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Ambient inhalable particulate matter (PM) is a serious health concern worldwide, but especially so in China where high PM concentrations affect huge populations. Atmospheric processes and emission sources cause spatial and temporal variations in PM concentration and chemical composition, but their influence on the toxicological characteristics of PM are still inadequately understood.In this study, we report an extensive chemical and toxicological characterization of size-segregated urban air inhalable PM collected in August and October 2013 from Nanjing, and assess the effects of atmospheric processes and likely emission sources. A549 human alveolar epithelial cells were exposed to day- and nighttime PM samples (25, 75, 150, 200, 300 mu g/ml) followed by analyses of cytotoxicity, genotoxicity, cell cycle, and inflammatory response.PM10-2.5 and PM0.2 caused the greatest toxicological responses for different endpoints, illustrating that particles with differing size and chemical composition activate distinct toxicological pathways in A549 cells. PM10-2.5 displayed the greatest oxidative stress and genotoxic responses; both were higher for the August samples compared with October. In contrast, PM0.2 and PM2.5-1.0 samples displayed high cytotoxicity and substantially disrupted cell cycle; August samples were more cytotoxic whereas October samples displayed higher cell cycle disruption. Several components associated with combustion, traffic, and industrial emissions displayed strong correlations with these toxicological responses. The lower responses for PM1.0-0.2 compared to PM0.2 and PM2.5-1.0 indicate diminished toxicological effects likely due to aerosol aging and lower proportion of fresh emission particles rich in highly reactive chemical components in the PM1.0-0.2 fraction.Different emission sources and atmospheric processes caused variations in the chemical composition and toxicological responses between PM fractions, sampling campaigns, and day and night. The results indicate different toxicological pathways for coarse-mode particles compared to the smaller particle fractions with typically higher content of combustion-derived components. The variable responses inside PM fractions demonstrate that differences in chemical composition influence the induced toxicological responses.

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.

Highlights • Both the 2D and 3D handheld MSOT systems hold promise for clinical translation. • The 2D MSOT handheld probe provides high resolution, sensitivity, accuracy and reliability. • The 3D MSOT handheld probe adds unique 3D capabilities and shortens imaging time., 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.

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., Highlights • Somatotopic CST tractography was done in 32 patients with eloquent brain tumours. • Seeding ROIs were defined by navigated TMS of the M1 hot spot (hand, foot, tongue). • Using the anterior pons as a second ROI yielded more plausible tracts than the PLIC. • Low FAT and oedema of the internal capsule were negative predictors.

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.

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, Highlights • Somatotopic DTI-tractography in 18 patients with motor-eloquent brain tumours • Comparing functional MRI versus navigated TMS for localization of seeding region • Use of nTMS yield more plausible CST tractographies in close tumour vicinity. • More rostral course of TMS-originated fibres as compared to functional MRI

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.

Introduction Imaging of the course of the corticospinal tract (CST) by diffusion tensor imaging (DTI) is useful for function-preserving tumour surgery especially of gliomas infiltrating the white matter. The integration of functional data such as navigated transcranial magnetic stimulation (nTMS) for the delineation of starting ROIs has improved the fibre tracking results in a multiple-ROI approach. However, alterations of MRI signals in and adjacent to brain tumours often lead to spurious tracking results. Parameters such as the minimal fibre track length (MFL) and the fractional anisotropy threshold (FAT) may reflect an unfavourable signal-to-noise ratio and, thus, the risk for non-plausible tractography results. Methods The CST of 32 patients with intracranial tumours was investigated by deterministic DTI (iPlanNet) and 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 anterior inferior pontine region (aiP). The plausibility of the fibre trajectories was assessed by a-priori defined anatomical criteria by two independent raters. As potential co-factors i.a. the FAT and the MFL were analysed. Results Low FAT values (cut-off of 0.105) and long MFL (cut-off 121.5 mm) led to less plausible fibre tracking results ( Figure ). 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. Conclusions In summary, we found excellent plausibility rates using a deterministic multiple-ROI approach with a cortical, nTMS-derived ROI and an additional ROI in the anterior pontine region. However, due to the technical limitations of the method, the results should always be interpreted with caution, especially when dealing with the FAT values lower than 0.105 or the MFL exceeding 121.5 mm.

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.

INTRODUCTION: Imaging of the course of the corticospinal tract (CST) by diffusion tensor imaging (DTI) is useful for function-preserving tumour surgery especially of gliomas infiltrating the white matter. The integration of functional data such as functional MRI (fMRI) or navigated transcranial magnetic stimulation (nTMS) for the delineation of starting Regions of Interest (ROI) can improve the fibre tracking results in a multiple-ROI approach. Here, both functional localizer methods are compared for the plausibility of the resulting fibre course. METHODS: 32 patients with intracerebral tumours were allocated to the prospective study. The cortical seeding ROIs were defined by the nTMS hot-spots or by the fMRI local-activation-maximum representing the primary motor area (M1) of the hand, the foot and the tongue. The CST originating from the contralesional M1 hand area was mapped as intra-individual reference. As subcortical ROI, we used the anterior inferior pontine region (aiP). The plausibility of the fibre trajectories was assessed by a-priori defined anatomical criteria by two independent raters. As potential co-factors i.a. the franctional anisotropy threshold (FAT) was analysed. RESULTS: Both methods revealed excellent plausibility results for the contralesional hand-CST (100%). NTMS seems to be favourable to construct the hand-CST on the lesional side (NTMS/fMRI: 97%/81%) whereas no significant difference could be observed for the foot- and the tongue-CST. Plausibility rates were significantly deteriorated at low FAT values (ROC-cut-off: FAT = 0.105) for both nTMS- and fMRI-derived CST (p < 0.001). The interrater reliability was excellent (Cohen's k = 0.96). CONCLUSIONS: In summary, we found excellent plausibility rates using a deterministic multiple-ROI approach with a cortical ROI defined by functional localizer methods. In comparison, nTMS was advantageous for the hand-CST tractography whereas both localizer methods revealed adequate results for the foot- and the tongue-CST. In general, tractography results at FAT lower than 0.105 should be interpreted with particular caution.