Dual-Modality Surface-Enhanced Resonance Raman Scattering and Multispectral Optoacoustic Tomography Nanoparticle Approach for Brain Tumor Delineation.

Difficulty in visualizing glioma margins intraoperatively remains a major issue in the achievement of gross total tumor resection and, thus, better clinical outcome of glioblastoma (GBM) patients. Here, the potential of a new combined optical + optoacoustic imaging method for intraoperative brain tumor delineation is investigated. A strategy using a newly developed gold nanostar synthesis method, Raman reporter chemistry, and silication method to produce dual-modality contrast agents for combined surface-enhanced resonance Raman scattering (SERRS) and multispectral optoacoustic tomography (MSOT) imaging is devised. Following intravenous injection of the SERRS-MSOT-nanostars in brain tumor bearing mice, sequential MSOT imaging is performed in vivo and followed by Raman imaging. MSOT is able to accurately depict GBMs three-dimensionally with high specificity. The MSOT signal is found to correlate well with the SERRS images. Because SERRS enables uniquely sensitive high-resolution surface detection, it could represent an ideal complementary imaging modality to MSOT, which enables real-time, deep tissue imaging in 3D. This dual-modality SERRS-MSOT-nanostar contrast agent reported here is shown to enable high precision depiction of the extent of infiltrating GBMs by Raman- and MSOT imaging in a clinically relevant murine GBM model and could pave new ways for improved image-guided resection of brain tumors.

Aggressive treatment of cerebral venous sinus thrombosis (CVT) with stent retrievers and local thrombolysis: why we need a registry.

Purpose Anticoagulation is the first-line therapy for cerebral venous sinus thrombosis (CVT). Endovascular treatment is increasingly applied in patients deteriorating despite anticoagulation with extensive thrombosis or contraindications for anticoagulation. Experience with stent retrievers in CVT is limited. Results We present three cases of severe CVT treated with stent-retrievers, thrombus aspiration and local thrombolysis. In two patients with extensive thrombosis, a partial recanalization was achieved, but only one of them showed significant improvement. Despite failed recanalization, the third patient recovered completely. Conclusions Limited experience with three cases indicates that recanalization may not necessarily result in favourable clinical outcome even in severely affected patients. Therefore, invasive procedures such as local thrombolysis and thrombectomy remain individual therapeutic options when anticoagulation fails and in patients with extensive thrombosis.

Lymph Node Micrometastases and In-Transit Metastases from Melanoma: In Vivo Detection with Multispectral Optoacoustic Imaging in a Mouse Model.

Purpose To study whether multispectral optoacoustic tomography (MSOT) can serve as a label-free imaging modality for the detection of lymph node micrometastases and in-transit metastases from melanoma on the basis of the intrinsic contrast of melanin in comparison to fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT). Materials and Methods The study was approved by the institutional animal care and use committee. Sequential MSOT was performed in a mouse B16F10 melanoma limb lymph node metastasis model (n = 13) to survey the development of macro-, micro- and in-transit metastases (metastases that are in transit from the primary tumor site to the local nodal basin) in vivo. The in vitro limit of detection was assessed in a B16F10 cell phantom. Signal specificity was determined on the basis of a simultaneous lymphadenitis (n = 4) and 4T1 breast cancer lymph metastasis (n = 2) model. MSOT was compared with intravenous FDG PET/CT. The diagnosis was assessed with histologic examination. Differences in the signal ratio (metastatic node to contralateral limb) between the two modalities were determined with the two-tailed paired t test. Results The mean signal ratios acquired with MSOT in micrometastases (2.5 ± 0.3, n = 6) and in-transit metastases (8.3 ± 5.8, n = 4) were higher than those obtained with FDG PET/CT (1.1 ± 0.5 [P < .01] and 1.3 ± 0.6 [P < .05], respectively). MSOT was able to help differentiate even small melanoma lymph node metastases from the other lymphadenopathies (P < .05 for both) in vivo, whereas FDG PET/CT could not (P > .1 for both). In vitro, the limit of detection was at an approximate cell density of five cells per microliter (P < .01). Conclusion MSOT enabled detection of melanoma lymph node micrometastases and in-transit metastases undetectable with FDG PET/CT and helped differentiate melanoma metastasis from other lymphadenopathies. (©) RSNA, 2016 Online supplemental material is available for this article.

Mechanical Thrombectomy of M2-Occlusion.

