{"paper_id":"3ef0b760-0342-4ca4-a0ff-07f42b2af106","body_text":"Sonolucent Cranial Windows Enable Bedside Ultrasound Identification of MRI- Concordant Glioblastoma Recurrence During Outpatient Surveillance | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Sonolucent Cranial Windows Enable Bedside Ultrasound Identification of MRI- Concordant Glioblastoma Recurrence During Outpatient Surveillance Griffin Thomas, Shoaib Syed, Samuel Latzman, Marcio Yuri Ferreira, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8904429/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background and Objective: Glioblastoma (GBM) is characterized by near-universal recurrence after surgical resection, necessitating close postoperative surveillance. Although MRI remains the gold standard for detecting tumor progression, fixed imaging intervals may delay recognition of recurrence. Sonolucent cranial implants enable transcranioplasty ultrasound (TCUS), offering a potential point-of-care adjunct for interval monitoring between scheduled MRI studies. We evaluated the feasibility of identifying sonographic findings concordant with MRI-confirmed GBM recurrence during routine outpatient follow-up. Methods We conducted a retrospective review of prospectively registered consecutive GBM patients who underwent tumor resection with placement of a sonolucent cranial implant (ClearFit®, Longeviti Inc., Baltimore, MD) at a single tertiary center (February 2023–November 2025). Patients were included if they developed MRI-confirmed recurrence and underwent TCUS within one month before or after the recurrence-detecting MRI. TCUS examinations were performed during routine outpatient visits and interpreted by a clinician blinded to MRI findings. MRIs were independently reviewed by board-certified neuroradiologists. TCUS findings were qualitatively compared with MRI-defined recurrence. Results Of 13 patients with sonolucent implants, 8 developed MRI-confirmed recurrence within 13 months of resection. Four underwent TCUS within one month of the recurrence-detecting MRI. In all four cases, TCUS demonstrated hyperechoic abnormalities spatially concordant with MRI-defined recurrence despite blinded interpretation. Examinations were safely performed in the outpatient setting. Conclusion TCUS through sonolucent cranial implants demonstrated concordant findings with MRI-confirmed GBM recurrence in this preliminary series, supporting its feasibility as a point-of-care adjunct for interval surveillance. Prospective studies are warranted to define standardized protocols and diagnostic performance. Glioblastoma Recurrence Transcranioplasty Ultrasound Sonolucent Cranioplasty Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Glioblastoma (GBM) is the most common primary malignant brain tumor in adults and remains associated with poor prognosis despite advances in surgical and adjuvant therapies. Following standard-of-care treatment with maximal safe resection followed by radiotherapy and temozolomide, median progression-free survival is approximately 7 months, with median overall survival near 15 months [ 1 , 2 ]. Nearly all patients ultimately experience tumor recurrence, underscoring the importance of close postoperative surveillance to inform timely clinical decision-making. Magnetic resonance imaging (MRI) is the current gold standard for monitoring disease progression in patients with GBM due to its superior soft-tissue resolution and ability to characterize contrast enhancement, edema, and treatment-related effects [ 3 ]. In clinical practice, MRI surveillance is typically performed at predefined intervals, most commonly every two to three months, in accordance with established treatment paradigms such as the Stupp protocol [ 2 ]. While effective, this interval-based approach creates a clinically relevant vulnerability: GBM recurrence may occur between scheduled imaging studies, delaying recognition of disease progression in a tumor known for rapid and heterogeneous growth [ 4 ]. In addition, MRI-based surveillance is associated with substantial resource utilization, scheduling constraints, and patient burden, limiting flexibility in individualized follow-up strategies [ 3 ]. Recent advances in neurosurgical reconstruction have introduced sonolucent polymethyl methacrylate (PMMA) cranial implants, which permit postoperative transcranial ultrasound imaging through the cranioplasty site. Transcranioplasty ultrasound (TCUS) has been shown to be feasible for intraoperative guidance and postoperative bedside assessment across a range of neurosurgical applications, including monitoring ventricular size in hydrocephalus, evaluating cerebral bypass patency, assessing mass effect, and identifying postoperative complications such as hematoma or pseudomeningocele [ 5 – 8 ]. These prior studies support TCUS as a safe, repeatable, and cost-effective point-of-care imaging modality capable of providing longitudinal intracranial assessment outside the constraints of conventional MRI scheduling. Despite increasing adoption of sonolucent cranial implants and expanding use of bedside ultrasound in neurosurgery, the role of TCUS in longitudinal oncologic surveillance has not been established. In particular, its utility for identifying glioblastoma recurrence during routine outpatient follow-up has not been systematically evaluated or correlated with MRI-confirmed progression. Moreover, even with MRI, differentiating true tumor recurrence from treatment-related changes such as pseudoprogression remains diagnostically challenging, highlighting the limitations of relying on infrequent, single–time point imaging assessments alone [ 9 ]. Establishing feasibility of interval signal detection using TCUS represents a necessary first step before questions of diagnostic accuracy, specificity, or clinical impact can be meaningfully addressed. In this study, we present the first clinical series evaluating the feasibility of outpatient TCUS performed through sonolucent cranial implants to identify sonographic imaging signatures concordant with MRI-confirmed GBM recurrence. By emphasizing blinded TCUS interpretation and a prespecified temporal window relative to recurrence-detecting MRI, we aim to assess whether TCUS can function as a practical adjunct for interval surveillance within existing GBM follow-up workflows, rather than as a replacement for standard MRI-based monitoring. METHODS Study design and Ethical Considerations Following the principles outlined in the Declaration of Helsinki and the Preferred Reporting of Case Series in Surgery (PROCESS) 2023 guidelines, we conducted a retrospective review of prospectively registered consecutive cases of patients with GBM who underwent tumor resection with reconstruction using a sonolucent cranial implant at a single tertiary neurosurgical center between February 2023 to November 2025 [ 10 ]. All patients provided written informed consent for surgical intervention, postoperative TCUS evaluation, and use of de-identified clinical and imaging data for research and publication purposes. As this study involved retrospective analysis of de-identified data obtained during routine clinical care, institutional review board approval was not required. Clinical trial number: not applicable. Patient Selection and Inclusion criteria Patients were eligible for inclusion if they met all of the following criteria: (1) Age ≥ 18 years at the time of surgery; (2) Histopathologically confirmed glioblastoma; (3) Tumor resection with placement of a sonolucent polymethyl methacrylate (PMMA) cranial implant (ClearFit®, Longeviti Neuro Solutions LLC, Hunt Valley, MD, USA); (4) Radiographic evidence of tumor recurrence identified on MRI during postoperative surveillance; and (5) Performance of transcranioplasty ultrasound (TCUS) within a prespecified temporal window of one month before or one month after the MRI study that identified recurrence. The temporal concordance window was defined a priori to maximize biological plausibility that TCUS and MRI reflected the same disease state, rather than to increase sample size. All cases meeting these criteria were included regardless of TCUS image quality. Standard chemoradiotherapy (Table 1 ) was defined as 6 weeks of radiotherapy with concurrent temozolomide chemotherapy followed by 6 cycles of adjuvant temozolomide chemotherapy for 5 days every 28 days, as prescribed in the Stupp protocol 2 . Transcranioplasty Ultrasound Acquisition and Interpretation TCUS examinations were performed during a routine outpatient clinic visits using a LOGIQ E10s ultrasound system (GE Healthcare, Chicago, IL, USA). Imaging was obtained using a 2–6 MHz broadband probe with a two-dimensional array and curved-linear geometry. The abdominal preset was used for grayscale structural imaging, and a vascular preset was employed when Doppler interrogation was indicated. Imaging depth was typically set between 6 and 8 cm to allow visualization of the resection cavity, surrounding parenchyma, ventricular system, and midline structures. Patients were imaged in the seated position without hair removal. The ultrasound probe was placed directly over the sonolucent cranial implant using standard ultrasound gel. Axial and sagittal sweeps were systematically acquired to assess intracranial anatomy, including the resection cavity margins, adjacent brain parenchyma, ventricular system, falx, septum pellucidum, choroid plexus, and third ventricle. When present, catheter position and Doppler flow signals were also evaluated. All TCUS examinations