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1. In vivo investigation of the multi-exponential T2 decay in human white matter at 7T: Implications for myelin water imaging at UHF

Author

Wiggermann, Vanessa, MacKay, Alex, Rauscher, Alexander, and Helms, Gunther

Subjects
Physics - Medical Physics, Quantitative Biology - Quantitative Methods
Abstract

Multicomponent T2-mapping using a gradient and spin-echo (GraSE) acquisition has become standard for myelin water imaging at 3T. Higher magnetic field strengths promise SNR benefits but face specific absorption rate limits and shortened T2 times. This study investigates compartmental T2 times in vivo and addresses advantages and challenges of multi-component T2-mapping at 7T. We acquired 3D multi-echo GraSE data in seven healthy adults at 7T, with three subjects scanned also at 3T. Stimulated echoes arising from B+1 inhomogeneities were accounted for by the extended phase graph (EPG) algorithm. We used the computed T2 distributions to determine T2 times that identify different water pools and assessed signal-to-noise and fit-to-noise characteristics of the signal estimation. We compared short T2 fractions and T2 properties of the intermediate water pool at 3T and 7T. Flip angle mapping confirmed that EPG accurately determined the larger inhomogeneity at 7T. Multi-component T2 analysis demonstrated shortened T2 times at 7T compared to 3T. Fit-to-noise and signal-to-noise ratios were improved at 7T but depended on B1 homogeneity. Lowering the shortest T2 to 8 ms and adjusting the T2 threshold that separates different water compartments to 20 ms, yielded short T2 fractions at 7T that conformed to 3T data. Short T2 fractions in myelin-rich white matter regions were lower at 7T than at 3T, and higher in iron-rich structures. Adjusting the T2 compartment boundaries was required due to the shorter T2 relaxation times at 7T. Shorter echo spacing would better sample the fast decaying signal but would increase peripheral nerve stimulation. We used a multi-echo 3D-GraSE sequence to characterize the multi-exponential T2 decay at 7T. We adapted T2 parameters for evaluation of the short T2 fraction. Obtained 7T multicomponent T2-maps were in good agreement with 3T data., Comment: reformatted submitted version: 6 pages, 5 figures, 2 supplements

Published
2021
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7. Quantitative magnetic resonance imaging reflects different levels of histologically determined myelin densities in multiple sclerosis, including remyelination in inactive multiple sclerosis lesions.

Author

Wiggermann, Vanessa, Endmayr, Verena, Hernández‐Torres, Enedino, Höftberger, Romana, Kasprian, Gregor, Hametner, Simon, and Rauscher, Alexander

Subjects
*MAGNETIC resonance imaging, *MYELIN, *OLIGODENDROGLIA, *MULTIPLE sclerosis, *MAGNETIZATION transfer, *MYELIN proteins, *POSTMORTEM changes, *WHITE matter (Nerve tissue)
Abstract

Magnetic resonance imaging (MRI) of focal or diffuse myelin damage or remyelination may provide important insights into disease progression and potential treatment efficacy in multiple sclerosis (MS). We performed post‐mortem MRI and histopathological myelin measurements in seven progressive MS cases to evaluate the ability of three myelin‐sensitive MRI scans to distinguish different stages of MS pathology, particularly chronic demyelinated and remyelinated lesions. At 3 Tesla, we acquired two different myelin water imaging (MWI) scans and magnetisation transfer ratio (MTR) data. Histopathology included histochemical stainings for myelin phospholipids (LFB) and iron as well as immunohistochemistry for myelin proteolipid protein (PLP), CD68 (phagocytosing microglia/macrophages) and BCAS1 (remyelinating oligodendrocytes). Mixed‐effects modelling determined which histopathological metric best predicted MWF and MTR in normal‐appearing and diffusely abnormal white matter, active/inactive, inactive, remyelinated and ischemic lesions. Both MWI measures correlated well with each other and histology across regions, reflecting the different stages of MS pathology. MTR data showed a considerable influence of components other than myelin and a strong dependency on tissue storage duration. Both MRI and histology revealed increased myelin densities in inactive compared with active/inactive lesions. Chronic inactive lesions harboured single scattered myelin fibres indicative of low‐level remyelination. Mixed‐effects modelling showed that smaller differences between white matter areas were linked to PLP densities and only to a small extent confounded by iron. MWI reflects differences in myelin lipids and proteins across various levels of myelin densities encountered in MS, including low‐level remyelination in chronic inactive lesions. [ABSTRACT FROM AUTHOR]

Published
2023
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13. Brain imaging abnormalities in mixed Alzheimer’s and subcortical vascular dementia

Author

Lee, Hyunwoo, primary, Wiggermann, Vanessa, additional, Rauscher, Alexander, additional, Kames, Christian, additional, Beg, Mirza Faisal, additional, Popuri, Karteek, additional, Tam, Roger, additional, Lam, Kevin, additional, Jacova, Claudia, additional, Shahinfard, Elham, additional, Sossi, Vesna, additional, Pettersen, Jacqueline A., additional, and Hsiung, Ging-Yuek Robin, additional

Published
2022
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14. Geriatric dementia care at Ontario Shores: A new model of care

