Clinical significance of post-interventional cerebral hyperdensities after endovascular mechanical thrombectomy in acute ischaemic stroke.

INTRODUCTION: This study aims to investigate the clinical significance of post-interventional cerebral hyperdensities (PCHD) after endovascular mechanical thrombectomy in acute ischaemic stroke. METHODS: Data of 102 consecutive patients who received post-interventional CT scans within 4.5 h after mechanical thrombectomy were analysed retrospectively. RESULTS: Sixty-two of 102 patients (60.8 %) had PCHD on their post-interventional CT scans. The most common site of PCHD was the basal ganglia. PCHD were persisting in 13 of 62 patients (21.0 %), and transient in the remaining 49 patients (79.0 %) within 24 h. Four patients with PCHD and four patients without PCHD suffered from parenchymal haemorrhage. Neither ASA nor Clopidogrel, Tirofiban or rtPA were risk factors for PCHD. Final infarction size was congruent with or bigger than areas of PCHD in 93.3 % of cases in our series. CONCLUSION: PCHD was not a risk factor for parenchymal haemorrhage in our series. The occurrence of PCHD was strongly related to the prior presence of infarction. PCHD was also a strong predictor for final infarction size.

Comparison of high-resolution X-ray and micro-CT for experimental evaluation of intracranial stent prototypes: quality evaluation beyond CE mark.

INTRODUCTION: As digital mammography and micro-computed tomography (CT) have been used for evaluation of stents deployed in experimental animal models, we compared the two methods regarding their sensitivity to detect abnormalities in three prototypes of intracranial stents. METHODS: Three different prototypes of intracranial stents (n = 84) were implanted in various animal models. Explanted stents were examined using digital mammography and micro-CT. The images were compared with respect to maintenance of material and form and the stents were compared to one another. Histological analysis was performed as well. RESULTS: In the open-cell stents, expansion of the stent cells was detected in the majority of cases (57.1 %) using micro-CT and less frequently using mammography (42.3 %). The closed-cell stent revealed kink stenoses in mammography as well as in micro-CT (3/7, 42.9 %). Detailed reconstructions of micro-CT images showed high-grade kink stenoses of the flow-diverter stent in two extremely curved vessels. Strut breaks were observed more frequently using micro-CT (6/84, 7.1 %) than by mammography (4/84, 4.8 %). Histology confirmed all changes of stent architecture. CONCLUSION: Significant changes of stent architecture can be observed and assessed even in the two-dimensional mammographic images. The use of micro-CT is recommended to detect subtle changes like single strut breaks and for three-dimensional information.

Quantitative multi-energy micro-CT: A simulation and phantom study for simultaneous imaging of four different contrast materials using an energy integrating detector.

Emerging from the development of single-energy Computed Tomography (CT) and Dual-Energy Computed Tomography, Multi-Energy Computed Tomography (MECT) is a promising tool allowing advanced material and tissue decomposition and thereby enabling the use of multiple contrast materials in preclinical research. The scope of this work was to evaluate whether a usual preclinical micro-CT system is applicable for the decomposition of different materials using MECT together with a matrix-inversion method and how different changes of the measurement-environment affect the results. A matrix-inversion based algorithm to differentiate up to five materials (iodine, iron, barium, gadolinium, residual material) by applying four different acceleration voltages/energy levels was established. We carried out simulations using different ratios and concentrations (given in fractions of volume units, VU) of the four different materials (plus residual material) at different noise-levels for 30 keV, 40 keV, 50 keV, 60 keV, 80 keV and 100 keV (monochromatic). Our simulation results were then confirmed by using region of interest-based measurements in a phantom-study at corresponding acceleration voltages. Therefore, different mixtures of contrast materials were scanned using a micro-CT. Voxel wise evaluation of the phantom imaging data was conducted to confirm its usability for future imaging applications and to estimate the influence of varying noise-levels, scattering, artifacts and concentrations. The analysis of our simulations showed the smallest deviation of 0.01 (0.003-0.15) VU between given and calculated concentrations of the different contrast materials when using an energy-combination of 30 keV, 40 keV, 50 keV and 100 keV for MECT. Subsequent MECT phantom measurements, however, revealed a combination of acceleration voltages of 30 kV, 40 kV, 60 kV and 100 kV as most effective for performing material decomposition with a deviation of 0.28 (0-1.07) mg/ml. The feasibility of our voxelwise analyses using the proposed algorithm was then confirmed by the generation of phantom parameter-maps that matched the known contrast material concentrations. The results were mostly influenced by the noise-level and the concentrations used in the phantoms. MECT using a standard micro-CT combined with a matrix inversion method is feasible at four different imaging energies and allows the differentiation of mixtures of up to four contrast materials plus an additional residual material.

