Increase In Lesion Volume Research Articles

Lesion Volume as a Predictor for Return to Work After Endovascular Treatment: A 4‐Year Prospective Cohort Study

BACKGROUND There are no known objective biomarkers for predicting return to work (RTW) in ischemic stroke survivors. This study aims to explore the predictive utility and defines a cutoff value of lesion volume on RTW after endovascular treatment. METHODS We included patients aged <65 years undergoing endovascular treatment at Oslo University Hospital between January 2017 and May 2019. Employment status was obtained at both baseline and a 4‐year follow‐up. Stroke lesion volumes were segmented using magnetic resonance imaging scans 24 hours after endovascular treatment. Logistic regression models were conducted to assess the impact of lesion volume on RTW status at follow‐up, adjusted for patients’ characteristics, stroke‐related factors, and treatment. We calculated the receiver operating characteristic curve to determine the optimal lesion volume cutoff. Machine learning regression models were used to assess the predictive abilities of baseline clinical and imaging variables for RTW. RESULTS Of the 109 individuals treated, 81 (74%) were employed at baseline. Among these, 60 completed 4‐year follow‐up with magnetic resonance imaging available for stroke lesion segmentation and were included in the analyses. Mean age at stroke onset was 51.8 years (range, 23.5–64.9 years), and 50% were female. Median lesion volume was 18 mL (interquartile ranges, 45—47 mL). After 4 years, 34 (57%) had successfully RTW. The odds for not RTW increased by 5% for every 1 mL increase in lesion volume (adjusted odds ratio, 1.05 [95% CI, 1.02–1.11]; P = 0.02). A lesion volume cutoff value of 29 cm 3 yielded a sensitivity of 0.91 and specificity of 0.65 for predicting RTW. Notably, the most influential feature in the machine learning model for predicting RTW was lesion volume. CONCLUSION Lesion volume was the most robust predictor of RTW 4 years after endovascular treatment. Our findings suggest that a cutoff of 29 cm 3 is suitable to distinguish between those with high and low chance of RTW.

Association of systolic blood pressure variability with cognitive decline in type 2 diabetes: A post hoc analysis of a randomized clinical trial.

We aimed to explore the association between visit-to-visit systolic blood pressure variability (BPV) and cognitive function in individuals with type 2 diabetes. We performed a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes (ACCORD-MIND) substudy. A total of 2867 diabetes patients with ≥3 BP measurements between the 4- and 20-month visits were included. Visit-to-visit systolic BPV was calculated. Cognitive decline was defined as a Mini-Mental State Exam (MMSE), Digit Symbol Substitution Test (DSST), or Rey Auditory Verbal Learning Test (RAVLT) score greater than 1 standard deviation (SD) below the baseline mean, or a Stroop test score more than 1 SD above the baseline mean. The associations of systolic BPV with risks of cognitive decline were examined using Cox proportional hazards models, and with changes in brain magnetic resonance imaging parameters were evaluated using mixed models. The risk of cognitive decline defined by the DSST score (but not by other scores) increased significantly with systolic BPV quartiles (p for trend = 0.008), and there was a 55% increased risk for BPV quartile 4 versus quartile 1 (hazard ratio = 1.55, 95% confidence interval 1.10-2.19). Furthermore, a positive correlation was observed between systolic BPV and change in white matter lesion volume (β = 0.07, 95% CI 0.01-0.13). A greater visit-to-visit systolic BPV was significantly associated with an increased risk of cognitive decline measured by DSST and an increase in white matter lesion volume in patients with type 2 diabetes.

The influence of the prolactin/vasoinhibin axis on post-stroke lesion volume, astrogliosis, and survival.

