A retinoid analogue, TTNPB, promotes clonal expansion of human pluripotent stem cells by upregulating CLDN2 and HoxA1.

Enzymatic dissociation of human pluripotent stem cells (hPSCs) into single cells during routine passage leads to massive cell death. Although the Rho-associated protein kinase inhibitor, Y-27632 can enhance hPSC survival and proliferation at high seeding density, dissociated single cells undergo apoptosis at clonal density. This presents a major hurdle when deriving genetically modified hPSC lines since transfection and genome editing efficiencies are not satisfactory. As a result, colonies tend to contain heterogeneous mixtures of both modified and unmodified cells, making it difficult to isolate the desired clone buried within the colony. In this study, we report improved clonal expansion of hPSCs using a retinoic acid analogue, TTNPB. When combined with Y-27632, TTNPB synergistically increased hPSC cloning efficiency by more than 2 orders of magnitude (0.2% to 20%), whereas TTNPB itself increased more than double cell number expansion compared to Y-27632. Furthermore, TTNPB-treated cells showed two times higher aggregate formation and cell proliferation compared to Y-27632 in suspension culture. TTNPB-treated cells displayed a normal karyotype, pluripotency and were able to stochastically differentiate into all three germ layers both in vitro and in vivo. TTNBP acts, in part, by promoting cellular adhesion and self-renewal through the upregulation of Claudin 2 and HoxA1. By promoting clonal expansion, TTNPB provides a new approach for isolating and expanding pure hPSCs for future cell therapy applications.

ALDH1A Inhibition Suppresses Colitis and Alters α4ß7 Integrin Expression on Activated T Cells in Mdr1a-/- Mice.

There are limited pharmacological treatment options for inflammatory bowel disease (IBD), and some of these options are expensive and administered by injection or infusion. Thus, new cheaper and easier (oral) treatment options are needed. ALDH1A enzymes produce retinoic acid that can affect intestinal diseases such as IBD by regulating immune cells in the gut. We previously demonstrated that an orally deliverable ALDH1A inhibitor, WIN 18,466, can suppress colitis in an acute mouse model of IBD. Here, we tested the efficacy of ALDH1A inhibition in a chronic mouse model of IBD. Mdr1a-/- mice were treated with a diet containing WIN 18,446 starting 1 week prior to inducing colitis by H. bilis inoculation. Treatment was continued until the study end point and colitis was monitored based on clinical symptoms and confirmed by histological analysis. Immune cell phenotypes in colon-draining lymph nodes (cMLN) were analyzed. WIN 18,446 treatment reduced clinical symptoms and improved histopathologic colitis scores. This was associated with decreased expression of the gut homing integrin, α4ß7, on T cells in cMLN; increased expression of CD103, a protein associated with tissue-resident memory T cells; and changes in dendritic cells, plasmacytoid dendritic cells and B cells in inhibitor-treated mice. ALDH1A inhibition broadly influences immune cells during colitis and is a potential new target for IBD treatment. Future studies will be needed to determine the efficacy of ALDH1A inhibition on active colitis and to evaluate its relative efficacy in comparison to approved drugs.

Meta-analysis assessing the sensitivity and specificity of 18F-FDG PET/CT for the diagnosis of prosthetic valve endocarditis (PVE) using individual patient data (IPD).

