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Purpose: The loss of olfactory function is known to occur in patients suffering from (behavioral variant) frontotemporal dementia ((bv)FTD) and Alzheimer's disease (AD), although different pathophysiological mechanisms underpin this clinical symptom in both disorders. This study assessed whether brain metabolism of the olfactory circuit as assessed by positron emission tomography (PET) imaging with 2-[fluorine-18]fluoro-2-deoxy-d-glucose ([ 18 F]-FDG) can distinguish these entities in different subsets of patients., Methods: Patients presenting with cognitive decline were included from a prospectively kept database: (1) bvFTD patients, (2) AD patients and (3) patients with logopenic primary progressive aphasia (PPA). Metabolic rates were calculated for different regions of the olfactory circuit for each subgroup and compared with a cohort of subjects with normal brain metabolism. Additionally, in patients with a logopenic PPA pattern on PET-imaging, statistical parametric mapping (SPM) analysis was performed., Results: The metabolism of subdivisions of the olfactory circuit as assessed by [ 18 F]-FDG PET brain imaging to bvFTD and AD from control subjects resulted in sensitivity/specificity rates of 95/87.5% and 80/83.3%, respectively. A sensitivity/specificity rate of 100/87.5% was achieved when used to differentiate AD from bvFTD. In patients with the PPA pattern on imaging, the underlying cause (either FTD or AD) could be determined with a sensitivity/specificity rate of 88/82%. SPM analysis concurred that different regions of the olfactory circuit were affected in patients suffering from AD PPA or bvFTD PPA., Conclusion: Metabolic dysfunction in the olfactory circuit is different in various neurodegenerative disorders. Further investigation of the correlations between the cerebral metabolism and the mechanisms which drive olfactory dysfunction is needed., (© 2024. The Author(s).)

Anatomy teachers urge students to come to education sessions at the dissection rooms as well-prepared as possible. To effectuate optimal preparation, assignments are designed to guide the students' learning processes. These assignment often include the use of anatomical figures in atlases. The role of augmented reality (AR) applications in helping students prepare for body donor-based teaching sessions at the dissection rooms remains quite elusive. Therefore, this study examines the effects of the use of an AR application compared to the use of anatomical atlases in helping students (n = 28) prepare for a neuroanatomy session at the dissection rooms with prosections. The study shows that students from both groups showed a similar improvement in anatomy test scores. The amount of experienced cognitive engagement, however, is higher in the experimental AR group. Based on these results, it can be suggested that an AR application is a valid method to help students prepare and could be an alternative to the use of anatomical atlases. Nevertheless, future studies should re-investigate this research question in larger cohorts. Also, it remains unknown whether cognitive engaged students are indeed the students who are better prepared for educational sessions at the dissection rooms., (© 2024. The Author(s).)

Background: Imaging techniques play a central role in modern medicine and therefore it would be beneficial for all medical students to incorporate radiology education in medical school curricula. However, a formal undergraduate radiology curriculum with well-defined learning objectives remains lacking in The Netherlands. This study aims to qualitatively ascertain opinions from clinicians (radiologists and non-radiologists) with regard to radiology education in the medical school curricula, including topics, teaching methods and strategies., Methods: A qualitative study with in-depth semi-structured interviews was conducted. Inclusion was carried out until saturation was achieved, after which 2 additional interviews were held. Interviews were conducted using open-ended questions, following a predefined topic list. The constant comparative method was applied in order to include new questions when unexpected topics arose during the interviews. All interviews were transcribed verbatim and coded using a thematic analysis approach. Codes were organized into categories and themes by discussion between the researchers., Results: Forty-four clinicians were interviewed (8 radiologists, 36 non-radiologists). The three main themes that were derived from the interviews were: (1) expectations of indispensable knowledge and skills on radiology, (2) organization of radiology education within the medical curriculum and (3) promising educational innovations for the radiology curriculum. The qualitative study design provides more in-depth knowledge on clinicians' views on educational topics., Conclusions: The themes and statements of this study provided new insights into educational methods, timing of radiology education and new topics to teach. More research is needed to gain consensus on these subjects and inclusion of the opinion of medical students with regard to radiology education is needed., (© 2024. The Author(s).)

