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18 pages, 1759 KB  
Article
Voluntary Wheel Running as Refinement Tool for Postoperative Severity Assessment and Humane Endpoint Detection in Rats with Brain Tumors
by Alina L. Ottlewski, Christine Häger, Elvis J. Hermann, Franck Fogaing Kamgaing, Mesbah Alam, Jannik D. Schwabe, Hauke Thiesler, Herbert Hildebrandt, Aylina Glasenapp, Marion Bankstahl, Steven R. Talbot, Joachim K. Krauss and Kerstin Schwabe
Brain Sci. 2026, 16(6), 635; https://doi.org/10.3390/brainsci16060635 - 13 Jun 2026
Viewed by 416
Abstract
Background: In rodent models of intracranial tumor development, evaluating the actual burden experienced by animals beyond procedural severity is essential for ethical and legal compliance. This study examined whether voluntary wheel running (VWR) could serve as a sensitive indicator of post-surgical burden following [...] Read more.
Background: In rodent models of intracranial tumor development, evaluating the actual burden experienced by animals beyond procedural severity is essential for ethical and legal compliance. This study examined whether voluntary wheel running (VWR) could serve as a sensitive indicator of post-surgical burden following subcutaneous transmitter implantation, tumor cell injection, and tumor resection. It also assessed whether VWR supports the detection of humane endpoints. VWR outcomes were compared with body weight, clinical scores, heart rate, and activity levels recorded via telemetry. Methods: Fourteen male BDIX rats were housed individually in cages equipped with a running wheel. Under general anesthesia, telemetric devices to monitor heart rate and activity were subcutaneously implanted. After recovery, glioblastoma BT4Ca cells were stereotaxically injected into the right frontal cortex. Eight days later, the resulting tumors were microsurgically resected. Body weight, VWR, heart rate, and general activity were continuously monitored until the animals reached humane endpoint criteria, indicated by sudden weight loss and clinical deterioration. Results: On average, body weight and VWR declined significantly after all surgical procedures, with tumor resection causing the most pronounced effect. As animals approached the endpoint, a marked drop in these parameters was observed, along with an increased clinical score (p < 0.05). Activity measures supported these findings, though less consistently than weight and VWR. Conclusions: Monitoring body weight and VWR enables an effective assessment of the actual postoperative burden experienced by rats undergoing surgeries of different procedural complexity. Moreover, VWR is a valuable supplementary tool for identifying humane endpoints alongside body weight and clinical scoring. Full article
(This article belongs to the Section Behavioral Neuroscience)
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17 pages, 12081 KB  
Review
Surgical Management of Traumatic Brain Injury Based on Intracranial Compliance: Toward Personalized Decision-Making
by Santiago Cardona-Collazos, Laura M. Loaiza-Cardona, Andres Salazar-Restrepo, Luigi Valentino Berra and Andres M. Rubiano
Brain Sci. 2026, 16(5), 538; https://doi.org/10.3390/brainsci16050538 - 20 May 2026
Viewed by 572
Abstract
Traditional surgical decision-making in traumatic brain injury (TBI) has relied on static intracranial pressure (ICP) thresholds and fixed volumetric criteria, an approach that inadequately reflects the dynamic physiological nature of secondary brain injury. These conventional metrics fail to capture the critical determinant of [...] Read more.
Traditional surgical decision-making in traumatic brain injury (TBI) has relied on static intracranial pressure (ICP) thresholds and fixed volumetric criteria, an approach that inadequately reflects the dynamic physiological nature of secondary brain injury. These conventional metrics fail to capture the critical determinant of clinical deterioration: the progressive loss of intracranial compliance, the brain’s capacity to buffer additional volume without harmful pressure escalation. This manuscript proposes a practical, compliance-based framework for selecting precise, personalized surgical strategies using real-time physiological, imaging, and neuromonitoring indicators. Based on the Intracranial Compartment Syndrome (ICCS) model, this approach translates the loss of compensatory reserve into actionable operative decisions. Compliance is assessed through multimodal tools, including ICP waveform morphology, cerebral oxygenation, and complementary noninvasive neuromonitoring. ICCS staging delineates three operative contexts: Stage 1, preserved compliance; Stage 2, compliance failure with maintained oxygenation requiring physiology-guided interventions to restore buffering capacity; and Stage 3, global decompensation with lost of compliance plus oxygenation failure requiring immediate, aggressive intervention for partial or total brain tissue survival. By shifting surgical reasoning from fixed anatomical thresholds to a physiology-centered assessment of intracranial compliance, this framework aims to enhance the timing, selection, and overall effectiveness of neurosurgical interventions in TBI. Full article
(This article belongs to the Section Systems Neuroscience)
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27 pages, 6465 KB  
Systematic Review
Are AI Neuroimaging Models Ready for Clinical Use? A Systematic Methodological Review
by Umid Sulaimanov, Nafiye Sanlier, Ariorad Moniri, Behman Demir, Yerkebulan Serikkanov, Ahmed Rasim Bayramoglu, Maryam Sabah Al-Jebur, Irem Uslu, Oyku Ozturk, Mariagrazia Nizzola, Erkin Ötleş, Simon Gashaw Ammanuel, Abdullah Keles, Ufuk Erginoglu and Mustafa K. Baskaya
J. Clin. Med. 2026, 15(9), 3441; https://doi.org/10.3390/jcm15093441 - 30 Apr 2026
Cited by 1 | Viewed by 898
Abstract
Background/Objectives: Artificial intelligence (AI) has rapidly expanded across medical imaging with proposed applications in diagnosis, prognostication, and surgical planning. Concerns remain regarding methodological robustness and clinical readiness for many published models. This systematic review aimed to conduct a methodological audit of AI [...] Read more.