IMPORTANCE: The use of 18F-FDG PET/CT in diagnostic algorithms for PVE has increased since publication of studies and guidelines advocating its use. The assessment of test accuracy has been limited by small study sizes. We undertook a systematic review using individual patient data (IPD) meta-analysis techniques. OBJECTIVE: To estimate the summary sensitivity and specificity of 18F-FDG PET/CT in diagnosing PVE. We also assessed the effect of patient factors on test accuracy as defined by changes in the odds ratios associated with each factor. The effect of the PET/CT study on the final diagnosis was also assessed when compared to the preliminary Duke classification to determine in which patient group 18F-FDG PET/CT had the greatest utility. STUDY SELECTION: Studies were included if PET/CT was performed for suspicion of PVE and IPD of both the PET/CT result and final diagnosis defined by a gold-standard assessment was available. There were 3 possible final diagnoses ("definite PVE," "possible PVE," and "rejected PVE"). RESULTS: Seventeen studies were included with IPD available for 537 patients (from 538 scans). The summary sensitivity and specificity were 85% (95% CI 74.2%-91.8%) and 86.5% (95% CI 75.8%-92.9%) respectively when patients with final diagnosis of "possible PVE" were classified as positive for PVE. When this group was classified as negative for PVE, sensitivity was 87.4% (95% CI 80.4%-92.1%) and specificity was 84.9% (95% CI 71.5%-92.6%). Patients with a known pathogen (especially coagulase negative staphylococcal species), elevated CRP, a biological or aortic valve infection appeared more likely to have an accurate PET/CT diagnosis. Those with a mechanical valve, prior antibiotic treatment or a transcatheter aortic valve replacement valve were less likely to have an accurate test. Time since valve implantation and the presence of surgical adhesive did not appear to affect test accuracy. Of the patients with a preliminary Duke classification of "possible PVE," 84% received a more conclusive final diagnosis of "definite" or "rejected" PVE after the PET/CT study. CONCLUSIONS AND RELEVANCE: 18F-FDG PET/CT has high sensitivity and specificity in diagnosing PVE and the diagnostic utility is greatest in patients with a preliminary Duke classification of "possible PVE." Some patient factors appear to affect test accuracy, though these results should be interpreted with caution given low patient numbers for subgroup analyses.

The Current State of Susceptibility-Weighted Imaging and Quantitative Susceptibility Mapping in Head Trauma.

Susceptibility-weighted imaging (SWI) is a MR imaging technique suited to detect structural and microstructural abnormalities in traumatic brain injury (TBI). This review article provide an insight in to the physics principles of SWI and its clinical application in unraveling the complex interaction of the biophysical mechanisms of head injury. Literature evidences support SWI as the most ideal sequence in detection of microbleeds, which is the "tip of the iceberg" biomarker of microvascular injuries. The review also detailed the emerging advance techniques of Quantitative susceptibility mapping (QSM) and artificial intelligence offer the ability to detect and follow the evolution of microbleeds in patient with chronic TBI. These new techniques offers a unique insight into the acute and chronic state of TBI.

Yellow droopy eyes: A case of obstructive jaundice from Burkitt's lymphoma with involvement of bilateral cavernous sinus.

Burkitt's lymphoma follows a lymphogenous spread early in the disease. The central nervous system can be involved via a hematogenous route but involvement of the cavernous sinus (CS) is rare and can be misdiagnosed as other pathology of primary neoplastic, infective, or vascular origin. We present a case of a 73-year-old gentleman with painless jaundice and subjective heaviness to his eyes that progressed to partial ptosis of the left eye, complete ptosis of the right eye with diplopia, found to have disseminated Burkitt's lymphoma with bilateral deposits to the CS. Early recognition of Burkitt's lymphoma with CS involvement is important as it often signifies disseminated disease with implications on chemotherapy regimen, treatment outcomes, and survival.

Susceptibility weighted imaging for qualitative grading of persistent arteriovenous shunting in deep-seated arteriovenous malformations after stereotactic radiation surgery.

BACKGROUND AND PURPOSE: To investigate Susceptibility Weighted Imaging (SWI) signal changes in the draining vein of deep-seated arterio-venous malformations (AVMs) following stereotactic radiosurgery (SRS). METHODS AND MATERIALS: This is a retrospective study of 32 patients with deep-seated AVMs who were treated with SRS. Pre-SRS treatment and post-SRS treatment MRI were performed at 6, 12, and 24-month intervals. Deep-seated AVMs were classified based on their anatomical location and venous drainage pattern. AVM nidal volume (cm3) was estimated using the ABC/2 method. AV shunting of the AVM draining veins were graded according to its SWI signal intensity: hyperintense (grade III), mixed signal intensity (grade II), hypointense (grade I) and absent (grade 0). Conventional time-of-flight (TOF)-MRA and contrast enhanced (CE)-MRA sequences were performed to document the patency of the vein. RESULTS: Pre-SRS treatment AVM draining veins were either grade III 18/32 (56%) or grade II 14/32 (44%). Using mixed effects analysis, we demonstrate that each month following the SRS treatment nidal volumes decreased at the rate of 0.51 cm3/per month (CI -0.61 to (-0.40)) p =.00. Following the treatment, there was a clinically significant relationship between the signal and nidal volume: signal 0 corresponded with average nidal volume of 1.81 cm3 (CI 1.40-2.21), signal 1 with nidal volume of 2.06 cm3 (CI 1.69-2.44), signal 2 with nidal volume 2.73 cm3 (CI 2.35-3.11) and signal 3 with nidal volume 3.13 cm3 (CI 2.70-3.56) p = .00. CONCLUSION: Post-SRS AVM draining veins shows a stepwise regression of the SWI signal grades which can be reliably used as a surrogate to monitor the reduction of AV shunting.

