Acute Lesions Research Articles

Magnetic Resonance Imaging Monitoring of Thermal Lesions Produced by Focused Ultrasound

Abstract Background: The main goal of the study was to find the magnetic resonance imaging (MRI) parameters that optimize contrast between tissue and thermal lesions produced by focused ultrasound (FUS) using T1-weighted (T1-W) and T2-weighted (T2-W) fast spin echo (FSE) sequences. Methods: FUS sonications were performed in ex vivo porcine tissue using a single-element FUS transducer of 2.6 MHz in 1.5 and 3 T MRI scanners. The difference in relaxation times as well as the impact of critical MRI parameters on the resultant contrast-to-noise ratio (CNR) between coagulated and normal tissues were assessed. Discrete and overlapping lesions were inflicted in tissue with simultaneous acquisition of T2-W FSE images. Results: FUS lesions are characterized by lower relaxation times than intact porcine tissue. CNR values above 80 were sufficient for proper lesion visualization. For T1-W imaging, repetition time values close to 1500 ms were considered optimum for obtaining sufficiently high CNR at the minimum time cost. Echo time values close to 50 ms offered the maximum lesion contrast in T2-W FSE imaging. Monitoring of acute FUS lesions during grid sonications was performed successfully. Lesions appeared as hypointense spots with excellent contrast from surrounding tissue. Conclusion: MRI monitoring of signal intensity changes during FUS sonication in grid patterns using optimized sequence parameters can provide useful information about lesion progression and the success of ablation. This preliminary study demonstrated the feasibility of the proposed monitoring method in ex vivo porcine tissue and should be supported by in vivo studies to assess its clinical potential.

The astrocyte-produced growth factor HB-EGF limits autoimmune CNS pathology

Central nervous system (CNS)-resident cells such as microglia, oligodendrocytes and astrocytes are gaining increasing attention in respect to their contribution to CNS pathologies including multiple sclerosis (MS). Several studies have demonstrated the involvement of pro-inflammatory glial subsets in the pathogenesis and propagation of inflammatory events in MS and its animal models. However, it has only recently become clear that the underlying heterogeneity of astrocytes and microglia can not only drive inflammation, but also lead to its resolution through direct and indirect mechanisms. Failure of these tissue-protective mechanisms may potentiate disease and increase the risk of conversion to progressive stages of MS, for which currently available therapies are limited. Using proteomic analyses of cerebrospinal fluid specimens from patients with MS in combination with experimental studies, we here identify Heparin-binding EGF-like growth factor (HB-EGF) as a central mediator of tissue-protective and anti-inflammatory effects important for the recovery from acute inflammatory lesions in CNS autoimmunity. Hypoxic conditions drive the rapid upregulation of HB-EGF by astrocytes during early CNS inflammation, while pro-inflammatory conditions suppress trophic HB-EGF signaling through epigenetic modifications. Finally, we demonstrate both anti-inflammatory and tissue-protective effects of HB-EGF in a broad variety of cell types in vitro and use intranasal administration of HB-EGF in acute and post-acute stages of autoimmune neuroinflammation to attenuate disease in a preclinical mouse model of MS. Altogether, we identify astrocyte-derived HB-EGF and its epigenetic regulation as a modulator of autoimmune CNS inflammation and potential therapeutic target in MS.

Calcium Chloride Treatment Enhances Antigen Production in Foot-and-Mouth Disease Vaccines for Serotypes SAT1 and SAT3.

Foot-and-mouth disease (FMD) is a highly contagious viral infection causing acute and severe vesicular lesions in cattle and pigs, which has prompted global vaccination policies. This study presents a technique for enhancing antigen yield in SAT1 BOT and SAT3 ZIM by treatment with calcium chloride (CaCl2). We tested changes in cell viability in BHK-21 suspension cells treated with varying concentrations of CaCl2. The optimal CaCl2 concentration was determined based on antigen yield. The timing of CaCl2 supplementation relative to FMD virus inoculation was tested. Finally, the optimal medium for antigen production was identified. We observed a concentration-dependent decrease in BHK-21 cell viability at >7.5 mM CaCl2. A CaCl2 concentration of 3 mM yielded the most antigens. CaCl2 supplementation relative to FMD virus infection was optimal 2 h before or with viral inoculation. CD-BHK 21 medium supplemented with CaCl2 was the most productive medium. Specifically, SAT1 BOT and SAT3 ZIM showed improved antigen production in CD-BHK 21 medium with 3 mM CaCl2, while Provero-1 and Cellvento BHK-200 media showed no significant enhancement. Overall, CaCl2 supplementation enhanced FMD antigen productivity. This study provides a useful framework for enhancing antigen production efficiently in the FMD vaccine industry.

