Contralateral Hemisphere Research Articles

Semiology and Neurophysiology of Clonic Seizures: A Report of 39 Patients.

Clonic seizures are currently defined as repetitive and rhythmic myoclonic contractions of a specific body part, producing twitching movements at a frequency of 0.2-5 Hz. There are few studies in the literature that have reported a detailed analysis of the semiology, neurophysiology, and lateralizing value of clonic seizures. In this article, we aim to report our findings from a retrospective review of 39 patients. We identified 39 patients (48 seizures) from our center who had been admitted with clonic seizures between 2016 and 2022. We performed a retrospective review of their video-EEG recordings for semiology and ictal EEG findings. Seventeen patients also had simultaneous surface-EMG (sEMG) electrodes placed on affected body parts, which were analyzed as well. The most common initial affected body parts were face, arm, and hand. In most of the cases, seizures propagated from lower face to upper face and distal hand to proximal arm. The most common seizure-onset zone was the perirolandic region, and the most common EEG seizure pattern was paroxysmal rhythmic monomorphic activity. The lateralizing value for EEG seizure onset to contralateral hemisphere in unilateral clonic seizures (n = 39) was 100%. All seizures recorded with sEMG electrodes demonstrated synchronous brief tetanic contractions of agonists and antagonists, alternating with synchronous silent periods. Arrhythmic clonic seizures were associated with periodic epileptiform discharges on the EEG, whereas rhythmic clonic seizures were associated with paroxysmal rhythmic monomorphic activity. Overall, the most common etiology was cerebrovascular injuries, followed by tumors. Clonic seizures are characterized by synchronized brief tetanic contractions of agonist and antagonistic muscles alternating with synchronized silent periods, giving rise to the visible twitching. The most common seizure onset zone is in the perirolandic region, which is consistent with the symptomatogenic zone being in the primary motor area. The lateralizing value of unilateral clonic seizures for seizure onset in the contralateral hemisphere is 100%.

444 Quantitative Mapping of Cerebral Blood Flow and Blood-Brain Barrier Water Exchange Rate (Kw) Reveals the Mechanobiological Impact of Cranioplasty: A Magnetic Resonance Imaging Study of Patients With Cranial Defects

INTRODUCTION: Large cranial defects may cause neurological decline due to brain shift, while cranioplasty may improve cognitive function, although the underlying mechanisms remain poorly understood. Blood-brain barrier (BBB) water exchange rate (Kw) is a novel magnetic resonance imaging (MRI) method which provides insights into the processes underlying the effects of cranioplasty. METHODS: Adult patients with cranial defects who were candidates for elective cranioplasty were consented and enrolled. Using a 3T MRI, we conducted baseline imaging on all patients, and repeated the imaging during the early post-cranioplasty period. The Kw and CBF were quantified, and asymmetry was calculated as the difference between the values on the ipsilateral and contralateral hemispheres relative to the cranial defect, divided by the sum of those values. Pairwise comparisons of the changes from baseline to post-cranioplasty period were performed using Wilcoxon signed-rank test. RESULTS: A total of 10 patients were enrolled (mean age: 35.4 ± 9.49, 9/10 men). The global CBF showed significant improvements after cranioplasty. There was a remarkable Kw asymmetry in the caudate area at baseline (low on defect side), which significantly improved post-operatively (median: -0.077 vs. 0.021, p = 0.049), while the changes in CBF in this area were not significant (median: -0.002 vs. 0.014, p = 0.160). Other brain regions yielded no significant changes in Kw asymmetry. CONCLUSIONS: Reduced Kw has been reported in cognitive decline and cerebral small vessel diseases, and may be related to impaired water circulation in the brain. We observed increased global CBF and Kw asymmetry in caudate which may reflect improved brain physiology and water circulation following cranioplasty. Kw is a non-invasive and non-contrast method that offers an opportunity to understand the intricate changes in brain homeostasis following reconstruction surgery.

Long-Term Region-Specific Mitochondrial Functionality Changes in Both Cerebral Hemispheres after fMCAo Model of Ischemic Stroke.