Author

Viau, Katelynn, Yaddaden, Amel, Lussier, Maxime, Bier, Nathalie, Earle, Julie, Duff-Woskosky, Andra, Bartfay, Wally, Desai, Chaitali, Zavitz, Karen, Horsburgh, Sheri, Gamble, Brenda, Lee, Linda, Hillier, Loretta M., Patel, Tejal, Molnar, Frank, Clarke, Jo-Anne, Borrie, Michael, Cammer, Allison, Morgan, Debra, Whiting, Susan, de Vos, Maya, Henri-Bhargava, Alexandre, Votova, Kristine, Delmar, Paul, Kerchner, Geoffrey A, Wang, Guoqiao, Bateman, Randall, Klein, Gregory, Andjelkovic, Mirjana, Abi-Saab, Danielle, Bullain, Szofia, Montoya, Alonso, Fontoura, Paulo, Doody, Rachelle, Tai, Elaine, Harvey, David, Hofmann, Carsten, Ristic, Smiljana, Rehal, Sunita, Voyle, Nicola, Baudler, Monika, Verreault, Phylicia, Rousseau, François, Keller, Evelyn, Simard, Alexandra, Azouaou, Nassima, Jarboui, Manel, Talleria, Lorraine, Duguay, Johanne, Mérette, Chantale, Labbé, Annie, de Arco, Rossana Peredo Nunez, Yous, Marie-Lee, Ploeg, Jenny, Kaasalainen, Sharon, Martin, Lori Schindel, Palumbo, Mary Val, Rambur, Betty, McKenna, Lori, Voyer, Philippe, Allaire, Émilie, Li, Bing, Thaut, Michael, Yogaparan, Thirumagal, Shanmuganathan, Thirunathan, Vickneswaran, Anicha, Sriharan, Sruthy, DeMarco, Mari L., Hsiung, Ging-Yuek Robin, Best, John R., Chertkow, Howard, Gauthier, Serge, Karlawish, Jason, Feldman, Howard, Spaner, Caroline, Christie, Brian, Musteata, Stela, Gawryluk, Jodie, Hofer, Scott, Henri-Bhargava, Alex, Kenny, Rebecca, Elliot, Valerie, Kosteniuk, Julie, Chow, Amanda Froehlich, Bayly, Melanie, O’Connell, Megan E., Kortzman, August, O’Connell, Megan, Kirk, Andrew, Conn, David, Sokoloff, Lisa, Feldman, Sid, Chau, James, Moser, Andrea, Lingum, Navena, Gingrich, Shaen, Shaikh, Salma, Rabheru, Kiran, Cassidy, Keri-Leigh, Checkland, Claire, Parsons, Daria, Massie, Ariane S., Mitchell, Julie Spence, Aksenchuk, Sophia, Lindsay, Barbara, Howard, Maria, Shaw, Courtney, Armitage, Gerrard, Capstick, Andrea, McNeil, Heather, Holyoke, Paul, Vines, Chanile, Giosa, Justine, Khan, Bilal, Shultz, Mary, BEAUCHET, Olivier, Sekhon, Harmehr, Allali, Gilles, Montembeault, Maxime, Brodeur, Catherine, Macoir, Joël, Maxwell, Colleen, Maclagan, Laura, Campitelli, Michael, Yao, Shenzhen, Dharma, Christoffer, Sherin, Tracey, Hogan, David, Bronskill, Susan, Ivo, Jessica, Faisal, Sadaf, McDougall, Aidan, Bauer, Jillian, Pritchard, Sarah, Chang, Feng, Mehta, Deval, Syed, Ali, Carter, Caitlin, Sharma, Shaambhavi, Nagge, Jeff, Naglie, Gary, Stasiulis, Elaine, Yamin, Stephanie, Vrkljan, Brenda, Tuokko, Holly, Sanford, Sarah, Porter, Michelle, Polgar, Jan, Myers, Anita, Moorhouse, Paige, Mazer, Barbara, Marshall, Shawn, Gélinas, Isabelle, Crizzle, Alexander, Byszewski, Anna, Belchior, Patricia, Bédard, Michel, Rapoport, Mark, Minish, Duane, Yetman, Linda, Stephenson, Margaret, McCloskey, Rose, Agbaku, Mansa, Jarrett, Pamela, Cavanagh, Jennifer, Loncar, Adele, Demers, Vickie, Gobessi, Linda, Lodha, Vinay, Scerbe, Andrea, Astell, Arlene, DesRoches, Andrea, Panyavin, Ivan, Feltz, Nick, Wittich, Walter, Aubin, Gabrielle, Hogan, Mariah, Swaminathan, Swathi, Altschuler, Aviva, Murphy, Kelly, Guthrie, Dawn, Williams, Nicole, Campos, Jennifer, Mick, Paul, Orange, Joseph B., Pichora-Fuller, M. Kathleen, Savundranayagam, Marie Y., Phillips, Natalie A., Giroud, Nathalie, Pichora-Fuller, Kathy, Al-Yawer, Faisal, Rehan, Sana, Phillips, Natalie, Beauchet, Olivier, Niculescu, Iulia, Iaboni, Andrea, Quirt, Hannah, Penko, Marion, Tsokas, Mario, Marshall, Cecelia, Flint, Alastair, McGilton, Katherine, O’Connell, Megan E, Stewart, Norma J, Seitz, Dallas, Daku, Jean, Hack, Tracy, Hoium, Faye, Kennett-Russill, Deb, Sauter, Kristen, Holley, Joanna, Wimhurst, Christine, Katchaluba, Janet, Mitchell, Debbie, Severina, Elmira, Dallaire-Théroux, Caroline, Saikali, Stéphan, Duchesne, Simon, Sivananthan, Saskia, Mirza, Saira, Saeed, Usman, Knight, Jo, Ramirez, Joel, Stuss, Donald, Yu, Di, Swardfager, Walter, Keith, Julia, Nestor, Sean, Black, Sandra, Masellis, Mario, Joyal, Marilyne, Kotz, Sonja A., Lenglos, Christophe, Renauld, Emmanuelle, Wilson, Maximiliano A., Fecteau, Shirley, Appel, Lora, Kisonas, Erika, Appel, Eva, Bartlett, Deanna, Klein, Jennifer, Rosenberg, Jarred, Smith, Christopher, Ali, Suad, Narang, Tanya, Wiseman, Micaela, Ein, Natalie, Orchanian-Cheff, Ani, Rylett, Jane, Hogan, David B., Rockwood, Kenneth, Dixon, Roger, Sun, Winnie, Hawkins, Stacey A., Awde, Carolee, Kay, Kelly, Huntsbarger, Deana, Ferrier, Erin, Sourial, Nadia, Arsenault-Lapierre, Genevieve, McAiney, Carrie, Vedel, Isabelle, Ingram, K. Jennifer, Frank, Andrew, Sabra, Iman, Wallace, Bruce, Breau, Michael, Sweet, Lisa, Goubran, Rafiq, Knoefel, Frank, Goubran, Rafik, Stroulia, Eleni, Ault, Laura, Kecskemet, Judith, Guseva, Elena, Lungu, Ovidiu, Goldman, Sondra, Wilchesky, Machelle, Johri, Fozia, Turner, Angelese, Lavoie, Monica, Tang-Wai, David, Leonard, Carol, Graham, Naida L., Rochon, Elizabeth, Middleton, Laura, Herrmann, Nathan, Oh, Paul, Regan, Kayla, Bechard, Lauren, Lanctôt, Krista, Freeman, Shannon, Pettersen, Jacqueline, Tomasone, Jennifer, Dupuis, Sherry, Giangregorio, Lora, Ferris, Rebecca, Stultz, Tim, Mallard, Kirsten, Campbell, Elaine, Chatterjee, Atri, Mackenzie, Ian, Reinshagen, Veronica Hirsh, Ducharme, Blake, Mousavi, Ali, Gill, Sascha, Mouches, Pauline, Wang, Meng, Rajasheskar, Deepthi, MacMaster, Frank, Forkert, Nils, Smith, Eric, Ismail, Zahinoor, Varatharajah, Breni, Camicioli, Richard, Gee, Myrlene, Zwiers, Angela, Sekhon, Ramnik, Charlton, Anna, Arsenault-Lapierre, Geneviève, Ingram, Jennifer, Hawkins, Stacey, Mousavi, SeyedAli, Mackenzie, Ian