Ventricular System Research Articles

Abstract 1492: Unveiling the re-programming of choroid plexus and leptomeningeal metastasis

Abstract Leptomeningeal metastasis (LM) is an increasingly common, fatal complication of breast and lung cancer. Despite aggressive treatment, neurologic deficits accumulate rapidly, and patients generally succumb to LM within months. We must expand our limited mechanistic knowledge of this disease. Under homeostatic conditions, choroid plexus (ChP), highly vascularized structures within the brain ventricles, restrict the entry of macromolecules and cells into the leptomeninges; however, select cancer cells can cross this barrier and grow within the leptomeningeal space. We hypothesize that interactions between cancer and ChP niche cells alter both the niche and the cancer cells, ultimately supporting LM.During neurogenesis, the ChP display substantial extracellular matrix (ECM) remodeling, which is elegantly modulated by dynamic spatiotemporal regulation of MMPs, Wnt signaling, among other effector proteins. Similarly, 2-photon imaging of ChP collected from mice harboring LM revealed a profound ECM remodeling of the ChP when compared with naïve mice. This remodeling was accompanied by increased levels of MMP2 and MMP9 in LM mice. Upon pharmacological inhibition of MMP2 and MMP9 in vivo, we observed a decrease in LM burden and increase in overall survival, which correlates with a decrease in ChP permeability. Interestingly, human CSF from patients with leptomeningeal metastases is also enriched in collagen 1 fragments, MMP2, MMP9 and TIMP1. TIMP1, a MMP9 natural inhibitor, is not present in complex with MMP9, suggesting a role of TIMP1 as a cytokine in LM progression. TIMP1 neutralization and knockout from the cancer cells leads to a decrease in LM burden and increase in overall survival. Together, these data suggest a provocative link between proteolysis and inflammation in LM progression. The use of clinically-annotated human samples and mouse models of LM, and the integration of transcriptomics and proteomics enabled us to identify key signaling pathways, and capture the re-programming of ChP niche and cancer cells that unlock the leptomeningeal space to cancer cells. The timeframe for this evolution will be further revealed by analysis of mouse and human samples at different stages of cancer progression. Citation Format: Ana Rita Nobre, Helen Wang, Rachel Estrera, Isaiah Osei-Gyening, Adrienne Boire. Unveiling the re-programming of choroid plexus and leptomeningeal metastasis [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 1492.

Volume enlargement of the choroid plexus and brain ventricles in drug-naïve, first-episode major depressive disorder

BackgroundWe investigated volumetric alterations in the bilateral choroid plexus (ChP) and brain ventricles of patients during their first episode of major depressive disorder (MDD) prior to antidepressant treatment. MethodsSeventy-one first-episode drug-naïve patients with MDD and seventy-four healthy control (HC) subjects were recruited. MRI data were obtained, and bilateral ChP and brain ventricle volumes were evaluated using segmentation, based on the adaptive multiscale and expectation maximization method. One-way multivariate analysis of covariance was used to calculate volumetric differences in the bilateral ChP and brain ventricles between the groups, and partial Pearson correlation analyses were used to investigate the relationship between the volumes of the bilateral ChP and brain ventricles. ResultsFirst-episode drug-naïve patients with MDD showed enlarged volumes of the bilateral ChP, bilateral lateral ventricle (LV), and third ventricle compared with HCs. The ChP volume positively correlated with the LV and third ventricle, but not with the fourth ventricle in patients with MDD, whereas it correlated with all four brain ventricles in HCs. We did not observe significant correlations between bilateral ChP volume and brain ventricles, HAMD scores, or symptom severity. LimitationsOur study populations differed in age and sex and we did not extensively measure the amount of neuroinflammation in the brain or blood, include a functional assessment, nor evaluate other neural comorbidities or neuropsychiatric conditions. ConclusionsOur study extends the existing research to suggest that illness-related alterations in ChP volume enlargement in first-episode antidepressant-naïve patients with MDD may serve as a trait measure.

Microcirculatory Impairment and Cerebral Injury in Hydrocephalus and the Effects of Cerebrospinal Fluid Diversion.