Cerebral ischemia/reperfusion (I/R) refers to a secondary brain injury that results in mitochondrial dysfunction of variable extent, leading to neuronal cell damage. The impact of this process has mainly been studied in the short term, from the early hours up to one week after blood flow reperfusion, and in the ischemic hemisphere only. The focus of this study was to assess the long-term impacts of I/R on mitochondrial functionality using high-resolution fluorespirometry to evaluate state-dependent activities in both ischemic (ipsilateral) and non-ischemic (contralateral) hemispheres of male mice 60, 90, 120, and 180 days after I/R caused by 60-min-long filament-induced middle cerebral artery occlusion (fMCAo). Our results indicate that in cortical tissues, succinate-supported oxygen flux (Complex I&II OXPHOS state) and H2O2 production (Complex II LEAK state) were significantly decreased in the fMCAo (stroke) group ipsilateral hemisphere compared to measurements in the contralateral hemisphere 60 and 90 days after stroke. In hippocampal tissues, during the Complex I&II ET state, mitochondrial respiration was generally lower in the ipsilateral compared to the contralateral hemisphere 90 days following stroke. An aging-dependent impact on mitochondria oxygen consumption following I/R injury was observed 180 days after surgery, wherein Complex I&II activities were lowest in both hemispheres. The obtained results highlight the importance of long-term studies in the field of ischemic stroke, particularly when evaluating mitochondrial bioenergetics in specific brain regions within and between separately affected cerebral hemispheres.

DYNAMIC ASSESSMENT OF CEREBRAL PERFUSION BLOOD FLOW IN THE EARLY POST-STROKE PERIOD ACCORDING TO NON-CONTRAST MRI DATA

HighlightsThe non-contrast perfusion MR sequence pCASL (pseudocontinuous arterial spin labeling) is a technique that allows specialist to quantify and trace the changes in cerebral blood flow in the early post-stroke period. At the same time, there is a change in perfusion indices not only in the ischemic stroke area, but also in visually intact areas of the ipsilateral and contralateral hemispheres of the brain, which indicates the involvement of the blood supply area and the brain as a whole in the pathological process. The obtained data on the dynamics in perfusion, verified by the results of cognitive tests, open up the prospect of a comprehensive study of stroke as a complex brain disease with the possibility of predictive assessment of rehabilitation. Aim. To assess the dynamics of microcirculatory changes in the brain in the early post-stroke period by non-contrast perfusion MRI.Methods. The study included 42 patients with acute ischemic stroke. The patients were examined by 3T MRI using the following sequences: DWI-EPI, 3D FLAIR-SPIR, T2-TSE, T1W 3D-TFE, and pseudocontinuous arterial spin labeling (pCASL) on 1–3 days, 7–10 days and 3 months later after the manifestation of acute ischemic stroke. The cerebral blood flow (CBF) was obtained in 4 supratentorial regions of the brain: in the ischemic stroke and contralateral areas, as well as in a visually intact area of the ipsilateral and contralateral hemispheres (mL/100g/min).Results. In the ischemic stroke area, CBF increased from 19.86±5.69 (mean+Std) to 27.57±4.86 by first to the second examination, which was associated with the infusion therapy, local inflammatory response and compensatory reperfusion. By the 3rd examination CBF decreased to 14.48±3.66 (Student t-test, p<0.05), which reflects cystic and atrophic transformation of the affected area. In visually intact white matter of the ipsilateral and contralateral hemispheres, CBF increased from hypoperfused to normoperfused from the first to the third examination. There was a significant decrease (p<0.001) in tissue blood flow (by 54% for the 1st, 38% for the 2nd, 67% for the 3rd examination) in the ischemia area relative to intact parts of the brain.Conclusion. The pCASL allowed us to assess CBF in the post-stroke period in the ischemic area and in visually intact area, nevertheless, it requires additional pre- and postprocessing of data to obtain quantitative values. At the same time, we observed changes in perfusion in the ischemic stroke area, and in the visually intact areas of the ipsilateral and contralateral hemispheres of the brain, indicating the involvement of the cerebral blood flow and brain as a whole in the pathological process.

White and gray matter integrity evaluated by MRI-DTI can serve as noninvasive and reliable indicators of structural and functional alterations in chronic neurotrauma

We aimed to evaluate whether white and gray matter microstructure changes observed with magnetic resonance imaging (MRI)-based diffusion tensor imaging (DTI) can be used to reflect the progression of chronic brain trauma. The MRI-DTI parameters, neuropathologic changes, and behavioral performance of adult male Wistar rats that underwent moderate (2.1 atm on day “0”) or repeated mild (1.5 atm on days “0” and “2”) traumatic brain injury (TBI or rmTBI) or sham operation were evaluated at 7 days, 14 days, and 1–9 months after surgery. Neurobehavioral tests showed that TBI causes long-term motor, cognitive and neurological deficits, whereas rmTBI results in more significant deficits in these paradigms. Both histology and MRI show that rmTBI causes more significant changes in brain lesion volumes than TBI. In vivo DTI further reveals that TBI and rmTBI cause persistent microstructural changes in white matter tracts (such as the body of the corpus callosum, splenium of corpus callus, internal capsule and/or angular bundle) of both two hemispheres. Luxol fast blue measurements reveal similar myelin loss (as well as reduction in white matter thickness) in ipsilateral and contralateral hemispheres as observed by DTI analysis in injured rats. These data indicate that the disintegration of microstructural changes in white and gray matter parameters analyzed by MRI-DTI can serve as noninvasive and reliable markers of structural and functional level alterations in chronic TBI.

