Towards a glioma model for surgical technique evaluation in the rat.

INTRODUCTION: Evaluation of new surgical techniques in animal models is frequently challenging. This article describes the pitfalls, peculiarities and the final best applicable model for evaluating surgical techniques for glioma resection. METHODS: The C6 glioma cell line and the Sprague-Dawley rat strain were selected. Fifty-thousand glioma cells were stereotactically transplanted in the left hemisphere of 137 male adult rats. Evaluation of solid tumour formation, tumour growth and scheduling of surgical resection was performed by MR scanning at 1, 2, and 4 weeks after transplantation and 3 and 6 months after tumour resection. Microsurgical tumour resection was performed with conventional techniques or with the waterjet dissector at a pressure of 6 bar. One subgroup of each surgical technique was sacrificed directly after surgery for histological analysis. The other subgroup was followed up for long-term analysis. RESULTS: The transplantation site was of great importance. After transplantation of tumour cells posterior to the bregma, intra-ventricular tumour growth with spreading occurred. Homogenous and reproducible tumour growth was achieved after grafting cells lateral - 3 mm, anterior + 1 mm, and - 2.5 mm ventral to the bregma. After development of solid tumours on MR imaging, animals were subjected to surgery. MR and intra-operative findings corresponded well. However, MRI and intra-operative none-detectable perivascular tumour spreading was histologically observed in the majority of cases. CONCLUSIONS: The presented glioma rat model consisting of the C6 cell line and Sprague-Dawley rats as recipients is a well-suited model to investigate surgical techniques and their impact on tumour therapy. However, the site of transplantation, the preparation of cell grafts and the technique of tumour growth evaluation is of utmost importance to achieve reliable results.

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.

Improvement of Neurovascular Imaging Using Ultra-High-Resolution Computed Tomography Angiography.

OBJECTIVE: To evaluate diagnostic image quality of ultra-high-resolution computed tomography angiography (UHR-CTA) in neurovascular imaging as compared to normal resolution CT-angiography (NR-CTA). MATERIAL AND METHODS: In this retrospective single-center study brain and neck CT-angiography was performed using an ultra-high-resolution computed tomography scanner (n = 82) or a normal resolution CT scanner (NR-CTA; n = 73). Ultra-high-resolution images were reconstructed with a 1024â€¯× 1024 matrix and a slice thickness of 0.25 mm, whereas NR-CT images were reconstructed with a 512â€¯× 512 matrix and a slice thickness of 0.5 mm. Three blinded neuroradiologists assessed overall image quality, artifacts, image noise, overall contrast and diagnostic confidence using a 4-point Likert scale. Furthermore, the visualization and delineation of supra-aortic arteries with an emphasis on the visualization of small intracerebral vessels was assessed using a cerebral vascular score, also utilizing a 4-point Likert scale. Quantitative analyses included signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), noise and the steepness of gray value transition. Radiation exposure was determined by comparison of computed tomography dose index (CTDIvol), dose length product (DLP) and mean effective dose. Interrater agreement was evaluated via determining Fleiss-Kappa. RESULTS: Ultra-high-resolution CT-angiography (UHR-CTA) yielded excellent image quality with superior quantitative (SNR: p < 0.001, CNR: p < 0.001, steepness of gray value transition: p < 0.001) and qualitative results (overall image quality: 4 (Inter quartile range (IQR) = 4-4); p < 0.001, diagnostic confidence: 4 (IQR = 4-4); p < 0.001) compared to NR-CT (overall image quality: 3 (IQR = 3-3), diagnostic confidence: 3 (IQR = 3-4)). Furthermore, UHR-CT enabled significantly superior delineation and visualization of all vascular segments, from proximal extracranial vessels to the smallest peripheral cerebral branches (e.g. , UHR-CTA PICA: 4 (3-4) vs. NR-CTA PICA: 3 (2-3); UHR-CTA P4: 4 (IQR = 3-4) vs. NR-CTA P4: 2 (IQR = 2-3); UHR-CTA M4: 4 (IQR = 4-4) vs. NR-CTA M4: 3 (IQR = 2-3); UHR-CTA A4: 4 (IQR = 3-4) vs. NR-CTA A4: 2 (IQR = 2-3); all p < 0.001). Noteworthy, a reduced mean effective dose was observed when applying UHR-CT (NR-CTA: 1.8 ± 0.3 mSv; UHR-CTA: 1.5 ± 0.5 mSv; p < 0.001). CONCLUSION: Ultra-high-resolution CT-angiography improves image quality in neurovascular imaging allowing the depiction and evaluation of small peripheral cerebral arteries. It may thus improve the detection of pathologies in small cerebrovascular lesions and the resulting diagnosis.

