A Diagnostic Biomarker for Cervical Myelopathy Based on Dynamic Magnetic Resonance Imaging.

STUDY DESIGN: Multicenter prospective observational study. OBJECTIVE: Diffusion tensor imaging in flexion extension improves the diagnosis of degenerative cervical myelopathy (DCM). We aimed to provide an imaging biomarker for the detection of DCM. SUMMARY OF BACKGROUND DATA: DCM is the most common form of spinal cord dysfunction in adults; however, imaging surveillance for myelopathy remains poorly characterized. PATIENTS AND METHODS: Symptomatic DCM patients were examined in maximum neck flexion-extension and neutral positions in a 3T-magnetic resonance imaging scanner and allocated to 2 groups: (1) Patients with visible intramedullary hyperintensity (IHIS) on T2-weighted imaging (IHIS+, n = 10); and (2) Patients without IHIS (IHIS-, n = 11). Range of motion, space available for the spinal cord, apparent diffusion coefficient (ADC), axial diffusivity (AD), radial diffusivity, and fractional anisotropy were measured and compared between the neck positions and between the groups as well as between control (C2/3) and pathologic segments. RESULTS: Significant differences between the control level (C2/3) and pathologic segments were appreciated for the IHIS+ group at neutral neck position in AD; at flexion in ADC and AD; and at neck extension in ADC, AD, and fractional anisotropy values. For the IHIS- group, significant differences between the control level (C2/3) and pathologic segments were found only for ADC values in neck extension. When comparing diffusion parameters between groups, radial diffusivity was significantly different in all 3 neck positions. CONCLUSION: Significant increases in ADC values between the control and pathologic segments were found for both groups in neck extension only. This may serve as a diagnostic tool to identify early changes in the spinal cord related to myelopathy to indicate potentially reversible spinal cord injury and support the indication for surgery in select circumstances.

Case report: Experience with the Cube Navigation System in complex access routes during CT-guided lumbosacral infiltration therapy.

Purpose: Computed tomography (CT)-guided infiltrations are a mainstay in the treatment of lower back pain. Needle placement is usually performed using the free-hand method, where the translation from the planned needle angle to the actual needle insertion angle is estimated. However, the free-hand method is especially challenging in cases where a double-oblique access route (out-of-plane) rather than an in-plane route is necessary. In this case series, we report our experience with the patient-mounted Cube Navigation System to guide needle placement for complex access routes in lumbar pain therapy. Research design and methods: We retrospectively analyzed the cases of five patients in whom a double-oblique access route was necessary for CT-guided lumbar infiltration pain treatment. Each of those procedures was done using the Cube Navigation System to provide navigational guidance. The mean patient age was 69 ± 13 years (range 58-82 years; all females). Technical success, procedure time, and number of control scans were determined retrospectively. Results: Technical success (i.e., positioning and accuracy) was obtained in all cases. Mean procedure time was 15 ± 7 min (10-22 min); on average, 2 ± 1 CT control scans were performed. There were no complications or material failures reported in the present study. Conclusion: Double-oblique punctures with the Cube Navigation System in this initial case series of complex access routes at the lumbar spine were accurate and the procedure was time efficient. In the authors' view, the Cube Navigation System has the potential to improve needle guidance for complex access routes, especially considering the ease of use of the device.

Striatal Iron Deposition in Recreational MDMA (Ecstasy) Users.

