped in the sagittal plane. As this knob lies on the surface of the brain, it can be stimulated non-invasively by transcranial magnetic stimulation (TMS). It was the aim of our study to identify the hand knob using fMRI and to reveal if the anatomical hand knob corresponds to the hand area of the motor cortex, as identified by TMS, by means of a frameless MRI-based neuronavigation system. METHODS Suprathreshold transcranial magnetic stimuli were applied over a grid on the left side of the scalp of 4 healthy volunteers. The motor evoked potentials (MEPs) were recorded from the contralateral small hand muscles, and the centers of gravity (CoG) of the MEPs were calculated. The exact anatomical localization of each point on the grid was determined using a frameless MRI-based neuronavigation system. In each subject, the hand area of the motor cortex was visualized using fMRI during sensorimotor activation achieved by clenching the right hand. RESULTS In all 4 subjects, the activated precentral site in the fMRI and the CoG of the MEP of all investigated muscles lay within the predicted anatomical area, the so-called hand knob. This knob had the form of an omega in two subjects and an epsilon in the other two subjects. CONCLUSIONS TMS is a reliable method for mapping the motor cortex. The CoG calculated from the motor output maps may be used as an accurate estimation of the location of the represented muscle in the motor cortex.

Three-dimensional visualization of the pyramidal tract in a neuronavigation system during brain tumor surgery: first experiences and technical note.

OBJECTIVETo integrate spatial three-dimensional information concerning the pyramidal tracts into a customized system for frameless neuronavigation during brain tumor surgery. METHODSFour consecutive patients with intracranial tumors in eloquent areas underwent diffusion-weighted and anatomic magnetic resonance imaging studies within 48 hours before surgery. Diffusion-weighted datasets were merged with anatomic data for navigation purposes. The pyramidal tracts were segmented and reconstructed for three-dimensional visualization. The reconstruction results, together with the fused-image dataset, were available during surgery in the environment of a customized neuronavigation system. RESULTSIn all four patients, the combination of reconstructed data and fused images was a helpful additional source of information concerning the tumor seat and topographical interaction with the pyramidal tract. In two patients, intraoperative motor cortex stimulation verified the tumor seat with regard to the precentral gyrus. CONCLUSIONDiffusion-weighted magnetic resonance imaging allows individual estimation of large fiber tracts applicable as important information in intraoperative neuronavigation and in planning brain tumor resection. A three-dimensional representation of fibers associated with the pyramidal tract during brain tumor surgery is feasible with the presented technique and is a helpful adjunct for the neurosurgeon. The main drawbacks include the length of time required for the segmentation procedure, the lack of direct intraoperative control of the pyramidal tract position, and brain shift. However, mapping of large fiber tracts and its intraoperative use for neuronavigation have the potential to increase the safety of neurosurgical procedures and to reduce surgical morbidity.

Functional magnetic resonance imaging and transcranial magnetic stimulation Complementary approaches in the evaluation of cortical motor function

Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) represent different approaches to mapping the motor cortex. fMRI identifies areas of hemodynamic changes during task performance while TMS provides electrophysiologic data concerning the localization and density of cortical motoneurons. Here we define the spatial correlation between fMRI and TMS maps and compared them with direct electrical cortical stimulation (ECS). We performed fMRI at 1.5 T on 3 normal subjects and 2 patients with mass lesions near the central sulcus using a multislice, asymmetric, spin-echo, echo-planar pulse sequence during the performance of a motor task. We also performed focal TMS with surface EMG recordings from the muscles primarily involved in the fMRI task. We coregistered the stimulation sites in real time with the fMRI maps using a frameless stereotactic system. In both patients we also performed ECS of the cortex during surgery under local anesthesia. fMRI maps were validated by the electro-physiologic data both pre- and intraoperatively. Our results suggest that regions of fMRI activation correspond spatially to areas of highest motoneuron density as demonstrated by electrophysiologic techniques.