Antibody Production Remains Intact Despite Loss of Bone Marrow B cells in Murine Norovirus Infected Stat1-/- Mice.

Murine norovirus (MNV), which can be used as a model system to study human noroviruses, can infect macrophages/ monocytes, neutrophils, dendritic, intestinal epithelial, T and B cells, and is highly prevalent in laboratory mice. We previously showed that MNV infection significantly reduces bone marrow B cell populations in a Stat1-dependent manner. We show here that while MNV-infected Stat1-/- mice have significant losses of bone marrow B cells, splenic B cells capable of mounting an antibody response to novel antigens retain the ability to expand. We also investigated whether increased granulopoiesis after MNV infection was causing B cell loss. We found that administration of anti-G-CSF antibody inhibits the pronounced bone marrow granulopoiesis induced by MNV infection of Stat1-/- mice, but this inhibition did not rescue bone marrow B cell losses. Therefore, MNV-infected Stat1-/- mice can still mount a robust humoral immune response despite decreased bone marrow B cells. This suggests that further investigation will be needed to identify other indirect factors or mechanisms that are responsible for the bone marrow B cell losses seen after MNV infection. In addition, this work contributes to our understanding of the potential physiologic effects of Stat1-related disruptions in research mouse colonies that may be endemically infected with MNV.

Fluid shear stress promotes embryonic stem cell pluripotency via interplay between ß-catenin and vinculin in bioreactor culture.

The expansion of pluripotent stem cells (PSCs) as aggregates in stirred suspension bioreactors is garnering attention as an alternative to adherent culture. However, the hydrodynamic environment in the bioreactor can modulate PSC behavior, pluripotency and differentiation potential in ways that need to be well understood. In this study, we investigated how murine embryonic stem cells (mESCs) sense fluid shear stress and modulate a noncanonical Wnt signaling response to promote pluripotency. mESCs showed higher expression of pluripotency marker genes, Oct4, Sox2, and Nanog in the absence of leukemia inhibitory factor (LIF) in stirred suspension bioreactors compared to adherent culture, a phenomenon we have termed mechanopluripotency. In bioreactor culture, fluid shear promoted the nuclear translocation of the less well-known pluripotency regulator ß-catenin and concomitant increase of c-Myc expression, an upstream regulator of Oct4, Sox2, and Nanog. We also observed similar ß-catenin nuclear translocation in LIF-free mESCs cultured on E-cadherin substrate under defined fluid shear stress conditions in flow chamber plates. mESCs showed lower shear-induced expression of pluripotency marker genes when ß-catenin was inhibited, suggesting that ß-catenin signaling is crucial to mESC mechanopluripotency. Key to this process is vinculin, which is known to rearrange and associate more strongly with adherens junctions in response to fluid shear. When the vinculin gene is disrupted, we observe that nuclear ß-catenin translocation and mechanopluripotency are abrogated. Our results indicate that mechanotransduction through the adherens junction complex is important for mESC pluripotency maintenance.

18F-FDG PET/CT in Osteoradionecrosis of the Hyoid.

Osteoradionecrosis (ORN) is a well-documented complication following radiation treatment for head and neck malignancy. Facial bones, mainly the mandible, laryngeal cartilage, and skull, are frequently involved sites for ORN. A rare site for ORN is the hyoid, with very limited cases described in the literature. Recognition of the imaging pattern of hyoid ORN is critical to avoid misdiagnosis of recurrent disease, prompting early treatment.