were interpreted by a clinician experienced in postoperative neurosurgical ultrasound who was blinded to contemporaneous and prior MRI findings at the time of interpretation. TCUS assessments were descriptive and qualitative, focusing on identification of abnormal echogenic regions relative to prior examinations and expected postoperative anatomy. This blinded interpretation protocol is part of an ongoing institutional effort to evaluate TCUS applications across a range of postoperative neurosurgical indications. Magnetic Resonance Imaging and Definition of Recurrence MRI surveillance was performed using either a Siemens MAGNETOM Vida 3.0T scanner or a Philips Ingenia Elition 3.0T scanner. Imaging protocols included pre-contrast and post-contrast T1-weighted imaging, T2-weighted imaging, T2 FLAIR, and diffusion-weighted imaging. Gadolinium-based contrast (gadobutrol) was administered intravenously at a standard dose of 0.1 mL/kg, with post-contrast imaging acquired within a consistent time window following injection. All MRI studies were interpreted by board-certified neuroradiologists who were blinded to TCUS findings. Tumor recurrence was defined based on new or progressive contrast enhancement and associated imaging features consistent with accepted neuro-oncology imaging criteria. Imaging Concordance Assessment For patients meeting inclusion criteria, TCUS findings were qualitatively compared with MRI-defined recurrence with respect to spatial location and relationship to the prior resection cavity. Concordance was defined as identification of sonographic abnormalities in regions corresponding to MRI-detected recurrence. Given the exploratory nature of this feasibility study and limited cohort size, formal diagnostic performance metrics were not calculated. RESULTS Cohort Overview Between February 2023 and February 2025, 13 adult patients with histopathologically confirmed GBM underwent tumor resection with placement of a sonolucent cranial implant at our institution and were enrolled in a prospectively maintained registry. These patients underwent postoperative surveillance with MRI and TCUS at intervals determined by individual treatment plans. During the surveillance period, 8 of the 13 patients (62%) developed MRI-confirmed tumor recurrence within 13 months of their initial resection. Among these patients, 4 met inclusion criteria for temporal concordance, having undergone TCUS within the prespecified window of one month before or after the MRI study that identified recurrence. These four patients comprise the analytic cohort for this feasibility analysis. Key clinical and imaging characteristics for all four cases are summarized in Table 1 and Table 2 . Imaging Concordance Between TCUS and MRI In all four patients meeting inclusion criteria, TCUS identified hyperechoic abnormalities spatially concordant with regions of MRI-defined recurrence, despite blinded interpretation. TCUS examinations were performed in the outpatient clinic setting without complications and at intervals ranging from 0 to 32 days relative to the recurrence-detecting MRI. Across cases, TCUS enabled visualization of abnormalities adjacent to the prior resection cavity, associated parenchymal changes, and relevant intracranial landmarks, including the ventricular system and midline structures. Two cases with representative, high-quality MRI and TCUS imaging are presented in detail below to illustrate imaging concordance. All four cases demonstrated spatial concordance between TCUS findings and MRI-defined recurrence. Illustrative Case Summaries Illustrative Case 1 A 73-year-old woman presented with cognitive symptoms and was found to have a left temporal glioblastoma. She underwent subtotal resection with placement of a sonolucent cranial implant. MRI surveillance demonstrated tumor recurrence 20 weeks after surgery, and the patient subsequently underwent repeat resection. Further MRI surveillance identified additional recurrence 11 weeks after the second resection. TCUS performed 15 weeks after the second resection demonstrated a hyperechoic abnormality at the medial margin of the resection cavity corresponding to nodular enhancement and T2 FLAIR hyperintensity on MRI (Fig. 1 ). The patient elected hospice care and died two months later. Illustrative Case 2 A 79-year-old woman underwent gross total resection of a right temporal glioblastoma with placement of a sonolucent cranial implant. MRI surveillance identified recurrence 19 weeks postoperatively. TCUS performed 14 days later demonstrated a hyperechoic abnormality at the posterior margin of the resection cavity corresponding to a newly enhancing lesion on MRI (Fig. 2 ). The patient declined further chemoradiotherapy. Non-Illustrated Cases Two additional patients met inclusion criteria for temporal concordance and demonstrated spatial concordance between TCUS findings and MRI-defined recurrence. In one patient, TCUS performed on the same day as MRI identified a hyperechoic abnormality at the posterolateral margin of the resection cavity corresponding to MRI findings. In the other patient, TCUS performed 12 days after MRI demonstrated a hyperechoic abnormality in the inferior temporal region corresponding to MRI-defined recurrence. Imaging intervals, lesion locations, and concordance for these cases are summarized in Table 1 and Table 2 . Summary of Findings Across all four cases, TCUS identified sonographic abnormalities spatially concordant with MRI-confirmed glioblastoma recurrence when performed within a prespecified temporal window and interpreted blinded to MRI findings. These observations establish feasibility of outpatient TCUS for identifying imaging signatures associated with tumor recurrence but do not assess diagnostic accuracy or distinguish tumor from treatment-related effects. Table 1 Patient Characteristics at Presentation Case Age/Sex Tumor Location Implant Location Molecular Details Extent of Initial Resection Initial Chemo/RT Treatment Plan 1 74/F Left temporal Left frontotemporal GBM, IDH-wildtype, MGMT methylated, EGFR amplified Subtotal resection Standard chemotherapy and RT followed by maintenance TMZ per Stupp protocol. 2 79/F Right temporal Right temporal GBM, IDH- wildtype, MGMT methylated Gross total resection Patient did not receive chemotherapy or RT 3 62/M Middle cranial fossa and right temporal lobe Right temporal GBM, IDH-wildtype, MGMT methylated Subtotal resection Standard chemotherapy and RT followed by maintenance TMZ per Stupp protocol 4 70/M Right temporal Right temporal GBM, IDH-wildtype, MGMT unmethylated, EGFR non-amplified Gross total resection Standard chemotherapy and RT followed by maintenance TMZ per Stupp protocol GBM: Glioblastoma, RT: Radiation Therapy, TMZ: Temozolomide, IDH: Isocitrate Dehydrogenase, MGMT: O 6 -methylguanine-DNA methyltransferase, EGFR: Epidermal Growth Factor Receptor Table 2 Patient Characteristics at Recurrence Case Age/Sex Surgery-Recurrence on MRI Interval Surgery-Recurrence on TCUS Interval MRI-TCUS Interval MRI Evidence of Recurrence TCUS Evidence of Recurrence Symptoms of Recurrence Management Change after Recurrence Reoperation after MRI and TCUS detection of tumor 1 74/F 78 days 110 days + 32 Increased contrast enhancement and T2 hyperintense regions in the left parahippocampal gyrus Region of hyperechoic signal at the medial margin of the left temporal resection cavity correlating with T1 hyperintensity on post-contrast MR at the region of the parahippocampal gyrus. Hydrocephalus Declined further treatment including chemotherapy or RT No 2 79/F 131 days 145 days + 14 Interval development of heterogenous enhancement in the right temporal lobe suspicious for tumoral disease Region of hyperechoic signal at the posterior-medial and posterolateral margin of the right temporal resection cavity correlating with hyperintense contrast-enhanced region at the left temporal lobe on T1 MR. Generalized lower leg weakness, emesis Declined further treatment including chemotherapy or RT No 3 62/M 125 days 125 days 0 Interval development of a peripheral area of enhancement in the right temporal lobe/posterior insula Hyperechoic signal at the posterolateral margin of the resection cavity correlating with hyperintense T1 post contrast MRI signal Decreased executive function, seizure, weakness, worsened balance and gait Gamma Knife Radiosurgery in 5 fractions Bevacizumab therapy No 4 70/M 337 days 349 days + 12 New expansile nodular lesion along the posterior lateral margin of the resection cavity Hyperechoic signal at the right inferior temporal lobe lateral to the right lateral ventricle correlating with T1 hyperintensity Denied new symptoms Carboplatin therapy Yes (gross total resection, pathology confirmed glioblastoma RT: Radiation Therapy DISCUSSION In this retrospective feasibility series, we demonstrate that transcranioplasty ultrasound (TCUS) performed through sonolucent cranial implants can identify sonographic abnormalities spatially concordant with MRI-confirmed glioblastoma recurrence during routine outpatient follow-up. Across all four cases meeting prespecified temporal criteria, TCUS identified abnormalities corresponding to regions of MRI-defined recurrence despite blinded interpretation. These findings establish feasibility of clinic-based TCUS as a point-of-care adjunct for interval surveillance in patients with GBM and provide a foundation for prospective evaluation. The clinical challenge motivating this work is not the inadequacy of MRI, but rather the rigidity of interval-based