Ischemic stroke is a significant global health issue, ranking fifth among all causes of death and a leading cause of serious long-term disability. Ischemic stroke leads to severe outcomes, including permanent brain damage and neuronal dysfunction. Therefore, decreasing and preventing neuronal injuries caused by stroke has been the focus of therapeutic research. In recent years, many studies have shown that fluctuations in hormonal levels influence the prognosis of ischemic stroke. Thus, it is relevant to understand the role of hormones in the pathophysiological mechanisms of ischemic stroke for preventing and treating this health issue. Here, we investigate the contribution of the prolactin/vasoinhibin axis, an endocrine system regulating blood vessel growth, immune processes, and neuronal survival, to the pathophysiology of ischemic stroke. Male mice with brain overexpression of prolactin or vasoinhibin by adeno-associated virus (AAV) intracerebroventricular injection or lacking the prolactin receptor (Prlr-/-) were exposed to transient middle cerebral artery occlusion (tMCAO) for 45 min followed by 48 h of reperfusion. Overexpression of vasoinhibin or the absence of the prolactin receptor led to an increased lesion volume and decreased survival rates in mice following tMCAO, whereas overexpression of prolactin had no effect. In addition, astrocytic distribution in the penumbra was altered, glial fibrillary acidic protein and S100b mRNA expressions were reduced, and interleukin-6 mRNA expression increased in the ischemic hemisphere of mice overexpressing vasoinhibin. Of note, prolactin receptor-null mice (Prlr-/-) showed a marked increase in serum vasoinhibin levels. Furthermore, vasoinhibin decreased astrocyte numbers in mixed hippocampal neuron-glia cultures. These observations suggest that increased vasoinhibin levels may hinder astrocytes' protective reactivity. Overall, this study suggests the involvement of the prolactin/vasoinhibin axis in the pathophysiology of ischemic stroke-induced brain injury and provides insights into the impact of its dysregulation on astrocyte reactivity and lesion size. Understanding these mechanisms could help develop therapeutic interventions in ischemic stroke and other related neurological disorders.

Contribution of new and chronic cortical lesions to disability accrual in multiple sclerosis.

Cortical lesions are common in multiple sclerosis and are associated with disability and progressive disease. We asked whether cortical lesions continue to form in people with stable white matter lesions and whether the association of cortical lesions with worsening disability relates to pre-existing or new cortical lesions. Fifty adults with multiple sclerosis and no new white matter lesions in the year prior to enrolment (33 relapsing-remitting and 17 progressive) and a comparison group of nine adults who had formed at least one new white matter lesion in the year prior to enrolment (active relapsing-remitting) were evaluated annually with 7 tesla (T) brain MRI and 3T brain and spine MRI for 2 years, with clinical assessments for 3 years. Cortical lesions and paramagnetic rim lesions were identified on 7T images. Seven total cortical lesions formed in 3/30 individuals in the stable relapsing-remitting group (median 0, range 0-5), four total cortical lesions formed in 4/17 individuals in the progressive group (median 0, range 0-1), and 16 cortical lesions formed in 5/9 individuals in the active relapsing-remitting group (median 1, range 0-10, stable relapsing-remitting versus progressive versus active relapsing-remitting P = 0.006). New cortical lesions were not associated with greater change in any individual disability measure or in a composite measure of disability worsening (worsening Expanded Disability Status Scale or 9-hole peg test or 25-foot timed walk). Individuals with at least three paramagnetic rim lesions had a greater increase in cortical lesion volume over time (median 16 µl, range -61 to 215 versus median 1 µl, range -24 to 184, P = 0.007), but change in lesion volume was not associated with disability change. Baseline cortical lesion volume was higher in people with worsening disability (median 1010 µl, range 13-9888 versus median 267 µl, range 0-3539, P = 0.001, adjusted for age and sex) and in individuals with relapsing-remitting multiple sclerosis who subsequently transitioned to secondary progressive multiple sclerosis (median 2183 µl, range 270-9888 versus median 321 µl, range 0-6392 in those who remained relapsing-remitting, P = 0.01, adjusted for age and sex). Baseline white matter lesion volume was not associated with worsening disability or transition from relapsing-remitting to secondary progressive multiple sclerosis. Cortical lesion formation is rare in people with stable white matter lesions, even in those with worsening disability. Cortical but not white matter lesion burden predicts disability worsening, suggesting that disability progression is related to long-term effects of cortical lesions that form early in the disease, rather than to ongoing cortical lesion formation.

A nomogram to predict severe COVID-19 patients with increased pulmonary lesions in early days.

This study aimed to predict severe coronavirus disease 2019 (COVID-19) progression in patients with increased pneumonia lesions in the early days. A simplified nomogram was developed utilizing artificial intelligence (AI)-based quantified computed tomography (CT). From 17 December 2019 to 20 February 2020, a total of 246 patients were confirmed COVID-19 infected in Jingzhou Central Hospital, Hubei Province, China. Of these patients, 93 were mildly ill and had follow-up examinations in 7 days, and 61 of them had enlarged lesions on CT scans. We collected the neutrophil-to-lymphocyte ratio (NLR) and three quantitative CT features from two examinations within 7 days. The three quantitative CT features of pneumonia lesions, including ground-glass opacity volume (GV), semi-consolidation volume (SV), and consolidation volume (CV), were automatically calculated using AI. Additionally, the variation volumes of the lesions were also computed. Finally, a nomogram was developed using a multivariable logistic regression model. To simplify the model, we classified all the lesion volumes based on quartiles and curve fitting results. Among the 93 patients, 61 patients showed enlarged lesions on CT within 7 days, of whom 19 (31.1%) developed any severe illness. The multivariable logistic regression model included age, NLR on the second time, an increase in lesion volume, and changes in SV and CV in 7 days. The personalized prediction nomogram demonstrated strong discrimination in the sample, with an area under curve (AUC) and the receiver operating characteristic curve (ROC) of 0.961 and a 95% confidence interval (CI) of 0.917-1.000. Decision curve analysis illustrated that a nomogram based on quantitative AI was clinically useful. The integration of CT quantitative changes, NLR, and age in this model exhibits promising performance in predicting the progression to severe illness in COVID-19 patients with early-stage pneumonia lesions. This comprehensive approach holds the potential to assist clinical decision-making.