Hydrocephalus is characterized by progressive enlargement of cerebral ventricles, resulting in impaired microvasculature and cerebral hypoperfusion. This study aimed to demonstrate the microvascular changes in hydrocephalic rats and the effects of cerebrospinal fluid (CSF) release on cerebral blood flow (CBF). On postnatal day 21 (P21), male Wistar rats were intracisternally injected with either a kaolin suspension or saline. On P47, Evan's ratio (ER) was measured using MRI. On P49, the arteriolar diameter and vascular density of the pia were quantified using a capillary video microscope. The CBF was measured using laser Doppler flowmetry. The expressions of NeuN and glial fibrillary acidic protein determined by immunochemical staining were correlated with the ER. The CBF and rotarod test performance were recorded before and after CSF release. The expressions of 4-hydroxynonenal (4-HNE) and c-caspase-3 were studied on P56. Ventriculomegaly was induced to varying degrees, resulting in the stretching and abnormal narrowing of pial arterioles, which regressed with increasing ER. Quantitative analysis revealed significant decreases in the arteriolar diameter and vascular density in the hydrocephalic group compared with those in the control group. In addition, the CBF in the hydrocephalic group decreased to 30%-50% of that in the control group. In hydrocephalus, the neurons appear distorted, and the expression of 4-HNE and reactive astrogliosis increase in the cortex. After CSF was released, improvements in the CBF and rotarod test performance were inversely associated with the ER. In addition, the levels of 4-HNE and c-caspase-3 were further elevated. Rapid ventricular dilatation is associated with severe microvascular distortion, vascular regression, cortical hypoperfusion, and cellular changes that impair the recovery of CBF and motor function after CSF release. Moreover, CSF release may induce reperfusion injury. This pathophysiology should be taken into account when treating hydrocephalus.

An Analysis of Two Aged Patients with Obstructive Hydrocephalus

What causes would you think of in an aged patient with hydrocephalus on his or her brain CT scan？These are two cases of obstructive hydrocephalus，that occurred with gradual mental loss and difficult walking due to the rigidity of both legs. A final diagnosis of obstructive hydrocephalus was established on the basis of their abnormal immunological tests；and drainage tubes were then inserted intracranially to alleviate the increased intracranial pressure（ICP），their total situations improved significantly. The authors realized that an autoimmune mechanism might be involved in a possible ependymitis inside their ventricular systems，and an earlier intervention of autoimmune may retard its natural process.

Aquaporin-4 inhibition attenuates Pentylenetetrazole-induced behavioral seizures and cognitive impairments in kindled rats

Epilepsy is a neurological condition distinguished by recurrent and unexpected seizures. Astrocytic channels and transporters are essential for maintaining normal neuronal functionality. The astrocytic water channel, aquaporin-4 (AQP4), which plays a pivotal role in regulating water homeostasis, is a potential target for epileptogenesis. In present study, we examined the effect of different doses (10, 50, 100 μM and 5 mM) of AQP4 inhibitor, 2-nicotinamide-1, 3, 4-thiadiazole (TGN-020), during kindling acquisition, on seizure parameters and seizure-induced cognitive impairments. Animals were kindled by injection of pentylenetetrazole (PTZ: 37.5 mg/kg, i.p.). TGN-020 was administered into the right lateral cerebral ventricle 30 min before PTZ every alternate day. Seizure parameters were assessed 20 min after PTZ administration. One day following the last PTZ injection, memory performance was investigated using spontaneous alternation in Y-maze and novel object recognition (NOR) tests. The inhibition of AQP4 during the kindling process significantly decreased the maximal seizure stage and seizure duration (two-way ANOVA, P = 0.0001) and increased the latency of seizure onset and the number of PTZ injections required to induce different seizure stages (one-way ANOVA, P = 0.0001). Compared to kindled rats, the results of the NOR tests showed that AQP4 inhibition during PTZ-kindling prevented recognition memory impairment. Based on these results, AQP4 could be involved in seizure development and seizure-induced cognitive impairment. More investigation is required to fully understand the complex interactions between seizure activity, water homeostasis, and cognitive dysfunction, which may help identify potential therapeutic targets for these conditions.