Edge-wise analysis reveals white matter connectivity associated with focal to bilateral tonic-clonic seizures.

Focal to bilateral tonic-clonic seizures (FBTCS) represent a challenging subtype of focal temporal lobe epilepsy (TLE) in terms of both severity and treatment response. Most studies have focused on regional brain analysis that is agnostic to the distribution of white matter (WM) pathways associated with a node. We implemented a more selective, edge-wise approach that allowed for identification of the individual connections unique to FBTCS. T1-weighted and diffusion-weighted images were obtained from 22 patients with solely focal seizures (FS), 43 FBTCS patients, and 65 age/sex-matched healthy participants (HPs), yielding streamline (STR) connectome matrices. We used diffusion tensor-derived STRs in an edge-wise approach to determine specific structural connectivity changes associated with seizure generalization in FBTCS compared to matched FS and HPs. Graph theory metrics were computed on both node- and edge-based connectivity matrices. Edge-wise analyses demonstrated that all significantly abnormal cross-hemispheric connections belonged to the FBTCS group. Abnormal connections associated with FBTCS were mostly housed in the contralateral hemisphere, with graph metric values generally decreased compared to HPs. In FBTCS, the contralateral amygdala showed selective decreases in the structural connection pathways to the contralateral frontal lobe. Abnormal connections in TLE involved the amygdala, with the ipsilateral side showing increases and the contralateral decreases. All the FS findings indicated higher graph metrics for connections involving the ipsilateral amygdala. Data also showed that some FBTCS connectivity effects are moderated by aging, recent seizure frequency, and longer illness duration. Data showed that not all STR pathways are equally affected by the seizure propagation of FBTCS. We demonstrated two key biases, one indicating a large role for the amygdala in the propagation of seizures, the other pointing to the prominent role of cross-hemispheric and contralateral hemisphere connections in FBTCS. We demonstrated topographic reorganization in FBTCS, pointing to the specific WM tracts involved.

A patient-specific circle of Willis blood flow model in predicting outcomes of balloon test occlusion.

Balloon test occlusion (BTO) evaluates cerebral ischemic tolerance before internal carotid artery (ICA) sacrifice but carries risks like dissection and thrombosis. This study introduces a new approach using a patient-specific circle of Willis (COW) blood flow model, based on non-invasive quantitative MR angiography (qMRA) measurements, to predict the outcomes of BTO. We developed individualized COW blood flow models for 43 patients undergoing BTO. These models simulated blood flow and pressure under normal conditions and with the ICA occlusion. We then compared the model's predictions of blood flow changes due to the simulated ICA occlusion to actual qMRA measurements before the BTO. For all 31 BTO failures, the ipsilateral hemisphere showed an average flow decrease of 15 ± 10% (mean ± standard deviation), compared to 3 ± 2% in the contralateral hemisphere. In all 12 BTO passes, these figures were 6 ± 3% and 1 ± 0.8%, respectively. Notably, all BTO passes had less than a 10% reduction in the ipsilateral hemisphere. In contrast, 65% of BTO failures and 67% single-photon emission computed tomography (SPECT) failures exhibited a decrease of 10% or more in the same region. Blood flow reduction exceeding 10% in the ipsilateral hemisphere during BTO is a strong predictor of failure in both BTO and SPECT. Our patient-specific COW blood flow models, incorporating detailed flow and arterial geometry data, offered valuable insights for predicting BTO outcomes. These models are especially beneficial for situations where conducting BTO or SPECT is clinically impractical.

Abstract 3355: Unraveling the molecular mechanisms of glioma migration: Exploring the role of cell intrinsic and stromal ephrin receptor-ligand signaling

