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2. Pain mechanisms in the transgender individual: a review.

Author

Anger, Jennifer, Case, Laura, Baranowski, Andrew, Berger, Ardin, Craft, Rebecca, Damitz, Lyn, Gabriel, Rodney, Harrison, Tracy, Kaptein, Kirsten, Lee, Sanghee, Murphy, Anne, Said, Engy, Smith, Stacey, Thomas, David, Valdés Hernández, Maria, Trasvina, Victor, Wesselmann, Ursula, and Yaksh, Tony

Subjects
gender affirming care, gender binary system, hormone replacement therapy (HRT), post operative pain, transgender (GLBT) issues
Abstract

SPECIFIC AIM: Provide an overview of the literature addressing major areas pertinent to pain in transgender persons and to identify areas of primary relevance for future research. METHODS: A team of scholars that have previously published on different areas of related research met periodically though zoom conferencing between April 2021 and February 2023 to discuss relevant literature with the goal of providing an overview on the incidence, phenotype, and mechanisms of pain in transgender patients. Review sections were written after gathering information from systematic literature searches of published or publicly available electronic literature to be compiled for publication as part of a topical series on gender and pain in the Frontiers in Pain Research. RESULTS: While transgender individuals represent a significant and increasingly visible component of the population, many researchers and clinicians are not well informed about the diversity in gender identity, physiology, hormonal status, and gender-affirming medical procedures utilized by transgender and other gender diverse patients. Transgender and cisgender people present with many of the same medical concerns, but research and treatment of these medical needs must reflect an appreciation of how differences in sex, gender, gender-affirming medical procedures, and minoritized status impact pain. CONCLUSIONS: While significant advances have occurred in our appreciation of pain, the review indicates the need to support more targeted research on treatment and prevention of pain in transgender individuals. This is particularly relevant both for gender-affirming medical interventions and related medical care. Of particular importance is the need for large long-term follow-up studies to ascertain best practices for such procedures. A multi-disciplinary approach with personalized interventions is of particular importance to move forward.

Published
2024

3. DNAm scores for serum GDF15 and NT-proBNP levels associate with a range of traits affecting the body and brain

Author

Gadd, Danni A., Smith, Hannah M., Mullin, Donncha, Chybowska, Ola, Hillary, Robert F., Kimenai, Dorien M., Bernabeu, Elena, Cheng, Yipeng, Fawns-Ritchie, Chloe, Campbell, Archie, Page, Danielle, Taylor, Adele, Corley, Janie, Del C. Valdés-Hernández, Maria, Maniega, Susana Muñoz, Bastin, Mark E., Wardlaw, Joanna M., Walker, Rosie M., Evans, Kathryn L., McIntosh, Andrew M., Hayward, Caroline, Russ, Tom C., Harris, Sarah E., Welsh, Paul, Sattar, Naveed, Cox, Simon R., McCartney, Daniel L., and Marioni, Riccardo E.

Published
2024
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4. Epigenetic scores of blood-based proteins as biomarkers of general cognitive function and brain health

Author

Smith, Hannah M., Moodie, Joanna E., Monterrubio-Gómez, Karla, Gadd, Danni A., Hillary, Robert F., Chybowska, Aleksandra D., McCartney, Daniel L., Campbell, Archie, Redmond, Paul, Page, Danielle, Taylor, Adele, Corley, Janie, Harris, Sarah E., Valdés Hernández, Maria, Muñoz Maniega, Susana, Bastin, Mark E., Wardlaw, Joanna M., Deary, Ian J., Boardman, James P., Mullin, Donncha S., Russ, Tom C., Cox, Simon R., and Marioni, Riccardo E.

Published
2024
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5. Stochastic Uncertainty Quantification Techniques Fail to Account for Inter-analyst Variability in White Matter Hyperintensity Segmentation

Author

Philps, Ben, del C. Valdes Hernandez, Maria, Munoz Maniega, Susana, Bastin, Mark E., Sakka, Eleni, Clancy, Una, Wardlaw, Joanna M., Bernabeu, Miguel O., Goos, Gerhard, Series Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Yap, Moi Hoon, editor, Kendrick, Connah, editor, Behera, Ardhendu, editor, Cootes, Timothy, editor, and Zwiggelaar, Reyer, editor

Published
2024
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6. Epigenetic and integrative cross-omics analyses of cerebral white matter hyperintensities on MRI

Author

Yang, Yunju, Knol, Maria J, Wang, Ruiqi, Mishra, Aniket, Liu, Dan, Luciano, Michelle, Teumer, Alexander, Armstrong, Nicola, Bis, Joshua C, Jhun, Min A, Li, Shuo, Adams, Hieab HH, Aziz, Nasir Ahmad, Bastin, Mark E, Bourgey, Mathieu, Brody, Jennifer A, Frenzel, Stefan, Gottesman, Rebecca F, Hosten, Norbert, Hou, Lifang, Kardia, Sharon LR, Lohner, Valerie, Marquis, Pascale, Maniega, Susana Muñoz, Satizabal, Claudia L, Sorond, Farzaneh A, Valdés Hernández, Maria C, van Duijn, Cornelia M, Vernooij, Meike W, Wittfeld, Katharina, Yang, Qiong, Zhao, Wei, Boerwinkle, Eric, Levy, Daniel, Deary, Ian J, Jiang, Jiyang, Mather, Karen A, Mosley, Thomas H, Psaty, Bruce M, Sachdev, Perminder S, Smith, Jennifer A, Sotoodehnia, Nona, DeCarli, Charles S, Breteler, Monique MB, Ikram, M Arfan, Grabe, Hans J, Wardlaw, Joanna, Longstreth, WT, Launer, Lenore J, Seshadri, Sudha, Debette, Stephanie, and Fornage, Myriam

Subjects
Health Sciences, Genetics, Aging, Brain Disorders, Neurosciences, Human Genome, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Middle Aged, Humans, Aged, White Matter, Genome-Wide Association Study, Brain, DNA Methylation, Magnetic Resonance Imaging, Epigenesis, Genetic, Protein-Arginine N-Methyltransferases, Repressor Proteins, epigenome-wide association study, white matter hyperintensities, cerebral small vessel disease, integrative cross-omics analysis, blood-brain barrier dysfunction, blood–brain barrier dysfunction, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

