Periodic Reporting for period 1 - StrokeMonitor (Monitoring of stroke patients with 3D ultrasound localization microscopy)
Reporting period: 2023-02-01 to 2024-07-31
The project addresses the significant issue of Delayed Cerebral Ischemia (DCI) in stroke patients, particularly those suffering from subarachnoid hemorrhage (SAH) following an aneurism rupture. Approximately thirty percent of patients who survive the initial treatment for SAH experience DCI, often as a result of vasospasm. Current monitoring methods, such as transcranial Doppler (TCD) sonography, CT angiography (CTA), and digital subtraction angiography (DSA), have notable limitations in terms of sensitivity, specificity, and their applicability at the bedside. This creates a critical need for a new method to monitor cerebral blood flow, especially in small arteries, to detect vasospasm and prevent DCI.
To address this need, the project proposes the development of a bedside neuro-imaging device that utilizes 3D vascular and perfusion imaging, capable of characterizing the brain circulation in real-time. This device, referred to as the Stroke Scanner, aims to provide high-resolution imaging of microvessels, enabling early detection of DCI and improved patient monitoring following SAH.
The primary objectives of the project include the creation of the Stroke Scanner as a portable and user-friendly device based on 3D vascular and perfusion imaging technology, which can be utilized at the bedside to monitor microcirculation in stroke patients. The project will also involve validation of the Stroke Scanner in small animal models to establish its efficacy in detecting changes in microcirculation related to DCI. Following this, a clinical prototype will be developed for human trials, focusing on its application in patients with subacute ischemic conditions. Additionally, the project aims to address existing monitoring gaps by providing a solution for continuous observation of hemorrhagic stroke patients, thereby filling the void left by current imaging modalities.
The expected impact of the Stroke Scanner is substantial, as it has the potential to revolutionize the monitoring of stroke patients by observing changes in the brain circulation and facilitating early detection of DCI. This advancement could lead to timely interventions, ultimately reducing morbidity and mortality associated with SAH. Furthermore, the project seeks to alleviate the economic burden of stroke care, which is considerable in the European Union.
To address this need, the project proposes the development of a bedside neuro-imaging device that utilizes 3D vascular and perfusion imaging, capable of characterizing the brain circulation in real-time. This device, referred to as the Stroke Scanner, aims to provide high-resolution imaging of microvessels, enabling early detection of DCI and improved patient monitoring following SAH.
The primary objectives of the project include the creation of the Stroke Scanner as a portable and user-friendly device based on 3D vascular and perfusion imaging technology, which can be utilized at the bedside to monitor microcirculation in stroke patients. The project will also involve validation of the Stroke Scanner in small animal models to establish its efficacy in detecting changes in microcirculation related to DCI. Following this, a clinical prototype will be developed for human trials, focusing on its application in patients with subacute ischemic conditions. Additionally, the project aims to address existing monitoring gaps by providing a solution for continuous observation of hemorrhagic stroke patients, thereby filling the void left by current imaging modalities.
The expected impact of the Stroke Scanner is substantial, as it has the potential to revolutionize the monitoring of stroke patients by observing changes in the brain circulation and facilitating early detection of DCI. This advancement could lead to timely interventions, ultimately reducing morbidity and mortality associated with SAH. Furthermore, the project seeks to alleviate the economic burden of stroke care, which is considerable in the European Union.
Throughout our project, we conducted both preclinical and clinical studies aimed at advancing the understanding and monitoring of Delayed Cerebral Ischemia (DCI). The preclinical studies utilized mouse models specifically designed to investigate DCI, with key objectives including the implementation of a micro-vasospasm model, assessing the sensitivity of transcranial volumetric ultrasound localization microscopy (ULM) in detecting cerebral micro-vasospasm, and comparing these findings with established clinical gold standards, such as T2-weighted Magnetic Resonance Imaging (MRI).
Our preclinical results were promising, as we successfully established a micro-vasospasm model in mice, which allowed us to explore the dynamics of cerebral vasospasm in a controlled environment. We found that transcranial volumetric ULM is sensitive to the detection of cerebral micro-vasospasm, effectively highlighting acute endothelin-induced vasospasm. This sensitivity indicates that ULM could serve as a valuable tool for real-time monitoring of microcirculation.
In parallel to these preclinical findings, we proceeded to the clinical phase of our project, where we employed a new prototype. This prototype enabled advanced perfusion imaging and ultrasensitive Doppler capabilities over the brain in three dimensions using a bedside ultrasound scanner. The clinical study involved twelve patients in intensive care units, allowing us to visualize the main vasculature of the brain in real-time.
A major achievement of the clinical study was the ability to obtain perfusion time-intensity curves, which provided critical insights into the perfusion dynamics of different brain regions. Our observations indicated that modifications in perfusion patterns appeared associated with poorer outcomes in patients experiencing DCI, suggesting a potential correlation between perfusion changes and the severity of DCI. However, there results are preliminary and require further analysis.