surveillance in a disease characterized by rapid and heterogeneous progression. Standard follow-up imaging schedules, typically every two to three months as established in the Stupp protocol, may allow clinically meaningful disease evolution to occur between scans [ 2 ]. TCUS offers a practical mechanism to increase surveillance frequency without imposing the logistical and resource constraints associated with additional MRI examinations [ 3 ]. In this context, TCUS is best conceptualized as a surveillance trigger rather than a diagnostic replacement, prioritizing early identification of interval change and timely escalation to conventional imaging when warranted. Importantly, TCUS shares interpretive limitations with other postoperative imaging modalities. Distinguishing tumor progression from treatment-related effects or peritumoral edema remains a fundamental challenge in glioblastoma surveillance and is not unique to ultrasound-based imaging [ 11 ]. On conventional grayscale ultrasound, echogenic abnormalities reflect alterations in tissue microstructure and acoustic interfaces rather than tumor-specific biology, resulting in overlap between infiltrative tumor, vasogenic edema, gliosis, and radiation-related change. Prior intraoperative and bedside ultrasound studies have consistently noted this limitation, emphasizing ultrasound’s strength in defining lesion geometry and interval change rather than definitive tissue characterization [ 12 – 14 ]. Moreover, even MRI faces diagnostic ambiguity in differentiating true tumor recurrence from pseudoprogression or radiation-related injury, particularly in the early post-treatment period [ 11 ]. Accordingly, the findings presented here should not be interpreted as evidence that TCUS can independently distinguish recurrence from treatment-related effects, but rather as support for its role in detecting interval deviation from an individual patient’s postoperative baseline. The feasibility demonstrated in this series builds upon prior work establishing the safety and utility of TCUS for postoperative neurosurgical assessment. Ultrasound through sonolucent cranial implants has been shown to reliably visualize intracranial structures for monitoring ventricular size, cerebral bypass patency, mass effect, and postoperative complications such as hematoma and pseudomeningocele [ 6 – 8 ]. Our findings extend these applications into the oncologic surveillance domain, demonstrating that TCUS can be integrated into outpatient workflows to monitor for imaging changes associated with tumor recurrence. Although formal cost-effectiveness was not evaluated in this study, TCUS represents a low-resource, point-of-care imaging modality that can be performed during routine outpatient visits without the infrastructure, scheduling demands, or patient burden associated with MRI. When conceptualized as an adjunctive surveillance tool rather than a replacement, TCUS may reduce unnecessary or prematurely triggered MRI examinations while enabling earlier recognition of interval change. The potential impact of TCUS on imaging utilization, workflow efficiency, and healthcare resource allocation warrants formal evaluation in prospective studies. Advances in ultrasound technology may further expand the utility of TCUS in neuro-oncologic surveillance. Doppler interrogation can provide complementary information regarding vascular patterns and flow, while contrast-enhanced ultrasound (CEUS) has demonstrated improved delineation of tumor perfusion and residual disease in intraoperative and experimental glioma imaging settings [ 12 – 16 ]. These techniques offer biologically informed signal beyond grayscale echogenicity and may improve tissue characterization. However, whether Doppler or CEUS can reliably differentiate recurrent tumor from treatment-related effects or pseudoprogression in the outpatient surveillance setting remains insufficiently studied and requires prospective validation. Incorporation of multiparametric ultrasound techniques into standardized TCUS protocols represents an important area for future investigation. Successful integration of TCUS into longitudinal GBM surveillance requires attention to several practical considerations. Reliable acoustic access to the region of interest depends on implant positioning and reconstruction strategy, emphasizing the importance of surgical planning when ultrasound-based follow-up is anticipated. Reproducible acquisition and interpretation necessitate operator training and standardized imaging protocols to ensure consistency across visits and readers. Furthermore, incorporation of TCUS into routine follow-up workflows requires coordination among surgical, oncologic, and radiologic teams to ensure that concerning sonographic findings prompt appropriate escalation rather than isolated interpretation. Limitations This study has several limitations. The cohort is small and derived from a single institution, precluding assessment of diagnostic performance metrics such as sensitivity or specificity. The retrospective design and reliance on qualitative imaging concordance limit generalizability. Additionally, TCUS interpretation was performed by experienced operators within a specialized program, and performance may differ in broader practice settings without standardized training. These limitations are inherent to early feasibility investigations and underscore the need for prospective, multicenter studies with harmonized acquisition protocols, blinded interpretation, and correlation with clinical outcomes. To address these challenges, we propose a structured framework for integrating TCUS into GBM surveillance pathways, spanning patient selection, standardized acquisition, and longitudinal interpretation anchored to interval change rather than single time-point appearance (Fig. 3 ). In this model, TCUS functions as a low-threshold, repeatable assessment tool performed during routine clinic visits. Clearly abnormal or evolving sonographic findings would prompt expedited MRI and multidisciplinary review, while stable examinations could support continued observation until scheduled imaging. Such an approach aligns with prior recommendations emphasizing TCUS as an adjunctive, rather than standalone, imaging modality. Abbreviations GBM: Glioblastoma MGMT: O 6 -methylguanine-DNA methyltransferase PMMA: Poly(methyl-methacrylate) TCUS: Transcranioplasty Ultrasound Declarations Statements and Declarations: No funding was received for the completion of this work. All authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Author Contribution Statement Conception and design : Randy S. D’Amico Acquisition of data: Seth Mejia, Artur Shlifer, Vadim Zhigin, Tamika Wong, Sanskruti (Sana) Bokil, Sara Massimo Analysis and interpretation of data: Griffin Thomas, Shoaib Syed, Marcio Yuri Ferreira, Seth Mejia, Randy S. D’Amico Drafting the article: Griffin Thomas, Shoaib Syed, Samuel Latzman, Marcio Yuri Ferreira, Randy S. D’Amico Critically reviewing the article: All authors Study Supervision: Randy D’Amico, Netanel Ben-Shalom Funding: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing Interests: The authors have no relevant financial or non-financial interests to disclose. References Schaff LR, Mellinghoff IK (2023) Glioblastoma and Other Primary Brain Malignancies in Adults: A Review. JAMA, 329(7): pp. 574–587 Stupp R et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. 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J Perinatol, 32(6): pp. 448 – 53 Wei R et al (2023) Application of intraoperative ultrasound in the resection of high-grade gliomas. Front Neurol 14:1240150 Wu H et al (2024) Progress in the application of ultrasound in glioma surgery. Front Med (Lausanne) 11:1388728 Prada F et al (2016) Identification of residual tumor with intraoperative contrast-enhanced ultrasound during glioblastoma resection. Neurosurg Focus 40(3):E7 Ferreira MY, Cardoso LJC, Huda S, Ben-Shalom N (2026) Intraoperative contrast-enhanced ultrasound-assisted resection of brain tumors: a systematic review and meta-analysis. Neurochirurgie Published online January 12. 