Cerebral white matter hyperintensities on MRI are markers of cerebral small vessel disease, a major risk factor for dementia and stroke. Despite the successful identification of multiple genetic variants associated with this highly heritable condition, its genetic architecture remains incompletely understood. More specifically, the role of DNA methylation has received little attention. We investigated the association between white matter hyperintensity burden and DNA methylation in blood at ∼450 000 cytosine-phosphate-guanine (CpG) sites in 9732 middle-aged to older adults from 14 community-based studies. Single CpG and region-based association analyses were carried out. Functional annotation and integrative cross-omics analyses were performed to identify novel genes underlying the relationship between DNA methylation and white matter hyperintensities. We identified 12 single CpG and 46 region-based DNA methylation associations with white matter hyperintensity burden. Our top discovery single CpG, cg24202936 (P = 7.6 × 10-8), was associated with F2 expression in blood (P = 6.4 × 10-5) and co-localized with FOLH1 expression in brain (posterior probability = 0.75). Our top differentially methylated regions were in PRMT1 and in CCDC144NL-AS1, which were also represented in single CpG associations (cg17417856 and cg06809326, respectively). Through Mendelian randomization analyses cg06809326 was putatively associated with white matter hyperintensity burden (P = 0.03) and expression of CCDC144NL-AS1 possibly mediated this association. Differentially methylated region analysis, joint epigenetic association analysis and multi-omics co-localization analysis consistently identified a role of DNA methylation near SH3PXD2A, a locus previously identified in genome-wide association studies of white matter hyperintensities. Gene set enrichment analyses revealed functions of the identified DNA methylation loci in the blood-brain barrier and in the immune response. Integrative cross-omics analysis identified 19 key regulatory genes in two networks related to extracellular matrix organization, and lipid and lipoprotein metabolism. A drug-repositioning analysis indicated antihyperlipidaemic agents, more specifically peroxisome proliferator-activated receptor-alpha, as possible target drugs for white matter hyperintensities. Our epigenome-wide association study and integrative cross-omics analyses implicate novel genes influencing white matter hyperintensity burden, which converged on pathways related to the immune response and to a compromised blood-brain barrier possibly due to disrupted cell-cell and cell-extracellular matrix interactions. The results also suggest that antihyperlipidaemic therapy may contribute to lowering risk for white matter hyperintensities possibly through protection against blood-brain barrier disruption.

Published
2023

10. Influence of threshold selection and image sequence in in-vivo segmentation of enlarged perivascular spaces

Author

Valdés Hernández, Maria del C., Duarte Coello, Roberto, Xu, William, Bernal, José, Cheng, Yajun, Ballerini, Lucia, Wiseman, Stewart J., Chappell, Francesca M., Clancy, Una, Jaime García, Daniela, Arteaga Reyes, Carmen, Zhang, Jun-Fang, Liu, Xiaodi, Hewins, Will, Stringer, Michael, Doubal, Fergus, Thrippleton, Michael J., Jochems, Angela, Brown, Rosalind, and Wardlaw, Joanna M.

Published
2024
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12. Reproducibility in the absence of selective reporting: An illustration from large‐scale brain asymmetry research

Author

Kong, Xiang‐Zhen, Mathias, Samuel R, Guadalupe, Tulio, Abé, Christoph, Agartz, Ingrid, Akudjedu, Theophilus N, Aleman, Andre, Alhusaini, Saud, Allen, Nicholas B, Ames, David, Andreassen, Ole A, Vasquez, Alejandro Arias, Armstrong, Nicola J, Asherson, Phil, Bergo, Felipe, Bastin, Mark E, Batalla, Albert, Bauer, Jochen, Baune, Bernhard T, Baur‐Streubel, Ramona, Biederman, Joseph, Blaine, Sara K, Boedhoe, Premika, Bøen, Erlend, Bose, Anushree, Bralten, Janita, Brandeis, Daniel, Brem, Silvia, Brodaty, Henry, Yüksel, Dilara, Brooks, Samantha J, Buitelaar, Jan, Bürger, Christian, Bülow, Robin, Calhoun, Vince, Calvo, Anna, Canales‐Rodríguez, Erick Jorge, Cannon, Dara M, Caparelli, Elisabeth C, Castellanos, Francisco X, Cendes, Fernando, Chaim‐Avancini, Tiffany Moukbel, Chantiluke, Kaylita, Chen, Qun‐lin, Chen, Xiayu, Cheng, Yuqi, Christakou, Anastasia, Clark, Vincent P, Coghill, David, Connolly, Colm G, Conzelmann, Annette, Córdova‐Palomera, Aldo, Cousijn, Janna, Crow, Tim, Cubillo, Ana, Dannlowski, Udo, de Bruttopilo, Sara Ambrosino, de Zeeuw, Patrick, Deary, Ian J, Demeter, Damion V, Di Martino, Adriana, Dickie, Erin W, Dietsche, Bruno, Doan, Nhat Trung, Doherty, Colin P, Doyle, Alysa, Durston, Sarah, Earl, Eric, Ehrlich, Stefan, Ekman, Carl Johan, Elvsåshagen, Torbjørn, Epstein, Jeffery N, Fair, Damien A, Faraone, Stephen V, Fernández, Guillén, Flint, Claas, Filho, Geraldo Busatto, Förster, Katharina, Fouche, Jean‐Paul, Foxe, John J, Frodl, Thomas, Fuentes‐Claramonte, Paola, Fullerton, Janice M, Garavan, Hugh, do Santos Garcia, Danielle, Gotlib, Ian H, Goudriaan, Anna E, Grabe, Hans Jörgen, Groenewold, Nynke A, Grotegerd, Dominik, Gruber, Oliver, Gurholt, Tiril, Haavik, Jan, Hahn, Tim, Hansell, Narelle K, Harris, Mathew A, Hartman, Catharina A, del Carmen Valdés Hernández, Maria, and Heslenfeld, Dirk

Subjects
Biological Psychology, Psychology, Neurosciences, Neurological, Adolescent, Adult, Aged, Brain Cortical Thickness, Cerebral Cortex, Datasets as Topic, Humans, Magnetic Resonance Imaging, Middle Aged, Multicenter Studies as Topic, Neuroimaging, Publication Bias, Reproducibility of Results, Young Adult, ENIGMA Laterality Working Group, P-hacking, multisite collaboration, publication bias, reproducibility, team science, Cognitive Sciences, Experimental Psychology, Biological psychology, Cognitive and computational psychology
Abstract

The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p-hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left-right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta-analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an "ideal publishing environment," that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically-used sample sizes.