Abciximab does not prevent ischemic lesions related to cerebral angiography: a randomized placebo-controlled trial.

BACKGROUND: To assess the efficiency of IIb/IIIa platelet receptor inhibition by abciximab in the prevention of silent embolism during digital subtraction angiography. METHODS: In this randomized, double-blind, prospective study, pre- and postangiographic diffusion-weighted magnetic resonance imaging (DWI) of 184 participants was evaluated for the occurrence of silent embolism. RESULTS: No significant relationship was found between the patients receiving abciximab before digital subtraction angiography (15 of 90; 16.7%) and patients in the placebo group (16 of 94; 17.0%) regarding postangiographic appearance of silent emboli (p = 0.9). CONCLUSIONS: IIb/IIIa receptor inhibition by abciximab does not diminish the occurrence of silent embolism during digital subtraction angiography. Our findings indicate that solid blood clots are not the origin of hyperintense lesions observed on DWI and enhance the role of alternative mechanisms.

Intraindividual comparison of selective intraarterial versus systemic intravenous 68Ga-DOTATATE PET/CT in patients with inoperable meningioma.

AIM: Here we describe the results of superselective intraarterial application of diagnostic Ga-68-DOTA0,Tyr3-octreotate (Ga-68-DOTATATE) in a series of patients with inoperable WHO grade II meningiomas which were no longer amenable to radiotherapy. METHODS: Four patients with inoperable WHO grade II meningioma underwent systemic venous infusion of Ga-68-DOTATATE followed by PET/CT. Ga-68-DOTATATE application was repeated intraarterially via transfemoral catheterization of vessels supplying the meningioma and another PET/CT was performed. RESULTS: Selective arterial infusion of Ga-68-DOTATATE increased the median value for the maximum standardized uptake value (SUV) by 2.6-fold (median venous: 7.1, median arterial: 21.6; range 2.0-5.0) and the median value for mean SUV by 2.7-fold (median venous: 4.3, median arterial: 11.2; range 1.6-5.6) compared to systemic intravenous infusion. Arterial application was well tolerated by all patients without complications. When compared to liver uptake, intravenous tracer uptake was insufficient for PRRT, whereas tracer uptake after superselective intraarterial tracer injection was sufficient to allow for peptide receptor radionuclide therapy (PRRT) in all patients. CONCLUSION: Insufficient tracer uptake in meningiomas after intravenous application of Ga-68-DOTATATE may be safely increased by a factor of 2-5 using transfemoral selective intraarterial tracer application.

Development of a Polymer-Based Biodegradable Neurovascular Stent Prototype: A Preliminary In Vitro and In Vivo Study.

Biodegradable stents are not established in neurovascular interventions. In this study, mechanical, radiological, and histological characteristics of a stent prototype developed for neurovascular use are presented. The elasticity and brittleness of PLA 96/4, PLDL 70/30, PCL, and PLGA 85/15 and 10/90 polymers in in vitro experiments are first analyzed. After excluding the inapt polymers, degradability and mechanical characteristics of 78 PLGA 85/15 and PLGA 10/90 stent prototypes are analyzed. After excluding PLGA 10/90 stents because of rapid loss of mass PLGA 85/15 stents in porcine in vivo experiments are analyzed. Angiographic occlusion rates 7 d, 1 month, 3 months, and 6 months after stent implantation are assessed. Histological outcome measures are the presence of signs of inflammation, endothelialization, and the homogeneity of degradation after six months. One case of stent occlusion occurs within the first 7 d. There is a prominent foreign-body reaction with considerable mononuclear and minor granulocytic inflammation combined with incomplete fragmental degradation of the struts. It is possible to produce a stent prototype with dimensions that fit the typical size of carotid arteries. Major improvements concerning thrombogenicity, degradation, and inflammatory response are required to produce biodegradable stents that are suitable for neurovascular interventions.

