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9. The EADC‐ADNI Harmonized Protocol for manual hippocampal segmentation on magnetic resonance: Evidence of validity

Author

Frisoni, Giovanni B, Jack, Clifford R, Bocchetta, Martina, Bauer, Corinna, Frederiksen, Kristian S, Liu, Yawu, Preboske, Gregory, Swihart, Tim, Blair, Melanie, Cavedo, Enrica, Grothe, Michel J, Lanfredi, Mariangela, Martinez, Oliver, Nishikawa, Masami, Portegies, Marileen, Stoub, Travis, Ward, Chadwich, Apostolova, Liana G, Ganzola, Rossana, Wolf, Dominik, Barkhof, Frederik, Bartzokis, George, DeCarli, Charles, Csernansky, John G, deToledo‐Morrell, Leyla, Geerlings, Mirjam I, Kaye, Jeffrey, Killiany, Ronald J, Lehéricy, Stephane, Matsuda, Hiroshi, O'Brien, John, Silbert, Lisa C, Scheltens, Philip, Soininen, Hilkka, Teipel, Stefan, Waldemar, Gunhild, Fellgiebel, Andreas, Barnes, Josephine, Firbank, Michael, Gerritsen, Lotte, Henneman, Wouter, Malykhin, Nikolai, Pruessner, Jens C, Wang, Lei, Watson, Craig, Wolf, Henrike, deLeon, Mony, Pantel, Johannes, Ferrari, Clarissa, Bosco, Paolo, Pasqualetti, Patrizio, Duchesne, Simon, Duvernoy, Henri, Boccardi, Marina, Initiative, EADC‐ADNI Working Group on The Harmonized Protocol for Manual Hippocampal Volumetry and for the Alzheimer's Disease Neuroimaging, Albert, Marilyn S, Bennet, David, Camicioli, Richard, Collins, D Louis, Dubois, Bruno, Hampel, Harald, denHeijer, Tom, Hock, Christofer, Jagust, William, Launer, Leonore, Maller, Jerome J, Mueller, Susan, Sachdev, Perminder, Simmons, Andy, Thompson, Paul M, Visser, Peter‐Jelle, Wahlund, Lars‐Olof, Weiner, Michael W, and Winblad, Bengt

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Brain Disorders, Biomedical Imaging, Clinical Research, Aged, Alzheimer Disease, Atrophy, Female, Functional Laterality, Hippocampus, Humans, Image Processing, Computer-Assisted, Imaging, Three-Dimensional, Internet, Magnetic Resonance Imaging, Male, Middle Aged, Neuroimaging, Organ Size, Reproducibility of Results, Hippocampal volumetry, Magnetic resonance, Alzheimer's disease, Biomarkers, Diagnostic criteria, Enrichment, Clinical trials, Validation, Harmonized protocol, Standard operating procedures, Manual segmentation, EADC-ADNI Working Group on The Harmonized Protocol for Manual Hippocampal Volumetry and for the Alzheimer's Disease Neuroimaging Initiative, Geriatrics, Clinical sciences, Biological psychology
Abstract

BackgroundAn international Delphi panel has defined a harmonized protocol (HarP) for the manual segmentation of the hippocampus on MR. The aim of this study is to study the concurrent validity of the HarP toward local protocols, and its major sources of variance.MethodsFourteen tracers segmented 10 Alzheimer's Disease Neuroimaging Initiative (ADNI) cases scanned at 1.5 T and 3T following local protocols, qualified for segmentation based on the HarP through a standard web-platform and resegmented following the HarP. The five most accurate tracers followed the HarP to segment 15 ADNI cases acquired at three time points on both 1.5 T and 3T.ResultsThe agreement among tracers was relatively low with the local protocols (absolute left/right ICC 0.44/0.43) and much higher with the HarP (absolute left/right ICC 0.88/0.89). On the larger set of 15 cases, the HarP agreement within (left/right ICC range: 0.94/0.95 to 0.99/0.99) and among tracers (left/right ICC range: 0.89/0.90) was very high. The volume variance due to different tracers was 0.9% of the total, comparing favorably to variance due to scanner manufacturer (1.2), atrophy rates (3.5), hemispheric asymmetry (3.7), field strength (4.4), and significantly smaller than the variance due to atrophy (33.5%, P < .001), and physiological variability (49.2%, P < .001).ConclusionsThe HarP has high measurement stability compared with local segmentation protocols, and good reproducibility within and among human tracers. Hippocampi segmented with the HarP can be used as a reference for the qualification of human tracers and automated segmentation algorithms.

Published
2015

12. Novel LAMC3pathogenic variant enriched in Finnish population causes malformations of cortical development and severe epilepsy

Author

Saarela, Anni, Timonen, Oskari, Kirjavainen, Jarkko, Liu, Yawu, Silvennoinen, Katri, Mervaala, Esa, and Kälviäinen, Reetta

Abstract

Recessive LAMC3mutations are recognized to cause epilepsy with cortical malformations characterized by polymicrogyria and pachygyria. The objective of this study was to describe the clinical picture and epilepsy phenotype of four patients with a previously undescribed LAMC3variant. All epilepsy patients treated in Kuopio Epilepsy Center (located in Kuopio, Finland) are offered the possibility to participate in a scientific study investigating biomarkers in epilepsy (Epibiomarker study). We have collected a comprehensive database of the study population, and are currently re‐evaluating our database regarding the patients with developmental and/or epileptic encephalopathy (DEE). If the etiology of epilepsy remains unknown in the clinical setting, we are performing whole exome sequencing to recognize the genetic causes. Among our study population of 323 DEE patients we recognized three patients with similar homozygous LAMC3c.1866del (p.(Phe623Serfs*10)) frameshift variant and one patient with a compound heterozygous mutation where the same frameshift variant was combined with an intronic LAMC3c.4231‐12C>G variant on another allele. All these patients have severe epilepsy and either bilateral agyria‐pachygyria or bilateral polymicrogyria in their clinical MRI scanning. Cortical malformations involve the occipital lobes in all our patients. Epilepsy phenotype is variable as two of our patients have DEE with epileptic spasms progressing to Lennox–Gastaut syndrome and intellectual disability. The other two patients have focal epilepsy without marked cognitive deficit. The four patients are unrelated. LAMC3c.1866del p.(Phe623Serfs*10) frameshift variant is enriched in the Finnish population. Only a few patients with epilepsy caused by LAMC3homozygous or compound heterozygous mutations have been described in the literature. To our knowledge, the variants discovered in our patients have not previously been published. Clinical phenotype appears to be more varied than previously assumed and patients with a milder phenotype and normal cognition have probably remained unrecognized.