Roles of mechanosensitive ion channel PIEZO1 in the pathogenesis of brain injury after experimental intracerebral hemorrhage

Secondary brain injury after intracerebral hemorrhage (ICH) is the main cause of poor prognosis in ICH patients, but the underlying mechanisms remain less known. The involvement of Piezo1 in brain injury after ICH was studied in a mouse model of ICH. ICH was established by injecting autologous arterial blood into the basal ganglia in mice. After vehicle, Piezo1 blocker, GsMTx4, Piezo1 activator, Yoda-1, or together with mannitol (tail vein injection) was injected into the left lateral ventricle of mouse brain, Piezo1 level and the roles of Piezo1 in neuronal injury, brain edema, and neurological dysfunctions after ICH were determined by the various indicated methods. Piezo1 protein level in neurons was significantly upregulated 24 h after ICH in vivo (human and mice). Piezo1 protein level was also dramatically upregulated in HT22 cells (a murine neuron cell line) cultured in vitro 24 h after hemin treatment as an in vitro ICH model. GsMTx4 treatment or together with mannitol significantly downregulated Piezo1 and AQP4 levels, markedly increased Bcl2 level, maintained more neurons alive, considerably restored brain blood flow, remarkably relieved brain edema, substantially decreased serum IL-6 level, and almost fully reversed the neurological dysfunctions at ICH 24 h group mice. In contrast, Yoda-1 treatment achieved the opposite effects. In conclusion, Piezo1 plays a crucial role in the pathogenesis of brain injury after ICH and may be a target for clinical treatment of ICH.

Central Neurocytoma Treated Using Supratentorial Ventricle Radiotherapy: A Single-Institution Analysis of Five Cases in Adjuvant or Salvage Settings After Surgery.

Central neurocytoma (CN) is an extremely rare tumor primarily located in the supratentorial ventricular system, categorized as a glioneuronal or neuronal tumor. This study presented a retrospective analysis of five CN patients who received adjuvant or salvage radiotherapy. Patients, aged 31-59 years, underwent radiation doses ranging from 60 Gy to 50.4 Gy over 27-30 fractions. All patients achieved effective local tumor control without severe complications. The median follow-up period was 51.7 months, demonstrating 100% overall and progression-free survival rates. Our study's clinical outcomes align with previous research, despite the limitation of a small sample size. Emphasizing the necessity for additional research, our findings added to the potential evidence of radiotherapy in managing CN. Larger, long-term studies were needed to confirm these promising results.

Implications of DNA Methylation Classification in Diagnosing Ependymoma

BackgroundEpendymoma is a central nervous system tumor that arises from the ependymal cells of the brain's ventricles and spinal cord. The histopathology of ependymomas is indistinguishable regardless of the site of origin, and the prognosis varies. Recent studies have revealed that the development site and prognosis reflect the genetic background. In this study, we used genome-wide DNA methylation array analysis to investigate the epigenetic background of ependymomas from different locations treated at our hospital. MethodsFour cases of posterior fossa ependymomas and 11 cases of spinal ependymomas were analyzed. ResultsDNA methylation profiling using the DKFZ methylation classifier showed that the methylation diagnoses of the two cases differed from the histopathological diagnoses, and two cases could not be classified. Tumor that spread from the brain to the spinal cord was molecularly distinguishable from other primary spinal tumors. ConclusionsAlthough adding DNA methylation classification to conventional diagnostic methods may be helpful, the diagnosis in some cases remains undetermined. This may affect decision-making regarding treatment strategies and follow-up. Further investigations are required to improve the diagnostic accuracy of these tumors.

Activation of Cannabinoid Type 2 Receptor in Microglia Reduces Neuroinflammation through Inhibiting Aerobic Glycolysis to Relieve Hypertension.

