Brain tumors – gliomas – are difficult to treat which is why they still constitute a death sentence for most of those affected Elke Hattingen uses a method that visualizes the tumor’s metabolic activity: metabolic imaging This allows her to look not only at the tumor itself but also its immediate environment which the tumor manipulates and needs to survive and grow they are among the most dreaded types of cancer: Glioblastomas are still fatal in most cases due to their rapid and aggressive growth They are tumors that grow out of the brain tissue itself they develop out of degenerated glial cells is to support and nourish the nervous system Gliomas are classified in four grades depending on their malignancy But as soon as the cancer begins to spread into healthy brain tissue known therapies can only buy time for the person affected This is because not all cancer cells can generally be eradicated and it is not possible with conventional diagnostic procedures to recognize the remaining cancer foci with absolute certainty Radiologist Elke Hattingen wants to change this She is a senior consultant at University Hospital Frankfurt where she is also the director of the Institute of Neuroradiology One of her team’s central tasks is to diagnose cancer or other brain diseases and monitor treatment by means of imaging techniques especially magnetic resonance imaging (MRI) on which Hattingen has been focusing for many years MRI is particularly suitable for visualizing soft tissue such as the brain and can produce high-resolution cross-sectional images As imaging is done with strong magnetic fields patients are not subjected to potentially harmful X-rays Neuroradiology has fascinated Hattingen since early on because you must use your “detective skills” We have to assemble all the pieces of the puzzle – clinical picture I still find that very exciting even after 25 years!” the disease is already at a relatively advanced stage by then because gliomas often do not affect brain function for a very long time the patient often has little time left despite treatment although the more aggressive forms are more prevalent in older people The first step is surgery to remove as much of the diseased brain tissue as possible Extensive radiation of the affected area then follows for example in areas of the brain responsible for important functions such as language or breathing even benign grade 1 gliomas are not always operable it is highly probable that undetected cancer cells will grow into new tumors after treatment has ended “MRI only ever shows us the tip of the iceberg,” says Hattingen who is still contributing her decades of experience to diagnostics and patient care despite her increasing organizational duties as head of the institute “We meanwhile know that a brain tumor in fact affects more or less the whole brain We want to use new methods to visualize the pathological changes that we cannot see with conventional MRI.” This should then improve both diagnosis and the monitoring of treatment Although it is possible to assess the tumor’s location and morphology and perhaps already diagnose glioma with conventional MRI and many years’ experience which is tailored to the individual patient we need to know the molecular profile of the cancer cells,” says Hattingen “but we cannot get any further with conventional imaging.” The tumor’s molecular fingerprint the genetic mutations that transform glial cells into cancerous ones determines which therapies are promising and to which drugs the cancer cells are most likely resistant doctors analyze the DNA of cancer cells obtained via a biopsy to visualize a tumor’s molecular fingerprint indirectly in the body and without invasive procedures “The molecular profile affects the tumor’s metabolism in a very specific manner Our metabolic MRI enables us to visualize these metabolic changes and in this way distinguish diseased from healthy tissue.” In addition to the tumor’s metabolic profile MRI is useful for examining many other biological characteristics: Especially changes in blood flow in pathologically altered regions of the brain the brain’s microstructure and texture as well as changes in its functionality are very revealing “Our innovative MRI gives us a deeper insight into tumor pathology but it also helps us diagnose brain diseases that otherwise do not show up on MRI scans such as schizophrenia or inflammatory diseases,” she adds MRI can show how far the tumor has already spread into healthy tissue and whether it is located in an important region of the brain such as the language center This information makes it easier to plan and perform the operation metabolic and conventional MRI are used in tandem and cerebral blood flow is measured to check whether treatment has been successful judging whether the tumor is growing again is extremely difficult: “The brain reacts to the aggressive therapy by swelling or through a disruption of the blood-brain barrier it is not possible to distinguish these changes from tumor growth on a normal MRI scan.” Increased blood flow and the presence of cell markers that indicate growth are clear signs that the tumor has returned This is where metabolic MRI helps to evaluate whether treatment has worked or should be terminated Hattingen emphasizes the tangible consequences for patients: “Treatment planning optimized in this way can certainly give some patients another three to five years with a good quality of life.” The new techniques can also be used for purposes other than cancer: It is now even possible to determine neurotransmitters in the brain directly in the patient’s head An imbalance of these neurotransmitters plays a role in epilepsy and presumably also in neurodegenerative diseases The measuring procedure is gentle on the patient and a whole metabolic profile can be detected at once all these examinations generate vast amounts of data that can meanwhile only be mastered with the help of artificial intelligence “We radiologists with our scans are just one element,” says Hattingen “Also relevant are the results of other examinations and information about the patient’s medical history previous illnesses and risk factors as well as genetic profiles Comprehending all this with normal statistics is no longer possible.” Diagnosis today is still largely based on the doctor’s experience “but if we want to make it better and more reliable we need artificial intelligence that can recognize patterns and take additional information into account.” It is important to Hattingen that humans remain the final authority and check the plausibility of all diagnoses made with AI then AI can save time when making a diagnosis and spare the patient unnecessary examinations “Precisely in times like these where there is a growing shortage of qualified staff I hope that AI will be a big help for us doctors,” she says Neuroradiologists do not have to worry that computer-assisted methods will put them out of work “What’s completely new for us is that we now also operate,” Hattingen is pleased to say neuroradiologists can remove blood clots from cerebral arteries in the event of a stroke if the arteries blocked by the clot are large enough to be reached via a catheter.” This often leads to a significant improvement or even a cure “Imagine if a patient comes to us who is paralyzed down one side and goes home cured “It makes our discipline even more exciting and also very attractive for the next generation of doctors.” The author / Larissa Tetsch studied biology and earned her doctoral degree in microbiology. She then worked in basic research and later in medical training. She has been working as a freelance science and medical journalist since 2015 and is also the managing editor of the science magazine “Biologie in unserer Zeit”.www.larissa-tetsch.de Futher issues of Forschung Fankfurt Frankfurter Städel Museum und Arbeitsbereich Altersmedizin der Goethe-Universität entwickeln App für Menschen mit Demenz Demenz ist bislang nicht heilbar Wie die klassische Methode der Hirnstrommessung bei der Schlaganfalltherapie eine Renaissance erlebt Die klinische Neurophysiologie befindet sich in einer spannenden Wie MRT-Bilder bei Diagnose und Therapie von Hirntumoren helfen können Hirntumoren – Gliome – sind schwer zu behandeln und deshalb Wie Präzisionsmedizin bei Risikoerkennung und Behandlung von Infarkten helfen kann Ein Meilenstein der modernen Herzmedizin wurde 1977 am Universitätsklinikum Frankfurt Wie die computergestützte Genommedizin nach den Ursachen ­kardiovaskulärer Erkrankungen sucht Medizinische Behandlungen sollen in Zukunft personalisiert sein Wie nicht-codierende RNA die Therapie von kardiovaskulären Erkrankungen revolutionieren könnte Auf den ersten Blick sind sogenannte nicht-codierende RNA (ncRNA) in Wie begeistern Biologielehrer*innen Schüler*innen für ihr Fach Im ersten „Workshop on Biological Sciences“ trafen acht Studierende des Kibbutzim College of Frankfurter Wissenschaftler vertritt deutsche Forschungslandschaft bei UN-Umweltkonferenzen bei denen der Fokus auf internationalem Abfallhandel und Chemikaliensicherheit liegt Die Goethe-Universität Frankfurt zuletzt als Joint Researcher am C3S und am Potsdam-Institut für Klimafolgenforschung Die Goethe-Universität ist mit dem House of Finance künftig Mitglied im Sustainable Finance Cluster Frankfurt am Main Neues Projekt „Visual Analytics für Bilder aus Kolonialen Kontexten“ (VABiKo) ist gestartet: eine DFG-finanzierte Kooperation der Universitätsbibliothek Frankfurt am Main April 2025 trafen sich zwanzig Promovierende und Postdocs der Rhein-Main-Universitäten (RMU) am traditionsreichen Eisernen Steg © 2024 Goethe-Universität Frankfurt am Main | Impressum | Datenschutzerklärung | Cookies verwalten From Quincy Jones, a towering creative figure who couldn't be contained to any one "thing," whether it be a genre of music or job description Affectionately known as "Q," Quincy was a luminary in every sense — a masterful arranger as well as a media mogul and cultural icon In this special episode of Jazz Night in America we honor Quincy's extraordinary jazz legacy with our host "Quincy cherished his jazz life and the people in it — even when he was making huge pop hits," McBride shares. "Only Q could've put organist Jimmy Smith on Michael Jackson's 'Bad!' " executive producer at NPR Music; Keith Jenkins vice president of visuals and music strategy at NPR A previous version of this story misspelled Art Farmer's last name Become an NPR sponsor Volume 13 - 2022 | https://doi.org/10.3389/fneur.2022.795573 Excluding persons from magnetic resonance imaging (MRI) research studies based on their medical history or because they have tattoos can create bias and compromise the validity and generalizability of study results we limited exclusion criteria for MRI and allowed participants with passive medical implants tattoos or permanent make-up to undergo MRI we could include 16.6% more people than would have been possible based on common recommendations We observed no adverse events or artifacts This supports that most passive medical implants tattoos and permanent make-up are MRI suitable and can be scanned in research settings the exact type of the implant must be identified first and not everyone might be aware of what medical device they have been implanted In clinical practice the presence of medical implants hardly ever poses a problem since the expected benefit from the imaging procedure outweighs the potential risk for the patient In non-clinical research settings and especially in studies using high-field MRI such participants are still often excluded as a precaution Whilst safety of a participant in the MRI is of utter importance stringent eligibility criteria introduce selection bias which may jeopardize the validity of a study Together with experts from the field of MR physics we investigated whether we could safely broaden eligibility criteria for 3 T MRI examination in a large population-based study allowing eligible participant with passive medical implants (even without MRI safety certificates) tattoos and permanent make-up to undergo 3 T MRI The study is based on the first 5,000 participants of the Rhineland Study We invite all inhabitants aged above 30 years from two geographically defined areas in Bonn The sole exclusion criteria was inability to provide informed consent Approval to undertake the study was obtained from the ethics committee of the University of Bonn The study is carried out in accordance with the recommendations of the International Council for Harmonization Good Clinical Practice standards We obtain written informed consent from all participants in accordance with the Declaration of Helsinki We established an MRI expert committee that developed the procedure for clarification of MRI suitability This committee included scientists from Population Health Sciences (VL Our procedure was as follows (Figure 1): Active implants (e.g. non-medical metal and metal splinters