R. A., Hirsh-Reinshagen, Veronica, Hsiung, Ging-Yuek. R., Gillingham, Susan M.E., Anderson, Nicole D., Alain, Claude, Georgievski, Georgi, Alfaro, Leonardo, McClenaghan, Meridith, Soares, Daniela, Matheson, Maureen, Stanoulis, Krisanne, Boyle, Daniel, Chau, Linh, Pelc, Jordan, Snash, Nadia, Byrne, Joanne, Elalouf, Karine, Alfaro, Andrea Urqueta, Johnson, Aaron, Marinier, Julie-Andrée, Kehayia, Eva, Gagné, Jean-Pierre, Murphy, Caitlin, Ellen, Ruth, Flowers, Brandi, Boulton, Karen Lee, Subotic, Arsenije, McCreary, Cheryl R., Nguyen, Amanda, Saad, Feryal, Alvarez, Ana, Beaudin, Andrew E, Pike, Bruce, Smith, Eric E, Hu, Sophie, Patten, Scott, Fick, Gordon, Sapkota, Shraddha, Mirza, Saira Saeed, Scott, Christopher J., Stuss, Donald T., Black, Sandra E., Le Blanc, Gabriella, Ducharme, Simon, Meilleur-Durand, Synthia, Lévesque, Marianne, St-Onge, Frédéric, Cunnane, Stephen, Villeneuve, Sylvia, Callahan, Brandy, Laforce, Robert, Cetin-Sahin, Deniz, Cummings, Greta G., Schuster, Tibor, Karanofsky, Mark, De Jesus, Belmir J., Cassani, Raymundo, Cecchi, Marco, Fadem, K. C., McGeown, William J., Falk, Tiago H., Chu, Charlene, Zdaniuk, Natalia, Wang, Rosalie, Ouellet, Marie-Christine, Cassivi-Joncas, Alison, Godard-Sebillotte, Claire, Rochette, Louis, Pelletier, Eric, Strumpf, Erin, Margo-Dermer, Eva, Silver, Hilah, Vafaei, Rod, Fok, Alice C, Hsiung, Ging-Yuek R., Ursenbach, Jake, Bethell, Jennifer, Neuman, Mark D, Bateman, Brian T, Hill, Andrea, Wunsch, Hannah, Ritchie, Kim, Cramm, Heidi, Aiken, Alice, Donnelly, Catherine, Goldie, Katie, Delara, Mahin, Ozzoude, Miracle, Varriano, Brenda, McLaughlin, Paula, Troyer, Angela, Bartha, Robert, Symons, Sean, Kwan, Donna, Tan, Brian, Swartz, Richard H., Saposnik, Gustavo, Tartaglia, Maria C., Ahuja, Manan, Siddhpuria, Shailee, Gormley, Jessica, Reppas, Christina, Wong, Eric, Lee, Justin, Patterson, Christopher, Walker, Jennifer, Warry, Wayne, Blind, Melissa, Allaby, Cheryl, Pitawanakwat, Karen, Zhao, Yantao, Lemieux, Andrine, Jacklin, Kristen, Crowshoe, Lindsay, Boehme, Gail, McKenna, Betty, Boyling, Elaine, Webkamigad, Sharlene, Bigeagle, Louise, Akan, Nicole, Wallace, Lindsay, Theou, Olga, Bennett, David, Darvesh, Sultan, Kirkland, Susan, Fisk, John, Andrew, Melissa, Cullen, Stephanie, Carroll, Susan, Mahon, Joel, Sarquis-Adamson, Yanina, Montero-Odasso, Manuel, Sharma, Nabina, Beaton, Derek, Roberts, Angela, Munoz, Doug, Swartz, Richard, Breen, David, Lang, Anthony, Fischer, COrrine, Fischer, Corrine, Kumar, Sanjeeve, Freedman, Morris, Finger, Elizabeth, Zinman, Lorne, Grimes, David A., Sunderland, Kelly M., Binns, Malcolm A., Strother, Stephen C., Mandzia, Jennifer, Orange, JB, Tartaglia, Carmela, El Shatshat, Amna, Rao, Praveen P.N., Teves, Julia, Bodkin, R Jack, Ho, Joanne M-W, Mehdizadeh, Sina, Dolatabadi, Elham, Ng, Kimberley-Dale, Arora, Twinkle, Jizmejian, Melody, Mansfield, Avril, Taati, Babak, Levy, Jake, Savard, Melissa, Pascoal, Tharick, Soucy, Jean-Paul, Rosa-Neto, Pedro, Martins, Felicia, Waller, Shannon, Flora, Parminder, Morland, Chris, Donovan, Steve, Fels, Deborah, Desai, Shital, Boger, Jennifer, Shashtri, Karan, Persaud, Deanna, Marashi, Sheida, Nedlund, Ann-Charlotte, Mäki-Petäjä-Leinonen, Anna, Nygård, Louise, Issakainen, Mervi, ryd, Charlotta, Pan, Yuhan, Joddrell, Phil, Dove, Erica, Owens, Hollis, Park, Elly, Liu, Lili, Kaufman, David, Simonian, Natalie, Chen, Ying, Sunderland, Kelly, Fraser, Julia, Swartz, Rick, Strother, Stephen, Legrand, Diego, Roberge, Pasquale, Vanasse, Alain, Bocti, Christian, Pirrie, Lorraine, Gray, Carolyn Steele, Nippak, Pria, Coughlan, Dave, Teselink, Johannes, Hermann, Nathan, Rasquinha, Fawn, Lanctot, Krista, Webber, Jodi, Woo, Kevin, Chamoun, Elicia, Coulombe, Valérie, Sellami, Leila, Paquette-Raynard, Emmanuelle, Gardner, Sandra, van Zon, Lorraine, Moy, Sally, Sidrak, Mariam, Sternhill, Janis, Feldman, Sidney, Karuza, Jurgis, Berall, Anna, Thomas, Neil, Mattek, Nora, Riley, Thomas, Reynolds, Christina, Marcoe, Jennifer, Sharma, Nicole, Kaye, Jeffrey, Jagtap, Shreya, Rotenberg, Shlomit, Vandermorris, Susan, Anderson, ND, Dawson, DR, Chater, Catherine, Soor, Jaspreet, Ji, Xiang, Koo, Morgan, Compagnone, Jordana, Kertes, Peter, Juby, Angela, Mager, Diana, Davis, Christopher, Jay, David, Blackburn, Toni, Brocks, Dion, Lee, Hyunwoo, Wiggermann, Vanessa, Rauscher, Alexander, Lam, Kevin, Tam, Roger, Popuri, Karteek, Beg, Mirza Faisal, Jacova, Claudia, Sossi, Vesna, Bindra, Jessica, Bouvier, Liziane, Monetta, Laura, Vitali, Paolo, Martel-Sauvageau, Vincent, Godin, Judith, McNeil, Shelly, McElhaney, Janet, Laughton, Thomas, Ho, Joanne, Tung, Jennifer, Dubé, Joseph B., Lin, Tianzhen, Best, Sarah, Truemner, Julia, Sargeant, Patricia L., Borrie, Michael J., Fogarty, Jennifer, Bassi, Nimi, Di Prospero, Cynthia, Whitehead, Victor, Pilon, Randi, Wong, Timothy, Elhayek, Nada, Dasgupta, Monidipa, Davis, Daniel, ORegan, Niamh, Kröger, Edeltraut, Furrer, Daniela, Wilcheski, Machelle, Morin, Michèle, Carmichael, Pierre-Hugues, Champoux, Nathalie, Monette, Johanne, Giguère, Anik, Aubin, Michèle, Durand, Pierre, Whiteside, Jena, Mele, Bria, Merrikh, Daria, Goodarzi, Zahra, Seary, Judith Anne, Bulley, Heather, Diciacca, Allison, Esseltine, Julia, Gaiger, Erin, Jankovic, Ivana, Mackenzie, Stephanie, McBride, Meghan, Knopp-Sihota, Jennifer A., Hoben, Mathias, Poss, Jeffrey W., Rachor, Geoffrey S., Estabrooks, Carole A., and Iroanyah, Ngozi