BACKGROUND: The common club drug MDMA (also known as ecstasy) enhances mood, sensory perception, energy, sociability, and euphoria. While MDMA has been shown to produce neurotoxicity in animal models, research on its potential neurotoxic effects in humans is inconclusive and has focused primarily on the serotonin system. METHODS: We investigated 34 regular, largely pure MDMA users for signs of premature neurodegenerative processes in the form of increased iron load in comparison to a group of 36 age-, sex-, and education-matched MDMA-naïve control subjects. We used quantitative susceptibility mapping, a novel tool able to detect even small tissue (nonheme) iron accumulations. Cortical and relevant subcortical gray matter structures were grouped into 8 regions of interest and analyzed. RESULTS: Significantly increased iron deposition in the striatum was evident in the MDMA user group. The effect survived correction for multiple comparisons and remained after controlling for relevant confounding factors, including age, smoking, and stimulant co-use. Although no significant linear relationship between measurements of the amounts of MDMA intake (hair analysis and self-reports) and quantitative susceptibility mapping values was observed, increased striatal iron deposition might nevertheless point to MDMA-induced neurotoxic processes. Additional factors (hyperthermia and simultaneous co-use of other substances) that possibly amplify neurotoxic effects of MDMA during the state of acute intoxication are discussed. CONCLUSIONS: The demonstrated increased striatal iron accumulation may indicate that regular MDMA users have an increased risk potential for neurodegenerative diseases with progressing age.

Long-term apparent diffusion coefficient value changes in patients undergoing radiosurgical treatment of meningiomas.

PURPOSE: A noninvasive method to predict the progress or treatment response of meningiomas is desirable to improve the tumor management. Studies showed that apparent diffusion coefficient (ADC) pretreatment values can predict treatment response in brain tumors. The aim of this study was to analyze changes of intratumoral ADC values in patients with meningiomas undergoing conservative or radiosurgery. METHOD: MR images of 51 patients with diagnose of meningiomas were retrospectively reviewed. Twenty-five patients undergoing conservative or radiosurgery treatment, respectively, were included in the study. The follow-up data ranged between 1 and 10 years. Based on ROI analysis, the mean ADC values, ADC10%min, and ADC90%max were evaluated at different time points during follow-up. RESULTS: Baseline ADC values in between both groups were similar. The ADCmean values, ADC10%min, and ADC90%max within the different groups did not show any significant changes during the follow-up times in the untreated (ADCmean over 10 years period: 0.87 ± 0.05 × 10-3 mm2/s) and radiosurgically treated (ADCmean over 4 years period: 1.02 ± 0.12 × 10-3 mm2/s) group. However, statistically significant difference was observed when comparing the ADCmean and ADC90%max values of untreated with radiosurgically treated (p < 0.0001) meningiomas. Also, ADC10%min revealed statistically significant difference between the untreated and the radiosurgery group (p < 0.05). CONCLUSIONS: ADC values in conservatively managed meningiomas remain stable during the follow-up. However, meningiomas undergoing radiosurgery reveal significant change of the mean ADC values over time, suggesting that ADC may reflect a change in the biological behavior of the tumor. These observations might suggest the value of ADC changes as an indicator of treatment response.

Angioplasty Using Drug-Coated Balloons in Ostial Vertebral Artery Stenosis.

BACKGROUND: Ostial vertebral artery stenosis (OVAS) is a relevant cause of acute ischemic posterior circulation stroke. Percutaneous trans-luminal angioplasty (PTA) might offer a promising treatment modality, but restenosis rate is high. So far, little is known about recanalization using drug-coated balloons (DCB) in OVAS. We aimed to show feasibility and safety of DCB-PTA in OVAS. METHODS: Retrospective, monocenter case series of 12 patients with ostial vertebral artery stenosis (≥50%) treated with PTA using a drug-coated balloon. RESULTS: Median age was 69.5 years (IQR 57-78.5) with a female rate of 41%. Patients were treated either with a SeQuent Please NEO or Neuro Elutax SV DEB. Median preinterventional stenosis degree was 75% (IQR 70-85) with a median lesion length of 4.5 mm (IQR 4-7.5). Median postinterventional stenosis degree was 40% (IQR 27-50). All treated vessels remained patent. No major complications such as dissection, vessel perforation, hemorrhage, or ischemic events occurred. Moreover, we did not detect any restenosis during a median follow-up period of 6.1 months. The clinical outcome was excellent with median mRS scale of 0 (IQR 0-1). CONCLUSIONS: PTA using drug-coated balloons is feasible and safe in patients with ostial vertebral artery stenosis.