Efficacy of different regimens of adjuvant radiochemotherapy for treatment of glioblastoma.

AIMS AND BACKGROUND: We retrospectively analyzed the impact of different adjuvant chemotherapy regimens in a group of patients treated for glioblastoma compared to patients receiving only postoperative radiotherapy. MATERIAL AND METHODS: Eighty-six consecutive patients underwent radiotherapy between January 2000 and December 2003: 52 patients received radiotherapy alone, 17 patients radiochemotherapy with low-dose temozolomide (20 mg/m(2)) + cyclooxygenase-2-inhibitors (200 mg), 6 patients radiochemotherapy with high-dose temozolomide (50 mg/m2). Eleven patients, with unfavorable prognostic factors, were treated with imatinib and 55/2.5 Gy. RESULTS: The groups treated with high- and low-dose temozolomide showed the longest overall survival (median, 21 months and 17 months, respectively). Median overall survival was 9 months for radiation alone and 4 months for the imatinib-treated group. The same positive trend of temozolomide on prolonged overall survival was confirmed when only patients submitted to maximally radical resection or patients with KPS >70 were considered. Differences in progression-free survival were not statistically significant. CONCLUSIONS: Patients treated with adjuvant temozolomide either inside or outside of study protocols had survival times similar to other reports or randomized studies. The absence of a significant influence of temozolomide on progression-free survival could depend on the unavoidable drawbacks and biases of retrospective investigations or on the definition of relapse used. The unsatisfactory results of radiotherapy plus imatinib may have been due to a high prevalence of unfavorable prognostic factors in the respective patients. The ongoing controlled trial will further define the efficacy of adjuvant/concomitant imatinib.

Active push deployment technique improves stent/vessel-wall interaction in endovascular treatment of acute stroke with stent retrievers.

BACKGROUND: The optimal interaction between stent struts and thrombus is crucial for successful revascularization in endovascular stroke therapy with stent retrievers. Deploying the stent retriever by actively pushing it into the thrombus increases the radial force with which the stent struts expand into the thrombus. OBJECTIVE: To examine the active push deployment (APD) technique in an in vitro model and present our clinical experience with this technique. METHODS: In an in vitro experiment we investigated the configuration of a Solitaire and a Trevo ProVue device (both 4×20 mm), depending on whether the devices were deployed using the APD technique or simple unsheathing. We retrospectively assessed the effectiveness and safety of this technique by analyzing 130 patients with large vessel occlusions (carotid T or M1 segment of the middle cerebral artery), who received endovascular treatment with a Trevo device (4×20 mm) that was deployed using the APD technique. RESULTS: In vitro experiment: the APD technique improved apposition of the devices to the vessel wall. There was widening of 30% (Trevo) and 19% (Solitaire) at the cost of a shortening of 5% and 4%, respectively, when the devices were deployed in a carotid T model. Clinical study: the revascularization rate (Thrombolysis in Cerebral Infarction ≥2b) with the Trevo device was 90%. There were no retriever-associated dissections or perforations in 278 retrieval maneuvers. CONCLUSIONS: The APD technique improves apposition of the tested devices to the vessel wall. The widening effect comes at the cost of minimal shortening of the devices. Our clinical experience shows that using the APD technique to deploy the Trevo device is effective and safe.

Endovascular Rescue Therapies for Refractory Vasospasm After Subarachnoid Hemorrhage: A Prospective Evaluation Study Using Multimodal, Continuous Event Neuromonitoring.