Subjects
Abstracts: Posters
Published
2020

15. Linking lesions in sensorimotor cortex to contralateral hand function in multiple sclerosis:A 7 T MRI study

Author

Madsen, Mads A.J., Wiggermann, Vanessa, Marques, Marta F.M., Lundell, Henrik, Cerri, Stefano, Puonti, Oula, Blinkenberg, Morten, Romme Christensen, Jeppe, Sellebjerg, Finn, Siebner, Hartwig R., Madsen, Mads A.J., Wiggermann, Vanessa, Marques, Marta F.M., Lundell, Henrik, Cerri, Stefano, Puonti, Oula, Blinkenberg, Morten, Romme Christensen, Jeppe, Sellebjerg, Finn, and Siebner, Hartwig R.

Abstract

Cortical lesions constitute a key manifestation of multiple sclerosis and contribute to clinical disability and cognitive impairment. Yet it is unknown whether local cortical lesions and cortical lesion subtypes contribute to domain-specific impairments attributable to the function of the lesioned cortex. In this cross-sectional study, we assessed how cortical lesions in the primary sensorimotor hand area relate to corticomotor physiology and sensorimotor function of the contralateral hand. Fifty relapse-free patients with relapsing-remitting or secondary-progressive multiple sclerosis and 28 healthy age- and sex-matched participants underwent whole-brain 7 T MRI to map cortical lesions. Brain scans were also used to estimate normalized brain volume, pericentral cortical thickness, white matter lesion fraction of the corticospinal tract, infratentorial lesion volume and the cross-sectional area of the upper cervical spinal cord. We tested sensorimotor hand function and calculated a motor and sensory composite score for each hand. In 37 patients and 20 healthy controls, we measured maximal motor-evoked potential amplitude, resting motor threshold and corticomotor conduction time with transcranial magnetic stimulation and the N20 latency from somatosensory-evoked potentials. Patients showed at least one cortical lesion in the primary sensorimotor hand area in 47 of 100 hemispheres. The presence of a lesion was associated with worse contralateral sensory (P = 0.014) and motor (P = 0.009) composite scores. Transcranial magnetic stimulation of a lesion-positive primary sensorimotor hand area revealed a decreased maximal motor-evoked potential amplitude (P < 0.001) and delayed corticomotor conduction (P = 0.002) relative to a lesion-negative primary sensorimotor hand area. Stepwise mixed linear regressions showed that the presence of a primary sensorimotor hand area lesion, higher white-matter lesion fraction of the corticospinal tract, reduced spinal cord cross-sec

Published
2022

16. Linking lesions in sensorimotor cortex to contralateral hand function in multiple sclerosis:a 7 T MRI study

Author

Madsen, Mads A. J., Wiggermann, Vanessa, Marques, Marta F. M., Lundell, Henrik, Cerri, Stefano, Puonti, Oula, Blinkenberg, Morten, Christensen, Jeppe Romme, Sellebjerg, Finn, Siebner, Hartwig R., Madsen, Mads A. J., Wiggermann, Vanessa, Marques, Marta F. M., Lundell, Henrik, Cerri, Stefano, Puonti, Oula, Blinkenberg, Morten, Christensen, Jeppe Romme, Sellebjerg, Finn, and Siebner, Hartwig R.