Risk Factors for Worsening Morphology and Visual Acuity in Eyes with Adult-Onset Foveomacular Vitelliform Dystrophy

PurposeTo explore clinical risk factors and optical coherence tomography (OCT) features associated with worse visual acuity (VA), progression of disease, choroidal neovascularization (CNV), and atrophy in eyes with adult-onset foveomacular vitelliform dystrophy (AOFVD). DesignSingle-center, retrospective, observational cohort study ParticipantsPatients seen at Duke Eye Center between January 2012 and May 2023 with a diagnosis of AOFVD confirmed via OCT and fundus autofluorescence. MethodsBaseline and final visit images from eyes with AOFVD were examined. Disease stage was assigned, and presence of atrophy or CNV was determined. Clinical and OCT features associated with progression to atrophy and CNV were determined using t-tests and chi-square analysis. Correlation with lower VA was determined using linear regression. Outcome MeasuresAssociation of clinical characteristics and OCT features with worse VA, progression of disease, CNV, and atrophy as determined by independent t-tests, chi-square analysis, and linear regression (p<0.05). Results101 eyes (63 patients) met inclusion criteria for this study, with mean follow-up duration of 48 months (SD 31 months). 51% of eyes progressed beyond baseline staging during follow-up; among baseline stage 1 eyes, incidence of atrophy was 0.068/person-year; incidence of CNV was 0.022/person-year. Risk factors for worse final VA were baseline presence of vitreomacular traction (VMT) (p=0.006), ellipsoid zone attenuation (p=0.024), increased lesion height and width (p<0.001). Predictors of progression include diabetes mellitus (p=0.012), statin use (p=0.031), presence of hyperreflective foci (p=0.012), and increased lesion width and volume (p=0.034, p=0.040). Predictors of atrophy include the baseline presence of VMT (p=0.018), decreased choroidal thickness (p=0.027), and greater maximal height, width, and volume of the lesion (p=0.031, p=0.020, p=0.009, respectively). Lower baseline VA (p=0.031) and increased lesion volume (p=0.042) were associated with CNV. ConclusionsClinical and OCT imaging features at baseline may prove useful in stratifying patient risk for progression, atrophy, CNV, and worse VA. Features such as statin use, diabetes, baseline VA, and laterality should be accounted for. OCT features such as lesion size, VMT, ellipsoid zone attenuation, choroidal thickness and hyperreflective foci may impart greater risk of poor outcomes. Future prospective analysis accounting for the time to development of atrophy and CNV is needed.

Consistency is key: influence of skull density ratio distribution on the formation of clinically effective lesions and long-term tremor suppression following treatment with MR-guided focused ultrasound.