BACKGROUND: Critical hypoperfusion and metabolic derangement are frequently encountered with refractory vasospasm. Endovascular rescue therapies (ERT) have proven beneficial in selected cases. However, angioplasty (AP) and intraarterial lysis (IAL) are measures of last resort and prospective, quantitative results regarding the efficacy (cerebral oxygenation, metabolism) are largely lacking. OBJECTIVE: To evaluate the efficacy of ERTs for medically refractory vasospasm using multimodal, continuous event neuromonitoring. METHODS: To detect cerebral compromise in a timely fashion, sedated patients with aneurysmal subarachnoid hemorrhage received continuous neuromonitoring (p ti O 2 measurement, intraparenchymal microdialysis). ERT (AP and/or IAL) was considered in cases of clinically relevant vasospasm refractory to conservative treatment measures. Oxygen saturation and cerebral and systemic metabolism before and after events of ERT was recorded. RESULTS: We prospectively included 13 consecutive patients and recorded a total of 25 ERT events: AP (n = 10), IAL (n = 11), or both (AP + IAL, n = 4). Average cerebral p ti O 2 was 10 ± 11 torr before and 49 ± 22 torr after ERT ( P < .001), with a lactate-pyruvate ratio decreasing from 146.6 ± 119.0 to 27.9 ± 10.7 after ERT ( P < .001). Comparable improvement was observed for each type of intervention (AP, IAL, or both). No significant alterations in systemic metabolism could be detected after ERT. CONCLUSION: Multimodal event neuromonitoring is able to quantify treatment efficacy in subarachnoid hemorrhage-related vasospasm. In our small cohort of highly selected cases, ERT was associated with improvement in cerebral oxygenation and metabolism with reasonable outcome. Event neuromonitoring may facilitate individual and timely optimization of treatment modality according to the individual clinical course.

Weekend effect in endovascular stroke treatment: do treatment decisions, procedural times, and outcome depend on time of admission?

BACKGROUND: Epidemiologic studies identified a 'weekend effect' or 'out-of-hours effect', which implies that procedural and clinical outcomes of patients with stroke, who are admitted out-of-hours, are less favorable than for patients admitted during working-hours. OBJECTIVE: To determine (1) whether our procedural times and clinical outcome were affected by an out-of-hours effect and (2) whether the decision in favor of, or against, endovascular stroke treatment (EST) depends on the time of admission. METHODS: Between February 2010 and January 2015, 6412 consecutive patients presenting with symptoms of acute ischemic stroke were evaluated for EST eligibility according to established local protocols and generally accepted consensus criteria, and dichotomized into working-hours and out-of-hours cohorts according to admission times. Within both groups, patients given EST were identified and the rate of treatment decision, procedural times, and clinical outcome were compared and analyzed. RESULTS: Clinical and radiological features of patients admitted in working-hours and out-of-hours did not differ significantly. Procedural times and clinical outcome were not affected by an out-of-hours effect (p≥0.054). 221/240 (92.1%) out-of-hours patients and 154/166 (92.8%) working-hours patients who were eligible for EST were transferred to the angiography suite for EST (p=0.798). The rationale not to treat patients who were eligible for EST did not differ between working-hours and out-of-hours admission (p=0.756). CONCLUSIONS: It is possible to produce competitive procedural times regardless of the time of admission and to prevent a treatment decision bias when standard operating procedures are applied consistently.

Optimizing endovascular stroke treatment: removing the microcatheter before clot retrieval with stent-retrievers increases aspiration flow.