Percutaneous transluminal angioplasty using the novel drug-coated balloon catheter SeQuent Please NEO for the treatment of symptomatic intracranial severe stenosis: feasibility and safety study.

OBJECTIVES: Intracranial arteriosclerotic disease is a relevant cause of ischemic stroke worldwide with a high recurrence rate despite best medical treatment. Following the SAMMPRIS trial, endovascular treatment has remained a second-line therapy. Meanwhile, there has been significant advances in device technology. SeQuent Please NEO is a novel polymer-free, drug-coated (paclitaxel/iopromide) balloon (DCB) primarily designed for cardiology. Because of its high flexibility and pushability, it may also be suitable for intracranial use. The aim of this study was to assess the feasibility and safety of SeQuent Please NEO DCB in symptomatic intracranial severe stenosis. METHODS: A single-center retrospective cohort study of patients with symptomatic intracranial severe stenosis treated with SeQuent Please NEO DCB was performed at a tertiary stroke center. RESULTS: Ten patients (all men, median age 73 years (IQR 69-77)) were included. Median pre-treatment stenosis grade was 78% (IQR 75-80%) with four internal carotid artery, two mid-basilar artery, and four vertebral artery lesions. Median post-treatment stenosis grade was 50% (IQR 45-53%). Successful angioplasty was achieved in all cases without technical failure. There were no cases of peri-procedural reocclusion and no deaths at median follow-up of 3 months (IQR 2-3). CONCLUSION: In this pilot study, SeQuent Please NEO DCB was feasible and safe in the treatment of symptomatic intracranial severe stenosis. It might represent a promising alternative to medical treatment in selected cases.

Longitudinal Imaging of Tumor Volume, Diffusivity, and Perfusion After Preoperative Endovascular Embolization in Supratentorial Hemispheric Meningiomas.

OBJECTIVE: To describe longitudinal image changes in supratentorial hemispheric meningiomas based on magnetic resonance imaging after preoperative embolization using calibrated microspheres. METHODS: A total of 14 patients with symptomatic supratentorial meningiomas were included in a prospective, mono-centric, mono-arm study. Magnetic resonance imaging changes on diffusion-weighted imaging, dynamic contrast susceptibility-perfusion-weighted imaging, susceptibility-weighted imaging, and magnetization-prepared rapid acquisition gradient-echo sequence T1-weighted postcontrast sequences 6 and 48 hours after embolization were evaluated and correlated with angiographic and clinical data. RESULTS: The mean age of the patients was 63 ± 12.7 years with an equal female/male ratio. Twelve meningiomas were World Health Organization grade I and II tumors. After embolization, baseline apparent diffusion coefficient (901 ± 166 mm2/s) decreased significantly within 6 hours (696 ± 115 mm2/s, P = 0.0008) as well within 48 hours (752 ± 134 mm2/s; P = 0.0147). Baseline mean ratio of relative cerebral blood volume (rCBV)tumor/rCBVwhite matter (3.67 ± 1.83) and relative cerebral blood flow (rCBF)tumor/rCBFwhite matter (2.89 ± 1.57) significantly decreased after embolization within 6 hours (rCBVtumor/rCBVwhite matter of 1.45 ± 0.9; P = 0.0007, rCBF of 1.16 ± 0.68; P = 0.0029) and 48 hours (rCBV of 1.50 ± 1.07; P = 0.0009, rCBFtumor/rCBFwhite matter of 1.19 ± 0.8; P = 0.003). The viable enhanced baseline mean tumor volume (54.3 ± 34.9 mm3) was sustainably and significantly diminished within 6 hours (26.6 ± 20.8 mm3; P = 0.02) and 48 hours (29.7 ± 22.5 mm3; P = 0.035) after embolization. There was a good correlation between angiographic devascularization rate and the embolized tumor volume at 6 hours (r = 0.7; P = 0.03) and 48 hours (r = 0.78; P = 0.041). CONCLUSIONS: Preoperative meningioma embolization with calibrated microspheres is safe and effectively induces a significant and sustainable tissue transformation over 48 hours.