Studies have shown that the chronic use of cannabis is associated with a decrease in blood pressure. Our previous studies prove that activating the cannabinoid type 2 (CB2) receptor in the brain can effectively reduce blood pressure in spontaneously hypertensive rats; however, the exact mechanism has not been clarified. The objective of this study is to demonstrate that activation of microglial CB2 receptors can effectively reduce the levels of TNF-α, IL-1β, and IL-6 in the paraventricular nucleus (PVN) through inhibiting aerobic glycolysis, thereby relieving hypertension. AngiotensinII (AngII) was administered to BV2 cells and C57 mice to induce hypertension and the release of proinflammatory cytokines. The mRNA and protein expression of the CB2 receptor, TNF-α, IL-1β, IL-6, and the PFK and LDHa enzymes were detected using RT-qPCR and Western blotting. The Seahorse XF Energy Metabolism Analyzer was used to measure the oxidative phosphorylation and aerobic glycolysis metabolic pathways in BV2 cells. The long-term effects of injecting JWH133, a selective CB2 receptor agonist, intraperitoneally on blood pressure were ascertained. ELISA was used to measure norepinephrine and lactic acid levels while immunofluorescence labeling was used to locate the CB2 receptor and c-Fos. By injecting pAAV-F4/80-GFP-mir30shRNA (AAV2-r-CB2shRNA) into the lateral cerebral ventricle, the CB2 receptor in microglia was specifically knocked down. Activation of CB2 receptors by the agonist JWH133 suppressed TNF-α, IL-1β, and IL-6 by inhibiting PFK and LDHa enzymes involved in glycolysis, as well as lactic acid accumulation, along with a reduction in glycoPER levels (marks of aerobic glycolysis) in AngII-treated BV2 cells. In AngII-treated mice, the administration of JWH133 specifically activated CB2 receptors on microglia, resulting in decreased expression levels of PFK, LDHa, TNF-α, IL-1β, and IL-6, subsequently leading to a decrease in c-Fos protein expression within PVN neurons as well as reduced norepinephrine levels in plasma, ultimately contributing to blood pressure reduction. The results suggest that activation of the microglia CB2 receptor decreases the neuroinflammation to relieve hypertension; the underlying mechanism is related to inhibiting aerobic glycolysis of microglia.

In vivo base editing of a pathogenic Eif2b5 variant improves vanishing white matter phenotypes in mice

Vanishing white matter (VWM) is a fatal leukodystrophy caused by recessive mutations in subunits of the eukaryotic translation initiation factor 2B. Currently, there are no effective therapies for VWM. Here, we assessed the potential of adenine base editing to correct human pathogenic VWM variants in mouse models. Using adeno-associated viral vectors, we delivered intein-split adenine base editors into the cerebral ventricles of newborn VWM mice, resulting in 45.9±5.9% correction of the Eif2b5R191H variant in the cortex. Treatment slightly increased mature astrocyte populations and partially recovered the integrated stress response (ISR) in female VWM animals. This led to notable improvements in bodyweight and grip strength in females, however, locomotor disabilities were not rescued. Further molecular analyses suggest that more precise editing (i.e. lower rates of bystander editing) as well as more efficient delivery of the base editors to deep brain regions and oligodendrocytes would have been required for a broader phenotypic rescue. Our study emphasizes the potential, but also identifies limitations, of current in vivo base editing approaches for the treatment of VWM or other leukodystrophies.

Mathematical model of the dependence between cerebral ventricular size and capillary pressure in laboratory animals