Overall, the combination of preclinical and clinical studies has demonstrated the feasibility and effectiveness of using advanced imaging techniques for monitoring cerebral micro-vasospasm and DCI. The findings from both phases of the project pave the way for future research and development aimed at enhancing the monitoring and treatment of patients at risk for DCI, ultimately contributing to improved patient management and outcomes.
Our preclinical results were promising, as we successfully established a micro-vasospasm model in mice, which allowed us to explore the dynamics of cerebral vasospasm in a controlled environment. We found that transcranial volumetric ULM is sensitive to the detection of cerebral micro-vasospasm, effectively highlighting acute endothelin-induced vasospasm. This sensitivity indicates that ULM could serve as a valuable tool for real-time monitoring of microcirculation.
In parallel to these preclinical findings, we proceeded to the clinical phase of our project, where we employed a new prototype. This prototype enabled advanced perfusion imaging and ultrasensitive Doppler capabilities over the brain in three dimensions using a bedside ultrasound scanner. The clinical study involved twelve patients in intensive care units, allowing us to visualize the main vasculature of the brain in real-time.
A major achievement of the clinical study was the ability to obtain perfusion time-intensity curves, which provided critical insights into the perfusion dynamics of different brain regions. Our observations indicated that modifications in perfusion patterns appeared associated with poorer outcomes in patients experiencing DCI, suggesting a potential correlation between perfusion changes and the severity of DCI. However, there results are preliminary and require further analysis.
Overall, the combination of preclinical and clinical studies has demonstrated the feasibility and effectiveness of using advanced imaging techniques for monitoring cerebral micro-vasospasm and DCI. The findings from both phases of the project pave the way for future research and development aimed at enhancing the monitoring and treatment of patients at risk for DCI, ultimately contributing to improved patient management and outcomes.
The results of our project have demonstrated significant advancements beyond the current state of the art in the monitoring and understanding of Delayed Cerebral Ischemia (DCI). The preclinical studies revealed the inherent challenges in modeling DCI in small animal models, indicating that existing methodologies may not fully capture the complexities of this condition. To address this limitation, we suggest that future research should explore alternative modeling approaches, such as blood injection techniques, which could provide a more comprehensive understanding of the pathophysiological characteristics of DCI.
In the clinical phase, the StrokeScanner has shown promise as a proof-of-concept device capable of imaging brain vasculature and assessing perfusion at the bedside. However, the current study involved a limited sample size of twelve patients, which restricts our ability to draw statistically significant conclusions regarding the variability of outcomes across a broader patient population. To fully realize the potential of the StrokeScanner, it is essential to conduct extended clinical studies involving a larger cohort of patients. This will not only help to validate the device's efficacy but also determine whether the information obtained through this advanced imaging modality translates into tangible benefits for patient diagnosis and monitoring.
The successful uptake and commercialization of the StrokeScanner will depend on several key factors. First, further research is necessary to establish robust clinical evidence supporting the device's utility in diverse clinical settings and indications. This includes demonstrating its effectiveness in improving patient outcomes and informing treatment decisions. Additionally, securing the required medical certifications will be crucial for market access and distribution.
Moreover, a supportive regulatory and standardization framework will be essential to facilitate the integration of the StrokeScanner into clinical practice. This includes addressing any intellectual property rights (IPR) considerations and ensuring that the technology meets the necessary safety and efficacy standards.
In summary, while our project has yielded promising results that advance the field of DCI monitoring, further research and validation are needed to ensure the successful uptake and impact of the StrokeScanner. By addressing these critical needs, we can enhance the potential for this innovative technology to improve patient care and outcomes in the management of DCI.
In the clinical phase, the StrokeScanner has shown promise as a proof-of-concept device capable of imaging brain vasculature and assessing perfusion at the bedside. However, the current study involved a limited sample size of twelve patients, which restricts our ability to draw statistically significant conclusions regarding the variability of outcomes across a broader patient population. To fully realize the potential of the StrokeScanner, it is essential to conduct extended clinical studies involving a larger cohort of patients. This will not only help to validate the device's efficacy but also determine whether the information obtained through this advanced imaging modality translates into tangible benefits for patient diagnosis and monitoring.
The successful uptake and commercialization of the StrokeScanner will depend on several key factors. First, further research is necessary to establish robust clinical evidence supporting the device's utility in diverse clinical settings and indications. This includes demonstrating its effectiveness in improving patient outcomes and informing treatment decisions. Additionally, securing the required medical certifications will be crucial for market access and distribution.
Moreover, a supportive regulatory and standardization framework will be essential to facilitate the integration of the StrokeScanner into clinical practice. This includes addressing any intellectual property rights (IPR) considerations and ensuring that the technology meets the necessary safety and efficacy standards.
In summary, while our project has yielded promising results that advance the field of DCI monitoring, further research and validation are needed to ensure the successful uptake and impact of the StrokeScanner. By addressing these critical needs, we can enhance the potential for this innovative technology to improve patient care and outcomes in the management of DCI.