Value of vendor-agnostic deep learning image denoising in brain computed tomography: A multi-scanner study.

To evaluate the effect of a vendor-agnostic deep learning denoising (DLD) algorithm on diagnostic image quality of non-contrast cranial computed tomography (ncCT) across five CT scanners.This retrospective single-center study included ncCT data of 150 consecutive patients (30 for each of the five scanners) who had undergone routine imaging after minor head trauma. The images were reconstructed using filtered back projection (FBP) and a vendor-agnostic DLD method. Using a 4-point Likert scale, three readers performed a subjective evaluation assessing the following quality criteria: overall diagnostic image quality, image noise, gray matter-white matter differentiation (GM-WM), artifacts, sharpness, and diagnostic confidence. Objective analysis included evaluation of noise, contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and an artifact index for the posterior fossa.In subjective image quality assessment, DLD showed constantly superior results compared to FBP in all categories and for all scanners (p<0.05) across all readers. The objective image quality analysis showed significant improvement in noise, SNR, and CNR as well as for the artifact index using DLD for all scanners (p<0.001).The vendor-agnostic deep learning denoising algorithm provided significantly superior results in the subjective as well as in the objective analysis of ncCT images of patients with minor head trauma concerning all parameters compared to the FBP reconstruction. This effect has been observed in all five included scanners. · Significant improvement of image quality for 5 scanners due to the vendor-agnostic DLD. · Subjects were patients with routine imaging after minor head trauma. · Reduction of artifacts in the posterior fossa due to the DLD. · Access to improved image quality even for older scanners from different vendors. · Kapper C, Müller L, Kronfeld A et al. Value of vendor-agnostic deep learning image denoising in brain computed tomography: A multi-scanner study. Fortschr Röntgenstr 2024; DOI 10.1055/a-2290-4781.

Brain connectivity networks underlying resting heart rate variability in acute ischemic stroke.

Acute strokes can affect heart rate variability (HRV), the mechanisms how are not well understood. We included 42 acute stroke patients (2-7 days after ischemic stroke, mean age 66 years, 16 women). For analysis of HRV, 20 matched controls (mean age 60.7, 10 women) were recruited. HRV was assessed at rest, in a supine position and individual breathing rhythmus for 5 min. The coefficient of variation (VC), the root mean square of successive differences (RMSSD), the powers of low (LF, 0.04-0.14 Hz) and high (HF, 0.15-0.50 Hz) frequency bands were extracted. HRV parameters were z-transformed related to age- and sex-matched normal subjects. Z-values < -1 indicate reduced HRV. Acute stroke lesions were marked on diffusion-weighted images employing MRIcroN and co-registered to a T1-weighted structural volume-dataset. Using independent component analysis (ICA), stroke lesions were related to HRV. Subsequently, we used the ICA-derived lesion pattern as a seed and estimated the connectivity between these brain regions and seven common functional networks, which were obtained from 50 age-matched healthy subjects (mean age 68.9, 27 women). Especially, LF and VC were frequently reduced in patients. ICA revealed one covarying lesion pattern for LF and one similar for VC, predominantly affecting the right hemisphere. Activity in brain areas corresponding to these lesions mainly impact on limbic (r = 0.55 ± 0.08) and salience ventral attention networks (0.61 ± 0.10) in the group with reduced LF power (z-score < -1), but on control and default mode networks in the group with physiological LF power (z-score > -1). No different connectivity could be found for the respective VC groups. Our results suggest that HRV alteration after acute stroke might be due to affecting resting-state brain networks.

Deep Learning Accelerated Brain Diffusion-Weighted MRI with Super Resolution Processing.