Susceptibility and Volume Measures of the Mammillary Bodies Between Mild Cognitively Impaired Patients and Healthy Controls.

PURPOSE: To investigate the baseline values and differences for susceptibility and volume of the mammillary bodies between mild cognitively impaired (MCI) patients and healthy controls (HCs), and further explore their differences in relation to gender, MCI subtypes and apolipoprotein E (APOE) genotypes. METHODS: T1-weighted and multi-echo gradient echo imaging sequences were acquired on a 3T MR scanner to evaluate the T1W based volume and susceptibility differences in the mammillary body for 47 MCI and 47 HCs. T-tests were performed to compare volume and susceptibility between groups, and right and left hemispheres. Correlation analysis was used to relate the volume and mean susceptibility as a function of age in MCI and HC groups separately, and to investigate the relationship of susceptibility with the neuro-psychological scales in the MCI group. RESULTS: Susceptibility was found to be elevated within the right mammillary body in MCI patients compared to HCs (p < 0.05). There were no differences for the mammillary body volumes between the MCI and HC groups, although there was a reduction in volume with age for the MCI group (p = 0.007). Women showed decreased mammillary body volume compared to men in the HC group (p = 0.004). No significant differences were found in relation to MCI subtypes and APOE genotypes. No significant correlations were observed between mammillary body susceptibility with neuro-psychological scales. CONCLUSION: This work provides a quantitative baseline for both the volume and susceptibility of the mammillary body which can be used for future studies of cognitive impairment patients underlying the pathology of the Papez circuit.

Developmental anomalies of the lateral portion of the cervical neural arch: Multimodal imaging and clinical implications.

OBJECTIVE: This study aimed to describe the imaging spectrum of developmental anomalies of the lateral portion of the cervical neural arch. METHOD: This was a five-year retrospective review of consecutive computed tomography (CT) scans of the cervical spine for structural anomalies of the cervical vertebral pedicle and facets. CT, radiographs and, when available, magnetic resonance imaging studies were independently reviewed. Anomalies were grouped into the following three categories: the absence of a pedicle, clefts in the vertebral arch or isolated dysmorphism of the facet. Clinical data on demographics and neurological outcomes were documented. RESULTS: Among 9134 consecutive patients undergoing a CT scan of the cervical spine, 18 (0.2%) patients were found to have developmental anomalies of the pedicle and facets. Findings included 7/18 (39%) with congenital absence of a pedicle, 8/18 (44%) with clefts in the vertebral arch and 3/18 (17%) with isolated dysmorphism of the articular facets. No acute neurological deficits or spinal cord injuries were reported. Associated chronic symptoms included neck pain 10/18 (56%), radiculopathy 7/18 (39%) and myelopathy 1/18 (6%). CONCLUSION: Developmental anomalies of the pedicle and facet may mimic traumatic spinal pathologies. Recognising a diverse spectrum of imaging findings is vital to prevent misdiagnosis and unnecessary intervention.

Quantitative Susceptibility Mapping for Characterization of Intraplaque Hemorrhage and Calcification in Carotid Atherosclerotic Disease.

BACKGROUND: Carotid artery intraplaque hemorrhage (IPH), an unstable component of atherosclerosis, is associated with an increased risk of stroke. PURPOSE: To investigate quantitative susceptibility mapping (QSM) as a tool for the evaluation of IPH and calcification in vivo. STUDY TYPE: Prospective. POPULATION: Ten healthy volunteers and 15 patients. FIELD STRENGTH/SEQUENCE: 3.0T Susceptibility-weighted imaging (SWI), magnetization-prepared rapid acquisition with gradient echo (MP-RAGE), T1 -weighted sampling perfection with application of optimized contrasts using different flip angle evolution (T1 -SPACE), T2 -weighted turbo spin-echo (T2 WI), and time-of-flight (TOF) sequences. ASSESSMENT: The vessel wall area of the carotid artery was measured with QSM and compared with T1 -SPACE on healthy volunteers. Four radiologists, blinded to clinical history and patient identity, determined the presence and area of IPH on MP-RAGE and QSM, as well as the area of calcification on T1 -SPACE and QSM. STATISTICAL TESTS: Bland-Altman analysis, Pearson correlation coefficients, linear regression analyses were performed to evaluate the concordance of area measurements. Cohen's kappa (κ) was analyzed to determine the agreement between IPH detections. The paired t-test was used to compare the group differences. RESULTS: In 423 matched slices, 20.1% (85/423) and 19.6% (83/423) were detected to have IPH on MP-RAGE and QSM, respectively. IPH detection by QSM and MP-RAGE showed good agreement (κ = 0.822, P < 0.001) between the two methods. There was no significant difference in IPH area measurements between QSM and MP-RAGE (7.28 mm2 ± 6.41 vs. 7.16 mm2 ± 5.99, P = 0.575). There was no significant difference in calcification area measurement between QSM and T1 -SPACE (3.51 mm2 ± 1.78 vs. 3.41 mm2 ± 2.02, P = 0.783). DATA CONCLUSION: QSM is a novel imaging tool for the identification of IPH in patients with carotid atherosclerosis and enables differentiation of IPH and calcification. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1 J. Magn. Reson. Imaging 2020;52:534-541.