10.1016/j.neuchi.2026.101774 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-8904429\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":602195481,\"identity\":\"4e718a86-d476-493c-b7f8-fc381502a86f\",\"order_by\":0,\"name\":\"Griffin Thomas\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+klEQVRIiWNgGAWjYFACHjApZ9/eAKIPMDCwMwNZbHh0sEG0GBvwAFUzJAAJZkbitCRukEggUot8fO/BRzdq6hi3S749+Ljyx53EfpCWD2WHcWoxPMaXbJxz7DCz5ey8ZMMzCc8SZzYzNjDOOIdHSxuPmXQO2wE2hts5ZpINCYdzNxxmbGDmbSOk5V8dD8PNMxAt+0Fa/uLRIs8G1JLbxixhcIMHagvQL8yMeLQYsOUYG+f2HTaQ7MkxNmxIO1w/A2jLwZ5z6bhtaT5j+DjnW119P/sZw4cNNoeN+dubDz74UWaN25YD2ESxCsJtacAnOwpGwSgYBaMABAACxlklf3aelAAAAABJRU5ErkJggg==\",\"orcid\":\"\",\"institution\":\"Northwell\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Griffin\",\"middleName\":\"\",\"lastName\":\"Thomas\",\"suffix\":\"\"},{\"id\":602195482,\"identity\":\"3d28b205-c9b3-45f7-be96-abe2c7892081\",\"order_by\":1,\"name\":\"Shoaib Syed\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Northwell\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Shoaib\",\"middleName\":\"\",\"lastName\":\"Syed\",\"suffix\":\"\"},{\"id\":602195483,\"identity\":\"6f645c14-4a8a-443f-bcf0-158767bb281e\",\"order_by\":2,\"name\":\"Samuel Latzman\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Northwell\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Samuel\",\"middleName\":\"\",\"lastName\":\"Latzman\",\"suffix\":\"\"},{\"id\":602195484,\"identity\":\"b235350d-8fbf-4c63-84fc-0b84329f7bec\",\"order_by\":3,\"name\":\"Marcio Yuri Ferreira\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Northwell\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Marcio\",\"middleName\":\"Yuri\",\"lastName\":\"Ferreira\",\"suffix\":\"\"},{\"id\":602195485,\"identity\":\"cf8a9b59-d79e-4d50-a0ec-69278aa2c8f5\",\"order_by\":4,\"name\":\"Seth Mejia\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Northwell\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Seth\",\"middleName\":\"\",\"lastName\":\"Mejia\",\"suffix\":\"\"},{\"id\":602195486,\"identity\":\"294e770a-1772-460f-8794-db12f10eb16b\",\"order_by\":5,\"name\":\"Artur Shlifer\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Northwell\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Artur\",\"middleName\":\"\",\"lastName\":\"Shlifer\",\"suffix\":\"\"},{\"id\":602195487,\"identity\":\"0b2d73a1-812e-4706-9a40-b9566c6e625d\",\"order_by\":6,\"name\":\"Vadim Zhigin\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Northwell\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Vadim\",\"middleName\":\"\",\"lastName\":\"Zhigin\",\"suffix\":\"\"},{\"id\":602195488,\"identity\":\"fbef9f65-0317-4403-8598-9db0fc22e94e\",\"order_by\":7,\"name\":\"Tamika Wong\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Northwell\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Tamika\",\"middleName\":\"\",\"lastName\":\"Wong\",\"suffix\":\"\"},{\"id\":602195489,\"identity\":\"2394f867-24ad-4b09-933d-63176721e504\",\"order_by\":8,\"name\":\"Sanskruti (Sana) Bokil\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Northwell\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Sanskruti\",\"middleName\":\"(Sana)\",\"lastName\":\"Bokil\",\"suffix\":\"\"},{\"id\":602195490,\"identity\":\"8cf266f9-3c5a-4127-a788-a6373715b414\",\"order_by\":9,\"name\":\"Sara Massimo\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Northwell\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Sara\",\"middleName\":\"\",\"lastName\":\"Massimo\",\"suffix\":\"\"},{\"id\":602195491,\"identity\":\"42bf98e5-ca02-40c0-a52f-4cbfd58aed85\",\"order_by\":10,\"name\":\"John A. Boockvar\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Northwell\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"John\",\"middleName\":\"A.\",\"lastName\":\"Boockvar\",\"suffix\":\"\"},{\"id\":602195492,\"identity\":\"ef28f1ec-4522-4558-9970-db2c4e1385bb\",\"order_by\":11,\"name\":\"Netanel Ben-Shalom\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Northwell\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Netanel\",\"middleName\":\"\",\"lastName\":\"Ben-Shalom\",\"suffix\":\"\"},{\"id\":602195493,\"identity\":\"8d6699ac-fbb9-47b4-b082-675a1ed3ba20\",\"order_by\":12,\"name\":\"Randy S. D’Amico\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Northwell\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Randy\",\"middleName\":\"S.\",\"lastName\":\"D’Amico\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2026-02-17 21:38:44\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-8904429/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-8904429/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":104338130,\"identity\":\"d91cdda6-65dc-4004-ab60-a8539299852f\",\"added_by\":\"auto\",\"created_at\":\"2026-03-10 16:18:13\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":303385,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eMRI and TCUS Imaging for Case 1\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAxial T2 FLAIR at separate slices (A, B), and post-contrast (C) MRI sequences obtained 78 days after surgery demonstrated left temporal periventricular hyperintensity and contrast enhancement near the location of the prior resection cavity. MRI images are rotated 90° counterclockwise to correlate with TCUS orientation. Corresponding TCUS (D) obtained 32 days after MRI-detected recurrence demonstrated a hyperechoic signal suspicious for recurrent disease abutting the lateral ventricles (shaded) corresponded to the hyperintense region seen on MRI. The midbrain and tentorium cerebelli are shaded blue and green, respectively, on the TCUS image for spatial orientation. A timeline of the patient’s resection and postoperative surveillance is portrayed below the imaging\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-8904429/v1/75d39aa182fb8bfdf67a9c9f.png\"},{\"id\":104779714,\"identity\":\"1c8097f9-fee0-44c3-8ffa-860224cb683c\",\"added_by\":\"auto\",\"created_at\":\"2026-03-17 07:45:06\",\"extension\":\"png\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":329018,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eMRI and TCUS Imaging for Case 2\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAxial T1 pre-contrast (A), post-contrast (B), T2 FLAIR (C) MRI sequences obtained 131 days after resection demonstrated a contrast-enhanced hyperintense region (arrowheads) with surrounding FLAIR edema (arrow) at the posterior aspect of the prior right temporal resection cavity. Corresponding TCUS (D) obtained 14 days thereafter demonstrated a hyperechoic signal, suspicious for recurrent disease at the posterior margin of the resection cavity. The tentorium cerebelli is shaded green on the TCUS image for spatial orientation. Note, the TCUS image has been rotated 180° to match the MRI orientation. A timeline of the patient’s resection and postoperative surveillance is portrayed below the imaging\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"2.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-8904429/v1/ee374426871f516a018646e4.png\"},{\"id\":104338128,\"identity\":\"ae111494-9b1f-4e48-b2df-6d0fe2d320ac\",\"added_by\":\"auto\",\"created_at\":\"2026-03-10 16:18:13\",\"extension\":\"png\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":120939,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eProposed TCUS Workflow\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eOur institution's workflow for integrating TCUS surveillance imaging into GBM care plans. Created in BioRender. (2026)\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"3.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-8904429/v1/8bd0c1070c39845372071286.png\"},{\"id\":104860506,\"identity\":\"3f7fba5b-2c49-4c90-ae40-655fa73301c1\",\"added_by\":\"auto\",\"created_at\":\"2026-03-18 05:11:12\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":1698076,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-8904429/v1/7231eca5-b0f4-45ab-8b12-f0b6af19c8ad.pdf\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Sonolucent Cranial Windows Enable Bedside Ultrasound Identification of MRI- Concordant Glioblastoma Recurrence During Outpatient Surveillance\",\"fulltext\":[{\"header\":\"INTRODUCTION\",\"content\":\"\\u003cp\\u003eGlioblastoma (GBM) is the most common primary malignant brain tumor in adults and remains associated with poor prognosis despite advances in surgical and adjuvant therapies. Following standard-of-care treatment with maximal safe resection followed by radiotherapy and temozolomide, median progression-free survival is approximately 7 months, with median overall survival near 15 months [\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e]. Nearly all patients ultimately experience tumor recurrence, underscoring the importance of close postoperative surveillance to inform timely clinical decision-making.\\u003c/p\\u003e \\u003cp\\u003eMagnetic resonance imaging (MRI) is the current gold standard for monitoring disease progression in patients with GBM due to its superior soft-tissue resolution and ability to characterize contrast enhancement, edema, and treatment-related effects [\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e]. In clinical practice, MRI surveillance is typically performed at predefined intervals, most commonly every two to three months, in accordance with established treatment paradigms such as the Stupp protocol [\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e]. While effective, this interval-based approach creates a clinically relevant vulnerability: GBM recurrence may occur between scheduled imaging studies, delaying recognition of disease progression in a tumor known for rapid and heterogeneous growth [\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e]. In addition, MRI-based surveillance is associated with substantial resource utilization, scheduling constraints, and patient burden, limiting flexibility in individualized follow-up strategies [\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eRecent advances in neurosurgical reconstruction have introduced sonolucent polymethyl methacrylate (PMMA) cranial implants, which permit postoperative transcranial ultrasound imaging through the cranioplasty site. Transcranioplasty ultrasound (TCUS) has been shown to be feasible for intraoperative guidance and postoperative bedside assessment across a range of neurosurgical applications, including monitoring ventricular size in hydrocephalus, evaluating cerebral bypass patency, assessing mass effect, and identifying postoperative complications such as hematoma or pseudomeningocele [\\u003cspan additionalcitationids=\\\"CR6 CR7\\\" citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e]. These prior studies support TCUS as a safe, repeatable, and cost-effective point-of-care imaging modality capable of providing longitudinal intracranial assessment outside the constraints of conventional MRI scheduling.