Published
2022

13. Proper Scoring Loss Functions Are Simple and Effective for Uncertainty Quantification of White Matter Hyperintensities

Author

Philps, Ben, Valdes Hernandez, Maria del C., Bernabeu Llinares, Miguel, Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Sudre, Carole H., editor, Baumgartner, Christian F., editor, Dalca, Adrian, editor, Mehta, Raghav, editor, Qin, Chen, editor, and Wells, William M., editor

Published
2023
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14. Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease

Author

Duperron, Marie-Gabrielle, Knol, Maria J., Le Grand, Quentin, Evans, Tavia E., Mishra, Aniket, Tsuchida, Ami, Roshchupkin, Gennady, Konuma, Takahiro, Trégouët, David-Alexandre, Romero, Jose Rafael, Frenzel, Stefan, Luciano, Michelle, Hofer, Edith, Bourgey, Mathieu, Dueker, Nicole D., Delgado, Pilar, Hilal, Saima, Tankard, Rick M., Dubost, Florian, Shin, Jean, Saba, Yasaman, Armstrong, Nicola J., Bordes, Constance, Bastin, Mark E., Beiser, Alexa, Brodaty, Henry, Bülow, Robin, Carrera, Caty, Chen, Christopher, Cheng, Ching-Yu, Deary, Ian J., Gampawar, Piyush G., Himali, Jayandra J., Jiang, Jiyang, Kawaguchi, Takahisa, Li, Shuo, Macalli, Melissa, Marquis, Pascale, Morris, Zoe, Muñoz Maniega, Susana, Miyamoto, Susumu, Okawa, Masakazu, Paradise, Matthew, Parva, Pedram, Rundek, Tatjana, Sargurupremraj, Muralidharan, Schilling, Sabrina, Setoh, Kazuya, Soukarieh, Omar, Tabara, Yasuharu, Teumer, Alexander, Thalamuthu, Anbupalam, Trollor, Julian N., Valdés Hernández, Maria C., Vernooij, Meike W., Völker, Uwe, Wittfeld, Katharina, Wong, Tien Yin, Wright, Margaret J., Zhang, Junyi, Zhao, Wanting, Zhu, Yi-Cheng, Schmidt, Helena, Sachdev, Perminder S., Wen, Wei, Yoshida, Kazumichi, Joutel, Anne, Satizabal, Claudia L., Sacco, Ralph L., Bourque, Guillaume, Lathrop, Mark, Paus, Tomas, Fernandez-Cadenas, Israel, Yang, Qiong, Mazoyer, Bernard, Boutinaud, Philippe, Okada, Yukinori, Grabe, Hans J., Mather, Karen A., Schmidt, Reinhold, Joliot, Marc, Ikram, M. Arfan, Matsuda, Fumihiko, Tzourio, Christophe, Wardlaw, Joanna M., Seshadri, Sudha, Adams, Hieab H. H., and Debette, Stéphanie

Published
2023
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15. Cerebral small vessel disease genomics and its implications across the lifespan.

Author

Sargurupremraj, Muralidharan, Suzuki, Hideaki, Jian, Xueqiu, Sarnowski, Chloé, Evans, Tavia E, Bis, Joshua C, Eiriksdottir, Gudny, Sakaue, Saori, Terzikhan, Natalie, Habes, Mohamad, Zhao, Wei, Armstrong, Nicola J, Hofer, Edith, Yanek, Lisa R, Hagenaars, Saskia P, Kumar, Rajan B, van den Akker, Erik B, McWhirter, Rebekah E, Trompet, Stella, Mishra, Aniket, Saba, Yasaman, Satizabal, Claudia L, Beaudet, Gregory, Petit, Laurent, Tsuchida, Ami, Zago, Laure, Schilling, Sabrina, Sigurdsson, Sigurdur, Gottesman, Rebecca F, Lewis, Cora E, Aggarwal, Neelum T, Lopez, Oscar L, Smith, Jennifer A, Valdés Hernández, Maria C, van der Grond, Jeroen, Wright, Margaret J, Knol, Maria J, Dörr, Marcus, Thomson, Russell J, Bordes, Constance, Le Grand, Quentin, Duperron, Marie-Gabrielle, Smith, Albert V, Knopman, David S, Schreiner, Pamela J, Evans, Denis A, Rotter, Jerome I, Beiser, Alexa S, Maniega, Susana Muñoz, Beekman, Marian, Trollor, Julian, Stott, David J, Vernooij, Meike W, Wittfeld, Katharina, Niessen, Wiro J, Soumaré, Aicha, Boerwinkle, Eric, Sidney, Stephen, Turner, Stephen T, Davies, Gail, Thalamuthu, Anbupalam, Völker, Uwe, van Buchem, Mark A, Bryan, R Nick, Dupuis, Josée, Bastin, Mark E, Ames, David, Teumer, Alexander, Amouyel, Philippe, Kwok, John B, Bülow, Robin, Deary, Ian J, Schofield, Peter R, Brodaty, Henry, Jiang, Jiyang, Tabara, Yasuharu, Setoh, Kazuya, Miyamoto, Susumu, Yoshida, Kazumichi, Nagata, Manabu, Kamatani, Yoichiro, Matsuda, Fumihiko, Psaty, Bruce M, Bennett, David A, De Jager, Philip L, Mosley, Thomas H, Sachdev, Perminder S, Schmidt, Reinhold, Warren, Helen R, Evangelou, Evangelos, Trégouët, David-Alexandre, International Network against Thrombosis (INVENT) Consortium, International Headache Genomics Consortium (IHGC), Ikram, Mohammad A, Wen, Wei, DeCarli, Charles, Srikanth, Velandai K, Jukema, J Wouter, Slagboom, Eline P, and Kardia, Sharon LR

Subjects
International Network against Thrombosis (INVENT) Consortium, International Headache Genomics Consortium, Humans, Alzheimer Disease, Hypertension, Medical History Taking, Risk Assessment, Risk Factors, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Stroke, Genome-Wide Association Study, Young Adult, Diffusion Tensor Imaging, Genetic Loci, Mendelian Randomization Analysis, Cerebral Small Vessel Diseases, White Matter, and over
Abstract

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.

Published
2020

16. Paranasal sinuses opacification on magnetic resonance imaging in relation to brain health in sporadic small vessel disease – Systematic review and pilot analysis

Author

Sáenz de Villaverde Cortabarría, Alba, Zhang, Jun-Fang, Valdés Hernández, Maria del C., Clancy, Una, Sakka, Eleni, Ferguson, Karen J., Wiseman, Stewart, Hewins, Will, Jaime García, Daniela, Stringer, Michael, Thrippleton, Michael, Chappell, Francesca, Doubal, Fergus, Wu, Yun-Cheng, and Wardlaw, Joanna M.

Published
2023
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17. Sleep quality, perivascular spaces and brain health markers in ageing - A longitudinal study in the Lothian Birth Cohort 1936

Author

Aribisala, Benjamin S., Valdés Hernández, Maria del C., Okely, Judith A., Cox, Simon R., Ballerini, Lucia, Dickie, David Alexander, Wiseman, Stewart J., Riha, Renata L., Muñoz Maniega, Susana, Radakovic, Ratko, Taylor, Adele, Pattie, Alison, Corley, Janie, Redmond, Paul, Bastin, Mark E., Deary, Ian, and Wardlaw, Joanna M.