Effect of Chronic Vitamin D Deficiency on the Development and Severity of DSS-Induced Colon Cancer in Smad3-/- Mice.

Both human epidemiologic data and animal studies suggest that low serum vitamin D increases the risk of inflammatory bowel disease (IBD) and consequently IBD-associated colorectal cancer. We tested the hypothesis that vitamin D deficiency increases the risk for colitis-associated colon cancer (CAC) by using an established CAC mouse model, 129-Smad3tm1Par/J (Smad3-/-) mice, which have defective transforming growth factor ß-signaling and develop colitis and CAC after the administration of dextran sodium sulfate (DSS). After determining a dietary regimen that induced chronic vitamin D deficiency in Smad3-/- mice, we assessed the effects of vitamin D deficiency on CAC. Decreasing dietary vitamin D from 1 IU/g diet (control diet) to 0.2 IU /g diet did not decrease serum 25-hydroxyvitamin D (25(OH)D) levels in Smad3-/- mice. A diet devoid of vitamin D (< 0.02 IU/g diet [no added vitamin D]; vitamin D-null) significantly decreased serum 25(OH)D levels in mice after 2 wk (null compared with control diet: 8.4 mg/mL compared with 12.2 ng/mL) and further decreased serum levels to below the detection limit after 9 wk but did not affect weight gain, serum calcium levels, bone histology, or bone mineral density. In light of these results, Smad3-/- mice were fed a vitamin D-null diet and given DSS to induce colitis. Unexpectedly, DSS-treated Smad3-/- mice fed a vitamin D-null diet had improved survival, decreased colon tumor incidence (8% compared with 36%), and reduced the incidence and severity of colonic dysplasia compared with mice fed the control diet. These effects correlated with increased epithelial cell proliferation and repair early in the disease, perhaps reducing the likelihood of developing chronic colitis and progression to cancer. Our results indicate that vitamin D deficiency is beneficial in some cases of CAC, possibly by promoting intestinal healing.

Cytokine Directed Chondroblast Trans-Differentiation: JAK Inhibition Facilitates Direct Reprogramming of Fibroblasts to Chondroblasts.

Osteoarthritis (OA) is a degenerative disease of the hyaline articular cartilage. This disease is progressive and may lead to disability. Researchers proposed many regenerative approaches to treat osteoarthritis, including stem cells. Trans-differentiation of a fully differentiated cell state directly into another different differentiated cell state avoids the disadvantages of fully reprogramming cells to induced pluripotent stem cells (iPSCs) in terms of faster reprogramming of the needed cells. Trans-differentiation also reduces the risk of tumor formation by avoiding the iPSC state. OSKM factors (Oct4, Sox2, Klf4, and cMyc) accompanied by the JAK-STAT pathway inhibition, followed by the introduction of specific differentiation factors, directly reprogrammed mouse embryonic fibroblasts to chondroblasts. Our results showed the absence of intermediate induced pluripotent stem cell formation. The resulting aggregates showed clear hyaline and hypertrophic cartilage. Tumor formation was absent in sub-cutaneous capsules transplanted in SCID mice.