\\u003c/p\\u003e \\u003cp\\u003eDespite increasing adoption of sonolucent cranial implants and expanding use of bedside ultrasound in neurosurgery, the role of TCUS in longitudinal oncologic surveillance has not been established. In particular, its utility for identifying glioblastoma recurrence during routine outpatient follow-up has not been systematically evaluated or correlated with MRI-confirmed progression. Moreover, even with MRI, differentiating true tumor recurrence from treatment-related changes such as pseudoprogression remains diagnostically challenging, highlighting the limitations of relying on infrequent, single\\u0026ndash;time point imaging assessments alone [\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e]. Establishing feasibility of interval signal detection using TCUS represents a necessary first step before questions of diagnostic accuracy, specificity, or clinical impact can be meaningfully addressed.\\u003c/p\\u003e \\u003cp\\u003eIn this study, we present the first clinical series evaluating the feasibility of outpatient TCUS performed through sonolucent cranial implants to identify sonographic imaging signatures concordant with MRI-confirmed GBM recurrence. By emphasizing blinded TCUS interpretation and a prespecified temporal window relative to recurrence-detecting MRI, we aim to assess whether TCUS can function as a practical adjunct for interval surveillance within existing GBM follow-up workflows, rather than as a replacement for standard MRI-based monitoring.\\u003c/p\\u003e\"},{\"header\":\"METHODS\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStudy design and Ethical Considerations\\u003c/h2\\u003e \\u003cp\\u003eFollowing the principles outlined in the \\u003cem\\u003eDeclaration of Helsinki\\u003c/em\\u003e and the Preferred Reporting of Case Series in Surgery (PROCESS) 2023 guidelines, we conducted a retrospective review of prospectively registered consecutive cases of patients with GBM who underwent tumor resection with reconstruction using a sonolucent cranial implant at a single tertiary neurosurgical center between February 2023 to November 2025 [\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e]. All patients provided written informed consent for surgical intervention, postoperative TCUS evaluation, and use of de-identified clinical and imaging data for research and publication purposes. As this study involved retrospective analysis of de-identified data obtained during routine clinical care, institutional review board approval was not required. Clinical trial number: not applicable.\\u003c/p\\u003e \\u003c/div\\u003e\\n\\u003ch3\\u003ePatient Selection and Inclusion criteria\\u003c/h3\\u003e\\n\\u003cp\\u003ePatients were eligible for inclusion if they met all of the following criteria: (1) Age\\u0026thinsp;\\u0026ge;\\u0026thinsp;18 years at the time of surgery; (2) Histopathologically confirmed glioblastoma; (3) Tumor resection with placement of a sonolucent polymethyl methacrylate (PMMA) cranial implant (ClearFit\\u0026reg;, Longeviti Neuro Solutions LLC, Hunt Valley, MD, USA); (4) Radiographic evidence of tumor recurrence identified on MRI during postoperative surveillance; and (5) Performance of transcranioplasty ultrasound (TCUS) within a prespecified temporal window of one month before or one month after the MRI study that identified recurrence. The temporal concordance window was defined a priori to maximize biological plausibility that TCUS and MRI reflected the same disease state, rather than to increase sample size. All cases meeting these criteria were included regardless of TCUS image quality. Standard chemoradiotherapy (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e) was defined as 6 weeks of radiotherapy with concurrent temozolomide chemotherapy followed by 6 cycles of adjuvant temozolomide chemotherapy for 5 days every 28 days, as prescribed in the Stupp protocol\\u003csup\\u003e2\\u003c/sup\\u003e.\\u003c/p\\u003e\\n\\u003ch3\\u003eTranscranioplasty Ultrasound Acquisition and Interpretation\\u003c/h3\\u003e\\n\\u003cp\\u003eTCUS examinations were performed during a routine outpatient clinic visits using a LOGIQ E10s ultrasound system (GE Healthcare, Chicago, IL, USA). Imaging was obtained using a 2\\u0026ndash;6 MHz broadband probe with a two-dimensional array and curved-linear geometry. The abdominal preset was used for grayscale structural imaging, and a vascular preset was employed when Doppler interrogation was indicated. Imaging depth was typically set between 6 and 8 cm to allow visualization of the resection cavity, surrounding parenchyma, ventricular system, and midline structures.\\u003c/p\\u003e \\u003cp\\u003ePatients were imaged in the seated position without hair removal. The ultrasound probe was placed directly over the sonolucent cranial implant using standard ultrasound gel. Axial and sagittal sweeps were systematically acquired to assess intracranial anatomy, including the resection cavity margins, adjacent brain parenchyma, ventricular system, falx, septum pellucidum, choroid plexus, and third ventricle. When present, catheter position and Doppler flow signals were also evaluated.\\u003c/p\\u003e \\u003cp\\u003eAll TCUS examinations were interpreted by a clinician experienced in postoperative neurosurgical ultrasound who was blinded to contemporaneous and prior MRI findings at the time of interpretation. TCUS assessments were descriptive and qualitative, focusing on identification of abnormal echogenic regions relative to prior examinations and expected postoperative anatomy. This blinded interpretation protocol is part of an ongoing institutional effort to evaluate TCUS applications across a range of postoperative neurosurgical indications.\\u003c/p\\u003e\\n\\u003ch3\\u003eMagnetic Resonance Imaging and Definition of Recurrence\\u003c/h3\\u003e\\n\\u003cp\\u003eMRI surveillance was performed using either a Siemens MAGNETOM Vida 3.0T scanner or a Philips Ingenia Elition 3.0T scanner. Imaging protocols included pre-contrast and post-contrast T1-weighted imaging, T2-weighted imaging, T2 FLAIR, and diffusion-weighted imaging. Gadolinium-based contrast (gadobutrol) was administered intravenously at a standard dose of 0.1 mL/kg, with post-contrast imaging acquired within a consistent time window following injection.\\u003c/p\\u003e \\u003cp\\u003eAll MRI studies were interpreted by board-certified neuroradiologists who were blinded to TCUS findings. Tumor recurrence was defined based on new or progressive contrast enhancement and associated imaging features consistent with accepted neuro-oncology imaging criteria.\\u003c/p\\u003e\\n\\u003ch3\\u003eImaging Concordance Assessment\\u003c/h3\\u003e\\n\\u003cp\\u003eFor patients meeting inclusion criteria, TCUS findings were qualitatively compared with MRI-defined recurrence with respect to spatial location and relationship to the prior resection cavity. Concordance was defined as identification of sonographic abnormalities in regions corresponding to MRI-detected recurrence. Given the exploratory nature of this feasibility study and limited cohort size, formal diagnostic performance metrics were not calculated.\\u003c/p\\u003e\"},{\"header\":\"RESULTS\",\"content\":\"\\u003cdiv id=\\\"Sec9\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eCohort Overview\\u003c/h2\\u003e \\u003cp\\u003eBetween February 2023 and February 2025, 13 adult patients with histopathologically confirmed GBM underwent tumor resection with placement of a sonolucent cranial implant at our institution and were enrolled in a prospectively maintained registry. These patients underwent postoperative surveillance with MRI and TCUS at intervals determined by individual treatment plans.\\u003c/p\\u003e \\u003cp\\u003eDuring the surveillance period, 8 of the 13 patients (62%) developed MRI-confirmed tumor recurrence within 13 months of their initial resection. Among these patients, 4 met inclusion criteria for temporal concordance, having undergone TCUS within the prespecified window of one month before or after the MRI study that identified recurrence. These four patients comprise the analytic cohort for this feasibility analysis. Key clinical and imaging characteristics for all four cases are summarized in Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e and Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e.\\u003c/p\\u003e \\u003c/div\\u003e\\n\\u003ch3\\u003eImaging Concordance Between TCUS and MRI\\u003c/h3\\u003e\\n\\u003cp\\u003eIn all four patients meeting inclusion criteria, TCUS identified hyperechoic abnormalities spatially concordant with regions of MRI-defined recurrence, despite blinded interpretation. TCUS examinations were performed in the outpatient clinic setting without complications and at intervals ranging from 0 to 32 days relative to the recurrence-detecting MRI. Across cases, TCUS enabled visualization of abnormalities adjacent to the prior resection cavity, associated parenchymal changes, and relevant intracranial landmarks, including the ventricular system and midline structures.\\u003c/p\\u003e \\u003cp\\u003eTwo cases with representative, high-quality MRI and TCUS imaging are presented in detail below to illustrate imaging concordance. All four cases demonstrated spatial concordance between TCUS findings and MRI-defined recurrence.