Bioresorbable zinc stent with ultra-thin center struts attenuates stent jail in porcine femoral artery bifurcations.

INTRODUCTION: An ultra-thin, fracture-resistant and bioresorbable stent may be advantageous for provisional stenting in vessel bifurcations, if catheter passage and side-branch post-dilatation is facilitated to prevent a 'stent jail' by struts obstructing the orifice of a major side branch. MATERIAL AND METHODS: We studied a highly radiopaque, slowly bioresorbable zinc alloy stent characterized by a novel design of a radiopaque-marked region of ultra-thin struts in the center of the stent. The stent is characterized by an extended range flexibility and high fracture resistance. Zn-stents and Zn-drug eluting stents (DES) were implanted opposite to rigid Nitinol stents into both femoral artery bifurcations of 21 juvenile pigs, followed for one and three months and studied by angiography and histomorphometry.Results and conclusion: Bare Zn-stents with thinner stent struts showed less neointimal hyperplasia compared to Zn-stents with thicker struts. Neointimal formation was further reduced by 12% in Zn-alloy DES. Both, bare Zn-stents and Zn-DES, can be precisely positioned into the femoral artery bifurcation, allowing easy balloon catheter passage through the very thin strut mesh. Side branch orifices remained open after Zn-stent deployment without stent jailing. No stent fractures or particles emboli occurred after the deployment. A Zn-stent with ultra-thin center struts may be useful for provisional stenting in vessel bifurcations.

Zn-alloy provides a novel platform for mechanically stable bioresorbable vascular stents.

Metallic Zn alloys have recently gained interest as potential candidates for developing platforms of bioresorbable vascular stents (BVS). Previous studies revealed that Mg alloys used for BVS can degrade too early, whereas PLLA materials may fail to provide effective scaffolding properties. Here we report on results of a new bioresorbable, metallic stent made from a Zn-Ag alloy studied in a porcine animal model of thrombosis and restenosis. While the tensile strength (MPa) of Zn-3Ag was higher than that of PLLA and resembled Mg's (WE43), fracture elongation (%) of Zn-3Ag was much greater (18-fold) than the PLLA's or Mg alloy's (WE43). Zn-3Ag exposed to HAoSMC culture medium for 30 days revealed degradation elements consisting of Zn, O, N, C, P, and Na at a 6 nm surface depth. Platelet adhesion rates and blood biocompatibility did not differ between Zn-3Ag, PLLA, Mg (WE43), and non-resorbable Nitinol (NiTi) stent materials. Balloon-expandable Zn-3Ag alloy BVS implanted into iliofemoral arteries of 15 juvenile domestic pigs were easily visible fluoroscopically at implantation, and their bioresorption was readily detectable via X-ray over time. Histologically, arteries with Zn-3Ag BVS were completely endothelialized, covered with neointima, and were patent at 1, 3, and 6 months follow-up with no signs of stent thrombosis. Zn-3Ag alloy appears to be a promising material platform for the fabrication of a new generation of bioresorbable vascular stents.

Biocompatibility of a novel zinc stent with a closed-cell-design.

Biomaterials made of zinc have been widely described to be antioxidative, hypothrombogenic, antiinflammatory and antiproliferative. Additionally in vivo zinc is toxic only in high concentrations and can completely be metabolized in vivo. Due to these properties zinc based vascular stents might be able to reduce the rate of restenosis in comparison to bare metal stents and zinc stents might be also able to limit the foreign body reaction. In the presented study we tested the biocompatibility and degradability of a stent made of zinc and characterized by a closed-cell-design to achieve high opening force and to increase stent stiffness. After 100 days of enzymatic and hydrolytic degradation in 15 ml blood serum (fetal calf serum) a significant loss of weight (1.72 wt% ) was measured. Zinc was compared to other metals in terms of degradation rates. After six weeks of incubation in physiologic sodium chloride solution zinc showed the slowest degradation time, 6 times less than stainless steel and 4 times less than magnesium. In the tests for cytotoxic effects the degraded zinc stent caused no changes in the LDH-release and cell membrane integrity (3T3 cells, mouse fibroblasts) respectively, in the cell activity/proliferation (MTS assay) and in the morphological characteristics of the cells and cell layers in comparison to the control material (polystyrene). Based on these results the tested zinc stent proved to be non-cytotoxic and to be characterized by degradation characteristics which might be advantageous in comparison to magnesium and stainless steel.

Primary motor cortex activation and lateralization in patients with tumors of the central region.