were considered absolute MRI contraindications Tattoos and permanent make-up were not considered contraindications and material of the tattoos and permanent make-up If participants indicated having passive devices we asked them to bring relevant medical documentation for these (surgery or release reports and with the explicit consent of the participant we called the hospital which implanted the passive device to ask for further information Specialized study technicians decided on MRI suitability based on available information and referred to the MRI expert committee where needed The expert committee decided on MRI suitability based on current knowledge in both scientific and clinical practice with the guiding principle to do no harm to participants In cases of doubt or whenever a possible MRI contraindication could not be ruled out Flowchart of the process of clarification of MRI suitability in the Rhineland Study aParticipant could have more than one absolute contraindication bOnly three participants had MRI safety certificates for their medical implants cAfter evaluating our procedure after 1 year the expert committee considered the following medical implants as MRI suitable without checking further documentation: hip and knee replacements plates and stiffening of the spinal cord < 13 cm dThree hundred and seventy-six participants had tattoos and/or permanent make-up eParticipants who were excluded according to stricter exclusion criteria at study start and could not be contacted for reinvitation fThree hundred and five participants had tattoos and/or permanent make-up One year after the introduction of this procedure 169 participants with medical implants had been discussed by the expert committee and subsequently been scanned without any problems the MRI expert committee made a list of medical implants that from then on could be considered as MRI suitable by the study technicians without further consulting the MRI expert committee This list included the following medical devices with or without relevant medical documentation: hip and knee replacements The 2005 cut-off was chosen because in recent years such implants are typically made of titanium A medical implant had to be implanted at least 6 weeks before the MRI examination we verbally informed all participants with medical implants tattoos and/or permanent make-up about the possibility of adverse events They were instructed to squeeze the alarm ball during the MRI examination as soon as they would feel any tingling sensation we would ask about their symptoms and document these as well For participants with head implants or permanent make-up we checked all scouts for possible artifacts which would require immediate stopping of MRI data acquisition this would include any artifacts on the scouts for head implants any artifact that would make the scan of the brain unreadable and FLAIR scans have been visually inspected for quality during the initial quality assessment of the Rhineland Study where two raters independently checked for artifacts that might affect the quality of automated brain segmentations We have calculated the proportion of adverse events that we could have detected with 90% and 80% confidence given our sample size of people with tattoos or medical implants (n = 305 and n = 544, respectively) (26) Figure 1 gives an overview of MRI suitability in the Rhineland Study 627 (12.5%) had an absolute contraindication and 810 (16.2%) had a passive medical implant We ultimately deemed 696 (85.9%) of the passive medical implants MRI suitable The expert committee discussed 373 cases and considered 352 of those as MRI suitable We excluded participants who could not provide enough information to assess suitability In total, 4,259 (85.2%) participants were considered eligible for MRI, of whom 3,639 (85.4%) were actually scanned [mean age 54.7 (SD = 13.7) years, 57.8% women (Table 1)] 35 (1.0%) had medical implants and tattoos and 11 had non-removable jewelry (wedding rings Characteristics of the participants of the Rhineland Study who underwent MRI Participants had up to six medical implants, mostly plates, screws, stents, clips, or hip- or knee-replacement (Figure 2) which were up to 48 years old with a median age of 7 years [interquartile range (IQR): 3–13 years] Frequency of eligible medical implants that were scanned at 3T in the Rhineland Study Participants could have multiple plates or screws Other implants (non-metal) included: hernia mesh Most participants were not aware of the material of the tattoo (73.2%) only 2.2% reported that it was tattoo ink that did not contain any metal 1.2% reported that their tattoo was self-made and 1.0% did not know the material of their tattoo but spontaneously reported that they got it outside of Europe or the USA None of the participants reported adverse events nor was the quality of any of the MR scout images reduced by any implants or permanent make-up There were no artifacts seen during the initial quality assessment due to permanent make-up or medical implants in the head which made the brain images unreadable With regard to tattoos, if we had followed the procedure from a recent study on MRI safety of tattoos, we would have had to exclude 182 of 376 participants who we considered eligible, because of tattoo location (head: n = 108, neck: n = 15, genital area: n = 2), tattoos covering more than 5% of the total body area (n = 28), tattoos bigger than 20 cm in diameter (n = 60), or tattoos <20 cm apart from each other (n = 21) (multiple reasons possible) (12) If we had followed most recent recommendations by the FDA that require an MRI safety certificate (1) we would have had to exclude all but 3 participants for their medical implant (807 of 810 participants) yielding an additional 693 eligible participants compared to these established practices and FDA guidelines we classified an additional 830 participants with tattoos or medical implants (45 had both) as MRI eligible (16.6% of our source population) the FDA guidelines can be interpreted more loosely allowing for an implant to be identified as MRI suitable based on other medical documentation we still would have had to exclude 589 of our 810 participants with passive medical implants With our given sample size for tattoos and medical implants we would be able to detect with 90% confidence adverse reactions in 0.8 and 0.4% we included all persons with tattoos and permanent make-up regardless of size or location None of the participants reported any adverse events The FDA recommends to exclude people from MRI for research purposes if their medical implant cannot be identified as MRI eligible (1). Of course, most studies do not solely base their guidelines for MRI eligibility on the FDA recommendation, but rather on a combination of resources, including expert knowledge or websites such as www.mrisafety.com it is essential to be able to identify medical implants in order to confirm eligibility We found that <0.5% of those with a passive medical implant had an MRI safety certificate Most of our participants had no relevant documentation to identify the medical implant and would therefore have been excluded had we strictly followed the FDA recommendations We were able to classify two thirds of these participants as MRI eligible based on information the participant provided verbally participants could not tell us what exact procedures they underwent nor when we could not out rule any potential risks for the participant to undergo MRI thereby reducing selection bias in research studies we defined adverse reactions as pressing the alarm ball during the MRI examination Previous studies have asked participants afterwards about their experience in the MRI We refrained from doing so since we instructed our participants extensively before entering the scanner to press the alarm ball whenever something would feel off A limitation of our study is that only 24 of our scanned participants had tattoos covering more than 5% of the total body area Although we asked participants about the material of their tattoos we did not specifically ask for the country where the tattoos had been made Additional studies are therefore required to investigate the MRI suitability of full-body tattoos and preferably including information on country where and material with which the tattoos were done While we visually checked the brain scout for artifacts in participants with head implants and permanent make-up at the beginning of the MRI examination we did not use automated metrics or quantitative assessments for this there were no artifacts that made the images unreadable We conclude that most passive medical implants (even without MRI safety certificates) and permanent make-up are eligible for 3 Tesla MRI research studies Our procedure could guide new research studies in the clarification of MRI suitability This is crucial to reduce selection bias in and thereby increase generalizability and validity of The datasets presented in this article are not readily available because of data protection regulations. Access to data can be provided to scientists in accordance with the Rhineland Study's Data Use and Access Policy. Requests to access the datasets should be directed to Rhineland Study's Data Use and Access Committee, UlMtRFVBQ0Bkem5lLmRl The studies involving human participants were reviewed and approved by University of Bonn The participants provided their written informed consent to participate in this study and MB contributed to conception and design of the study VL performed the statistical analysis and wrote the first draft of the manuscript All authors contributed to data acquisition and analysis and read and approved the submitted version The Rhineland Study at the DZNE is predominantly funded by the Federal Ministry of Education and Research (BMBF) and the Ministry of Culture and Science of the German State of North Rhine-Westphalia 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 All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher The authors would like to thank Sascha Brunheim for his feedback on a pre-final version of the manuscript 1. ^Available online at: https://www.ismrm.org/mr-safety-links/ (accessed January 27 1. US Food Drug Administration. MRI (Magnetic Resonance Imaging): Benefits and Risks. (2017). Available online at: https://www.fda.gov/radiation-emitting-products/mri-magnetic-resonance-imaging/benefits-and-risks (accessed February 14 Google Scholar Magnetic resonance safety update 2002: implants and devices PubMed Abstract | CrossRef Full Text | Google Scholar MRI and implanted medical devices: basic interactions with an emphasis on heating ACR guidance document on MR safe practices: 2013 Are titanium implants actually safe for magnetic resonance imaging examinations 6. Shellock F, Karacozoff AM. Reference Manual for Magnetic Resonance Safety, Implants Devices. Shellock R D Services (2020). Available online at: https://www.mrisafety.com (accessed January 27 Google Scholar MRI interaction with tattoo pigments: case report Tattoo-induced skin burn during MR imaging PubMed Abstract | CrossRef Full Text | Google Scholar PubMed Abstract | CrossRef Full Text | Google Scholar First-degree burns on MRI due to nonferrous tattoos PubMed Abstract | CrossRef Full Text | Google Scholar Tattoo-induced skin “burn” during magnetic resonance imaging in a professional football player: a case report Safety of tattoos in persons undergoing MRI Magnetic resonance imaging and permanent cosmetics (tattoos): survey of complications and adverse events Two-dimensional accelerated MP-RAGE imaging with flexible linear reordering Effects of refocusing flip angle modulation and view ordering in 3D fast spin echo Optimized three-dimensional fast-spin-echo MRI PubMed Abstract | CrossRef Full Text | Google Scholar Segmented K-space blipped-controlled aliasing in parallel imaging for high spatiotemporal resolution EPI Blipped-controlled aliasing in parallel imaging for simultaneous multislice echo planar imaging with reduced g-factor penalty Evaluation of slice accelerations using multiband echo planar imaging at 3 T Interslice leakage artifact reduction technique for simultaneous multislice acquisitions Compressed sensing diffusion spectrum imaging for accelerated diffusion microstructure MRI in long-term population imaging Rapid whole-brain resting-state fMRI at 3 T: Efficiency-optimized three-dimensional EPI versus repetition time-matched simultaneous-multi-slice EPI Effect of windowing and zero-filled reconstruction of MRI data on spatial resolution and acquisition strategy Controlled aliasing in volumetric parallel imaging (2D CAIPIRINHA) A simple formula for the calculation of sample size in pilot studies 27. Fryar CD, Kruszon-Moran, D, Gu, Q, Ogden, CL,. Mean Body Weight, Height, Waist Circumference, Body Mass Index Among Adults: United States, 1999–2000 Through 2015–2016. National Health Statitics Report, U. S. Department of Health Human Services, New York, United States (2018). p. 1–16. Available online at: https://www.cdc.gov/nchs/data/nhsr/nhsr122-508.pdf Google Scholar Stöcker T and Breteler MMB (2022) Safety of Tattoos and Medical Implants in Population-Based 3T Magnetic Resonance Brain Imaging: The Rhineland Study Received: 15 October 2021; Accepted: 25 February 2022; Published: 22 March 2022 Copyright © 2022 Lohner, Enkirch, Hattingen, Stöcker and Breteler. 