Advanced diffusion MRI provides evidence for altered axonal microstructure and gradual peritumoral infiltration in GBM in comparison to brain metastases.

PURPOSE: In contrast to peritumoral edema in metastases, GBM is histopathologically characterized by infiltrating tumor cells within the T2 signal alterations. We hypothesized that depending on the distance from the outline of the contrast-enhancing tumor we might reveal imaging evidence of gradual peritumoral infiltration in GBM and predominantly vasogenic edema around metastases. We thus investigated the gradual change of advanced diffusion metrics with the peritumoral zone in metastases and GBM. METHODS: In 30 patients with GBM and 28 with brain metastases, peritumoral T2 hyperintensity was segmented in 33% partitions based on the total volume beginning at the enhancing tumor margin and divided into inner, middle and outer zones. Diffusion Tensor Imaging (DTI)-derived fractional anisotropy and mean diffusivity as well as Diffusion Microstructure Imaging (DMI)-based parameters Dax-intra, Dax-extra, V­CSF and V-intra were employed to assess group-wise differences between inner and outer zones as well as within-group gradients between the inner and outer zones. RESULTS: In metastases, fractional anisotropy and Dax-extra were significantly reduced in the inner zone compared to the outer zone (FA p = 0.01; Dax-extra p = 0.03). In GBM, we noted a reduced Dax-extra and significantly lower intraaxonal volume fraction (Dax-extra p = 0.008, V­intra p = 0.006) accompanied by elevated axial intraaxonal diffusivity in the inner zone (p = 0.035). Between-group comparison of the outer to the inner zones revealed significantly higher gradients in metastases over GBM for FA (p = 0.04) as well as the axial diffusivity in the intra- (p = 0.02) and extraaxonal compartment (p < 0.001). CONCLUSION: Our findings provide evidence of gradual alterations within the peritumoral zone of brain tumors. These are compatible with predominant (vasogenic) edema formation in metastases, whereas our findings in GBM are in line with an axonal destructive component in the immediate peritumoral area and evidence of tumor cell infiltration with accentuation in the tumor's vicinity.

Gray-White Matter Blurring of the Temporal Pole Associated With Hippocampal Sclerosis: A Microstructural Study Involving 3 T MRI and Ultrastructural Histopathology.

Hippocampal sclerosis (HS) is often associated with gray-white matter blurring (GMB) of the anterior temporal lobe. In this study, twenty patients with unilateral temporal lobe epilepsy and HS were studied with 3 T MRI including T1 MP2RAGE and DTI/DMI sequences. Anterior temporal lobe white matter T1 relaxation times and diffusion measures were analyzed on the HS side, on the contralateral side, and in 10 normal controls. Resected brain tissue of three patients without GMB and four patients with GMB was evaluated ultrastructurally regarding axon density and diameter, the relation of the axon diameter to the total fiber diameter (G-ratio), and the thickness of the myelin sheath. Hippocampal sclerosis GMB of the anterior temporal lobe was related to prolonged T1 relaxation and axonal loss. A less pronounced reduction in axonal fraction was also found on imaging in GMB-negative temporal poles compared with normal controls. Contralateral values did not differ significantly between patients and normal controls. Reduced axonal density and axonal diameter were histopathologically confirmed in the temporopolar white matter with GMB compared to temporal poles without. These results confirm that GMB can be considered an imaging correlate for disturbed axonal maturation that can be quantified with advanced diffusion imaging.

Deep brain stimulation electrodes may rotate after implantation-an animal study.

Directional deep brain stimulation (dDBS) electrodes allow to steer the electrical field in a specific direction. When implanted with torque, they may rotate for a certain time after implantation. The aim of this study was to evaluate whether and to which degree leads rotate in the first 24 h after implantation using a sheep brain model. dDBS electrodes were implanted in 14 sheep heads and 3D rotational fluoroscopy (3D-RF) scans were acquired to visualize the orientation of the electrode leads. Electrode leads were clockwise rotated just above the burr holes (180° n = 6, 360° n = 6, 2 controls) and 3D-RF scans were again acquired after 3, 6, 13, 17, and 24 h, respectively. One hundred eighty degree rotated electrodes showed an initial rotation of 83.5° (range: 35.4°-128.3°) and a rotation of 114.0° (range: 57°-162°) after 24 h. With 360° torsion, mean initial rotation was 201° (range: 3.3°-321.4°) and mean rotation after 24 h 215.7° (range 31.9°-334.7°), respectively. Direct postoperative imaging may not be accurate for determining the rotation of dDBS electrodes if torque is present.