Abstract Diffuse invasion, a hallmark of malignant gliomas, makes these tumors surgically incurable and is the ultimate cause of death. While glioma cells can migrate along blood vessels and in neuron-rich regions, their preferred route of migration is along white matter (WM) tracts, which allows tumor cells to spread to the contralateral hemisphere with devastating neurocognitive consequences. The underlying mechanisms of in vivo glioma cell migration are poorly understood. There is emerging evidence that glioblastoma multiforme (GBM) cells may hijack migration mechanisms used during brain development. Accordingly, we used a neonatal plasmid electroporation GBM model (CRISPR-Cas9, -Cre,gRNAs targeting NF1, p53, PTEN, and piggyBac-glast) to generate a highly penetrant diffusely invasive glioma models with preference for migration along myelinated fiber tracts including the corpus callosum (CC). To test the in vivo role of integrin-mediated migration, tumors were generated using conditional integrin β1f/f (ITGB1) or focal adhesion kinase (FAKf/f) mice. Both ITGB1 and FAK null GBM cells (confirmed by western blot analysis) showed diffuse infiltration similar to WT mice, suggesting that integrin signaling is not essential for in vivo GBM cell migration. Next, we tested the role ephrin-signaling using a series of transgenic neonatal mice, including EPH-B1-/-, -B2-/-, -B1/2-/-, -kinase-dead (KD) and a gain-of-function mutant). EPH1/2-/- GBM, but not the other genetic models, consistently formed tumors which showed no diffuse single-cell infiltration, but rather grew as a solid expanding mass. An extensive panel of in vitro studies comparing WT and EPHB1/2-/- GBM patterns of growth and migration, including time-lapse random walk, neurosphere radial migration, migration along patterned surfaces, and laminin-coated confined 3D channels, showed similar patterns of migration, despite the marked differences in vivo. These contrasting in vivo and in vitro results raise the possibility that EPH-B1/2 receptors may require their cognate ephrin ligands to facilitate migration through the WM tracts. To test this hypothesis, we are using Ephrin-B1f/f, B2f/f mice for in vivo cell-type specific deletion in WM tract stroma cells and primary astrocytes derived from these mice for ex vivo co-culture studies. Our preliminary data suggest that EPH/EPHRIN interactions may regulate GBM cell migration. Citation Format: Jesung Moon, Xiaofei Gao, Peiguo Ding, Fnu Bilal, Smita Rindhe, Ning Gao, Digant P. Dave, Mark Henkemeyer, Elizabeth A. Maher, Robert M. Bachoo. Unraveling the molecular mechanisms of glioma migration: Exploring the role of cell intrinsic and stromal ephrin receptor-ligand signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3355.

Abstract 4159: Noninvasive measurement of murine glioblastoma in vivo with a benchtop ultrasound instrument

Abstract The purpose of this study was to evaluate a new in vivo approach for rapidly measuring tumor volumes in rodent models for glioblastoma (GBM). GBM is the most common primary brain tumor with <5% of patients surviving >5 years post diagnosis. These poor outcomes underscore the importance of researching new treatment options, and murine models play a vital role in this. Noninvasive measurements of murine GBM tumors are commonly performed using CT and MRI but these tools are costly and time-consuming to use. BLI can quickly detect the presence of GBM cells in vivo, but image data can be challenging to correlate to tumor volume. In this study we demonstrate the feasibility of imaging GBM in vivo through the intact mouse skull using a benchtop robotic ultrasound scanner. This approach could offer researchers a means to quickly size tumors in the murine brain noninvasively. To test feasibility of this approach, a female athymic nude mouse aged 16 weeks was implanted with 2e5 U87 GBM cells in the brain. The tumor was given 25 days to develop prior to ultrasound imaging. After imaging, the brain was harvested for ex vivo validation of tumor presence and volume. Imaging was performed using a Vega ultrasound system (Revvity, Waltham, MA, USA) with the mouse in supine position and fur removed from head with depilatory cream. In vivo imaging consisted of a contrast-enhanced acoustic angiography (AA) scan to assess tumor perfusion. An ex vivo B-mode scan of the brain was collected after sacrificing the animal to validate the location and size of the tumor without interference from the skull. The tumor volumes were measured in each image and compared. 3D segmentations in the ex vivo and in vivo images yielded volumes of 43.1 mm3 and 44.6 mm3, respectively, a 3.5% variance. In the in vivo AA image, the borders of the tumor were adequately well-defined for volume estimation, despite some shadowing from the sagittal suture of the skull. In the B-mode image of the excised brain, the tumor appeared hyperechoic compared to the contralateral hemisphere. Images were acquired in < 2 min. This pilot study demonstrates a potential alternative to CT and MRI for monitoring of GBM volumes in vivo. Citation Format: Thomas M. Kierski, Juan D. Rojas, Morrent Thang, Shawn D. Hingtgen, Phillip G. Durham, Paul A. Dayton, Tomek J. Czernuszewicz, Ryan C. Gessner. Noninvasive measurement of murine glioblastoma in vivo with a benchtop ultrasound instrument [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4159.

MicroRNA-133b Dysregulation in a Mouse Model of Cervical Contusion Injury.