Published
2023
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18. Cerebrovascular Reactivity in Patients With Small Vessel Disease: A Cross-Sectional Study

Author

Sleight, Emilie, Stringer, Michael S., Clancy, Una, Arteaga, Carmen, Jaime Garcia, Daniela, Hewins, Will, Jochems, Angela C.C., Hamilton, Olivia K.L., Manning, Cameron, Morgan, Alasdair G., Locherty, Rachel, Cheng, Yajun, Liu, Xiaodi, Zhang, Junfang, Hamilton, Iona, Jardine, Charlotte, Brown, Rosalind, Sakka, Eleni, Kampaite, Agniete, Wiseman, Stewart, Valdés-Hernández, Maria C., Chappell, Francesca M., Doubal, Fergus N., Marshall, Ian, Thrippleton, Michael J., and Wardlaw, Joanna M.

Published
2023
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19. Sex Differences in Poststroke Cognitive Impairment: A Multicenter Study in 2343 Patients With Acute Ischemic Stroke

Author

Exalto, Lieza G., Weaver, Nick A., Kuijf, Hugo J., Aben, Hugo P., Bae, Hee-Joon, Best, Jonathan G., Bordet, Régis, Chen, Christopher P.L.H., van der Giessen, Ruben S., Godefroy, Olivier, Gyanwali, Bibek, Hamilton, Olivia K.L., Hilal, Saima, Huenges Wajer, Irene M.C., Kim, Jonguk, Kappelle, L. Jaap, Kim, Beom Joon, Köhler, Sebastian, de Kort, Paul L.M., Koudstaal, Peter J., Lim, Jae-Sung, Makin, Stephen D.J., Mok, Vincent C.T., van Oostenbrugge, Robert J., Roussel, Martine, Staals, Julie, Valdés-Hernández, Maria del C., Venketasubramanian, Narayanaswamy, Verhey, Frans R.J., Wardlaw, Joanna M., Werring, David J., Xu, Xin, van Zandvoort, Martine J.E., Biesbroek, J. Matthijs, Chappell, Francesca M., and Biessels, Geert Jan

Published
2023
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20. Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting

Author

Chauhan, Ganesh, Adams, Hieab HH, Satizabal, Claudia L, Bis, Joshua C, Teumer, Alexander, Sargurupremraj, Muralidharan, Hofer, Edith, Trompet, Stella, Hilal, Saima, Smith, Albert Vernon, Jian, Xueqiu, Malik, Rainer, Traylor, Matthew, Pulit, Sara L, Amouyel, Philippe, Mazoyer, Bernard, Zhu, Yi-Cheng, Kaffashian, Sara, Schilling, Sabrina, Beecham, Gary W, Montine, Thomas J, Schellenberg, Gerard D, Kjartansson, Olafur, Guðnason, Vilmundur, Knopman, David S, Griswold, Michael E, Windham, B Gwen, Gottesman, Rebecca F, Mosley, Thomas H, Schmidt, Reinhold, Saba, Yasaman, Schmidt, Helena, Takeuchi, Fumihiko, Yamaguchi, Shuhei, Nabika, Toru, Kato, Norihiro, Rajan, Kumar B, Aggarwal, Neelum T, De Jager, Philip L, Evans, Denis A, Psaty, Bruce M, Rotter, Jerome I, Rice, Kenneth, Lopez, Oscar L, Liao, Jiemin, Chen, Christopher, Cheng, Ching-Yu, Wong, Tien Y, Ikram, Mohammad K, van der Lee, Sven J, Amin, Najaf, Chouraki, Vincent, DeStefano, Anita L, Aparicio, Hugo J, Romero, Jose R, Maillard, Pauline, DeCarli, Charles, Wardlaw, Joanna M, del C. Valdés Hernández, Maria, Luciano, Michelle, Liewald, David, Deary, Ian J, Starr, John M, Bastin, Mark E, Maniega, Susana Muñoz, Slagboom, P Eline, Beekman, Marian, Deelen, Joris, Uh, Hae-Won, Lemmens, Robin, Brodaty, Henry, Wright, Margaret J, Ames, David, Boncoraglio, Giorgio B, Hopewell, Jemma C, Beecham, Ashley H, Blanton, Susan H, Wright, Clinton B, Sacco, Ralph L, Wen, Wei, Thalamuthu, Anbupalam, Armstrong, Nicola J, Chong, Elizabeth, Schofield, Peter R, Kwok, John B, van der Grond, Jeroen, Stott, David J, Ford, Ian, Jukema, J Wouter, Vernooij, Meike W, Hofman, Albert, Uitterlinden, André G, van der Lugt, Aad, Wittfeld, Katharina, Grabe, Hans J, Hosten, Norbert, von Sarnowski, Bettina, Völker, Uwe, Levi, Christopher, and Jimenez-Conde, Jordi

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Brain Disorders, Genetics, Cardiovascular, Prevention, Aging, Cerebrovascular, Stroke, Human Genome, 2.1 Biological and endogenous factors, Good Health and Well Being, Stroke Genetics Network (SiGN), the International Stroke Genetics Consortium (ISGC), METASTROKE, Alzheimer's Disease Genetics Consortium (ADGC), and the Neurology Working Group of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveTo explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts.MethodsWe performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI.ResultsThe mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10-8; and LINC00539/ZDHHC20, p = 5.82 × 10-9. Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p [BI] = 9.38 × 10-25; p [SSBI] = 5.23 × 10-14 for hypertension), smoking (p [BI] = 4.4 × 10-10; p [SSBI] = 1.2 × 10-4), diabetes (p [BI] = 1.7 × 10-8; p [SSBI] = 2.8 × 10-3), previous cardiovascular disease (p [BI] = 1.0 × 10-18; p [SSBI] = 2.3 × 10-7), stroke (p [BI] = 3.9 × 10-69; p [SSBI] = 3.2 × 10-24), and MRI-defined white matter hyperintensity burden (p [BI] = 1.43 × 10-157; p [SSBI] = 3.16 × 10-106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p ≤ 0.0022), without indication of directional pleiotropy.ConclusionIn this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.

Published
2019

22. Perivascular Spaces Segmentation in Brain MRI Using Optimal 3D Filtering

Author

Ballerini, Lucia, Lovreglio, Ruggiero, Valdes-Hernandez, Maria del C., Ramirez, Joel, MacIntosh, Bradley J., Black, Sandra E., and Wardlaw, Joanna M.