Embolus Retriever with Interlinked Cages versus other stent retrievers in acute ischemic stroke: an observational comparative study.

BACKGROUND AND PURPOSE: Given the promising performance of the new Embolus Retriever with Interlinked Cages (ERIC) in smaller case series, we sought to assess the efficacy and safety of mechanical thrombectomy (MT) with ERIC compared with other stent retrievers (SRs) in acute ischemic stroke due to large vessel occlusion (LVO). METHODS: We reviewed the databases of two comprehensive stroke centers in in Germany and Switzerland for MT due to LVO in the anterior circulation with either ERIC or another SR as a first device. Co-primary outcome was defined as successful recanalization (Thrombolysis in Cerebral Infarction 2b/3) after the first device and favorable outcome (modified Rankin Scale score 0-2) at 90 days' follow-up. Multiple logistic regression analysis was applied to adjust for potential confounders. RESULTS: 183 consecutive patients with stroke were treated with either ERIC (49%) or a SR (51%) as the first device and successful recanalization was seen in 82% and 57%, respectively (P<0.001). Adding SR to futile ERIC recanalization or vice versa increased final recanalization rates (ERIC: 87%, SR: 79%). The use of ERIC as a first device resulted in favorable clinical outcome in 50% compared with 35% when a SR was used (P=0.038), an effect driven by age, stroke severity, presence of carotid-T-occlusion, and general anesthesia and not by the device deployed. CONCLUSION: The use of ERIC as a first device appeared to be associated with higher rates of successful recanalization and resulted in better functional outcome. However, favorable outcome was not attributable to ERIC. Most importantly, both device types complemented one another and improved final recanalization rates when used successively.

Neuro Elutax SV drug-eluting balloon versus Wingspan stent system in symptomatic intracranial high-grade stenosis: a single-center experience.

BACKGROUND: Intracranial atherosclerotic disease is a well-known cause of ischemic stroke. Following the SAMMPRIS trial, medical treatment is favored over stenting. Drug-eluting balloons (DEB) are widely used in coronary angioplasty, showing better results than bare-surface balloons. There is little evidence of DEB employment in intracranial stenosis, especially of paclitaxel-eluted balloons (pDEB). The Neuro Elutax SV (Aachen Resonance) is the first CE certificated pDEB for intracranial use. OBJECTIVE: To compare pDEB Neuro Elutax SV (ElutaxDEB) with the Wingspan/Gateway stent system (WingspanStent). MATERIALS AND METHODS: A single-center, open-label, retrospective cohort study of 19 patients with symptomatic atherosclerotic intracranial high-grade stenosis treated with either ElutaxDEB or WingspanStent from a tertiary stroke center in Switzerland. RESULTS: Eight patients (42%) received ElutaxDEB. Median clinical follow-up was 10 months for the WingspanStent and 9.5 months for ElutaxDEB (P=0.36). No differences were found in the clinical baseline characteristics, with a median stenosis grade of 80% for the WingspanStent and 81% for the ElutaxDEB (P=0.87). The compound endpoint 'ischemic re-event and/or restenosis' was significantly lower for ElutaxDEB (13% vs 64%; P=0.03, OR 0.08 (95% CI 0.007 to 0.93; P=0.043) than for the WingspanStent. CONCLUSIONS: The ElutaxDEB may be a promising alternative treatment for patients with symptomatic high-grade intracranial stenosis showing a significantly lower rate of ischemic re-events or restenosis in comparison with the WingspanStent-treated patients with a similar safety profile. Further studies will be needed to definitively elucidate the role of pDEB in the management of symptomatic intracranial high-grade stenosis.

Magnetic Resonance Imaging Signal Characteristics of Medishield: Early Postoperative Profile in a Rabbit Interlaminotomy Model.

