Safety and effectiveness of large volume coils in the treatment of small aneurysms.

BACKGROUND AND PURPOSE: Large volume soft design coils facilitate quicker aneurysm filling and high packing density. Our purpose was to analyze the feasibility, safety, and effectiveness of the Penumbra Coil 400 (PC400) system in the treatment of small aneurysms. MATERIALS AND METHODS: A retrospective analysis of prospective data collected at three different centers was performed on consecutive aneurysms <10 mm treated with the PC400 system. A total of 92 aneurysms were included in the study. Feasibility, procedure safety, angiographic and clinical results, and follow-up results were evaluated. RESULTS: Mean aneurysm size was 5.8±2.0 mm. An average of 2.5±1.3 coils with a mean length of 18±16 cm per aneurysm was used, resulting in a mean packing density of 45.6±14.4%. The thromboembolic event rate was 3.3% and no procedural aneurysm rupture was observed. Immediate adequate occlusion was achieved in 66% of aneurysms. During a mean follow-up period of 7.4 months the number of adequate occlusions increased to 91%. CONCLUSIONS: Large volume PC 400 coils are safe and effective in the treatment of small aneurysms with a low thromboembolic complication rate and no hemorrhagic events. High packing densities are achieved with a low average number of coils used per aneurysm treated. The aneurysms demonstrated progressive occlusion over time, which probably suggests stability in the long term.

Intracranial artery velocity measurement using 4D PC MRI at 3 T: comparison with transcranial ultrasound techniques and 2D PC MRI.

INTRODUCTION: 4D phase contrast MR imaging (4D PC MRI) has been introduced for spatiotemporal evaluation of intracranial hemodynamics in various cerebrovascular diseases. However, it still lacks validation with standards of reference. Our goal was to compare blood flow quantification derived from 4D PC MRI with transcranial ultrasound and 2D PC MRI. METHODS: Velocity measurements within large intracranial arteries [internal carotid artery (ICA), basilar artery (BA), and middle cerebral artery (MCA)] were obtained in 20 young healthy volunteers with 4D and 2D PC MRI, transcranial Doppler sonography (TCD), and transcranial color-coded duplex sonography (TCCD). Maximum velocities at peak systole (PSV) and end diastole (EDV) were compared using regression analysis and Bland-Altman plots. RESULTS: Correlation of 4D PC MRI measured velocities was higher in comparison with TCD (r = 0.49-0.66) than with TCCD (0.35-0.44) and 2D PC MRI (0.52-0.60). In mid-BA and ICA C7 segment, a significant correlation was found with TCD (0.68-0.81 and 0.65-0.71, respectively). No significant correlation was found in carotid siphon. On average over all volunteers, PSVs and EDVs in MCA were minimally underestimated compared with TCD/TCCD. Minimal overestimation of velocities was found compared to TCD in mid-BA and ICA C7 segment. CONCLUSION: 4D PC MRI appears as valid alternative for intracranial velocity measurement consistent with previous reference standards, foremost with TCD. Spatiotemporal averaging effects might contribute to vessel size-dependent mild underestimation of velocities in smaller (MCA), and overestimation in larger-sized (BA and ICA) arteries, respectively. Complete spatiotemporal flow analysis may be advantageous in anatomically complex regions (e.g. carotid siphon) relative to restrictions of ultrasound techniques.

Characteristics of ischemic brain lesions after stenting or endarterectomy for symptomatic carotid artery stenosis: results from the international carotid stenting study-magnetic resonance imaging substudy.