Upregulation of prostate-specific membrane antigen (PSMA) in neovasculature has been described in glioblastoma multiforme (GBM), whereas vasculature in nonaffected brain shows hardly any expression of PSMA. It is unclear whether PSMA-targeting tracer uptake on PET is based on PSMA-specific binding to neovasculature or aspecific uptake in tumor. Here, we quantified uptake of various PSMA-targeting tracers in GBM and correlated this with PSMA expression in tumor biopsy samples from the same patients. Methods: Fourteen patients diagnosed with de novo ( n = 8) or recurrent ( n = 6) GBM underwent a preoperative PET scan after injection of 1.5 MBq/kg [ 68 Ga]Ga-PSMA-11 ( n = 7), 200 MBq of [ 18 F]DCFpyl ( n = 3), or 200 MBq of [ 18 F]PSMA-1007 ( n = 4). Uptake in tumor and tumor-to-background ratios, with contralateral nonaffected brain as background, were determined. In a subset of patients, PSMA expression levels from different regions in the tumor tissue samples ( n = 40), determined using immunohistochemistry ( n = 35) or RNA sequencing ( n = 13), were correlated with tracer uptake on PET. Results: Moderate to high (SUV max , 1.3-20.0) heterogeneous uptake was found in all tumors irrespective of the tracer type used. Uptake in nonaffected brain was low, resulting in high tumor-to-background ratios (6.1-359.0) calculated by dividing SUV max of tumor by SUV max of background. Immunohistochemistry showed variable PSMA expression on endothelial cells of tumor microvasculature, as well as on dispersed individual cells (of unknown origin), and granular staining of the neuropil. No correlation was found between in vivo uptake and PSMA expression levels (for immunohistochemistry, r = -0.173, P = 0.320; for RNA, r = -0.033, P = 0.915). Conclusion: Our results indicate the potential use of various PSMA-targeting tracers in GBM. However, we found no correlation between PSMA expression levels on immunohistochemistry and uptake intensity on PET. Whether this may be explained by methodologic reasons, such as the inability to measure functionally active PSMA with immunohistochemistry, tracer pharmacokinetics, or the contribution of a disturbed blood-brain barrier to tracer retention, should still be investigated., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Objectives: The goal of this project is to explore the views, expectations and preferences of patients with an unruptured intracranial aneurysm regarding the use of AR in patient education. Methods: To gain an in-depth understanding of the patients' perspective, a face-to-face interview study was conducted using an interview protocol with a predefined topic list. All interviews were audio-recorded and transcribed verbatim afterwards. Transcripts were analyzed using thematic content analyses. Coding was performed using Atlas.ti software. Results: Seventeen interviews were conducted. The views, expectations and preferences of patients regarding patient education with AR could be subdivided into 15 categories, which could be grouped into 4 general themes: 1) experiences with current patient education, 2) expectations of AR in patient education, 3) opportunities and limitations of AR, and 4) out-of-hospital use of an AR application. Patients' expectations were predominantly positive regarding improving patients' understanding of their medical situation and doctor-patient communication. Discusssion: This study suggests that patients with unruptured intracranial aneurysms are open to receive patient education regarding their disease with AR. Patients expect that AR models can help patients with intra-cranial aneurysms better understand their disease, treatment options and risks. Additionally, patients expect AR could improve doctor-patient communication., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Urlings, Abma, Aquarius, Aalbers, Bartels, Maal, Henssen and Boogaarts.)

Although an increased usage and development of 3D technologies is observed in healthcare over the last decades, full integration of these technologies remains challenging. The goal of this project is to qualitatively explore challenges, pearls, and pitfalls of AR/VR/3D printing applications usage in the medical field of a university medical center. Two rounds of face-to-face interviews were conducted using a semi-structured protocol. First an explorative round was held, interviewing medical specialists (8), PhD students (7), 3D technology specialists (5), and university teachers (3). In the second round, twenty employees in high executive functions of relevant departments were interviewed on seven statements that resulted from the first interviewing round. Data analysis was performed using direct content analyses. The first interviewing round resulted in challenges and opportunities in 3D technology usage that were grouped in 5 themes: aims of using AR/VR/3D printing (1), data acquisition (2), data management plans (3), software packages and segmentation tools (4), and output data and reaching end-user (5). The second interviewing round resulted in an overview of ideas and insights on centralization of knowledge, improving implementation of 3D technology in daily healthcare, reimbursement of 3D technologies, recommendations for further studies, and requirement of using certified software. An overview of challenges and opportunities of 3D technologies in healthcare was provided. Well-designed studies on clinical effectiveness, implementation and cost-effectiveness are warranted for further implementation into the clinical setting., (© 2023. The Author(s).)