Background/Objectives: Artificial intelligence (AI) has rapidly expanded across medical imaging with proposed applications in diagnosis, prognostication, and surgical planning. Concerns remain regarding methodological robustness and clinical readiness for many published models. This systematic review aimed to conduct a methodological audit of AI imaging studies relevant to contemporary neurosurgical practice—including intracranial, cerebrovascular, spinal, and connectomics-based applications—published in 2025. Methods: Following PRISMA guidelines and PROSPERO registration (CRD420261284068), PubMed was searched for studies published in 2025 evaluating machine learning or deep learning applications in MRI- or CT-based imaging. Three reviewers independently extracted data on validation strategy, data leakage risk, human comparator use, calibration reporting, and CLAIM/TRIPOD-AI adherence. Risk of bias was assessed using PROBAST+AI. Results: Of 1776 screened records, 91 studies met the inclusion criteria. China led contributions (54.9%), oncology was the most common domain (37.4%), and MRI was the predominant modality (67.0%). External validation was reported in 75.8% of studies, and 66.0% used multicenter cohorts. Data leakage risk was low in 93.4%. However, only 18.7% included human comparators, calibration was reported in 30.8%, and none achieved full CLAIM/TRIPOD-AI compliance. Conclusions: AI imaging studies published in 2025 demonstrate encouraging progress in multicenter design and external validation. However, persistent gaps in human benchmarking, calibration, and reporting suggest further methodological development is needed. Full article
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18 pages, 3224 KB  
Case Report
Left Pulvinar Thalamic Tumor with Ventricular Atrial Extension Presenting as Network-Level Cognitive and Gait Dysfunction
by Florin Mihail Filipoiu, Stefan Oprea, Cosmin Pantu, Matei Șerban, Răzvan-Adrian Covache-Busuioc, Corneliu Toader, Mugurel Petrinel Radoi, Octavian Munteanu and Raluca Florentina Tulin
Diagnostics 2026, 16(6), 836; https://doi.org/10.3390/diagnostics16060836 - 11 Mar 2026
Viewed by 680
Abstract
Background and Clinical Significance: Deep thalamic and periventricular lesions are uncommon in adults but can result in significant loss of function because of their convergence on three interdependent processes: thalamocortical state regulation, throughput of periventricular long association systems, and ventricular compartmental compliance. The [...] Read more.
Background and Clinical Significance: Deep thalamic and periventricular lesions are uncommon in adults but can result in significant loss of function because of their convergence on three interdependent processes: thalamocortical state regulation, throughput of periventricular long association systems, and ventricular compartmental compliance. The resulting combination of executive control collapse, retrieval-weighted language fragility, and load-sensitive gait instability may occur early after a lesion forms an atrial/posterior horn interface, and pressure-linked autonomic symptoms may be late to develop. Screening deficits will likely be minimal and therefore underreported. Objective/Aim: To present a thalamic–atrial/posterior horn tumor case with quantified load-sensitive cognitive–language–gait dysfunction and to detail a physiology-guided, sequence-driven decompression approach emphasizing ventricular relaxation and perforator-preserving, interface-limited thalamic resection. Case Presentation: A 56-year-old female patient experienced a 3-month, rapidly progressive decline in her cognitive and language abilities. The clinical progression was not stepwise or punctuated by a single “sentinel” event. She had a moderate level of cognitive impairment consistent with both Broca’s and Wernicke’s aphasias (MoCA: 22/30) and suffered from significant interference effects and increased cost of task-switching. Her ability to generate novel responses and name objects was significantly impaired; however, she was able to repeat words and phrases appropriately. In addition, she exhibited a severe sustained attention signature and a high error rate during dual-task performance, indicating severe gait instability, although her overall global anchors were nearly neutral (GCS 15; FOUR 15/16; NIHSS 2). Nausea and vomiting occurred simultaneously with the cognitive and language decline, suggesting decreased intracranial compliance. MRI revealed a heterogeneous left-sided thalamic tumor extending into the posterior horn of the lateral ventricle. The tumor caused deformation of the lateral ventricle and midline displacement. The patient underwent microsurgical intervention using a physiology-conscious sequence of graded cerebrospinal fluid (CSF) equilibration and primary mechanical removal of the tumor from the ventricular system. Additionally, decompression of the thalamus was performed in a manner that was cognizant of the boundaries formed by the perforating arteries of the thalamus. Early resolution of pressure symptoms was noted postoperatively. Objective measures demonstrated significant improvement in the patient’s executive functioning, language skills, attentional errors, and dual-task performance stability. The patient remained functionally independent at discharge and at subsequent follow-up visits. Surveillance imaging did not demonstrate any evidence of tumor recurrence. Conclusions: The clinical presentation described above is supportive of a model in which the synergy between deep network damage and distortion of the posterior ventricular compartment amplifies network dysfunction. Additionally, the use of quantitative stress-phenotyping makes it possible to identify deep network pathology early in its course. Finally, the physiology-guided decompression approach that was used in this case has the potential to increase functional reserve in patients with pathology that requires millimeter transitions. Full article
(This article belongs to the Special Issue Brain/Neuroimaging 2025–2026)
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12 pages, 2490 KB  
Article
First-in-Human Prospective, Observational, and Comparative Clinical Study of Simultaneous Invasive and Non-Invasive Intracranial Pressure Pulse Wave Monitoring
by Indre Lapinskiene, Edvinas Chaleckas, Vilma Putnynaite, Laimonas Bartusis, Yasin Hamarat, Aidanas Preiksaitis, Mindaugas Serpytis, Vytautas Petkus, Saulius Vosylius and Arminas Ragauskas
Sensors 2026, 26(5), 1403; https://doi.org/10.3390/s26051403 - 24 Feb 2026
Viewed by 768
Abstract
Monitoring intracranial pressure (ICP) dynamics is critical for the management of traumatic brain injury, stroke, other neurosurgical conditions, and cerebral blood flow autoregulation; however, invasive ICP monitoring carries risks such as infection, hemorrhage, and sensor zero drift. Increasing evidence suggests that ICP waveform [...] Read more.