BACKGROUND AND PURPOSE: In a substudy of the International Carotid Stenting Study (ICSS), more patients had new ischemic brain lesions on diffusion-weighted magnetic resonance imaging (MRI) after stenting (CAS) than after endarterectomy (CEA). In the present analysis, we compared characteristics of diffusion-weighted MRI lesions. METHODS: Number, individual and total volumes, and location of new diffusion-weighted MRI lesions were compared in patients with symptomatic carotid stenosis randomized to CAS (n=124) or CEA (n=107) in the ICSS-MRI substudy. RESULTS: CAS patients had higher lesion numbers than CEA patients (1 lesion, 15% vs 8%; 2-5 lesions, 19% vs 5%; >5 lesions, 16% vs 4%). The overall risk ratio for the expected lesion count with CAS versus CEA was 8.8 (95% confidence interval, 4.4-17.5; P<0.0001) and significantly increased among patients with lower blood pressure at randomization, diabetes mellitus, stroke as the qualifying event, left-side stenosis, and if patients were treated at centers routinely using filter-type protection devices during CAS. Individual lesions were smaller in the CAS group than in the CEA group (P<0.0001). Total lesion volume per patient did not differ significantly. Lesions in the CAS group were more likely to occur in cortical areas and subjacent white matter supplied by leptomeningeal arteries than lesions in the CEA group (odds ratio, 4.2; 95% confidence interval, 1.7-10.2; P=0.002). CONCLUSIONS: Compared with patients undergoing CEA, patients treated with CAS had higher numbers of periprocedural ischemic brain lesions, and lesions were smaller and more likely to occur in cortical areas and subjacent white matter. These findings may reflect differences in underlying mechanisms of cerebral ischemia.

Flow diversion treatment: intra-aneurismal blood flow velocity and WSS reduction are parameters to predict aneurysm thrombosis.

BACKGROUND: To evaluate the haemodynamic changes induced by flow diversion treatment in cerebral aneurysms, resulting in thrombosis or persisting aneurysm patency over time. METHOD: Eight patients with aneurysms at the para-ophthalmic segment of the internal carotid artery were treated by flow diversion only. The clinical follow-up ranged between 6 days and 12 months. Computational fluid dynamics (CFD) analysis of pre- and post-treatment conditions was performed in all cases. True geometric models of the flow diverter were created and placed over the neck of the aneurysms by using a virtual stent-deployment technique, and the device was simulated as a true physical barrier. Pre- and post-treatment haemodynamics were compared, including mean and maximal velocities, wall-shear stress (WSS) and intra-aneurysmal flow patterns. The CFD study results were then correlated to angiographic follow-up studies. RESULTS: Mean intra-aneurysmal flow velocities and WSS were significantly reduced in all aneurysms. Changes in flow patterns were recorded in only one case. Seven of eight aneurysms showed complete occlusion during the follow-up. One aneurysm remaining patent after 1 year showed no change in flow patterns. One aneurysm rupturing 5 days after treatment showed also no change in flow pattern, and no change in the maximal inflow velocity. CONCLUSIONS: Relative flow velocity and WSS reduction in and of itself may result in aneurysm thrombosis in the majority of cases. Flow reductions under aneurysm-specific thresholds may, however, be the reason why some aneurysms remain completely or partially patent after flow diversion.

MTR variations in normal adult brain structures using balanced steady-state free precession.

INTRODUCTION: Magnetization transfer (MT) is sensitive to the macromolecular environment of water protons and thereby provides information not obtainable from conventional magnetic resonance imaging (MRI). Compared to standard methods, MT-sensitized balanced steady-state free precession (bSSFP) offers high-resolution images with significantly reduced acquisition times. In this study, high-resolution magnetization transfer ratio (MTR) images from normal appearing brain structures were acquired with bSSFP. METHODS: Twelve subjects were studied on a 1.5 T scanner. MTR values were calculated from MT images acquired in 3D with 1.3 mm isotropic resolution. The complete MT data set was acquired within less than 3.5 min. Forty-one brain structures of the white matter (WM) and gray matter (GM) were identified for each subject. RESULTS: MTR values were higher for WM than GM. In general, MTR values of the WM and GM structures were in good accordance with the literature. However, MTR values showed more homogenous values within WM and GM structures than previous studies. CONCLUSIONS: MT-sensitized bSSFP provides isotropic high-resolution MTR images and hereby allows assessment of reliable MTR data in also very small brain structures in clinically feasible acquisition times and is thus a promising sequence for being widely used in the clinical routine. The present normative data can serve as a reference for the future characterization of brain pathologies.

Quantification of fat infiltration in oculopharyngeal muscular dystrophy: comparison of three MR imaging methods.

