Digital twins are increasingly proposed as patient-specific, dynamically updated computational representations that integrate multimodal data to support prediction, monitoring, and personalized care. In cognitive decline and dementia, their potential is considerable because disease progression is slow, heterogeneous, and shaped by biological, cognitive, clinical, and social factors. However, digital twins will remain clinically incomplete unless they capture sex- and gender-related differences in disease burden, symptom presentation, testing performance, care pathways, treatment exposure, and support needs. Women carry a disproportionate burden of Alzheimer’s disease and related dementias and often show better early verbal-memory performance, which can mask disease and delay diagnosis. Electronic health records, natural language processing, digital cognitive assessment, gamified testing, and longitudinal monitoring apps together provide an important technological basis for gender-aware twins. This paper argues that the digital twin should be understood not as a single tool, but as an integrative IT framework combining interoperable assessment, prediction, follow-up, and support components, co-developed with patients, caregivers, relatives, and clinicians to better address women’s diagnostic and long-term care needs across the care continuum. 

Early detection of cognitive impairment is crucial for timely intervention in conditions like dementia and Parkinson’s disease. While the Mini-Cog is a validated tool for such screening, its traditional clinical format may disengage some users. This study introduces a gamified, narrative-based version of the Mini-Cog as a web-mobile application, tested with 30 healthy volunteers (ages 45–72) and one patient. Two story variantswere developed, featuring a mayor and a dinosaur, embedded in a relaxed everyday narrative mentioning a park, bakery, and birthday party. Feedback highlights positiveengagement through visuals and icons, with suggestions or age-adapted stories and improved screen adaptation. Results support the feasibility of gamified cognitive screening whi

Deep Brain Stimulation (DBS) is an effective treatment for movement disorders. Optimizing stimulation parameters remains, however, a trial-and-error process. Datadriven models leveraging Probabilistic Mapping have shown promise in predicting DBS outcomes, yet current studies rely on chronic stimulation data. This study explores the feasibility of using intra-operative stimulation test data for DBS effect prediction. Probabilistic volumes of beneficial and adverse effects were computed from intra-operative stimulation test data of 65 patients (23 with Essential Tremor + 42 with Parkinson’s Disease). A prediction dataset was generated including clinical, morphological, stimulation features along with features derived from probabilistic maps and simulated Volumes of Tissue Activated. Three machine learning models (Adaboost, Support Vector Classifier and Naïve Bayes) were implemented to predict stimulation effects in a classification task. The models were validated in a leave-one-out crossvalidation and their performances were compared. All the developed models were able to predict DBS outcome classes. The best predictive performance was achieved by the Adaboost model with a maximum balanced accuracy of 0.71 on 3 classes. These results show that intra-operative stimulation test data can predict DBS effects with a similar approach and comparable accuracy to post-operative monopolar review data.

Purpose Fluorescence-guided surgery applying 5-aminolevulinic acid (5-ALA) in high-grade gliomas is an established method in adults. In children, results have so far been ambiguous. The aim of this study was to investigate 5-ALA-induced fluorescence in pediatric brain tumors by using the surgical microscope and a spectroscopic hand-held probe. Methods Fourteen randomly selected children (age 4-17) with newly MRI-verified brain tumors were included. No selection was based on the suspected diagnosis prior to surgery. All patients received 5-ALA (20 mg /kg) either orally or via a gastric tube prior to surgery. Intratumoral fluorescence was detected with the microscope and the probe. Moreover, fluorescence in the skin of the forearm was measured. Histopathology samples revealed seven low-grade gliomas, four medulloblastomas, one diffuse intrinsic pontine glioma, one glioblastoma and one atypical meningioma. Blood samples were analyzed, and potential clinical side effects were monitored. Results Microscopically, vague fluorescence was visible in two patients. Intratumoral fluorescence could be detected in five patients with the probe, including the two patients with vague microscopic fluorescence. Three of the oldest children had PpIX fluorescence in the skin. Nine children did not show any fluorescence in the tumor or in the skin. No clinical side effects or laboratory adverse events were observed. Conclusion Fluorescence could not be used to guide surgery in this study, neither with the surgical microscope nor with the hand-held probe. In nine children, no fluorescence was discerned and children with noticeable fluorescence were all older than nine years. 5-ALA was considered safe to apply in children.