Monitoring intracranial pressure (ICP) dynamics is critical for the management of traumatic brain injury, stroke, other neurosurgical conditions, and cerebral blood flow autoregulation; however, invasive ICP monitoring carries risks such as infection, hemorrhage, and sensor zero drift. Increasing evidence suggests that ICP waveform morphology provides clinically relevant information beyond mean ICP value alone. In this first-in-human prospective comparative clinical study, we evaluated the feasibility and accuracy of a novel, fully passive, non-invasive ICP pulse waveform monitoring system (Archimedes 02) based on the detection of eyeball mechanical movement. Fifteen intensive care unit patients (6 males, 9 females; mean age 57.1 ± 18.8 years) with clinically indicated invasive ICP monitoring or external ventricular drainage were enrolled. Three-minute monitoring sessions were performed to simultaneously acquire non-invasive ICP pulse waveforms, invasive ICP waveforms, and invasive radial artery blood pressure (ABP) waveforms. Averaged waveforms were derived for each patient and compared graphically and using correlation analysis. Non-invasive ICP pulse waves recorded with Archimedes 02 showed a strong correlation with invasive ICP waveforms (R¯ = 0.965). In contrast, correlations between non-invasive ICP and ABP waveforms (R¯ = 0.699), as well as between invasive ICP and ABP waveforms (R¯ = 0.749), were lower. These findings indicate that the non-invasive signal primarily reflects ICP dynamics rather than arterial blood pressure. This novel non-invasive ICP monitoring approach has the potential to enhance neurocritical care, particularly in settings where invasive monitoring is impractical or unavailable. Further validation in larger and more diverse patient populations is warranted. Full article
(This article belongs to the Section Electronic Sensors)
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36 pages, 5121 KB  
Article
Peripheral Artery Disease (P.A.D.): Vascular Hemodynamic Simulation Using a Printed Circuit Board (PCB) Design
by Claudiu N. Lungu, Aurelia Romila, Aurel Nechita and Mihaela C. Mehedinti
Bioengineering 2026, 13(2), 241; https://doi.org/10.3390/bioengineering13020241 - 19 Feb 2026
Viewed by 1241
Abstract
Background: Arterial stenosis produces nonlinear changes in vascular impedance that are challenging to investigate in real time using either benchtop flow phantoms or high-fidelity computational fluid dynamics (CFD) models. Objective: This study aimed to develop and evaluate a low-cost printed circuit board (PCB) [...] Read more.