BACKGROUND: There is growing evidence for the efficacy of mechanical thrombectomy in acute stroke patients with large-vessel occlusions in the anterior circulation. Although distal occlusions of the middle cerebral artery (MCA) can cause severe clinical symptoms, endovascular therapy is not considered here as the first choice. The aim of our study was to prove the efficacy and safety of mechanical thrombectomy for distal occlusion types in the anterior circulation (M2-segment). METHODS: Stentretriever-based thrombectomy was performed in 119 patients with acute MCA occlusions between October 2011 and April 2013: 104 (87.4%) were M1- and 15 (12.6%) M2-occlusions. These groups were compared with regard to recanalization success, periprocedural complications, hemorrhage, and modified Rankin Scale (mRS) at 90 days. RESULTS: Thrombolysis in cerebral infarction 2b/3 reperfusion was more frequent in M2- than in M1-occlusions (93.3% versus 76.0%; P = .186). There was no significant difference in the mean National Institutes of Health Stroke Scale between the M1- and the M2-group both at admission and at discharge (16.18 ± 7.30 versus 13.73 ± 8.30, P = .235; 9.36 ± 8.60 versus 7.43 ± 9.84, P = .446). A good clinical outcome (mRS 0-2) at 3 months was more frequent in the M2-group (60% versus 43.3%; P = .273) and mortality was higher in the M1-group (21.2% versus 6.7%; P = .297). There were 3 periprocedural complications in the M1- and none in the M2-group. CONCLUSIONS: Endovascular treatment of M2-occlusions in severely affected patients is not associated with a higher procedural risk or postprocedural hemorrhage. Compared with M1-occlusions, there was a greater chance for a good angiographic and clinical result in our case series. Therefore, stentretriever-based thrombectomy should also be considered for patients with severe symptoms because of an acute M2-occlusion.

The phenox clot retriever as part of a multimodal mechanical thrombectomy approach in acute ischemic stroke: single center experience in 56 patients.

Purpose. We analyzed our experience with the phenox clot retriever as part of a multimodal mechanical thrombectomy (MTE) approach in acute ischemic stroke. Methods. 56 patients were treated by MTE with the phenox clot retriever alone or in combination with other modalities. Results. Overall we achieved TICI 2b/3 reperfusion rates of 61,9%. In multimodally treated patients we achieved reperfusion rates of 72,8%. There were 3 (5,5%) severe adverse events, all symptomatic intracranial hemorrhages. The mean angio to reperfusion times (ART) were 74 minutes for phenox-only procedures and 51 minutes for multimodal procedures. A chronological analysis showed a reduction of ART from 70,5 to 49,4 minutes and an increase of TICI 2b/3 recanalizations from 53,8% to 81,8%. Throughout the observation period there was a significant shift towards multimodal procedures with simultaneous increase of TICI 2b/3 reperfusions. Both effects are partially attributable to our institutional learning curve. NIHSS improvement could be seen in 54% (n = 28) overall and in 73% (n = 15) of MCA recanalizations. Conclusions. The phenox clot retriever is a safe and effective tool for MTE in acute stroke patients, with faster and better reperfusion results when used as part of a multimodal strategy. Clinical improvement is more frequent in MCA recanalizations.

Intracranial Rescue Stent Angioplasty After Stent-Retriever Thrombectomy : Multicenter Experience.

PURPOSE: Stent-retriever thrombectomy (SRT) for acute intracranial large artery occlusion (LAO) may not result in permanent recanalization in rare cases, e.g. due to an underlying stenosis or dissection. In this specific patient group, rescue stent angioplasty (RSA) may be the only treatment option to achieve permanent vessel patency and potentially a good clinical outcome. To date, the experience with RSA is limited. METHODS: In this retrospective analysis, interventional and clinical data of patients with acute intracranial LAO of the anterior and posterior circulation who underwent RSA after SRT due to an underlying lesion between 2012-2017 in four neurovascular centers were studied. RESULTS: In this study 34 patients (mean age 67 years) were included whereby 18 patients had anterior circulation LAO and 16 patients posterior circulation LAO. The SRT maneuver count ranged between 1 and 15 (median 2). Indications for RSA were an immediate re-occlusion in 25 (74%), and a persistent high-grade stenosis in 9 patients (26%). The RSA was technically feasible in 33 patients (97%). A mTICI 2b/3 result was obtained in 26 patients (76%). Median onset-to-recanalization time was 248 min (range 80-650 min). After 3 months 10/34 patients (29%) had a good clinical outcome (modified Rankin Scale, mRS 0-2). In detail, 4/18 patients (22%) with anterior circulation LAO and 6/16 patients (38%) with posterior circulation LAO were functionally independent. CONCLUSION: The use of RSA can be considered for acute intracranial LAO in cases with immediate re-occlusion or high-grade stenosis after SRT alone.