BACKGROUND: Stereotactic neurosurgical brain biopsies are afflicted with risks of inconclusive results and hemorrhage. Such complications can necessitate repeated trajectories and prolong surgical time.

OBJECTIVE: To develop and introduce a 1-insertion stereotactic biopsy kit with direct intraoperative optical feedback and to evaluate its applicability in 3 clinical cases.

METHODS: An in-house forward-looking probe with optical fibers was designed to fit the outer cannula of a side-cutting biopsy kit. A small aperture was made at the tip of the outer cannula and the edges aligned with the optical probe inside. Stereotactic biopsies were performed using the Leksell Stereotactic System. Optical signals were measured in millimeter steps along the preplanned trajectory during the insertion. At the region with the highest 5-aminolevulinic acid (5-ALA)-induced fluorescence, the probe was replaced by the inner cannula, and tissue samples were taken. The waiting time for pathology diagnosis was noted.

RESULTS: Measurements took 5 to 10 minutes, and the surgeon received direct visual feedback of intraoperative 5-ALA fluorescence, microcirculation, and tissue gray-whiteness. The 5-ALA fluorescence corroborated with the pathological findings which had waiting times of 45, 50, and 75 minutes. Because only 1 trajectory was required and the patient could be prepared for the end of surgery immediately after sampling, this shortened the total surgical time.

CONCLUSION: A 1-insertion stereotactic biopsy procedure with real-time optical guidance has been presented and successfully evaluated in 3 clinical cases. The method can be modified for frameless navigation and thus has great potential to improve safety and diagnostic yield for both frameless and frame-based neurosurgical biopsy procedures.

Electrical stimulation of the deep parts of the brain is the standard answer for patients subject to drug-refractory movement disorders. Collective analysis of data collected during surgeries are crucial in order to provide more systematic planning assistance and understanding the physiological mechanisms of action. To that end, the process of normalizing anatomies captured with Magnetic Resonance imaging across patients is a key component. In this work, we present the optimization of a workflow designed to create group-specific anatomical templates: a group template is refined iteratively using the results of successive non-linear image registrations with refinement steps in the in the basal-ganglia area. All non-linear registrations were executed using the Advanced Normalization Tools (ANTs) and the quality of the normalization was measured using spacial overlap of anatomical structures manually delineated during the planning of the surgery. The parameters of the workflow evaluated were: the use of multiple modalities sequentially or together during each registration to the template, the number of iterations in the template creation and the fine settings of the non-linear registration tool. Using the T1 and white matter attenuated inverse recovery modalities (WAIR) together produced the best results, especially in the center of the brain. The optimal numbers of iterations of the template creation were higher than those from the literature and our previous works. Finally, the setting of the non-linear registration tool that improved results the most was the activation of the registration with the native voxel sizes of images, as opposed to down-sampled version of the images. The normalization process was optimized over our previous study and allowed to obtain the best possible anatomical normalization of this specific group of patient. It will be used to summarize and analyze peri-operative measurements during test stimulation. The aim is that the conclusions obtained from this analysis will be useful for assistance during the planning of new surgeries. © 2021, Springer Nature Switzerland AG.

Laser induced thermal therapy (LITT) emerged in recent years as a minimal invasive treatment method for otherwise oftentimes inoperable brain tumors, such as glioblastomas. During the thermal ablation process, the procedure carries the risk of destroying healthy brain tissue adjacent to the tumor. Limitations in the spatial distribution of the real-time monitoring MR thermography system currently allow only a rough representation of the damage zone during surgery. For this reason, improved pre-operative simulations of tissue heating and the resulting tissue damage could be valuable to optimize clinical treatment protocols while minimizing the risks of the procedure. In this study a method is presented, to simulate the ablation process of the LITT with the finite elements method (FEM) using the simulation software COMSOL MULTIPHYSICS. Thereby the temperature distribution is displayed and, based on this, the extent of the tissue damage during the process is simulated. Therefore, relevant parameters for the ablation process, such as optical and thermal properties, blood per-fusion, and the interface between healthy and tumor tissue were investigated and their influence on temperature distribution and extent of tissue damage was described.

BACKGROUND Accurate stereotactic biopsies of brain tumors are imperative for diagnosis and tailoring of the therapy. Repetitive needle insertions enhance risks of brain lesioning, hemorrhage, and complications due to prolonged procedure.