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

Perivascular Spaces (PVS) are a recently recognised feature of Small Vessel Disease (SVD), also indicating neuroinflammation, and are an important part of the brain's circulation and glymphatic drainage system. Quantitative analysis of PVS on Magnetic Resonance Images (MRI) is important for understanding their relationship with neurological diseases. In this work, we propose a segmentation technique based on the 3D Frangi filtering for extraction of PVS from MRI. Based on prior knowledge from neuroradiological ratings of PVS, we used ordered logit models to optimise Frangi filter parameters in response to the variability in the scanner's parameters and study protocols. We optimized and validated our proposed models on two independent cohorts, a dementia sample (N=20) and patients who previously had mild to moderate stroke (N=48). Results demonstrate the robustness and generalisability of our segmentation method. Segmentation-based PVS burden estimates correlated with neuroradiological assessments (Spearman's $\rho$ = 0.74, p $<$ 0.001), suggesting the great potential of our proposed method

Published
2017
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23. Probabilistic Deep Learning with Adversarial Training and Volume Interval Estimation - Better Ways to Perform and Evaluate Predictive Models for White Matter Hyperintensities Evolution

Author

Rachmadi, Muhammad Febrian, Valdés-Hernández, Maria del C., Maulana, Rizal, Wardlaw, Joanna, Makin, Stephen, Skibbe, Henrik, Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Woeginger, Gerhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Rekik, Islem, editor, Adeli, Ehsan, editor, Park, Sang Hyun, editor, and Schnabel, Julia, editor

Published
2021
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24. Selective Motion Artefact Reduction via Radiomics and k-space Reconstruction for Improving Perivascular Space Quantification in Brain Magnetic Resonance Imaging

Author

Bernal, Jose, Xu, William, Valdés-Hernández, Maria d. C., Escudero, Javier, Jochems, Angela C. C., Clancy, Una, Doubal, Fergus N., Stringer, Michael S., Thrippleton, Michael J., Touyz, Rhian M., Wardlaw, Joanna M., Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Woeginger, Gerhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Papież, Bartłomiej W., editor, Yaqub, Mohammad, editor, Jiao, Jianbo, editor, Namburete, Ana I. L., editor, and Noble, J. Alison, editor

Published
2021
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25. Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume.

Author

Vojinovic, Dina, Adams, Hieab H, Jian, Xueqiu, Yang, Qiong, Smith, Albert Vernon, Bis, Joshua C, Teumer, Alexander, Scholz, Markus, Armstrong, Nicola J, Hofer, Edith, Saba, Yasaman, Luciano, Michelle, Bernard, Manon, Trompet, Stella, Yang, Jingyun, Gillespie, Nathan A, van der Lee, Sven J, Neumann, Alexander, Ahmad, Shahzad, Andreassen, Ole A, Ames, David, Amin, Najaf, Arfanakis, Konstantinos, Bastin, Mark E, Becker, Diane M, Beiser, Alexa S, Beyer, Frauke, Brodaty, Henry, Bryan, R Nick, Bülow, Robin, Dale, Anders M, De Jager, Philip L, Deary, Ian J, DeCarli, Charles, Fleischman, Debra A, Gottesman, Rebecca F, van der Grond, Jeroen, Gudnason, Vilmundur, Harris, Tamara B, Homuth, Georg, Knopman, David S, Kwok, John B, Lewis, Cora E, Li, Shuo, Loeffler, Markus, Lopez, Oscar L, Maillard, Pauline, El Marroun, Hanan, Mather, Karen A, Mosley, Thomas H, Muetzel, Ryan L, Nauck, Matthias, Nyquist, Paul A, Panizzon, Matthew S, Pausova, Zdenka, Psaty, Bruce M, Rice, Ken, Rotter, Jerome I, Royle, Natalie, Satizabal, Claudia L, Schmidt, Reinhold, Schofield, Peter R, Schreiner, Pamela J, Sidney, Stephen, Stott, David J, Thalamuthu, Anbupalam, Uitterlinden, Andre G, Valdés Hernández, Maria C, Vernooij, Meike W, Wen, Wei, White, Tonya, Witte, A Veronica, Wittfeld, Katharina, Wright, Margaret J, Yanek, Lisa R, Tiemeier, Henning, Kremen, William S, Bennett, David A, Jukema, J Wouter, Paus, Tomas, Wardlaw, Joanna M, Schmidt, Helena, Sachdev, Perminder S, Villringer, Arno, Grabe, Hans Jörgen, Longstreth, WT, van Duijn, Cornelia M, Launer, Lenore J, Seshadri, Sudha, Ikram, M Arfan, and Fornage, Myriam

Subjects
Lateral Ventricles, Humans, Organ Size, Genome, Human, Aged, Middle Aged, Genome-Wide Association Study, Human Genome, Aging, Genetics, 2.1 Biological and endogenous factors, Neurological
Abstract

The volume of the lateral ventricles (LV) increases with age and their abnormal enlargement is a key feature of several neurological and psychiatric diseases. Although lateral ventricular volume is heritable, a comprehensive investigation of its genetic determinants is lacking. In this meta-analysis of genome-wide association studies of 23,533 healthy middle-aged to elderly individuals from 26 population-based cohorts, we identify 7 genetic loci associated with LV volume. These loci map to chromosomes 3q28, 7p22.3, 10p12.31, 11q23.1, 12q23.3, 16q24.2, and 22q13.1 and implicate pathways related to tau pathology, S1P signaling, and cytoskeleton organization. We also report a significant genetic overlap between the thalamus and LV volumes (ρgenetic = -0.59, p-value = 3.14 × 10-6), suggesting that these brain structures may share a common biology. These genetic associations of LV volume provide insights into brain morphology.

Published
2018

26. Exome Chip Analysis Identifies Low-Frequency and Rare Variants in MRPL38 for White Matter Hyperintensities on Brain Magnetic Resonance Imaging

Author

Jian, Xueqiu, Satizabal, Claudia L, Smith, Albert V, Wittfeld, Katharina, Bis, Joshua C, Smith, Jennifer A, Hsu, Fang-Chi, Nho, Kwangsik, Hofer, Edith, Hagenaars, Saskia P, Nyquist, Paul A, Mishra, Aniket, Adams, Hieab HH, Li, Shuo, Teumer, Alexander, Zhao, Wei, Freedman, Barry I, Saba, Yasaman, Yanek, Lisa R, Chauhan, Ganesh, van Buchem, Mark A, Cushman, Mary, Royle, Natalie A, Bryan, R Nick, Niessen, Wiro J, Windham, Beverly G, DeStefano, Anita L, Habes, Mohamad, Heckbert, Susan R, Palmer, Nicholette D, Lewis, Cora E, Eiriksdottir, Gudny, Maillard, Pauline, Mathias, Rasika A, Homuth, Georg, Valdés-Hernández, Maria del C, Divers, Jasmin, Beiser, Alexa S, Langner, Sönke, Rice, Kenneth M, Bastin, Mark E, Yang, Qiong, Maldjian, Joseph A, Starr, John M, Sidney, Stephen, Risacher, Shannon L, Uitterlinden, André G, Gudnason, Vilmundur G, Nauck, Matthias, Rotter, Jerome I, Schreiner, Pamela J, Boerwinkle, Eric, van Duijn, Cornelia M, Mazoyer, Bernard, von Sarnowski, Bettina, Gottesman, Rebecca F, Levy, Daniel, Sigurdsson, Sigurdur, Vernooij, Meike W, Turner, Stephen T, Schmidt, Reinhold, Wardlaw, Joanna M, Psaty, Bruce M, Mosley, Thomas H, DeCarli, Charles S, Saykin, Andrew J, Bowden, Donald W, Becker, Diane M, Deary, Ian J, Schmidt, Helena, Kardia, Sharon LR, Ikram, M Arfan, Debette, Stéphanie, Grabe, Hans J, Longstreth, WT, Seshadri, Sudha, Launer, Lenore J, and Fornage, Myriam