Background: Arterial stenosis produces nonlinear changes in vascular impedance that are challenging to investigate in real time using either benchtop flow phantoms or high-fidelity computational fluid dynamics (CFD) models. Objective: This study aimed to develop and evaluate a low-cost printed circuit board (PCB) analog capable of reproducing the hemodynamic effects of progressive arterial stenosis through an R–L–C mapping of vascular mechanics. Methods: A lumped-parameter (0D) electrical network was constructed in which voltage represented pressure, current represented flow, resistance modeled viscous losses, capacitance corresponded to vessel compliance, and inductance represented fluid inertance. A variable resistor simulated focal stenosis and was adjusted incrementally to represent progressive narrowing. Input Uin, output Uout, peak-to-peak Vpp, and mean Vavg voltages were recorded at a driving frequency of 50 Hz. Physiological correspondence was established using the canonical relationships. R=8μlπr4, L=plπr2, C=3πr32Eh, where μ is blood viscosity, ρ is density, E is Young’s modulus, and h is wall thickness. A calibration constant was applied to convert measured voltage differences into pressure differences. Results: As simulated stenosis increased, the circuit exhibited a monotonic rise in Uout and Vpp, with a precise inflection beyond mid-range narrowing—consistent with the nonlinear growth in pressure loss predicted by fluid dynamic theory. Replicate measurements yielded stable, repeatable traces with no outliers under nominal test conditions. Qualitative trends matched those of surrogate 0D and CFD analyses, showing minimal changes for mild narrowing (≤25%) and a sharp increase in pressure loss for moderate to severe stenoses (≥50%). The PCB analog uses a simplified, lumped-parameter representation driven by a fixed-frequency sinusoidal excitation and therefore does not reproduce fully characterized physiological systolic–diastolic waveforms or heart–arterial coupling. In addition, the present configuration is intended for relatively straight peripheral arterial segments and is not designed to capture the complex geometry and branching of specialized vascular beds (e.g., intracranial circulation) or strongly curved elastic vessels (e.g., the thoracic aorta). Conclusions: The PCB analog successfully reproduces the characteristic hemodynamic signatures of arterial stenosis in real time and at low cost. The model provides a valuable tool for educational and research applications, offering rapid and intuitive visualization of vascular behavior. Current accuracy reflects assumptions of Newtonian, laminar, and lumped flow; future work will refine calibration, quantify uncertainty, and benchmark results against physiological measurements and full CFD simulations. Full article
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20 pages, 1210 KB  
Review
First Breath Matters: Out-of-Hospital Mechanical Ventilation in Patients with Traumatic Brain Injury
by Victoria Brinker, Aristomenis Exadaktylos, Wolf Hautz and Mairi Ziaka
J. Clin. Med. 2025, 14(23), 8443; https://doi.org/10.3390/jcm14238443 - 28 Nov 2025
Viewed by 2153
Abstract
Invasive mechanical ventilation (MV) is often a lifesaving intervention in patients with traumatic brain injury (TBI) to optimize gas exchange and prevent secondary brain injury, thereby avoiding the deleterious effects of both hypoxia and hyperoxia, as well as hypocapnia and hypercapnia. However, MV [...] Read more.
Invasive mechanical ventilation (MV) is often a lifesaving intervention in patients with traumatic brain injury (TBI) to optimize gas exchange and prevent secondary brain injury, thereby avoiding the deleterious effects of both hypoxia and hyperoxia, as well as hypocapnia and hypercapnia. However, MV in these patients represents a unique clinical challenge, as it must take into account multiple parameters, including cerebral autoregulation and autoregulatory reserves, brain compliance, cerebral dynamics such as intracranial pressure (ICP), cerebral perfusion pressure (CPP), and cerebral blood flow (CBF), as well as systemic hemodynamics and respiratory system mechanics. Moreover, the detrimental effects of MV on extracranial organs and systems are well established, with the lungs being the most vulnerable, particularly when non-protective ventilation strategies involving high tidal volumes (TV) and inspiratory pressures are applied. Currently, the optimal ventilation approach in patients with TBI, with or without LI, remains incompletely defined. While protective ventilation practices are recommended for a large number of critically ill patients, their application in individuals with acute brain injury (ABI) may adversely affect cerebral and systemic hemodynamics, as well as brain physiology, potentially leading to secondary damage and poor clinical outcomes. Because the consequences of TBI, such as secondary brain damage and lung complications, begin shortly after the primary event, the role of prehospital MV in these patients is crucial. However, existing data from the out-of-hospital setting are scarce. Thus, in the present review, we aim to summarize the available evidence on MV in patients with TBI, with an emphasis on the prehospital setting. Full article
(This article belongs to the Special Issue Ventilation in Critical Care Medicine: 2nd Edition)
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43 pages, 1246 KB  
Review
The Glymphatic–Venous Axis in Brain Clearance Failure: Aquaporin-4 Dysfunction, Biomarker Imaging, and Precision Therapeutic Frontiers
by Daniel Costea, Nicolaie Dobrin, Catalina-Ioana Tataru, Corneliu Toader, Matei Șerban, Răzvan-Adrian Covache-Busuioc, Octavian Munteanu and Ionut Bogdan Diaconescu
Int. J. Mol. Sci. 2025, 26(21), 10546; https://doi.org/10.3390/ijms262110546 - 30 Oct 2025
Cited by 19 | Viewed by 5480
Abstract
The identification of brain clearance failure as a precursor to a large variety of neurodegenerative diseases has shifted fluid dynamics from a secondary to a tertiary target of brain health. The identification of the glymphatic system, detailing cerebrospinal fluid entry along perivascular spaces [...] Read more.