Published
2024
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13. Predicting AD conversion: comparison between prodromal AD guidelines and computer assisted PredictAD tool.

Author

Liu, Yawu, Mattila, Jussi, Ruiz, Miguel Ángel Muñoz, Paajanen, Teemu, Koikkalainen, Juha, van Gils, Mark, Herukka, Sanna-Kaisa, Waldemar, Gunhild, Lötjönen, Jyrki, Soininen, Hilkka, and Alzheimer's Disease Neuroimaging Initiative

Subjects
Alzheimer's Disease Neuroimaging Initiative, Humans, Alzheimer Disease, Diagnosis, Computer-Assisted, Sensitivity and Specificity, Decision Support Techniques, Software, Aged, Female, Male, Practice Guidelines as Topic, Prodromal Symptoms, Cognitive Dysfunction, Diagnosis, Computer-Assisted, General Science & Technology
Abstract

PurposeTo compare the accuracies of predicting AD conversion by using a decision support system (PredictAD tool) and current research criteria of prodromal AD as identified by combinations of episodic memory impairment of hippocampal type and visual assessment of medial temporal lobe atrophy (MTA) on MRI and CSF biomarkers.MethodsAltogether 391 MCI cases (158 AD converters) were selected from the ADNI cohort. All the cases had baseline cognitive tests, MRI and/or CSF levels of Aβ1-42 and Tau. Using baseline data, the status of MCI patients (AD or MCI) three years later was predicted using current diagnostic research guidelines and the PredictAD software tool designed for supporting clinical diagnostics. The data used were 1) clinical criteria for episodic memory loss of the hippocampal type, 2) visual MTA, 3) positive CSF markers, 4) their combinations, and 5) when the PredictAD tool was applied, automatically computed MRI measures were used instead of the visual MTA results. The accuracies of diagnosis were evaluated with the diagnosis made 3 years later.ResultsThe PredictAD tool achieved the overall accuracy of 72% (sensitivity 73%, specificity 71%) in predicting the AD diagnosis. The corresponding number for a clinician's prediction with the assistance of the PredictAD tool was 71% (sensitivity 75%, specificity 68%). Diagnosis with the PredictAD tool was significantly better than diagnosis by biomarkers alone or the combinations of clinical diagnosis of hippocampal pattern for the memory loss and biomarkers (p≤0.037).ConclusionWith the assistance of PredictAD tool, the clinician can predict AD conversion more accurately than the current diagnostic criteria.

Published
2013

15. 24-month intervention with a specific multinutrient in people with prodromal Alzheimer's disease (LipiDiDiet): a randomised, double-blind, controlled trial

Author

Hallikainen, Ilona, Hallikainen, Merja, Helisalmi, Seppo, Lappalainen, Tarja, Liu, Yawu, Paajanen, Teemu, Wahlund, Lars-Olof, Freund-Levi, Yvonne, Andreasen, Niels, Hagman, Göran, Lindblom, Stina, Fassbender, Klaus, Riemenschneider, Matthias, Grimm, Marcus OW, Klees-Rollmann, Aline, Luley, Maxine, Lyros, Epameinondas, Schomburg, Robert, Kennel, Jennifer, Ramelli, Daniela, Frölich, Lutz, Hausner, Lucrezia, Laske, Christoph, Leyhe, Thomas, Mychajliw, Christian, Koehler, Niklas, Schiekofer, Stephan, Klünemann, Hans, Schröder, Johannes, Lütjohann, Dieter, Scheltens, Philip, van Rossum, Ineke, Scheltens, Nienke, Bertens, Daniela, ten Kate, Mara, Barkhof, Frederik, Henselmans, Johanna ML, Roks, Gerwin, van Hees, Anneke MJ, Ellison, Noel, Soininen, Hilkka, Solomon, Alina, Visser, Pieter Jelle, Hendrix, Suzanne B, Blennow, Kaj, Kivipelto, Miia, and Hartmann, Tobias

Published
2017
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16. Brain volumes and cortical thickness on MRI in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER)

Author

Stephen, Ruth, Liu, Yawu, Ngandu, Tiia, Antikainen, Riitta, Hulkkonen, Juha, Koikkalainen, Juha, Kemppainen, Nina, Lötjönen, Jyrki, Levälahti, Esko, Parkkola, Riitta, Pippola, Pauliina, Rinne, Juha, Strandberg, Timo, Tuomilehto, Jaakko, Vanninen, Ritva, Kivipelto, Miia, Soininen, Hilkka, Solomon, Alina, and for the FINGER study group

Published
2019
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17. The EADC-ADNI Harmonized Protocol for manual hippocampal segmentation on magnetic resonance: Evidence of validity

Author

Albert, Marilyn S., Bennet, David, Camicioli, Richard, Collins, D. Louis, Dubois, Bruno, Hampel, Harald, denHeijer, Tom, Hock, Christofer, Jagust, William, Launer, Leonore, Maller, Jerome J., Mueller, Susan, Sachdev, Perminder, Simmons, Andy, Thompson, Paul M., Visser, Peter-Jelle, Wahlund, Lars-Olof, Weiner, Michael W., Winblad, Bengt, Frisoni, Giovanni B., Jack, Clifford R., Jr., Bocchetta, Martina, Bauer, Corinna, Frederiksen, Kristian S., Liu, Yawu, Preboske, Gregory, Swihart, Tim, Blair, Melanie, Cavedo, Enrica, Grothe, Michel J., Lanfredi, Mariangela, Martinez, Oliver, Nishikawa, Masami, Portegies, Marileen, Stoub, Travis, Ward, Chadwich, Apostolova, Liana G., Ganzola, Rossana, Wolf, Dominik, Barkhof, Frederik, Bartzokis, George, DeCarli, Charles, Csernansky, John G., deToledo-Morrell, Leyla, Geerlings, Mirjam I., Kaye, Jeffrey, Killiany, Ronald J., Lehéricy, Stephane, Matsuda, Hiroshi, O'Brien, John, Silbert, Lisa C., Scheltens, Philip, Soininen, Hilkka, Teipel, Stefan, Waldemar, Gunhild, Fellgiebel, Andreas, Barnes, Josephine, Firbank, Michael, Gerritsen, Lotte, Henneman, Wouter, Malykhin, Nikolai, Pruessner, Jens C., Wang, Lei, Watson, Craig, Wolf, Henrike, deLeon, Mony, Pantel, Johannes, Ferrari, Clarissa, Bosco, Paolo, Pasqualetti, Patrizio, Duchesne, Simon, Duvernoy, Henri, and Boccardi, Marina