Hemispheric lateralization is a frequently encountered phenomenon of cortical function. It describes the functional specialization of a region on one side of the brain for a given task. It is well characterized in motor and sensory, as well as language systems and becomes more and more known for various cognitive domains. While in the adult healthy brain hemispheric lateralization is mostly set, pathological processes may lead to cortical reorganization. In these cases neuroplasticity of the corresponding region in the non-dominant hemisphere seems to play an important role. In a previous study we investigated language associated regions in right-handed patients with frontal and temporal tumors of the left hemisphere. We observed a marked change of language lateralization in these patients towards the non-dominant hemisphere as measured by functional MRI (Partovi et al., 2012). In the present study we evaluated activation and lateralization of cortical motor areas in patients with tumors of the central region. BOLD fMRI was performed during unilateral voluntary movements of the contralesional hand in 87 patients. Individual correlations of measured BOLD-signals with the model hemodynamic reference function were determined on a ROI basis in single subjects and compared to those of 16 healthy volunteers. In volunteers the strongest activation is usually found in the M1 hand representation contralateral to the movement, while a weaker homotopic co-activation is observed in ipsilateral M1 (Stippich et al., 2007a). In the patient group our results show significant changes of motor activations, ranging from a reduction of M1 lateralization to equalization of M1 activations or even inversion of M1 lateralization during contralesional movements. This study corroborates in a large patient group the idea that lesions affecting M1 may lead to functional reorganization of cortical motor systems and in particular equalize hemispheric lateralization. However, it is not yet clear whether these changes are only an epiphenomenon or indeed reflect an attempt of recovery of brain function.

Effects of covert and overt paradigms in clinical language fMRI.

RATIONALE AND OBJECTIVES: The aim of this study was to assess the intrasubject and intersubject reproducibility of functional magnetic resonance imaging (fMRI) language paradigms on language localization and lateralization. MATERIALS AND METHODS: Fourteen healthy volunteers were enrolled prospectively and underwent language fMRI using visually triggered covert and overt sentence generation (SG) and word generation (WG) paradigms. Semiautomated analysis of all functional data was performed using Brain Voyager on an individual basis. Regions of interest for Broca's area, Wernicke's area, and their contralateral homologues were drawn. The Euclidean coordinates of the center of gravidity (x, y, and z) of the respective blood oxygenation level-dependent (BOLD) activation cluster, and the correlation of the measured hemodynamic response to the applied reference function (r), relative BOLD signal change as BOLD signal characteristics were measured in each region of interest. Regional lateralization indexes were calculated for Broca's area, Wernicke's area, and their contralateral homologues separately. Wilcoxon's signed-rank test was applied for statistical comparisons (P values < .05 were considered significant). Ten of the 14 volunteers had three repeated measurements to test intrasession reproducibility and intersession reproducibility. RESULTS: Overall activation rates for the four paradigms were 89% for covert SG, 82% for overt SG, 89% for covert WG, and 100% for overt WG. When comparing covert and overt paradigms, language localization was significantly different in 17% (Euclidean coordinates) and 19% (BOLD signal characteristics), respectively. Language lateralization was significantly different in 75%. Intrasubject and intersubject reproducibility was excellent, with 3.3% significant differences among all five parameters for language localization and 0% significant differences for language lateralization using covert paradigms. CONCLUSIONS: Covert language paradigms (SG and WG) provided highly robust and reproducible localization and lateralization of essential language centers for scans performed on the same and different days. Their overt counterparts achieved confirmatory localization but lower lateralization capabilities. Reference data for presurgical application are provided.

Clinical functional MRI of sensorimotor cortex using passive motor and sensory stimulation at 3 Tesla.

PURPOSE: To establish a passive motor paradigm for clinical functional MRI (fMRI) that could be beneficial for patients with motor or attention deficits who are not able to perform active motor tasks. MATERIALS AND METHODS: A novel standardized sensorimotor fMRI protocol was applied in 16 healthy volunteers at 3 Tesla (T) using active and passive motor tasks as well as sensory stimulation of hands and feet. Data analysis was carried out individually using a dynamic thresholding routine. RESULTS: Active motor tasks yielded time efficient and robust blood-oxygen-level-dependent (BOLD) signals in primary motor cortex. Noteworthy, it was possible to achieve equal activation levels within identical anatomical localization for passive and active motor tasks with these paradigms. CONCLUSION: Patients unable to perform active movements can benefit from paradigms with passive motor and sensory stimulation. Therefore, we recommend these paradigms for functional somatotopic mapping of the central region at 3T in clinical routine.

Altered somatosensory processing in trigeminal neuralgia.