Inhibition of Dorsal Root Ganglia Transient Receptor Potential Ankyrin 1 Upregulation Contributes to the Protective Effect of Morphine Against Gastric Mucosal Damage Induced by Water-Immersion Restraint Stress.

The pathogenesis mechanism of acute gastric mucosal lesions (AGML) is still unclear; further exploration is urgently needed to find a new therapeutic target. This study aimed to investigate whether morphine might regulate the expression and function of transient receptor potential ankyrin 1 (TRPA1) through a cyclic adenosine monophosphate/protein kinase A (cAMP/PKA)-dependent pathway, thereby alleviating gastric mucosal lesions caused by water-immersion restraint stress (WIRS). Rats were administered with intrathecal morphine, TRPA1 antagonist (HC-030031), µ-opioid receptor antagonist, or protein kinase A inhibitor (H-89), respectively, before WIRS. After 6 hours of WIRS, microscopic lesions, hematoxylin and eosin staining, and transmission electron microscopy were applied to assess the damage of the gastric mucosa. Real-time polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay were conducted to detect the levels of TRPA1 and substance P (SP) in the dorsal root ganglia (DRG) and gastric tissues. In addition, immunofluorescence was used to explore the possible co-expression of TRPA1 and µ-opioid receptors in the DRG. The results indicated that WIRS upregulated TRPA1 and SP in gastric mucosa, and HC-030031 or H-89 could alleviate gastric mucosal lesions caused by WIRS (P < .0001). Morphine was found to suppress both WIRS-induced gastric mucosal lesions (P < .0001) and the upregulation of TRPA1 (P = .0086) and SP (P = .0013). Both TRPA1 and SP play important roles in the pathogenesis of WIRS-induced AGML. Exogenous gastroprotective strategies reduce elevated levels of TRPA1 via the cAMP/PKA-dependent pathway. Inhibition of TRPA1 upregulation in the DRG is critical for intrathecal morphine preconditioning-induced gastric protection.

Current views on the functional role of hydrogen and its kinetics in the human body

The purpose of this overview was to present historical data on the discovery of hydrogen and a brief summary of its physical properties that form the basis for its use in aeronautics. Information is provided on the use of hydrogen, a biologically neutral molecule, in medicine as a diagnostic indicator for penetrating wounds of the gastrointestinal tract, the determination of local blood flow using the hydrogen clearance method, the use of the hydrogen breath test for the diagnosis of malabsorption and carbohydrate intolerance, achlorhydria, the diagnosis of bacterial overgrowth syndrome, the assessment of biodegradation of magnesium-containing implants, the orocecal transit time, and during deep-sea diving. The reasons for the sharp increase in the doctors’ interest in studying the biological role of hydrogen after the discovery of its antioxidant properties by a group of Japanese scientists (2007) are analyzed. In order to increase antioxidant protection of the body, data from recent research on ways to increase its concentration in the body through the supply of exogenous gas by inhalation or by administering hydrogen-rich water or saline solution is presented. Particular attention is paid to a critical analysis of studies on the kinetics of hydrogen by different routes, its concentration in blood and tissues, inhalation, and the use of hydrogen-rich water. Based on an analysis of publications, that the use of molecular hydrogen to relieve oxidative stress in the tissues of the intestines, liver and lungs is most promising, since its highest concentration is found in these tissues. Fermentation of carbohydrates has also been shown to increase the production of hydrogen by the intestinal microbiota. Considering that a large number of molecular hydrogen generators appeared on the market, the data on the requirements for their safety are summarized. Considerations on the use of molecular hydrogen for the purpose of antioxidant protection of the body in cardiology, gastroenterology, pulmonology, and other areas of medicine are based on modern views on the mechanisms of antioxidant, anti-apoptotic, cytoprotective, and anti-inflammatory effects of hydrogen. Particular attention is paid to the analysis of experimental and clinical research on the use of hydrogen in acute and chronic lung lesions, therapy of acute and chronic COVID-19 infection.Conclusion. Based on an analysis of the literature and our own data, a conclusion was drawn on the safety and prospects of the clinical use of molecular hydrogen in a wide range of concentrations in many diseases with the pathogenesis based on oxidative stress. In particular, the need for additional research was highlighted to clarify the regimen, frequency, duration and concentrations of hydrogen used, and a personalized approach to the combination of endogenous (from the intestinal microbiota) and exogenous hydrogen in various diseases.