BACKGROUND: Flow control during endovascular stroke treatment with stent-retrievers is crucial for successful revascularization. The standard technique recommended by stent-retriever manufacturers implies obstruction of the respective access catheter by the microcatheter, through which the stent-retriever is delivered. This, in turn, results in reduced aspiration during thrombectomy. In order to maximize aspiration, we fully retract the microcatheter out of the access catheter before thrombectomy-an approach we term the 'bare wire thrombectomy' (BWT) technique. We verified the improved throughput with systematic in vitro studies and assessed the clinical effectiveness and safety of this method. METHODS: We compared aspiration flow of water through various access catheters (5-8 F) with a Rebar microcatheter (0.18 inch and 0.27 inch) and a Trevo stent-retriever using the standard technique and the BWT technique in vitro. We also retrospectively analyzed 302 retrieval maneuvers in 117 patients who received endovascular treatment with a stent-retriever between February 2010 and April 2015. RESULTS: In the in vitro experiment, removal of the microcatheter in all tested settings resulted in significantly increased aspiration flow through the access catheter (p<0.001). This effect was particularly pronounced in access catheters with a diameter of ≤7 F. In the clinical study, the revascularization rate (Thrombolysis In Cerebral Infarction ≥2b) was 91%. There were no complications associated with the BWT technique in 302 retrieval maneuvers. CONCLUSIONS: The BWT technique results in improved aspiration flow rates compared with the standard deployment technique. Our clinical data show that the BWT technique is effective and safe.

Feasibility of combined surgical and endovascular carotid access for interventional treatment of ischemic stroke.

BACKGROUND: Rapid recanalization of occluded vessels is crucial for good clinical outcome in acute ischemic stroke. Endovascular treatment is usually performed via a transfemoral approach, but catheterization of the carotid arteries can be problematic in cases of difficult anatomy or vascular pathologies in some cases. OBJECTIVE: To describe our experience with a technique involving surgical access to the carotid artery and consecutive transcarotid endovascular thrombectomy in patients with acute stroke. METHODS: In a retrospective review of a prospectively maintained registry we identified 6 patients who underwent acute endovascular thrombectomy via a surgical access to the carotid artery. RESULTS: Admission National Institute of Health Stroke Scale (NIHSS) ranged from 7 to 23. Intracranial recanalization (thrombolysis in cerebral infarction, TICI≥2b) was achieved in all patients (100%). Recanalization was achieved within 19±5 min after establishing carotid access. One patient developed a small neck hematoma, which was surgically removed without complications. No complications related to endovascular therapy were seen. At 3 months' follow-up, five patients had survived. Three patients (50%) had regained excellent neurological function (modified Rankin Scale, mRS 0-1). CONCLUSIONS: Surgical carotid access for endovascular stroke treatment is feasible, with considerable advantages, in patients with expected problematic access or for whom transfemoral endovascular carotid access has failed.

Molecular Ultrasound Imaging of αvß3-Integrin Expression in Carotid Arteries of Pigs After Vessel Injury.

OBJECTIVES: Interventions such as balloon angioplasty can cause vascular injury leading to platelet activation, thrombus formation, and inflammatory response. This induces vascular smooth muscle cell activation and subsequent re-endothelialization with expression of αvß3-integrin by endothelial cells and vascular smooth muscle cell. Thus, poly-N-butylcyanoacrylate microbubbles (MBs) targeted to αvß3-integrin were evaluated for monitoring vascular healing after vessel injury in pigs using molecular ultrasound imaging. MATERIALS AND METHODS: Approval for animal experiments was obtained. The binding specificity of αvß3-integrin-targeted MB to human umbilical vein endothelial cells was tested with fluorescence microscopy. In vivo imaging was performed using a clinical ultrasound system and an 8-MHz probe. Six mini pigs were examined after vessel injury in the left carotid artery. The right carotid served as control. Uncoated MB, cDRG-coated MB, and αvß3-integrin-specific cRGD-coated MB were injected sequentially. Bound MBs were assessed 8 minutes after injection using ultrasound replenishment analysis. Measurements were performed 2 hours, 1 and 5 weeks, and 3 and 6 months after injury. In vivo data were validated by immunohistochemistry. RESULTS: Significantly stronger binding of cRGD-MB than MB and cDRG-MB to human umbilical vein endothelial cells was found (P < 0.01). As vessel injury leads to upregulation of αvß3-integrin, cRGD-MBs bound significantly stronger (P < 0.05) in injured carotid arteries than at the counter side 1 week after vessel injury and significant differences could also be observed after 5 weeks. After 3 months, αvß3-integrin expression decreased to baseline and binding of cRGD-MB was comparable in both vessels. Values remained at baseline also after 6 months. CONCLUSIONS: Ultrasound imaging with RGD-MB is promising for monitoring vascular healing after vessel injury. This may open new perspectives to assess vascular damage after radiological interventions.