Skull density ratio (SDR) influences the permeability of the skull to the ultrasound waves used in magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of tremor. SDR values vary across the skull and the mean value is known to be predictive of sonication thermal increase. The aim of this investigation was to explore the effects of the SDR distribution on clinical outcomes following treatment with MRgFUS. Data from 61 patients with essential or dystonic tremor treated with MRgFUS targeting the ventral intermediate nucleus (Vim) were retrospectively analyzed. Tremor suppression was assessed using the Clinical Rating Scale for Tremor (CRST) and hand tremor score (HTS). Vim ablation volume was measured on the T1-weighted MR image acquired both at 1 day and 12 months after treatment. The numerical distribution of SDR values measured for each element in the ultrasound transducer was quantified by calculating the mean, standard deviation, skewness, entropy, and kurtosis of the SDR histogram. The effect of the SDR metrics on change in CRST and HTS was examined using a linear mixed-effects model. Additionally, the effect of the regional distribution of SDR values was explored in an element-wise analysis between patients with above- and below-average tremor suppression. A significant positive effect was found between SDR kurtosis and improvement in CRST (β = 0.33, p = 0.004) and HTS (β = 0.38, p < 0.001). The effect was found to be significant at 1 month posttreatment (CRST: β = 0.415, p = 0.008; HTS: β = 0.369, p = 0.016), and at the most recent clinical follow-up (CRST: β = 0.395, p < 0.001; HTS: β = 0.386, p < 0.001). One hundred seventy-one significant elements were identified in the element-wise analysis. The mean percentage difference from the mean SDR in these elements was associated with improvement in CRST (β = 0.27, p < 0.008) and HTS (β = 0.27, p < 0.015). Higher SDR kurtosis was associated with increased lesion volume at 12 months (p = 0.040) and less reduction in volume relative to the day-1 lesion volume (p = 0.007). Greater SDR kurtosis was associated with larger, more stable lesions at 12 months posttreatment and increased tremor suppression at long-term follow-up. SDR kurtosis may provide a more meaningful prognostic factor than the mean SDR.

High-grade prostate cancer demonstrates preferential growth in the cranio-caudal axis and provides discrimination of disease grade in an MRI parametric model.

To determine if multiparametric MRI prostate cancer (PC) lesion dimensions in different axes could distinguish between PC, grade group (GG) >2, and GG >3 on targeted transperineal biopsy and create and validate a predictive model on a separate cohort. The maximum transverse, anterio-posterior, and cranio-caudal lesion dimensions were assessed against the presence of any cancer, GG >2, and GG >3 on biopsy by binary logistic regression. The optimum multivariate models were evaluated on a separate cohort. One hundred and ninety-three lesions from 148 patients were evaluated. Increased lesion volume, Prostate Specific Antigen (PSA), Prostate Imaging Reporting and Data System score, and decreased Apparent Diffusion Coefficient (ADC) were associated with increased GG (P < .001). The ratio of cranio-caudal to anterior-posterior lesion dimension increased from 1.20 (95% CI, 1.14-1.25) for GG ≤ 3 to 1.43 (95% CI, 1.28-1.57) for GG > 3 (P = .0022). The cranio-caudal dimension of the lesion was the strongest predictor of GG >3 (P = .000, area under the receiver operator characteristic curve [AUC] = 0.81). The best multivariate models had an AUC of 0.84 for cancer, 0.88 for GG > 2, and 0.89 for GG > 3. These models were evaluated on a separate cohort of 40 patients with 61 lesions. They demonstrated an AUC, sensitivity, and specificity of 0.82, 82.3%, and 55.5%, respectively, for the detection of cancer. For GG > 2, the models achieved an AUC of 0.84, sensitivity of 91.7%, and specificity of 69.4%. Additionally, for GG > 3, the models showed an AUC of 0.92, sensitivity of 88.9%, and specificity of 98.1%. Cranio-caudal lesion dimension when used in conjunction with other parameters can create a model superior to the Prostate Imaging Reporting and Data Systems score in predicting cancer. Higher-grade PC has a propensity to grow in the cranio-caudal direction, and this could be factored into MRI-based predictive models of prostate biopsy grade.

Rani terapijski odgovor na gama nož stereotaksičnu radiohirugiju u slučaju metastaza na mozgu kod primarnog karcinoma dojke

Introduction: Brain metastases represent the most common intracranial malignancy in the adult population, while breast cancer represents the leading cause of brain metastases among women. Brain metastases have increased in recent years due to improved therapeutic control of systemic disease and better diagnostic tools. Stereotactic radiosurgery (SRS) is used in patients with brain tumors to achieve local disease control, preserve the quality of life, and extend patient survival. This study aimed to evaluate the effects of SRS in patients with brain metastases from breast cancer through analysis of magnetic resonance imaging (MRI) parameters of the brain. Methods: Brain MRI was conducted in 30 adult female patients before and 3-6 months after SRS treatment. Radiological analysis was used to estimate lesion volumes before and after SRS. Results: Patients were categorized into four groups based on therapeutic response: 1 - complete response (CR) with loss of the lesion, 2 - partial response (PR) with more than 50% reduction in lesion volume, 3 - disease progression (PD) with more than 25% increase in lesion volume, 4 - stable disease (SD) if the patient did not display PR or PD. Among all patients, it was found that CR was present in 0 (0%), PR in 15 (50%), PD in 1 (3%), and SD in 14 (47%) patients. Following the SRS treatment, a statistically significant reduction in tumor volume was observed (p&lt;0.001). Conclusion: Radiological volumetric analysis of brain metastases after SRS showed a statistically significant reduction in lesion volume, demonstrating effective local disease control.