IgG4-Related Infiltrative Kidney Disease without Extrarenal Organ Involvement: A Case Report

Background: IgG4-related disease (RD) is a systemic condition that can affect nearly all organs. Renal involvement encompasses interstitial nephritis, membranous nephropathy, and renal infiltrative lesions. Symptomatic IgG4-related kidney disease (RKD) without extrarenal organ manifestations is an exceptionally rare occurrence. Case Report: The authors present a case of 48-year-old male with isolated renal IgG4-RD presented with abdominal pain. Laboratory investigations revealed acute kidney injury, proteinuria, and hypoalbuminemia. Whole abdominal computed tomography (CT) scan disclosed infiltrative lesions in both kidneys and ureters, accompanied by hydronephrosis. Kidney biopsy demonstrated lymphocytic and plasma cell infiltration, with 82 plasma cells per high power field (HPF), storiform fibrosis, and the absence of obliterative phlebitis. After receiving corticosteroid treatment, the patient’s renal function improved, and the infiltrative lesions went into remission. Conclusion: Isolated renal IgG4-RD is a rare and challenging diagnosis. The disease can manifest as acute interstitial nephritis, glomerular disease, retroperitoneal fibrosis, or, rarely, as mass or infiltrative lesions. Corticosteroid therapy is likely to yield favorable responses, hence, prompt diagnosis is crucial. Delayed diagnosis may result in organ fibrosis and dysfunction. Keywords: IgG4-related disease; IgG4-related kidney disease; Infiltrative renal disease

Diffusion basis spectrum imaging and diffusion tensor imaging predict persistent black hole formation in multiple sclerosis

Background and objectivesDiffusion basis spectrum imaging (DBSI) extracts multiple anisotropic and isotropic diffusion tensors, providing greater histopathologic specificity than diffusion tensor imaging (DTI). Persistent black holes (PBH) represent areas of severe tissue damage in multiple sclerosis (MS), and a high PBH burden is associated with worse MS disability. This study evaluated the ability of DBSI and DTI to predict which acute contrast-enhancing lesions (CELs) would persist as T1 hypointensities (i.e. PBHs) 12 months later. We expected that a higher radial diffusivity (RD), representing demyelination, and higher DBSI-derived isotropic non-restricted fraction, representing edema and increased extracellular space, of the acute CEL would increase the likelihood of future PBH development. MethodsIn this prospective cohort study, relapsing MS patients with ≥1 CEL(s) underwent monthly MRI scans for 4 to 6 months until gadolinium resolution. DBSI and DTI metrics were quantified when the CEL was most conspicuous during the monthly scans. To determine whether the CEL became a PBH, a follow-up MRI was performed at least 12 months after the final monthly scan. ResultsThe cohort included 20 MS participants (median age 33 years; 13 women) with 164 CELs. Of these, 59 (36 %) CELs evolved into PBHs. At Gd-max, DTI RD and AD of all CELs increased, and both metrics were significantly elevated for CELs which became PBHs, as compared to non-black holes (NBHs). DTI RD above 0.74 conferred an odds ratio (OR) of 7.76 (CI 3.77–15.98) for a CEL becoming a PBH (AUC 0.80, CI 0.73–0.87); DTI axial diffusivity (AD) above 1.22 conferred an OR of 7.32 (CI 3.38–15.86) for becoming a PBH (AUC 0.75, CI 0.66–0.83). DBSI RD and AD did not predict PBH development in a multivariable model. At Gd-max, DBSI restricted fraction decreased and DBSI non-restricted fraction increased in all CELs, and both metrics were significantly different for CELs which became PBHs, as compared to NBHs. A CEL with a DBSI non-restricted fraction above 0.45 had an OR of 4.77 (CI 2.35–9.66) for becoming a PBH (AUC 0.74, CI 0.66–0.81); a CEL with a DBSI restricted fraction below 0.07 had an OR of 9.58 (CI 4.59–20.02) for becoming a PBH (AUC 0.80, 0.72–0.87). ConclusionOur findings suggest that greater degree of edema/extracellular space in a CEL is a predictor of tissue destruction, as evidenced by PBH evolution.