Published
2015
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20. 24-month intervention with a specific multinutrient in people with prodromal Alzheimer's disease (LipiDiDiet): a randomised, double-blind, controlled trial

Author

Soininen, Hilkka, Solomon, Alina, Visser, Pieter Jelle, Hendrix, Suzanne B., Blennow, Kaj, Kivipelto, Miia, Hartmann, Tobias, Hallikainen, Ilona, Hallikainen, Merja, Helisalmi, Seppo, Lappalainen, Tarja, Liu, Yawu, Paajanen, Teemu, Wahlund, Lars-Olof, Freund-Levi, Yvonne, Andreasen, Niels, Hagman, Göran, Lindblom, Stina, Fassbender, Klaus, Riemenschneider, Matthias, Grimm, Marcus O. W., Klees-Rollmann, Aline, Luley, Maxine, Lyros, Epameinondas, Schomburg, Robert, Kennel, Jennifer, Ramelli, Daniela, Frölich, Lutz, Hausner, Lucrezia, Laske, Christoph, Leyhe, Thomas, Mychajliw, Christian, Koehler, Niklas, Schiekofer, Stephan, Klünemann, Hans, Schröder, Johannes, Lütjohann, Dieter, Scheltens, Philip, Van Rossum, Ineke, Scheltens, Nienke, Bertens, Daniela, Ten Kate, Mara, Barkhof, Frederik, Henselmans, Johanna M. L., Roks, Gerwin, Van Hees, Anneke M. J., and Ellison, Noel

Published
2022
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21. Interpretable surface-based detection of focal cortical dysplasias: a Multi-centre Epilepsy Lesion Detection study

Author

Spitzer, Hannah, primary, Ripart, Mathilde, additional, Whitaker, Kirstie, additional, D’Arco, Felice, additional, Mankad, Kshitij, additional, Chen, Andrew A, additional, Napolitano, Antonio, additional, De Palma, Luca, additional, De Benedictis, Alessandro, additional, Foldes, Stephen, additional, Humphreys, Zachary, additional, Zhang, Kai, additional, Hu, Wenhan, additional, Mo, Jiajie, additional, Likeman, Marcus, additional, Davies, Shirin, additional, Güttler, Christopher, additional, Lenge, Matteo, additional, Cohen, Nathan T, additional, Tang, Yingying, additional, Wang, Shan, additional, Chari, Aswin, additional, Tisdall, Martin, additional, Bargallo, Nuria, additional, Conde-Blanco, Estefanía, additional, Pariente, Jose Carlos, additional, Pascual-Diaz, Saül, additional, Delgado-Martínez, Ignacio, additional, Pérez-Enríquez, Carmen, additional, Lagorio, Ilaria, additional, Abela, Eugenio, additional, Mullatti, Nandini, additional, O’Muircheartaigh, Jonathan, additional, Vecchiato, Katy, additional, Liu, Yawu, additional, Caligiuri, Maria Eugenia, additional, Sinclair, Ben, additional, Vivash, Lucy, additional, Willard, Anna, additional, Kandasamy, Jothy, additional, McLellan, Ailsa, additional, Sokol, Drahoslav, additional, Semmelroch, Mira, additional, Kloster, Ane G, additional, Opheim, Giske, additional, Ribeiro, Letícia, additional, Yasuda, Clarissa, additional, Rossi-Espagnet, Camilla, additional, Hamandi, Khalid, additional, Tietze, Anna, additional, Barba, Carmen, additional, Guerrini, Renzo, additional, Gaillard, William Davis, additional, You, Xiaozhen, additional, Wang, Irene, additional, González-Ortiz, Sofía, additional, Severino, Mariasavina, additional, Striano, Pasquale, additional, Tortora, Domenico, additional, Kälviäinen, Reetta, additional, Gambardella, Antonio, additional, Labate, Angelo, additional, Desmond, Patricia, additional, Lui, Elaine, additional, O’Brien, Terence, additional, Shetty, Jay, additional, Jackson, Graeme, additional, Duncan, John S, additional, Winston, Gavin P, additional, Pinborg, Lars H, additional, Cendes, Fernando, additional, Theis, Fabian J, additional, Shinohara, Russell T, additional, Cross, J Helen, additional, Baldeweg, Torsten, additional, Adler, Sophie, additional, and Wagstyl, Konrad, additional

Published
2022
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22. Interpretable surface-based detection of focal cortical dysplasias:a Multi-centre Epilepsy Lesion Detection study