LST-AI: A deep learning ensemble for accurate MS lesion segmentation

Automated segmentation of brain white matter lesions is crucial for both clinical assessment and scientific research in multiple sclerosis (MS). Over a decade ago, we introduced an engineered lesion segmentation tool, LST. While recent lesion segmentation approaches have leveraged artificial intelligence (AI), they often remain proprietary and difficult to adopt. As an open-source tool, we present LST-AI, an advanced deep learning-based extension of LST that consists of an ensemble of three 3D U-Nets.LST-AI explicitly addresses the imbalance between white matter (WM) lesions and non-lesioned WM. It employs a composite loss function incorporating binary cross-entropy and Tversky loss to improve segmentation of the highly heterogeneous MS lesions. We train the network ensemble on 491 MS pairs of T1-weighted and FLAIR images, collected in-house from a 3T MRI scanner, and expert neuroradiologists manually segmented the utilized lesion maps for training. LST-AI also includes a lesion location annotation tool, labeling lesions as periventricular, infratentorial, and juxtacortical according to the 2017 McDonald criteria, and, additionally, as subcortical. We conduct evaluations on 103 test cases consisting of publicly available data using the Anima segmentation validation tools and compare LST-AI with several publicly available lesion segmentation models.Our empirical analysis shows that LST-AI achieves superior performance compared to existing methods. Its Dice and F1 scores exceeded 0.62, outperforming LST, SAMSEG (Sequence Adaptive Multimodal SEGmentation), and the popular nnUNet framework, which all scored below 0.56. Notably, LST-AI demonstrated exceptional performance on the MSSEG-1 challenge dataset, an international WM lesion segmentation challenge, with a Dice score of 0.65 and an F1 score of 0.63—surpassing all other competing models at the time of the challenge. With increasing lesion volume, the lesion detection rate rapidly increased with a detection rate of >75% for lesions with a volume between 10 mm3 and 100 mm3. Given its higher segmentation performance, we recommend that research groups currently using LST transition to LST-AI. To facilitate broad adoption, we are releasing LST-AI as an open-source model, available as a command-line tool, dockerized container, or Python script, enabling diverse applications across multiple platforms.

Interactions of optic radiation lesions with retinal and brain atrophy in early multiple sclerosis.

Retrograde trans-synaptic neuroaxonal degeneration is considered a key pathological factor of subclinical retinal neuroaxonal damage in multiple sclerosis (MS). We aim to evaluate the longitudinal association of optic radiation (OR) lesion activity with retinal neuroaxonal damage and its role in correlations between retinal and brain atrophy in people with clinically isolated syndrome and early MS (pweMS). Eighty-five pweMS were retrospectively screened from a prospective cohort (Berlin CIS cohort). Participants underwent 3T magnetic resonance imaging (MRI) for OR lesion volume and brain atrophy measurements and optical coherence tomography (OCT) for retinal layer thickness measurements. All pweMS were followed with serial OCT and MRI over a median follow-up of 2.9 (interquartile range: 2.6-3.4) years. Eyes with a history of optic neuritis prior to study enrollment were excluded. Linear mixed models were used to analyze the association of retinal layer thinning with changes in OR lesion volume and brain atrophy. Macular ganglion cell-inner plexiform layer (GCIPL) thinning was more pronounced in pweMS with OR lesion volume increase during follow-up compared to those without (Difference: -0.82 μm [95% CI:-1.49 to -0.15], p = 0.018). Furthermore, GCIPL thinning correlated with both OR lesion volume increase (β [95% CI] = -0.27 [-0.50 to -0.03], p = 0.028) and brain atrophy (β [95% CI] = 0.47 [0.25 to 0.70], p < 0.001). Correlations of GCIPL changes with brain atrophy did not differ between pweMS with or without OR lesion increase ( = 5.92e-7 , p = 0.762). Faster GCIPL thinning rate is associated with increased OR lesion load. Our results support the value of GCIPL as a sensitive biomarker reflecting both posterior visual pathway pathology and global brain neurodegeneration.

Composite Fibrin/Carbon Microfiber Implants for Bridging Spinal Cord Injury: A Translational Approach in Pigs.