Bipolar endo-epicardial RF ablation: Animal feasibility study

BackgroundBipolar radiofrequency ablation (B-RFA) is a method used to treat the arrhythmia substrate resistant to unipolar ablation. Few studies have addressed endo-epicardial B-RFA. ObjectiveThe aim of the study was to evaluate chronic lesions resulting from endo-epicardial B-RFA and to determine optimal settings for such procedures in an animal model. MethodsIn 7 pigs, up to 5 radiofrequency applications per animal were performed with 2 electrodes placed on both sides of the left ventricular free wall. Current was delivered for 60 seconds by a generator dedicated for B-RFA with power settings of 25, 30, 35, 40, and 50 W. ResultsAt 12 weeks after ablation, 31 lesions were assessed. Their maximal cross-sectional area ranged from 7.2 to 68 mm2 and correlated with total power delivered (r = 0.53), with temperature increment at the endocardial catheter (r = 0.65), and inversely with temperature decrement at the epicardial catheter (r = 0.54). For power values between 30 and 40 W, the lesion area did not differ significantly (P = .92). Lesion depth ranged from 1.9 to 11 mm and correlated with impedance decrement (r = 0.5). Lesions were transmural in 8 cases. Lesion depth/wall thickness ratio was on average 0.6 ± 0.3, with the smallest value for 25 W (0.5 ± 0.3) and the largest for 50 W (0.8 ± 0.3). Steam pops occurred at a power range of 30–50 W, with an incidence of 1 in 5 applications, with 1 case of fatal tamponade at 40 W. Impedance decrement, endocardial catheter temperature increment, and endocardial electrogram amplitude decrement were greater during applications with steam pops. ConclusionChronic lesions resulting from endo-epicardial B-RFA appear smaller and less often transmural compared with acute lesions described in the literature. The incidence of steam pops during endo-epicardial B-RFA is relatively high even at low powers.

IMPACT OF ULTRAVIOLET RADIATION ON HUMAN SKIN OWING TO OZONE DEPLETION

&lt;p&gt;Depletion of ozone molecules in the stratospheric layer surges the flow of ultraviolet (UV) rays on the surface of the earth. Generally, UV rays are the hazardous energy waves emitted from the sun that can cause acute and chronic effects on bio species. Exposure to UV rays in humans causes skin problems such as wrinkles, leathery skin, liver spots, actinic keratosis, and solar elastosis. It is also stated to be a basic premise for skin melanoma. Raising environmental pollution and natural disasters triggered the ozone depletion crisis into global criteria. The proposed work is developed with the intent to analyse the harmful effects of UV radiation on human skin. It detects the skin diseases raised due to UV rays and categorizes them based on chronic intensity using the convolution neural network. The deep learning network Multires U-Net is developed to classify acute and chronic UV skin lesions based on intensity. The proposed technique achieved 95% model accuracy in the testing and training process. Hence the proposed model has better efficiency in the detection of UV lesions.&lt;/p&gt;&#x0D;

Clinical factors for delayed neuropsychiatric sequelae from acute carbon monoxide poisoning: a retrospective study.

Delayed neuropsychiatric sequelae (DNS), which seriously affect the daily lives of patients, are the most common complications of carbon monoxide (CO) poisoning. No uniform screening tool is available for identifying high-risk groups. Therefore, in this study, we aimed to explore whether conventional laboratory indicators and imaging data from primary hospitals could predict the occurrence of DNS. This retrospective observational study was conducted in a single-center primary hospital from January 1, 2021 to May 31, 2023. Participants included patients aged >18 years with acute CO poisoning. Patients with complete recovery in the acute phase were followed up by telephone and outpatient visits, and the presence of DNS was determined according to the occurrence of new neurological symptoms within 6 weeks after discharge. We obtained demographic, laboratory, and imaging data from the medical records and performed a univariate analysis. A multivariate logistic regression model was used to identify independent clinical predictors of DNS. A total of 73 patients were included in the study, of whom 25 (34.2%) developed DNS. Multivariate logistic regression analysis revealed that a longer duration of CO exposure (adjusted odds ratio (AOR): 1.262, 95% confidence interval (CI): 1.069-1.490) and the presence of acute brain lesions on diffusion-weighted imaging (DWI) (AOR: 5.117, 95% CI: 1.430-18.315) were independent risk factors for DNS. Receiver operating characteristic analyses of the duration of CO exposure were performed (area under the curve (AUC): 0.825; 95% CI: 0.731-0.918) with a cut-off value of 5.5 h, and DNS was predicted with a sensitivity of 96% and a specificity of 66.7%. High cranial DWI signal within 24 h and duration of poisoning longer than 5.5 h are independent predictors of DNS. The predictive effects of conventional laboratory indicators require further standardized and large-sample studies.