PURPOSE: To analyze and compare three quantitative MRI methods to determine the degree of muscle involvement in oculopharyngeal muscular dystrophy (OPMD). MATERIALS AND METHODS: Muscle fat content (MFC) was determined based on water-fat quantification using a 2-point Dixon (2PD) method and on a histogram analysis of the free induction decay (FID) signal of a gradient-spoiled steady-state free precession (SSFP) sequence. In addition, transverse relaxation times (T2) of muscle tissue were calculated using a monoexponential decay model. RESULTS: We observed an increased mean MFC in OPMD patients as compared to healthy controls with the adductor magnus and soleus muscles being the most involved muscles in the thigh and calf, respectively. Furthermore, strong correlations (0.78 < R² < 0.94) between different quantitative MR methods were observed. Fewer outliers, however, were obtained by the 2PD method and T2 measurements, suggesting these methods being superior to the SSFP-FID method. CONCLUSION: Quantitative MR techniques, such as fast multiecho Dixon methods and T2 imaging, can reliably differentiate between healthy and dystrophic muscles in OPMD, even if muscles are only marginally affected. Quantitative methods thus represent a promising tool that may be able to monitor more objectively the individual disease progression and treatment response in future clinical trials in muscular dystrophies.

Effect of flow diversion treatment on very small ruptured aneurysms.

BACKGROUND: Ruptured aneurysms of < 2 mm are not amenable to endovascular coiling and therefore pose a significant treatment challenge. OBJECTIVE: To test recently introduced flow diverters that allow endovascular reconstruction via another method and may represent a new treatment option for such lesions. PATIENTS AND METHODS: Three female patients presented with acute subarachnoid hemorrhage. An aneurysm of < 2 mm was identified in all patients as the cause of bleeding. The aneurysms were located at the C2 segment of the internal carotid in 2 patients and on the basilar bifurcation in the other. All patients had failed early endovascular treatment attempts. Flow diversion with the SILK flow diverter was offered as an alternative in each patient. RESULTS: SILK deployment successfully eliminated the aneurysms in all 3 instances. One of the aneurysms was excluded from contrast material visualization immediately after stent deployment. Transient thrombotic complication was observed in the case of the basilar artery aneurysm. It resolved with the administration of intraarterial tirofiban. There was no treatment-related morbidity, and none of the aneurysms reruptured after SILK implantation during a clinical follow-up of at least 4 months (range, 4-10 months). Imaging follow-up showed complete vessel remodeling in all cases. CONCLUSION: Flow diversion treatment prevented rebleeding during the follow-up period. Reverse remodeling of the concerned vascular segment with delayed disappearance of the aneurysm was observed in each case.

High-profile flow diverter (silk) implantation in the basilar artery: efficacy in the treatment of aneurysms and the role of the perforators.

BACKGROUND AND PURPOSE: The introduction of flow diverters (FDs) has expanded the possibilities for reconstructive treatment of difficult intracranial aneurysms. Concern remains as to the long-term patency of the perforating arteries and side branches covered during stent placement. Our purpose was to evaluate the performance of and early effect on covered branches after implantation of the Silk FD in the treatment of basilar artery aneurysms. METHODS: Twelve patients with an aneurysm of the basilar artery that was treated by implantation of the Silk FD were included in our retrospective study. Both unruptured and previously ruptured, formerly untreated, and recurrent aneurysms were treated. During follow-up, patients were monitored for clinical evolution, patency of the covered vessels, and aneurysmal obliteration. RESULTS: Of the 2 ruptured aneurysms, 1 was initially treated by FD implantation. The FD covered the basilar bifurcation and the origin of a P1 segment of the posterior cerebral artery in 9 cases, the origin of the superior cerebellar artery in 9, and of the anterior inferior cerebellar artery in 3. There was 1 acute basilar artery occlusion a few hours after FD implantation. During a mean follow-up of 16 weeks, 3 patients experienced a symptomatic neurologic event. CONCLUSIONS: Implantation of the Silk FD in the basilar artery was feasible and well tolerated in most cases to date. However, late ischemic events affecting perforating arteries may occur after FD implantation, suggesting that the indication should be restricted to otherwise untreatable aneurysms in this location.

New ischaemic brain lesions on MRI after stenting or endarterectomy for symptomatic carotid stenosis: a substudy of the International Carotid Stenting Study (ICSS).