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Read our WAMU Privacy Notice This website uses cookies so that we can provide you with the best user experience possible Cookie information is stored in your browser and performs functions such as recognising you when you return to our website and helping our team to understand which sections of the website you find most interesting and useful Strictly Necessary Cookie should be enabled at all times so that we can save your preferences for cookie settings we will not be able to save your preferences This means that every time you visit this website you will need to enable or disable cookies again German international Grand Prix rider Gabriele Steffan passed away on 10 March 2022 Gabriel  was born in Essen and lived in Hattingen where she ran her own dressage stable with her husband Friedel Photo © Julia Rau Her career started in Rhineland where she competed under her maiden name Gabriele Puth She won silver at the 1974 German Youth Riders Championships and got team gold at the European Championships She was the 1975 Rhinelander regional champion on her career making horse Anarchist (by Abendwind x Domspatz) She moved from Young Riders' level to Grand Prix with him and competed for a team spot for the 1980 Olympic Games in Moscow Trained by the legendary Fritz Tempelmann and later on by Heinz Lammers Gabriele received the Golden Rider's Badge for 10 S-level victories at the age of 20 She met her future husband Friedel Steffan at Dressage Stable Lammers and married him in 1982 Gabriele was one of Westfalia's most successful small tour riders in the 1990s and early 2000s with the Oldenburg stallion Adamo (by Aktuell x Futuro) In 2000 she and Friedel established their own business in Hattingen Her last Grand Prix horse was the Oldenburg Sympathico (by Strohmann xx x Weltmeister) which she began showing in 2000 through 2006 At that time she was the regional team trainer for pony riders in Westfalia Tragedy hit the pair in 2006 when Sympathico died during a training session from an aortic rupture The horse collapsed and died on top of Gabriele and she got severely injured She regained her health but had to relearn everything Gabriele did not truly overcome this blow and quit competition sport although her life continued to revolve around horses In 2008 the Westfalian equestrian federation honoured her with a "trainers' medal" for her achievements as a trainer and for developing young talented riders Related LinksSteffan's national show results Scores: 2004 CDI OlfenScores: 2001 CDI Munster2018 PS Online Colt Auction Horse in the Spotlight: De Niro's Donnerhall Stalls for Rent at Durondeau Dressage in Peer, Belgium Exceptionally Well Located Equestrian Facility in Wellington, Florida Well-built Equestrian Estate With Multiple Business Opportunities in Sweden Stable Units for Rent at Lotje Schoots' Equestrian Center in Houten (NED) For Rent: Several Apartments and Stable Wing at High-End Equestrian Facility Stable Wing Available at Reiterhof Wensing on Dutch/German border Real Estate: Well-Appointed Country House with Extensive Equestrian Facility in the U.K. Rémi Blot Please enable JS and disable any ad blocker TULSA, OK — The Crosby Group, a global provider in lifting, rigging, and material handling hardware, has completed the acquisition of Feubo, a global provider of offshore mooring components for the oil and gas and wind energy markets. Financial terms of the transaction were not disclosed. The acquisition, effective Jan. 14, includes the Feubo facility located in Hattingen, Germany that will become Crosby’s center of excellence for mooring components, as well as a key engineering and innovation center. Oliver Feuerstein, CEO of Feubo, will continue to lead the Feubo team and operation. Robert Desel, CEO of Crosby, said: “We are thrilled to expand our offshore product portfolio and end-market reach with this acquisition. Feubo’s position as a leader and innovator in mooring components, and the opportunity to leverage its world-class engineering and innovation competency, made this a compelling addition to Crosby.” Feuerstein added: “This is an exciting new chapter for Feubo, its employees, and customers. With Crosby’s global presence we can increase our reach and increase the pace of innovation. We look forward to joining the Crosby team, who share the same values as us—safety, reliability and innovation.” Feubo is an innovator, developer and seller offshore mooring components for the oil and gas and wind energy markets. The company supplies the market with products such as kenter shackles, anchor shackles, swivels, sockets and other accessories. Feubo is based in Hattingen, Germany. Hypertrophic olivary degeneration (HOD) is a pathology of the inferior olivary nucleus (ION) that occurs after injuries to the Guillain-Mollaret triangle (GMT). Lacking a diagnostic gold standard, diagnosis is usually based on T2 or FLAIR imaging and expert rating. To facilitate precise HOD diagnosis in future studies, we assessed the reliability of this rater-based approach and explored alternative, quantitative analysis. While the rater-based approach yielded the best performance on T2 imaging, a quantitative, more sensitive HOD diagnosis based on ION intensities in PD and DTI imaging seems possible. Volume 13 - 2022 | https://doi.org/10.3389/fneur.2022.950191 This article is part of the Research TopicAI Enhanced Diffusion MRI in NeuroimagingView all 4 articles Purpose: Hypertrophic olivary degeneration (HOD) is a pathology of the inferior olivary nucleus (ION) that occurs after injuries to the Guillain-Mollaret triangle (GMT) diagnosis is usually based on T2 or FLAIR imaging and expert rating To facilitate precise HOD diagnosis in future studies we assessed the reliability of this rater-based approach and explored alternative Methods: Patients who had suffered strokes in the GMT and a matched control group prospectively underwent an MRI examination including T2 Diffusion tensor imaging (DTI) was additionally performed in the patient group Employing an easily reproducible segmentation approach and mean diffusivity (MD) between both IONs were calculated The interrater reliability was best for FLAIR followed by T2 and PD (Fleiss κ = 0.87 / 0.77 / 0.65) The 3 raters diagnosed HOD in 38–46% (FLAIR) False-positive findings in the control group were less frequent in T2 than in PD and FLAIR (2.2% / 8.9% / 6.7%) the intensity difference between both IONs on PD was significantly increased in comparison with the control group These patients also showed significantly decreased FA and increased MD Conclusion: While the rater-based approach yielded the best performance on T2 imaging more sensitive HOD diagnosis based on ION intensities in PD and DTI imaging seems possible Stages (1) and (2): No changes within the first 24 h after suffering the causal lesion followed by degeneration of fibers around the ION; not visible on MRI Stage (3): Hypertrophy of neurons and neurites starting at around 3 weeks; T2 hyperintensity of the ION Stages (4) and (5): Additional hypertrophy of astrocytes starting at approximately 6 months neurons begin to dissolute at approximately 9 months while gemistocytic astrocytes remain present; T2 hyperintensity and enlargement of the ION Stage (6): Final stage with neuronal disappearance at around 3–4 years; lasting T2 hyperintensity and atrophy of the ION Our objective was to assess the reliability of the commonly employed T2-w/FLAIR sequences and the rater-based approach for HOD diagnosis analyze the possible benefit of additional PD-w brain stem imaging and explore reproducible quantitative approaches for the diagnosis of HOD The study was conducted together with an ongoing multicenter study on the incidence and clinical features of HOD after stroke lesions in the GMT (German Clinical Trials Register ID: DRKS00020549, the trial protocol has previously been published (22)) We prospectively enrolled patients who met the following inclusion criteria: (i) Stroke with topo-anatomical relation to the GMT (ii) Sufficient clinical condition for an additional MRI examination (iii) At least 18 years old at initial diagnosis (iv) Written and informed consent could be obtained Enrolled patients were examined with a dedicated MR protocol The examinations were conducted at a minimum of 3 months after the initial stroke event the incidence and dynamic of the patients' symptoms will be published separately in the final analysis of the ongoing clinical trial an age- and sex-matched control group of healthy subjects was recruited for the current imaging study Disease control subjects were examined with a short version of the protocol including only the FLAIR and double echo PD/T2-w sequences We performed two separate analyses, namely, a rater-based analysis and a quantitative analysis. For processing the MRI data, the FMRIB's Software Library (FSL, version 5.0.10, https://fsl.fmrib.ox.ac.uk/fsl) toolbox was used to analyze DTI data, and the software ITK-SNAP (version 3.6.0, www.itksnap.org, (33)) was used for segmentation For the reviewer-based analysis, we generated a “blinded” test dataset, so reviewers would not be influenced by the visible presence or absence of lesions within the GMT. Therefore, all individual PD, T2-w, and FLAIR datasets were cropped in all three dimensions to include only the medulla oblongata with the ION and to exclude the other structures of the GMT in the cerebellum and mesencephalon. An example of the cropped images is shown in Figures 1A–C and FLAIR datasets of the patients and disease controls were then sorted in random order all of whom with more than 6 years of experience in the field of neuroradiology The reviewers were asked to identify the presence and laterality of a HOD separately in every individual PD-w The ratio of patients to disease controls within the test dataset was not disclosed and FLAIR (C) images that were used for the rater-based analysis The segmentation of the anterior quadrants of the medulla oblongata is shown as semitransparent overlay on the PD-w image in (D) with an additional indication of the anterior median fissure (arrow) and the posterolateral sulcus (arrowhead) the right ION is hyperintense and possibly enlarged Images (E) and (F) show the corresponding FA and MD maps as interpolated and color-coded a decrease in FA and an increase in MD are recognizable in the right ION Four additional PD-w, T2-w, and FLAIR datasets derived from additional disease controls were used as a training set to allow the reviewers to adapt to the cropped images and the visual appearance of the PD-w sequence (refer to Supplementary Figure 1 for examples) For the quantitative analysis, a segmentation of the medulla oblongata with a focus on accessibility and reproducibility was established. Using the anterior median fissure and the posterolateral sulcus as easily identifiable anatomical landmarks, the medulla oblongata can be divided into quadrants (Figure 1D) the medulla oblongata was segmented into quadrants on four consecutive slices on the two sequences with 2 mm slice thickness (T2/PD-w DTI) and on two corresponding slices on the FLAIR sequences with 4 mm slice thickness an 8-mm section of the medulla oblongata was segmented on all sequences As the anatomical information of the FA and MD maps is limited through the limited in-plane resolution (2 × 2 mm2) the co-registered T1 MPRAGE datasets were used for additional anatomical reference we computed the average intensities within the anterior quadrants of the medulla oblongata containing the ION the percentage differences between the mean intensities of the two quadrants were calculated for PD-w T2-w and FLAIR datasets (mean intensity a [side with higher mean]−mean intensity b[side with lower mean]/mean intensity b [side with lower mean]) the ROI with the lower intensity was used as reference resulting in positive percentage differences Based on the distribution of values of these differences in the control cohort a threshold containing 99% of all expectable values was calculated for each of the three sequences (threshold = distribution mean + 2.576*standard deviation) intensity differences exceeding this threshold were considered indicative of HOD As there was no option for a comparison to the control cohort the percentage differences for the FA and MD maps were calculated slightly different considering the individual side that a HOD could be anticipated based on the causal index lesion as prior knowledge (mean intensity