Our previous research studies have demonstrated the role of microRNA133b (miR133b) in healing the contused spinal cord when administered either intranasally or intravenously 24 h following an injury. While our data showed beneficial effects of exogenous miR133b delivered within hours of a spinal cord injury (SCI), the kinetics of endogenous miR133b levels in the contused spinal cord and rostral/caudal segments of the injury were not fully investigated. In this study, we examined the miR133b dysregulation in a mouse model of moderate unilateral contusion injury at the fifth cervical (C5) level. Between 30 min and 7 days post-injury, mice were euthanized and tissues were collected from different areas of the spinal cord, ipsilateral and contralateral prefrontal motor cortices, and off-targets such as lung and spleen. The endogenous level of miR133b was determined by RT-qPCR. We found that after SCI, (a) most changes in miR133b level were restricted to the injured area with very limited alterations in the rostral and caudal parts relative to the injury site, (b) acute changes in the endogenous levels were predominantly specific to the lesion site with delayed miR133b changes in the motor cortex, and (c) ipsilateral and contralateral hemispheres responded differently to unilateral SCI. Our results suggest that the therapeutic window for exogenous miR133b therapy begins earlier than 24 h post-injury and potentially lasts longer than 7 days.

Distribution, development, and identity of retinal ganglion cells labeled in the Sert-Cre reporter mouse.

The mouse retina contains over 40 types of retinal ganglion cells (RGCs) that differ in morphology, function, or gene expression. RGCs also differ by whether their axons target the brain.s ipsilateral or contralateral hemisphere. Contralaterally projecting RGCs (contraRGCs) are widespread in mouse retina, whereas ipsilateral projecting RGCs (ipsiRGCs) are confined to the ventro-temporal (VT) crescent of retina. In this study, we employed the Sert-Cre transgenic line, which had been reported to selectively label ipsiRGCs, to study ipsiRGCs during development. Although the number of Cre-expressing ipsiRGCs did not significantly increase with postnatal age, the region of retina that they occupied did, and by adulthood represented ~30% of the retinal surface. Unexpectedly, genetic ablation of Sert-Cre cells failed to fully disrupt ipsilateral projecting retinal axons, suggesting that not all ipsiRGCs generated Cre in Sert-Cre mice. To test this hypothesis, we retrogradely labeled ipsiRGCs in Sert-Cre mice which revealed that not all ipsiRGCs are labeled in Sert-Cre mice and a small population of contraRGCs flanking the VT crescent generates Cre in this line. These results do not negate the usefulness of the Sert-Cre mouse but do raise important caveats to the interpretation of such studies.

Evaluation of the contralateral hemisphere with DWI in pediatric patients with Dyke-Davidoff-Masson syndrome.

Dyke-Davidoff-Masson Syndrome (DDMS) is a clinical syndrome that causes different clinical symptoms and is defined by volume decrement in one cerebral hemisphere. In this study, we aimed to evaluate the involvement of the normal-appearing contralateral hemisphere in 16 pediatric patients with DDMS using diffusion-weighted imaging (DWI). Brain MRIs were retrospectively reviewed between January 2014 and January 2023. Sixteen pediatric patients radiologically compatible with DDMS were included in the study. Sixteen children who had undergone brain MRI, most commonly for headaches and whose MRI findings had been completely normal, were included as the control group. Apparent diffusion coefficient (ADC) values of the deep gray and white matter of the normal-appearing hemisphere in the patient group were calculated and compared with that of the control group. The ADC values of the gray and white matters of the patient and control groups were not statistically different. However, in the patient group, the ADC values of the gray and white matters in males were remarkably lower than in females (p = 0.038, p = 0.037, respectively). The difference in the ADC values of the contralateral hemisphere between females and males in the patient group suggests that the normal-appearing hemisphere may have been affected by DDMS. Although, the exact mechanism of this effect is not known. Therefore, in patients with DDMS, contralateral hemisphere involvement in cerebral hemiatrophy and hemispherectomy should be evaluated clinically and radiologically.

Prognostic Value of Apparent Diffusion Coefficient (ADC) in Patients with Diffuse Gliomas.

This study aimed to evaluate potential posttreatment changes in ADC values within the tissue surrounding the enhancing lesion, particularly in areas not exhibiting MRI characteristics of involvement. Additionally, the objective was to investigate the correlations among ADC values, treatment response, and survival outcomes in individuals diagnosed with gliomas. This retrospective study included a total of 49 patients that underwent either stereotactic biopsy or maximal surgical resection. Histologically confirmed as Grade III or IV gliomas, all cases adhered to the 2016 and 2021 WHO classifications, with subsequent radio-chemotherapy administered post-surgery. Patients were divided into two groups: short and long survival groups. Baseline and follow-up MRI scans were obtained on a 1.5 T MRI scanner. Two ROI circles were positioned near the enhancing area, one ROI in the NAWM ipsilateral to the neoplasm and another symmetrically in the contralateral hemisphere on ADC maps. At follow-up there was a significant difference in both ipsilateral and contralateral NAWM between the two groups, -0.0857 (p = 0.004) and -0.0607 (p = 0.037), respectively. There was a weak negative correlation between survival and ADC values in ipsilateral and contralateral NAWM at the baseline with the correlation coefficient -0.328 (p = 0.02) and -0.302 (p = 0.04), respectively. The correlation was stronger at the follow-up. The findings indicate that ADC values in normal-appearing white matter (NAWM) may function as a prognostic biomarker in patients with diffuse gliomas.