The identification of brain clearance failure as a precursor to a large variety of neurodegenerative diseases has shifted fluid dynamics from a secondary to a tertiary target of brain health. The identification of the glymphatic system, detailing cerebrospinal fluid entry along perivascular spaces and exit via perivenous and meningeal lymphatic pathways, provided a challenge to previous diffusion models and established aquaporin-4–dependent astroglial polarity as a governing principle of solute transport. Multiple lines of evidence now support a coupled glymphatic–venous axis, wherein vasomotion, venous outflow, and lymphatic drainage are functionally interrelated. Failure of any axis will cascade and affect the entire axis, linking venous congestion, aquaporin-4 disassembly, and meningeal lymphatic failure to protein aggregation, neuroinflammation, edema, and intracranial hypertension. Specific lines of evidence from diffusion tensor imaging along vascular spaces, clearance MRI, and multi-omic biomarkers can provide a measure of transport. Therapeutic strategies are rapidly advancing from experimental strategies to translational approval, including behavioral optimization, closed-loop sleep stimulation, vascular and lymphatic therapies, focused ultrasound, pharmacological polarity recoupling, and regenerative bioengineering. Novel computational approaches, such as digital twin dynamic modeling and adaptive trial designs, suggest that clearance measures may serve as endpoints to be approved by the FDA. This review is intended to bridge relevant mechanistic and translational reviews, focusing on impaired clearance as an exploitable systems defect rather than an incapacitating secondary effect. Improving our understanding of the glymphatic-venous axis Injury may lead to future target strategies that advance cognitive resilience, alleviate disease burden, and improve quality of life. By clarifying the glymphatic–venous axis, we provide a mechanistic link between impaired interstitial clearance and the pathological accumulation of amyloid-β, tau, and α-synuclein in neurodegenerative diseases. The repair of aquaporin-4 polarity, venous compliance, and lymphatic drainage might therefore open new avenues for the diagnosis and treatment of Alzheimer’s and Parkinson’s disease, supplying both biomarkers of disease progression and new targets for early intervention. These translational implications not only locate clearance failure as an epiphenomenon of neurodegeneration but, more importantly, as a modifiable driver of the course of neurodegeneration. Full article
(This article belongs to the Special Issue Molecular Insights in Neurodegeneration)
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16 pages, 1030 KB  
Article
Hyperostosis Cranii Ex Vacuo in Shunted Children: A Proposed Fifth Subtype of CSF Overdrainage Syndrome
by Mateusz Zajączkowski, Łukasz Klasa, Olga Milczarek and Stanisław Kwiatkowski
Int. J. Transl. Med. 2025, 5(4), 51; https://doi.org/10.3390/ijtm5040051 - 28 Oct 2025
Viewed by 1874
Abstract
Background: Cerebrospinal fluid (CSF) shunting remains a crucial intervention in the treatment of paediatric hydrocephalus. Overdrainage syndrome is a well-recognised but potentially severe complication, in which hyperostosis cranii ex vacuo—diffuse thickening of the cranial bones—emerges as an adaptive response to chronic intracranial hypotension. [...] Read more.
Background: Cerebrospinal fluid (CSF) shunting remains a crucial intervention in the treatment of paediatric hydrocephalus. Overdrainage syndrome is a well-recognised but potentially severe complication, in which hyperostosis cranii ex vacuo—diffuse thickening of the cranial bones—emerges as an adaptive response to chronic intracranial hypotension. Currently, no established diagnostic criteria exist to reliably identify and classify this phenomenon, nor are there defined strategies to prevent associated complications of reduced intracranial compliance. Objective: This study aimed to characterise the morphoradiological and clinical phenotype of hyperostosis cranii ex vacuo in paediatric patients with long-term shunt dependency and to propose its classification as a fifth subtype of CSF overdrainage syndrome with direct implications for long-term neurosurgical care. Methods: A retrospective observational study was conducted on nine paediatric patients with radiologically confirmed diffuse calvarial thickening secondary to surgical treatment of hydrocephalus. Quantitative morphometric analysis of frontal, parietal, and occipital bones, sella turcica dimensions, and dural enhancement was performed using high-resolution neuroimaging. Clinical records were reviewed for hydrocephalus aetiology, shunt revision history, and neurological impairment. Results: All patients exhibited a mean two-fold increase in age-adjusted calvarial thickness. Premature craniosynostosis was identified in 33.3% of cases. Diffuse pachymeningeal enhancement was noted in all patients with contrast-enhanced imaging. Neurological comorbidities included epilepsy, spastic paraparesis, and features of Chiari type I malformation. Conclusions: Hyperostosis cranii ex vacuo represents a distinct and underrecognised consequence of chronic CSF overdrainage. We propose preliminary diagnostic criteria and a structured management pathway—from radiological recognition through ICP assessment to tiered surgical intervention. Formal recognition of this entity as a fifth subtype of CSF overdrainage syndrome may enhance early diagnosis, improve risk stratification, and guide long-term surveillance of shunted children. Full article
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17 pages, 1876 KB  
Article
Shunt Dysfunction Assessment in Shunted Patients via Multiparametric Non-Invasive ICP Waveform Monitoring
by Raphael Bertani, Gabriel Semione, Milene Zanella Capitanio, Sérgio Brasil, Sávio Batista, Gabriel André da Silva Mendes, Caio Perret, Christian Ferreira, Wellingson Silva Paiva and Fernando Campos Gomes Pinto
Biomedicines 2025, 13(10), 2436; https://doi.org/10.3390/biomedicines13102436 - 7 Oct 2025
Viewed by 1241
Abstract
Background/Objectives: Ventriculoperitoneal shunts are the standard treatment for adults diagnosed with several CSF disorders, but often face dysfunction, leading interest in non-invasive methods for diagnosing shunt issues. This study evaluates the potential of non-invasive intracranial pressure waveform monitoring (nICPw) with the brain4care [...] Read more.