OBJECTIVES: To investigate the clinical feasibility and image quality of accelerated brain diffusion-weighted imaging (DWI) with deep learning image reconstruction and super resolution. METHODS: 85 consecutive patients with clinically indicated MRI at a 3 T scanner were prospectively included. Conventional diffusion-weighted data (c-DWI) with four averages were obtained. Reconstructions of one and two averages, as well as deep learning diffusion-weighted imaging (DL-DWI), were accomplished. Three experienced readers evaluated the acquired data using a 5-point Likert scale regarding overall image quality, overall contrast, diagnostic confidence, occurrence of artefacts and evaluation of the central region, basal ganglia, brainstem, and cerebellum. To assess interrater agreement, Fleiss' kappa (Ï°) was determined. Signal intensity (SI) levels for basal ganglia and the central region were estimated via automated segmentation, and SI values of detected pathologies were measured. RESULTS: Intracranial pathologies were identified in 35 patients. DL-DWI was significantly superior for all defined parameters, independently from applied averages (p-value <0.001). Optimum image quality was achieved with DL-DWI by utilizing a single average (p-value <0.001), demonstrating very good (80.9%) to excellent image quality (14.5%) in nearly all cases, compared to 12.5% with very good and 0% with excellent image quality for c-MRI (p-value <0.001). Comparable results could be shown for diagnostic confidence. Inter-rater Fleiss' Kappa demonstrated moderate to substantial agreement for virtually all defined parameters, with good accordance, particularly for the assessment of pathologies (p = 0.74). Regarding SI values, no significant difference was found. CONCLUSION: Ultra-fast diffusion-weighted imaging with super resolution is feasible, resulting in highly accelerated brain imaging while increasing diagnostic image quality.

Single-Energy Metal Artifact Reduction (SEMAR) in Ultra-High-Resolution CT Angiography of Patients with Intracranial Implants.

PURPOSE: To evaluate the effects of single-energy metal artifact reduction (SEMAR) on image quality of ultra-high-resolution CT-angiography (UHR-CTA) with intracranial implants after aneurysm treatment. METHODS: Image quality of standard and SEMAR-reconstructed UHR-CT-angiography images of 54 patients who underwent coiling or clipping was retrospectively evaluated. Image noise (i.e., index for metal-artifact strength) was analyzed in close proximity to and more distally from the metal implant. Frequencies and intensities of metal artifacts were additionally measured and intensity-differences between both reconstructions were compared in different frequencies and distances. Qualitative analysis was performed by two radiologists using a four-point Likert-scale. All measured results from both quantitative and qualitative analysis were then compared between coils and clips. RESULTS: Metal artifact index (MAI) and the intensity of coil-artifacts were significantly lower in SEMAR than in standard CTA in close vicinity to and more distally from the coil-package (p < 0.001, each). MAI and the intensity of clip-artifacts were significantly lower in close vicinity (p = 0.036; p < 0.001, respectively) and more distally from the clip (p = 0.007; p < 0.001, respectively). In patients with coils, SEMAR was significantly superior in all qualitative categories to standard images (p < 0.001), whereas in patients with clips, only artifacts were significantly less (p < 0.05) for SEMAR. CONCLUSION: SEMAR significantly reduces metal artifacts in UHR-CT-angiography images with intracranial implants and improves image quality and diagnostic confidence. SEMAR effects were strongest in patients with coils, whereas the effects were minor in patients with titanium-clips due to the absent of or minimal artifacts.

Ultra-High-Resolution CT of the Head and Neck with Deep Learning Reconstruction-Assessment of Image Quality and Radiation Exposure and Intraindividual Comparison with Normal-Resolution CT.