a [ side with expected HOD]−mean intensity b [contralateral side]/mean intensity a[side with expected HOD]) This resulted in both positive and negative percentage differences allowing for an easier graphical interpretation The calculated MD and FA differences were then compared between patient subgroups whose evaluation of the PD-w datasets was or was not indicative of HOD Statistical testing was done employing GraphPad Prism (Version 9.3.1 The interrater reliability was analyzed using the Fleiss' kappa We used the Kolmogorov-Smirnov-Lilliefors test to test for normal distributions we compared different measurements within the same group with the paired t-test and intergroup differences with the Welch test intergroup differences were tested with the Wilcoxon-Mann-Whitney test We indicated all used tests in the “Results” section A p-value of < 0.05 was deemed to indicate significance We recruited 15 patients and 19 disease control subjects The datasets of 4 control subjects were used as a training set for the reviewers and not included in the analysis as explained in the “Materials and methods” section PD/T2-w datasets were available in all patients and disease controls FLAIR data were only available in 13 out of 15 patients (due to technical issues and severe motion artifacts respectively) and in all 19 disease controls DTI datasets were available in 14 patients and not acquired in disease controls All results are summarized in Table 2 Lacking a gold standard for the diagnosis of HOD a classic calculation of sensitivity and specificity was not feasible we evaluated the interrater reliability within the patient cohort The interrater reliability was best for the FLAIR datasets (κ = 0.87) followed by the T2-w (κ = 0.77) and PD-w datasets (κ = 0.65) we analyzed the percentage of HOD diagnosis for the three reviewers individually in the patient datasets The highest percentage of HOD diagnosis was made in the PD-w datasets (mean 60%; range 53.3–66.7%) with a notable difference in the T2-w and FLAIR datasets (mean 44.4 and 43.6% respectively; range 40–46.7 and 38.5–46.2% As the lower interrater reliability within the PD-w datasets led to an increased number of divergent ratings the difference in the percentage of HOD diagnosis was less pronounced if a consensual diagnosis of all three reviewers was required (HOD diagnosis on PD-w: 40%; T2-w: 33.3%; FLAIR: 38.5%) To assess the specificity of the three sequences we evaluated the percentage of false-positive findings for the three reviewers individually in the control group datasets While there was a mean of only 2.2% false-positive HOD diagnosis in the T2-w datasets (corresponding to a single false-positive finding in all ratings) there was a mean of 6.7 and 8.9% false-positive diagnosis in the FLAIR and PD-w datasets Since the laterality of the HOD was noted by the reviewers it was also possible to identify false-positive findings in the patient cohort if the side of the HOD diagnosis does not correspond to the expected side considering the causative index lesion While none of these false-positive diagnoses were found in the T2-w datasets a mean of 2.6% false-positive findings appeared in the FLAIR datasets and a mean of 8.9% false-positive findings appeared in the PD-w datasets The segmentation ROIs in the left and right anterior medulla oblongata of the patient cohort had a mean volume of 554 mm3 containing a mean of 567 individual voxels in PD/T2-w and a mean of 39 individual voxels in the DTI-based datasets The percentage intensity differences between the two anterior quadrants of the medulla oblongata for all individual patients (filled marks) and controls (empty marks) calculated on PD-w (A) The dotted lines indicate the threshold below that 99% of the value distribution of disease controls is to be expected values above the threshold are deemed indicative of HOD in the patient cohort It is noted that patient number 2 has a false-positive finding in T2-w (B) due to T2 hypointensities in the left anterior medulla oblongata MD (diamonds) and FA (crosses) percentage differences between the two anterior quadrants of the medulla oblongata for all individual patients (A) boxes extend from the 25th to 75th percentiles with a line indicating the median whiskers indicate the minimum and maximum] demonstrate that patients who had conspicuous findings in the quantitative PD analysis showed significantly lower FA (FA_PD + p = 0.002) values on the side where a HOD was to be expected than patients without conspicuous findings in the quantitative PD analysis (FA_PD-; MD_PD-) This prospective study aimed to assess the reliability of detecting HOD in the common rater-based approach on T2-w As the main findings of the reviewer-based analysis the interrater reliability was best for FLAIR followed by T2-w and PD-w (Fleiss κ = 0.87 / 0.77 / 0.65) and HOD was more likely to be diagnosed based on PD-w than on T2 or FLAIR by the blinded raters false-positive findings of HOD were much less frequent in T2-w compared with PD-w and FLAIR Quantitative analyses showed a significant increase in PD-w intensity differences between the left and right ION in 53.3% of patients with strokes in the GMT these patients also showed significantly decreased FA and increased MD values in the medulla oblongata on the side of expected HOD occurrence The implications of the findings for clinical and research practice will be outlined in the following because this allowed for both a precise localization of the index lesion on MRI and a precise determination of the index lesion onset it is yet unknown how frequently a lesion within the GMT causes a HOD and to what extent the anatomical structures in the GMT must be affected As we included patients prior to the diagnosis of HOD to avoid a sampling bias it is reasonable to assume that not all recruited patients developed HOD Together with the missing gold standard for a HOD diagnosis this made it difficult to assess the actual sensitivity and specificity of the diagnostic approaches while a comparison of different sequences and methods was feasible our data suggest that the use of a T2-w sequence is most suitable for a rater-based approach and is likely very robust in relation to specificity Concerning retrospective studies analyzing MRI data that have not been optimized for the imaging of the brain stem the question remains to what degree the validity of a reviewer-based approach can be affected by the imaging quality and resolution We chose the craniocaudal ROI dimension of 8 mm as it covered most of the medulla oblongata in all 30 subjects while preventing the inclusion of adjacent structures The ensuing ROIs were relatively large in size and thereby robust but included not only the ION but also the pyramidal tracts Since we normalized our measurements in individual subjects to the contralateral side the partial volume effect should nevertheless be largely suppressed in the final result This supports the prior assumption that high differences of PD-w intensity in the left and right anterior quadrant of the medulla oblongata indeed indicate the presence of HOD In comparison with the rater-based approach the sensitivity of the quantitative analysis based on the PD-w datasets might be higher especially if unanimous ratings are required (53.3% vs our study suggests the use of T2-w images for the rater-based diagnosis of HOD rather than FLAIR or PD-weighted sequences the rater-based approach yielded good results quantitative HOD diagnosis based on PD-w and possibly additional DTI data seems feasible and might have a higher sensitivity than the rater-based alternative it might be of interest to include quantitative diagnostic measures to improve the repeatability and comparability of the results As it is most important for future studies on the epidemiologic symptoms and therapy of HOD to reliably assess the presence of a HOD our study did focus on establishing the diagnosis rather than the extent The raw data supporting the conclusions of this article will be made available by the authors upon reasonable request The studies involving human participants were reviewed and approved by the Review Board of the Ethical Committee at the University Hospital Frankfurt as of February 10th without further requests (project number: 19-467) The patients/participants provided their written informed consent to participate in this study Writing (original draft preparation): ES and MS-P All authors contributed to the article and approved the submitted version This study was being funded by the junior researcher scholarship program of the Faculty of Medicine at the Goethe University Frankfurt and our medical technical radiology assistants for their support in this study The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fneur.2022.950191/full#supplementary-material Georges Charles Guillain (1876-1961) and Pierre Mollaret (1898-1987) and their legacy to neuroanatomy: the forgotten triangle of Guillain-Mollaret Imaging Features of Hypertrophic Olivary Degeneration Enlargement of the inferior olivary nucleus in association with lesions of the central tegmental tract or dentate nucleus Deux cas de myoclonies 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reliability An integrated approach to correction for off-resonance effects and subject movement in diffusion MR imaging Optimization of diffusion-weighted single-refocused spin-echo EPI by reducing eddy-current artifacts and shortening the echo time findings in nonlesional hypertrophic olivary degeneration Bilateral hypertrophic olivary degeneration following brainstem insult: a retrospective review and examination of causative pathology Hypertrophy of the inferior olivary nucleus in patients with progressive supranuclear palsy Multiple sclerosis lesion detection in the brain: a comparison of fast fluid-attenuated inversion recovery and conventional T2-weighted dual spin echo T2 FLAIR artifacts at 3-T brain magnetic resonance imaging Identifying quantitative imaging features of posterior fossa syndrome in longitudinal MRI Foerch C and Schaller-Paule MA (2022) Qualitative and quantitative detectability of hypertrophic olivary degeneration in T2 Received: 22 May 2022; Accepted: 27 June 2022; Published: 03 August 2022 Copyright © 2022 Steidl, Rauch, Hattingen, Breuer, Schüre, Grapengeter, Shrestha, Foerch and Schaller-Paule. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) *Correspondence: Martin A. Schaller-Paule, bWFydGluLnNjaGFsbGVyQGtndS5kZQ== †ORCID: Schaller-Paule https://orcid.org/0000-0003-1447-9908 Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. 94% of researchers rate our articles as excellent or goodLearn more about the work of our research integrity team to safeguard the quality of each article we publish. Volume 14 - 2020 | https://doi.org/10.3389/fnhum.2020.00262 Cerebral lesions may cause degeneration and neuroplastic reorganization in both the ipsi- and the contralesional hemisphere presumably creating an imbalance of primarily inhibitory interhemispheric influences produced via transcallosal pathways The two hemispheres are thought to mutually hamper neuroplastic reorganization of the other hemisphere The results of preceding degeneration and neuroplastic reorganization of white matter may be reflected by Diffusion Tensor Imaging-derived diffusivity parameters such as fractional anisotropy (FA) we applied Diffusion Tensor Imaging (DTI) to contrast the white matter status of the contralesional hemisphere of young lesioned brains with and without contralateral influences by comparing patients after hemispherotomy to those who had not undergone neurosurgery DTI was applied to 43 healthy controls (26 females mean age ± SD: 25.07 ± 11.33 years) and two groups of in total 51 epilepsy patients with comparable juvenile brain lesions (32 females mean age ± SD: 25.69 ± 12.77 years) either after hemispherotomy (30 of 51 patients) or without neurosurgery (21 of 51 patients) FA values were compared between these groups using the unbiased tract-based spatial statistics approach A voxel-wise ANCOVA controlling for age at scan yielded significant group differences in FA A post hoc t-test between hemispherotomy patients and healthy controls revealed widespread supra-threshold voxels in the contralesional hemisphere of hemispherotomy patients indicating comparatively higher FA values (p < 0.05 showed extensive supra-threshold voxels indicating lower FA values in the contralesional hemisphere as compared to healthy controls (p < 0.05 Whereas lower FA values are suggestive of pronounced contralesional degeneration in the non-surgery group higher FA values in the hemispherotomy group may be interpreted as a result of preceding plastic remodeling whether juvenile brain lesions are associated with contralesional degeneration or reorganization partly depends on the ipsilesional hemisphere Contralesional reorganization as observed in hemispherotomy patients was most likely enabled