OBJECTIVE: Application of Medishield to the nerve root is common during spinal surgery to create a mechanical barrier from pain mediators and reduce scar formation. However, Medishield's signal characteristics on magnetic resonance imaging (MRI) have not yet been examined. METHODS: Microsurgical interlaminotomy was performed on 2 lower lumbar segments in 17 adult New Zealand white rabbits. After dural exposure, applications of 1 mL (autologous blood clot or Medishield) were randomized for each level. On postoperative days 1 through 3, various MRI sequences in 1.5T were performed including T1-weighted, T2-w, T1-gadolinium-weighted, susceptibility-weighted and turbo inversion recovery magnitude (TIRM) sequence. Signaling characteristics were analyzed by 3 blinded observers. Inter-rater agreement was calculated using Fleiss's kappa coefficient (κ). Positive and negative likelihood ratios in detecting Medishield by MRI were determined. RESULTS: Of 24 MRIs performed, TIRM sequence identified Medishield with the highest likelihood ratio. Medishield's positive likelihood ratio was highest (5.8) on postoperative day 1 with interobserver agreement of 93% (κ = 0.75); these rates declined to 2.5 and 1.4 on postoperative days 2 and 3 with interobserver agreements of 71% (κ = 0.43) and 83% (κ = 0.67), respectively. Medishield adherence was confirmed in each rabbit by histologic examinations. CONCLUSION: Understanding that radiologic detection of Medishield diminished over time as its signal characteristics became less distinguishable from a blood clot is essential in clinical practice. Medishield was detected on postoperative day 1 but not 2 days later after hemodynamic changes had occurred. These results may provide a guide for postoperative findings, such as differential diagnosis of hematoma.

Diffusion tensor imaging for target volume definition in glioblastoma multiforme.

INTRODUCTION: Diffusion tensor imaging (DTI) is an MR-based technique that may better detect the peritumoural region than MRI. Our aim was to explore the feasibility of using DTI for target volume delineation in glioblastoma patients. MATERIALS AND METHODS: MR tensor tracts and maps of the isotropic (p) and anisotropic (q) components of water diffusion were coregistered with CT in 13 glioblastoma patients. An in-house image processing program was used to analyse water diffusion in each voxel of interest in the region of the tumour. Tumour infiltration was mapped according to validated criteria and contralateral normal brain was used as an internal control. A clinical target volume (CTV) was generated based on the T1-weighted image obtained using contrast agent (T1Gd), tractography and the infiltration map. This was compared to a conventional T2-weighted CTV (T2-w CTV). RESULTS: Definition of a diffusion-based CTV that included the adjacent white matter tracts proved highly feasible. A statistically significant difference was detected between the DTI-CTV and T2-w CTV volumes (p < 0.005, t = 3.480). As the DTI-CTVs were smaller than the T2-w CTVs (tumour plus peritumoural oedema), the pq maps were not simply detecting oedema. Compared to the clinical planning target volume (PTV), the DTI-PTV showed a trend towards volume reduction. These diffusion-based volumes were smaller than conventional volumes, yet still included sites of tumour recurrence. CONCLUSION: Extending the CTV along the abnormal tensor tracts in order to preserve coverage of the likely routes of dissemination, whilst sparing uninvolved brain, is a rational approach to individualising radiotherapy planning for glioblastoma patients.

Differentiation between calcification and hemorrhage in brain tumors using susceptibility-weighted imaging: a pilot study.

OBJECTIVE: Our aim was to develop a robust method to differentiate calcification from hemorrhage in gliomas. Histopathologic examination was performed to validate hemorrhage and calcification. CONCLUSION: Phase images from eleven patients with glioma yielded statistically significant phase-shift values for calcification and hemorrhage compared with normal brain, whereas CT showed substantial overlap of Hounsfield units. Phase image analysis correctly differentiated between intratumoral calcification and hemorrhage in 86% of cases.

Focal changes in diffusivity on apparent diffusion coefficient MR imaging and amino acid uptake on PET do not colocalize in nonenhancing low-grade gliomas.