Endovascular retrieval of a dislocated coil in the peroneal artery with a stent retriever.

We present a patient who underwent successful removal of a fully detached platinum coil from the peroneal artery using a Solitaire™ stent retriever (Covidien, Irvine, CA) that is usually used in endovascular stroke treatment.

Retinal Vessel Analysis (RVA) in the Context of Subarachnoid Hemorrhage - A Proof of Concept Study.

BACKGROUND: Timely detection of impending delayed cerebral ischemia after subarachnoid hemorrhage (SAH) is essential to improve outcome, but poses a diagnostic challenge. Retinal vessels as an embryological part of the intracranial vasculature are easily accessible for analysis and may hold the key to a new and non-invasive monitoring technique. This investigation aims to determine the feasibility of standardized retinal vessel analysis (RVA) in the context of SAH. METHODS: In a prospective pilot study, we performed RVA in six patients awake and cooperative with SAH in the acute phase (day 2-14) and eight patients at the time of follow-up (mean 4.6±1.7months after SAH), and included 33 age-matched healthy controls. Data was acquired using a manoeuvrable Dynamic Vessel Analyzer (Imedos Systems UG, Jena) for examination of retinal vessel dimension and neurovascular coupling. RESULTS: Image quality was satisfactory in the majority of cases (93.3%). In the acute phase after SAH, retinal arteries were significantly dilated when compared to the control group (124.2±4.3MU vs 110.9±11.4MU, p<0.01), a difference that persisted to a lesser extent in the later stage of the disease (122.7±17.2MU, p<0.05). Testing for neurovascular coupling showed a trend towards impaired primary vasodilation and secondary vasoconstriction (p = 0.08, p = 0.09 resp.) initially and partial recovery at the time of follow-up, indicating a relative improvement in a time-dependent fashion. CONCLUSION: RVA is technically feasible in patients with SAH and can detect fluctuations in vessel diameter and autoregulation even in less severely affected patients. Preliminary data suggests potential for RVA as a new and non-invasive tool for advanced SAH monitoring, but clinical relevance and prognostic value will have to be determined in a larger cohort.

Technical note: A toy as tool: a low-cost image analysis system for the evaluation of tumor size in experimental small animal models.

Image analysis systems are an essential tool in measurements of size of intraparenchymal tumors or lesions in experimental small animal models. Conventional image analysis systems are relatively expensive. We therefore compared the performance of a professional image analysis system with an inexpensive setup by evaluating tumor size in an orthotopic glioma mouse model. The maximum cross-sectional tumor area of H&E stained brain-slides of two groups of mice (treatment and control group) was measured by two independent investigators using a professional image analysis system (Leica DM IRB microscope) with the Leica Quantimet 500c software, and a low-cost-system (Intel QX3 microscope) with a non-commercial image analysis software. Mean tumor volumes were calculated and the results from each of the image analysis systems, investigators, and treatment effects were compared. The tumor volumes as measured with the low-cost and the professional system differed between -3.7 and +7.5% (P = 0.69-0.99). Measurements made by investigator A and B differed between -7.0 and +3.9% (P = 0.69-0.88). Treatment in all cases significantly reduced the tumor volume between 58.4 and 62.7% (P = 0.0002 or 0.0003), regardless of the investigator or the used image analysis system. We therefore conclude that the QX3 low-cost microscope in combination with a non-commercial image-analysis software represents an inexpensive solution to reliably analyze the size of regions of interest, if they provide a sufficient contrast. However, the low-cost setup due to its low resolution definitely limits a detailed analysis of histologic features.

Glioblastoma and cerebral microvascular endothelial cell migration in response to tumor-associated growth factors.