Abstract

Cortical lesions constitute a key manifestation of multiple sclerosis and contribute to clinical disability and cognitive impairment. Yet it is unknown whether local cortical lesions and cortical lesion subtypes contribute to domain-specific impairments attributable to the function of the lesioned cortex. In this cross-sectional study, we assessed how cortical lesions in the primary sensorimotor hand area relate to corticomotor physiology and sensorimotor function of the contralateral hand. Fifty relapse-free patients with relapsing-remitting or secondary-progressive multiple sclerosis and 28 healthy age- and sex-matched participants underwent whole-brain 7 T MRI to map cortical lesions. Brain scans were also used to estimate normalized brain volume, pericentral cortical thickness, white matter lesion fraction of the corticospinal tract, infratentorial lesion volume and the cross-sectional area of the upper cervical spinal cord. We tested sensorimotor hand function and calculated a motor and sensory composite score for each hand. In 37 patients and 20 healthy controls, we measured maximal motor-evoked potential amplitude, resting motor threshold and corticomotor conduction time with transcranial magnetic stimulation and the N20 latency from somatosensory-evoked potentials. Patients showed at least one cortical lesion in the primary sensorimotor hand area in 47 of 100 hemispheres. The presence of a lesion was associated with worse contralateral sensory (P = 0.014) and motor (P = 0.009) composite scores. Transcranial magnetic stimulation of a lesion-positive primary sensorimotor hand area revealed a decreased maximal motor-evoked potential amplitude (P < 0.001) and delayed corticomotor conduction (P = 0.002) relative to a lesion-negative primary sensorimotor hand area. Stepwise mixed linear regressions showed that the presence of a primary sensorimotor hand area lesion, higher white-matter lesion fraction of the corticospinal tract, reduced spinal cord cross-sectio

Published
2022

18. Brain Imaging Abnormalities in Mixed Alzheimer’s and Subcortical Vascular Dementia

Author

Lee, Hyunwoo, Wiggermann, Vanessa, Rauscher, Alexander, Kames, Christian, Beg, Mirza Faisal, Popuri, Karteek, Tam, Roger, Lam, Kevin, Jacova, Claudia, Shahinfard, Elham, Sossi, Vesna, Pettersen, Jacqueline A., and Hsiung, Ging-Yuek Robin

Abstract

ABSTRACT:Background:A large proportion of Alzheimer’s disease (AD) patients have coexisting subcortical vascular dementia (SVaD), a condition referred to as mixed dementia (MixD). Brain imaging features of MixD presumably include those of cerebrovascular disease and AD pathology, but are difficult to characterize due to their heterogeneity.Objective:To perform an exploratory analysis of conventional and non-conventional structural magnetic resonance imaging (MRI) abnormalities in MixD and to compare them to those observed in AD and SVaD.Methods:We conducted a cross-sectional, region-of-interest-based analysis of 1) hyperintense white-matter signal abnormalities (WMSA) on T2-FLAIR and hypointense WMSA on T1-weighted MRI; 2) diffusion tensor imaging; 3) quantitative susceptibility mapping; and 4) effective transverse relaxation rate (R2*) in N = 17 participants (AD:5, SVaD:5, MixD:7). General linear model was used to explore group differences in these brain imaging measures.Results:Model findings suggested imaging characteristics specific to our MixD group, including 1) higher burden of WMSAs on T1-weighted MRI (versus both AD and SVaD); 2) frontal lobar preponderance of WMSAs on both T2-FLAIR and T1-weighted MRI; 3) higher fractional anisotropy values within normal-appear white-matter tissues (versus SVaD, but not AD); and 4) lower R2* values within the T2-FLAIR WMSA areas (versus both AD and SVaD).Conclusion:These findings suggest a preliminary picture of the location and type of brain imaging characteristics associated with MixD. Future imaging studies may employ region-specific hypotheses to distinguish MixD more rigorously from AD or SVaD.

Published
2023
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20. Associations between white matter hyperintensities and cognitive dysfunction in Alzheimer’s, vascular and mixed dementias

Author

Lee, Hyunwoo, primary, Wiggermann, Vanessa, additional, Rauscher, Alexander, additional, Beg, Mirza Faisal, additional, Popuri, Karteek, additional, Tam, Roger, additional, Lam, Kevin, additional, Liu‐Ambrose, Teresa, additional, Dao, Elizabeth, additional, Keridy, Walid Ahmed Al, additional, Jacova, Claudia, additional, Sossi, Vesna, additional, Pettersen, Jacqueline, additional, Benavente, Oscar R., additional, and Hsiung, Ging‐Yuek Robin, additional

Published
2020
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21. Pilot study of MRI white matter tissue properties in Alzheimer’s, vascular and mixed dementias

Author

Lee, Hyunwoo, primary, Wiggermann, Vanessa, additional, Rauscher, Alexander, additional, Beg, Mirza Faisal, additional, Popuri, Karteek, additional, Tam, Roger, additional, Lam, Kevin, additional, Jacova, Claudia, additional, Sossi, Vesna, additional, Pettersen, Jacqueline, additional, Benavente, Oscar R., additional, and Hsiung, Ging‐Yuek Robin, additional

Published
2020
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22. Lobar distribution of white matter abnormalities in Alzheimer’s, vascular and mixed dementias

Author

Lee, Hyunwoo, primary, Wiggermann, Vanessa, additional, Rauscher, Alexander, additional, Beg, Mirza Faisal, additional, Popuri, Karteek, additional, Tam, Roger, additional, Lam, Kevin, additional, Jacova, Claudia, additional, Sossi, Vesna, additional, Pettersen, Jacqueline, additional, Benavente, Oscar R., additional, and Hsiung, Ging‐Yuek Robin, additional

Published
2020
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26. Gradient and spin echo magnetic resonance imaging for the characterization of myelin health in multiple sclerosis