The post-treatment imaging surveillance of gliomas is challenged by distinguishing tumor progression (TP) from treatment-related abnormalities (TRA). Sophisticated imaging techniques, such as perfusion-weighted magnetic resonance imaging (MRI PWI) and positron-emission tomography (PET) with a variety of radiotracers, have been suggested as being more reliable than standard imaging for distinguishing TP from TRA. However, it remains unclear if any technique holds diagnostic superiority. This meta-analysis provides a head-to-head comparison of the diagnostic accuracy of the aforementioned imaging techniques. Systematic literature searches on the use of PWI and PET imaging techniques were carried out in PubMed, Embase, the Cochrane Library, ClinicalTrials.gov and the reference lists of relevant papers. After the extraction of data on imaging technique specifications and diagnostic accuracy, a meta-analysis was carried out. The quality of the included papers was assessed using the QUADAS-2 checklist. Nineteen articles, totaling 697 treated patients with glioma (431 males; mean age ± standard deviation 50.5 ± 5.1 years) were included. The investigated PWI techniques included dynamic susceptibility contrast (DSC), dynamic contrast enhancement (DCE) and arterial spin labeling (ASL). The PET-tracers studied concerned [S-methyl- 11 C]methionine, 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG), O-(2-[ 18 F]fluoroethyl)-L-tyrosine ([ 18 F]FET) and 6-[ 18 F]-fluoro-3,4-dihydroxy-L-phenylalanine ([ 18 F]FDOPA). The meta-analysis of all data showed no diagnostic superior imaging technique. The included literature showed a low risk of bias. As no technique was found to be diagnostically superior, the local level of expertise is hypothesized to be the most important factor for diagnostically accurate results in post-treatment glioma patients regarding the distinction of TRA from TP.

Background: In a considerable subgroup of glioma patients treated with (chemo) radiation new lesions develop either representing tumor progression (TP) or treatment-related abnormalities (TRA). Quantitative diffusion imaging metrics such as the Apparent Diffusion Coefficient (ADC) and Fractional Anisotropy (FA) have been reported as potential metrics to noninvasively differentiate between these two phenomena. Variability in performance scores of these metrics and absence of a critical overview of the literature contribute to the lack of clinical implementation. This meta-analysis therefore critically reviewed the literature and meta-analyzed the performance scores., Methods: Systematic searching was carried out in PubMed, EMBASE and The Cochrane Library. Using predefined criteria, papers were reviewed. Diagnostic accuracy values of suitable papers were meta-analyzed quantitatively., Results: Of 1252 identified papers, 10 ADC papers, totaling 414 patients, and 4 FA papers, with 154 patients were eligible for meta-analysis. Mean ADC values of the patients in the TP/TRA groups were 1.13 × 10 -3 mm 2 /s (95% CI 0.912 × 10 -3 -1.32 × 10 -3 mm 2 /s) and 1.38 × 10 -3 mm 2 /s (95% CI 1.33 × 10 -3 -1.45 × 10 -3 mm 2 /s, respectively. Mean FA values of TP/TRA was 0.19 (95% CI 0.189-0.194) and 0.14 (95% CI 0.137-0.143) respectively. A significant mean difference between ADC and FA values in TP versus TRA was observed (p = 0.005)., Conclusions: Quantitative ADC and FA values could be useful for distinguishing TP from TRA on a meta-level. Further studies using serial imaging of individual patients are warranted to determine the role of diffusion imaging in glioma patients., (© 2022. The Author(s).)