Determining the Orientation of Directional Deep Brain Stimulation Electrodes Using 3D Rotational Fluoroscopy.

BACKGROUND AND PURPOSE: New deep brain stimulation leads with electrode contacts that are split along their circumference allow steering of the electrical field in a predefined direction. However, imaging-assisted directional stimulation requires detailed knowledge of the exact orientation of the electrode array. The purpose of this study was to evaluate whether this information can be obtained by rotational 3D fluoroscopy. MATERIALS AND METHODS: Two directional leads were inserted into a 3D-printed plaster skull filled with gelatin. The torsion of the lead tip versus the lead at the burr-hole level was investigated. Then, 3 blinded raters evaluated 12 3D fluoroscopies with random lead orientations. They determined the lead orientation considering the x-ray marker only and considering the overlap of the gaps between the contact segments. Intraclass correlation coefficients and an extended version of the Bland-Altman plot were used to determine interrater reliability and agreement of the measurements of the different raters. RESULTS: Electrode torsion of up to 35° could be demonstrated. Evaluation of the lead rotation considering the x-ray marker only revealed limits of agreement of ±9.37° and an intraclass correlation coefficient of 0.9975. In addition, taking into account the lines resulting from overlapping of the gaps between the electrode segments, the limits of agreement to the mean were ±2.44° and an intraclass correlation coefficient of 0.9998. CONCLUSIONS: In directional deep brain stimulation systems, rotational 3D fluoroscopy combined with the described evaluation method allows for determining the exact orientation of the leads, enabling the full potential of imaging-assisted personalized programming.

Effects of deep brain stimulation of the cerebellothalamic pathways on the sense of smell.

The cerebellum and the motor thalamus, connected by cerebellothalamic pathways, are traditionally considered part of the motor-control system. Yet, functional imaging studies and clinical studies including patients with cerebellar disease suggest an involvement of the cerebellum in olfaction. Additionally, there are anecdotal clinical reports of olfactory disturbances elicited by electrical stimulation of the motor thalamus and its neighbouring subthalamic region. Deep brain stimulation (DBS) targeting the cerebellothalamic pathways is an effective treatment for essential tremor (ET), which also offers the possibility to explore the involvement of cerebellothalamic pathways in the sense of smell. This may be important for patient care given the increased use of DBS for the treatment of tremor disorders. Therefore, 21 none-medicated patients with ET treated with DBS (13 bilateral, 8 unilateral) were examined with "Sniffin' Sticks," an established and reliable method for olfactory testing. Patients were studied either with DBS switched on and then off or in reversed order. DBS impaired odor threshold and, to a lesser extent, odor discrimination. These effects were sub-clinical as none of the patients reported changes in olfactory function. The findings, however, demonstrate that olfaction can be modulated in a circumscribed area of the posterior (sub-) thalamic region. We propose that the impairment of the odor threshold with DBS is related to effects on an olfacto-motor loop, while disturbed odor discrimination may be related to effects of DBS on short-term memory.

Intramedullary hemangioblastomas: timing of surgery, microsurgical technique and follow-up in 23 patients.