Dural Arteriovenous Shunts: A New Classification of Craniospinal Epidural Venous Anatomical Bases and Clinical Correlations

Background and Purpose— The craniospinal epidural spaces can be categorized into 3 different compartments related to their specific drainage role of the bone and central nervous system, the ventral epidural, dorsal epidural, and lateral epidural groups. We propose this new classification system for dural arteriovenous shunts and compare demographic, angiographic, and clinical characteristics of dural arteriovenous shunts that develop in these 3 different locations. Methods— Three hundred consecutive cases (159 females, 141 males; mean age: 47 years; range, 0 to 87 years) were reviewed for patient demographics, clinical presentation, multiplicity, presence of cortical and spinal venous reflux, and outflow restrictions and classified into the 3 mentioned groups. Results— The ventral epidural group (n=150) showed a female predominance, more benign clinical presentations, lower rate of cortical and spinal venous reflux, and no cortical and spinal venous reflux without restriction of the venous outflow. The dorsal epidural group (n=67) had a lower mean age and a higher rate of multiplicity. The lateral epidural group (n=63) presented later in life with a male predominance, more aggressive clinical presentations, and cortical and spinal venous reflux without evidence of venous outflow restriction. All differences were statistically significant (P<0.001). Conclusion— Dural arteriovenous shunts predictably drain either in pial veins or craniofugally depending on the compartment involved by the dural arteriovenous shunt. Associated conditions (outflow restrictions, high-flow shunts) may change that draining pattern. The significant differences between the groups of the new classification support the hypothesis of biological and/or developmental differences in each epidural region and suggest that dural arteriovenous shunts are a heterogeneous group of diseases.

Dangerous Extracranial–Intracranial Anastomoses and Supply to the Cranial Nerves: Vessels the Neurointerventionalist Needs to Know

SUMMARY: Transarterial embolization in the external carotid artery (ECA) territory has a major role in the endovascular management of epistaxis, skull base tumors, and dural arteriovenous fistulas. Knowledge of the potential anastomotic routes, identification of the cranial nerve supply from the ECA, and the proper choice of embolic material are crucial to help the interventionalist avoid neurologic complications during the procedure. Three regions along the skull base constitute potential anastomotic routes between the extracranial and intracranial arteries: the orbital, the petrocavernous, and the upper cervical regions. Branches of the internal maxillary artery have anastomoses with the ophthalmic artery and petrocavernous internal carotid artery (ICA), whereas the branches of the ascending pharyngeal artery are connected to the petrocavernous ICA. Branches of both the ascending pharyngeal artery and the occipital artery have anastomoses with the vertebral artery. To avoid cranial nerve palsy, one must have knowledge of the supply to the lower cranial nerves: The petrous branch of the middle meningeal artery and the stylomastoid branch of the posterior auricular artery form the facial arcade as the major supply to the facial nerve, and the neuromeningeal trunk of the ascending pharyngeal artery supplies the lower cranial nerves (CN IX–XII).

Spinal vascular malformations

Spinal vascular malformations are rare diseases that consist of true inborn cavernomas and arteriovenous malformations (including perimedullary fistulae, glomerular and juvenile AVMs) and presumably acquired dural arteriovenous fistulae. This review article gives an overview of the imaging features both on MRI and angiography, the differential diagnoses, the clinical symptomatology and the potential therapeutic approaches to these diseases. It is concluded that MRI is the diagnostic modality of first choice in suspected spinal vascular malformation and should be complemented by selective spinal angiography. Treatment in symptomatic patients offers an improvement in the prognosis, but should be performed in specialized centers. Patients with spinal cord cavernomas and perimedullary fistulae type I are surgical candidates. Dural arteriovenous fistulae can either be operated upon or can be treated by an endovascular approach, the former being a simple, quick and secure approach to obliterate the fistula, while the latter is technically demanding. In spinal arteriovenous malformations, the endovascular approach is the method of first choice; in selected cases, a combined therapy might be sensible.