Author

Wiggermann, Vanessa

Abstract

Multiple sclerosis (MS) is a complex, autoimmune disease that results in demyelination and neurodegeneration. Magnetic resonance imaging (MRI) is an essential cornerstone of MS diagnosis and clinical decision making, however, clinical MRIs lack specificity to the pathological mechanisms influencing myelin health. In this thesis, two quantitative MRI techniques were probed for their potential to study myelin health in MS. First, multi-echo spin-echo myelin water imaging (MWI) was tested for its specificity to myelin lipids, proteins and iron. We demonstrated to-date unknown sensitivity of MWI and identified MS lesion changes indicative of late-stage remyelination. Thereafter, the accuracy of MWI and its potential application at ultra-high magnetic fields were investigated. Using signal simulations, the dependence of the non-negative least-squares analysis on processing and tissue parameters was described. Myelin underestimations due to B⁺₁-inhomogeneities and noise were shown to be minimized by adjusting the T₂ range according to the echo time. To translate MWI to 7T, T₂ tissue properties in seven healthy subjects were studied in comparison to 3T. We demonstrated the feasibility of 7T-MWI and discussed current limitations in assessing short T₂ times. Secondly, susceptibility-sensitive MRI was explored, which provides greater sensitivity, albeit possibly lower specificity to myelin, than MWI. Using the phase component, we showed that the MS lesion contrast is typically not driven by iron accumulation. In simulations and with post-mortem data, it was demonstrated that iron and myelin loss in combination determine the lesions’ appearance. Thereafter, the potential of the technique to become a marker of tissue damage and repair was evaluated by studying the evolution and pathological underpinnings of acute MS lesions in eleven patients over five years. Current models and their shortcomings were discussed. Finally, two technical developments were introduced. First, a multi-dynamic, high-spatial resolution susceptibility-sensitive imaging approach was presented for visualizing the central vein sign. Using phantom and in vivo data, qualitative and quantitative agreement of the proposed approach with other imaging strategies was demonstrated. Secondly, FLAIR² was introduced, a novel contrast that improves contrast-to-noise, while shortening scan time. The potential of FLAIR² to aid automated lesion segmentation was demonstrated on real-world multi-centre clinical data.

Published
2020
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27. Myelin Damage in Normal Appearing White Matter Contributes to Impaired Cognitive Processing Speed in Multiple Sclerosis

Author

Abel, Shawna, primary, Vavasour, Irene, additional, Lee, Lisa Eunyoung, additional, Johnson, Poljanka, additional, Ackermans, Nathalie, additional, Chan, Jillian, additional, Dvorak, Adam, additional, Schabas, Alice, additional, Wiggermann, Vanessa, additional, Tam, Roger, additional, Kuan, Annie J., additional, Morrow, Sarah A., additional, Wilken, Jeffrey, additional, Laule, Cornelia, additional, Rauscher, Alexander, additional, Bhan, Virender, additional, Sayao, Ana‐Luiza, additional, Devonshire, Virginia, additional, Li, David KB, additional, Carruthers, Robert, additional, Traboulsee, Anthony, additional, and Kolind, Shannon H., additional

Published
2019
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28. IC-P-083: CORRELATION OF QUANTITATIVE SUSCEPTIBILITY MAPPING AND COGNITIVE DYSFUNCTION IN MIXED ALZHEIMER'S AND VASCULAR DEMENTIA

Author

Lee, Hyunwoo, primary, Wiggermann, Vanessa, additional, Rauscher, Alexander, additional, Kames, Christian, additional, Beg, Mirza Faisal, additional, Jacova, Claudia, additional, Sossi, Vesna, additional, Benavente, Oscar R., additional, Pettersen, Jacqueline A., additional, and Robin Hsiung, Ging-Yuek, additional

Published
2019
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31. Regional Myelin-Specific MRI Abnormalities in Susac Syndrome Suggests Demyelination is a Pathologic Feature (P5.2-061)

Author

Johnson, Poljanka, primary, Chan, Jillian, additional, Vavasour, Irene, additional, Abel, Shawna, additional, Lee, Lisa Eunyoung, additional, Yong, Heather, additional, Wiggermann, Vanessa, additional, Laule, Cornelia, additional, Woolfenden, Andrew, additional, Traboulsee, Anthony, additional, Li, David, additional, Tam, Roger, additional, Kolind, Shannon, additional, and Carruthers, Robert, additional

Published
2019
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32. Non-negative least squares fitting of multi-exponential T2 decay data: Are we able to accurately measure the fraction of myelin water?

Author

Wiggermann, Vanessa, Vavasour, Irene M, Hernandez-Torres, Ernedino, Helms, Gunther, MacKay, Alex L, Rauscher, Alexander, Wiggermann, Vanessa, Vavasour, Irene M, Hernandez-Torres, Ernedino, Helms, Gunther, MacKay, Alex L, and Rauscher, Alexander

Abstract

The ability to determine the myelin water fraction (MWF) in vivo is essential to assessments of neurodevelopmental myelination and myelin damage in neurodegenerative diseases. The analysis of multi-exponential T2 decay data relies on the non-negative-least-squares (NNLS) fitting, which may be sensitive to the chosen fitting parameters. We performed simulations to explore the outcomes of NNLS under different parameter selection. The lowest allowed T2 was found to have the largest effect on correctly estimating the T2 of different water pools as well as the MWF. Lower refocusing FAs led to further underestimation of the MWF.

Published
2019

33. In vivo investigation of the multi‐exponential T2 decay in human white matter at 7 T: Implications for myelin water imaging at UHF.

Author

Wiggermann, Vanessa, MacKay, Alexander L., Rauscher, Alexander, and Helms, Gunther

Subjects
WHITE matter (Nerve tissue), MAGNETIC resonance imaging, MYELIN, MAGNETIC flux density, NEURAL stimulation
Abstract

Introduction: Multi‐component T2 mapping using a gradient‐ and spin‐echo (GraSE) acquisition has become standard for myelin water imaging at 3 T. Higher magnetic field strengths promise signal‐to‐noise ratio benefits but face specific absorption rate limits and shortened T2 times. This study investigates compartmental T2 times in vivo and addresses advantages and challenges of multi‐component T2 mapping at 7 T. Methods: We acquired 3D multi‐echo GraSE data in seven healthy adults at 7 T, with three subjects also scanned at 3 T. Stimulated echoes arising from B1+ inhomogeneities were accounted for by the extended phase graph (EPG) algorithm. We used the computed T2 distributions to determine T2 times that identify different water pools and assessed signal‐to‐noise and fit‐to‐noise characteristics of the signal estimation. We compared short T2 fractions and T2 properties of the intermediate water pool at 3 T and 7 T. Results: Flip angle mapping confirmed that EPG accurately determined the larger B1+ inhomogeneity at 7 T. Multi‐component T2 analysis demonstrated shortened T2 times at 7 T compared with 3 T. Fit‐to‐noise and signal‐to‐noise ratios were improved at 7 T but depended on B1+ homogeneity. Adjusting the shortest T2 to 8 ms and the T2 threshold that separates different water compartments to 20 ms yielded short T2 fractions at 7 T that conformed to 3 T data. Short T2 fractions in myelin‐rich white matter regions were lower at 7 T than at 3 T, and higher in iron‐rich structures. Discussion: Adjusting the T2 compartment boundaries was required due to the shorter T2 relaxation times at 7 T. Shorter echo spacing would better sample the fast decaying signal but would increase peripheral nerve stimulation. Multi‐channel transmission will improve T2 measurements at 7 T. Conclusion: We used a multi‐echo 3D GraSE sequence to characterize the multi‐exponential T2 decay at 7 T. We adapted T2 parameters for evaluation of the short T2 fraction. Obtained 7 T multi‐component T2 maps were in good agreement with 3 T data. [ABSTRACT FROM AUTHOR]

Published
2021
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34. Multi‐spin echo T2 relaxation imaging with compressed sensing (METRICS) for rapid myelin water imaging.