Author

Spitzer, Hannah, Ripart, Mathilde, Whitaker, Kirstie, D’Arco, Felice, Mankad, Kshitij, Chen, Andrew A., Napolitano, Antonio, De Palma, Luca, De Benedictis, Alessandro, Foldes, Stephen, Humphreys, Zachary, Zhang, Kai, Hu, Wenhan, Mo, Jiajie, Likeman, Marcus, Davies, Shirin, Güttler, Christopher, Lenge, Matteo, Cohen, Nathan T., Tang, Yingying, Wang, Shan, Chari, Aswin, Tisdall, Martin, Bargallo, Nuria, Conde-Blanco, Estefanía, Pariente, Jose Carlos, Pascual-Diaz, Saül, Delgado-Martínez, Ignacio, Pérez-Enríquez, Carmen, Lagorio, Ilaria, Abela, Eugenio, Mullatti, Nandini, O’Muircheartaigh, Jonathan, Vecchiato, Katy, Liu, Yawu, Caligiuri, Maria Eugenia, Sinclair, Ben, Vivash, Lucy, Willard, Anna, Kandasamy, Jothy, McLellan, Ailsa, Sokol, Drahoslav, Semmelroch, Mira, Kloster, Ane G., Opheim, Giske, Ribeiro, Letícia, Yasuda, Clarissa, Rossi-Espagnet, Camilla, Hamandi, Khalid, Tietze, Anna, Barba, Carmen, Guerrini, Renzo, Gaillard, William Davis, You, Xiaozhen, Wang, Irene, González-Ortiz, Sofía, Severino, Mariasavina, Striano, Pasquale, Tortora, Domenico, Kälviäinen, Reetta, Gambardella, Antonio, Labate, Angelo, Desmond, Patricia, Lui, Elaine, O’Brien, Terence, Shetty, Jay, Jackson, Graeme, Duncan, John S., Winston, Gavin P., Pinborg, Lars H., Cendes, Fernando, Theis, Fabian J., Shinohara, Russell T., Cross, J. Helen, Baldeweg, Torsten, Adler, Sophie, Wagstyl, Konrad, Spitzer, Hannah, Ripart, Mathilde, Whitaker, Kirstie, D’Arco, Felice, Mankad, Kshitij, Chen, Andrew A., Napolitano, Antonio, De Palma, Luca, De Benedictis, Alessandro, Foldes, Stephen, Humphreys, Zachary, Zhang, Kai, Hu, Wenhan, Mo, Jiajie, Likeman, Marcus, Davies, Shirin, Güttler, Christopher, Lenge, Matteo, Cohen, Nathan T., Tang, Yingying, Wang, Shan, Chari, Aswin, Tisdall, Martin, Bargallo, Nuria, Conde-Blanco, Estefanía, Pariente, Jose Carlos, Pascual-Diaz, Saül, Delgado-Martínez, Ignacio, Pérez-Enríquez, Carmen, Lagorio, Ilaria, Abela, Eugenio, Mullatti, Nandini, O’Muircheartaigh, Jonathan, Vecchiato, Katy, Liu, Yawu, Caligiuri, Maria Eugenia, Sinclair, Ben, Vivash, Lucy, Willard, Anna, Kandasamy, Jothy, McLellan, Ailsa, Sokol, Drahoslav, Semmelroch, Mira, Kloster, Ane G., Opheim, Giske, Ribeiro, Letícia, Yasuda, Clarissa, Rossi-Espagnet, Camilla, Hamandi, Khalid, Tietze, Anna, Barba, Carmen, Guerrini, Renzo, Gaillard, William Davis, You, Xiaozhen, Wang, Irene, González-Ortiz, Sofía, Severino, Mariasavina, Striano, Pasquale, Tortora, Domenico, Kälviäinen, Reetta, Gambardella, Antonio, Labate, Angelo, Desmond, Patricia, Lui, Elaine, O’Brien, Terence, Shetty, Jay, Jackson, Graeme, Duncan, John S., Winston, Gavin P., Pinborg, Lars H., Cendes, Fernando, Theis, Fabian J., Shinohara, Russell T., Cross, J. Helen, Baldeweg, Torsten, Adler, Sophie, and Wagstyl, Konrad

Abstract

One outstanding challenge for machine learning in diagnostic biomedical imaging is algorithm interpretability. A key application is the identification of subtle epileptogenic focal cortical dysplasias (FCDs) from structural MRI. FCDs are difficult to visualize on structural MRI but are often amenable to surgical resection. We aimed to develop an open-source, interpretable, surface-based machine-learning algorithm to automatically identify FCDs on heterogeneous structural MRI data from epilepsy surgery centres worldwide. The Multi-centre Epilepsy Lesion Detection (MELD) Project collated and harmonized a retrospective MRI cohort of 1015 participants, 618 patients with focal FCD-related epilepsy and 397 controls, from 22 epilepsy centres worldwide. We created a neural network for FCD detection based on 33 surface-based features. The network was trained and cross-validated on 50% of the total cohort and tested on the remaining 50% as well as on 2 independent test sites. Multidimensional feature analysis and integrated gradient saliencies were used to interrogate network performance. Our pipeline outputs individual patient reports, which identify the location of predicted lesions, alongside their imaging features and relative saliency to the classifier. On a restricted ‘gold-standard’ subcohort of seizure-free patients with FCD type IIB who had T1 and fluid-attenuated inversion recovery MRI data, the MELD FCD surface-based algorithm had a sensitivity of 85%. Across the entire withheld test cohort the sensitivity was 59% and specificity was 54%. After including a border zone around lesions, to account for uncertainty around the borders of manually delineated lesion masks, the sensitivity was 67%. This multicentre, multinational study with open access protocols and code has developed a robust and interpretable machine-learning algorithm for automated detection of focal cortical dysplasias, giving physicians greater confidence in the identification of subtle M