Biomaterials may enhance neural repair after spinal cord injury (SCI) and testing their functionality in large animals is essential to achieve successful clinical translation. This work developed a porcine contusion/compression SCI model to investigate the consequences of myelotomy and implantation of fibrin gel containing biofunctionalized carbon microfibers (MFs). Fourteen pigs were distributed in SCI, SCI/myelotomy, and SCI/myelotomy/implant groups. An automated device was used for SCI. A dorsal myelotomy was performed on the lesion site at 1 day post-injury for removing cloths and devitalized tissue. Bundles of MFs coated with a conducting polymer and cell adhesion molecules were embedded in fibrin gel and used to bridge the spinal cord cavity. Reproducible lesions of about 1 cm in length were obtained. Myelotomy and lesion debridement caused no further neural damage compared to SCI alone but had little positive effect on neural regrowth. The MFs/fibrin gel implant facilitated axonal sprouting, elongation, and alignment within the lesion. However, the implant also increased lesion volume and was ineffective in preventing fibrosis, thus precluding functional neural regeneration. Our results indicate that myelotomy and lesion debridement can be advantageously used for implanting MF-based scaffolds. However, the implants need refinement and pharmaceuticals will be necessary to limit scarring.

AB-452674-4 SHORT AND SWEET: EXPLORING HIGH POWER, SHORT DURATION RADIOFREQUENCY ABLATION STRATEGIES FOR OPTIMAL LESION FORMATION

High power, short duration (HPSD) radiofrequency (RF) ablation allows for wider, more uniform ablation lesion formation as compared to moderate power, moderate duration ablation. Ablation with HPSD capitalizes on the resistive heating phase providing immediate heating to the target tissue while preventing the consequences of conductive heating. Understanding the threshold where resistive heating transitions to conductive heating may allow for optimization of parameters to favor resistive heating. Additionally, HPSD lesion application has been associated with a lower risk of complications, including cardiac perforation and atrioesophageal fistulas. To assess lesion formation with variations in RF duration and contact force utilizing a HPSD strategy in an ex vivo model. This study utilized recently harvested swine heart tissue ablated using a contact force sensing irrigation ablation catheter submerged in a saline bath with a target temperature of 36 °C and an impedance of 140 Ω. Step 1 compared various RF durations (1-5, 8, and 10 seconds(s)) with 50 Watts (W) and an average of 10g of force applied to the epicardial surface of the left ventricle. Six lesions were applied for each time duration. For step two of the procedure, we assessed the impact of contact force (1g, 5g, 10g, 20g) on lesion size and depth using 50 W and 5s RF duration. Five lesions were applied for each amount of contact force. The tissue was stained in a 2,3,5-Triphenyltetrazolium chloride bath prior to measurements. Of the 42 lesions created utilizing HPSD with variable durations of RF duration, application of >3s resulted in the creation of visual lesions within the tissue. There was an increase in lesion volume with longer duration ablation application (50W/10g), with 5, 8 and 10s durations generating lesion volumes of 16.8mm3, 26.8mm3 and 40.6mm3, respectively. All 20 lesion applications with varying degrees of contact force (50W/5s) resulted in visual lesions. There was an increase in lesion volume with higher contact force plateauing at 10 g, compared to 20g (28.9mm3 vs 31.9mm3, respectively). In an animal model, a HPSD ablation strategy focused on short duration lesion application with lower contact forces (50W/5s/10g) created lesions of similar volume to 20g of force application. In the initial 10s of lesion formation, a force >10g may have a lesser role and may potentially represent a transition point between resistive and conductive heating.

Exploring the neuroprotective effects of montelukast on brain inflammation and metabolism in a rat model of quinolinic acid-induced striatal neurotoxicity