Lack of Effect of Murine Norovirus Infection on the CD4+ CD45RBhigh T-cell Adoptive Transfer Mouse Model of Inflammatory Bowel Disease.

Murine norovirus (MNV) infection is highly prevalent in laboratory mice. Although MNV infection does not typically induce clinical disease in most laboratory mice, infection may nonetheless affect mouse models of disease by altering immune responses. We previously reported that MNV altered the bacterial-induced mouse model of inflammatory bowel disease (IBD) using Helicobacter-infected Mdr1a-/- mice. Therefore, we hypothesized that MNV infection would exacerbate another mouse model of IBD, the T-cell adoptive transfer (AT) model. In this model, Helicobacter infection is used to accelerate the progression of IBD induced by AT of naïve CD4+CD45RBhigh T cells into B6.129S7- Rag1tm1Mom/J (Rag1-/-) mice. We evaluated the effects of MNV infection in both Helicobacter-accelerated as well as Helicobacter-free AT models. In our studies, Helicobacter-infected Rag1-/- mice that received CD4+CD45RBhigh T cells through AT rapidly developed weight loss and typhlocolitis; MNV infection had no effect on disease severity or rate of progression. In the absence of Helicobacter infection, progression of IBD caused by AT of CD4+CD45RBhigh T cells was slower and typhlocolitis was less severe; this inflammation likewise was unaltered by MNV infection. These results indicate that MNV infection does not alter IBD progression and severity in the CD4+CD45RBhigh T-cell AT model in Rag1-/- mice.

Validation studies for germ-free Smad3-/- mice as a bio-assay to test the causative role of fecal microbiomes in IBD.

While the association between microbiomes and inflammatory bowel disease (IBD) is well known, establishing causal relationships between the two is difficult in humans. Germ-free (GF) mice genetically susceptible to IBD can address this question. Smad3-/- mice with defective transforming growth factor ß signaling are a model of IBD and colon cancer. They develop IBD upon colonization with Helicobacter under specific pathogen-free conditions, suggesting a role of the microbiome in IBD in this model. Thus, we rederived Smad3-/- mice GF to determine the potential of using these mice for testing the causative role of microbiomes in IBD. We found that fecal microbiomes from mice with IBD cause more severe gut inflammation in GF Smad3-/- and wild type mice compared to microbiomes from healthy mice and that Helicobacter induces gut inflammation within the context of other microbiomes but not by itself. Unexpectedly, GF Smad3+/+ and Smad3+/- mice given IBD microbiomes develop IBD despite their lack of disease in SPF conditions upon Helicobacter infection. This was not unique to the background strain of our Smad3 model (129); both wild type C57BL/6 and 129 strains developed IBD upon fecal transfer. However, wild type Swiss Webster stock was not susceptible, indicating that the genetic background of recipient mice influences the severity of IBD following fecal transfer. Our data suggest that the microbiome is an independent risk factor contributing to IBD development, and careful characterization of new GF models is needed to understand potential sources of confounding factors influencing microbiome studies in these mice.

Magnetic Resonance Imaging Criteria for Post-Concussion Syndrome: A Study of 127 Post-Concussion Syndrome Patients.

The purpose of this study was to assess the frequency of structural lesions on conventional magnetic resonance imaging (MRI) of the brain in a large prospective cohort of post-concussion syndrome (PCS) patients. Conventional 3T MRI was used to evaluate 127 prospectively enrolled PCS patients and 29 controls for non-specific white matter hyperintensities (WMH) and traumatic structural lesions, including encephalomalacia, atrophy, microhemorrhage, subarachnoid hemorrhage, and cortical siderosis. All PCS patients had a clinical diagnosis of one or more concussions based on the Concussion in Sport Group (CISG) consensus statements. Patients with recognized intracranial hemorrhage on prior head computed tomography (CT) and MRI were excluded. The differences between the PCS and control groups were analyzed. Four patients in the PCS group (3.1%) had positive findings, which included microhemorrhages in two patients and encephalomalacia in another two patients. None of these lesions was present in the control group, but there was no statistical difference between the two groups (p = 0.5 for microhemorrhage and p = 0.5 for encephalomalacia). In the PCS group, 28 patients (22%) had WMH (15.7% had 1-10 lesions and 6.3% had >10 lesions), and these results did not differ from the age-matched control (20.6%, all with 1-10 lesions; p = 0.9) The location of the WMH showed no significant difference in the number of juxtacortical WMH between the PCS and control groups (p = 0.5). Structural lesions were rare in PCS in this study, and the presence of such findings suggests a more severe form of traumatic brain injury. Our data support the role for MRI in the diagnosis of PCS by exclusion of atrophy, encephalomalacia, and all forms of intracranial hemorrhage. The presence of WMH irrespective of number is not an exclusion. This is the first description of the MRI criteria for PCS.