Published
2022

23. Atlas of lesion locations and postsurgical seizure freedom in focal cortical dysplasia:A MELD study

Author

Wagstyl, Konrad, Whitaker, Kirstie, Raznahan, Armin, Seidlitz, Jakob, Vértes, Petra E., Foldes, Stephen, Humphreys, Zachary, Hu, Wenhan, Mo, Jiajie, Likeman, Marcus, Davies, Shirin, Lenge, Matteo, Cohen, Nathan T., Tang, Yingying, Wang, Shan, Ripart, Mathilde, Chari, Aswin, Tisdall, Martin, Bargallo, Nuria, Conde-Blanco, Estefanía, Pariente, Jose Carlos, Pascual-Diaz, Saül, Delgado-Martínez, Ignacio, Pérez-Enríquez, Carmen, Lagorio, Ilaria, Abela, Eugenio, Mullatti, Nandini, O'Muircheartaigh, Jonathan, Vecchiato, Katy, Liu, Yawu, Caligiuri, Maria, Sinclair, Ben, Vivash, Lucy, Willard, Anna, Kandasamy, Jothy, McLellan, Ailsa, Sokol, Drahoslav, Semmelroch, Mira, Kloster, Ane, Opheim, Giske, Yasuda, Clarissa, Zhang, Kai, Hamandi, Khalid, Barba, Carmen, Guerrini, Renzo, Gaillard, William Davis, You, Xiaozhen, Wang, Irene, González-Ortiz, Sofía, Severino, Mariasavina, Striano, Pasquale, Tortora, Domenico, Kalviainen, Reetta, Gambardella, Antonio, Labate, Angelo, Desmond, Patricia, Lui, Elaine, O'Brien, Terry, Shetty, Jay, Jackson, Graeme, Duncan, John S., Winston, Gavin P., Pinborg, Lars, Cendes, Fernando, Cross, Judith Helen, Baldeweg, Torsten, Adler, Sophie, Wagstyl, Konrad, Whitaker, Kirstie, Raznahan, Armin, Seidlitz, Jakob, Vértes, Petra E., Foldes, Stephen, Humphreys, Zachary, Hu, Wenhan, Mo, Jiajie, Likeman, Marcus, Davies, Shirin, Lenge, Matteo, Cohen, Nathan T., Tang, Yingying, Wang, Shan, Ripart, Mathilde, Chari, Aswin, Tisdall, Martin, Bargallo, Nuria, Conde-Blanco, Estefanía, Pariente, Jose Carlos, Pascual-Diaz, Saül, Delgado-Martínez, Ignacio, Pérez-Enríquez, Carmen, Lagorio, Ilaria, Abela, Eugenio, Mullatti, Nandini, O'Muircheartaigh, Jonathan, Vecchiato, Katy, Liu, Yawu, Caligiuri, Maria, Sinclair, Ben, Vivash, Lucy, Willard, Anna, Kandasamy, Jothy, McLellan, Ailsa, Sokol, Drahoslav, Semmelroch, Mira, Kloster, Ane, Opheim, Giske, Yasuda, Clarissa, Zhang, Kai, Hamandi, Khalid, Barba, Carmen, Guerrini, Renzo, Gaillard, William Davis, You, Xiaozhen, Wang, Irene, González-Ortiz, Sofía, Severino, Mariasavina, Striano, Pasquale, Tortora, Domenico, Kalviainen, Reetta, Gambardella, Antonio, Labate, Angelo, Desmond, Patricia, Lui, Elaine, O'Brien, Terry, Shetty, Jay, Jackson, Graeme, Duncan, John S., Winston, Gavin P., Pinborg, Lars, Cendes, Fernando, Cross, Judith Helen, Baldeweg, Torsten, and Adler, Sophie

Abstract

Objective: Drug-resistant focal epilepsy is often caused by focal cortical dysplasias (FCDs). The distribution of these lesions across the cerebral cortex and the impact of lesion location on clinical presentation and surgical outcome are largely unknown. We created a neuroimaging cohort of patients with individually mapped FCDs to determine factors associated with lesion location and predictors of postsurgical outcome. Methods: The MELD (Multi-centre Epilepsy Lesion Detection) project collated a retrospective cohort of 580 patients with epilepsy attributed to FCD from 20 epilepsy centers worldwide. Magnetic resonance imaging-based maps of individual FCDs with accompanying demographic, clinical, and surgical information were collected. We mapped the distribution of FCDs, examined for associations between clinical factors and lesion location, and developed a predictive model of postsurgical seizure freedom. Results: FCDs were nonuniformly distributed, concentrating in the superior frontal sulcus, frontal pole, and temporal pole. Epilepsy onset was typically before the age of 10 years. Earlier epilepsy onset was associated with lesions in primary sensory areas, whereas later epilepsy onset was associated with lesions in association cortices. Lesions in temporal and occipital lobes tended to be larger than frontal lobe lesions. Seizure freedom rates varied with FCD location, from around 30% in visual, motor, and premotor areas to 75% in superior temporal and frontal gyri. The predictive model of postsurgical seizure freedom had a positive predictive value of 70% and negative predictive value of 61%. Significance: FCD location is an important determinant of its size, the age at epilepsy onset, and the likelihood of seizure freedom postsurgery. Our atlas of lesion locations can be used to guide the radiological search for subtle lesions in individual patients. Our atlas of regional seizure freedom rates and associated predictive model can be used to estimate individua

Published
2022

28. Research diagnostic criteria for Alzheimer’s disease: findings from the LipiDiDiet randomized controlled trial

Author

Rosenberg, Anna, Solomon, Alina, Soininen, Hilkka, Visser, Pieter Jelle, Blennow, Kaj, Hartmann, Tobias, Kivipelto, Miia, Hallikainen, Ilona, Hallikainen, Merja, Helisalmi, Seppo, Lappalainen, Tarja, Liu, Yawu, Paajanen, Teemu, Wahlund, Lars-Olof, Freund-Levi, Yvonne, Hagman, G. ran, Fassbender, Klaus, Riemenschneider, Matthias, Grimm, Marcus O. W., Klees-Rollmann, Aline, Luley, Maxine, Lyros, Epameinondas, Schomburg, Robert, Ramelli, Daniela, Kennel, Jennifer, Frölich, Lutz, Hausner, Lucrezia, Laske, Christoph, Leyhe, Thomas, Mychajliw, Christian, Koehler, Niklas, Schiekofer, Stephan, Klünemann, Hans, Schröder, Johannes, Lütjohann, Dieter, Scheltens, Philip, van Rossum, Ineke, Scheltens, Nienke, Bertens, Daniela, ten Kate, Mara, Barkhof, Frederik, Ingala, Silvia, Henselmans, Johanna M. L., Roks, Gerwin, van Hees, Anneke M. J., van Oudenhoven, Floor M., Hendrix, Suzanne B., Ellison, Noel, Neurology, Amsterdam Neuroscience - Neurodegeneration, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, and Amsterdam Neuroscience - Neuroinfection & -inflammation