Subjects
Epidemiology, Health Sciences, Alzheimer's Disease Related Dementias (ADRD), Dementia, Human Genome, Cerebrovascular, Clinical Research, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Stroke, Brain Disorders, Acquired Cognitive Impairment, Neurodegenerative, Aging, Minority Health, Genetics, Neurosciences, Biotechnology, 2.1 Biological and endogenous factors, Neurological, Brain, Cohort Studies, Exome, Genetic Variation, Humans, Magnetic Resonance Imaging, Mitochondrial Proteins, White Matter, cerebral small vessel disease, exome, magnetic resonance imaging, meta-analysis, white matter, neuroCHARGE Working Group, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Neurology & Neurosurgery, Clinical sciences, Allied health and rehabilitation science
Abstract

Background and Purpose- White matter hyperintensities (WMH) on brain magnetic resonance imaging are typical signs of cerebral small vessel disease and may indicate various preclinical, age-related neurological disorders, such as stroke. Though WMH are highly heritable, known common variants explain a small proportion of the WMH variance. The contribution of low-frequency/rare coding variants to WMH burden has not been explored. Methods- In the discovery sample we recruited 20 719 stroke/dementia-free adults from 13 population-based cohort studies within the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, among which 17 790 were of European ancestry and 2929 of African ancestry. We genotyped these participants at ≈250 000 mostly exonic variants with Illumina HumanExome BeadChip arrays. We performed ethnicity-specific linear regression on rank-normalized WMH in each study separately, which were then combined in meta-analyses to test for association with single variants and genes aggregating the effects of putatively functional low-frequency/rare variants. We then sought replication of the top findings in 1192 adults (European ancestry) with whole exome/genome sequencing data from 2 independent studies. Results- At 17q25, we confirmed the association of multiple common variants in TRIM65, FBF1, and ACOX1 ( P

Published
2018

27. Pain mechanisms in the transgender individual: a review

Author

Anger, Jennifer T., primary, Case, Laura K., additional, Baranowski, Andrew P., additional, Berger, Ardin, additional, Craft, Rebecca M., additional, Damitz, Lyn Ann, additional, Gabriel, Rodney, additional, Harrison, Tracy, additional, Kaptein, Kirsten, additional, Lee, Sanghee, additional, Murphy, Anne Z., additional, Said, Engy, additional, Smith, Stacey Abigail, additional, Thomas, David A., additional, Valdés Hernández, Maria del C., additional, Trasvina, Victor, additional, Wesselmann, Ursula, additional, and Yaksh, Tony L., additional

Published
2024
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28. General and specific patterns of cortical gene expression as spatial correlates of complex cognitive functioning

Author

Moodie, Joanna E., primary, Harris, Sarah E., additional, Harris, Mathew A., additional, Buchanan, Colin R., additional, Davies, Gail, additional, Taylor, Adele, additional, Redmond, Paul, additional, Liewald, David C. M., additional, Valdés Hernández, Maria del C., additional, Shenkin, Susan, additional, Russ, Tom C., additional, Muñoz Maniega, Susana, additional, Luciano, Michelle, additional, Corley, Janie, additional, Stolicyn, Aleks, additional, Shen, Xueyi, additional, Steele, Douglas, additional, Waiter, Gordon, additional, Sandu, Anca‐Larisa, additional, Bastin, Mark E., additional, Wardlaw, Joanna M., additional, McIntosh, Andrew, additional, Whalley, Heather, additional, Tucker‐Drob, Elliot M., additional, Deary, Ian J., additional, and Cox, Simon R., additional

Published
2024
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29. Retinal Biomarkers Discovery for Cerebral Small Vessel Disease in an Older Population

Author

Ballerini, Lucia, Fetit, Ahmed E., Wunderlich, Stephan, Lovreglio, Ruggiero, McGrory, Sarah, Valdes-Hernandez, Maria, MacGillivray, Tom, Doubal, Fergus, Deary, Ian J., Wardlaw, Joanna, Trucco, Emanuele, Filipe, Joaquim, Editorial Board Member, Ghosh, Ashish, Editorial Board Member, Kotenko, Igor, Editorial Board Member, Prates, Raquel Oliveira, Editorial Board Member, Zhou, Lizhu, Editorial Board Member, Papież, Bartłomiej W., editor, Namburete, Ana I. L., editor, Yaqub, Mohammad, editor, and Noble, J. Alison, editor

Published
2020
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30. A Framework for Jointly Assessing and Reducing Imaging Artefacts Automatically Using Texture Analysis and Total Variation Optimisation for Improving Perivascular Spaces Quantification in Brain Magnetic Resonance Imaging

Author

Bernal, Jose, Valdés-Hernández, Maria, Ballerini, Lucia, Escudero, Javier, Jochems, Angela C. C., Clancy, Una, Doubal, Fergus N., Stringer, Michael S., Thrippleton, Michael J., Touyz, Rhian M., Wardlaw, Joanna M., Filipe, Joaquim, Editorial Board Member, Ghosh, Ashish, Editorial Board Member, Kotenko, Igor, Editorial Board Member, Prates, Raquel Oliveira, Editorial Board Member, Zhou, Lizhu, Editorial Board Member, Papież, Bartłomiej W., editor, Namburete, Ana I. L., editor, Yaqub, Mohammad, editor, and Noble, J. Alison, editor

Published
2020
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31. Analysis of Spatial Spectral Features of Dynamic Contrast-Enhanced Brain Magnetic Resonance Images for Studying Small Vessel Disease

Author

Bernal, Jose, Valdés-Hernández, Maria del C., Escudero, Javier, Armitage, Paul A., Makin, Stephen, Touyz, Rhian M., Wardlaw, Joanna M., Barbosa, Simone Diniz Junqueira, Editorial Board Member, Filipe, Joaquim, Editorial Board Member, Ghosh, Ashish, Editorial Board Member, Kotenko, Igor, Editorial Board Member, Zhou, Lizhu, Editorial Board Member, Zheng, Yalin, editor, Williams, Bryan M., editor, and Chen, Ke, editor

Published
2020
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32. Relationship between inferior frontal sulcal hyperintensities on brain MRI, ageing and cerebral small vessel disease

Author

Zhang, Jun-Fang, Lim, Hwee Fang, Chappell, Francesca M., Clancy, Una, Wiseman, Stewart, Valdés-Hernández, Maria C., Garcia, Daniela Jaime, Bastin, Mark E., Doubal, Fergus N., Hewins, Will, Cox, Simon R., Maniega, Susana Muñoz, Thrippleton, Michael, Stringer, Michael, Jardine, Charlotte, McIntyre, Donna, Barclay, Gayle, Hamilton, Iona, Kesseler, Lucy, Murphy, Madeleine, Perri, Carol Di, Wu, Yun-Cheng, and Wardlaw, Joanna M.