Background/Objectives: Ventriculoperitoneal shunts are the standard treatment for adults diagnosed with several CSF disorders, but often face dysfunction, leading interest in non-invasive methods for diagnosing shunt issues. This study evaluates the potential of non-invasive intracranial pressure waveform monitoring (nICPw) with the brain4care (B4C) system to distinguish overdrainage, underdrainage, and normal shunt function in patients with CSF disorders. Methods: In this single-center, observational study at Hospital das Clínicas, Brazil, adult patients with CSF shunts were enrolled. Patients were categorized as Overdrainage or Underdrainage, based on clinical parameters, with an Asymptomatic group. The B4C system provided nICPw monitoring, and six parameters (including various P2/P1 ratios) were analyzed via MANOVA and ANOVA. Results: Among 30 patients (6 overdrainage, 6 underdrainage, 18 asymptomatic), five asymptomatic patients were excluded from the main analysis due to incomplete data collection, leaving 25 patients. Overdrainage patients had significantly higher ΔP2/P1 values (0.618 ± 0.210) than asymptomatic ones (0.227 ± 0.171). After excluding outliers, differences were more pronounced (H = 10.89; p < 0.01). Underdrainage patients had intermediate ΔP2/P1 values (0.387 ± 0.179) and consistently higher P2/P1 averages (>1.3). ROC analysis indicated that ΔP2/P1 > 0.3 suggested shunt dysfunction (AUC = 0.731), while the highest P2/P1 offered stronger discrimination (AUC = 0.782). A global average P2/P1 > 1.3 was linked to underdrainage, with the lowest P2/P1 values differentiating overdrainage (0.948 ± 0.321) from underdrainage (1.143 ± 0.156). Conclusions: nICPw monitoring with the B4C system demonstrated potential for detecting shunt dysfunction. Combining parameters, especially ΔP2/P1 and highest P2/P1, improves diagnostic accuracy, offering a non-invasive method that may aid in distinguishing normal from abnormal shunt function. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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31 pages, 921 KB  
Article
Relationship Between RAP and Multi-Modal Cerebral Physiological Dynamics in Moderate/Severe Acute Traumatic Neural Injury: A CAHR-TBI Multivariate Analysis
by Abrar Islam, Kevin Y. Stein, Donald Griesdale, Mypinder Sekhon, Rahul Raj, Francis Bernard, Clare Gallagher, Eric P. Thelin, Francois Mathieu, Andreas Kramer, Marcel Aries, Logan Froese and Frederick A. Zeiler
Bioengineering 2025, 12(9), 1006; https://doi.org/10.3390/bioengineering12091006 - 22 Sep 2025
Cited by 1 | Viewed by 1424
Abstract
Background: The cerebral compliance (or compensatory reserve) index, RAP, is a critical yet underutilized physiological marker in the management of moderate-to-severe traumatic brain injury (TBI). While RAP offers promise as a continuous bedside metric, its broader cerebral physiological context remains partly understood. This [...] Read more.
Background: The cerebral compliance (or compensatory reserve) index, RAP, is a critical yet underutilized physiological marker in the management of moderate-to-severe traumatic brain injury (TBI). While RAP offers promise as a continuous bedside metric, its broader cerebral physiological context remains partly understood. This study aims to characterize the burden of impaired RAP in relation to other key components of cerebral physiology. Methods: Archived data from 379 moderate-to-severe TBI patients were analyzed using descriptive and threshold-based methods across three RAP states (impaired, intact/transitional, and exhausted). Agglomerative hierarchical clustering, principal component analysis, and kernel-based clustering were applied to explore multivariate covariance structures. Then, high-frequency temporal analyses, including vector autoregressive integrated moving average impulse response functions (VARIMA IRF), cross-correlation, and Granger causality, were performed to assess dynamic coupling between RAP and other physiological signals. Results: Impaired and exhausted RAP states were associated with elevated intracranial pressure (p = 0.021). Regarding AMP, impaired RAP was associated with elevated levels, while exhausted RAP was associated with reduced pulse amplitude (p = 3.94 × 10−9). These two RAP states were also associated with compromised autoregulation and diminished perfusion. Clustering analyses consistently grouped RAP with its constituent signals (ICP and AMP), followed by brain oxygenation parameters (brain tissue oxygenation (PbtO2) and regional cerebral oxygen saturation (rSO2)). Cerebral autoregulation (CA) indices clustered more closely with RAP under impaired autoregulatory states. Temporal analyses revealed that RAP exhibited comparatively stronger responses to ICP and arterial blood pressure (ABP) at 1-min resolution. Moreover, when comparing ICP-derived and near-infrared spectroscopy (NIRS)-derived CA indices, they clustered more closely to RAP, and RAP demonstrated greater sensitivity to changes in these ICP-derived CA indices in high-frequency temporal analyses. These trends remained consistent at lower temporal resolutions as well. Conclusion: RAP relationships with other parameters remain consistent and differ meaningfully across compliance states. Integrating RAP into patient trajectory modelling and developing predictive frameworks based on these findings across different RAP states can map the evolution of cerebral physiology over time. This approach may improve prognostication and guide individualized interventions in TBI management. Therefore, these findings support RAP’s potential as a valuable metric for bedside monitoring and its prospective role in guiding patient trajectory modeling and interventional studies in TBI. Full article
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20 pages, 7186 KB  
Article
A Novel Approach to Non-Invasive Intracranial Pressure Wave Monitoring: A Pilot Healthy Brain Study
by Andrius Karaliunas, Laimonas Bartusis, Solventa Krakauskaite, Edvinas Chaleckas, Mantas Deimantavicius, Yasin Hamarat, Vytautas Petkus, Toma Stulge, Vytenis Ratkunas, Guven Celikkaya, Ingrida Januleviciene and Arminas Ragauskas
Sensors 2025, 25(13), 4042; https://doi.org/10.3390/s25134042 - 28 Jun 2025
Cited by 4 | Viewed by 3908
Abstract
Intracranial pressure (ICP) pulse wave morphology, including the ratios of the three characteristic peaks (P1, P2, and P3), offers valuable insights into intracranial dynamics and brain compliance. Traditional invasive methods for ICP pulse wave monitoring pose significant risks, highlighting the need for non-invasive [...] Read more.