Aim: To adapt a mathematical model describing the interaction between fluid media and brain matter for the purpose of definition of the dependence between brain ventricle size and capillary pressure in laboratory animals of two genotypes, BALB/c and C57BL/6. Material and methods. The study included 4 male mice of each inbred strain C57BL/6 and BALB/c at the age of 12 weeks. The brain and cerebrospinal fluid system images were obtained using an 11.7 T horizontal MR scanner (Bruker, BioSpec 117/16 USR, Germany). An axial section at the level of -0.5 mm from bregma was chosen as the geometry for mathematical modelling. To describe the data obtained, the mathematical model was adapted by selecting a scale factor based on the known values of the cerebrospinal fluid formation rate for humans and mice. Results and discussion. The same qualitative pattern of relationship between capillary pressure and mean ventricular wall displacement was observed for all animals considered. Although the selected genetic strains of BALB/c and C57Bl mice differ significantly in terms of cerebral ventricle size, these differences in animal genotype did not affect the nature of this relationship. Changing the parameters of the fluid media interaction in the area of compression or moderate ventricular dilation almost does not lead to an exit from the physiologically acceptable capillary pressure value. In this case, the size of the ventricles changes significantly. In the area of large ventricular dilation, in contrast, there is little change in ventricular size, and this is accompanied by a dramatic increase in capillary pressure far beyond physiologic limits. Thus, the change in ventricular size is an adaptive process associated with pressure fluctuations caused by changes in intracranial fluid flow. The mere fact that some of the values reach the zone of physiologically unacceptable pressures associated, in fact, with death, provided that there is practically no change in ventricular size indicates that such a situation is rarely realized and is possible in case of violation of intracranial fluid media flows associated with the fact that the increase in ventricular size limits adaptive capabilities. Conclusions. The presented animal model will further increase the understanding of the pattern we have established and allow us to move on to attempts at prediction.

Expanded clinical phenotype and untargeted metabolomics analysis in RARS2-related mitochondrial disorder: a case report

BackgroundRARS2-related mitochondrial disorder is an autosomal recessive mitochondrial encephalopathy caused by biallelic pathogenic variants in the gene encoding the mitochondrial arginyl-transfer RNA synthetase 2 (RARS2, MIM *611524, NM_020320.5). RARS2 catalyzes the transfer of L-arginine to its cognate tRNA during the translation of mitochondrially-encoded proteins. The classical presentation of RARS2-related mitochondrial disorder includes pontocerebellar hypoplasia (PCH), progressive microcephaly, profound developmental delay, feeding difficulties, and hypotonia. Most patients also develop severe epilepsy by three months of age, which consists of focal or generalized seizures that frequently become pharmacoresistant and lead to developmental and epileptic encephalopathy (DEE).Case presentationHere, we describe a six-year-old boy with developmental delay, hypotonia, and failure to thrive who developed an early-onset DEE consistent with Lennox-Gastaut Syndrome (LGS), which has not previously been observed in this disorder. He had dysmorphic features including bilateral macrotia, overriding second toes, a depressed nasal bridge, retrognathia, and downslanting palpebral fissures, and he did not demonstrate progressive microcephaly. Whole genome sequencing identified two variants in RARS2, c.36 + 1G > T, a previously unpublished variant that is predicted to affect splicing and is, therefore, likely pathogenic and c.419 T > G (p.Phe140Cys), a known pathogenic variant. He exhibited significant, progressive generalized brain atrophy and ex vacuo dilation of the supratentorial ventricular system on brain MRI and did not demonstrate PCH. Treatment with a ketogenic diet (KD) reduced seizure frequency and enabled him to make developmental progress. Plasma untargeted metabolomics analysis showed increased levels of lysophospholipid and sphingomyelin-related metabolites.ConclusionsOur work expands the clinical spectrum of RARS2-related mitochondrial disorder, demonstrating that patients can present with dysmorphic features and an absence of progressive microcephaly, which can help guide the diagnosis of this condition. Our case highlights the importance of appropriate seizure phenotyping in this condition and indicates that patients can develop LGS, for which a KD may be a viable therapeutic option. Our work further suggests that analytes of phospholipid metabolism may serve as biomarkers of mitochondrial dysfunction.

Subdural hygromas After Decompressive Craniotomies

Subdural hygromas occur after various brain interventions, are often asymptomatic but sometimes may require surgical treatment. They can develop in the immediate postoperative period, but they are more common a few weeks or even months after surgery. Subdural hygromas are particularly common after decompressive craniotomy in patients with traumatic brain injury or massive stroke. The pathogenesis is explained by the fact that a large bone defect causes a pressure difference in the skull, and a concomitant displacement of the ventricular system disrupts the normal cerebrospinal fluid circulation, contributing to the redistribution of cerebrospinal fluid flow into the subdural space.We review data from contemporary studies on subdural hygromas after decompressive craniotomy, their risk factors, and management strategies. We also present our case of recurrent subdural hygroma in a patient operated on for a ruptured aneurysm of the middle cerebral artery.