High-Resolution MRI Vessel Wall Imaging in Acute Aneurysmal Subarachnoid Hemorrhage : Spatiotemporal Pattern and Clinicoradiologic Implications.

PURPOSE: The spatiotemporal pattern of vessel wall changes was investigated on two time point magnetic resonance images (MRI) in patients with aneurysmal subarachnoid hemorrhages (aSAH) and its association with clinicoradiologic severity score and delayed cerebral ischemia (DCI) was analyzed. METHODS: A total of 32 prospectively enrolled patients with aSAH (mean age 56.94 years; 9 male and 23 female) underwent vessel wall imaging (VWI) MRI. Of the patients 20 completed two time point MRIs early and late during the admission, 10 patients only had early MRI and 2 patients only had late MRI. Timing of early MRI had a mean of 2.5 days (range 1-6 days) and late MRI had a mean of 10.5 days (range 7-16 days) from time of admission. Spatiotemporal pattern of vessel wall enhancement (VWE), vasospasm, diffusion-weighted imaging (DWI) lesion burden (grade 0-III) and infarcts were analyzed against the clinicoradiologic severity score (high-risk: vasograde red and yellow, low-risk: vasograde green) and DCI. RESULTS: On the early MRI, mild VWE alone was significantly more frequent in the high-risk group (36.7% versus 20.0%; P = 0.024). On the late MRI, vasospasm was significantly more frequent in the high-risk group (27.2% versus 4.5%; P = 0.022). Vasospasm infrequently showed mild VWE (6.67% on early MRI and 9.09% on late MRI). Both mild VWE alone on early MRI and on late MRI were significantly associated with development of DCI during the admission (P = 0.034 and P = 0.035, respectively). CONCLUSION: Mild VWE on early MRI and vasospasm on late MRI were significantly more prevalent in high-risk and DCI patients suggesting VWI might enable imaging of early neuroinflammatory changes which are part of the pathomechanism of vasospasm and DCI.

Iodine-stained fragmented thromboembolism.

AIM: Iodine-stained fragmented thromboembolism (ISFT) is a rare phenomenon encountered in the immediate aftermath of mechanical thrombectomy or rarely as a complication of post-carotid stenting. The aim was to describe the imaging appearance and discuss its pathophysiology. METHOD: This is a retrospective review of patients who underwent mechanical thrombectomy for acute stroke at a single institution over the period of one year. All patients underwent the standard acute stroke imaging protocol (CT head, CT angiogram (CTA) and CT brain perfusion) and when clinically appropriate followed by catheter angiogram and mechanical thrombectomy. ISFT was defined as an arterial luminal filling defect with Hounsfield density equal to or greater than iodine seen on the biplanar CT or conventional CT. The presence and location of ISFT were documented. Standard CT angiogram (CTA) or magnetic resonance angiogram (MRA) was performed 24-48 hours after the neurointerventional procedure to assess for recanalization, volume of infarction and the fate of the ISFT. RESULTS: ISFTs were identified in eight (five males and three females, age range 18-80 years) out of 49 patients in the following locations: distal M1 (n = 1), M2 (n = 4), M3 (n = 1), A1 (n = 1), distal A2 (n = 1). ISFT and vessel recanalization occurred in five patients on follow-up. ISFT and vessel occlusion persisted in two patients. CONCLUSION: ISFT is likely the result of mechanical disruption of a thromboembolus, and porosity of the thromboembolus fragment may transiently retain iodinated contrast. Recognition of this entity may be important to aid detection of residual thromboembolism and avoid misinterpretation as calcified thromboembolism.