Abstract WP219: Diffusion Weighted Imaging Characteristics in Deep White and Gray Matter Structures in Pediatric Patients With Moyamoya Disease

Background: Moyamoya Disease (MMD) is a steno-occlusive arteriopathy associated with transient ischemic attacks, stroke, and cognitive impairments. In adult MMD, normal-appearing deep gray and white matter structures (NADWM) show diffusion changes that are associated with cognitive impairments. Apparent diffusion coefficient [ADC] measures the mean diffusion and is sensitive to these changes. The association of ADC changes in NADWM in pediatric MMD is not clear. Our objective is to determine whether ADC is elevated in NADWM in pediatric MMD patients. Hypothesis: ADC values in NADWM will be elevated in MMD patients compared to controls. Methods: Twenty-nine MMD patients and no stroke and 7 healthy controls (HC) were included in a single center, retrospective study. Diffusion and T1-weighted images were analyzed. We constructed a script implementing a convolutional neural network (CNN) based approach to segment and binarize cortical regions of interest (ROI) and allow extraction of ADC values (units =[x10 -6 mm 2 /s]). Segmented ROIs included: 1) all white matter (WM), and NADWM including: 2) thalamus, 3) caudate, 4) putamen, 5) globus pallidus, 6) hippocampus. Mean ADC values were compared for: 1) all ROIs between MMD and controls, and 2) all ROIs in the MMD affected and the contralateral hemispheres within the MMD group. Results: Patients were on average 7.7 + 5.4 years at MMD diagnosis. In all WM, MMD patients had significantly higher ADC values than controls in the left (mean= 865.7 + 101.6 versus 762.4 + 21.6, p=0.01) and right hemispheres (mean= 869.9 + 104.9 versus 761.0 + 21.3, p=.01), respectively. In NADGM, there were no significant differences found between the MMD and control groups in any of the NADGM ROIs. In the NADGM of MMD patients, higher ADC values were found in the putamen (mean= 778.2 + 46.0, p=0.041), hippocampus (mean=1009.5 + 58.6, p=0.005) and all NAWM (mean= 860.3 + 57.0, p<0.0001) in the MMD affected compared to the contra-lesional hemisphere. Conclusions: In pediatric patients with MMD, we found elevated ADC values in deep gray and white matter structures in the diseased hemisphere indicating alterations in the underlying microstructure. Our future analysis will integrate hemodynamic profiles and cognitive outcomes.

Mapping Motor Neuroplasticity after Successful Surgical Brachial Plexus Reconstruction Using Navigated Transcranial Magnetic Stimulation (nTMS).

Brachial plexus reconstruction (BPR) consists of the complex surgical restoration of nerve structures. To further understand the underlying motor cortex changes and evaluate neuroplasticity after a successful surgery, we performed a navigated transcranial magnetic stimulation (nTMS) study mapping the postoperative motor representation of the formerly plegic arm. We conducted a prospective nTMS study mapping the musculocutaneous nerve as a representative, prominent target of BPR including a patient (n = 8) and a control group (n = 10). Measurements like resting motor threshold (RMT), cortical motor area location, and size were taken. Mathematical analysis was performed using MATLAB 2022, statistical analysis was performed using SPSS 26, and nTMS mapping was performed using the Nexstim NBS 5.1 system. Mapping was feasible in seven out of eight patients. Median RMT on the affected hemisphere was 41% compared to 50% on the unaffected hemisphere and they were 37% and 36% on the left and right hemispheres of the control group. The motor area location showed a relocation of bicep brachii representation at the middle precentral gyrus of the corresponding contralateral hemisphere. Motor area size was increased compared to the control group and the patient's unaffected, ipsilateral hemisphere. Understanding cortical reorganization is important for potential future treatments like therapeutic nTMS. The issue of motor neuroplasticity in patients with brachial plexus lesions is worth exploring in further studies.

Abstract TP295: Temporal Characterization of Immune Responses in the Rat Brain Following Ischemic Stroke Using In-Depth Flow Cytometry Panels