Consensus guidelines for the management of primary supra-tentorial intraventricular tumour for low- and middle-income countries.

Almost any primary or metastatic brain tumour can manifest in intraventricular (IV) locations. These tumours may either originate within the ventricular system or extend into the IV space through growth. Such neoplasms represent a broad spectrum, with supratentorial IV tumours forming a heterogeneous group. This group includes primary ependymal tumours, central neurocytomas, choroid plexus tumours, and notably, meningiomas, as well as a variety of non-neoplastic, benign, glial, and metastatic lesions that can secondarily invade the IV compartment. Often presenting with nonspecific symptoms, these tumours can lead to delayed medical attention. The diversity in potential diagnoses, combined with their deep and complex locations, poses significant management challenges. This paper aims to delineate optimal management strategies, underscoring the importance of multidisciplinary care, especially in settings with limited resources, to effectively navigate the complexities associated with treating intraventricular brain tumours.

Consensus guidelines for the management of intracranial ependymoma for low- and middle-income countries.

This paper presents comprehensive consensus guidelines for the management of intracranial ependymoma, neoplasms arising from ependymal cells in the central nervous system's ventricular system, in low- and middleincome countries (LMICs). Acknowledging the distinct epidemiological patterns of ependymomas, notably their higher incidence in paediatric patients, and variable survival rates, these guidelines emphasize tailored management approaches for different age groups. An expert panel, comprising specialists in neuro-oncology, convened to address gaps in diagnosis and management within LMICs, considering the varying clinical presentation based on tumour size and location. Emphasizing surgical intervention as the cornerstone of treatment, the guidelines also address challenges such as intraoperative bleeding and tumour location impacting complete resection. The role of molecular subgrouping in stratifying treatment and predicting prognosis is highlighted, alongside a careful consideration of radiotherapy timing, dose, and volume based on risk factors. Chemotherapy's role, especially in paediatric cases, is explored. The paper synthesizes current research and expert opinions, including the need for standardisation, genetic testing, and exploration of less invasive treatment modalities, to address the unique healthcare infrastructure challenges in LMICs. The guidelines also emphasize multidisciplinary teams, aiming to bridge the care gap between high-income countries and LMICs, and improve survival rates and quality of life for patients with intracranial ependymoma. This article serves as a valuable resource for clinicians, researchers, and policymakers in Pakistan and beyond, facilitating the development of evidence-based strategies in diverse healthcare settings.

Volume changes of deep brain structures in episodic migraine

AbstractBackground and PurposeGray matter (GM) volumes have previously shown variations in different regions in patients with migraine, particularly in cortical regions. This study focused on comparative volumetric assessment of deep brain structures, including GM and cerebrospinal fluid (CSF), in patients with and without migraine. Furthermore, a relationship between the measured volumes and clinical features of migraine was investigated.MethodsIn a cross‐sectional study, 30 patients with episodic migraine and 30 subjects without migraine were investigated through brain MRI. The migraine group had a mean ± standard deviation (SD) age of 39 ± 12 (77% female, 23% male), and the control group had a mean ± SD age of 40.5 ± 11 (70% female, 30% male). Groups were matched in terms of age, gender, and comorbidities. T1‐weighted images were transferred to an automated MRI analysis tool to measure the volumes of interested regions.ResultsOur results showed that GM volumes of caudate nuclei, thalami, mammillary bodies, right nucleus accumbens, and CSF volumes of lateral ventricles in migraine group were significantly higher compared to the control group. In addition, migraine was independently associated with a higher volume of caudates, thalami, mammillary bodies, and lateral ventricles but a lower volume of the third and fourth ventricles. An analysis of migraine clinical features revealed that a longer duration of migraine was associated with a lower GM volume of the right mammillary body and higher CSF volumes of lateral ventricles, and the third ventricle.ConclusionOur study supported the hypothesis that migraine is independently associated with the volumes of deep brain structures, specifically the thalamus, caudate, mammillary body, and ventricular system.