Intracranial pressure (ICP) pulse wave morphology, including the ratios of the three characteristic peaks (P1, P2, and P3), offers valuable insights into intracranial dynamics and brain compliance. Traditional invasive methods for ICP pulse wave monitoring pose significant risks, highlighting the need for non-invasive alternatives. This pilot study investigates a novel non-invasive method for monitoring ICP pulse waves through closed eyelids, using a specially designed, liquid-filled, fully passive sensor system named ‘Archimedes 02’. To our knowledge, this is the first technological approach that enables the non-invasive monitoring of ICP pulse waveforms via closed eyelids. This study involved 10 healthy volunteers, aged 26–39 years, who underwent resting-state non-invasive ICP pulse wave monitoring sessions using the ‘Archimedes 02’ device while in the supine position. The recorded signals were processed to extract pulse waves and evaluate their morphological characteristics. The results indicated successful detection of pressure pulse waves, showing the expected three peaks (P1, P2, and P3) in all subjects. The calculated P2/P1 ratios were 0.762 (SD = ±0.229) for the left eye and 0.808 (SD = ±0.310) for the right eye, suggesting normal intracranial compliance across the cohort, despite variations observed in some individuals. Physiological tests—the Valsalva maneuver and the Queckenstedt test, both performed in the supine position—induced statistically significant increases in the P2/P1 and P3/P1 ratios, supporting the notion that non-invasively recorded pressure pulse waves, measured through closed eyelids, reflect intracranial volume and pressure dynamics. Additionally, a transient hypoemic/hyperemic response test performed in the upright position induced signal changes in pressure recordings from the ‘Archimedes 02’ sensor that were consistent with intact cerebral blood flow autoregulation, aligning with established physiological principles. These findings indicate that ICP pulse waves and their dynamic changes can be monitored non-invasively through closed eyelids, offering a potential method for brain monitoring in patients for whom invasive procedures are not feasible. Full article
(This article belongs to the Special Issue Integrated Sensor Systems for Medical Applications)
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15 pages, 5480 KB  
Article
Investigating Delayed Rupture of Flow Diverter-Treated Giant Aneurysm Using Simulated Fluid–Structure Interactions
by Pablo Jeken-Rico, Yves Chau, Aurèle Goetz, Jacques Sedat and Elie Hachem
Bioengineering 2025, 12(3), 305; https://doi.org/10.3390/bioengineering12030305 - 18 Mar 2025
Cited by 1 | Viewed by 2454
Abstract
Giant intracranial aneurysms are frequently treated shortly after discovery due to their increased risk of rupture and commonly symptomatic nature. Among available treatments, flow diverters are often the sole viable option, though they carry a rare but serious risk of delayed post-operative rupture. [...] Read more.
Giant intracranial aneurysms are frequently treated shortly after discovery due to their increased risk of rupture and commonly symptomatic nature. Among available treatments, flow diverters are often the sole viable option, though they carry a rare but serious risk of delayed post-operative rupture. The underlying mechanisms of these ruptures remain unknown, due to the biomechanical complexity of giant aneurysms and challenges in replicating in vivo hemodynamic conditions within numerical simulation frameworks. This study presents a novel fluid–structure interaction simulation of a giant intracranial aneurysm treated with a flow diverter, based on high-resolution rotational angiography imaging. The resulting hemodynamics are compared to three established delayed-rupture hypotheses involving pressure rises, chaotic flow and autolysis. When considering wall compliance, the analysis reveals a consistent phase shift, dampening in pressure cycles, and an increased aneurysmal flow. These findings highlight the need for revisiting existing hypotheses and provide a foundation for advancing both computational modelling and clinical management strategies for giant intracranial aneurysms. Full article
(This article belongs to the Special Issue Interventional Radiology and Vascular Medicine)
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54 pages, 5783 KB  
Article
Characterization of RAP Signal Patterns, Temporal Relationships, and Artifact Profiles Derived from Intracranial Pressure Sensors in Acute Traumatic Neural Injury
by Abrar Islam, Amanjyot Singh Sainbhi, Kevin Y. Stein, Nuray Vakitbilir, Alwyn Gomez, Noah Silvaggio, Tobias Bergmann, Mansoor Hayat, Logan Froese and Frederick A. Zeiler
Sensors 2025, 25(2), 586; https://doi.org/10.3390/s25020586 - 20 Jan 2025
Cited by 2 | Viewed by 2967
Abstract
Goal: Current methodologies for assessing cerebral compliance using pressure sensor technologies are prone to errors and issues with inter- and intra-observer consistency. RAP, a metric for measuring intracranial compensatory reserve (and therefore compliance), holds promise. It is derived using the moving correlation between [...] Read more.