Published
2021
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34. Retinal capillary microvessel morphology changes are associated with vascular damage and dysfunction in cerebral small vessel disease

Author

Wiseman, Stewart J, Zhang, Jun-Fang, Gray, Calum, Hamid, Charlene, Valdés Hernández, Maria del C, Ballerini, Lucia, Thrippleton, Michael J, Manning, Cameron, Stringer, Michael, Sleight, Emilie, Muñoz Maniega, Susana, Morgan, Alasdair, Cheng, Yajun, Arteaga, Carmen, Jaime Garcia, Dany, Clancy, Una, Doubal, Fergus N, Dhillon, Baljean, MacGillivray, Tom, Wu, Yun-Cheng, and Wardlaw, Joanna M

Published
2023
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35. Strategic infarct locations for post-stroke cognitive impairment: a pooled analysis of individual patient data from 12 acute ischaemic stroke cohorts

Author

Weaver, Nick A, Kuijf, Hugo J, Aben, Hugo P, Abrigo, Jill, Bae, Hee-Joon, Barbay, Mélanie, Best, Jonathan G, Bordet, Régis, Chappell, Francesca M, Chen, Christopher P L H, Dondaine, Thibaut, van der Giessen, Ruben S, Godefroy, Olivier, Gyanwali, Bibek, Hamilton, Olivia K L, Hilal, Saima, Huenges Wajer, Irene M C, Kang, Yeonwook, Kappelle, L Jaap, Kim, Beom Joon, Köhler, Sebastian, de Kort, Paul L M, Koudstaal, Peter J, Kuchcinski, Gregory, Lam, Bonnie Y K, Lee, Byung-Chul, Lee, Keon-Joo, Lim, Jae-Sung, Lopes, Renaud, Makin, Stephen D J, Mendyk, Anne-Marie, Mok, Vincent C T, Oh, Mi Sun, van Oostenbrugge, Robert J, Roussel, Martine, Shi, Lin, Staals, Julie, del C Valdés-Hernández, Maria, Venketasubramanian, Narayanaswamy, Verhey, Frans R J, Wardlaw, Joanna M, Werring, David J, Xin, Xu, Yu, Kyung-Ho, van Zandvoort, Martine J E, Zhao, Lei, Biesbroek, J Matthijs, and Biessels, Geert Jan

Published
2021
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38. Detectability and accuracy of computational measurements of in-silico and physical representations of enlarged perivascular spaces from magnetic resonance images

Author

Highfield Research Group, Brain, Cancer, Circulatory Health, Regenerative Medicine and Stem Cells, Beeldverwerking ISI, Structure and Connections, Neurologen, Duarte Coello, Roberto, Valdés Hernández, Maria Del C, Zwanenburg, Jaco J M, van der Velden, Moniek, Kuijf, Hugo J, De Luca, Alberto, Moyano, José Bernal, Ballerini, Lucia, Chappell, Francesca M, Brown, Rosalind, Jan Biessels, Geert, Wardlaw, Joanna M, Highfield Research Group, Brain, Cancer, Circulatory Health, Regenerative Medicine and Stem Cells, Beeldverwerking ISI, Structure and Connections, Neurologen, Duarte Coello, Roberto, Valdés Hernández, Maria Del C, Zwanenburg, Jaco J M, van der Velden, Moniek, Kuijf, Hugo J, De Luca, Alberto, Moyano, José Bernal, Ballerini, Lucia, Chappell, Francesca M, Brown, Rosalind, Jan Biessels, Geert, and Wardlaw, Joanna M

Published
2024

39. Quantitative T1 brain mapping in early relapsing-remitting multiple sclerosis: longitudinal changes, lesion heterogeneity and disability.

Author

Harper, James G., York, Elizabeth N., Meijboom, Rozanna, Kampaite, Agniete, Thrippleton, Michael J., Kearns, Patrick K. A., Valdés Hernández, Maria del C., Chandran, Siddharthan, Waldman, Adam D., Akula, Amit, Baranzini, Sergio, Barret, Fiona, Bastin, Mark, Batchelor, Chris, Beswick, Emily, Brown, Fraser, Brunton, Tracy, Carod Artal, Javier, Chang, Jessie, and Chen, Yingdi

Subjects
BRAIN mapping, MULTIPLE sclerosis, DISEASE relapse, WHITE matter (Nerve tissue), BASAL ganglia, PEOPLE with disabilities
Abstract

Objectives: To quantify brain microstructural changes in recently diagnosed relapsing-remitting multiple sclerosis (RRMS) using longitudinal T1 measures, and determine their associations with clinical disability. Methods: Seventy-nine people with recently diagnosed (< 6 months) RRMS were recruited from a single-centre cohort sub-study, and underwent baseline and 1-year brain MRI, including variable flip angle T1 mapping. Median T1 was measured in white matter lesions (WML), normal-appearing white matter (NAWM), cortical/deep grey matter (GM), thalami, basal ganglia and medial temporal regions. Prolonged T1 (≥ 2.00 s) and supramedian T1 (relative to cohort WML values) WML voxel counts were also measured. Longitudinal change was assessed with paired t-tests and compared with Bland-Altman limits of agreement from healthy control test-retest data. Regression analyses determined relationships with Expanded Disability Status Scale (EDSS) score and dichotomised EDSS outcomes (worsening or stable/improving). Results: Sixty-two people with RRMS (mean age 37.2 ± 10.9 [standard deviation], 48 female) and 11 healthy controls (age 44 ± 11, 7 female) contributed data. Prolonged and supramedian T1 WML components increased longitudinally (176 and 463 voxels, respectively; p <.001), and were associated with EDSS score at baseline (p <.05) and follow-up (supramedian: p <.01; prolonged: p <.05). No cohort-wide median T1 changes were found; however, increasing T1 in WML, NAWM, cortical/deep GM, basal ganglia and thalami was positively associated with EDSS worsening (p <.05). Conclusion: T1 is sensitive to brain microstructure changes in early RRMS. Prolonged WML T1 components and subtle changes in NAWM and GM structures are associated with disability. Clinical relevance statement: MRI T1 brain mapping quantifies disability-associated white matter lesion heterogeneity and subtle microstructural damage in normal-appearing brain parenchyma in recently diagnosed RRMS, and shows promise for early objective disease characterisation and stratification. Key Points: • Quantitative T1 mapping detects brain microstructural damage and lesion heterogeneity in recently diagnosed relapsing-remitting multiple sclerosis. • T1 increases in lesions and normal-appearing parenchyma, indicating microstructural damage, are associated with worsening disability. • Brain T1 measures are objective markers of disability-relevant pathology in early multiple sclerosis. [ABSTRACT FROM AUTHOR]