Hemangioblastomas are highly vascularised tumors of the central nervous system and account for 1.5-2.5% of all spinal cord tumors. Because of the rarity of these tumors, surgical experience is often limited and, therefore, treatment and indications for timing of surgery are discussed controversial. The authors reviewed their data of 23 consecutive patients with respect to timing of surgery, microsurgical technique, and follow-up. Clinical records of 23 consecutive patients with intramedullary hemangioblastomas who underwent first surgery in our department between 1990 and 2005 were reviewed. In three cases the tumors were localised at the craniocervical junction; four patients had a single tumor in the cervical spine, six patients multiple tumors in the cervical and thoracic spine, eight patients in the thoracic spine only, one patient in the conus region, and one patient had multiple tumors located in the thoracic and lumbar spine. In eight patients, a von-Hippel-Lindau disease (VHL) was associated. The neurological follow-up was evaluated according to the classification of McCormick. Operation was recommended to every symptomatic patient as early as possible. In asymptomatic patients with a sporadic tumor surgery was discussed for diagnostic purposes at any time. In VHL patients, surgery was recommended if tumor growth was observed on MRI in the next practicable time. All tumors were diagnosed by magnetic resonance imaging and in all cases but one a DSA was performed. All patients were treated microsurgically through a posterior approach. The tumors in the spinal cord were removed microsurgically through a partial hemilaminectomy (n = 1), a hemilaminectomy (n = 15), or laminectomy (n = 4) and at the craniocervical junction (n = 3) through a suboccipital craniotomy. During follow-up after 6 months, 18 patients remained neurologically stable (17 in McCormick grade I and 1 in McCormick grade II) and 5 patients recovered to a better status (3 from grade III to II, 2 from grade II to I). There was one complication with a CSF fistula and one recurrence/incomplete removal. Following the above-mentioned principles of microsurgical removal of intramedullary hemangioblastomas, operation is possible with a low procedure-related morbidity and can be recommended especially in VHL patients with progressive symptoms or tumor growth during follow-up. Patients without VHL most frequently require hemangioblastoma resection for diagnostic purposes and/or because symptoms prompted an imaging work-up that lead to the discovery of the tumor.

Thalamic deep brain stimulation improves eyeblink conditioning deficits in essential tremor.

Several lines of evidence point to a disturbance of olivo-cerebellar pathways in essential tremor (ET). For example, subjects with ET exhibit deficits in eyeblink conditioning, a form of associative learning which is known to depend on the integrity of olivo-cerebellar circuits. Deep brain stimulation (DBS) of the ventrolateral thalamus is an established therapy for ET. If tremor in ET is related to the same pathology of the olivo-cerebellar system as impaired eyeblink conditioning, one may expect modulation of eyeblink conditioning by DBS. Delay eyeblink conditioning was assessed in 11 ET subjects treated with DBS (ET-DBS subjects) who were studied on two consecutive days with DBS switched off (day 1) and on (day 2). For comparison, 11 age-matched ET subjects without DBS (ET subjects) and 11 age-matched healthy controls were studied. On day 1, eyeblink conditioning was diminished in ET-DBS subjects and in ET subjects compared with controls. When DBS was switched on ET-DBS subjects exhibited conditioning rates within the range of controls on day 2, while ET subjects improved only minimally. Improved eyeblink conditioning in ET-DBS subjects suggests that thalamic DBS counteracts a functional disturbance of olivo-cerebellar circuits which is thought to be responsible for eyeblink conditioning deficits in ET. Modulation of cerebello-thalamic and/or thalamo-cortico-cerebellar pathways by DBS may play a role.

A less invasive surgical concept for the resection of spinal meningiomas.