OBJECTIVES: To assess the benefits of ultra-high-resolution CT (UHR-CT) with deep learning-based image reconstruction engine (AiCE) regarding image quality and radiation dose and intraindividually compare it to normal-resolution CT (NR-CT). METHODS: Forty consecutive patients with head and neck UHR-CT with AiCE for diagnosed head and neck malignancies and available prior NR-CT of a different scanner were retrospectively evaluated. Two readers evaluated subjective image quality using a 5-point Likert scale regarding image noise, image sharpness, artifacts, diagnostic acceptability, and assessability of various anatomic regions. For reproducibility, inter-reader agreement was analyzed. Furthermore, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and slope of the gray-value transition between different tissues were calculated. Radiation dose was evaluated by comparing CTDIvol, DLP, and mean effective dose values. RESULTS: UHR-CT with AiCE reconstruction led to significant improvement in subjective (image noise and diagnostic acceptability: p < 0.000; ICC ≥ 0.91) and objective image quality (SNR: p < 0.000; CNR: p < 0.025) at significantly lower radiation doses (NR-CT 2.03 ± 0.14 mSv; UHR-CT 1.45 ± 0.11 mSv; p < 0.0001) compared to NR-CT. CONCLUSIONS: Compared to NR-CT, UHR-CT combined with AiCE provides superior image quality at a markedly lower radiation dose. With improved soft tissue assessment and potentially improved tumor detection, UHR-CT may add further value to the role of CT in the assessment of head and neck pathologies.

Ultrafast Brain MRI Protocol at 1.5 T Using Deep Learning and Multi-shot EPI.

RATIONALE AND OBJECTIVES: To evaluate clinical feasibility and image quality of a comprehensive ultrafast brain MRI protocol with multi-shot echo planar imaging and deep learning-enhanced reconstruction at 1.5T. MATERIALS AND METHODS: Thirty consecutive patients who underwent clinically indicated MRI at a 1.5 T scanner were prospectively included. A conventional MRI (c-MRI) protocol, including T1-, T2-, T2*-, T2-FLAIR, and diffusion-weighted images (DWI)-weighted sequences were acquired. In addition, ultrafast brain imaging with deep learning-enhanced reconstruction and multi-shot EPI (DLe-MRI) was performed. Subjective image quality was evaluated by three readers using a 4-point Likert scale. To assess interrater agreement, Fleiss' kappa (Ï°) was determined. For objective image analysis, relative signal intensity levels for grey matter, white matter, and cerebrospinal fluid were calculated. RESULTS: Time of acquisition (TA) of c-MRI protocols added up to 13:55 minutes, whereas the TA of DLe-MRI-based protocol added up to 3:04 minutes, resulting in a time reduction of 78%. All DLe-MRI acquisitions yielded diagnostic image quality with good absolute values for subjective image quality. C-MRI demonstrated slight advantages for DWI in overall subjective image quality (c-MRI: 3.93 [+/- 0.25] vs DLe-MRI: 3.87 [+/- 0.37], P = .04) and diagnostic confidence (c-MRI: 3.93 [+/- 0.25] vs DLe-MRI: 3.83 [+/- 3.83], P = .01). For most evaluated quality scores, moderate interobserver agreement was found. Objective image evaluation revealed comparable results for both techniques. CONCLUSION: DLe-MRI is feasible and allows for highly accelerated comprehensive brain MRI within 3minutes at 1.5 T with good image quality. This technique may potentially strengthen the role of MRI in neurological emergencies.

DSA-Based 2D Perfusion Measurements in Delayed Cerebral Ischemia to Estimate the Clinical Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage: A Technical Feasibility Study.

(1) Background: To predict clinical outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH) and delayed cerebral ischemia (DCI) by assessment of the cerebral perfusion using a 2D perfusion angiography (2DPA) time-contrast agent (CA) concentration model. (2) Methods: Digital subtraction angiography (DSA) data sets of n = 26 subjects were acquired and post-processed focusing on changes in contrast density using a time-concentration model at three time points: (i) initial presentation with SAH (T0); (ii) vasospasm-associated acute clinical impairment (T1); and (iii) directly after endovascular treatment (T2) of SAH-associated large vessel vasospasm (LVV), which resulted in n = 78 data sets. Maximum slope (MS in SI/ms), time-to-peak (TTP in ms), and maximum amplitude of a CA bolus (dSI) were measured in brain parenchyma using regions of interest (ROIs). First, acquired parameters were standardized to the arterial input function (AIF) and then statistically analyzed as mean values. Additionally, data were clustered into two subsets consisting of patients with regredient or with stable/progredient symptoms (or Doppler signals) after endovascular treatment (n = 10 vs. n = 16). (3) Results: Perfusion parameters (MS, TTP, and dSI) differed significantly between T0 and T1 (p = 0.003 each). Significant changes between T1 and T2 were only detectable for MS (0.041 ± 0.016 vs. 0.059 ± 0.026; p = 0.011) in patients with regredient symptoms at T2 (0.04 ± 0.012 vs. 0.066 ± 0.031; p = 0.004). For dSI, there were significant differences between T0 and T2 (5095.8 ± 2541.9 vs. 3012.3 ± 968.3; p = 0.001), especially for those with stable symptoms at T2 (5685.4 ± 2967.2 vs. 3102.8 ± 1033.2; p = 0.02). Multiple linear regression analysis revealed that a) the difference in MS between T1 and T2 and b) patient's age (R = 0.6; R2 = 0.34; p = 0.009) strongly predict the modified Rankin Scale (mRS) at discharge. (4) Conclusions: 2DPA allows the direct measurement of treatment effects in SAH associated DCI and may be used to predict outcomes in these critically ill patients.