BACKGROUND: The International Carotid Stenting Study (ICSS) of stenting and endarterectomy for symptomatic carotid stenosis found a higher incidence of stroke within 30 days of stenting compared with endarterectomy. We aimed to compare the rate of ischaemic brain injury detectable on MRI between the two groups. METHODS: Patients with recently symptomatic carotid artery stenosis enrolled in ICSS were randomly assigned in a 1:1 ratio to receive carotid artery stenting or endarterectomy. Of 50 centres in ICSS, seven took part in the MRI substudy. The protocol specified that MRI was done 1-7 days before treatment, 1-3 days after treatment (post-treatment scan), and 27-33 days after treatment. Scans were analysed by two or three investigators who were masked to treatment. The primary endpoint was the presence of at least one new ischaemic brain lesion on diffusion-weighted imaging (DWI) on the post-treatment scan. Analysis was per protocol. This is a substudy of a registered trial, ISRCTN 25337470. FINDINGS: 231 patients (124 in the stenting group and 107 in the endarterectomy group) had MRI before and after treatment. 62 (50%) of 124 patients in the stenting group and 18 (17%) of 107 patients in the endarterectomy group had at least one new DWI lesion detected on post-treatment scans done a median of 1 day after treatment (adjusted odds ratio [OR] 5.21, 95% CI 2.78-9.79; p<0.0001). At 1 month, there were changes on fluid-attenuated inversion recovery sequences in 28 (33%) of 86 patients in the stenting group and six (8%) of 75 in the endarterectomy group (adjusted OR 5.93, 95% CI 2.25-15.62; p=0.0003). In patients treated at a centre with a policy of using cerebral protection devices, 37 (73%) of 51 in the stenting group and eight (17%) of 46 in the endarterectomy group had at least one new DWI lesion on post-treatment scans (adjusted OR 12.20, 95% CI 4.53-32.84), whereas in those treated at a centre with a policy of unprotected stenting, 25 (34%) of 73 patients in the stenting group and ten (16%) of 61 in the endarterectomy group had new lesions on DWI (adjusted OR 2.70, 1.16-6.24; interaction p=0.019). INTERPRETATION: About three times more patients in the stenting group than in the endarterectomy group had new ischaemic lesions on DWI on post-treatment scans. The difference in clinical stroke risk in ICSS is therefore unlikely to have been caused by ascertainment bias. Protection devices did not seem to be effective in preventing cerebral ischaemia during stenting. DWI might serve as a surrogate outcome measure in future trials of carotid interventions. FUNDING: UK Medical Research Council, the Stroke Association, Sanofi-Synthélabo, European Union, Netherlands Heart Foundation, and Mach-Gaensslen Foundation.

Time-resolved three-dimensional (3D) phase-contrast (PC) balanced steady-state free precession (bSSFP).

In this study the feasibility of a time-resolved, three-dimensional (3D), three-directional flow-sensitive balanced steady-state free precession (bSSFP) sequence is demonstrated. Due to its high signal-to-noise ratio (SNR) in blood and cerebrospinal fluid (CSF) this type of sequence is particularly effective for acquisition of blood and CSF flow velocities. Flow sensitivity was achieved with the phase-contrast (PC) technique, implementing a custom algorithm for calculation of optimal gradient parameters. Techniques to avoid the most important sources of bSSFP-related artifacts (including distortion due to eddy currents and signal voids due to flow-related steady-state disruption) are also presented. The technique was validated by means of a custom flow phantom, and in vivo experiments on blood and CSF were performed to demonstrate the suitability of this sequence for human studies. Accurate depiction of blood flow in the cerebral veins and of CSF flow in the cervical portion of the neck was obtained. Possible applications of this technique might include the study of CSF flow patterns, direct in vivo study of pathologies such as hydrocephalus and Chiari malformation, and validation for the existing CSF circulation model.

Thrombolysis in stroke mimics: frequency, clinical characteristics, and outcome.