OBJECTIVE: Glioma cell migration is determined by a complex interplay between soluble motogens and extracellular matrix components. Several growth factors are thought to be involved in glioma cell migration; however, little is known about their motogenic potency relative to one another. METHODS: Using modified Boyden chamber assays, we compared the chemotactic effects of scatter factor/hepatocyte growth factor (SF/HGF), transforming growth factor (TGF)-alpha, TGF-beta1, TGF-beta2, epidermal growth factor (EGF), fibroblast growth factor (FGF)-1, FGF-2, insulin-like growth factor (IGF)-1, IGF-2, platelet-derived growth factor (PDGF)-AA, PDGF-BB, vascular endothelial growth factor (VEGF), pleiotrophin (PTN), and midkine (MK) in concentrations ranging from 1 pmol/L to 50 nmol/L on three different human glioblastoma cell lines. Checkerboard analyses distinguished between chemotaxis and chemokinesis. We further investigated the motogenic effects on human cerebral microvascular endothelial cells and analyzed receptor expression profiles. RESULTS: SF/HGF was the most potent chemotactic factor for all three glioblastoma cell lines, inducing up to 33-fold stimulation of migration. TGF-alpha showed the second strongest effect (up to 17-fold stimulation), and FGF-1 was also chemotactic for all three glioblastoma cell lines analyzed (maximal 4-fold effect). EGF, FGF-2, IGF-1, IGF-2, TGF-beta1, and TGF-beta2 were chemotactic for one or two of the cell lines (2- to 4-fold effects), whereas PDGF-AA, PDGF-BB, VEGF, PTN, and MK had no effect. In contrast, the most potent stimulators of cerebral microvascular endothelial cell migration were PDGF-AA (4-fold) and PDGF-BB (6-fold). CONCLUSION: The expression levels of SF/HGF and TGF-alpha as well as their respective receptors, MET and EGFR, are known to correlate with glioma malignancy grade. The particularly strong motogenic effects of these two growth factors suggest that they could be promising targets for an antimigratory component of glioma therapy, at least in comparison with the 12 other factors that were analyzed.

[Current concepts for experimental micro-CT in small animals]. / Aktueller Stand der Mikro-CT in der experimentellen Kleintierbildgebung.

The number of publications describing the use of micro-computed tomography (microCT) for preclinical in vivo imaging of small animals has risen considerably within the last few years. The purpose of this review is to familiarize the reader with the basic principles of microCT, to present successful experimental approaches in order of the evaluated organ system, and to highlight limitations that need to be considered when planning microCT-based studies.

First experiences with low-dose anti-angiogenic treatment in gliomatosis cerebri with signs of angiogenic activity.

BACKGROUND: Gliomatosis cerebri is a rare primary cerebral tumour entity characterized by diffuse infiltrative growth patterns representing a WHO grade III malignancy. The prognosis is dismal and therapeutical options are still controversial. In contrast to other high-grade gliomas, angiogenesis is thought to be absent in gliomatosis cerebri. PATIENTS AND METHODS: Despite this assumption, histopathological analyses of samples of six patients with gliomatosis cerebri were performed and surprisingly there was angiogenic activity with expression of vascular endothelial growth factor and cyclooxygenase 2. It was therefore decided to administer continuous low-dose chemotherapy with temozolomide and celecoxib for antiangiogenic treatment in the four patients that were in good clinical condition following external radiotherapy. RESULTS: In all patients, treatment was well tolerated and MRI follow-up showed no tumour progression for at least six months. One patient died due to pulmonary embolism 9 months after diagnosis; another patient survived 15 months after diagnosis with progressive disease in the last follow-up MRI before death. Two other patients at the present time are still in a stable clinical condition without signs of tumour progression in MRI (12 and 18 months). CONCLUSION: From our initial experience in a small number of patients with gliomatosis cerebri with signs of angiogenic activity, we conclude that low-dose chemotherapy might provide a promising approach for treatment of these patients and that overexpression of angiogenic factors such as VEGF or COX-2 seems to be more frequent than hitherto reported.