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In RRMS, AHR ligand levels were globally decreased and associated with disease duration and neurologic disability. In SPMS and PPMS, serum AHR agonistic activity was decreased and correlated with disease severity. Finally, in longitudinal serum samples of patients with RRMS, decreased AHR agonistic activity was linked to progressive CNS atrophy and increased lesion load.<br /><br /> These findings suggest that serum AHR agonist levels negatively correlate with disability in RRMS and PMS and decrease longitudinally in correlation with MRI markers of disease progression. Thus, serum AHR agonistic activity may serve as novel biomarker for disability progression in MS.<br /><br />These findings suggest that serum AHR agonist levels negatively correlate with disability in RRMS and PMS and decrease longitudinally in correlation with MRI markers of disease progression. Thus, serum AHR agonistic activity may serve as novel biomarker for disability progression in MS.Glioblastoma is a lethal brain tumor that exhibits heterogeneity and resistance to therapy. Our understanding of tumor homeostasis is limited by a lack of genetic tools to selectively identify tumor states and fate transitions. Here, we use glioblastoma subtype signatures to construct synthetic genetic tracing cassettes and investigate tumor heterogeneity at cellular and molecular levels, in vitro and in vivo. Through synthetic locus control regions, we demonstrate that proneural glioblastoma is a hardwired identity, whereas mesenchymal glioblastoma is an adaptive and metastable cell state driven by proinflammatory and differentiation cues and DNA damage, but not hypoxia. Importantly, we discovered that innate immune cells divert glioblastoma cells to a proneural-to-mesenchymal transition that confers therapeutic resistance. Our synthetic genetic tracing methodology is simple, scalable, and widely applicable to study homeostasis in development and diseases. In glioblastoma, the method causally links distinct (micro)environmental, genetic, and pharmacologic perturbations and mesenchymal commitment. SIGNIFICANCE Glioblastoma is heterogeneous and incurable. Here, we designed synthetic reporters to reflect the transcriptional output of tumor cell states and signaling pathways' activity. This method is generally applicable to study homeostasis in normal tissues and diseases. In glioblastoma, synthetic genetic tracing causally connects cellular and molecular heterogeneity to therapeutic responses.This article is highlighted in the In This Issue feature, p. 521.Analogous to hearing restoration via cochlear implants, vestibular function could be restored via vestibular implants that electrically stimulate vestibular nerve branches to encode head motion. This study presents the technical feasibility and first imaging results of CT for vestibular implants in 8 participants of the first-in-human Multichannel Vestibular Implant Early Feasibility Study. Imaging characteristics of 8 participants (3 men, 5 women; median age, 59.5 years; range, 51-66 years) implanted with a Multichannel Vestibular Implant System who underwent a postimplantation multislice CT (n = 2) or flat panel CT (n = 6) are reported. The device comprises 9 platinum electrodes inserted into the ampullae of the 3 semicircular canals and 1 reference electrode inserted in the common crus. Electrode insertion site, positions, length and angle of insertion, and number of artifacts were assessed. Individual electrode contacts were barely discernible in the 2 participants imaged using multislice CT. Electrode and osseous structures were detectable but blurred so that only 12 of the 18 stimulating electrode contacts could be individually identified. Flat panel CT could identify all 10 electrode contacts in all 6 participants. The median reference electrode insertion depth angle was 9° (range, -57.5° to 45°), and the median reference electrode insertion length was 42 mm (range, -21-66 mm). Flat panel CT of vestibular implants produces higher-resolution images with fewer artifacts than multidetector row CT, allowing visualization of individual electrode contacts and quantification of their locations relative to vestibular semicircular canals and ampullae. As multichannel vestibular implant imaging improves, so will our understanding of the relationship between electrode placement and vestibular performance.<br /><br /> Efficient detection of metastases is important for patient' treatment. This prospective study was to explore the clinical value of contrast-enhanced T2 FLAIR in imaging brain metastases using half-dose gadobenate dimeglumine.<br /><br /> In vitro signal intensity of various gadolinium concentrations was explored by spin-echo T1-weighted imaging and T2 FLAIR. Then, 46 patients with lung cancer underwent nonenhanced T2 FLAIR before administration of half-dose gadobenate dimeglumine and 3 consecutive contrast-enhanced T2 FLAIR sequences followed by 1 spin-echo T1WI after administration of half-dose gadobenate dimeglumine. After an additional dose of 0.05 mmol/kg, 3D brain volume imaging was performed. All brain metastases were classified as follows solid-enhancing, ≥ 5 mm (group A); ring-enhancing, ≥ 5 mm (group B); and lesion diameter of &lt;5 mm (group C). The contrast ratio of the lesions on 3 consecutive phases of contrast-enhanced T2 FLAIR was measured, and the percentage increase of contrast-enhanced T2 FLAIR among the 3 groups was compared.<br /><br /> In vitro, the maximal signal intensity was achieved in T2 FLAIR at one-eighth to one-half of the contrast concentration needed for maximal signal intensity in T1WI. In vivo, the mean contrast ratio values of metastases on contrast-enhanced T2 FLAIR for the 3 consecutive phases ranged from 63.64% to 83.05%. The percentage increase (PI) values of contrast-enhanced T2 FLAIR were as follows PI<br /><br /> &lt; PI<br /><br /> (<br /><br /> = .001) and PI<br /><br /> &lt; PI<br /><br /> (<br /><br /> &lt; .001). [https://www.selleckchem.com/products/z-devd-fmk.html ZDEVDFMK] The degree of enhancement of brain metastases on contrast-enhanced T2 FLAIR was lower than on 3D brain volume imaging (<br /><br /> &lt; .001) in group A, and higher than on 3D brain volume imaging (<br /><br /> &lt; .001) in group C.