BACKGROUND: The surgical strategy for spinal meningiomas usually consists of laminectomy, initial tumour debulking, identification of the interface between tumour and spinal cord, resection of the dura including the matrix of the tumour, and duroplasty. The objective of this study was to investigate whether a less invasive surgical strategy consisting of hemilaminectomy or laminectomy, tumour removal and coagulation of the tumour matrix allows comparable surgical and clinical results to be obtained, especially without an increase of the recurrence rate as reported in the literature. PATIENTS AND METHODS: Between 1990 and 2005, 61 patients (11 men, 50 women) underwent surgery for spinal meningioma. All patients were treated microsurgically by a posterior approach. In 56 of the 61 patients, the above outlined - less invasive - surgical technique with tumour removal and coagulation of the tumour matrix was performed. In 5 patients, dura resection and duroplasty was additionally performed. Electrophysiological monitoring was routinely used since 1996. Recurrence was defined as new onset or worsening of symptoms and radiological confirmation of tumour growth. The pre-and post-operative clinical status was measured by the Frankel grading system. RESULTS: Pre-operatively, 40 patients were in Frankel grade D, 13 patients in grade C, 6 patients in grade E and 1 patient each in grade A and B. Following surgery no patient presented a permanent worsening of clinical symptoms. All patients who initially presented with a Frankel grades A-C (n = 15) recovered to a better grade at the time of follow-up. Patients who presented with Frankel grade D remained in stable condition (n = 27) or recovered to a better neurological status (n = 13). Two patients experienced a temporary worsening of their symptoms, but subsequently improved to a better state than pre-operatively. Two (3.3%) complications (pseudomeningocele, wound infection) requiring surgery, were encountered. The pseudomeningocele developed in a patient who underwent durotomy. During the follow-up period of 2 months to 10 years (mean 31.3 months), 3 patients (5%) required surgery for symptomatic recurrence: 1 patient had 2 recurrences that occurred 4 and 7 years after first tumour removal and matrix coagulation, 1 recurrence occurred 1 year after tumour removal that was accompanied by matrix coagulation in a patient with a diffuse anterocranial tumour extension and 1 occurred 3 years after tumour removal and durotomy. Two patients showed a small recurrence on MRI during follow-up after 2 and 5 years, respectively, without any symptoms requiring surgery. CONCLUSIONS: The high rate of favourable clinical results combined with the low rate of recurrences supports our less invasive surgical concept, which does not aim for resection of the dural matrix of the spinal meningioma.

Combined motor and somatosensory evoked potentials for intraoperative monitoring: intra- and postoperative data in a series of 69 operations.

The primary objective of neurophysiologic monitoring during surgery is to avoid permanent neurological injury resulting from surgical manipulation. To prevent motor deficits, either somatosensory (SSEP) or transcranial motor evoked potentials (MEP) are applied. This prospective study was conducted to evaluate if the combined use of SSEP and MEP might be beneficial. Combined SSEP/MEP monitoring was attempted in 100 consecutive procedures, including intracranial and spinal operations. Repetitive transcranial electric motor cortex stimulation was used to elicit MEP from muscles of the upper and lower limb. Stimulation of the tibial and median nerves was performed to record SSEP. Critical SSEP/MEP changes were defined as decreases in amplitude of more than 50% or increases in latency of more than 10% of baseline values. The operation was paused or the surgical strategy was modified in every case of SSEP/MEP changes. Combined SSEP/MEP monitoring was possible in 69 out of 100 operations. In 49 of the 69 operations (71%), SSEP/ MEP were stable, and the patients remained neurologically intact. Critical SSEP/ MEP changes were seen in six operations. Critical MEP changes with stable SSEP occurred in 12 operations. Overall, critical MEP changes were recorded in 18 operations (26%). In 12 of the 18 operations, MEP recovered to some extent after modification of the surgical strategy, and the patients either showed no (n = 10) or only a transient motor deficit (n = 2). In the remaining six operations, MEP did not recover and the patients either had a transient (n = 3) or a permanent (n = 3) motor deficit. Critical SSEP changes with stable MEP were observed in two operations; both patients did not show a new motor deficit. Our data again confirm that MEP monitoring is superior to SSEP monitoring in detecting impending impairment of the functional integrity of cerebral and spinal cord motor pathways during surgery. Detection of MEP changes and adjustment of the surgical strategy might allow to prevent irreversible pyramidal tract damage. Stable SSEP/MEP recordings reassure the surgeon that motor function is still intact and surgery can be continued safely. The combined SSEP/ MEP monitoring becomes advantageous, if one modality is not recordable.

Growth and rupture mechanism of partially thrombosed aneurysms.