by the complete neurosurgical deafferentation of the ipsilesional hemisphere and the disinhibition of the neuroplastic potential of the contralesional hemisphere The main argument of this study is that hemispherotomy may be seen as a major plastic stimulus and as a prerequisite for contralesional neuroplastic remodeling in patients with juvenile brain lesions FA may inform investigators about the microstructural white matter status we used DTI to evaluate contralesional white matter changes after extended unilateral early brain lesions in the absence or presence of the ipsilesional hemisphere by comparing epilepsy patients who had undergone transsylvian functional hemispherotomy (hemispherotomy group) to nonsurgical patients with similar pathologies (non-surgery group) the influence of the hemispherotomy on the plastic reorganization of the ipsilesional hemisphere could be estimated that neuroplastic reorganization as indicated by higher FA could be observed in both patient groups but was more pronounced in the hemispherotomy group The study was approved by the local Institutional Review Board and all participants and/or their legal guardians gave written informed consent Magnetic resonance imaging data was acquired using a 3T Magnetom Trio (Siemens Healthineers) T2 and DTI data were collected for all patients and healthy controls a new head coil was implemented in October 2014 leading to minimal changes in sequence parameters: all scans acquired before the scanner update were run with an eight-channel-coil and a scanning routine containing a 3D MPRAGE sequence (resolution = 1.0 × 1.0 × 1.0 mm3 a 3D T2-weighted sequence (resolution = 1.0 × 1.0 × 1.0 mm3 and a single-shot diffusion-weighted sequence (resolution = 1.72 × 1.72 × 1.7 mm3 flip angle = 90°) with 60 diffusion-encoding directions and a b-value of 1,000 s/mm2 as well as six baseline volumes with a b-value of 0 s/mm2 Sequences acquired after the scanner update were run with a 32-channel head-coil equally including a MPRAGE sequence (resolution = 0.8 × 0.8 × 0.8 mm3 T2-weighted sequence (resolution = 0.8 × 0.8 × 0.8 mm3 and a single-shot diffusion-weighted sequence (resolution 1.72 × 1.72 × 1.7 mm3 Diffusion tensors were fitted to each voxel in the corrected DTI data and FA was calculated the mean of each patients’ six b0 baseline volumes was calculated as a reference image for a boundary-based registration (BBR) to the respective T1-weighted volume Mean fractional anisotropy (FA) skeleton and canonical lesion mask Mean FA skeleton (red to yellow) of all subjects and canonical lesion mask (rainbow) created from all patients shown on the FMRIB58_FA template Volumes of patients with left-hemispheric lesions are flipped along the x-axis Coordinates are provided in MNI standard space Resulting clusters were thickened to aid visualization whereas results of all other contrasts applied to show intergroup FA differences were corrected for family-wise error (A) Voxel-wise post hoc tests in FA between hemispherotomy group and healthy controls (B) Voxel-wise post hoc tests in FA between non-surgery group and healthy controls tests were corrected for family-wise error and p < 0.05 z indicates axial coordinate in MNI standard space Please note that the canonical lesions masks differ between the post hoc tests as they are built out of the individual lesion masks of the respective groups contrasted Skeletonized results were thickened for visualization purposes Results of the intragroup comparison did not survive correction for multiple comparisons The opposite contrasts did not yield significant results Voxel-wise t-test in FA between hemispherotomy subgroups with early-onset and late-onset pathologies (p < 0.05 Copper voxels indicate a canonical lesion mask A voxel-wise regression analysis aiming to explain FA values by lesion size did not yield statistically significant results (p > 0.45) even when omitting a correction for multiple comparisons (p > 0.10) we contrast contralesional FA differences of two epilepsy patient groups with juvenile brain lesions after hemispherotomy and without neurosurgery Our hypothesis was partly confirmed by the comparison between patients after hemispherotomy and healthy controls resulting in widespread supra-threshold voxels which indicated higher FA values and most likely extensive neuroplastic reorganization in the hemispherotomy group the same comparison with the non-surgery group left us with widespread supra-threshold voxels indicating comparatively lower FA values most likely indicating more pronounced degeneration in nonsurgical patients Hemispherotomy/the removal of ipsilesional influences seems to be a prerequisite for contralesional neuroplastic remodeling The juvenile brain lesion creates an interhemispheric imbalance with prevailing inhibitory influences These inhibitory influences are removed by the procedure of hemispherotomy By downregulating the excitability of the contralesional hemisphere by upregulating the excitability of the ipsilesional hemisphere or by combining both recoveries after stroke may be facilitated Non-invasive brain stimulation has not been applied to hemispherotomy patients our results inspire trials aimed at “preparing” patients for surgery by downregulating the ipsilesional hemisphere and anticipating the postoperative status The preservation of these connections is most likely reflected by comparatively higher FA values in the contralesional frontal lobe whereas patients with late lesions had to recruit ipsilesional regions for functional compensation as indicated by comparatively higher FA values in the residual ipsilesional brainstem As it is too late for the preservation of the (contralesional) uncrossed pyramidal tract the ipsilesional hemisphere itself has to compensate the lesion A future longitudinal study investigating how white matter microstructure changes before and after hemispherotomy would be one way to overcome some of the limitations of the current study Lower FA values unexpectedly found in the white matter infrastructure of the contralesional hemisphere of epilepsy patients with juvenile brain lesion when compared to healthy controls most likely reflect secondary degeneration and may constitute the structural correlate of diaschisis This degeneration may be aggravated and neuroplastic reorganization in this hemisphere may be hindered by the inhibitory influence of the ipsilesional hemisphere produced via transcallosal pathways The contrasting result of higher FA values in the contralesional hemisphere in a group of patients with similar pathologies who had undergone hemispherotomy as compared to healthy controls may be interpreted as a correlate of preceding neuroplastic reorganization of the contralesional hemisphere This reorganization has most likely been enabled by the lacking inhibitory influence of the ipsilesional hemisphere resulting in the disinhibition of the contralesional one Our study probes models of interhemispheric balance by applying it to two patient groups with early brain lesions after and without hemispherotomy The pattern of degenerative and plastic structural alterations is most likely a result of interhemispheric inhibition and that the procedure of hemispherotomy should be seen as a major plastic stimulus for reorganization in the contralesional hemisphere Complete disconnection of inhibitory influences from the ipsilesional hemisphere releases the full rehabilitative potential of the contralesional hemisphere for functional recovery in patients with extended unilateral lesions The data that support the findings of this study are available on request from the corresponding author The data are not publicly available as they contain information that could compromise the privacy of research participants The studies involving human participants were reviewed and approved by Ethics Committee of the Medical Faculty of the University of Bonn Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin and TR contributed to the conception and design of the study JG wrote the first draft of the manuscript CH and TR wrote sections of the manuscript All authors contributed to manuscript revision JG and CP have contributed equally to this work Funded by the BONFOR research commission of the medical faculty of the University of Bonn (2015–6–08) JG and LE hold a promotion scholarship of the BonnNi graduate school funded by the Else-Kröner-Fresenius-Stiftung CP holds a promotion scholarship of the BONFOR research commission of the medical faculty of the University of Bonn Part of the results of this study was presented as a talk (“Contralesional white matter alterations with and without ipsilesional influences”) at the 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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) *Correspondence: Theodor Rüber, dGhlb2Rvci5ydWViZXJAdWtib25uLmRl † These authors have contributed equally to this work Clinical Trial Registration: HOD-IS is a registered trial at https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00020549. Volume 12 - 2021 | https://doi.org/10.3389/fneur.2021.675123 Introduction: Ischemic and hemorrhagic strokes in the brainstem and cerebellum with injury to the functional loop of the Guillain-Mollaret triangle (GMT) can trigger a series of events that result in secondary trans-synaptic neurodegeneration of the inferior olivary nucleus this leads to a condition called hypertrophic olivary degeneration (HOD) Characteristic clinical symptoms of HOD progress slowly over months and consist of a rhythmic palatal tremor Diffusion Tensor Imaging (DTI) with tractography is a promising method to identify functional pathway lesions along the cerebello-thalamo-cortical connectivity and to generate a deeper understanding of the HOD pathophysiology The incidence of HOD development following stroke and the timeline of clinical symptoms have not yet been determined in prospective studies—a prerequisite for the surveillance of patients at risk Methods and Analysis: Patients with ischemic and hemorrhagic strokes in the brainstem and cerebellum with a topo-anatomical relation to the GMT are recruited within certified stroke units of the Interdisciplinary Neurovascular Network of the Rhine-Main Matching lesions are identified using a predefined MRI template Eligible patients are prospectively followed up and present at 4 and 8 months after the index event a clinical neurological examination and brain MRI Fiberoptic endoscopic evaluation of swallowing is optional if palatal tremor is encountered Study Outcomes: The primary endpoint of this prospective clinical multicenter study is to determine the frequency of radiological HOD development in patients with a posterior fossa stroke affecting the GMT at 8 months after the index event Secondary endpoints are identification of (1) the timeline and relevance of clinical symptoms (2) lesion localizations more prone to HOD occurrence and (3) the best MR-imaging regimen for HOD identification (4) DTI tractography data are used to analyze individual pathway lesions The aim is to contribute to the epidemiological and pathophysiological understanding of HOD and hereby facilitate future research on therapeutic and prophylactic measures Clinical Trial Registration: HOD-IS is a registered trial at https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00020549 Figure 2. T2-weighted MRI of a 59-year-old patient suffering from pontine-mesencephalic bleeding (A,B) affecting the central tegmental tract on the left (arrows). Within 13 months, the patient developed a HOD (C) with hyperintensity of the left olive (arrowhead) accompanied by the clinical syndrome of a palatal tremor, a pendular nystagmus, and a Holmes tremor [adapted with permission from Foerch et al. (10)] increased awareness of HOD is pre-conditional for improved disease management Knowledge of the disease incidence and pathophysiological mechanisms is a prerequisite for clinical surveillance of patients at risk To follow up those patients and offer symptom-specific support it is first required that we create a timeline of radiological HOD occurrence and the chronological onset of clinical symptoms matching fiber tract pathology to a corresponding clinical course of HOD would be of scientific value Advanced imaging techniques have been sporadically applied in HOD patients in this regard to visualize fiber tracts associated with HOD development. Diffusion tensor imaging (DTI) with tractography can be used to analyze the change in fiber tract volume following injury in the GMT (14–16) The use of this method systematically to investigate the HOD development and more precisely understand the injury to brainstem connectivity is promising beyond merely pinpointing down a lesion to an anatomic localization on MRI or in ex-vivo pathological studies the distinction between affected and unaffected patients allows us to identify contributing factors to HOD occurrence no such prospective acquisition of