Abstract WP129: Half of Acute Cortical Lesions in Minor Acute Ischemic Stroke Patients Persist on Flair at 30-day

Introduction: Ischemic lesions seen on acute DWI often result in chronic infarction on FLAIR. However, in minor stroke a proportion of cortical lesions seem to disappear. The objective of this study was to characterize the persistence rate of acute cortical lesions on FLAIR and associated imaging markers on 3DT1 at 30-day. Methods: Consented minor stroke patients (NIHSS&lt;6) presented acutely (&lt;24 hrs) received MRI at baseline, 5-day, and 30-day. One qualifying cortical lesion per patient was evaluated on baseline DWI for volume, white matter involvement, and on follow-up FLAIR for signal intensity ratio (SIR): comparison of lesion vs contralateral homologous tissue. Three independent raters blinded to hemisphere and exact location of the DWI lesion evaluated 3DT1 and FLAIR on follow-up (Figure). Results: Of 159 consented patients, 30 met criteria, and lesions of 28 patients (18%) evolved as hyperintense on FLAIR at 5-day. The 28 patients had a median age of 70 years, 54% female, median admit NIHSS of 2, and 32% were treated with IV alteplase. Of the 28 lesions, 17 (61%) had white matter involvement at baseline, and 14 (50%) were not evident on FLAIR at 30-day. Comparing those hyperintense vs not evident on FLAIR, raters identified 79% vs 21% (p&lt;0.003) cavitation in white matter, 36% vs 0% (p&lt;0.01) cavitation in gray matter, 57% vs 0% (p&lt;0.001) laminar necrosis, and 100% vs 14% (p&lt;0.001) cortical thinning on 3DT1. Lesions that persisted on FLAIR vs lesions not evident at 30-day had larger baseline DWI lesion volume: 2.2mL vs 0.3mL (p=0.024), and differences in SIR: 1.63 vs 1.3 (p=0.009) at 5-day, and 1.56 vs 1.1 (p=0.003) at 30-day. Conclusions: Half of the acute cortical lesions persisted on FLAIR at 30-day. Imaging markers on 3DT1 were more frequently associated with FLAIR evident lesions, but in ~1/3 of lesions not hyperintense, readers identified 3DT1 changes. Quantitative analysis is underway to confirm this observation.

Abstract TP150: Magnetic Resonance Imaging Predictors of Atrial Fibrillation in Cryptogenic Stroke Cases

Introduction: Ischemic stroke is a leading cause of death and disability in the US, with 20-40% of cases, classified as cryptogenic or with an unexplained cause. Detection of one cause, paroxysmal atrial fibrillation (AF), is critical to ensuring optimal treatment with direct oral anticoagulant (DOAC). Currently, the most reliable AF detection strategy is use of an insertable cardiac monitor (ICM). However, earlier detection of occult cardioembolic patterns using MRI may promote earlier decisions for DOAC use. The overall goal of this study is to determine if MRI lesion patterns are predictive of AF detection by ICM. Methodology: Cases of consecutive patients (1/1/2015 - 12/31/2017) with MRI-confirmed stroke performed 48h from time last known well and prior to endovascular treatment were retrospectively analyzed. The primary outcome, presence of occult atrial fibrillation, was detected by ICM placement within 90 days and follow-up within 180 days from stroke. Four imaging patterns were tested as predictors of AF: i) acute stroke lesion involving multiple vascular territories (MVT, i.e. right or left carotid and/or posterior circulation), ii) MVT plus wedge-shaped cortical infarct or chronic stroke on FLAIR, iii) MVT involving 3 territories, and iv) MVT in 3 territories plus chronic FLAIR lesion. Adjustment variables were based on univariate logistic regression predictors of AF at P ≤0.1000. Results: Of the 101 cases in this analysis, the median age was 63 years and 49.5% male. Stroke in multiple vascular territories MVT was present in 22/101 (22%) at baseline. The total AF 6-month detection rate was 36/101 (36%). The imaging pattern most predictive of AF was pattern ii, MVT plus chronic FLAIR with an unadjusted odds ratio (OR) of 3.47, 95% CI of 0.3442-2.1731, P=.0073. The adjusted OR (age ≥ 55, history of stroke, and history of TIA,) was 3.26, 95% CI: 1.0358-11.1860, P =.0480. Conclusion: The presence of acute lesions in MVT and a chronic FLAIR lesion may be a biomarker of occult cardioembolic source that could be used early after the onset of stroke to determine optimal DOAC use for secondary prevention and potential risk reduction of stroke recurrence from suspected but unproven cardioembolic source. Funding: Lone Star Stroke Research Consortium

Ultrafast Brain MRI with Deep Learning Reconstruction for Suspected Acute Ischemic Stroke.