BACKGROUND AND PURPOSE: Intravenous thrombolysis for acute ischemic stroke is usually based on clinical assessment, blood test results, and CT findings. Intravenous thrombolysis of stroke mimics may occur but has not been studied in detail. METHODS: We determined frequency, clinical characteristics, and outcome of mimic patients versus patients with stroke treated with intravenous thrombolysis using data of a prospective, single-center thrombolysis data bank. RESULTS: Among 250 patients, 243 (97.2%) had strokes and 7 (2.8%) were mimics. Seizure was the most frequent diagnosis among mimics. There was a trend toward lower National Institutes of Health Stroke Scale scores in mimics (9.9+/-4.2) compared with strokes (13.7+/-5.4; P=0.06). Global aphasia without hemiparesis was the presenting symptom in 3 (42.9%) mimics versus 8 (3.3%) strokes (P=0.002). Orolingual angioedema, symptomatic intracranial hemorrhage, and asymptomatic intracranial hemorrhage occurred in 3 (1.2%), 13 (5.3%), and 30 (12.3%) patients with stroke, but were absent in mimics. After 3 months, 6 (85.7%) mimics and 86 (35.4%) strokes had a modified Rankin Scale score of 0 to 1 (P=0.01). CONCLUSIONS: Only few patients receiving intravenous thrombolysis did eventually have a final diagnosis other than stroke, ie, mostly seizures. Their outcome was favorable. Although clinical features differed between the stroke and the mimic groups, the differences were not distinctive enough to allow assigning individual patients to either of the groups. Multimodal neuroimaging or electroencephalographic recordings may be helpful for this assignment. However, their potential benefit has to be weighed against the potential harm of delayed thrombolysis.

Reduced cerebrovascular reserve at CO2 BOLD MR imaging is associated with increased risk of periinterventional ischemic lesions during carotid endarterectomy or stent placement: preliminary results.

PURPOSE: To determine whether any initial reductions in cardiovascular reserve (CVR) normalize after carotid revascularization and-because reduced CVR represents a risk factor for ischemic events-whether patients who develop periinterventional infarction have more severely reduced pretreatment CVR than those who do not. MATERIALS AND METHODS: Ethics committee approval and informed consent were obtained. Twenty-four consecutive patients with symptomatic high-grade internal carotid artery stenosis (seven women; mean age, 73.1 years +/- 9.4 [standard deviation]) were recruited from a prospective, randomized trial that compared carotid artery stent placement with endarterectomy. Magnetic resonance (MR) imaging, including CO(2) blood oxygen level-dependent (BOLD) MR, was performed 1-3 days before, 1-3 days after, and 1 month after carotid revascularization (carotid artery stent placement, n = 13; carotid endarterectomy, n = 11). RESULTS: Mean CVR in the ipsilateral middle cerebral artery (MCA) territory was reduced prior to treatment (mean DeltaT2* in ipsilateral territory, 1.92% +/- 1.18; mean DeltaT2* in contralateral territory, 2.28% +/- 1.15 [P < .05]) and normalized after treatment (mean DeltaT2* 1-3 days after treatment in ipsilateral territory, 2.66% +/- 1.01; that in contralateral territory, 2.48% +/- 1.27 [P > .05]; mean DeltaT2* 1 month after treatment in ipsilateral territory, 2.27% +/- 1.05; that in contralateral territory, 2.14% +/- 0.96 [P > .05]). Those patients who developed new periinterventional infarcts (n = 7 with punctate foci of restricted diffusion) had greater reduction of CVR in the ipsilateral MCA territory prior to treatment (relative reduction, 32.5% +/- 46.0; P < .05) than those who did not develop infarction (n = 17; relative reduction, 9.2% +/- 55.9). CONCLUSION: CO(2) BOLD MR imaging could be used successfully to monitor the hemodynamic effects of carotid revascularization; initial reductions in CVR normalized after carotid revascularization. Severely reduced pretreatment CVR was associated with increased occurrence of new periinterventional therapy infarction.

Double-reference cross-correlation algorithm for separation of the arteries and veins from 3D MRA time series.