UNLABELLED: Low-grade gliomas (LGGs) may harbor malignant foci, which are characterized by increased tumor cellularity and angiogenesis. We used diffusion-weighted MR imaging (apparent diffusion coefficient [ADC]) and PET with the amino acid O-(2-(18)F-fluorethyl)-L-tyrosine ((18)F-FET) to search for focal changes of diffusion (ADC) and amino acid uptake and to investigate whether focal changes in these parameters colocalize within LGGs. METHODS: We retrospectively selected 18 patients with nonenhancing LGG. All patients had undergone (18)F-FET PET and MR imaging for preoperative evaluation or for therapy monitoring in recurrent or progressive LGG. Region-of-interest analysis was performed to compare (18)F-FET uptake and ADC values in areas with focal intratumoral maximum metabolic activity and diffusion restriction and between tumor and normal brain. (18)F-FET uptake was normalized to the mean cerebellar uptake (ratio). ADC values were also compared with the (18)F-FET uptake on a voxel-by-voxel basis across the whole tumor. RESULTS: The mean focal maximum (mean ± SD, 1.69 ± 0.85) and global (18)F-FET uptake in tumors (1.14 ± 0.41) exceeded that of normal cortex (0.85 ± 0.09) and cerebrospinal fluid (0.82 ± 0.20). ADC values in the area with most restricted diffusion (1.07 ± 0.22 × 10(-3) mm(2)/s) and in the whole tumor (1.38 ± 0.27 × 10(-3) mm(2)/s) were in the range between normal cortex (0.73 ± 0.06 × 10(-3) mm(2)/s) and cerebrospinal fluid (2.84 ± 0.09 × 10(-3) mm(2)/s). (18)F-FET uptake did not correlate with corresponding (colocalizing) ADC values, either in the area with focal maximum metabolic activity or in the area with most restricted diffusion or in the whole tumor. CONCLUSION: There is no congruency between (18)F-FET uptake and diffusivity in nonenhancing LGG. Diffusion restriction in these tumors most likely represents changes in brain and tumor cell densities as well as alteration of water distribution and is probably not directly correlated with the density of tumor cells.

Cortical hemosiderin is associated with seizures in patients with newly diagnosed malignant brain tumors.

Hemorrhage is common in brain tumors. Due to characteristic magnetic field changes induced by hemosiderin it can be detected using susceptibility weighted MRI (SWI). Its relevance to clinical syndromes is unclear. Here we investigated the patterns of intra-tumoral SWI positivity (SWI(pos)) as a surrogate for hemosiderin with regard to the prevalence of epilepsy. We report on 105 patients with newly diagnosed supra-tentorial gliomas and brain metastasis. The following parameters were recorded from pre-operative MRI: (1) SWI(pos) defined as dot-like or fine linear signal changes; (2) allocation of SWI(pos) to tumor compartments (contrast enhancement, central hypointensity, non-enhancing area outside contrast-enhancement); (3) allocation of SWI(pos) to include the cortex, or SWI(pos) in subcortical tumor parts only; (4) tumor size on T2 weighted and gadolinium-enhanced T1 images. 80 tumors (76 %) showed SWI(pos) (4/14 diffuse astrocytoma WHO II, 5/9 anaplastic astrocytoma WHO III, 41/46 glioblastoma WHO IV, 30/36 metastasis). The presence of SWI(pos) depended on tumor size but not on patient's age, medication with antiplatelet drugs or anticoagulation. Seizures occurred in 60 % of patients. Cortical SWI(pos) significantly correlated with seizures in brain metastasis (p = 0.044), and as a trend in glioblastoma (p = 0.062). Cortical SWI(pos) may confer a risk for seizures in patients with newly diagnosed brain metastasis and glioblastoma. Whether development of cortical SWI(pos) induced by treatment or by the natural course of tumors also leads to the new onset of seizures has to be addressed in longitudinal studies in larger patient cohorts.