Author

Dvorak, Adam V., Wiggermann, Vanessa, Gilbert, Guillaume, Vavasour, Irene M., MacMillan, Erin L., Barlow, Laura, Wiley, Neale, Kozlowski, Piotr, MacKay, Alex L., Rauscher, Alexander, and Kolind, Shannon H.

Subjects
COMPRESSED sensing, ECHO, MYELIN, RELAXATION for health, REFERENCE values
Abstract

Purpose: Myelin water imaging (MWI) provides a valuable biomarker for myelin, but clinical application has been restricted by long acquisition times. Accelerating the standard multi‐echo T2 acquisition with gradient echoes (GRASE) or by 2D multi‐slice data collection results in image blurring, contrast changes, and other issues. Compressed sensing (CS) can vastly accelerate conventional MRI. In this work, we assessed the use of CS for in vivo human MWI, using a 3D multi spin‐echo sequence. Methods: We implemented multi‐echo T2 relaxation imaging with compressed sensing (METRICS) and METRICS with partial Fourier acceleration (METRICS‐PF). Scan‐rescan data were acquired from 12 healthy controls for assessment of repeatability. MWI data were acquired for METRICS in 9 m:58 s and for METRICS‐PF in 7 m:25 s, both with 1.5 × 2 × 3 mm3 voxels, 56 echoes, 7 ms ΔTE, and 240 × 240 × 170 mm3 FOV. METRICS was compared with a novel multi‐echo spin‐echo gold‐standard (MSE‐GS) MWI acquisition, acquired for a single additional subject in 2 h:2 m:40 s. Results: METRICS/METRICS‐PF myelin water fraction had mean: repeatability coefficient 1.5/1.1, coefficient of variation 6.2/4.5%, and intra‐class correlation coefficient 0.79/0.84. Repeatability metrics comparing METRICS with METRICS‐PF were similar, and both sequences agreed with reference values from literature. METRICS images and quantitative maps showed excellent qualitative agreement with those of MSE‐GS. Conclusion: METRICS and METRICS‐PF provided highly repeatable MWI data without the inherent disadvantages of GRASE or 2D multi‐slice acquisition. CS acceleration allows MWI data to be acquired rapidly with larger FOV, higher estimated SNR, more isotropic voxels and more echoes than with previous techniques. The approach introduced here generalizes to any multi‐component T2 mapping application. [ABSTRACT FROM AUTHOR]

Published
2020
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35. Myelin Damage in Normal Appearing White Matter Contributes to Impaired Cognitive Processing Speed in Multiple Sclerosis.

Author

Abel, Shawna, Vavasour, Irene, Lee, Lisa Eunyoung, Johnson, Poljanka, Ackermans, Nathalie, Chan, Jillian, Dvorak, Adam, Schabas, Alice, Wiggermann, Vanessa, Tam, Roger, Kuan, Annie J., Morrow, Sarah A., Wilken, Jeffrey, Laule, Cornelia, Rauscher, Alexander, Bhan, Virender, Sayao, Ana‐Luiza, Devonshire, Virginia, Li, David KB, and Carruthers, Robert

Subjects
MYELIN, MULTIPLE sclerosis, COGNITION disorders, CORPUS callosum, WHITE matter (Nerve tissue), MYELIN proteins, SPEED
Abstract

Background and Purpose: Cognitive impairment is a core symptom in multiple sclerosis (MS). Damage to normal appearing white matter (NAWM) is likely involved. We sought to determine if greater myelin heterogeneity in NAWM is associated with decreased cognitive performance in MS.Methods: A total of 27 participants with MS and 13 controls matched for age, sex, and education underwent myelin water imaging (MWI) from which the myelin water fraction (MWF) was calculated. Corpus callosum, superior longitudinal fasciculus, and cingulum were chosen as regions of interest (ROIs) a priori based on their involvement in MS-related cognitive impairment. Cognitive performance was assessed using the Symbol Digit Modalities Test (SDMT). Pearson ́s product moment correlations were performed to assess relationships between cognitive performance and myelin heterogeneity (variance of MWF within an ROI).Results: In MS, myelin heterogeneity in all three ROIs was significantly associated with performance on the SDMT. These correlations ranged from moderate (r = -.561) to moderately strong (r = -.654) and were highly significant (P values ranged from .001 to .0002). Conversely, myelin heterogeneity was not associated with SDMT performance in controls in any ROI (P > .108).Conclusion: Increased myelin heterogeneity in NAWM is associated with decreased cognitive processing speed performance in MS. [ABSTRACT FROM AUTHOR]

Published
2020
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36. Longitudinal advanced MRI case report of white matter radiation necrosis

Author

Wiggermann, Vanessa, primary, Lapointe, Emmanuelle, additional, Litvin, Ludmila, additional, Graf, Carina, additional, Hernández‐Torres, Enedino, additional, McKenzie, Michael, additional, Vavasour, Irene M., additional, Laule, Cornelia, additional, MacMillan, Erin L., additional, Li, David K. B., additional, Kolind, Shannon H., additional, Rauscher, Alexander, additional, and Traboulsee, Anthony L., additional

Published
2018
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39. Cover Image, Volume 30, Issue 8

Author

Wiggermann, Vanessa, primary, Hametner, Simon, additional, Hernández-Torres, Enedino, additional, Kames, Christian, additional, Endmayr, Verena, additional, Kasprian, Gregor, additional, Höftberger, Romana, additional, Li, David K.B., additional, Traboulsee, Anthony, additional, and Rauscher, Alexander, additional

Published
2017
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42. Increased mean R2* in the deep gray matter of multiple sclerosis patients: Have we been measuring atrophy?