\\u003c/p\\u003e \\u003cdiv id=\\\"Sec11\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eIllustrative Case Summaries\\u003c/h2\\u003e \\u003cp\\u003eIllustrative Case 1\\u003c/p\\u003e \\u003cp\\u003eA 73-year-old woman presented with cognitive symptoms and was found to have a left temporal glioblastoma. She underwent subtotal resection with placement of a sonolucent cranial implant. MRI surveillance demonstrated tumor recurrence 20 weeks after surgery, and the patient subsequently underwent repeat resection. Further MRI surveillance identified additional recurrence 11 weeks after the second resection. TCUS performed 15 weeks after the second resection demonstrated a hyperechoic abnormality at the medial margin of the resection cavity corresponding to nodular enhancement and T2 FLAIR hyperintensity on MRI (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). The patient elected hospice care and died two months later.\\u003c/p\\u003e \\u003cp\\u003eIllustrative Case 2\\u003c/p\\u003e \\u003cp\\u003eA 79-year-old woman underwent gross total resection of a right temporal glioblastoma with placement of a sonolucent cranial implant. MRI surveillance identified recurrence 19 weeks postoperatively. TCUS performed 14 days later demonstrated a hyperechoic abnormality at the posterior margin of the resection cavity corresponding to a newly enhancing lesion on MRI (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e). The patient declined further chemoradiotherapy.\\u003c/p\\u003e \\u003cp\\u003eNon-Illustrated Cases\\u003c/p\\u003e \\u003cp\\u003eTwo additional patients met inclusion criteria for temporal concordance and demonstrated spatial concordance between TCUS findings and MRI-defined recurrence. In one patient, TCUS performed on the same day as MRI identified a hyperechoic abnormality at the posterolateral margin of the resection cavity corresponding to MRI findings. In the other patient, TCUS performed 12 days after MRI demonstrated a hyperechoic abnormality in the inferior temporal region corresponding to MRI-defined recurrence. Imaging intervals, lesion locations, and concordance for these cases are summarized in Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e and Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec12\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eSummary of Findings\\u003c/h2\\u003e \\u003cp\\u003eAcross all four cases, TCUS identified sonographic abnormalities spatially concordant with MRI-confirmed glioblastoma recurrence when performed within a prespecified temporal window and interpreted blinded to MRI findings. These observations establish feasibility of outpatient TCUS for identifying imaging signatures associated with tumor recurrence but do not assess diagnostic accuracy or distinguish tumor from treatment-related effects.\\u003c/p\\u003e\\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 1\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003ePatient Characteristics at Presentation\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"7\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c6\\\" colnum=\\\"6\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c7\\\" colnum=\\\"7\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCase\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eAge/Sex\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eTumor Location\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eImplant Location\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eMolecular Details\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003eExtent of Initial Resection\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003eInitial Chemo/RT Treatment Plan\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e1\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e74/F\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eLeft temporal\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eLeft frontotemporal\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eGBM, IDH-wildtype, MGMT methylated, EGFR amplified\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003eSubtotal resection\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003eStandard chemotherapy and RT followed by maintenance TMZ per Stupp protocol.\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e2\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e79/F\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eRight temporal\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eRight temporal\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eGBM, IDH- wildtype, MGMT methylated\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003eGross total resection\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003ePatient did not receive chemotherapy or RT\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e3\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e62/M\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eMiddle cranial fossa and right temporal lobe\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eRight temporal\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eGBM, IDH-wildtype, MGMT methylated\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003eSubtotal resection\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003eStandard chemotherapy and RT followed by maintenance TMZ per Stupp protocol\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e4\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e70/M\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eRight temporal\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eRight temporal\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eGBM, IDH-wildtype, MGMT unmethylated, EGFR non-amplified\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003eGross total resection\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003eStandard chemotherapy and RT followed by maintenance TMZ per Stupp protocol\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"7\\\"\\u003eGBM: Glioblastoma, RT: Radiation Therapy, TMZ: Temozolomide, IDH: Isocitrate Dehydrogenase, MGMT: O\\u003csup\\u003e6\\u003c/sup\\u003e-methylguanine-DNA methyltransferase,\\u003c/td\\u003e\\u003c/tr\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"7\\\"\\u003eEGFR: Epidermal Growth Factor Receptor\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab2\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 2\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003ePatient Characteristics at Recurrence\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"10\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c6\\\" colnum=\\\"6\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c7\\\" colnum=\\\"7\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c8\\\" colnum=\\\"8\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c9\\\" colnum=\\\"9\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c10\\\" colnum=\\\"10\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCase\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eAge/Sex\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eSurgery-Recurrence on MRI Interval\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eSurgery-Recurrence on TCUS Interval\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eMRI-TCUS Interval\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003eMRI Evidence of Recurrence\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003eTCUS Evidence of Recurrence\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003eSymptoms of Recurrence\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003eManagement Change after Recurrence\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c10\\\"\\u003e \\u003cp\\u003eReoperation after MRI and TCUS detection of tumor\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e1\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e74/F\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e78 days\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e110 days\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e+\\u0026thinsp;32\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003eIncreased contrast enhancement and T2 hyperintense regions in the left parahippocampal gyrus\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003eRegion of hyperechoic signal at the medial margin of the left temporal resection cavity correlating with T1 hyperintensity on post-contrast MR at the region of the parahippocampal gyrus.\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003eHydrocephalus\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003eDeclined further treatment including chemotherapy or RT\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e \\u003cp\\u003eNo\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e2\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e79/F\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e131 days\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e145 days\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e+\\u0026thinsp;14\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003eInterval development of heterogenous enhancement in the right temporal lobe suspicious for tumoral disease\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003eRegion of hyperechoic signal at the posterior-medial and posterolateral margin of the right temporal resection cavity correlating with hyperintense contrast-enhanced region at the left temporal lobe on T1 MR.