SUMMARY: Within the group of giant and large aneurysms the subgroup of the so-called "partially thrombosed" aneurysms can be differentiated according to clinical and neuroimaging findings. The present study was carried out to determine the site of bleeding of these aneurysms and what implications concerning their pathomechanism can be drawn from these findings. Twenty patients aged two to 77 (mean 44) years who exhibited a partially thrombosed aneurysm that had recently bled were included. Images (MRI including T1 pre- and postcontrast and T2 weighted images in multiple planes, CT and digital subtraction angiography) and patients' charts were reviewed. MRI showed an onion-skin appearance of the thrombus in 19 patients, rim enhancement of the aneurysm wall (either partial or complete) in 17, and a perifocal edema in 16 patients. The acute hemorrhage was typically crescent-shaped and located at the periphery of the aneurysm, distant from the perfused lumen of the aneurysm within the thrombosed part of the aneurysm. The current denomination "partially thrombosed" intracranial arterial aneurysms leads to the presumption that thrombus is present endoluminal whereas in fact the site of hemorrhage is within the vessel wall. A more accurate nomination would, therefore, be "aneurysms with intramural hemorrhage". The enhancing wall and the edematous reaction of the adjacent brain parenchyma might be a sign for an inflammatory pathomechanism which is reinforced by histological and pathophysiological studies. This disease should be regarded as a clinical entity separate from saccular or non-thrombosed giant or large aneurysms.

Electrophysiological proof of diffusion-weighted imaging-derived depiction of the deep-seated pyramidal tract in human.

In the living human brain the pyramidal tract (PT) can be displayed with magnetic resonance diffusion-weighted imaging (DWI). Although this imaging technique is already being used for planning and performing neurosurgical procedures in the PT vicinity, there is a lack of verification of DWI accuracy in other areas outside the directly subcortical PT parts. Before definitive electrode placement into the subthalamic nucleus (STN) in patients with Parkinson disease (PD) for chronic stimulation, the stimulation effect on PD symptoms and the side-effects, namely PT activation at the level of the internal capsule (IC), are electrophysiologically tested. To analyze DWI accuracy by matching the stereotactic coordinates of the electrophysiologically proven IC position with these of the DWI-derived IC display, DWI was added to the routine MRI work-up in the stereotactic frame prior to functional surgery in 6 patients. In all of the 10 displayed fiber tracts, concordant findings for imaging and macrostimulation were made. The authors proved for the first time that DWI correctly depicts the deep seated, principle motor pathways in the living human brain. Due to methodical limitations of this study the accuracy of the proven IC display is limited to 3 mm which has proven to be sufficient for the planning and performance of neurosurgical procedures in the vicinity of large fiber tracts.

Magnetic versus manual guidewire manipulation in neuroradiology: in vitro results.

INTRODUCTION: Standard microguidewires used in interventional neuroradiology have a predefined shape of the tip that cannot be changed while the guidewire is in the vessel. We evaluated a novel magnetic navigation system (MNS) that generates a magnetic field to control the deflection of a microguidewire that can be used to reshape the guidewire tip in vivo without removing the wire from the body, thereby potentially facilitating navigation along tortuous paths or multiple acute curves. METHOD: The MNS consists of two permanent magnets positioned on either side of the fluoroscopy table that create a constant precisely controlled magnetic field in the defined region of interest. This field enables omnidirectional rotation of a 0.014-inch magnetic microguidewire (MG). Speed of navigation, accuracy in a tortuous vessel anatomy and the potential for navigating into in vitro aneurysms were tested by four investigators with differing experience in neurointervention and compared to navigation with a standard, manually controlled microguidewire (SG). RESULTS: Navigation using MG was faster (P=0.0056) and more accurate (0.2 mistakes per trial vs. 2.6 mistakes per trial) only in less-experienced investigators. There were no statistically significant differences between the MG and the SG in the hands of experienced investigators. One aneurysm with an acute angulation from the carrier vessel could be navigated only with the MG while the SG failed, even after multiple reshaping manoeuvres. CONCLUSION: Our findings suggest that magnetic navigation seems to be easier, more accurate and faster in the hands of less-experienced investigators. We consider that the features of the MNS may improve the efficacy and safety of challenging neurointerventional procedures.

Time Resolved 3D MRA. Applications for Interventional Neuroradiology.