Abstract

Background: To explore the utility of the International Working Group (IWG)-1 criteria in recruitment for Alzheimer’s disease (AD) clinical trials, we applied the more recently proposed research diagnostic criteria to individuals enrolled in a randomized controlled prevention trial (RCT) and assessed their disease progression. Methods: The multinational LipiDiDiet RCT targeted 311 individuals with IWG-1 defined prodromal AD. Based on centrally analyzed baseline biomarkers, participants were classified according to the IWG-2 and National Institute on Aging–Alzheimer’s Association (NIA-AA) 2011 and 2018 criteria. Linear mixed models were used to investigate the 2-year change in cognitive and functional performance (Neuropsychological Test Battery NTB Z scores, Clinical Dementia Rating-Sum of Boxes CDR-SB) (criteria × time interactions; baseline score, randomization group, sex, Mini-Mental State Examination (MMSE), and age also included in the models). Cox models adjusted for randomization group, MMSE, sex, age, and study site were used to investigate the risk of progression to dementia over 2 years. Results: In total, 88%, 86%, and 69% of participants had abnormal cerebrospinal fluid (CSF) β-amyloid, total tau, and phosphorylated tau, respectively; 64% had an A+T+N+ profile (CSF available for N = 107). Cognitive-functional decline appeared to be more pronounced in the IWG-2 prodromal AD, NIA-AA 2011 high and intermediate AD likelihood, and NIA-AA 2018 AD groups, but few significant differences were observed between the groups within each set of criteria. Hazard ratio (95% CI) for dementia was 4.6 (1.6–13.7) for IWG-2 prodromal AD (reference group no prodromal AD), 7.4 (1.0–54.7) for NIA-AA 2011 high AD likelihood (reference group suspected non-AD pathology SNAP), and 9.4 (1.2–72.7) for NIA-AA 2018 AD (reference group non-Alzheimer’s pathologic change). Compared with the NIA-AA 2011 high AD likelihood group (abnormal β-amyloid and neuronal injury markers), disease progression was similar in the intermediate AD likelihood group (medial temporal lobe atrophy; no CSF available). Conclusions: Despite being less restrictive than the other criteria, the IWG-1 criteria reliably identified individuals with AD pathology. More pragmatic and easily applicable selection criteria might be preferred due to feasibility in certain situations, e.g., in multidomain prevention trials that do not specifically target β-amyloid/tau pathologies. Trial registration: Netherlands Trial Register, NL1620. Registered on 9 March 2009.

Published
2021
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30. Change in CAIDE Dementia Risk Score and Neuroimaging Biomarkers During a 2-Year Multidomain Lifestyle Randomized Controlled Trial : Results of a Post-Hoc Subgroup Analysis

Author

Stephen, Ruth, Ngandu, Tiia, Liu, Yawu, Peltonen, Markku, Antikainen, Riitta, Kemppainen, Nina, Laatikainen, Tiina, Lötjönen, Jyrki, Rinne, Juha, Strandberg, Timo, Tuomilehto, Jaakko, Vanninen, Ritva, Soininen, Hilkka, Kivipelto, Miia, Solomon, Alina, for the FINGER Study Group, HUS Internal Medicine and Rehabilitation, Timo Strandberg / Principal Investigator, Department of Medicine, Clinicum, University of Helsinki, Tampere University, and Seinäjoen keskussairaala VA

Subjects
Male, Aging, THE JOURNAL OF GERONTOLOGY: Biological Sciences, PREDICTION, HIPPOCAMPAL VOLUME, Health Behavior, Neuroimaging, BLOOD-PRESSURE, PROGRESSION, Gerona/1, Risk Assessment, Hippocampus, Factors Associated With Cognitive Decline and Aging, AcademicSubjects/MED00280, Cognition, Humans, BRAIN ATROPHY, Correlation of Data, Geriatric Assessment, Aged, Prevention, NEURODEGENERATION, Organ Size, PREVENT COGNITIVE IMPAIRMENT, Brain Cortical Thickness, Magnetic Resonance Imaging, FINNISH GERIATRIC INTERVENTION, Heart Disease Risk Factors, Positron-Emission Tomography, 3121 General medicine, internal medicine and other clinical medicine, LINK, Risk reduction, AcademicSubjects/SCI00960, SERUM-LIPIDS, Female, Dementia, 3111 Biomedicine, Risk Reduction Behavior
Abstract

The CAIDE (Cardiovascular Risk Factors, Aging and Dementia) Risk Score is a validated tool estimating dementia risk. It was previously associated with imaging biomarkers. However, associations between dementia risk scores (including CAIDE) and dementia-related biomarkers have not been studied in the context of an intervention. This study investigated associations between change in CAIDE score and change in neuroimaging biomarkers (brain magnetic resonance imaging [MRI] and Pittsburgh Compound B-positron emission tomography [PiB-PET] measures) during the 2-year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) (post-hoc analyses). FINGER targeted at-risk older adults, aged 60-77 years, from the general population. Participants were randomized to either multidomain intervention (diet, exercise, cognitive training, and vascular risk management) or control group (general health advice). Neuroimaging (MRI and PiB-PET) data from baseline and 2-year visits were used. A toal of 112 participants had repeated brain MRI measures (hippocampal, total gray matter, and white matter lesion volumes, and Alzheimer's disease signature cortical thickness). Repeated PiB-PET scans were available for 39 participants. Reduction in CAIDE score (indicating lower dementia risk) during the intervention was associated with less decline in hippocampus volume in the intervention group, but not the control group (Randomization group × CAIDE change interaction β coefficient =-0.40, p =. 02). Associations for other neuroimaging measures were not significant. The intervention may have benefits on hippocampal volume in individuals who succeed in improving their overall risk level as indicated by a reduction in CAIDE score. This exploratory finding requires further testing and validation in larger studies. publishedVersion