\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003eGeneralized lower leg weakness, emesis\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003eDeclined further treatment including chemotherapy or RT\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e \\u003cp\\u003eNo\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e3\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e62/M\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e125 days\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e125 days\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003eInterval development of a peripheral area of enhancement in the right temporal lobe/posterior insula\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003eHyperechoic signal at the posterolateral margin of the resection cavity correlating with hyperintense T1 post contrast MRI signal\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003eDecreased executive function, seizure, weakness, worsened balance and gait\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003eGamma Knife Radiosurgery in 5 fractions\\u003c/p\\u003e \\u003cp\\u003eBevacizumab therapy\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e \\u003cp\\u003eNo\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e4\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e70/M\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e337 days\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e349 days\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e+\\u0026thinsp;12\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003eNew expansile nodular lesion along the posterior lateral margin of the resection cavity\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003eHyperechoic signal at the right inferior temporal lobe lateral to the right lateral ventricle correlating with T1 hyperintensity\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003eDenied new symptoms\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003eCarboplatin therapy\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e \\u003cp\\u003eYes (gross total resection, pathology confirmed glioblastoma\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"10\\\"\\u003eRT: Radiation Therapy\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"DISCUSSION\",\"content\":\"\\u003cp\\u003eIn this retrospective feasibility series, we demonstrate that transcranioplasty ultrasound (TCUS) performed through sonolucent cranial implants can identify sonographic abnormalities spatially concordant with MRI-confirmed glioblastoma recurrence during routine outpatient follow-up. Across all four cases meeting prespecified temporal criteria, TCUS identified abnormalities corresponding to regions of MRI-defined recurrence despite blinded interpretation. These findings establish feasibility of clinic-based TCUS as a point-of-care adjunct for interval surveillance in patients with GBM and provide a foundation for prospective evaluation.\\u003c/p\\u003e \\u003cp\\u003eThe clinical challenge motivating this work is not the inadequacy of MRI, but rather the rigidity of interval-based surveillance in a disease characterized by rapid and heterogeneous progression. Standard follow-up imaging schedules, typically every two to three months as established in the Stupp protocol, may allow clinically meaningful disease evolution to occur between scans [\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e]. TCUS offers a practical mechanism to increase surveillance frequency without imposing the logistical and resource constraints associated with additional MRI examinations [\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e]. In this context, TCUS is best conceptualized as a surveillance trigger rather than a diagnostic replacement, prioritizing early identification of interval change and timely escalation to conventional imaging when warranted.\\u003c/p\\u003e \\u003cp\\u003eImportantly, TCUS shares interpretive limitations with other postoperative imaging modalities. Distinguishing tumor progression from treatment-related effects or peritumoral edema remains a fundamental challenge in glioblastoma surveillance and is not unique to ultrasound-based imaging [\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e]. On conventional grayscale ultrasound, echogenic abnormalities reflect alterations in tissue microstructure and acoustic interfaces rather than tumor-specific biology, resulting in overlap between infiltrative tumor, vasogenic edema, gliosis, and radiation-related change. Prior intraoperative and bedside ultrasound studies have consistently noted this limitation, emphasizing ultrasound\\u0026rsquo;s strength in defining lesion geometry and interval change rather than definitive tissue characterization [\\u003cspan additionalcitationids=\\\"CR13\\\" citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e]. Moreover, even MRI faces diagnostic ambiguity in differentiating true tumor recurrence from pseudoprogression or radiation-related injury, particularly in the early post-treatment period [\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e]. Accordingly, the findings presented here should not be interpreted as evidence that TCUS can independently distinguish recurrence from treatment-related effects, but rather as support for its role in detecting interval deviation from an individual patient\\u0026rsquo;s postoperative baseline.\\u003c/p\\u003e \\u003cp\\u003eThe feasibility demonstrated in this series builds upon prior work establishing the safety and utility of TCUS for postoperative neurosurgical assessment. Ultrasound through sonolucent cranial implants has been shown to reliably visualize intracranial structures for monitoring ventricular size, cerebral bypass patency, mass effect, and postoperative complications such as hematoma and pseudomeningocele [\\u003cspan additionalcitationids=\\\"CR7\\\" citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e]. Our findings extend these applications into the oncologic surveillance domain, demonstrating that TCUS can be integrated into outpatient workflows to monitor for imaging changes associated with tumor recurrence.\\u003c/p\\u003e \\u003cp\\u003eAlthough formal cost-effectiveness was not evaluated in this study, TCUS represents a low-resource, point-of-care imaging modality that can be performed during routine outpatient visits without the infrastructure, scheduling demands, or patient burden associated with MRI. When conceptualized as an adjunctive surveillance tool rather than a replacement, TCUS may reduce unnecessary or prematurely triggered MRI examinations while enabling earlier recognition of interval change. The potential impact of TCUS on imaging utilization, workflow efficiency, and healthcare resource allocation warrants formal evaluation in prospective studies.\\u003c/p\\u003e \\u003cp\\u003eAdvances in ultrasound technology may further expand the utility of TCUS in neuro-oncologic surveillance. Doppler interrogation can provide complementary information regarding vascular patterns and flow, while contrast-enhanced ultrasound (CEUS) has demonstrated improved delineation of tumor perfusion and residual disease in intraoperative and experimental glioma imaging settings [\\u003cspan additionalcitationids=\\\"CR13 CR14 CR15\\\" citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e]. These techniques offer biologically informed signal beyond grayscale echogenicity and may improve tissue characterization. However, whether Doppler or CEUS can reliably differentiate recurrent tumor from treatment-related effects or pseudoprogression in the outpatient surveillance setting remains insufficiently studied and requires prospective validation. Incorporation of multiparametric ultrasound techniques into standardized TCUS protocols represents an important area for future investigation.\\u003c/p\\u003e \\u003cp\\u003eSuccessful integration of TCUS into longitudinal GBM surveillance requires attention to several practical considerations. Reliable acoustic access to the region of interest depends on implant positioning and reconstruction strategy, emphasizing the importance of surgical planning when ultrasound-based follow-up is anticipated. Reproducible acquisition and interpretation necessitate operator training and standardized imaging protocols to ensure consistency across visits and readers. Furthermore, incorporation of TCUS into routine follow-up workflows requires coordination among surgical, oncologic, and radiologic teams to ensure that concerning sonographic findings prompt appropriate escalation rather than isolated interpretation.\\u003c/p\\u003e \\u003cdiv id=\\\"Sec14\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eLimitations\\u003c/h2\\u003e \\u003cp\\u003eThis study has several limitations. The cohort is small and derived from a single institution, precluding assessment of diagnostic performance metrics such as sensitivity or specificity. The retrospective design and reliance on qualitative imaging concordance limit generalizability. Additionally, TCUS interpretation was performed by experienced operators within a specialized program, and performance may differ in broader practice settings without standardized training. These limitations are inherent to early feasibility investigations and underscore the need for prospective, multicenter studies with harmonized acquisition protocols, blinded interpretation, and correlation with clinical outcomes.\\u003c/p\\u003e \\u003cp\\u003eTo address these challenges, we propose a structured framework for integrating TCUS into GBM surveillance pathways, spanning patient selection, standardized acquisition, and longitudinal interpretation anchored to interval change rather than single time-point appearance (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e). In this model, TCUS functions as a low-threshold, repeatable assessment tool performed during routine clinic visits. Clearly abnormal or evolving sonographic findings would prompt expedited MRI and multidisciplinary review, while stable examinations could support continued observation until scheduled imaging. Such an approach aligns with prior recommendations emphasizing TCUS as an adjunctive, rather than standalone, imaging modality.