Introduction: Rat models are widely used in stroke research as they are well suited for behavior studies and brain imaging techniques. However, methods for studying immune responses and identifying distinct leukocyte subsets in rats lag behind mice in part due to lack of specific antibodies for flow cytometry. Several flow cytometry antibody panels have been used to study the immune response of the rat brain after stroke, but they did not distinguish between pro- and anti-inflammatory macrophages, which is critical for stroke-induced neuroinflammation research. Here, we developed flow cytometry panels to measure myeloid and lymphoid leukocyte subsets in rat brain, blood, and spleen, with an emphasis on macrophage subtypes, and validated them in an ischemic stroke model. Method: Adult male (8-12 wk old) Nude and Sprague Dawley (SD) rats were subjected to distal MCAO. Ipsi- and contralateral hemispheres, blood, and spleen were collected and analyzed by flow cytometry at different time points post-stroke. Cell populations were sorted using FACS and characterized using qPCR or morphological analysis to confirm our FACS gating strategy. Results: We discriminated microglia, 3 monocyte/macrophage subsets, granulocytes, dendritic cells, NK cells, B cells, and T cells in the brain and periphery. The temporal profile of leukocyte subsets after stroke resembled those observed in mice, validating the reliability of our antibody panels: granulocytes and monocytes peaked in the first 2-3 days post-stroke, B and T cells peaked around 4-5 days, followed by a gradual increase of ‘microglia’ over 14 days. Using a combination of CD43 and His48 to differentiate monocyte/macrophage subpopulations, we observed a shift in these subsets over time, akin to the shift from pro- to anti-inflammatory macrophages reported in stroke-injured mouse brains. Notably, Nude rats differed from the SD rats in terms of His48 expression; SD rat brain monocyte/macrophage population was predominantly His48lo, while Nude rats had both His48lo and His48hi subsets. Conclusion: Our flow cytometry panels for rats distinguished leukocyte subsets, including monocyte/macrophage subpopulations, providing a valuable tool to study the complex immune responses in rat models of neurological disorders.

Contralateral delay activity and alpha lateralization reflect retinotopic and screen-centered reference frames in visual memory

The visual system represents objects in a lateralized manner, with contralateral cortical hemispheres responsible for left and right visual hemifields. This organization extends to visual short-term memory (VSTM), as evidenced by electrophysiological indices of VSTM maintenance: contralateral delay activity (CDA) and alpha-band lateralization. However, it remains unclear if VSTM represents object locations in gaze-centered (retinotopic) or screen-centered (spatiotopic) coordinates, especially after eye movements. In two experiments, participants encoded the colors of target objects and made a lateral saccade during the maintenance interval, thereby shifting the object’s location on the retina. A non-lateralized probe stimulus was then presented at the new fixation for a change detection task. The CDA maintained lateralization towards the target’s original retinotopic location, unaffected by subsequent saccades, and did not invert polarity even when a saccade brought that location into the opposite hemifield. We also found conventional alpha lateralization towards the target’s location before a saccade. After a saccade, however, alpha was lateralized towards the screen center regardless of the target’s original location, even in a control condition without any memory requirements. This suggests that post-saccadic alpha-band lateralization reflects attentional processes unrelated to memory, while pre- and post-saccade CDA reflect VSTM maintenance in a retinotopic reference frame.

Abstract WP217: 4D Flow MRI Monitoring of Pediatric Brain Arteriovenous Malformations: A Feasibility Study

Introduction: While some brain arteriovenous malformations (bAVM) demonstrate long-term stability, others demonstrate dynamic changes (new aneurysms or venous outflow stenosis) that confer higher rupture risk even after apparent cure. The objective of this study is to evaluate the feasibility and efficacy of 4D Flow MRI to quantitatively assess the hemodynamic changes in pediatric bAVMs following treatment and its use for early detection of high-risk changes. Methods: We have prospectively enrolled 20 children (mean age 11.8 ± 3.8 years) with bAVM into a single center cohort study. 4D Flow MRI was acquired in a transverse slab covering the circle of Willis using prospective gating, compressed sensing, and a resolution of 0.7 x 0.7 x 1.0 mm 3 on a 3T GE Discovery MR750 scanner. MRI at baseline and post-intervention (6-month and 1-year follow up) has been acquired for 5 patients thus far. 4D Flow data was post-processed by segmenting the main cerebral arteries and calculating cardiac-averaged flow rates in cross-sections orthogonal to the centerline of each vessel segment. Results: The flow rate accuracy was evaluated by calculating the flow conservation at the right/left internal carotid and basilar junctions, yielding average errors of 10.7% ± 12.7, 14.0% ± 9.5, and 19.3% ± 13.8 respectively. The hemisphere containing the bAVM received an average of 57.2% ± 2.8 of total brain flow at baseline, which decreased to an average of 51.2% ± 2.9 1-year follow-up. In 2 of 5 patients, the flow laterality between hemispheres flipped post-intervention with increased flow to the contralateral hemisphere. In all the post-intervention studies, we observed a decrease in flow and maximum velocities, as well as an increase in pulsatility index, in the primary feeding arteries to the bAVM (Figure). Conclusion: These preliminary results indicate that 4D Flow MRI may be a robust and useful tool for monitoring changes in intracranial flow patterns after bAVM treatment in children.