DTI fiber tracking data in HOD patients has been described in the literature so far Moreover, proton density (PD)-weighted imaging was shown to be well-suited for detecting infratentorial lesions in the posterior fossa, yielding good contrast between cerebrospinal fluid (CSF) and brainstem lesions (17, 18) it can be hypothesized that double-echo sequences (including T2- and PD-weighted datasets) are superior in the detection of HOD compared to conventional T2-weighted imaging and provide an improved detectability of the underlying lesion to the GMT This study is designed to prospectively determine the frequency of HOD following ischemic or hemorrhagic lesions in the Guillain-Mollaret triangle and to examine the development of the associated clinical syndrome the implementation of advanced imaging methods will be prospectively applied to correlate the clinical findings over time with the respective fiber tract injury and generate a pathophysiological timeline of HOD development the patient cohort is well-suited to compare the detectability of radiological HOD in T2- and PD-weighted data The study does not include medication or the admission of computed tomography (CT) or other sources of radiation at any point which shows an MRI template with the regions of interest Fiberoptic endoscopic footage (FEES) of two patients (A,B) with HOD and dysphagia who showed involuntary movements of the soft palate and pharynx due to rhythmic contraction of the levator veli palatine so-called palatal tremor (images used with permission from Dr Applying these numbers to the local prerequisites an equivalent of 1,927 strokes in the brainstem and cerebellum in the 2-year study period can be estimated for the recruiting centers the study templates with the regions of interest were applied on 40 consecutive brainstem and cerebellar strokes in a pilot run in 2018 which showed that 35% of strokes had a general topo-anatomical relation to the GMT 674 stroke patients with lesions affecting the region of interest can be expected in the recruiting centers strict application of exclusion criteria showed that only a smaller portion of those patients could have been recruited especially due to a lack of MR-feasibility and progressed disability due to the index stroke and advanced patient age (reflected in mRS > 4) the SARS-Covid-19 pandemic unforeseeably complicates recruitment the targeted number of patients to include in this study is n = 100 leaving a necessarily large scope for expected recruitment failures and patient exclusions the proportion of patients developing HOD as well as the timeline of HOD development will be determined Written informed consent is mandatory for recruitment Patients are excluded from the study if explicit consent to participate in the study cannot be given due to coma or lack of legal competence Further exclusion criteria are visibility of new operative injury on MRI (e.g. contraindications to perform MR-imaging (such as pacemakers and a modified Rankin Scale (mRS) of more than four points All patients are asked to undergo follow-up MR-imaging done at the Brain Imaging Center (BIC) of the Goethe University Frankfurt a clinical neurological examination is performed by a study physician following a study exam catalog and Holmes tremor of the upper limbs are specifically evaluated by a physician with experience in the field The individual disability outcome is measured by the modified Rankin Scale (mRS) during each study visit the patient is offered an evaluation of dysphagia by a speech-language pathologist MRI examinations are performed on a 3T whole-body MRI scanner (MAGNETOM Prisma, Siemens Healthineers, Erlangen, Germany) using a body transmit and a 20-channel phased-array head/neck receive coil (Siemens Healthineers, Erlangen, Germany). As an anatomical reference, a T1-weighted data set with whole-brain coverage and an isotropic resolution of 1 mm are acquired using a 3D magnetization-prepared rapid-gradient-echo imaging (MP-RAGE) sequence (22) acquired with a long repetition time (TR) and a relatively short echo time (TE) are compared to both T2-weighted and fluid-attenuated inversion recovery (FLAIR) images For best detection sensitivity of radiological HOD an infratentorial axial T2-weighted sequence of the brainstem is included as a gold standard with the following parameters: matrix size 448 × 358 PD- and T2-weighted images are recorded simultaneously via a double-echo turbo spin echo sequence (TE 12 and 96 ms) with the following parameters: matrix size 384 × 384 In correspondence with the local clinical routine protocol FLAIR images covering the entire brain are acquired with a matrix size of 320 × 224 Diffusion MRI with region-of-interest-based deterministic tractography using TrackVis in sagittal (A) and coronal (B) view rendered as described with MR data from the protocol pilot run (3T MAGNETOM Prisma Brain Imaging Center Frankfurt) obtained from a healthy 32-year-old male test subject FEES are performed with an Olympus ENF-P4 laryngoscope attached to a camera (rpCam62 S/N) and a color monitor (17′ -TFT-EIZO FEES procedures are performed by a neurologist and a speech-language pathologist having several years of experience with the diagnostic tool A standardized FEES protocol will be followed strictly All swallowing trials are rated by an experienced speech pathologist according to the Penetration Aspiration Scale Secondary endpoint values are the radiological incidence of HOD at 4 months after the index event Further secondary endpoints are the presence of HOD-specific symptoms in the clinical exam at follow-up and the impact of HOD development on disability outcome (mRS) The PD-weighted images of all patients will be reviewed by three blinded raters with a specialization in neuroradiology and rated for their quality of HOD identification in comparison to simultaneously acquired T2-weighted images The DTI images will be analyzed for each individual patient with respect to lesion location within the fiber tracts of the GMT and quantitative imaging parameters such as mean diffusivity and fractional anisotropy and will be reviewed This is the first prospective study aimed to determine the incidence of HOD following ischemic and hemorrhagic stroke with injury inflicted to the GMT clinical and pathophysiological aspects of HOD will be assessed as secondary targets The development and clinical application of a region-of-interest template and identification of lesions in the GMT more prone to cause HOD is a key component of the study In order to prevent a selection bias and include patients as objectively as possible the radiological template for patient recruitment is designed to be generous in size around key structures of the GMT also patients with partial or minor affection of GMT structures can be included in the study allowing for a more differentiated analysis the influence of the specific lesion location in the GMT on the probability of HOD development is still unknown This study aims to investigate whether the effect of structures such as the DN or RN is associated with an increased risk of HOD compared to other localizations Knowledge of a specific incidence based on lesion location justifies a prospective follow-up of stroke patients at risk of developing HOD Though no treatment or prophylaxis for HOD exists yet prospective therapeutic measures could be explored such as inhibiting the excitatory fiber tracts involved in HOD development by medicinal GABAergic modulation the frequency and extent of characteristic symptoms in HOD patients are still unknown and can be firstly described in this study No study in the literature has systematically assessed whether HOD frequently causes a clinical syndrome in the patient or is mostly a coincidental radiological finding without relevance in most The information available in the literature is based on case reports of mostly symptomatic patients in whom diagnostic workup revealed underlying HOD which is why the real number of asymptomatic HOD patients may lie considerably higher Clinical follow-up examinations allow us to define a much clearer chronological pattern of the syndrome of HOD and facilitate the assignment of those symptoms to HOD in the future Information on the time-point of symptom onset can be used as a landmark for the clinical surveillance of patients at risk of developing HOD This study can provide insight into whether the HOD is a disease affecting numerous patients after stroke or rather mostly a radiological phenomenon rarely of relevance to the individual HOD symptoms may often falsely be attributed to the primary stroke lesion instead of a novel pathology if physicians fail to identify the two-stage dynamic in the patient's history and are not aware of HOD PT in particular easily remains undetected in clinical routine if not checked for it remains unclear if PT patients are likely to develop dysphagia or mostly suppress the tremor during the swallowing process and are not functionally affected Improved understanding of dysphagia in PT patients is necessary to detect defective swallowing mechanisms very early and prevent silent aspiration an additional dysphagia assessment with FEES will be offered to the patient The DTI fiber tractography is thus promising to illustrate the chronological course of fiber tract degeneration in HOD and associate the anatomical lesions from routine T2-weighted MR images to the respective fiber tract injury lesion areas most vulnerable for HOD development can be identified and a comparison of fiber tract volumes between symptomatic and asymptomatic HOD could be undertaken The HOD is not a common radiological diagnosis and changes in conventional T2-weighted images may often be too subtle for a confident diagnosis This study aims to provide the clinical radiologist with a more sensitive and specific sequence to confirm the suspicion of HOD: double-echo PD-weighted images with long TR are available on most clinical MR-scanners and are hypothesized to generate more contrast in the brainstem allowing for a more certain and hereby more common diagnosis This is an exploratory study design offering first-ever prospective data on epidemiological and pathophysiological aspects of HOD which is why the outcomes cannot be anticipated the targeted sample of 100 patients will be too low to allow for an exact calculation of disease incidence but will provide an estimation of the magnitude even though a digital template of lesion locations has been created the expected patient cohort will likely be inhomogeneous The distribution between ischemic infarction and hemorrhages and between cerebellar and mesencephalic pathologies is not randomized nor matched the findings cannot be generalized and will have to be asserted to specific lesion locations and constellations and extensive lesion volume are excluded in this study this study does not allow for the description of the risk of HOD development in this collective of severely disabled patients which must be taken into account when interpreting the results An unforeseeable obstacle to overcome in 2020/2021 is surely the SARS-Covid-19 pandemic which complicates patient recruitment as well as the availability of both imaging and clinical visits due to ever-changing local safety restrictions To engage with changing lockdown restrictions a scheduling tolerance of 4 weeks is granted for each study visit This study does not include therapeutic interventions and no medication is or will be administered MRI is performed without a contrast medium Patients are thoroughly instructed about MRIs (such as the associated risks and complications like pacemakers Patients are thoroughly instructed about risks concerning FEES for which written informed consent is mandatory The studies involving human participants were reviewed and approved by the institutional Review Board of the Ethical Committee at the University Hospital Frankfurt as of February 10th 2020 without further requests (project number: 19-467) MS-P conceived the study and gained ethics approval and EH were involved in image data processing and image development MS-P wrote the first draft of the manuscript and JK critically reviewed the study protocol and approved the final version of the manuscript We would like to acknowledge the whole Core Structure and the team of the Brain Imaging Center Frankfurt for their kind help in setting up the MRI protocols for the study we would like to thank Felix Wicke for his kind epidemiological and statistical counseling The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fneur.2021.675123/full#supplementary-material CrossRef Full Text | Google Scholar Google Scholar Hypertrophic olivary degeneration and palatal or oculopalatal tremor PubMed Abstract | CrossRef Full Text | Google Scholar Hypertrophe degeneration der olive : ursache neuerlicher neurologischer symptome nach schlaganfall Sur la dégénération pseudo-hypertrophique de l'olive bulbaire Google Scholar Deux cas de myoclonies synchrones et rythmées vélo-pharyngo-laryngo-oculo-diaphragmatiques: le problème anatomique et physiologique Google Scholar Hypertrophic olivary degeneration: case series and review of literature Diffusion tensor imaging in hypertrophic olivary degeneration Diffusion tensor imaging in a case of pontine bleeding showing hypertrophic olivary degeneration and cerebellar ataxia Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis-clinical implementation in the diagnostic process CrossRef Full Text | Google Scholar The Lausanne Stroke Registry: analysis of 1,000 consecutive patients with first stroke New England medical center posterior circulation stroke registry: I Optimization of 3-D MP-RAGE sequences for structural brain imaging PubMed Abstract | CrossRef Full Text Hattingen E and Foerch C (2021) Multicenter Prospective Analysis of Hypertrophic Olivary Degeneration Following Infratentorial Stroke (HOD-IS): Evaluation of Disease Epidemiology Received: 02 March 2021; Accepted: 10 June 2021; Published: 16 July 2021 Copyright © 2021 Schaller-Paule, Steidl, Shrestha, Deichmann, Steinmetz, Seiler, Lapa, Steiner, Thonke, Weidauer, Konczalla, Hattingen and Foerch. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) In the clinical routine, detection of focal cortical dysplasia (FCD) by visual inspection is challenging. Still, information about the presence and location of FCD is highly relevant for prognostication and treatment decisions. Therefore, this study aimed to develop, describe and test a method for the calculation of synthetic anatomies using multiparametric quantitative MRI (qMRI) data and surface-based analysis, which allows for an improved visualization of FCD. The synthetically enhanced FLAIR-anatomies showed higher signal levels than conventional FLAIR-data at the FCD sites (p = 0.005). In addition, the enhanced FLAIR-anatomies exhibited higher signal levels at the FCD sites than in the corresponding contralateral regions (p = 0.005). However, false positive findings occurred, so careful comparison with conventional datasets is mandatory. Synthetically enhanced FLAIR-anatomies resulting from surface-based multiparametric qMRI-analyses have the potential to improve the visualization of FCD and, accordingly, the treatment of the respective patients. Volume 14 - 2020 | https://doi.org/10.3389/fnins.2020.00622 This article is part of the Research TopicAdvanced Imaging Methods in NeuroscienceView all 37 articles detection of focal cortical dysplasia (FCD) by visual inspection is challenging information about the presence and location of FCD is highly relevant for prognostication and treatment decisions describe and test a method for the calculation of synthetic anatomies using multiparametric quantitative MRI (qMRI) data and surface-based analysis which allows for an improved visualization of FCD T2- and PD-maps and conventional clinical datasets of patients with FCD and epilepsy were acquired Tissue segmentation and delineation of the border between white matter and cortex was performed In order to detect blurring at this border a surface-based calculation of the standard deviation of each quantitative parameter (T1 and PD) was performed across the cortex and the neighboring white matter for each cortical vertex The resulting standard deviations combined with measures of the cortical thickness were used to enhance the signal of conventional FLAIR-datasets The resulting synthetically enhanced FLAIR-anatomies were compared with conventional MRI-data utilizing regions of interest based analysis techniques Results: The synthetically enhanced FLAIR-anatomies showed higher signal levels than conventional FLAIR-data at the FCD sites (p = 0.005) the enhanced FLAIR-anatomies exhibited higher signal levels at the FCD sites than in the corresponding contralateral regions (p = 0.005) so careful comparison with conventional datasets is mandatory Conclusion: Synthetically enhanced FLAIR-anatomies resulting from surface-based multiparametric qMRI-analyses have the potential to improve the visualization of FCD and clinicians need this information for treatment decisions In the present preliminary technical study it was aimed to develop a method which allows for an improved visualization of FCD The potential advantage is that the technique integrates information from different complementary parameters (T1 The method utilizes a reconstruction of WM and pial surfaces and boundary-based analysis techniques which integrate information about the course and orientation of the WM and pial surfaces when reading parameter values and measuring the cortical thickness The results of the calculation are used to highlight FCD areas in FLAIR datasets this method has the potential to aid visual assessment of image data thus helping to reduce the number of undetected lesions potentially allowing for a more effective treatment the purpose of this study was to develop and describe the method to show representative data and to quantify the improvement in image contrast via comparison with conventional MRI datasets using a regions of interest (ROI) based analysis MRI-acquisition was performed for 10 patients with neuroradiologically diagnosed FCD based on clinical MRI-data (three females mean ± SD: 29.6 ± 11.7 years) and five healthy subjects (three females mean ± SD: 24.4 ± 5.1 years) The studies involving human participants were reviewed and approved by the respective local board (Ethik-Kommission des Fachbereichs Medizin des Universitätsklinikums der Goethe-Universität) The patients/participants provided written informed consent to participate in this study The study was performed according to the principles formulated in the Declaration of Helsinki A 3 Tesla (T) MRI-scanner “Magnetom TRIO” (Siemens Medical Solutions Signal reception was performed with an 8-channel phased-array head coil and radiofrequency (RF) transmission with a body coil Functions included in MatLab (MathWorks, Natick, MA, United States), the FMRIB-Software-Library version 5.0.7 (FSL, Oxford) (Smith et al., 2004) and FreeSurfer version 6.0.1 (Athinoula A. Martinos Center for Biomedical Imaging, Boston) (Fischl et al., 2004) were used for analysis two gradient echo (GE)-datasets with different TE were acquired and processed with FSL PRELUDE and FUGUE: TE [1,2] = [4.89 ms,7.35 ms] B1-mapping was performed as reported in the literature (Volz et al., 2010) two GE-datasets were recorded (reference and magnetization prepared) The magnetization preparation consisted in an RF-pulse rotating the longitudinal magnetization by an angle β (nominal value: β0 = 45°) comparison of this dataset with the reference-data allows for the determination of the local β and B1 follows from deviations of β from β0 resolution and volume coverage as for B0-mapping For PD-mapping, a method described in the literature (Volz et al., 2012a) was used the PD-weighted datasets resulting from the VFA-acquisition with the lower excitation angle were corrected for T1- T2∗- and B1-effects and for inhomogeneities of the receive-coil profile (RCP) For the correction of signal-losses in the VFA-data induced by T2∗-relaxation effects during the finite TE of 6.7 ms two GE-datasets with different TE were acquired: TE [1,2] = [4.3 ms,11 ms] Synthetic T1-weighted magnetization-prepared rapid gradient-echo (MP-RAGE) anatomies were obtained as described previously (Gracien et al., 2019), using B0-corrected T1-maps and pseudo-PD-maps derived from T1-data via the Fatouros equation (Fatouros et al., 1991; Volz et al., 2012b) The virtual acquisition-parameters assumed for the synthetic data were: TR = 1900 ms volume coverage) were identical to the respective parameters of the underlying T1-maps Additional conventional MRI-acquisitions comprised MP-RAGE (Mugler and Brookeman, 1990) and FLAIR-datasets obtained with the following parameters: matrix-size: 256 × 256 × 192 matrix size: 256 × 220 × 160 All datasets were inspected by a senior neuroradiologist and by an experienced neurologist to assure absence of artifacts Segmentation of the cerebral cortex and WM identification of the boundary between WM and the cortex and measurement of the cortical thickness were conducted by applying the Freesurfer script “recon-all” to the synthetic MP-RAGE-data To avoid edge errors by including zero voxels in the smoothing process an edge preserving algorithm was used: both the respective qMRI-map (WM or non-WM) and its corresponding mask were smoothed separately (kernel with full width at half maximum of 1.5 mm) calculating subsequently the quotient (smoothed map divided by smoothed mask) Voxels outside of the respective masks were excluded voxels of the WM- and non-WM maps were recombined The following algorithm was applied twice with different input data using either the original qMRI-maps or smoothed versions of these maps: After boundary-based coregistration of the T2-maps to the synthetic MP-RAGE-anatomies with BBRegister original or smoothed versions of the qMRI-maps were used to obtain values of the three investigated parameters (T1 avoiding areas close to the inner and outer cortex boundary the cortex was subdivided into layers which were labeled according to their respective positions inside the cortex given in percent of the cortical thickness (0% corresponding to the WM/cortex-boundary and 100% to the outer surface of the cortex) This subdivision was performed with a resolution of 1% Only qMRI values from layers between the 20% and the 40% mark were read and averaged mirroring the cortex at the WM/cortex-boundary Standard deviations (SD) of these four values were calculated for each qMRI-parameter and each subject and were saved in surface-datasets the cortical thickness (T) was obtained vertex-wise by applying Freesurfer to the synthetic MP-RAGE-anatomies The SD-values and T were then combined according to the following formula in a surface-based analysis: A representative surface-based Q-map is demonstrated in Figure 1. The low values (hot colors) above the lateral sulcus corresponded to the location of an FCD. Figure 1 shows two different ranges for Q: 0–500 (top) and 0–1000 (bottom) Visual inspection revealed that FCD-areas are characterized by low Q-values these datasets would already be suitable for visual FCD-detection as the Q-maps do not show anatomical information they were rather used to enhance the signal in conventional FLAIR-datasets as described in the following paragraph Results of the surface-based analysis demonstrated for a representative patient the scaling in the first row resulting in an improved signal-to-noise-ratio The area with focally decreased values (hot colors) corresponds to the location of an FCD To avoid zero-values for the subsequent division step, Q-values were increased by a minimal constant value of 0.0001. The surface-datasets were then projected into 3D-space with mri_surf2vol. To reduce effects of values above a threshold Q0 = 500, which had been empirically chosen (cf. Figure 1) the datasets were filtered by calculating the quotient Q0/Q resulting in high or low values for Q < Q0 or Q > Q0 Very high values of the resulting quotient-maps above 1000 (corresponding to very low Q-values) were excluded to reduce artifacts in regions where cortical values cannot be read such as areas of the medial hemispheres (corpus callosum and the third ventricle) Datasets were smoothed with a Gaussian kernel (sigma: 3 mm) and a constant value of 1.0 was added The parameter R can be assumed to be approximately 1.0 in normal tissue and to be increased in FCD-areas (where Q is low) R is a suitable parameter for enhancing signal intensities in the clinical FLAIR-images either with (Rs) or without (Ru) initial smoothing The average of both R-maps was then multiplied with the conventional FLAIR-anatomy which had previously been coregistered to the synthetic MP-RAGE-dataset ROIs with the dimensions 2 × 2 × 1 mmł were manually chosen in the conventional FLAIR-datasets representing regions where the FCDs are located and the corresponding contralateral cerebral control areas ROIs were placed by an experienced neurologist and by a senior specialist in neuroradiology deciding by consensus mean values of signal intensities were read from the conventional and enhanced FLAIR-datasets averaged across the group and compared via Wilcoxon tests P-values below 0.05 were considered significant for all tests To visualize the effect of FCD (marked with an arrow) on quantitative parameter values at the WM/cortex-junction, Figure 2 shows the result of the tissue segmentation superimposed on the T2-map The blue line indicates the junction between cortex and WM and the red line the cortical surface as a result of a smooth WM/cortex-junction Tissue segmentation for a representative patient The FCD and the resulting increased subcortical T2-values are marked with an arrow signal intensities across the FCD-ROIs were higher in the enhanced FLAIR-datasets (mean ± standard error of the mean: 202.41 ± 45.90) than in the conventional FLAIR-datasets (77.38 ± 6.16 p = 0.005) and higher than in the corresponding contralateral regions in the enhanced FLAIR-data (55.22 ± 2.35 The FCD-signal in the enhanced in comparison to the conventional datasets was increased in 9/10 patients (relative increase: 66.27 ± 16.19% while no relevant increase could be observed for one patient (0.80%) The final enhanced anatomies generated with this method for improved visualization of FCD and three clinical gold standard datasets (Wellmer et al., 2013) are presented in Figure 3 for four representative patients (rows), showing (from left to right) the conventional T2-weighted (TE = 67 ms), the FLAIR- and the MP-RAGE-datasets and the enhanced FLAIR-datasets. The subject in the first row corresponds to the subject shown in Figure 2 Representative datasets of four patients with FCD (rows) For the subjects shown in the first three rows focal cortical (rows 1 and 2 in the conventional FLAIR-datasets row 2 in the T2-weighted dataset) and subcortical (FLAIR/T2-weighted: rows 1 and 3) hyperintensities and cortical thickening (FLAIR/T2-weighted: row 2) were observed Subcortical hypointensities (rows 1 and 3) and slight cortical thickening (rows 2 and 3) were observed in the conventional MP-RAGE datasets the signal intensity is strongly increased in the enhanced FLAIR-datasets in the FCD areas The FCDs of the participants in the first and third row are clearly visible in the conventional MRI-datasets the lesion in the second row is less prominent the strong signal in the enhanced dataset could help to guide the physician’s eyes when analyzing the images For the subject in the last row of Figure 3 diagnosed with an FCD in the left praecentral sulcus only subtle cortical thickening was visible in the MP-RAGE dataset and a slight hyperintensity in the conventional FLAIR-image such subtle changes might be easily missed when assessing the conventional clinical data the stronger signal in the synthetically enhanced FLAIR-dataset as demonstrated in the fourth column is indicative of this FCD whose data are shown in the first and second row underwent surgical resection of the lesions after data acquisition and analysis Histopathological assessment revealed FCDs type IIa (row 1) and type IIb (row 2) Examples for artifacts in datasets of two healthy subjects (rows) The method presented in this preliminary technical study utilizes multiparametric qMRI-acquisition and surface-based analysis and combines assessment of the non-uniformity of qMRI-values across the junction between cortical GM and WM with vertex-wise measurements of the cortical thickness This information is used to enhance the signal in conventional FLAIR-datasets in regions with a blurring at the WM/cortex-border or increased cortical thickness We observed an increased signal in the enhanced FLAIR-datasets in regions where FCDs are located the method might be helpful to visualize and detect FCD Since the method was built utilizing the presented patients’ data a clinical evaluation of the method based on this group of patients would not be appropriate and was beyond the scope of this study Importantly, qMRI-maps are intrinsically corrected for hardware effects such as inhomogeneities of the static magnetic field B0, the transmitted RF field B1 and the RCP (Cercignani et al., 2018) The respective hardware-effects in conventional datasets are problematic for FCD-detection because they yield signal non-uniformities which may impair tissue segmentation or the analysis of properties of the cortex and of the WM/cortex-border pooled data acquired with different hardware may display different signal non-uniformities thus rendering the analysis more difficult and requiring appropriate correction procedures When using conventional MRI-data for improved FCD-visualization such effects can be reduced with intensity correction/normalization-procedures the use of qMRI-data which are free from such hardware effects should be particularly advantageous for FCD-detection A method using solely T1-data to derive maps of the cortical extent and of the smoothness at borders between WM and voxels with GM-characteristics was described recently (Nöth et al., 2020) T1-maps were used for a custom-built segmentation and creation of maps of the cortical extent the T1-gradients at the WM/GM-border were calculated to generate maps for identification of regions with a blurring at this junction The cortical extent and junction-maps were used to enhance the signal of synthetic DIR-datasets While in the previous work the analysis was performed voxel-wise across the whole brain the multiparametric method presented here is based on the reconstruction of the cortical and WM-surfaces Another key difference is that the method presented here analyzes the junction between the cortex and the potentially abnormal WM while the previous method creates a GM-characteristics-mask including GM and FCD-related abnormalities in WM and investigates the border between this mask and normal-appearing WM junction- and thickness-analyses were combined in the present work to simplify the clinical assessment It should be noted that in the approach chosen here, the surface-datasets were first projected into 3D-space before smoothing was performed. A promising alternative approach which better respects the folded topology of the cortex (Lerch and Evans, 2005) would be to apply surface-based smoothing first this approach is potentially problematic if an FCD is located on both sides of a sulcus FCD-associated changes could be more closely spaced in 3D-space forming a relatively compact area and thus high average R-values upon smoothing the FCD region might appear expanded in the surface-based dataset both approaches should be considered and tested the presented method enhances the signal of conventional FLAIR-datasets because clinicians are used to FLAIR-contrasts which in general provide sufficient anatomical information for localization of the FCD To pave the way of this method or other approaches toward the clinical application future studies with larger cohorts will need to compare different methods to evaluate whether surface-based multimodal approaches are beneficial as compared to other techniques These studies could also integrate diffusion tensor imaging (DTI) techniques to increase the sensitivity or to confirm the findings the enhanced datasets need to be compared carefully with conventional anatomies to confirm or reject each potential lesion as the proposed method includes smoothing steps the spatial extent of an FCD should not be estimated from the enhanced FLAIR-dataset for example when planning surgical treatment Since radiological evaluation of the presented method should not be based on the data used to develop the algorithm future studies investigating different cohorts of FCD patients are required to evaluate the sensitivity and specificity of the method the presented multiparametric surface-based qMRI-method seems to be helpful to improve visualization of FCD Accurate FCD-detection is of high relevance in the clinical routine because undetected lesions might in many cases result in wrong treatment decisions the presented method might help to reduce false negative findings and improve the treatment of the respective FCD patients conventional anatomies remain the gold-standard for FCD-detection and the enhanced datasets should be carefully compared with routine datasets The datasets for this article are not available publicly or upon direct request because data sharing does not comply with the institutional ethics approval The studies involving human participants were reviewed and approved by the Ethik-Kommission des Fachbereichs Medizin des Universitätsklinikums der Goethe-Universität R-MG contributed to the conception and design of the study and R-MG executed the study and acquired the data MM and R-MG designed the presented method and performed the statistical analysis MM and R-MG wrote the first draft of the manuscript All authors reviewed the statistical analysis and the manuscript contributed to the manuscript revision and approved the submitted version EH has received speaker’s honoraria from BRACCO SK has received speaker’s honoraria from Desitin and UCB and educational grants from AD-Tech FR has received honoraria for presentations and consultations from EISAI and Cerbomed as well as research grants from UCB and the Hessonian Ministries of Science and Arts and of Social Affairs and Integration HS has received speaker’s honoraria from Bayer The remaining 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 This work was supported by the State of Hesse with a LOEWE-Grant to the CePTER-Consortium (http://www.uni-frankfurt.de/67689811) and by the Clinician Scientists program at Goethe University Frankfurt The sponsors did not influence the study design nor the collection international league against epilepsy; 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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) *Correspondence: René-Maxime Gracien, UmVuZS1NYXhpbWUuR3JhY2llbkBrZ3UuZGU= Colossal Do stories and artists like this matter to you? Become a Colossal Member now Join more than 200,000 subscribers and get the best of art and visual culture from Colossal Copyright © 2025 Colossal. See our Terms of Service and Privacy Policy German Grand Prix rider Andrea Timpe got injured in a riding accident which took place at the regional dressage show at equestrian centre Nierenhof in Hattingen her 10-year old Westfalian gelding For the Memory (by Florencio x Spitzweg) spooked The 32-year old Andrea lost consciousness and was immediately brought to the hospital where she was diagnosed with a concussion and some bruises She is still hospitalized as she will undergo an MRI on Tuesday 11 July which will determine whether she can recover at home or not "Timpe told Eurodressage from the hospital Timpe made her CDI debut at small tour level with For the Memory this year She competed him at the CDI's in Lier and Nieuw en St she was supposed to make her debut on the German senior Grand Prix team at the Nations Cup CDIO Falsterbo in Sweden this weekend "I can't make it to Falsterbo and I am so sad for it," said Timpe "It was a dream to ride for the German team." Please enable JavaScript to view this page correctly This website is using a security service to protect itself from online attacks The action you just performed triggered the security solution There are several actions that could trigger this block including submitting a certain word or phrase You can email the site owner to let them know you were blocked Please include what you were doing when this page came up and the Cloudflare Ray ID found at the bottom of this page The once-omnipresent Woolworths brand could make its return to British high streets the retailer’s chief executive has said The retailer collapsed in 2009 following the global financial crisis however its German division was rescued by HH Holding HH Holdings chief Roman Heini told Retail Week that bringing the Woolworths brand back to British high streets is on his “bucket list” where it is known as ‘Woolworth’ The majority of its stores are based in Germany but the brand has recently found success in Poland and Austria Heini – who has formerly held executive positions at both Aldi and Lidl – has been Woolworth chief executive since 2020 He told Retail Week that despite challenges he believes there is an opportunity to “make Woolworth great again” Woolworths originated in the US but had operated in the UK for 100 years before its collapse the retailer had 807 British stores but problems with finances and increased competition led to the brand’s exit Woolworth Germany told the BBC it was “unable to confirm any plans for Woolworth to return to the UK market” but did not rule out the brand’s return in principle The retailer’s offer has changed since it was a UK mainstay and childrenswear towards clothing and homeware at more affordable prices Heini told Retail Week that of the 10,000 products that Woolworth sells Heini feels optimistic about its reception in the UK: “I don’t know of any brands where the recognition will be as high as it is in Britain Ikea has opened its flagship store on London’s Oxford Street as the retailer looks to expand its presence within city centres The Swedish homeware retailer’s new store at 214 Oxford.. Supermarket Income REIT has entered into a joint strategic venture (JV) with funds managed by Blue Owl Capital a US-based asset manager with over $250bn (£188bn) of assets under management... The owner of Hobbycraft is planning to close at least nine stores as part of a company voluntary arrangement (CVA) set to be launched this week © 2025 Completely Property Technology Limited part of The Completely Group Limited Schalke will unbedingt Abwehrchef Ko Itakura verpflichten eine Kaufoption ist im Leihvertrag verankert