Learning Spatio-Temporal Model of Disease Progression With NeuralODEs From Longitudinal Volumetric Data.

Robust forecasting of the future anatomical changes inflicted by an ongoing disease is an extremely challenging task that is out of grasp even for experienced healthcare professionals. Such a capability, however, is of great importance since it can improve patient management by providing information on the speed of disease progression already at the admission stage, or it can enrich the clinical trials with fast progressors and avoid the need for control arms by the means of digital twins. In this work, we develop a deep learning method that models the evolution of age-related disease by processing a single medical scan and providing a segmentation of the target anatomy at a requested future point in time. Our method represents a time-invariant physical process and solves a large-scale problem of modeling temporal pixel-level changes utilizing NeuralODEs. In addition, we demonstrate the approaches to incorporate the prior domain-specific constraints into our method and define temporal Dice loss for learning temporal objectives. To evaluate the applicability of our approach across different age-related diseases and imaging modalities, we developed and tested the proposed method on the datasets with 967 retinal OCT volumes of 100 patients with Geographic Atrophy and 2823 brain MRI volumes of 633 patients with Alzheimer's Disease. For Geographic Atrophy, the proposed method outperformed the related baseline models in the atrophy growth prediction. For Alzheimer's Disease, the proposed method demonstrated remarkable performance in predicting the brain ventricle changes induced by the disease, achieving the state-of-the-art result on TADPOLE cross-sectional prediction challenge dataset.

Improve the diagnosis of idiopathic normal pressure hydrocephalus by combining abnormal cortical thickness and ventricular morphometry.

The primary imaging markers for idiopathic Normal Pressure Hydrocephalus (iNPH) emphasize morphological measurements within the ventricular system, with no attention given to alterations in brain parenchyma. This study aimed to investigate the potential effectiveness of combining ventricular morphometry and cortical structural measurements as diagnostic biomarkers for iNPH. A total of 57 iNPH patients and 55 age-matched healthy controls (HC) were recruited in this study. Firstly, manual measurements of ventricular morphology, including Evans Index (EI), z-Evans Index (z-EI), Cella Media Width (CMW), Callosal Angle (CA), and Callosal Height (CH), were conducted based on MRI scans. Cortical thickness measurements were obtained, and statistical analyses were performed using surface-based morphometric analysis. Secondly, three distinct models were developed using machine learning algorithms, each based on a different input feature: a ventricular morphology model (LVM), a cortical thickness model (CT), and a fusion model (All) incorporating both features. Model performances were assessed using 10-fold cross validation and tested on an independent dataset. Model interpretation utilized Shapley Additive Interpretation (SHAP), providing a visualization of the contribution of each variable in the predictive model. Finally, Spearman correlation coefficients were calculated to evaluate the relationship between imaging biomarkers and clinical symptoms. iNPH patients exhibited notable differences in cortical thickness compared to HC. This included reduced thickness in the frontal, temporal, and cingulate cortices, along with increased thickness in the supracentral gyrus. The diagnostic performance of the fusion model (All) for iNPH surpassed that of the single-feature models, achieving an average accuracy of 90.43%, sensitivity of 90.00%, specificity of 90.91%, and Matthews correlation coefficient (MCC) of 81.03%. This improvement in accuracy (6.09%), sensitivity (11.67%), and MCC (11.25%) compared to the LVM strategy was significant. Shap analysis revealed the crucial role of cortical thickness in the right isthmus cingulate cortex, emerging as the most influential factor in distinguishing iNPH from HC. Additionally, significant correlations were observed between the typical triad symptoms of iNPH patients and cortical structural alterations. This study emphasizes the significant role of cortical structure changes in the diagnosis of iNPH, providing a novel insights for assisting clinicians in improving the identification and detection of iNPH.

Correlation between Transcranial Ultrasound and CT Head to Detect Clinically Significant Conditions in Post-craniectomy Patients Performed by Emergency Physician: A Pilot Study.

