Periodic Reporting for period 1 - DeepBrainVascu (Atlas of the Human Deep Brain Nuclei, Connections, and Vasculature)
Periodo di rendicontazione: 2023-03-01 al 2024-08-31
The problem Deep brain stimulation (DBS) surgery is used to treat symptoms of neuropsychiatric and movement disorders for which other treatment options have been exhausted. The treatment is extremely invasive and not without risk. During DBS surgery, a microelectrode is lowered deep into the brain with the aim to stimulate small subcortical nuclei to alleviate symptoms such as rigidity and tremor in PD. Surgical planning involves combining magnetic resonance images (MRI) of the patient with brain anatomy atlases to optimize electrode placement during surgery. Studies using DBS in PD patients show that a suboptimal placement of electrodes in, for example, the Subthalamic Nucleus (STN) or Globus Pallidus (GP), can yield changes in cognitive processes (e.g. attention, mental speed, response inhibition) and affective states (e.g. depression, hypomania, anxiety, hypersexuality, and hallucinations). These unwanted side effects of DBS may be the result of the stimulation of non-motor zones within these nuclei, the stimulation of white matter connections, or the dysregulation of blood flow to neighboring areas (Horn et al., 2017). Crucially, electrode implantation changes the physiology (Noor et al., 2016) and can disrupt local blood vessels (Kozai et al., 2014), leading to poor outcomes. These effects are likely due to the limited information used to dictate the location of implantation. To date, leading commercial systems (e.g. Boston Scientific, Medtronics) rely on stereotactic coordinates and classical anatomy atlases of the target structures. Research software such as Lead-DBS are actively trying to remedy this by integrating information representing different important facets of the relevant structure and physiology.
The main challenge here is that the human subcortex is a highly crowded brain area, which consists of hundreds of unique, small grey matter nuclei constituting approximately ¼ of total human brain volume. These nuclei are inter-connected in complex networks and pathways involved in decision making, reward processing, attention modulation, as well as motor and sensory activity. They are richly vascularized with major arterial trees and veins passing through them to support their energy demands, which often change rapidly in disease, including in PD (Paul and Elabi, 2022). Importantly, the impact of mapping them in human brain MRI atlases has only recently been recognized, in part due to my efforts to raise awareness (Forstmann et al., 2017; Terra Incognita workshop; NeuroImage special issue).
The main challenge here is that the human subcortex is a highly crowded brain area, which consists of hundreds of unique, small grey matter nuclei constituting approximately ¼ of total human brain volume. These nuclei are inter-connected in complex networks and pathways involved in decision making, reward processing, attention modulation, as well as motor and sensory activity. They are richly vascularized with major arterial trees and veins passing through them to support their energy demands, which often change rapidly in disease, including in PD (Paul and Elabi, 2022). Importantly, the impact of mapping them in human brain MRI atlases has only recently been recognized, in part due to my efforts to raise awareness (Forstmann et al., 2017; Terra Incognita workshop; NeuroImage special issue).
Description of the Action and timescale This project is structured in three phases: During phase one, manual segmentations will be performed on existing UHF-7T MRI postmortem and in-vivo structural data that was collected during the ERC Stg and CoG projects, while a first market assessment will be conducted using a prototype. In phase two, detailed probabilistic atlases including the vasculature will be created in standard MNI-space and a 3D app developed. The commercialization strategy will be determined and implemented. During phase three, the atlas and 3D app will be transferred to the commercial companies (see also Tab. 1, 2). During the development of our product, we will invite neurosurgeons from the AUMC, MUMC, as well collaborators from the anatomy department to provide input and feedback on our developments.
RA 1-3 (time schedule below based on 16 hrs a week)
6 months: The RA‘s are familiarized with the existing structural UHF-7T MRI data. These include several different MR contrasts including MP2RAGE T1-weighted images, T2*-weighted images, a
quantitative susceptibility maps (QSM). Together with the PI and assistant professor (see Tab. 3), the RA’s are trained to segment the DBS target areas.
Done.
12 months: The RA’s continue to segment subcortical structures and vasculature in UHF-7T MRI data of different age groups. Validation analyses will be performed including interrater-reliability analyses and postmortem data validation. Subsequently, probabilistic atlases will be created in standard MNI-space. Together with a technician and postdocs, a 3D app will be created and an interface for educational purposes will be built.
Ongoing.
18 months: The product including the probabilistic atlas maps and 3D app will be finalized and transferred to the commercial partners including Boston Scientific (see Tab. 1). To ensure that our end product will meet the requirements for implementation into existing products of Boston Scientific, we are already working together with their R&D department to ensure that our product will meet the technical needs for implementation in their software. Also, hospitals including the AMC as well as MUMC will be contacted for the distribution of the 3D app and as well as the learning material including the probabilistic atlases of the DBS target areas.
Ongoing.
RA 1-3 (time schedule below based on 16 hrs a week)
6 months: The RA‘s are familiarized with the existing structural UHF-7T MRI data. These include several different MR contrasts including MP2RAGE T1-weighted images, T2*-weighted images, a
quantitative susceptibility maps (QSM). Together with the PI and assistant professor (see Tab. 3), the RA’s are trained to segment the DBS target areas.
Done.
12 months: The RA’s continue to segment subcortical structures and vasculature in UHF-7T MRI data of different age groups. Validation analyses will be performed including interrater-reliability analyses and postmortem data validation. Subsequently, probabilistic atlases will be created in standard MNI-space. Together with a technician and postdocs, a 3D app will be created and an interface for educational purposes will be built.
Ongoing.
18 months: The product including the probabilistic atlas maps and 3D app will be finalized and transferred to the commercial partners including Boston Scientific (see Tab. 1). To ensure that our end product will meet the requirements for implementation into existing products of Boston Scientific, we are already working together with their R&D department to ensure that our product will meet the technical needs for implementation in their software. Also, hospitals including the AMC as well as MUMC will be contacted for the distribution of the 3D app and as well as the learning material including the probabilistic atlases of the DBS target areas.
Ongoing.