Trigeminal neuralgia (TN) is a pain state characterized by intermittent unilateral pain attacks in one or several facial areas innervated by the trigeminal nerve. The somatosensory cortex is heavily involved in the perception of sensory features of pain, but it is also the primary target for thalamic input of nonpainful somatosensory information. Thus, pain and somatosensory processing are accomplished in overlapping cortical structures raising the question whether pain states are associated with alteration of somatosensory function itself. To test this hypothesis, we used functional magnetic resonance imaging to assess activation of primary (SI) and secondary (SII) somatosensory cortices upon nonpainful tactile stimulation of lips and fingers in 18 patients with TN and 10 patients with TN relieved from pain after successful neurosurgical intervention in comparison with 13 healthy subjects. We found that SI and SII activations in patients did neither depend on the affected side of TN nor differ between operated and nonoperated patients. However, SI and SII activations, but not thalamic activations, were significantly reduced in patients as compared to controls. These differences were most prominent for finger stimulation, an area not associated with TN. For lip stimulation SI and SII activations were reduced in patients with TN on the contra- but not on the ipsilateral side to the stimulus. These findings suggest a general reduction of SI and SII processing in patients with TN, indicating a long-term modulation of somatosensory function and pointing to an attempt of cortical adaptation to potentially painful stimuli.

Gender-specific strategy use and neural correlates in a spatial perspective taking task.

In the context of the present study spatial perspective taking refers to the ability to translocate one's own egocentric viewpoint to somebody else's viewpoint in space. We adopted a spatial perspective taking paradigm and performed a functional magnetic resonance imaging study to assess gender differences of neural activity during perspective taking. 24 healthy subjects (12 male/12 female) were asked to systematically either take their own (first-person-perspective, 1PP) or another person's perspective (third-person-perspective, 3PP). Presented stimuli consisted of a virtual scenery with an avatar and red balls around him that had to be counted, if visible, from 1PP or 3PP. Reaction time was increased and correctness scores were decreased during the cognitively more effortful 3PP condition. Correctness scores showed a trend towards a more pronounced decline of performance during 3PP as compared to 1PP in female subjects. Female subjects correctness scores declined by 6.7% from 1PP to 3PP, while in male subjects this performance decline was only 2.7%. Debriefings after the experiment, reaction times depending on angle of rotation and error rates suggest that males are more likely to employ an object-based strategy in contrast to a consistently employed egocentric perspective transformation in females. In the whole group, neural activity was increased in the parieto-occipital, right inferior frontal and supplementary motor areas, confirming previous studies. With respect to gender, male subjects showed stronger activation in the precuneus and the right inferior frontal gyrus than female subjects in a region-of-interest approach. In a subgroup of male subjects whose strategy reports suggest object-based strategies these differences seem to be more pronounced. In conclusion, the differential recruitment of brain regions most likely reflects different strategies in solving this spatial perspective taking task.

fMRI reflects functional connectivity of human somatosensory cortex.

Unilateral sensory stimulation reliably elicits contralateral somatotopic activation of primary (SI) and secondary (SII) somatosensory cortex. There is an ongoing debate about the occurrence and nature of concomitant ipsilateral SI and SII activation. Here we used functional magnetic resonance imaging (fMRI) in healthy human subjects with unilateral tactile stimulation of fingers and lips, to compare somatosensory activation patterns from distal and proximal body parts. We hypothesized that fMRI in humans should reflect the functional connectivity of somatosensory cortex as predicted by animal studies. We show that both unilateral finger and lip stimulations activate contra- and ipsilateral SI and SII cortices with high detection frequency. Correlations of BOLD-signals to the applied hemodynamic reference function were significantly higher in contralateral as compared to ipsilateral SI and SII cortices for both finger and lip stimulation, reflecting strong contribution of contralateral thalamocortical input. Furthermore, BOLD-signal correlations were higher in SI than in SII activations on the contralateral but not on the ipsilateral side. While these asymmetries within and across hemispheres were consistent for finger and lip stimulations, indicating analogous underlying organizing principles, they were less prominent for lip stimulation. Somatotopic organization was detected in SI but not in SII representations of fingers and lips. These results qualitatively and quantitatively support the prevalent concepts of anatomical and functional connectivity in the somatosensory system and therefore may allow interpretation of sensory evoked fMRI signals in terms of normal human brain function. Thus, the assessment of human somatosensory function with fMRI may permit in the future investigations of pathological conditions.

Localizing and lateralizing language in patients with brain tumors: feasibility of routine preoperative functional MR imaging in 81 consecutive patients.