Author

Hernández‐Torres, Enedino, Wiggermann, Vanessa, Machan, Lindsay, Sadovnick, A. Dessa, Li, David K.B., Traboulsee, Anthony, Hametner, Simon, Rauscher, Alexander, and Hernández-Torres, Enedino

Subjects
MULTIPLE sclerosis, DIFFUSION tensor imaging, ATROPHY, MAGNETIC susceptibility, MAGNETIC resonance
Abstract

Background: Magnetic resonance relaxometry studies in multiple sclerosis (MS) have suggested that iron accumulates within deep gray matter (DGM) structures early in the disease course. However, the commonly utilized mean R2* and magnetic susceptibility measures reflect regional iron concentration but not a structure's total iron content. Thus, tissue atrophy could impact mean R2* and magnetic susceptibility estimates.Purpose: To demonstrate that both average iron concentration and total iron content need to be reported in order to distinguish between atrophy-related and definite magnetic susceptibility changes.Study Type: Observational.Population: The study was performed on 30 healthy controls (HCs) and 39 people with definite MS.Field Strength/sequence: 3T Philips Achieva using an 8-channel SENSE head coil. R2* data were acquired using a multiecho gradient echo sequence and diffusion tensor imaging data were acquired using an echo-planar sequence.Assessment: Total iron content in DGM structures was assessed by calculating the sum of all R2* values within a region (denoted as R2mass* ) and compared to the mean R2* as a measure of iron concentration.Statistical Test: Significant group differences were investigated in a linear regression model. All DGM structures were assessed individually and the significance threshold was adjusted using the Bonferroni-Holm correction for multiple comparisons.Results: There was an increased mean DGM R2* in MS patients compared to HCs (significant in the pallidus, P = 0.0051). In contrast, R2mass* in patients was found to be lower in the thalamus and the caudate (P = 0.0011) compared to HCs, and similar between the two cohorts in the other DGM regions.Data Conclusion: An increase in mean R2* may not necessarily reflect increased iron accumulation. We propose R2mass* as an additional metric to account for the effects of tissue atrophy when assessing tissue content changes, such as iron deposition or loss.Level Of Evidence: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:201-208. [ABSTRACT FROM AUTHOR]

Published
2019
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43. The role of iron and myelin in orientation dependent R2* of white matter.

Author

Kor, Daniel, Birkl, Christoph, Ropele, Stefan, Doucette, Jonathan, Xu, Tianyou, Wiggermann, Vanessa, Hernández‐Torres, Enedino, Hametner, Simon, and Rauscher, Alexander

Subjects
MYELIN, IRON, DIOXYGENASES, NEURODEGENERATION, MULTIPLE sclerosis, MAGNETIC fields
Abstract

Brain myelin and iron content are important parameters in neurodegenerative diseases such as multiple sclerosis (MS). Both myelin and iron content influence the brain's R2* relaxation rate. However, their quantification based on R2* maps requires a realistic tissue model that can be fitted to the measured data. In structures with low myelin content, such as deep gray matter, R2* shows a linear increase with increasing iron content. In white matter, R2* is not only affected by iron and myelin but also by the orientation of the myelinated axons with respect to the external magnetic field. Here, we propose a numerical model which incorporates iron and myelin, as well as fibre orientation, to simulate R2* decay in white matter. Applying our model to fibre orientation‐dependent in vivo R2* data, we are able to determine a unique solution of myelin and iron content in global white matter. We determine an averaged myelin volume fraction of 16.02 ± 2.07% in non‐lesional white matter of patients with MS, 17.32 ± 2.20% in matched healthy controls, and 18.19 ± 2.98% in healthy siblings of patients with MS. Averaged iron content was 35.6 ± 8.9 mg/kg tissue in patients, 43.1 ± 8.3 mg/kg in controls, and 47.8 ± 8.2 mg/kg in siblings. All differences in iron content between groups were significant, while the difference in myelin content between MS patients and the siblings of MS patients was significant. In conclusion, we demonstrate that a model that combines myelin‐induced orientation‐dependent and iron‐induced orientation‐independent components is able to fit in vivo R2* data. [ABSTRACT FROM AUTHOR]

Published
2019
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44. Longitudinal advanced MRI case report of white matter radiation necrosis.

Author

Wiggermann, Vanessa, Lapointe, Emmanuelle, Litvin, Ludmila, Graf, Carina, Hernández‐Torres, Enedino, McKenzie, Michael, Vavasour, Irene M., Laule, Cornelia, MacMillan, Erin L., Li, David K. B., Kolind, Shannon H., Rauscher, Alexander, and Traboulsee, Anthony L.

Subjects
*EFFECT of radiation on cells, *NUCLEAR magnetic resonance spectroscopy, *CEREBRAL arteriovenous malformations, *NECROSIS, *RADIATION, *MAGNETIC resonance imaging, *STEREOTACTIC radiosurgery
Abstract

Radiation necrosis mostly occurs in and near the radiation field. We used magnetic resonance imaging to study radiation‐induced necrosis of atypical onset, severity, and extent following stereotactic radiosurgery for a symptomatic arteriovenous malformation. Susceptibility‐sensitive imaging, T1‐relaxation, myelin water imaging, and magnetic resonance spectroscopy were acquired three times up to 52 months postradiosurgery. Increasing water content outside the radiation field, contralateral neuronal loss, and gliosis were detected over time. Our findings suggest that radiation‐induced vasculopathic changes spread more diffusely than previously described. An autoimmune response to brain antigens could underlie white matter changes outside the initial radiation field. [ABSTRACT FROM AUTHOR]

Published
2019
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46. Multi‐echo GRE imaging of knee cartilage

Author

Yuen, Joanna, primary, Hung, Jachin, additional, Wiggermann, Vanessa, additional, Robinson, Simon D., additional, McCormack, Robert, additional, d'Entremont, Agnes G., additional, and Rauscher, Alexander, additional

Published
2016
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47. Anisotropic cerebral vascular architecture causes orientation dependency in cerebral blood flow and volume measured with dynamic susceptibility contrast magnetic resonance imaging

Author

Hernández-Torres, Enedino, primary, Kassner, Nora, additional, Forkert, Nils Daniel, additional, Wei, Luxi, additional, Wiggermann, Vanessa, additional, Daemen, Madeleine, additional, Machan, Lindsay, additional, Traboulsee, Anthony, additional, Li, David, additional, and Rauscher, Alexander, additional

Published
2016
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