Published
2024
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40. Predicting the Evolution of White Matter Hyperintensities in Brain MRI Using Generative Adversarial Networks and Irregularity Map

Author

Rachmadi, Muhammad Febrian, del C. Valdés-Hernández, Maria, Makin, Stephen, Wardlaw, Joanna M., Komura, Taku, Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Woeginger, Gerhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Shen, Dinggang, editor, Liu, Tianming, editor, Peters, Terry M., editor, Staib, Lawrence H., editor, Essert, Caroline, editor, Zhou, Sean, editor, Yap, Pew-Thian, editor, and Khan, Ali, editor

Published
2019
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45. Magnetic Resonance Imaging Tissue Signatures Associated With White Matter Changes Due to Sporadic Cerebral Small Vessel Disease Indicate That White Matter Hyperintensities Can Regress

Author

Jochems, Angela C. C., primary, Muñoz Maniega, Susana, additional, Clancy, Una, additional, Arteaga, Carmen, additional, Jaime Garcia, Daniela, additional, Chappell, Francesca M., additional, Hewins, Will, additional, Locherty, Rachel, additional, Backhouse, Ellen V., additional, Barclay, Gayle, additional, Jardine, Charlotte, additional, McIntyre, Donna, additional, Gerrish, Iona, additional, Kampaite, Agniete, additional, Sakka, Eleni, additional, Valdés Hernández, Maria, additional, Wiseman, Stewart, additional, Bastin, Mark E., additional, Stringer, Michael S., additional, Thrippleton, Michael J., additional, Doubal, Fergus N., additional, and Wardlaw, Joanna M., additional

Published
2024
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47. Impact of long-term white matter hyperintensity changes on mobility and dexterity

Author

Jochems, Angela C C, primary, Muñoz Maniega, Susana, additional, Chappell, Francesca M, additional, Clancy, Una, additional, Arteaga, Carmen, additional, Jaime Garcia, Daniela, additional, Hamilton, Olivia K L, additional, Hewins, Will, additional, Locherty, Rachel, additional, Backhouse, Ellen V, additional, Barclay, Gayle, additional, Jardine, Charlotte, additional, McIntyre, Donna, additional, Gerrish, Iona, additional, Cheng, Yajun, additional, Liu, Xiaodi, additional, Zhang, Junfang, additional, Kampaite, Agniete, additional, Sakka, Eleni, additional, Valdés Hernández, Maria, additional, Wiseman, Stewart, additional, Stringer, Michael S, additional, Thrippleton, Michael J, additional, Doubal, Fergus N, additional, and Wardlaw, Joanna M, additional

Published
2024
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48. Influence of threshold selection and image sequence in in-vivo segmentation of enlarged perivascular spaces

Author

Valdés Hernández, Maria del C, primary, Coello, Roberto Duarte, additional, Xu, William, additional, Bernal, José, additional, Cheng, Yajun, additional, Ballerini, Lucia, additional, Wiseman, Stewart J., additional, Chappell, Francesca M., additional, Clancy, Una, additional, García, Daniela Jaime, additional, Reyes, Carmen Arteaga, additional, Zhang, Jun-Fang, additional, Liu, Xiaodi, additional, Hewins, Will, additional, Stringer, Michael, additional, Doubal, Fergus, additional, Thrippleton, Michael J., additional, Jochems, Angela, additional, Brown, Rosalind, additional, and Wardlaw, Joanna M., additional

Published
2023
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49. The Meta VCI Map consortium for meta-analyses on strategic lesion locations for vascular cognitive impairment using lesion-symptom mapping: Design and multicenter pilot study

Author

DeCarli, C., Fletcher, E.A., Maillard, P., Barnes, J., Sudre, C.H., Schott, J.M., Ikram, M.A., Papma, J.M., Steketee, R.M.E., Vernooij, M.W., Bordet, R., Lopes, R., Huang, C.-W., Frayne, R., McCreary, C.R., Smith, E.E., Backes, W., Köhler, S., van Oostenbrugge, R.J., Staals, J., Verhey, F., Cheng, C.Y., Kalaria, R.N., Werring, D., Hsu, J.L., Huang, K.-L., van der Grond, J., Jukema, J.W., van der Mast, R.C., Nijboer, T.C.W., Yu, K.-H., Schmidt, R., Pirpamer, L., MacIntosh, B.J., Robertson, A.D., de Leeuw, F.-E., Tuladhar, A.M., Chaturvedi, N., Tillin, T., Brodaty, H., Sachdev, P., Barkhof, F., van der Flier, W.M., Kappelle, L.J., Weaver, Nick A., Zhao, Lei, Biesbroek, J. Matthijs, Kuijf, Hugo J., Aben, Hugo P., Bae, Hee-Joon, Caballero, Miguel Á.A., Chappell, Francesca M., Chen, Christopher P.L.H., Dichgans, Martin, Duering, Marco, Georgakis, Marios K., van der Giessen, Ruben S., Gyanwali, Bibek, Hamilton, Olivia K.L., Hilal, Saima, vom Hofe, Elise M., de Kort, Paul L.M., Koudstaal, Peter J., Lam, Bonnie Y.K., Lim, Jae-Sung, Makin, Stephen D.J., Mok, Vincent C.T., Shi, Lin, Valdés Hernández, Maria C., Venketasubramanian, Narayanaswamy, Wardlaw, Joanna M., Wollenweber, Frank A., Wong, Adrian, Xin, Xu, and Biessels, Geert Jan

Published
2019
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50. Super Resolution Convolutional Neural Networks for Increasing Spatial Resolution of H Magnetic Resonance Spectroscopic Imaging

Author

Cengiz, Sevim, Valdes-Hernandez, Maria del C., Ozturk-Isik, Esin, Diniz Junqueira Barbosa, Simone, Series editor, Chen, Phoebe, Series editor, Du, Xiaoyong, Series editor, Filipe, Joaquim, Series editor, Kara, Orhun, Series editor, Kotenko, Igor, Series editor, Liu, Ting, Series editor, Sivalingam, Krishna M., Series editor, Washio, Takashi, Series editor, Valdés Hernández, María, editor, and González-Castro, Víctor, editor

Published
2017
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