Dynamic 18F-FDG PET Lymphography for In Vivo Identification of Lymph Node Metastases in Murine Melanoma.

Positron lymphography using 18F-FDG followed by Cerenkov-guided resection of lymph nodes in healthy mice has previously been introduced by our group. Our aim in this study was to further assess the technique's potential beyond merely localizing sentinel lymph nodes. We now aimed to evaluate the potential of positron lymphography to characterize the nodes with respect to their tumor status in order to identify metastatic lymph nodes. We explored whether metastatic nodes could be distinguished from normal nodes via dynamic 18F-FDG lymphography, to then be resected under Cerenkov imaging guidance. Methods: A murine melanoma cell line highly metastatic to lymph nodes (B16F10) was implanted subcutaneously on the dorsal hind paw of C57 mice while the tumor-free contralateral leg served as an intraindividual control. A model of reactive lymph nodes after concanavalin A challenge served as an additional control to provide nonmalignant inflammatory lymphadenopathy. Dynamic PET/CT imaging was performed immediately after injection of 18F-FDG around the tumor or intracutaneously in the contralateral footpad. Furthermore, PET/CT and Cerenkov studies were performed repeatedly over time to follow the course of metastatic spread. In selected mice, popliteal lymph nodes underwent Cerenkov luminescence imaging. Hematoxylin and eosin staining was done to verify the presence of lymphatic melanoma infiltration. Results: Positron lymphography using 18F-FDG was successfully performed on tumor-bearing and non-tumor-bearing mice, as well as on controls bearing sites of inflammation; the results clearly identified the sentinel lymph node basin and delineated the lymphatic drainage. Significantly prolonged retention of activity was evident in metastatic nodes as compared with controls without tumor. On the basis of these results, the contrast in detection and identification of metastatic lymph nodes was distinct and could be used for guided lymph node resection, such as by using Cerenkov luminescence imaging. However, retention after 18F-FDG lymphography was also seen in acute inflammatory lymphadenopathy. Conclusion: In a tumor model, significantly longer retention of the radiotracer during 18F-FDG lymphography was seen in metastatic than nonmetastatic lymph nodes, allowing for differentiation between the two and for selective resection of tumor-bearing nodes using Cerenkov imaging. Inflammation can be better differentiated in a subacute state.

Functional MRI vs. navigated TMS to optimize M1 seed volume delineation for DTI tractography. A prospective study in patients with brain tumours adjacent to the corticospinal tract.

BACKGROUND: DTI-based tractography is an increasingly important tool for planning brain surgery in patients suffering from brain tumours. However, there is an ongoing debate which tracking approaches yield the most valid results. Especially the use of functional localizer data such as navigated transcranial magnetic stimulation (nTMS) or functional magnetic resonance imaging (fMRI) seem to improve fibre tracking data in conditions where anatomical landmarks are less informative due to tumour-induced distortions of the gyral anatomy. We here compared which of the two localizer techniques yields more plausible results with respect to mapping different functional portions of the corticospinal tract (CST) in brain tumour patients. METHODS: The CSTs of 18 patients with intracranial tumours in the vicinity of the primary motor area (M1) were investigated by means of deterministic DTI. The core zone of the tumour-adjacent hand, foot and/or tongue M1 representation served as cortical regions of interest (ROIs). M1 core zones were defined by both the nTMS hot-spots and the fMRI local activation maxima. In addition, for all patients, a subcortical ROI at the level of the inferior anterior pons was implemented into the tracking algorithm in order to improve the anatomical specificity of CST reconstructions. As intra-individual control, we additionally tracked the CST of the hand motor region of the unaffected, i.e., non-lesional hemisphere, again comparing fMRI and nTMS M1 seeds. The plausibility of the fMRI-ROI- vs. nTMS-ROI-based fibre trajectories was assessed by a-priori defined anatomical criteria. Moreover, the anatomical relationship of different fibre courses was compared regarding their distribution in the anterior-posterior direction as well as their location within the posterior limb of the internal capsule (PLIC). RESULTS: Overall, higher plausibility rates were observed for the use of nTMS- as compared to fMRI-defined cortical ROIs (p < 0.05) in tumour vicinity. On the non-lesional hemisphere, however, equally good plausibility rates (100%) were observed for both localizer techniques. fMRI-originated fibres generally followed a more posterior course relative to the nTMS-based tracts (p < 0.01) in both the lesional and non-lesional hemisphere. CONCLUSION: NTMS achieved better tracking results than fMRI in conditions when the cortical tract origin (M1) was located in close vicinity to a brain tumour, probably influencing neurovascular coupling. Hence, especially in situations with altered BOLD signal physiology, nTMS seems to be the method of choice in order to identify seed regions for CST mapping in patients.