BackgroundOne intrastriatal administration of quinolinic acid (QA) in rats induces a lesion with features resembling those observed in Huntington’s disease. Our aim is to evaluate the effects of the cysteinyl leukotriene receptor antagonist montelukast (MLK), which exhibited neuroprotection in different preclinical models of neurodegeneration, on QA-induced neuroinflammation and regional metabolic functions.MethodsThe right and left striatum of Sprague Dawley and athymic nude rats were injected with QA and vehicle (VEH), respectively. Starting from the day before QA injection, animals were treated with 1 or 10 mg/kg of MLK or VEH for 14 days. At 14 and 30 days post-lesion, animals were monitored with magnetic resonance imaging (MRI) and positron emission tomography (PET) using [18F]-VC701, a translocator protein (TSPO)-specific radiotracer. Striatal neuroinflammatory response was measured post-mortem in rats treated with 1 mg/kg of MLK by immunofluorescence. Rats treated with 10 mg/kg of MLK also underwent a [18F]-FDG PET study at baseline and 4 months after lesion. [18F]-FDG PET data were then used to assess metabolic connectivity between brain regions by applying a covariance analysis method.ResultsMLK treatment was not able to reduce the QA-induced increase in striatal TSPO PET signal and MRI lesion volume, where we only detected a trend towards reduction in animals treated with 10 mg/kg of MLK. Post-mortem immunofluorescence analysis revealed that MLK attenuated the increase in striatal markers of astrogliosis and activated microglia in the lesioned hemisphere. We also found a significant increase in a marker of anti-inflammatory activity (MannR) and a trend towards reduction in a marker of pro-inflammatory activity (iNOS) in the lesioned striatum of MLK—compared to VEH-treated rats. [18F]-FDG uptake was significantly reduced in the striatum and ipsilesional cortical regions of VEH-treated rats at 4 months after lesion. MLK administration preserved glucose metabolism in these cortical regions, but not in the striatum. Finally, MLK was able to counteract changes in metabolic connectivity and measures of network topology induced by QA, in both lesioned and non-lesioned hemispheres.ConclusionsOverall, MLK treatment produced a significant neuroprotective effect by reducing neuroinflammation assessed by immunofluorescence and preserving regional brain metabolism and metabolic connectivity from QA-induced neurotoxicity in cortical and subcortical regions.

Predictors of long-term disability in multiple sclerosis patients using routine magnetic resonance imaging data: A 15-year retrospective study.

Early identification of patients at high risk of progression could help with a personalised treatment strategy. Magnetic resonance imaging (MRI) measures have been proposed to predict long-term disability in multiple sclerosis (MS), but a reliable predictor that can be easily implemented clinically is still needed. Assess MRI measures during the first 5years of the MS disease course for the ability to predict progression at 10+ years. Eighty-two MS patients (53 females), with ≥10years of clinical follow-up and having two MRI scans, were included. Clinical data were obtained at baseline, follow-up and at ≥10years. White matter lesion (WML) counts and volumes, and four linear brain sizes were measured on T2/FLAIR 'Fluid-Attenuated-Inversion-Recovery' and T1-weighted images. Baseline and follow-up inter-caudate diameter (ICD) and third ventricular width (TVW) measures correlated positively with Expanded Disability Status Scale, ≥10 or more of WMLs showed a high sensitivity in predicting progression, at ≥10years. A steeper rate of lesion volume increase was observed in subjects converting to secondary progressive MS. The sensitivity and specificity of both ICD and TVW, to predict disability at ≥10years were 60% and 64%, respectively. Despite advances in brain imaging and computerised volumetric analysis, ICD and TVW remain relevant as they are simple, fast and have the potential in predicting long-term disability. However, in this study, despite the statistical significance of these measures, the clinical utility is still not reliable.

High fat diet exacerbates long-term metabolic, neuropathological, and behavioral derangements in an experimental mouse model of traumatic brain injury

AimsTraumatic brain injury (TBI) constitutes a serious public health concern. Although TBI targets the brain, it can exert several systemic effects which can worsen the complications observed in TBI subjects. Currently, there is no FDA-approved therapy available for its treatment. Thus, there has been an increasing need to understand other factors that could modulate TBI outcomes. Among the factors involved are diet and lifestyle. High-fat diets (HFD), rich in saturated fat, have been associated with adverse effects on brain health. Main methodsTo study this phenomenon, an experimental mouse model of open head injury, induced by the controlled cortical impact was used along with high-fat feeding to evaluate the impact of HFD on brain injury outcomes. Mice were fed HFD for a period of two months where several neurological, behavioral, and molecular outcomes were assessed to investigate the impact on chronic consequences of the injury 30 days post-TBI. Key findingsTwo months of HFD feeding, together with TBI, led to a notable metabolic, neurological, and behavioral impairment. HFD was associated with increased blood glucose and fat-to-lean ratio. Spatial learning and memory, as well as motor coordination, were all significantly impaired. Notably, HFD aggravated neuroinflammation, oxidative stress, and neurodegeneration. Also, cell proliferation post-TBI was repressed by HFD, which was accompanied by an increased lesion volume. SignificanceOur research indicated that chronic HFD feeding can worsen functional outcomes, predispose to neurodegeneration, and decrease brain recovery post-TBI. This sheds light on the clinical impact of HFD on TBI pathophysiology and rehabilitation as well.

Chronic demyelination of rabbit lesions is attributable to failed oligodendrocyte progenitor cell repopulation.