The main objective is to detect clinically significant conditions by transcranial ultrasound (TCS) in post-decompressive craniectomy (DC) patients who come to the emergency department. This was a cross-sectional observational study. We studied 40 post-DC patients. After primary stabilization, TCS was done. Computer tomography of head was done within 2 hours of performing TCS. The correlation between both modalities were assessed by the measurement of lateral ventricle (LV) (Bland-Altman plot), Midline shift and mass lesion. Additionally, normal cerebral anatomy, 3rd and 4th ventricles and external ventricular drainage (EVD) catheter visualization were also done. About 14/40 patients came with non-neurosurgical complaints and 26/40 patients came with neurosurgical complaints. Patients with non-neurosurgical complaints (4/14) had mass lesions and 1/14 had MLS. Patients with neurosurgical complaints (11/26) had mass lesions and about 5 patients had MLS. A good correlation was found between TCS and CT of head in measuring LV right (CT head = 17.4 ± 13.8 mm and TCS = 17.1 ± 14.8 mm. The mean difference (95% CI) = [0.28 (-1.9 to 1.33), ICC 0.93 (0.88-0.96)], Left [CT head = 17.8 ± 14.4 mm and TCS = 17.1 ± 14.2 mm, the mean difference (95% CI) 0.63 (-1.8 to 0.61), ICC 0.96 (0.93-0.98)], MLS [CT head = 6.16 ± 3.59 (n = 7) and TCS = 7.883 ± 4.17 (n = 6)] and mass lesions (kappa 0.84 [0.72-0.89] [95% CI] p-value < 0.001). The agreement between both modalities for detecting mass lesions is 93.75%. Point of care ultrasound (POCUS) is a bedside, easily operable, non-radiation hazard and dynamic imaging tool that can be used for TCS as a supplement to CT head in post-DC patients in emergency as well as in ICU. However, assessment of the ventricular system (pre/post-EVD insertion), monitoring of regression/progression of mass lesion, etc. can be done with TCS. Repeated scans are possible in less time which can decrease the frequency of CT head. Chouhan R, Sinha TP, Bhoi S, Kumar A, Agrawal D, Nayer J, et al. Correlation between Transcranial Ultrasound and CT Head to Detect Clinically Significant Conditions in Post-craniectomy Patients Performed by Emergency Physician: A Pilot Study. Indian J Crit Care Med 2024;28(3):299-306.

Comparison of the mathematical modelling results of the relationship between cerebral ventricular size and capillary pressure based on experimental and clinical data

Aim of the study was to compare the results of mathematical modelling of the dependence between brain ventricle size and capillary pressure for humans and animals based on the equations of multicomponent poroelastic filtration for brain parenchyma. Material and methods. The study included two groups of animals - 4 male mice of each inbred line C57Bl/6 and BALB/C at the age of 12 weeks – and 4 healthy volunteers. The brain and cerebrospinal fluid system images of mice were obtained using an 11.7 T horizontal MR scanner, group of humans were examined using the Ingenia 3.0 T MRI scanner. An axial section at the level of –0.5 mm from bregma in the mouse groups and a frontal slice at the level of the middle of the bodies of the lateral and third ventricles, posterior to the foramen of Monroe in the human group were chosen as the geometry for mathematical modelling. Mathematical modelling is based on the stationary mathematical model of multicomponent poroelastic filtration. Multiple linear regression of mean ventricular wall displacement on fluid media interaction parameters was constructed to compare results obtained. Regression coefficients were compared using nonparametric analysis of variance based on the Kraskell–Wallis criterion and post-hoc Dunn’s criterion with Hill’s correction Results. A qualitative coincidence in the behavior of capillary pressure and mean ventricular wall displacement was demonstrated for the human and mouse groups. No significant differences were found between the two animal lines. For the animals characterized by small ventricular size (BALB/c), greater similarity to humans is observed than for the genetic line with hypertrophied ventricles (C57Bl/6). A significant difference between humans and mice is observed only for capillary-venous interaction. Conclusions. The low variance within groups and insignificant discrepancy between groups indicate the possibility of further accumulation of empirical data to establish correction coefficients of the animal model, which will bring it more in line with the model for humans. Thus, the analyzed models are sufficiently comparable with each other.