Background Deep learning (DL)-accelerated MRI can substantially reduce examination times. However, studies prospectively evaluating the diagnostic performance of DL-accelerated MRI reconstructions in acute suspected stroke are lacking. Purpose To investigate the interchangeability of DL-accelerated MRI with conventional MRI in patients with suspected acute ischemic stroke at 1.5 T. Materials and Methods In this prospective study, 211 participants with suspected acute stroke underwent clinically indicated MRI at 1.5 T between June 2022 and March 2023. For each participant, conventional MRI (including T1-weighted, T2-weighted, T2*-weighted, T2 fluid-attenuated inversion-recovery, and diffusion-weighted imaging; 14 minutes 18 seconds) and DL-accelerated MRI (same sequences; 3 minutes 4 seconds) were performed. The primary end point was the interchangeability between conventional and DL-accelerated MRI for acute ischemic infarction detection. Secondary end points were interchangeability regarding the affected vascular territory and clinically relevant secondary findings (eg, microbleeds, neoplasm). Three readers evaluated the overall occurrence of acute ischemic stroke, affected vascular territory, clinically relevant secondary findings, overall image quality, and diagnostic confidence. For acute ischemic lesions, size and signal intensities were assessed. The margin for interchangeability was chosen as 5%. For interrater agreement analysis and interrater reliability analysis, multirater Fleiss κ and the intraclass correlation coefficient, respectively, was determined. Results The study sample consisted of 211 participants (mean age, 65 years ± 16 [SD]); 123 male and 88 female). Acute ischemic stroke was confirmed in 79 participants. Interchangeability was demonstrated for all primary and secondary end points. No individual equivalence indexes (IEIs) exceeded the interchangeability margin of 5% (IEI, -0.002 [90% CI: -0.007, 0.004]). Almost perfect interrater agreement was observed (P > .91). DL-accelerated MRI provided higher overall image quality (P < .001) and diagnostic confidence (P < .001). The signal properties of acute ischemic infarctions were similar in both techniques and demonstrated good to excellent interrater reliability (intraclass correlation coefficient, ≥0.8). Conclusion Despite being four times faster, DL-accelerated brain MRI was interchangeable with conventional MRI for acute ischemic lesion detection. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Haller in this issue.

Abstract 53: Patients With Tandem Lesions Undergoing Thrombectomy Have Increased In-Hospital Stroke Recurrence Risk

Introduction: Mechanical Thrombectomy improves outcomes in patients with acute ischemic stroke due to large vessel occlusion. Nearly 15% of patients have a tandem extracranial and intracranial occlusion. There is limited data on in-hospital outcomes in patients with acute tandem lesions undergoing thrombectomy. Methods: We included patients hospitalized with acute ischemic stroke and large vessel occlusion undergoing thrombectomy at our comprehensive stroke center over a 7-year period. Data on demographics and baseline risk factors, occlusion site, and acute treatment was pulled from the stroke registry. Records were reviewed for the study outcome which was recurrent ischemic stroke during the in-hospital period, defined as new or worsening neurological symptoms due to new infarct or extension of the infarct. All outcomes were confirmed by a second neurologist. Patients were followed for 90-days and received a 90-day call to determine their modified rankin scale. We defined good functional outcome as 90-day mRS 0-2. We used fisher’s exact test and t-tests to compare categorical and continuous variables and built binary logistic regression model to compare 90-day mRS across the two groups (tandem vs. non-tandem lesions), adjusting for age and NIHSS scale. Results: We identified a total of 1347 patients (mean age 72 years, 51% women) who underwent thrombectomy and 226 (16.7%) had tandem lesions and 108/226 (47.8%) underwent acute stenting. Patients with tandem lesions were more likely to be men (60.6% vs. 46.6%,), have hyperlipidemia (60.9% vs. 52.1%), coronary artery disease (25.3% vs. 19.0%), smokers (35.9% vs. 20.5%) and less likely to have atrial fibrillation (20.0% vs. 46.2%) and history of congestive heart failure (8.0% vs. 16.8%), all p&lt;0.05. Patients tandem occlusions were more likely to have in-hospital recurrent ischemic stroke (8.0% vs. 4.1%, p = 0.012). Acute stenting was not associated with improved functional outcome at 90-days (aOR 0.86, 95% CI 0.41-1.82, p = 0.703). Conclusion: In this large cohort of thrombectomy patients, patients with tandem lesions had increased in-hospital recurrent stroke and acute stenting in this sub-group was not associated with improved functional outcome at 90-days.