PURPOSE: To present a novel postprocessing technique for artery/vein separation and background suppression from contrast-enhanced time-resolved magnetic resonance angiography datasets in order to improve the diagnosis of vessel pathologies and arteriovenous fistulas. MATERIALS AND METHODS: Ten normal, two pathologic datasets of the brain, and one hand angiography dataset were postprocessed. Cross-correlation maps between the signal time course of every voxel in the dataset and selected arterial and venous references regions of interest (ROIs) were obtained; these maps were subsequently nonlinearly transformed to obtain two indices representing the likelihood of a voxel belonging to a vessel category. Red-green-blue (RGB) color encoding was utilized to depict synthetic arteriogram and venogram images in a single diagnostically meaningful image. RESULTS: The technique enabled correct visual separation of vessels on various datasets, as evaluated by two expert neuroradiologists, and also highlighted characteristics of flow in arteriovenous fistulas. A quantitative comparison with existing techniques showed better separation performance on 3 out of 10 normal datasets and higher stability to acquisition characteristics and contrast agent bolus dispersion. CONCLUSION: This method can be helpful in the diagnosis of vascular diseases in subjects where bolus dispersion makes it difficult to discriminate between arteries and veins with standard methods (subtraction or correlation analysis).

In vivo visualization and analysis of 3-D hemodynamics in cerebral aneurysms with flow-sensitized 4-D MR imaging at 3 T.

INTRODUCTION: Blood-flow patterns and wall shear stress (WSS) are considered to play a major role in the development and rupture of cerebral aneurysms. These hemodynamic aspects have been extensively studied in vitro using geometric realistic aneurysm models. The purpose of this study was to evaluate the feasibility of in vivo flow-sensitized 4-D MR imaging for analysis of intraaneurysmal hemodynamics. METHODS: Five cerebral aneurysms were examined using ECG-gated, flow-sensitized 4-D MR imaging at 3 T in three patients. Postprocessing included quantification of flow velocities, visualization of time-resolved 2-D vector graphs and 3-D particle traces, vortical flow analysis, and estimation of WSS. Flow patterns were analyzed in relation to aneurysm geometry and aspect ratio. RESULTS: Magnitude, spatial and temporal evolution of vortical flow differed markedly among the aneurysms. Particularly unstable vortical flow was demonstrated in a wide-necked parophthalmic ICA aneurysm (high aspect ratio). Relatively stable vortical flow was observed in aneurysms with a lower aspect ratio. Except for a wide-necked cavernous ICA aneurysm (low aspect ratio), WSS was reduced in all aneurysms and showed a high spatial variation. CONCLUSION: In vivo flow-sensitized 4-D MR imaging can be applied to analyze complex patterns of intraaneurysmal flow. Flow patterns, distribution of flow velocities, and WSS seem to be determined by the vascular geometry of the aneurysm. Temporal and spatial averaging effects are drawbacks of the MR-based analysis of flow patterns as well as the estimation of WSS, particularly in small aneurysms. Further studies are needed to establish a direct link between definitive flow patterns and different aneurysm geometries.

Display of dural sinuses with time-resolved, contrast-enhanced three-dimensional MR venography.

BACKGROUND: Time-resolved (TR) contrast-enhanced 3D MR angiography has recently received considerable attention for the workup of cerebrovascular diseases, foremost dural arteriovenous fistula and arteriovenous malformation, and potentially for the evaluation of dural sinus thrombosis. Thereby, the dynamic visualization of cerebral vessels is enabled similar to the principle of digital subtraction angiography. Yet, its voxel size is relatively large due to an inherent trade-off between the desired spatial and temporal resolutions. The goal of this study was to evaluate whether the limited spatial resolution of TR MR venography (MRV) is sufficient to visualize dural venous sinuses. METHODS: The prospective study included 20 patients without compromise of cerebral venous outflow. Two neuroradiologists independently graded the quality of visualization of 11 predefined dural venous sinuses on images of fast TR contrast-enhanced MRV (1.5 s/dataset; voxel size, 2 x 2 x 2.2 mm; acquisition time, 37.5 s) in comparison to time-of-flight (TOF) MRV (voxel size, 0.8 x 0.8 x 4 mm; acquisition time, 3 min 51 s) and steady-state contrast-enhanced 3D (VIBE) MRV (voxel size, 1.1 x 0.9 x 1.5 mm; acquisition time, 2 min 46 s). RESULTS: The torcular Herophili (p < 0.001), left (p < 0.001) and right (p < 0.01) transverse sinus, and right jugular bulb (p < 0.05) were visualized better at TR MRV than at TOF MRV. For visualization of the small inferior sagittal sinus, TR MRV was inferior to VIBE (p < 0.001) and TOF (p < 0.05) sequences. The visibility of all other dural sinuses was equal. CONCLUSION: Despite the inferior spatial resolution, TR MRV depicted some large dural sinuses more clearly than TOF MRV. To overcome the visualization of smaller venous structures, TR MRV can be applied complementarily with high-resolution steady-state contrast-enhanced MRV.