Goal: Current methodologies for assessing cerebral compliance using pressure sensor technologies are prone to errors and issues with inter- and intra-observer consistency. RAP, a metric for measuring intracranial compensatory reserve (and therefore compliance), holds promise. It is derived using the moving correlation between intracranial pressure (ICP) and the pulse amplitude of ICP (AMP). RAP remains largely unexplored in cases of moderate to severe acute traumatic neural injury (also known as traumatic brain injury (TBI)). The goal of this work is to explore the general description of (a) RAP signal patterns and behaviors derived from ICP pressure transducers, (b) temporal statistical relationships, and (c) the characterization of the artifact profile. Methods: Different summary and statistical measurements were used to describe RAP’s pattern and behaviors, along with performing sub-group analyses. The autoregressive integrated moving average (ARIMA) model was employed to outline the time-series structure of RAP across different temporal resolutions using the autoregressive (p-order) and moving average orders (q-order). After leveraging the time-series structure of RAP, similar methods were applied to ICP and AMP for comparison with RAP. Finally, key features were identified to distinguish artifacts in RAP. This might involve leveraging ICP/AMP signals and statistical structures. Results: The mean and time spent within the RAP threshold ranges ([0.4, 1], (0, 0.4), and [−1, 0]) indicate that RAP exhibited high positive values, suggesting an impaired compensatory reserve in TBI patients. The median optimal ARIMA model for each resolution and each signal was determined. Autocorrelative function (ACF) and partial ACF (PACF) plots of residuals verified the adequacy of these median optimal ARIMA models. The median of residuals indicates that ARIMA performed better with the higher-resolution data. To identify artifacts, (a) ICP q-order, AMP p-order, and RAP p-order and q-order, (b) residuals of ICP, AMP, and RAP, and (c) cross-correlation between residuals of RAP and AMP proved to be useful at the minute-by-minute resolution, whereas, for the 10-min-by-10-min data resolution, only the q-order of the optimal ARIMA model of ICP and AMP served as a distinguishing factor. Conclusions: RAP signals derived from ICP pressure sensor technology displayed reproducible behaviors across this population of TBI patients. ARIMA modeling at the higher resolution provided comparatively strong accuracy, and key features were identified leveraging these models that could identify RAP artifacts. Further research is needed to enhance artifact management and broaden applicability across varied datasets. Full article
(This article belongs to the Special Issue Sensing Signals for Biomedical Monitoring)
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12 pages, 2226 KB  
Article
The Neurological and Hemodynamics Safety of an Airway Clearance Technique in Patients with Acute Brain Injury: An Analysis of Intracranial Pressure Pulse Morphology Using a Non-Invasive Sensor
by Daniela de Almeida Souza, Gisele Francini Devetak, Marina Wolff Branco, Reinaldo Luz Melo, Jean Lucas Tonial, Ana Marcia Delattre and Silvia Regina Valderramas
Sensors 2024, 24(21), 7066; https://doi.org/10.3390/s24217066 - 2 Nov 2024
Cited by 2 | Viewed by 3021
Abstract
Patients with acute brain injury (ACI) often require mechanical ventilation (MV) and are subject to pulmonary complications, thus justifying the use of Airway Clearance Techniques (ACTs), but their effects on intracranial pressure (ICP) are unknown. This study investigates the neurological and hemodynamics safety [...] Read more.
Patients with acute brain injury (ACI) often require mechanical ventilation (MV) and are subject to pulmonary complications, thus justifying the use of Airway Clearance Techniques (ACTs), but their effects on intracranial pressure (ICP) are unknown. This study investigates the neurological and hemodynamics safety of an ACT called ventilator hyperinflation (VHI) in patients with ACI. This was a randomized clinical equivalence trial, which included patients aged ≥ 18 years with a clinical diagnosis of hemorrhagic stroke, with symptom onset within 48 h. The participants were randomly allocated to the Experimental Group (EG, n = 15), which underwent VHI followed by tracheal aspiration (TA), and the Control Group (CG, n = 15), which underwent TA only. Neurological safety was verified by analyzing the morphology of the ICP wave through the non-invasive B4C sensor, which detects bone deformation of the skull, resulting in a P2/P1 ratio and TTP, and hemodynamics through a multi-parameter monitor. Evaluations were recorded during five instances: T1 (baseline/pre-VHI), T2 (post-VHI and before TA), T3 (post-TA), T4 and T5 (monitoring 10 and 20 min after T3). The comparison between groups showed that there was no effect of the technique on the neurological variables with a mean P2/P1 ratio [F (4,112) = 1.871; p = 0.120; np2 = 0.063] and TTP [F (4,112) = 2.252; p = 0.068; np2 = 0.074], and for hemodynamics, heart rate [F (4,112) = 1.920; p = 0.112; np2 = 0.064] and mean arterial pressure [F(2.73, 76.57) = 0.799; p = 0.488; np2 = 0.028]. Our results showed that VHI did not pose a neurological or hemodynamics risk in neurocritical patients after ACI. Full article
(This article belongs to the Special Issue Advanced Non-Invasive Sensors: Methods and Applications)
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