To investigate the applicability and performance of automated machine learning (AutoML) for potential applications in diagnostic neuroradiology. In the medical sector, there is a rapidly growing demand for machine learning methods, but only a limited number of corresponding experts. The comparatively simple handling of AutoML should enable even non-experts to develop adequate machine learning models with manageable effort. We aim to investigate the feasibility as well as the advantages and disadvantages of developing AutoML models compared to developing conventional machine learning models. We discuss the results in relation to a concrete example of a medical prediction application. In this retrospective IRB-approved study, a cohort of 107 patients who underwent gross total meningioma resection and a second cohort of 31 patients who underwent subtotal resection were included. Image segmentation of the contrast enhancing parts of the tumor was performed semi-automatically using the open-source software platform 3D Slicer. A total of 107 radiomic features were extracted by hand-delineated regions of interest from the pre-treatment MRI images of each patient. Within the AutoML approach, 20 different machine learning algorithms were trained and tested simultaneously. For comparison, a neural network and different conventional machine learning algorithms were trained and tested. With respect to the exemplary medical prediction application used in this study to evaluate the performance of Auto ML, namely the pre-treatment prediction of the achievable resection status of meningioma, AutoML achieved remarkable performance nearly equivalent to that of a feed-forward neural network with a single hidden layer. However, in the clinical case study considered here, logistic regression outperformed the AutoML algorithm. Using independent test data, we observed the following classification results (AutoML/neural network/logistic regression): mean area under the curve = 0.849/0.879/0.900, mean accuracy = 0.821/0.839/0.881, mean kappa = 0.465/0.491/0.644, mean sensitivity = 0.578/0.577/0.692 and mean specificity = 0.891/0.914/0.936. The results obtained with AutoML are therefore very promising. However, the AutoML models in our study did not yet show the corresponding performance of the best models obtained with conventional machine learning methods. While AutoML may facilitate and simplify the task of training and testing machine learning algorithms as applied in the field of neuroradiology and medical imaging, a considerable amount of expert knowledge may still be needed to develop models with the highest possible discriminatory power for diagnostic neuroradiology., (© 2022. The Author(s).)

Background: In neuro-oncology, dynamic susceptibility contrast magnetic resonance (DSC-MR) perfusion imaging emerged as a tool to aid in the diagnostic work-up and to surveil effectiveness of treatment. However, it is believed that a significant variability exists with regard to the measured in DSC-MR perfusion parameters. The aim of this study was to assess the observer variability in measured DSC-MR perfusion parameters in patients before and after treatment. In addition, we investigated whether region-of-interest (ROI) shape impacted the observer variability., Materials and Methods: Twenty non-treated patients and a matched group of twenty patients post-treatment (neurosurgical resection and post-chemoradiotherapy) were included. Six ROIs were independently placed by three readers: circular ROIs and polygonal ROIs covering 1) the tumor hotspot; 2) the peritumoral region (T2/FLAIR-hyperintense region) and 3) the whole tumor region. A two-way random Intra-class coefficient (ICC) model was used to assess variability in measured DSC-MRI perfusion parameters. The perfusion metrics as assessed by the circular and the polygonal ROI were compared by use of the dependent T-test., Results: In the non-treated group, circular ROIs showed good-excellent overlap (ICC-values ranging from 0.741-0.963) with the exception of those representing the tumor hotspot. Polygonal ROIs showed lower ICC-values, ranging from 0.113 till 0.856. ROI-placement in the posttreatment group showed to be highly variable with a significant deterioration of ICC-values. Furthermore, perfusion metric assessment in similar tumor regions was not impacted by ROI shape., Discussion: This study shows that posttreatment quantitative interpretation of DSC-MR perfusion imaging is highly variable and should be carried out with precaution. Pretreatment assessment of DSC-MR images, however, could be carried out be a single reader in order to provide valid data for further analyses., (© 2022. The Author(s).)