Clinical feasibility and validation of the accelerated T2 mapping sequence GRAPPATINI in brain imaging.

Rationale and objectives: To prospectively evaluate feasibility and robustness of an accelerated T2 mapping sequence (GRAPPATINI) in brain imaging and to assess its synthetic T2-weighted images (sT2w) in comparison with a standard T2-weighted sequence (T2 TSE). Material and methods: Volunteers were included to evaluate the robustness and consecutive patients for morphological evaluation. They were scanned on a 3 T MR-scanner. Healthy volunteers underwent GRAPPATINI of the brain three times (day 1: scan/rescan; day 2: follow-up). Patients between the ages of 18 and 85 years who were able to provide written informed consent and who had no MRI contraindications were included. For morphological comparison two radiologists with 5 and 7 years of experience in brain MRI evaluated image quality using a Likert scale (1 being poor, 4 being excellent) in a blinded and randomized fashion. Results: Images were successfully acquired in ten volunteers with a mean age of 25 years (ranging from 22 to 31 years) and 52 patients (23 men/29 women) with a mean age of 55 years (range of 22-83 years). Most brain regions showed repeatable and reproducible T2 values (rescan: CoV 0.75%-2.06%, ICC 69%-92.3%; follow-up: CoV 0.41%-1.59%, ICC 79.4%-95.8%), except for the caudate nucleus (rescan: CoV 7.25%, ICC 66.3%; follow-up: CoV 4.78%, ICC 80.9%). Image quality of sT2w was rated inferior to T2 TSE (median for T2 TSE: 3; sT2w: 1-2), but measurements revealed good interrater reliability of sT2w (lesion counting: ICC 0.85; diameter measure: ICC 0.68 and 0.67). Conclusion: GRAPPATINI is a feasible and robust T2 mapping sequence of the brain on intra- and intersubject level. The resulting sT2w depict brain lesions comparable to T2 TSE despite its inferior image quality.

Beyond Glioma: The Utility of Radiomic Analysis for Non-Glial Intracranial Tumors.

The field of radiomics is rapidly expanding and gaining a valuable role in neuro-oncology. The possibilities related to the use of radiomic analysis, such as distinguishing types of malignancies, predicting tumor grade, determining the presence of particular molecular markers, consistency, therapy response, and prognosis, can considerably influence decision-making in medicine in the near future. Even though the main focus of radiomic analyses has been on glial CNS tumors, studies on other intracranial tumors have shown encouraging results. Therefore, as the main focus of this review, we performed an analysis of publications on PubMed and Web of Science databases, focusing on radiomics in CNS metastases, lymphoma, meningioma, medulloblastoma, and pituitary tumors.

Influence of neurovascular anatomy on perforation site in different mouse strains using the filament perforation model for induction of subarachnoid hemorrhage.