Small Paracentral Acute Middle Maculopathy Lesions as Biomarker of Vascular Morbidity: Natural Course

Background: To evaluate the incidence rate of small paracentral acute middle maculopathy (PAMM) lesions in healthy fellow eyes of patients with retinal vein occlusions (RVO). Methods: Patients with unilateral branch RVO or central RVO who were followed up for at least one year were included. Fellow healthy eyes were examined with 6 mm optical coherence tomography angiography scans at baseline and at the end of the follow-up. Small resolved PAMM lesions were displayed using structural en face projections of the slab between two segmentation lines of the outer plexiform layer with 0 µm and −9 µm offset. New lesions were identified by overlaying baseline and final structural en face projections. Results: A total of 41 eyes of 41 patients (12 females and 29 males, mean age 63.5 ± 10.1 years) were included. The mean follow-up was 23.6 ± 11.4 months. Among all RVO patients, small resolved PAMM lesions in healthy fellow eyes were found in 39 patients (95.1%). In the whole cohort, the median number of PAMM lesions was 5.5 (95% CI 3.0 to 8.0) (mean 6.5 ± 5.7) at baseline, which increased statistically significantly to 5.5 (95% CI 3.8 to 8.2) (mean 6.7 ± 5.7) at the end of the follow-up period (p = 0.03). Eight (19.5%) patients demonstrated new lesions, with a median number of new lesions of 1 (ranged 1 to 2). Conclusions: Small PAMM lesions seem to be a slowly progressing retinal vascular biomarker.

Abstract TP154: Association of Left Ventricular Hypertrophy With Ischemic Lesions After Intracerebral Hemorrhage

Background: Ischemic lesions on diffusion weighted imaging (DWI) occur in one-third of intracerebral hemorrhage (ICH). Due to conflicting prior studies, it is uncertain if the degree of systolic blood pressure reduction increases the risk. Patients with severe, chronic hypertension may be more vulnerable to the development of ischemia after ICH due to altered cerebral autoregulatory limits. Using cardiac remodeling as a biomarker for severe chronic hypertension, we hypothesized that the presence of left ventricular hypertrophy (LVH) is associated with DWI lesions. Methods: Patients with spontaneous ICH enrolled in the Intracerebral Hemorrhage Outcomes Project who underwent DWI imaging and transthoracic echocardiography (TTE) during hospitalization were included. Lesions were identified as hyperintensities &gt;10mm remote from the hematoma with corresponding low ADC signal. LVH presence was identified using clinically obtained TTE reports with imaging evidence of moderate-severe left ventricular wall thickness. The relationship between LVH and DWI ischemic lesions was assessed with logistic regression modeling after adjusting for age, ICH volume, intraventricular hemorrhage, hypertension history, and blood pressure change within 24 hours. A secondary analysis using linear regression assessed the association with the number of DWI lesions adjusting for similar covariates. Results: Of 187 patients analyzed, DWI lesions were observed in 30.5% and LVH was seen in 23.5%. In our logistic regression analyses, we identified that LVH was associated with DWI lesions (adjusted OR 2.77, CI: 1.19-6.40). Separate sensitivity analyses adjusting for sex (OR 2.47, CI 1.05-5.83) and race (OR 2.52, CI 1.08-5.91) did not change these relationships. In secondary analysis, we identified that LVH was associated with increased DWI lesion number (B 1.018, CI 0.40-1.63 ). Discussion: LVH is associated with the presence and burden of DWI lesions. Further work is required to assess aggregate relationships of chronic hypertension/LVH, acute blood pressure change, ischemic lesions, and ICH outcomes to determine whether patients with LVH necessitate different acute blood pressure treatment goals.

"Long-term MRI findings in Ankylosing spondylitis patients treated with TNF inhibitors for a decade".

This study aims to evaluate the active and chronic lesions in sacroiliac joints and lumbar spine over a decade of TNFi therapy in patients with AS. The study enrolled patients with AS under treatment with a TNFi for over a decade. The patients underwent a new MRI scan of their lumbar spine and sacroiliac joint (SIJ). Two readers evaluated all images. Inflammation of SIJ(SIS), SIJ structural damage (SSS) including Fat Metaplasia, Erosions, Backfill and Ankylosis, and Spondyloarthritis Research Consortium of Canada Bone marrow edema (SPARCC) spine score were recorded. In the study, 15 patients were included, with 80% being male. The mean age during their first MRI was 38.1 (± 11.9) years old, and the majority (86.7%) tested positive for HLA-B27. While TNFi improved both BASDAI and BASFI scores, there was a noticeable increase in MRI acute lesions in the SIJ over time, where the median score increased from 0 (0-4) to 3 (0-10) after ten years (p = 0.028). After a decade of treatment, the median SPARCC spine score also increased from 0 (0-9) to 5 (0-16), p = 0.093. Finally, it was observed that there was a significant positive correlation between ESR and SIS erosions in cases of chronic lesions (r = 0.819, p < 0.001). While TNFi have significantly improved the treatment of AS, this study shows that acute lesions can still develop despite treatment. A personalized approach that adapts MRI assessment to each patient's specific requirements may help detect changes early and enable doctors to intervene promptly to prevent further damage.

Relationships of Hematocrit With Chronic Covert and Acute Symptomatic Lacunar Ischemic Lesions.