Sine Spin flat detector CT can improve cerebral soft tissue imaging: a retrospective in vivo study

BackgroundFlat detector computed tomography (FDCT) is frequently applied for periinterventional brain imaging within the angiography suite. Novel technical developments such as the Sine Spin FDCT (S-FDCT) may provide an improved cerebral soft tissue contrast. This study investigates the effect of S-FDCT on the differentiation between gray and white matter compared to conventional FDCT (C-FDCT) and multidetector computed tomography (MDCT).MethodsA retrospective analysis of a prospectively maintained patient database was performed, including patients who underwent mechanical thrombectomy in our institution and received S-FDCT or C-FDCT as well as MDCT. Differentiation between gray and white matter on the contralateral hemisphere to the ischemic stroke was analyzed quantitatively by contrast-to-noise ratio (CNR) and qualitatively (5-point ordinal scale).ResultsIn a cohort of 109 patients, MDCT demonstrated the best differentiation between gray and white matter compared to both FDCT techniques (p ≤ 0.001). Comparing both generations of FDCT, S-FDCT provided better visibility of the basal ganglia (p = 0.045) and the supratentorial cortex (p = 0.044) compared to C-FDCT both in quantitative and qualitative analyses. Median CNR were as follows: S-FDCT 2.41 (interquartile range [IQR] 1.66–3.21), C-FDCT 0.96 (0.46–1.70), MDCT 3.43 (2.83–4.17). For basal ganglia, median score and IQR were as follows: S-FDCT 2.00 (2.00–3.00), C-FDCT 1.50 (1.00–2.00), MDCT 5.00 (4.00–5.00).ConclusionsThe novel S-FDCT improves the periinterventional imaging quality of cerebral soft tissue compared to C-FDCT. Thus, it may improve the diagnosis of complications within the angiography suite. MDCT provides the best option for x-ray-based imaging of the brain tissue.Relevance statementFlat detector computed tomography is a promising technique for cerebral soft tissue imaging, while the novel Sine Spin flat detector computed tomography technique improves imaging quality compared to conventional flat detector computed tomography and thus may facilitate periinterventional diagnosis of gray and white matter.Key points• Flat detector computed tomography (FDCT) is frequently applied for periinterventional brain imaging.• The potential of novel Sine Spin FDCT (S-FDCT) is unknown so far.• S-FDCT improves the visibility of cerebral soft tissue compared to conventional FDCT.• Multidetector computed tomography is superior to both FDCT techniques.• S-FDCT may facilitate the evaluation of brain parenchyma within the angiography suite.Graphical

Abstract 89: Portable, Low-Field Magnetic Resonance Imaging: Determining Mismatch Following Acute Ischemic Stroke

Background and Aims: Treatment options for acute ischemic stroke (AIS) are uniquely dependent on the time of stroke onset. Intravenous thrombolysis must be administered within 4.5 hours of symptoms commencing, yet a subset of patients wake-up with symptoms and time of onset is unknown. Mismatch between fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging (DWI) MRI can be used to qualify wake-up strokes for thrombolysis. This has been shown to lead to improved functional outcomes in multicenter trials (WAKE-UP, MR-WITNESS). However, access to MRI is a barrier to differential diagnosis and subsequent treatment. Recent advances in portable, low-field MRI (LF-MRI) offer a solution to increase access to MRI technologies and circumvent the limitations of conventional systems. As such, in this pilot study, we sought to establish the utility of portable LF-MRI to identify DWI-FLAIR mismatch following AIS. Methods: Patients with a diagnosis of AIS presenting to Emergency Department or Intensive Care Unit of the Yale New Haven Hospital or Massachusetts General Hospital from January 2020 to June 2023 underwent DWI and FLAIR acquisition on a 0.064T MRI (Hyperfine Research Inc.) at <4.5 hours ( n =7), 4.5-6 hours ( n =7), and 6-48 hours ( n =110) since last known well (LKW). Conventional high-field (HF) MR images were acquired within 72 hours of LF-MRI. HF-DWI images were co-registered to LF-FLAIR and the hyperintense DWI stroke lesion segmented and superimposed on the FLAIR. The segmentation was mirrored to the contralateral hemisphere of the LF-FLAIR to establish a FLAIR signal intensity ratio (SIR). Results: The FLAIR SIR on images <4.5 hours since LKW was 0.98±0.08. The SIR for cases 4.5-6 hours was 1.34±0.33. Cases 6-48 hours produced a SIR of 1.56±0.36. The SIR at <4.5 hours was significantly less than that observed >6 hours since LKW ( p =0.03). Conclusion: This pilot study demonstrates that a 0.064T portable MRI is capable of distinguishing hyperacute stroke from later stroke onset using FLAIR SIR. Future research is needed in a larger cohort to determine if this imaging technology can be used to guide thrombolysis in the setting of wake-up stroke.