BACKGROUND: Filament perforation is a widely-used method to induce subarachnoid hemorrhage (SAH) in mice. Whereas the perforation site has been assumed to be in the branching of middle cerebral artery (MCA) and anterior cerebral artery (ACA), we recently observed more proximal perforations. METHODS: Filament perforation was performed in CD1- (n = 10) and C57Bl/6N-mice (n = 9) ex vivo. The filament was left in place and the perforation site was microscopically assessed. Digital subtraction angiography (DSA) was performed in CD1- (n = 9) and C57Bl/6J-mice (n = 29) and anatomical differences of the internal carotid artery (ICA) were determined. RESULTS: Whereas in C57Bl/6N-mice perforation occurred in the proximal intracranial ICA in 89% (n = 8), in CD1-mice the perforation site was in the proximal ICA in 50% (n = 5), in the branching between MCA and ACA in 40% (n = 4), and in the proximal ACA in 10% (n = 1). DSA revealed a stronger angulation (p<0.001) of the ICA in CD1-mice (163.5±2.81°) compared to C57Bl/6J-mice (124.5±5.49°). Body weight and ICA-angle showed no significant correlation in C57Bl/6J- (r = -0.06, pweight/angle = 0.757) and CD1-mice (r = -0.468, pweight/angle = 0.242). CONCLUSION: Filament perforation in mice occurs not only at the hitherto presumed branching between MCA and ACA, but seems to depend on mouse strain and anatomy as the proximal intracranial ICA may also be perforated frequently.

Intrahematomal Ultrasound Enhances RtPA-Fibrinolysis in a Porcine Model of Intracerebral Hemorrhage.

Catheter-based ultrasound-thrombolysis has been successfully used in a small clinical trial in order to enhance recombinant tissue plasminogen activator (rtPA)-fibrinolysis, for the treatment of spontaneous intracerebral hemorrhages (ICHs). The aim of this study was to investigate the ultra-early effects of ultrasound on hematoma and the surrounding brain tissue in a porcine ICH-model. To achieve this, 21 pigs with a right frontal ICH were randomly assigned to four groups: (1) drainage (n = 3), (2) drainage + rtPA (n = 6), (3) drainage + ultrasound (n = 6), and (4) drainage + ultrasound + rtPA (n = 6). The hematoma volume assessment was performed using cranial MRI before and after the treatments. Subsequently, the brain sections were analyzed using HE-staining and immunohistochemistry. The combined treatment using rtPA and ultrasound led to a significantly higher hematoma reduction (62 ± 5%) compared to the other groups (Group 1: 2 ± 1%; Group 2: 30 ± 12%; Group 3: 18 ± 8% (p < 0.0001)). In all groups, the MRI revealed an increase in diffusion restriction but neither hyper- or hypoperfusion, nor perihematomal edema. HE stains showed perihematomal microhemorrhages were equally distributed in each group, while edema was more pronounced within the control group. Immunohistochemistry did not reveal any ultra-early side effects. The combined therapy of drainage, rtPA and ultrasound is a safe and effective technique for hematoma-reduction and protection of the perihematomal tissue in regard to ultra-early effects.

Modeling Vestibular Compensation: Neural Plasticity Upon Thalamic Lesion.

The present study in rats was conducted to identify brain regions affected by the interruption of vestibular transmission and to explore selected aspects of their functional connections. We analyzed, by positron emission tomography (PET), the regional cerebral glucose metabolism (rCGM) of cortical, and subcortical cerebral regions processing vestibular signals after an experimental lesion of the left laterodorsal thalamic nucleus, a relay station for vestibular input en route to the cortical circuitry. PET scans upon galvanic vestibular stimulation (GVS) were conducted in each animal prior to lesion and at post-lesion days (PLD) 1, 3, 7, and 20, and voxel-wise statistical analysis of rCGM at each PLD compared to pre-lesion status were performed. After lesion, augmented metabolic activation by GVS was detected in cerebellum, mainly contralateral, and in contralateral subcortical structures such as superior colliculus, while diminished activation was observed in ipsilateral visual, entorhinal, and somatosensory cortices, indicating compensatory processes in the non-affected sensory systems of the unlesioned side. The changes in rCGM observed after lesion resembled alterations observed in patients suffering from unilateral thalamic infarction and may be interpreted as brain plasticity mechanisms associated with vestibular compensation and substitution. The second set of experiments aimed at the connections between cortical and subcortical vestibular regions and their neurotransmitter systems. Neuronal tracers were injected in regions processing vestibular and somatosensory information. Injections into the anterior cingulate cortex (ACC) or the primary somatosensory cortex (S1) retrogradely labeled neuronal somata in ventral posteromedial (VPM), posterolateral (VPL), ventrolateral (VL), posterior (Po), and laterodorsal nucleus, dorsomedial part (LDDM), locus coeruleus, and contralateral S1 area. Injections into the parafascicular nucleus (PaF), VPM/VPL, or LDDM anterogradely labeled terminal fields in S1, ACC, insular cortex, hippocampal CA1 region, and amygdala. Immunohistochemistry showed tracer-labeled terminal fields contacting cortical neurons expressing the µ-opioid receptor. Antibodies to tyrosine hydroxylase, serotonin, substance P, or neuronal nitric oxide-synthase did not label any of the traced structures. These findings provide evidence for opioidergic transmission in thalamo-cortical transduction.