Published
2021

32. Interpretable surface-based detection of focal cortical dysplasias: a MELD study

Author

Spitzer, Hannah, primary, Ripart, Mathilde, additional, Whitaker, Kirstie, additional, Napolitano, Antonio, additional, De Palma, Luca, additional, De Benedictis, Alessandro, additional, Foldes, Stephen, additional, Humphreys, Zachary, additional, Zhang, Kai, additional, Hu, Wenhan, additional, Mo, Jiajie, additional, Likeman, Marcus, additional, Davies, Shirin, additional, Guttler, Christopher, additional, Lenge, Matteo, additional, Cohen, Nathan T., additional, Tang, Yingying, additional, Wang, Shan, additional, Chari, Aswin, additional, Tisdall, Martin, additional, Bargallo, Nuria, additional, Conde-Blanco, Estefanía, additional, Pariente, Jose Carlos, additional, Pascual-Diaz, Saül, additional, Delgado-Martínez, Ignacio, additional, Pérez-Enríquez, Carmen, additional, Lagorio, Ilaria, additional, Abela, Eugenio, additional, Mullatti, Nandini, additional, O’Muircheartaigh, Jonathan, additional, Vecchiato, Katy, additional, Liu, Yawu, additional, Caligiuri, Maria, additional, Sinclair, Ben, additional, Vivash, Lucy, additional, Willard, Anna, additional, Kandasamy, Jothy, additional, McLellan, Ailsa, additional, Sokol, Drahoslav, additional, Semmelroch, Mira, additional, Kloster, Ane, additional, Opheim, Giske, additional, Ribeiro, Letícia, additional, Yasuda, Clarissa, additional, Rossi-Espagnet, Camilla, additional, Hamandi, Khalid, additional, Tietze, Anna, additional, Barba, Carmen, additional, Guerrini, Renzo, additional, Gaillard, William Davis, additional, You, Xiaozhen, additional, Wang, Irene, additional, González-Ortiz, Sofía, additional, Severino, Mariasavina, additional, Striano, Pasquale, additional, Tortora, Domenico, additional, Kalviainen, Reetta, additional, Gambardella, Antonio, additional, Labate, Angelo, additional, Desmond, Patricia, additional, Lui, Elaine, additional, O’Brien, Terence, additional, Shetty, Jay, additional, Jackson, Graeme, additional, Duncan, John, additional, Winston, Gavin, additional, Pinborg, Lars, additional, Cendes, Fernando, additional, Theis, Fabian J., additional, Shinohara, Russell T., additional, Cross, J Helen, additional, Baldeweg, Torsten, additional, Adler, Sophie, additional, and Wagstyl, Konrad, additional

Published
2021
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33. Occupational complexity and neuroimaging measures of structural MRI and PET‐amyloid in a randomized controlled trial: FINGER

Author

Rydström, Anders, primary, Stephen, Ruth, additional, Kåreholt, Ingemar, additional, Darin‐Mattsson, Alexander, additional, Liu, Yawu, additional, Ngandu, Tiia, additional, Rinne, Juha O, additional, Kemppainen, Nina, additional, Antikainen, Riitta L, additional, Bäckman, Lars, additional, Sindi, Shireen, additional, Soininen, Hilkka, additional, Strandberg, Timo, additional, Tuomilehto, Jaakko, additional, Kivipelto, Miia, additional, Solomon, Alina, additional, and Mangialasche, Francesca, additional

Published
2021
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34. Atlas of lesion locations and postsurgical seizure freedom in focal cortical dysplasia: A MELD study

Author

Wagstyl, Konrad, primary, Whitaker, Kirstie, additional, Raznahan, Armin, additional, Seidlitz, Jakob, additional, Vértes, Petra E., additional, Foldes, Stephen, additional, Humphreys, Zachary, additional, Hu, Wenhan, additional, Mo, Jiajie, additional, Likeman, Marcus, additional, Davies, Shirin, additional, Lenge, Matteo, additional, Cohen, Nathan T., additional, Tang, Yingying, additional, Wang, Shan, additional, Ripart, Mathilde, additional, Chari, Aswin, additional, Tisdall, Martin, additional, Bargallo, Nuria, additional, Conde‐Blanco, Estefanía, additional, Pariente, Jose Carlos, additional, Pascual‐Diaz, Saül, additional, Delgado‐Martínez, Ignacio, additional, Pérez‐Enríquez, Carmen, additional, Lagorio, Ilaria, additional, Abela, Eugenio, additional, Mullatti, Nandini, additional, O'Muircheartaigh, Jonathan, additional, Vecchiato, Katy, additional, Liu, Yawu, additional, Caligiuri, Maria, additional, Sinclair, Ben, additional, Vivash, Lucy, additional, Willard, Anna, additional, Kandasamy, Jothy, additional, McLellan, Ailsa, additional, Sokol, Drahoslav, additional, Semmelroch, Mira, additional, Kloster, Ane, additional, Opheim, Giske, additional, Yasuda, Clarissa, additional, Zhang, Kai, additional, Hamandi, Khalid, additional, Barba, Carmen, additional, Guerrini, Renzo, additional, Gaillard, William Davis, additional, You, Xiaozhen, additional, Wang, Irene, additional, González‐Ortiz, Sofía, additional, Severino, Mariasavina, additional, Striano, Pasquale, additional, Tortora, Domenico, additional, Kalviainen, Reetta, additional, Gambardella, Antonio, additional, Labate, Angelo, additional, Desmond, Patricia, additional, Lui, Elaine, additional, O'Brien, Terry, additional, Shetty, Jay, additional, Jackson, Graeme, additional, Duncan, John S., additional, Winston, Gavin P., additional, Pinborg, Lars, additional, Cendes, Fernando, additional, Cross, Judith Helen, additional, Baldeweg, Torsten, additional, and Adler, Sophie, additional

Published
2021
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37. Role of Dynamic Susceptibility Contrast Perfusion MRI in Glioma Progression Evaluation

Author

Quan, Guanmin, Zhang, Kexin, Liu, Yawu, Ren, Jia-Liang, Huang, Deyou, Wang, Weiwei, and Yuan, Tao

Subjects
Article Subject
Abstract

Accurately and quickly differentiating true progression from pseudoprogression in glioma patients is still a challenge. This study aims to explore if dynamic susceptibility contrast- (DSC-) MRI can improve the evaluation of glioma progression. We enrolled 65 glioma patients with suspected gadolinium-enhancing lesion. Longitudinal MRI follow-up (mean 590 days, range: 210–2670 days) or re-operation (n = 3) was used to confirm true progression (n = 51) and pseudoprogression (n = 14). We assessed the diagnostic performance of each MRI variable and the different combinations. Our results showed that the relative cerebral blood volume (rCBV) in the true progression group (1.094, 95%CI: 1.135–1.636) was significantly higher than that of the pseudoprogression group (0.541 ± 0.154) p

Published
2021
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43. White Matter Changes on Diffusion Tensor Imaging in the FINGER Randomized Controlled Trial

Author

FINGER Study Grp, Stephen, Ruth, Solomon, Alina, Ngandu, Tiia, Levälahti, Esko, Rinne, Juha O., Kemppainen, Nina, Parkkola, Riitta, Antikainen, Riitta, Strandberg, Timo, Kivipelto, Miia, Soininen, Hilkka, Liu, Yawu, HUS Internal Medicine and Rehabilitation, Timo Strandberg / Principal Investigator, Department of Medicine, Clinicum, Geriatrian yksikkö, University of Helsinki, and Helsinki University Hospital Area