Functional MRI, DTI and neurophysiology in horizontal gaze palsy with progressive scoliosis.

INTRODUCTION: Horizontal gaze palsy with progressive scoliosis (HGPPS) is an autosomal recessive disease due to a mutation in the ROBO3 gene. This rare disease is of particular interest because the absence, or at least reduction, of crossing of the ascending lemniscal and descending corticospinal tracts in the medulla predicts abnormal ipsilateral sensory and motor systems. METHODS: We evaluated the use of functional magnetic resonance imaging (fMRI) for the first time in this disease and compared it to diffusion tensor imaging (DTI) tractography and neurophysiological findings in the same patient with genetically confirmed ROBO3 mutation. RESULTS: As expected, motor fMRI, somatosensory evoked potentials (SSEP) and motor evoked potentials (MEP) were dominantly ipsilateral to the stimulation side. DTI tractography revealed ipsilateral ascending and descending connectivity in the brainstem yet normal interhemispheric connections in the corpus callosum. Auditory fMRI revealed bilateral auditory activation to monaural left-sided auditory stimulation. No significant cortical activation was observed after monaural right-sided stimulation, a hearing defect having been excluded. Prosaccades fMRI showed no activations in the eye-movement network. CONCLUSION: Motor fMRI confirmed the established findings of DTI and neurophysiology in the same patient. In suspected HGPPS, any technique appears appropriate for further investigation. Auditory fMRI suggests that a monaural auditory system with bilateral auditory activations might be a physiological advantage as compared to a binaural yet only unilateral auditory system, in analogy to anisometropic amblyopia. Moving-head fMRI studies in the future might show whether the compensatory head movements instead of normal eye movements activate the eye-movement network.

Diffusion-weighted imaging in stroke attributable to internal carotid artery dissection: the significance of vessel patency.

BACKGROUND AND PURPOSE: In stroke attributable to spontaneous dissection of the internal carotid artery (sICAD), arterial patency may influence the pattern and extent of cerebral ischemia. METHODS: In 40 consecutive patients with stroke caused by sICAD, we compared the number, size and pattern of cerebral diffusion-weighted imaging lesions between patients with stenotic sICAD (n=15) and occlusive sICAD (n=25). RESULTS: Patients with stenotic sICAD had more ischemic lesions (median 5, interquartile range 1 to 10) than patients with occlusive sICAD (2, 1 to 3; P=0.014). Lesion diameters were larger in occlusive sICAD (62, 50 to 99 mm) than in stenotic sICAD (25, 10 to 50 mm; P=0.007). Border-zone infarction occurred only in stenotic sICAD (7/15, 47%). Most patients with occlusive sICAD had territorial infarcts (22/25, 88%). CONCLUSIONS: In stroke attributable to sICAD, diffusion-weighted imaging characteristics may be influenced by the patency of the carotid artery. Differences in the pathogenesis of cerebral ischemia might exist between patients with stenotic and those with occlusive sICAD.

The clinical significance of diffusion-weighted MR imaging in stroke and TIA patients.