SUMMARY: The decision for endovascular treatment of cranial dural AV fistulae and angiomas and their follow-up after treatment is usually based on conventional DSA. New techniques of magnetic resonance angiography (MRA) facilitate high temporal and spatial resolution images.The purpose of this study was to evaluate the applicability and clinical use of a newly developed 3D dynamic MRA protocol on a 3T scanner for neurointerventional planning and decisionmaking. Using a 3T whole body scanner, a three-dimensional dynamic contrast enhanced MRA sequence with parallel imaging, and intelligent kspace readout (Keyhole and "CENTRA" kspace filling) was added to structural MRI and time-of-flight MRA in seven patients. DSA was performed in each patient following MR examination. In all patients MRA allowed the identification and correct classification of the vascular lesion. Hemodynamic characteristics and venous architecture were clearly demonstrated. Larger feeding arteries could be identified in all cases. Smaller feeding vessels were overlooked in dynamic MRA and only depicted in conventional DSA High temporal and spatial resolution 3D MRA may correctly identify and classify fistulae and angiomas and help to reduce the number of pre- or post-interventional invasive diagnostic angiograms.

Clinical applications of 2-D dynamic contrast-enhanced MR subtraction angiography in neurosurgery -- preliminary results.

OBJECTIVES: Advances in MR hardware performance and imaging techniques have enabled us to perform sub-second frame rate contrast enhanced MR angiographies as a clinical routine, resulting in subtraction angiographies with temporal resolutions similar to those obtained by conventional DSA. In this manuscript, we describe the technique of 2-D dynamic contrast-enhanced MR subtraction angiography and its possible applications in neurosurgery. METHODS: A T (1)-weighted gradient-echo sequence with short TR and TE values was performed during the intravenous bolus application of MR contrast media. This sequence had a temporal resolution of up to 0.34 seconds per image and was performed in 28 patients harbouring arteriovenous malformations (n = 12), dural AV fistulas (n = 3), meningiomas (n = 8), glomus tympanicum or jugulare tumours (n = 3), and haemangioperizytomas (n = 2). Arterial digital subtraction angiography (DSA) was performed in all patients and compared to the MRA sequences with respect to differentiation into early, late arterial and venous phases, detectability of normal vessels, detection of the pathology, feeding arteries, capillary blush, early draining veins, and hyper-vascularization. RESULTS: In all 28 investigated cases and all pathological entities separation of early and late arterial phases, capillary phases, early and late venous phases was possible. The proximal portions of the major cerebral arteries, the capillary blush and the venous anatomy including the tributaries to the large sinuses could be well defined and correlated well with the gold standard, i. e. DSA. CONCLUSIONS: Dynamic contrast enhanced MR angiography will prove helpful in 1) the follow-up of AVMs since early venous drainage can be visualised; 2) the demonstration of dural AVF, which can be recognised as an early filling of a dural sinus during the early arterial phase; and 3) the characterisation of the degree of vascularisation of brain tumours.

Motor evoked potentials following highly frequent transcranial magnetoelectrical motor cortex stimulation: normal data and potential modulation by stimulation-dependent inhibitory and activating mechanisms.

OBJECTIVE: To determine the normal values (latency, amplitude) of motor evoked potentials (MEP) of the abductor pollicis brevis (APB) and tibialis anterior (TA) muscle after high-frequency repetitive transcranial magnetic stimulation of the motor cortex (rTCMS), and to evaluate stimulation-dependent MEP modulations. PATIENTS AND METHODS: 29 healthy volunteers underwent rTCMS with 2 and 4 stimuli. The interstimulus interval (ISI) was 2, 3, and 4 ms respectively, which corresponded to frequencies between 250 and 500 stimuli/s. The evoked potentials of the relaxed and voluntarily contracted APB and TA were registered. RESULTS: Depending on the frequency and number of stimuli, the mean corticomuscular latency to the relaxed APB varied between 22.2 and 22.9 ms, and to the relaxed TA between 30.4 and 32.0 ms. The intra- and interindividual variability of the amplitudes was substantial. Voluntary contraction of the target muscle always led to a decrease in latency and increase in amplitude (p < 0.05). CONCLUSION: The high variability of the amplitudes does not allow the computation of meaningful normal values. The latencies after rTCMS are close to those of normal data after single TCMS, which indicates that in awake humans identical cortical and spinal structures are similarly activated. The discrete variations of latency and amplitude after changing the frequency and stimulus number suggest that inhibitory and excitatory mechanisms on the cortical and/or spinal level modulate the muscle response.