OBJECTIVE To investigate clinical benefits of a combined 5-aminolaevulinic acid (5-ALA) fluorescence and laser Doppler flowmetry system for the detection of malignant brain tumor and blood vessels in stereotactic biopsies.

METHODS Planning of targets and trajectories was followed by optical measurements in 20 patients, using the Leksell Stereotactic System and a manual insertion device. Fluorescence spectra, microvascular blood flow, and tissue grayness were recorded each millimeter along the paths. Biopsies were taken at preplanned positions. The diagnoses were compared with the fluorescence signals. The recordings were plotted against measurement positions and compared. Sites indicating a risk of hemorrhage were counted as well as the time for the procedures.

RESULTS Signals were recorded along 28 trajectories, and 78 biopsies were collected. The final diagnosis showed 17 glioblastomas, 2 lymphomas, and 1 astrocytoma grade III. Fluorescence was seen along 23 of the paths with 4 having the peak of 5-ALA fluorescence 3 mm or more from the precalculated target. There was increased microcirculation in 40 of 905 measured positions. The measurement time for each trajectory was 5 to 10 min.

CONCLUSION The probe provided direct feedback of increased blood flow along the trajectory and of malignant tissue in the vicinity of the target. The method can increase the precision and the safety of the biopsy procedure and reduce time.

Deep brain stimulation (DBS) is an intervention used for several neurological conditions such as Parkinson’s disease. To evaluate the clinical response in relation to anatomical location, electric field simulation using the finite element method is commonly used. The models presented in different studies are varying in complexity and this study aims to evaluate the effect of including anisotropy in the tissue model using homogenous tissue with varying level of anisotropy both parallel and perpendicular to the DBS lead. As a benchmark, data from one patient was included and simulations was performed in zona incerta (Zi) and the internal capsule (IC). The parameters investigated were impedance, volume within the 0.2 V/mm isosurface, radial and longitudinal expansion as well as visual representation of the isosurface. The investigations show that both the impedance and volume are increasing with increasing anisotropy together with the electric field isosurface in the principal direction of the anisotropy. When comparing different stimulation modes, current control (CC) stimulation had a steeper increase with increasing anisotropy for all parameters compared to voltage control (VC) stimulation. This could be due to a joint effect of the anisotropy and the increasing impedance. The result from the patient simulations are in the anisotropy range where simulations from the homogenous models starts to have a higher slope for all parameters. This indicates that including anisotropy in computer models will be of importance in areas of high anisotropy.

Electrical stimulation of the deep parts of the brain is the standard answer for patients subject to drug-refractory movement disorders. Collective analysis of data collected during surgeries are crucial in order to provide more systematic planning assistance and understanding the physiological mechanisms of action. To that end, the process of normalizing anatomies captured with Magnetic Resonance imaging across patients is a key component. In this work, we present the optimization of a workflow designed to create group specific anatomical templates: a group template is refined iteratively using the results of successive non-linear image registrations. I norder to improve the results in the basal-ganglia area, the process is refined in this specific volume of interest. All non-linear registrations were executed using the Advanced Normalization Tools (ANTs). The quality of the normalization was measured using the manual delineation of anatomical structures produced during the planning of the surgery and their spacial overlap after trans- formation in the template space by means of Dice coefficient and mean surface distance. The parameters of the workflow evaluated were: the use of multiple modalities sequentially or together during each registration to the template, the number of iterations in the template creation and the fine settings of the non-linear registration tool. Using the T1 and white matter attenuated inverse recovery modalities together produced the best results, especially in the center of the brain. The optimal numbers of iterations of the template creation were higher than those advised in the literature and our previous works. Finally, the setting of the nonlinear registration tool that improved results the most was the activation of the registrationwith the native voxel sizes of images, as opposed to down-sampled version of the images. Theuse of the delineation of the anatomical structures as a mean to measure the quality of the anatomical template of a group of patient allowed to optimize the normalization process and obtain the best possible anatomical normalization of this specific group of patient. The most crucial points were the combination of multiple modalities in order to maximize the quality of information available during image registration and the activation of the registration with native voxel size. The anatomical template of the group will be used to summarize and analyze peri-operative measurements during test stimulation. The aim is that the conclusions obtained from this analysis will be useful for assistance during the planning of new surgeries.