Longitudinal imaging and evaluation of SAH-associated cerebral large artery vasospasm in mice using micro-CT and angiography.

Longitudinal in vivo imaging studies characterizing subarachnoid hemorrhage (SAH)-induced large artery vasospasm (LAV) in mice are lacking. We developed a SAH-scoring system to assess SAH severity in mice using micro CT and longitudinally analysed LAV by intravenous digital subtraction angiography (i.v. DSA). Thirty female C57Bl/6J-mice (7 sham, 23 SAH) were implanted with central venous ports for repetitive contrast agent administration. SAH was induced by filament perforation. LAV was assessed up to 14 days after induction of SAH by i.v. DSA. SAH-score and neuroscore showed a highly significant positive correlation (rsp = 0.803, p < 0.001). SAH-score and survival showed a negative significant correlation (rsp = -0.71, p < 0.001). LAV peaked between days 3-5 and normalized on days 7-15. Most severe LAV was observed in the internal carotid (Δmax = 30.5%, p < 0.001), anterior cerebral (Δmax = 21.2%, p = 0.014), middle cerebral (Δmax = 28.16%, p < 0.001) and basilar artery (Δmax = 23.49%, p < 0.001). Cerebral perfusion on day 5 correlated negatively with survival time (rPe = -0.54, p = 0.04). Arterial diameter of the left MCA correlated negatively with cerebral perfusion on day 3 (rPe = -0.72, p = 0.005). In addition, pseudoaneurysms arising from the filament perforation site were visualized in three mice using i.v. DSA. Thus, micro-CT and DSA are valuable tools to assess SAH severity and to longitudinally monitor LAV in living mice.

Identification of High-Risk Atypical Meningiomas According to Semantic and Radiomic Features.

Up to 60% of atypical meningiomas (World Health Organization (WHO) grade II) reoccur within 5 years after resection. However, no clear radiological criteria exist to identify tumors with higher risk of relapse. In this study, we aimed to assess the association of certain radiomic and semantic features of atypical meningiomas in MRI with tumor recurrence. We identified patients operated on primary atypical meningiomas in our department from 2007 to 2017. An analysis of 13 quantitatively defined radiomic and 11 qualitatively defined semantic criteria was performed based on preoperative MRI scans. Imaging characteristics were assessed along with clinical and survival data. The analysis included 76 patients (59% women, mean age 59 years). Complete tumor resection was achieved in 65 (86%) cases, and tumor relapse occurred in 17 (22%) cases. Mean follow-up time was 41.6 (range 3-168) months. Cystic component was significantly associated with tumor recurrence (odds ratio (OR) 21.7, 95% confidence interval (CI) 3.8-124.5) and shorter progression-free survival (33.2 vs. 80.7 months, p < 0.001), whereas radiomic characteristics had no predictive value in univariate analysis. However, multivariate analysis demonstrated significant predictive value of high cluster prominence (hazard ratio (HR) 5.89 (1.03-33.73) and cystic component (HR 20.21 (2.46-166.02)) for tumor recurrence. The combination of radiomic and semantic features might be an effective tool for identifying patients with high-risk atypical meningiomas. The presence of a cystic component in these tumors is associated with a high risk of tumor recurrence.

Pharmacokinetics of the cannabinoid receptor ligand [18 F]MK-9470 in the rat brain - Evaluation of models using microPET.