The failure of remyelination in the human CNS contributes to axonal injury and disease progression in multiple sclerosis (MS). In contrast to regions of chronic demyelination in the human brain, remyelination in murine models is preceded by abundant oligodendrocyte progenitor cell (OPC) repopulation, such that OPC density within regions of demyelination far exceeds that of normal white matter (NWM). As such, we hypothesized that efficient OPC repopulation was a prerequisite of successful remyelination, and that increased lesion volume may contribute to the failure of OPC repopulation in human brain. In this study, we characterized the pattern of OPC activation and proliferation following induction of lysolecithin-induced chronic demyelination in adult rabbits. The density of OPCs never exceeded that of NWM and oligodendrocyte density did not recover even at 6months post-injection. Rabbit OPC recruitment in large lesions was further characterized by chronic Sox2 expression in OPCs located in the lesion core and upregulation of quiescence-associated Prrx1 mRNA at the lesion border. Surprisingly, when small rabbit lesions of equivalent size to mouse were induced, they too exhibited reduced OPC repopulation. However, small lesions were distinct from large lesions as they displayed an almost complete lack of OPC proliferation following demyelination. These differences in the response to demyelination suggest that both volume dependent and species-specific mechanisms are critical in the regulation of OPC proliferation and lesion repopulation and suggest that alternate models will be necessary to fully understand the mechanisms that contribute to failed remyelination in MS.

Mechanisms of central brain atrophy in multiple sclerosis

Background: Change in ventricular volume has been suggested as surrogate measure of central brain atrophy (CBA) applicable to the everyday management of multiple sclerosis (MS) patients. Objectives: We investigated the contribution of inflammatory activity (including the severity of lesional tissue damage) to CBA. Methods: Fifty patients with relapsing–remitting multiple sclerosis (RRMS) were enrolled. Lesional activity during 4 years of follow-up was analysed using custom-build software, which segmented expanding part of the chronic lesions, new confluent lesions and new free-standing lesions. The degree of lesional tissue damage was assessed by change in mean diffusivity (MD). Volumetric change of lateral ventricles was used to measure CBA. Results: During follow-up, ventricles expanded on average by 12.6% ± 13.7% (mean ± SD). There was a significant increase of total lesion volume, 69.3% of which was due to expansion of chronic lesions. Correlation between volume of combined lesional activity and CBA (r2 = 0.67) increased when lesion volume was adjusted by the degree of tissue damage severity (r2 = 0.81). Regression analysis explained 90% of CBA variability, revealing that chronic lesion expansion was by far the largest contributor to ventricular enlargement. Discussion: CBA is almost entirely explained by the combination of the volume and severity of lesional activity. The expansion of chronic lesions plays a central role in this process.

Chronic lesion activity and disability progression in secondary progressive multiple sclerosis

ObjectiveSlowly expanding lesions (SELs), a subgroup of chronic white matter lesions that gradually expand over time, have been shown to predict disability accumulation in primary progressive multiple sclerosis (MS) disease....

Comparison of radiofrequency ablation from the coronary cusps and endocardial left ventricular outflow tract for left ventricular summit ventricular arrhythmias in a porcine and infrared thermal model.

The coronary cusps (CCs) are utilized as an alternative vantage point for radiofrequency catheter ablation (RFCA) of left ventricularsummit ventricular arrhythmias but are sometimes a challenge despite favorable activation timing and pace mapping. Ex vivo experiments were performed in 12 intact porcine hearts submerged in a 37°C saline bath. Radiofrequency (RF) applications were delivered with an irrigated contact force sensing catheter oriented 45° to the endocardial left ventricular outflow tract (LVOT) surface and nadir of the CCs using different dosing parameters. Sections were stained in 2% triphenyltetrazolium chloride and lesion dimensions were measured. Thermal infrared imaging analysis was used to compare time-to-lethal tissue temperature and depth/area of lethal isotherms. A total of 60 RF applications were performed under different dosing parameters for (1) 30, 40, and 50 Watts (W) × 30 s and (2) 40 W × 30, 45, and 60 s. Lesion depth was greater with RFCA from LVOT than from the CCs (maximum depth 6.11vs. 2.68 mm). Longer RF duration led to larger lesion volume in the CC group (40 W × 30 s: 8.1 ± 0.4 vs. 40 W × 60 s: 10.1 ± 0.96 mm; p = .002). One steam pop occurred in both the LVOT (50 W × 30 s) and CC groups (40 W × 60 s). Time-to-reach lethal temperature of 58°C was longer in the CC group than in the LVOT group (4.7 vs. 11.3 s; p = .02) CONCLUSIONS: RFCA from the CC led comparatively to shallower lesion depth than from the LVOT. Longer RF duration led to an increase in lesion volume during ablation from CCs.