Subjects
3112 Neurosciences, PREVENT COGNITIVE IMPAIRMENT, Alzheimer's disease, DEGRADATION, diffusion tensor imaging, 3124 Neurology and psychiatry, INTEGRITY, ALZHEIMERS-DISEASE, FINNISH GERIATRIC INTERVENTION, AGE, DYSMYELINATION, randomized controlled trial, ASTROCYTIC HYPERTROPHY, VOXELWISE ANALYSIS, sense organs, MICROSTRUCTURE, dementia
Abstract

Background: Early pathological changes in white matter microstructure can be studied using the diffusion tensor imaging (DTI). It is not only important to study these subtle pathological changes leading to cognitive decline, but also to ascertain how an intervention would impact the white matter microstructure and cognition in persons at-risk of dementia. Objectives: To study the impact of a multidomain lifestyle intervention on white matter and cognitive changes during the 2-year Finnish Geriatric Intervention Study to prevent Cognitive Impairment and Disability (FINGER), a randomized controlled trial in at-risk older individuals (age 60-77 years) from the general population. Methods: This exploratory study consisted of a subsample of 60 FINGER participants. Participants were randomized to either a multidomain intervention (diet, exercise, cognitive training, and vascular risk management, n = 34) or control group (general health advice, n = 26). All underwent baseline and 2-year brain DTI. Changes in fractional anisotropy (FA), diffusivity along domain (F1) and non-domain (F2) diffusion orientations, mean diffusivity (MD), axial diffusivity (AxD), radial diffusivity (RD), and their correlations with cognitive changes during the 2-year multidomain intervention were analyzed. Results: FA decreased, and cognition improved more in the intervention group compared to the control group (p

Published
2020

44. MELD Project: Atlas of lesion locations and postsurgical seizure freedom in focal cortical dysplasia

Author

Wagstyl, Konrad, primary, Whitaker, Kirstie, additional, Raznahan, Armin, additional, Seidlitz, Jakob, additional, Vértes, Petra E, additional, Foldes, Stephen, additional, Humphreys, Zachary, additional, Hu, Wenhan, additional, Mo, Jiajie, additional, Likeman, Marcus, additional, Davies, Shirin, additional, Lenge, Matteo, additional, Cohen, Nathan T, additional, Tang, Yingying, additional, Wang, Shan, additional, Ripart, Mathilde, additional, Chari, Aswin, additional, Tisdall, Martin, additional, Bargallo, Nuria, additional, Conde-Blanco, Estefanía, additional, Pariente, Jose Carlos, additional, Pascual-Diaz, Saül, additional, Delgado-Martínez, Ignacio, additional, Pérez-Enríquez, Carmen, additional, Lagorio, Ilaria, additional, Abela, Eugenio, additional, Mullatti, Nandini, additional, O’Muircheartaigh, Jonathan, additional, Vecchiato, Katy, additional, Liu, Yawu, additional, Caligiuri, Maria, additional, Sinclair, Ben, additional, Vivash, Lucy, additional, Willard, Anna, additional, Kandasamy, Jothy, additional, McLellan, Ailsa, additional, Sokol, Drahoslav, additional, Semmelroch, Mira, additional, Kloster, Ane, additional, Opheim, Giske, additional, Yasuda, Clarissa, additional, Zhang, Kai, additional, Hamandi, Khalid, additional, Barba, Carmen, additional, Guerrini, Renzo, additional, Gaillard, William Davis, additional, You, Xiaozhen, additional, Wang, Irene, additional, González-Ortiz, Sofía, additional, Severino, Mariasavina, additional, Striano, Pasquale, additional, Tortora, Domenico, additional, Kalviainen, Reetta, additional, Gambardella, Antonio, additional, Labate, Angelo, additional, Desmond, Patricia, additional, Lui, Elaine, additional, O’Brien, Terry, additional, Shetty, Jay, additional, Jackson, Graeme, additional, Duncan, John S, additional, Winston, Gavin P, additional, Pinborg, Lars, additional, Cendes, Fernando, additional, Cross, J Helen, additional, Baldeweg, Torsten, additional, and Adler, Sophie, additional

Published
2021
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47. White Matter Hyperintensities Are No Major Confounder for Alzheimer’s Disease Cerebrospinal Fluid Biomarkers

Author

van Waalwijk van Doorn, Linda J.C., primary, Ghafoorian, Mohsen, additional, van Leijsen, Esther M.C., additional, Claassen, Jurgen A.H.R., additional, Arighi, Andrea, additional, Bozzali, Marco, additional, Cannas, Jorge, additional, Cavedo, Enrica, additional, Eusebi, Paolo, additional, Farotti, Lucia, additional, Fenoglio, Chiara, additional, Fortea, Juan, additional, Frisoni, Giovanni B., additional, Galimberti, Daniela, additional, Greco, Viviana, additional, Herukka, Sanna-Kaisa, additional, Liu, Yawu, additional, Lleó, Alberto, additional, de Mendonça, Alexandre, additional, Nobili, Flavio M., additional, Parnetti, Lucilla, additional, Picco, Agnese, additional, Pikkarainen, Maria, additional, Salvadori, Nicola, additional, Scarpini, Elio, additional, Soininen, Hilkka, additional, Tarducci, Roberto, additional, Urbani, Andrea, additional, Vilaplana, Eduard, additional, Meulenbroek, Olga, additional, Platel, Bram, additional, Verbeek, Marcel M., additional, and Kuiperij, H. Bea, additional

Published
2021
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50. Detecting Amyloid Positivity in Elderly With Increased Risk of Cognitive Decline

Author

Pekkala, Timo, primary, Hall, Anette, additional, Ngandu, Tiia, additional, Gils, Mark van, additional, Helisalmi, Seppo, additional, Hänninen, Tuomo, additional, Kemppainen, Nina, additional, Liu, Yawu, additional, Lötjönen, Jyrki, additional, Paajanen, Teemu, additional, Rinne, Juha O., additional, Soininen, Hilkka, additional, Kivipelto, Miia, additional, and Solomon, Alina, additional

Published
2020
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