\\u003c/p\\u003e\\u003c/div\\u003e\"},{\"header\":\"Abbreviations\",\"content\":\"\\u003cp\\u003eGBM: Glioblastoma\\u003c/p\\u003e\\n\\u003cp\\u003eMGMT: O\\u003csup\\u003e6\\u003c/sup\\u003e-methylguanine-DNA methyltransferase\\u003c/p\\u003e\\n\\u003cp\\u003ePMMA: Poly(methyl-methacrylate)\\u003c/p\\u003e\\n\\u003cp\\u003eTCUS: Transcranioplasty Ultrasound\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eStatements and Declarations:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNo funding was received for the completion of this work. All authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthor Contribution Statement\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConception and design\\u003c/strong\\u003e: Randy S. D\\u0026rsquo;Amico\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAcquisition of data:\\u003c/strong\\u003e Seth Mejia, Artur Shlifer, Vadim Zhigin, Tamika Wong, Sanskruti (Sana) Bokil, Sara Massimo\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAnalysis and interpretation of data:\\u003c/strong\\u003e Griffin Thomas, Shoaib Syed, Marcio Yuri Ferreira, Seth Mejia, Randy S. D\\u0026rsquo;Amico\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eDrafting the article:\\u003c/strong\\u003e Griffin Thomas, Shoaib Syed, Samuel Latzman, Marcio Yuri Ferreira, Randy S. D\\u0026rsquo;Amico\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCritically reviewing the article:\\u0026nbsp;\\u003c/strong\\u003eAll authors\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eStudy Supervision:\\u003c/strong\\u003e Randy D\\u0026rsquo;Amico, Netanel Ben-Shalom\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFunding:\\u003c/strong\\u003e The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCompeting Interests: \\u003c/strong\\u003eThe authors have no relevant financial or non-financial interests to disclose.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eSchaff LR, Mellinghoff IK (2023) \\u003cem\\u003eGlioblastoma and Other Primary Brain Malignancies in Adults: A Review.\\u003c/em\\u003eJAMA, 329(7): pp. 574\\u0026ndash;587\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eStupp R et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987\\u0026ndash;996\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSilva-Aravena F et al (2025) Optimizing MRI Scheduling in High-Complexity Hospitals: A Digital Twin and Reinforcement Learning Approach. Bioeng (Basel), 12(6)\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eJoshua Nahm MS, Schumann EH, Vu M, Hsu SH, Zhu J-J (2023) \\u003cem\\u003eOverall Survival in Patients with Recurrent Glioblastomas with Combination Chemotherapy and Tumor Treating Fields (TTF).\\u003c/em\\u003eJournal of Clinical Oncology, 41\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eOmer Doron MYF, Huda S, Singh V, Shlifer A, Wong T, Singh F, Massimo S, Mejia S, Suffren B, Ablyazova F, Randy D\\u0026rsquo;amico (2026) John A. Boockvar, David Langer, Netanel Ben-Shalom, \\u003cem\\u003eNeurosurgical Stethoscope-Advancing Bedside Imaging in Neurosurgery through Sonolucent Cranial Implants-A Case Series.\\u003c/em\\u003e Oper Neurosurg\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eAllen BC et al (2023) Transcranial ultrasonography to detect intracranial pathology: A systematic review and meta-analysis. J Neuroimaging 33(3):333\\u0026ndash;358\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eHashmi E et al (2025) The Utility of Ultrasound Through a Sonolucent Implant in the Perioperative Management of Subdural Hematoma: Three Exemplificative Cases. Oper Neurosurg\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eRychen J et al (2025) Bedside Sonographic Ventricular Monitoring Through a Sonolucent Cranial Implant for Weaning of External Ventricular Drain After Aneurysmal Subarachnoid Hemorrhage. Oper Neurosurg\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eOldrini B et al (2020) MGMT genomic rearrangements contribute to chemotherapy resistance in gliomas. Nat Commun 11(1):3883\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMathew G et al (2023) Preferred Reporting Of Case Series in Surgery (PROCESS) 2023 guidelines. Int J Surg 109(12):3760\\u0026ndash;3769\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eLee J et al (2020) Discriminating pseudoprogression and true progression in diffuse infiltrating glioma using multi-parametric MRI data through deep learning. Sci Rep 10(1):20331\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ePinto PS et al (2012) \\u003cem\\u003eWhite-gray matter echogenicity ratio and resistive index: sonographic bedside markers of cerebral hypoxic-ischemic injury/edema?\\u003c/em\\u003e J Perinatol, 32(6): pp. 448\\u0026thinsp;\\u0026ndash;\\u0026thinsp;53\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eWei R et al (2023) Application of intraoperative ultrasound in the resection of high-grade gliomas. Front Neurol 14:1240150\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eWu H et al (2024) Progress in the application of ultrasound in glioma surgery. Front Med (Lausanne) 11:1388728\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ePrada F et al (2016) Identification of residual tumor with intraoperative contrast-enhanced ultrasound during glioblastoma resection. Neurosurg Focus 40(3):E7\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eFerreira MY, Cardoso LJC, Huda S, Ben-Shalom N (2026) Intraoperative contrast-enhanced ultrasound-assisted resection of brain tumors: a systematic review and meta-analysis. Neurochirurgie Published online January 12. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1016/j.neuchi.2026.101774\\u003c/span\\u003e\\u003cspan address=\\\"10.1016/j.neuchi.2026.101774\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Glioblastoma, Recurrence, Transcranioplasty Ultrasound, Sonolucent Cranioplasty\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-8904429/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-8904429/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003ch2\\u003eBackground and Objective:\\u003c/h2\\u003e \\u003cp\\u003eGlioblastoma (GBM) is characterized by near-universal recurrence after surgical resection, necessitating close postoperative surveillance. Although MRI remains the gold standard for detecting tumor progression, fixed imaging intervals may delay recognition of recurrence. Sonolucent cranial implants enable transcranioplasty ultrasound (TCUS), offering a potential point-of-care adjunct for interval monitoring between scheduled MRI studies. We evaluated the feasibility of identifying sonographic findings concordant with MRI-confirmed GBM recurrence during routine outpatient follow-up.\\u003c/p\\u003e\\u003ch2\\u003eMethods\\u003c/h2\\u003e \\u003cp\\u003eWe conducted a retrospective review of prospectively registered consecutive GBM patients who underwent tumor resection with placement of a sonolucent cranial implant (ClearFit\\u0026reg;, Longeviti Inc., Baltimore, MD) at a single tertiary center (February 2023\\u0026ndash;November 2025). Patients were included if they developed MRI-confirmed recurrence and underwent TCUS within one month before or after the recurrence-detecting MRI. TCUS examinations were performed during routine outpatient visits and interpreted by a clinician blinded to MRI findings. MRIs were independently reviewed by board-certified neuroradiologists. TCUS findings were qualitatively compared with MRI-defined recurrence.\\u003c/p\\u003e\\u003ch2\\u003eResults\\u003c/h2\\u003e \\u003cp\\u003eOf 13 patients with sonolucent implants, 8 developed MRI-confirmed recurrence within 13 months of resection. Four underwent TCUS within one month of the recurrence-detecting MRI. In all four cases, TCUS demonstrated hyperechoic abnormalities spatially concordant with MRI-defined recurrence despite blinded interpretation. Examinations were safely performed in the outpatient setting.\\u003c/p\\u003e\\u003ch2\\u003eConclusion\\u003c/h2\\u003e \\u003cp\\u003eTCUS through sonolucent cranial implants demonstrated concordant findings with MRI-confirmed GBM recurrence in this preliminary series, supporting its feasibility as a point-of-care adjunct for interval surveillance. Prospective studies are warranted to define standardized protocols and diagnostic performance.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Sonolucent Cranial Windows Enable Bedside Ultrasound Identification of MRI- Concordant Glioblastoma Recurrence During Outpatient Surveillance\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2026-03-10 16:18:08\",\"doi\":\"10.21203/rs.3.rs-8904429/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"c80b118b-d945-4514-a64b-d26a6f0b4b7c\",\"owner\":[],\"postedDate\":\"March 10th, 2026\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2026-03-18T05:10:39+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2026-03-10 16:18:08\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-8904429\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-8904429\",\"identity\":\"rs-8904429\",\"version\":[\"v1\"]},\"buildId\":\"XKTyCvWXoU3ODBz1xrDgd\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}