Red blood cell (RBC) concentrations are known to associate with ischemic stroke. It is unclear whether RBC concentrations associate specifically with small vessel disease lacunar infarcts. We investigated the hypothesis that RBC concentrations associate with both chronic covert and acute symptomatic brain MRI lacunar infarcts. A cross-sectional observational analysis was performed across 2 cohorts with available hematocrit (as the assessment of RBC concentration exposure) and MRI outcome data. The primary setting was a population-based cohort of stroke-free, older adult (>50 years) participants from the Northern Manhattan Study (NOMAS) enrolled between 2003 and 2009. A second replication sample consisted of patients admitted with acute stroke and enrolled into the Columbia Stroke Registry (CSR) between 2005 and 2020. Associations of hematocrit with (1) chronic, covert lacunar infarcts and (2) symptomatic (i.e., acute) lacunar strokes were separately assessed from the NOMAS and CSR cohorts, respectively, using general additive models after adjusting for relevant covariates. Of 1,218 NOMAS participants analyzed, 6% had chronic, covert lacunar infarcts. The association between hematocrit and these covert lacunar infarcts was U-shaped (χ2 = 9.21 for nonlinear associations; p = 0.03), with people with hematocrit extremes being more likely to have covert lacunar infarcts. Of the 1,489 CSR patients analyzed, 23% had acute lacunar strokes. In this sample, only the relationships of increased hematocrit concentrations and lacunar strokes were replicated (adjusted coefficient β = 0.020; SE = 0.009; p = 0.03). We identified relationships of hematocrit with MRI lacunar infarcts in both stroke-free and ischemic stroke cohorts, respectively. The relationship between increased hematocrit concentrations with lacunar infarcts was replicated in both cohorts. Further studies are required to clarify the mechanisms behind the relationships of hematocrit with ischemic cerebral small vessel disease.

Ischemic and hemorrhagic stroke lesion environments differentially alter the glia repair potential of neural progenitor cell and immature astrocyte grafts

Using cell grafting to direct glia-based repair mechanisms in adult CNS injuries represents a potential therapeutic strategy for supporting functional neural parenchymal repair. However, glia repair directed by neural progenitor cell (NPC) grafts is dramatically altered by increasing lesion size, severity, and mode of injury. To address this, we studied the interplay between astrocyte differentiation and cell proliferation of NPC in vitro to generate proliferating immature astrocytes (ImA) using hysteretic conditioning. ImA maintain proliferation rates at comparable levels to NPC but showed robust immature astrocyte marker expression including Gfap and Vimentin. ImA demonstrated enhanced resistance to myofibroblast-like phenotypic transformations upon exposure to serum enriched environments in vitro compared to NPC and were more effective at scratch wound closure in vitro compared to quiescent astrocytes. Glia repair directed by ImA at acute ischemic striatal stroke lesions was equivalent to NPC but better than quiescent astrocyte grafts. While ischemic injury environments supported enhanced survival of grafts compared to healthy striatum, hemorrhagic lesions were hostile towards both NPC and ImA grafts leading to poor survival and ineffective modulation of natural wound repair processes. Our findings demonstrate that lesion environments, rather than transcriptional pre-graft states, determine the survival, cell-fate, and glia repair competency of cell grafts applied to acute CNS injuries.

Early involvement of peripherally derived monocytes in inflammation in an NMO-like mouse model

Neuromyelitis optica (NMO) is an autoimmune inflammatory disease that primarily affects the optic nerve and spinal cord within the central nervous system (CNS). Acute astrocyte injury caused by autoantibodies against aquaporin 4 (NMO-IgG) is a well-established key factor in the pathogenesis, ultimately leading to neuronal damage and patient disability. In addition to these humoral immune processes, numerous innate immune cells were found in the acute lesions of NMO patients. However, the origin and function of these innate immune cells remain unclear in NMO pathogenesis. Therefore, this study aims to analyze the origin and functions of these innate immune cells in an NMO-like mouse model and evaluate their role in the pathophysiology of NMO. The expression of Tmem119 on Iba1 + cells in brain tissue disappeared immediately after the injection of NMO-IgG + human complement mixture, while the expression of P2ry12 remained well-maintained at 1 day after injection. Based on these observations, it was demonstrated that monocytes infiltrate the brain during the early stages of the pathological process and are closely associated with the inflammatory response through the expression of the proinflammatory cytokine IL-1β. Understanding the variations in the expression patterns of P2ry12, Tmem119, and other markers could be helpful in distinguishing between these cell types and further analyzing their functions. Therefore, this research may contribute to a better understanding of the mechanisms and potential treatments for NMO.