Background: Molecular characterization plays a crucial role in glioma classification which impacts treatment strategy and patient outcome. Dynamic susceptibility contrast (DSC) and dynamic contrast enhanced (DCE) perfusion imaging have been suggested as methods to help characterize glioma in a non-invasive fashion. This study set out to review and meta-analyze the evidence on the accuracy of DSC and/or DCE perfusion MRI in predicting IDH genotype and 1p/19q integrity status., Methods: After systematic literature search on Medline, EMBASE, Web of Science and the Cochrane Library, a qualitative meta-synthesis and quantitative meta-analysis were conducted. Meta-analysis was carried out on aggregated AUC data for different perfusion metrics., Results: Of 680 papers, twelve were included for the qualitative meta-synthesis, totaling 1384 patients. It was observed that CBV, ktrans, Ve and Vp values were, in general, significantly higher in IDH wildtype compared to IDH mutated glioma. Meta-analysis comprising of five papers (totaling 316 patients) showed that the AUC of CBV, ktrans, Ve and Vp were 0.85 (95%-CI 0.75-0.93), 0.81 (95%-CI 0.74-0.89), 0.84 (95%-CI 0.71-0.97) and 0.76 (95%-CI 0.61-0.90), respectively. No conclusive data on the prediction of 1p/19q integrity was available from these studies., Conclusions: Future research should aim to predict 1p/19q integrity based on perfusion MRI data. Additionally, correlations with other clinically relevant outcomes should be further investigated, including patient stratification for treatment and overall survival., (© 2022. The Author(s).)

The use of Augmented Reality (AR) in anatomical education has been promoted by numerous authors. Next to financial and ethical advantages, AR has been described to decrease cognitive load while increasing student motivation and engagement. Despite these advantages, the effects of AR on learning outcome varies in different studies and an overview and aggregated outcome on learning anatomy is lacking. Therefore, a meta-analysis on the effect of AR vs. traditional anatomical teaching methods on learning outcome was performed. Systematic database searches were conducted by two independent investigators using predefined inclusion and exclusion criteria. This yielded five papers for meta-analysis totaling 508 participants; 240 participants in the AR-groups and 268 participants in the control groups. (306 females/202 males). Meta-analysis showed no significant difference in anatomic test scores between the AR group and the control group (- 0.765 percentage-points (%-points); P = 0.732). Sub analysis on the use of AR vs. the use of traditional 2D teaching methods showed a significant disadvantage when using AR (- 5.685%-points; P = 0.024). Meta-regression analysis showed no significant co-relation between mean difference in test results and spatial abilities (as assessed by the mental rotations test scores). Student motivation and/or engagement could not be included since studies used different assessment tools. This meta-analysis showed that insufficient evidence is present to conclude AR significantly impacts learning outcome and that outcomes are significantly impacted by students' spatial abilities. However, only few papers were suitable for meta-analysis, indicating that there is a need for more well-designed, randomized-controlled trials on AR in anatomy education research., (© 2021. The Author(s).)

Neuroanatomy as a subject is important to learn, because a good understanding of neuroanatomy supports the establishment of a correct diagnosis in neurological patients. However, rapid changes in curricula reduced time assigned to study (neuro)anatomy. Therefore, it is important to find alternative teaching methods to study the complex three-dimensional structure of the brain. The aim of this manuscript was to explore the effectiveness of Virtual Reality (VR) in comparison with Radiological Data (RaD) as suitable learning methods to build knowledge and increase motivation for learning neuroanatomy. Forty-seven students (mean age of 19.47 ± 0.54 years; 43 females; 4 males) were included; 23 students comprised the VR group. Both methods showed to improve knowledge significantly, the improvement between groups was not different. The RaD group showed to have a significantly higher score on expectancy than students in the VR group. Task value scores regarding finding a task interesting, useful and fun were found to be significantly different in favor of the VR group. Consequently, significant higher Motivation scores were found in the VR group. Motivation and expectancy, however, did not moderate learning results, whereas task value impacted the results in favour of the VR group. This study concludes that VR and RaD are effective and diverting methods to learn neuroanatomy, with VR being more motivating than RaD. Future research should investigate motivation and task value when using VR over a longer period of time.