PURPOSE: To prospectively assess the feasibility of standardized presurgical functional magnetic resonance (MR) imaging for localizing the Broca and Wernicke areas and for lateralizing language function. MATERIALS AND METHODS: The study was approved by the responsible ethics commission, and patients gave written informed consent. Eighty-one patients (36 female and 45 male patients; age range, 7-75 years) with different brain tumors underwent blood oxygen level-dependent functional MR imaging at 1.5 T with two paradigms: sentence generation (SG) and word generation (WG). Functional MR imaging measurements, data processing, and evaluation were fully standardized by using dedicated software. Four regions of interest were evaluated in each patient: the Broca and Wernicke areas and their anatomic homologues in the right hemisphere. Statistics were calculated. RESULTS: The SG and WG paradigms were successfully completed by all (100%) and 70 (86%) patients, respectively. Success rates in localizing and lateralizing language were 96% for the Broca and Wernicke areas with the SG paradigm, 81% for the Broca area and 80% for the Wernicke area with the WG paradigm, and 98% for both areas when the SG and WG paradigms were used in combination. Functional localizations were consistent for SG and WG paradigms in the inferior frontal gyrus (Broca area) and the superior temporal, supramarginal, and angular gyri (Wernicke area). Surgery was not performed in seven patients (9%) and was modified in two patients (2%) because of functional MR imaging findings. CONCLUSION: Functional MR imaging proved to be feasible during routine diagnostic neuroimaging for localizing and lateralizing language function preoperatively.

Volumetric measurement of the pontomesencephalic cistern in patients with trigeminal neuralgia and healthy controls.

OBJECTIVE: Most so-called idiopathic trigeminal neuralgias (TN) are caused by neurovascular compression. Does the size of the cerebellopontine cistern play a role in favoring a neurovascular conflict? The aim of this prospective study was to measure the volume of the parapontine cistern in patients with idiopathic TN and to perform a comparison with healthy controls. METHODS: In 25 patients with unilateral idiopathic TN and 17 healthy participants, high-resolution 1.5-T magnetic resonance imaging scans of the parapontine region and the trigeminal nerve were performed. A coronal T2-weighted, true fast imaging steady-state precession sequence with a slice thickness of 0.9 mm was used to define the surrounding cerebrospinal fluid space from the trigeminal root entry zone to Meckel's cave. The volume of the pontomesencephalic cistern was calculated using a standardized method. RESULTS: The mean difference of the volume of the affected and opposite side was 13% in patients with TN. In all patients, a significantly smaller volume of the cistern was found on the affected side (P < 0.01). Healthy controls showed a mean volumetric side difference of 9%, which was not significant (P > 0.05). CONCLUSION: High-resolution magnetic resonance imaging scans are able to demonstrate significant volumetric differences of the pontomesencephalic cistern in patients with unilateral TN. A smaller cistern may be correlated with the occurrence of a neurovascular compression, and these findings support the neurovascular compression theory in idiopathic TN.

Time-efficient localization of the human secondary somatosensory cortex by functional magnetic resonance imaging.

Standardized, robust and time-efficient localization of the human secondary somatosensory cortex (S2) is a challenge in clinical blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). A fully automated tactile stimulation was optimized in seven right-handed volunteers at 1.5 T for minimum scan time, high BOLD signals and robust localization of S2 by systematically varying the applied block-design. All volunteers had six different fMRI measurements of five stimulation-baseline-cycles (sbc) each with equal block duration that was changed between the measurements from 6 s to 30 s. Additional data sets of 4, 3 and 2 cycles were generated post hoc resulting in a total of 168 data sets that were evaluated individually for BOLD-signal intensity (dS%), correlation to the hemodynamic reference function (r) and Euclidean coordinates (x, y, z). Using different block-designs the S2 activation was highly variable regarding the localization rate (lr), the hemispheric symmetry and the BOLD-signals. The protocol with 3 cycles, a block duration (dp) of 15 s and a total scan time (dt) of 105 s most robustly localized S2 (contralateral: lr=71.4%, r=0.65, dS=1.01%; ipsilateral: lr=100%, r=0.6, dS=1.14%) whereas the most time-efficient protocol to localize SI (sbc=5, dp=6 s, dt=66 s) provided no robust localization of S2. Compared to other published fMRI protocols a scan time reduction up to 86% was achieved.

Fully automated localization of the human primary somatosensory cortex in one minute by functional magnetic resonance imaging.

A clinical functional magnetic resonance imaging (fMRI) protocol based on a fully automated tactile stimulation was optimized in 10 right-handed volunteers at 1.5 T for minimum scan time, high BOLD-signals and robust localization of the primary somatosensory cortex (S1) by systematically varying the applied block design. All volunteers had six different fMRI measurements of 5 stimulation/baseline cycles each with equal block duration that was changed between the measurements from 6 to 30 s. Data sets of 4, 3 and 2 cycles were generated post hoc resulting in a total of 240 data sets that were evaluated individually for BOLD-signal intensity (dS%), correlation to the hemodynamic reference function (r) and Euclidean coordinates (x, y, z). The protocol with 5 cycles, a block duration of 6 s and a total scan time of 66 s provided the best BOLD-signal characteristics (dS% = 1.15, r = 0.78). Compared to the mean scan time of other clinical fMRI protocols (174 s) a reduction of 62% was achieved.