PURPOSE: The positron emission tomography ligand [18 F]MK-9470 is an inverse agonist that binds reversibly and with high affinity to the cannabinoid type 1 receptor. Due to its slow brain kinetics, care is required in the definition of its dissociation rates from the receptor. The goal of this study was to investigate pharmacokinetic analysis methods using an arterial input function. METHODS: Five Sprague-Dawley rats received injections of 13 to 25 MBq of [18 F]MK-9470 and were scanned over a period of 90 min. Arterial blood samples were collected throughout the scan. Data were analyzed using four different compartmental models: a reversible one-tissue model, reversible two tissue models with and without parameter constraints and an irreversible two-tissue model. The outcome values were goodness of fit measures (Akaike information criterion; standard error), pharmacokinetic modeling parameters (volume of distribution; irreversible uptake constant) and intersubject variability. RESULTS: Goodness of fit measures indicated that the experimental data are more adequately described by a two-tissue model than a one-tissue model. Differences in mean Akaike information criterion values between all two-tissue models were < 5%. Mean standard errors of model parameters were lowest for the irreversible model (range: 1% to 6%). The irreversible model delivered plausible results for all animals that were less variable compared to results of the other two-tissue models. CONCLUSIONS: A reversible two-tissue model may not deliver stable results for all animals and regions within a 90-min microPET study protocol. Stable parameters for all animals and regions are obtained when an irreversible model is used. If the acquisition time of the experiment is limited, an irreversible model provides a consistent distribution of composite outcome parameters, suggesting its suitability for use in future studies.

Cortex-wide BOLD fMRI activity reflects locally-recorded slow oscillation-associated calcium waves.

Spontaneous slow oscillation-associated slow wave activity represents an internally generated state which is characterized by alternations of network quiescence and stereotypical episodes of neuronal activity - slow wave events. However, it remains unclear which macroscopic signal is related to these active periods of the slow wave rhythm. We used optic fiber-based calcium recordings of local neural populations in cortex and thalamus to detect neurophysiologically defined slow calcium waves in isoflurane anesthetized rats. The individual slow wave events were used for an event-related analysis of simultaneously acquired whole-brain BOLD fMRI. We identified BOLD responses directly related to onsets of slow calcium waves, revealing a cortex-wide BOLD correlate: the entire cortex was engaged in this specific type of slow wave activity. These findings demonstrate a direct relation of defined neurophysiological events to a specific BOLD activity pattern and were confirmed for ongoing slow wave activity by independent component and seed-based analyses.

Resection of C6 gliomas in rats with the aid of the waterjet technique.

OBJECTIVES: While clinically the safety and efficacy of waterjet resection of brain tumors have been shown, evidence that waterjet dissection improves tumor resection radicality in comparison with conventional techniques is still missing. In the present study, resection radicality and tumor-free long-term survival of both techniques were evaluated in a C6-glioma model. MATERIAL AND METHODS: Fifty-thousand C6-glioma cells were stereotactically transplanted in the left frontal lobe of 100 male Sprague-Dawley rats. After MRI-scanning for evaluation of tumor extension, microsurgical tumor resection was performed with conventional techniques (n=50) or with the waterjet dissector at pressures of 6bar (n=50). Twenty-five animals of each group were sacrificed after surgery for histological analysis. For analysis of survival after tumor resection, twenty-five animals of each group were followed-up to analyze tumor-free survival using the Kaplan Meier method. RESULTS: In the waterjet group, the resection cavity was free of C6-tumor cells in 10/25 (40%) rats showing a trend (p=0.3) towards better resection radicality compared to the rats that were treated conventionally (7/10; 28%). R1-resection with up to 250C6 cells/object slice was found in 14/25 (56%) rats after waterjet dissection compared to 6/25 (24%) rats treated conventionally showing significance (p<0.01). Probability of survival was 38% after 2 weeks and 20% after 6 months in the waterjet group compared to 30% and 16% respectively in the conventional group. Diffuse tumor cell spreading with possible influence on survival was shown in 47/50 rats. CONCLUSION: In this experimental model, waterjet tumor resection did reveal significantly better resection radicality compared to the conventional technique. Although a direct transfer of these results to human glioma surgery is prohibited, the waterjet technique might contribute to the best possible resection radicality in human gliomas. Nevertheless, tumor cell spreading remains a major problem. Further studies have to address that the surgical results - in deed - improve the postoperative outcome.