BACKGROUND AND PURPOSE: Diffusion-weighted magnetic resonance imaging (DWI) is an advanced imaging technique that allows non-invasive evaluation of water diffusibility in brain tissue. The following report focuses on the clinical significance of DWI in stroke and TIA patients SUMMARY OF REVIEW: (1) TIA patients demonstrate DWI lesions at a rate of 1 in 6 to 2 in 3. Symptom duration, speech or motor symptoms and aetiology seem to correlate with the rate of DWI positivity. (2) In stroke patients, the DWI detection rate of ischaemic lesions is >95%. Small lesion size and location in the brainstem increase the risk of false-negative DW-images. A negative DW-image in a patient with stroke-like symptoms should stimulate the search for an alternative diagnosis. However, one half of such patients can be expected to have ischaemic stroke as the best final diagnosis. (3) Infarct age determination based on DWI characteristics is not possible in the first few hours. However, the combined interpretation of DWI-images and apparent diffusion coefficient (ADC) maps enables the distinction of infarcts ?5 day old from infarcts >10 days old. On average in DW-images alone, the hyperintense signal disappears after two months. Normalisation can occur as early as one month and as late as four and a half months. (4) DWI lesion size is a prognostic marker of stroke outcome. However, in a mixed stroke population, outcome prediction by DWI cannot replace clinical outcome scores. (5) The mismatch concept hypothesises that DWI lesions reflect irreversibly infarcted tissue that is surrounded by an area of reduced perfusion. The larger the perfusion-diffusion mismatch the more tissue is potentially salvageable, e.g., by early reperfusion. Although this concept is appealing, more recent data have shown that DWI lesions are not necessarily irreversibly damaged tissue and that perfusion abnormalities tend to overestimate the ischaemic penumbra. More recently, the mismatch between clinical stroke severity as measured with the NIH-stroke Scale Score (NIHSSS) and the volume of DWI lesions has been introduced. (6) In posterior circulation stroke, DWI lesion detection rate is significantly lower than in anterior circulation stroke. (7) DWI features provide important information about stroke aetiology. Multiple DWI lesions in more than one circulation suggest cardioembolism. However, this assignment should be restricted to DWI lesions showing the same appearance on ADC-maps. In patients with lacunar syndromes, every fourth to sixth patient can be expected to have >1 DWI lesion, indicating an embolic mechanism. Thus, DWI findings may be clinically useful to tailor the aetiological work-up, which may result in early implementation of specific treatment for secondary stroke prevention. (8) DWI may detect clinically silent ischaemic lesions after carotid interventions. A systematic review reported the rate of new DWI lesions as being significantly higher in carotid stenting patients (37%) compared to carotid endarterectomy patients (10%). As caveats, all studies included were non randomized trials. In addition, the clinical significance of these lesions is unclear. Studies, comparing the risk of silent ischaemia in carotid stenting versus endarterectomy patients and evaluating the value of DWI as surrogate marker in a randomised, prospective setting are currently under way. CONCLUSION: DWI provides clinically useful information and has the means to improve the quality of diagnosis, treatment, and outcome prediction in stroke and TIA patients.

Mapping continuous neuronal activation without an ON-OFF paradigm: initial results of BOLD ceiling fMRI.

Standard functional magnetic resonance imaging (fMRI) requires alternations between activation (ON) and baseline (OFF) periods to map the haemodynamic response to neuronal activation. Consequently, standard fMRI cannot map continuous activations in conditions like tinnitus without an ON-OFF paradigm. We present a novel approach to fMRI that allows mapping of continuous neuronal activation. Compared with standard fMRI, we introduced the application of CO(2) as potent vasodilator. CO(2) induces a 'global' blood oxygenation level-dependent (BOLD) response. The neurovascular coupling in conjunction with the limited cerebral vasodilation implies a limitation or ceiling of the BOLD response. We hypothesize that active areas exhibit a reduced CO(2)-induced DeltaBOLD due to pre-existing 'local' task-induced BOLD response. This putative reduction in DeltaBOLD might be exploited for mapping of continuous neuronal activation. BOLD ceiling fMRI was tested in the auditory system. Six healthy subjects performed three runs: only continuous monaural auditory; only 10% CO(2); simultaneous auditory and CO(2) stimulation. First, we demonstrated the ceiling of DeltaBOLD during continuous auditory activation. According to the known predominantly contralateral auditory processing, monaural auditory stimulation reduced predominantly contralateral (0.41 +/- 0.13%; P < 0.00001) and significantly less (P < 0.0001) ipsilateral DeltaBOLD (0.33 +/- 0.17%; P < 0.00001). The non-auditory area was not affected. Second, this BOLD ceiling was exploited to generate an initial activation map of continuous auditory activation (ON period). In contrast to standard fMRI, an OFF period without neuronal activation was not required. BOLD ceiling fMRI is proposed as a complement to standard fMRI for those conditions where ON-OFF paradigms are impossible.