<br /><br /> Small or ring-enhancing metastases can be better visualized on delayed contrast-enhanced T2 FLAIR using a half-dose high-relaxivity contrast agent.<br /><br />Small or ring-enhancing metastases can be better visualized on delayed contrast-enhanced T2 FLAIR using a half-dose high-relaxivity contrast agent.<br /><br /> The optimal treatment for symptomatic nonacute intracranial ICA occlusion is uncertain, and endovascular recanalization remains a technical challenge. Our purpose was to report multicenter clinical results of endovascular recanalization for medically refractory, nonacute, intracranial ICA occlusion and to propose a new angiographic classification to explore which subgroups of patients are most amenable to this treatment.<br /><br /> From January 2015 to December 2019, thirty-six consecutive patients who underwent endovascular recanalization for refractory, nonacute, atherosclerotic intracranial ICA occlusion at 3 stroke centers were analyzed retrospectively. The patients were divided into 3 types according to an angiographic classification. Rates of technical success, periprocedural complications, and any stroke or death within 30 days along with follow-up results were evaluated.<br /><br /> The overall technical success rate was 80.6% (29/36), and the rate of any stroke or death within 30 days was 16.7% (6/36). The recanalizaangiographic classification proposed is conducive to the selection of suitable patients and difficulty in grading.<br /><br /> Aneurysm wall enhancement has been proposed as a biomarker for inflammation and instability. However, the mechanisms of aneurysm wall enhancement remain unclear. We used 7T MR imaging to determine the effect of flow in different regions of the wall.<br /><br /> Twenty-three intracranial aneurysms imaged with 7T MR imaging and 3D angiography were studied with computational fluid dynamics. Local flow conditions were compared between aneurysm wall enhancement and nonenhanced regions. Aneurysm wall enhancement regions were subdivided according to their location on the aneurysm and relative to the inflow and were further compared.<br /><br /> On average, wall shear stress was lower in enhanced than in nonenhanced regions (<br /><br /> = .05). Aneurysm wall enhancement regions at the neck had higher wall shear stress gradients (<br /><br /> = .05) with lower oscillations (<br /><br /> = .05) than nonenhanced regions. In contrast, aneurysm wall enhancement regions at the aneurysm body had lower wall shear stress (<br /><br /> = .01) and wall shear stress gradients (<br /><br /> = .008) taneurysm wall enhancement seems to depend on the location of the region on the aneurysm sac. Regions at the neck and close to the inflow tend to be exposed to higher wall shear stress and wall shear stress gradients. Regions at the body, dome, or far from the inflow tend to be exposed to uniformly low wall shear stress and have more aneurysm wall enhancement.<br /><br /> Intracranial hemorrhage (ICH) is an important event that is diagnosed on head NCCT. Increased NCCT utilization in busy hospitals may limit timely identification of ICH. RAPID ICH is an automated hybrid 2D-3D convolutional neural network application designed to detect ICH that may allow for expedited ICH diagnosis. We determined the accuracy of RAPID ICH for ICH detection and ICH volumetric quantification on NCCT.<br /><br /> NCCT scans were evaluated for ICH by RAPID ICH. Consensus detection of ICH by 3 neuroradiology experts was used as the criterion standard for RAPID ICH comparison. ICH volume was also automatically determined by RAPID ICH in patients with intraparenchymal or intraventricular hemorrhage and compared with manually segmented ICH volumes by a single neuroradiology expert. ICH detection accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratios by RAPID ICH were determined.<br /><br /> We included 308 studies. RAPID ICH correctly identified 151/158 ICH cases and 143/150 ICH-negative cases, which resulted in high sensitivity (0.956, CI 0.911-0.978), specificity (0.953, CI 0.907-0.977), positive predictive value (0.956, CI 0.911-0.978), and negative predictive value (0.953, CI 0.907-0.977) for ICH detection. The positive likelihood ratio (20.479, CI 9.928-42.245) and negative likelihood ratio (0.046, CI 0.023-0.096) for ICH detection were similarly favorable. RAPID ICH volumetric quantification for intraparenchymal and intraventricular hemorrhages strongly correlated with expert manual segmentation (correlation coefficient <br /><br />  = 0.983); the median absolute error was 3 mL.<br /><br /> RAPID ICH is highly accurate in the detection of ICH and in the volumetric quantification of intraparenchymal and intraventricular hemorrhages.<br /><br />RAPID ICH is highly accurate in the detection of ICH and in the volumetric quantification of intraparenchymal and intraventricular hemorrhages.<br /><br /> Selective ophthalmic artery infusion chemotherapy has improved ocular outcomes in children with retinoblastoma. Our aim was to correlate quantitative tumor reduction and dichotomous therapeutic response with technical and adjunctive factors during selective ophthalmic artery infusion chemotherapy for retinoblastoma. An understanding of such factors may improve therapeutic efficacy.<br /><br /> All patients with retinoblastoma treated by selective ophthalmic artery infusion chemotherapy at a single center during a 9-year period were reviewed. Only first-cycle treatments for previously untreated eyes were studied. Adjunctive factors (intra-arterial verapamil, intranasal oxymetazoline external carotid balloon occlusion) and technical factors (chemotherapy infusion time, fluoroscopy time) were documented by medical record review. Quantitative tumor reduction was determined by blinded comparison of retinal imaging acquired during examination under anesthesia before and 3-4 weeks after treatment. The dichotomous therapeutic response was classified according to quantitative tumor reduction as satisfactory (≥ 50%) or poor (&lt;50%).