Performance of a Multispectral Optoacoustic Tomography (MSOT) System equipped with 2D vs. 3D Handheld Probes for Potential Clinical Translation.

A handheld approach to optoacoustic imaging is essential for the clinical translation. The first 2- and 3-dimensional handheld multispectral optoacoustic tomography (MSOT) probes featuring real-time unmixing have recently been developed. Imaging performance of both probes was determined in vitro and in a brain melanoma metastasis mouse model in vivo. T1-weighted MR images were acquired for anatomical reference. The limit of detection of melanoma cells in vitro was significantly lower using the 2D than the 3D probe. The signal decrease was more profound in relation to depth with the 3D versus the 2D probe. Both approaches were capable of imaging the melanoma tumors qualitatively at all time points. Quantitatively, the 2D approach enabled closer anatomical resemblance of the tumor compared to the 3D probe, particularly at depths beyond 3 mm. The 3D probe was shown to be superior for rapid 3D imaging and, thus, holds promise for more superficial target structures.

Improved nTMS- and DTI-derived CST tractography through anatomical ROI seeding on anterior pontine level compared to internal capsule.

Imaging of the course of the corticospinal tract (CST) by diffusion tensor imaging (DTI) is useful for function-preserving tumour surgery. The integration of functional localizer data into tracking algorithms offers to establish a direct structure-function relationship in DTI data. However, alterations of MRI signals in and adjacent to brain tumours often lead to spurious tracking results. We here compared the impact of subcortical seed regions placed at different positions and the influences of the somatotopic location of the cortical seed and clinical co-factors on fibre tracking plausibility in brain tumour patients. The CST of 32 patients with intracranial tumours was investigated by means of deterministic DTI and neuronavigated transcranial magnetic stimulation (nTMS). The cortical seeds were defined by the nTMS hot spots of the primary motor area (M1) of the hand, the foot and the tongue representation. The CST originating from the contralesional M1 hand area was mapped as intra-individual reference. As subcortical region of interests (ROI), we used the posterior limb of the internal capsule (PLIC) and/or the anterior inferior pontine region (aiP). The plausibility of the fibre trajectories was assessed by a-priori defined anatomical criteria. The following potential co-factors were analysed: Karnofsky Performance Scale (KPS), resting motor threshold (RMT), T1-CE tumour volume, T2 oedema volume, presence of oedema within the PLIC, the fractional anisotropy threshold (FAT) to elicit a minimum amount of fibres and the minimal fibre length. The results showed a higher proportion of plausible fibre tracts for the aiP-ROI compared to the PLIC-ROI. Low FAT values and the presence of peritumoural oedema within the PLIC led to less plausible fibre tracking results. Most plausible results were obtained when the FAT ranged above a cut-off of 0.105. In addition, there was a strong effect of somatotopic location of the seed ROI; best plausibility was obtained for the contralateral hand CST (100%), followed by the ipsilesional hand CST (>95%), the ipsilesional foot (>85%) and tongue (>75%) CST. In summary, we found that the aiP-ROI yielded better tracking results compared to the IC-ROI when using deterministic CST tractography in brain tumour patients, especially when the M1 hand area was tracked. In case of FAT values lower than 0.10, the result of the respective CST tractography should be interpreted with caution with respect to spurious tracking results. Moreover, the presence of oedema within the internal capsule should be considered a negative predictor for plausible CST tracking.

Structural and Functional Magnetic Resonance Imaging: Mild Cognitive Impairment and Alzheimer Disease.

Magnetic resonance (MR) imaging is playing an increasingly pivotal role in the clinical management of dementia, including Alzheimer disease (AD). In addition to established MR imaging procedures, the introduction of advanced instrumentation such as 7-T MR imaging, as well as novel MR imaging sequences such as arterial spin labeling, MR spectroscopy, diffusion tensor imaging, and resting-state functional MR imaging, may open new pathways toward improved diagnosis of AD even in early stages of disease such as mild cognitive impairment (MCI). This article describes the typical findings of established and new MR imaging procedures in healthy aging, MCI, and AD.