Invasive motor Cortex Stimulation (iMCS) was introduced in the 1990's for the treatment of chronic neuropathic orofacial pain (CNOP), although its effectiveness remains doubtful. However, CNOP is known to be a heterogeneous group of orofacial pain disorders, which can lead to different responses to iMCS. Therefore, this paper investigated (1) whether the effectiveness of iMCS is significantly different among different CNOP disorders and (2) whether other confounding factors can be impacting iMCS results in CNOP. A systematic review and meta-analysis using a linear mixed-model was performed. Twenty-three papers were included, totaling 140 CNOP patients. Heterogeneity of the studies showed to be 55.8%. A visual analogue scale (VAS) measured median pain relief of 66.5% (ranging from 0-100%) was found. Linear mixed-model analysis showed that patients suffering from trigeminal neuralgia responded significantly more favorable to iMCS than patients suffering from dysfunctional pain syndromes (p = 0.030). Also, patients suffering from CNOP caused by (supra)nuclear lesions responded marginally significantly better to iMCS than patients suffering from CNOP due to trigeminal nerve lesions (p = 0.049). No other confounding factors were elucidated. This meta-analysis showed that patients suffering from trigeminal neuralgia and patients suffering from (supra)nuclear lesions causing CNOP responded significantly more favorable than others on iMCS. No other confounding factors were found relevant.

Background: Various studies reported changes in grey matter volumes and modifications in functional connectivity of cortical and subcortical structures in patients suffering from trigeminal neuralgia (TN) and trigeminal neuropathic pain (TNP). This study meta-analyzed the concordant structural and functional changes in foci and provide further understanding of the anatomy and biology of TN/TNP., Methods: Relevant articles on magnetic resonance imaging (MRI) and functional MRI in TN/TNP, published before August 2018, were searched for on PubMed and Embase. Following exclusion of unsuitable studies, a meta-analysis was performed using activation likelihood estimation (ALE)., Results: In total, 322 paper were identified, 11 of which could be included based on the predefined inclusion and exclusion criteria. Eight papers, totaling 279 subjects, discussing structural changes and four papers, totaling 102 subjects, discussing functional changes were included (i.e., one paper investigated both structural and functional alterations). ALE analysis showed that in TN/TNP, grey matter decreases are found in the thalamus, (anterior) cingulate gyrus, bilateral striatum, the superior-, middle- and transverse temporal gyrus, subcallosal gyrus, the bilateral insular cortex, the pre- and postcental gyrus, the middle frontal gyrus bilaterally and the anterior cerebellar lobe. Grey matter increases were seen in the periaqueductal grey (PAG). Increased resting state functional organization was found within the bilateral middle- and superior frontal gyri, the (posterior) cingulate cortex and the thalamus/pulvinar., Conclusions: Structural and functional changes meta-analyzed in this paper may contribute to elucidating the central pathophysiological mechanisms involved in TN/TNP. These results may be used as biomarkers to predict the response to medication and, ideally, in the future to offer personalized treatments., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Chronic intractable shoulder pain (CISP) is defined as shoulder pain which is present for longer than 6 months and does not respond to standard treatments like medication, physical therapy, rehabilitation, selective nerve blocks and local infiltrations, or orthopedic procedures. The etiology of CISP may be very diverse, varying from many orthopedic conditions to non-orthopedic conditions. The fact that the suprascapular nerve is one of the most important nerves supplying the shoulder region makes this nerve an interesting target in treating patients suffering shoulder pain. Invasive treatment options are peripheral nerve blocks, temporary electrical stimulation, and neurostimulation. To our best knowledge, thus far there are only a few reports describing the technique of permanent neurostimulation of the suprascapular nerve. In this article we present a patient suffering shoulder pain after she underwent surgery for cervical stenosis. After a step by step treatment protocol was done, we finally offered her trial stimulation of the suprascapular nerve. A single quad lead was implanted via a posterior approach under fluoroscopic and ultrasound guidance. Two weeks after successful stimulation, we implanted a permanent neuromodulation system. Permanent neurostimulation of the suprascapular nerve and its end branches may be a new interesting target in treating patients suffering shoulder pain due to various etiologies. In our patient the follow-up period is 9 months with an excellent result in pain relief, we observed no complications thus far, especially no dislocation or breakage of the lead. In this report, literature on this subject is reviewed, and our technique is well documented with additional anatomical illustrations.