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1. Safety and Efficacy of Tenecteplase and Alteplase in Patients With Tandem Lesion Stroke: A Post Hoc Analysis of the EXTEND-IA TNK Trials.

Author

Yogendrakumar, Vignan, Churilov, Leonid, Mitchell, Peter J., Kleinig, Timothy J., Yassi, Nawaf, Thijs, Vincent, Wu, Teddy, Shah, Darshan, Bailey, Peter, Dewey, Helen M., Choi, Philip M.C., Ma, Alice, Wijeratne, Tissa, Garcia-Esperon, Carlos, Cloud, Geoffrey, Chandra, Ronil V., Cordato, Dennis J., Yan, Bernard, Sharma, Gagan, and Desmond, Patricia M.

Published
2023
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2. Tenecteplase Treatment and Thrombus Characteristics Associated With Early Reperfusion: An EXTEND-IA TNK Trials Analysis.

Author

Yogendrakumar, Vignan, Churilov, Leonid, Guha, Prodipta, Beharry, James, Mitchell, Peter J., Kleinig, Timothy J., Yassi, Nawaf, Thijs, Vincent, Wu, Teddy Y., Brown, Helen, Dewey, Helen M., Wijeratne, Tissa, Yan, Bernard, Sharma, Gagan, Desmond, Patricia M., Parsons, Mark W., Donnan, Geoffrey A., Davis, Stephen M., Campbell, Bruce C.V., and Dowling, Richard

Published
2023
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3. Safety and Efficacy of Tenecteplase and Alteplase in Patients With Tandem Lesion Stroke

Author

Yogendrakumar, Vignan, Churilov, Leonid, Mitchell, Peter J., Kleinig, Timothy J., Yassi, Nawaf, Thijs, Vincent, Wu, Teddy, Shah, Darshan, Bailey, Peter, Dewey, Helen M., Choi, Philip M.C., Ma, Alice, Wijeratne, Tissa, Garcia-Esperon, Carlos, Cloud, Geoffrey, Chandra, Ronil V., Cordato, Dennis J., Yan, Bernard, Sharma, Gagan, Desmond, Patricia M., Parsons, Mark W., Donnan, Geoffrey A., Davis, Stephen M., Campbell, Bruce C.V., Dowling, Richard, Bush, Steven, Scroop, Rebecca, Simpson, Marion, Brooks, Mark, Asadi, Hamed, Ang, Timothy, Miteff, Ferdinand, Levi, Christopher, Rodrigues, Edrich, Zhao, Henry, Ng, Felix, Alemseged, Fana, Salvaris, Patrick, Rice, Henry, de Villiers, Laetitia, Brown, Helen, Redmond, Kendal, Leggett, David, Fink, John, Collecutt, Wayne, Kraemer, Thomas, Muller, Claire, Coulthard, Alan, Mitchell, Ken, Clouston, John, Mahady, Kate, Field, Deborah, O’Brien, Bill, Clissold, Benjamin, Clissold, Anna, Bolitho, Leslie, Bonavia, Luke, Bhattacharya, Arup, Wright, Alistair, Mamun, Abul, O’Rourke, Fintan, Worthington, John, Wong, Andrew, Ma, Henry, Phan, Thanh, Chong, Winston, Slater, Lee-Anne, Krause, Martin, Harrington, Timothy, Faulder, Kenneth, Steinfort, Brendan, and Bladin, Christopher

Published
2023
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4. Tenecteplase Treatment and Thrombus Characteristics Associated With Early Reperfusion: An EXTEND-IA TNK Trials Analysis

Author

Yogendrakumar, Vignan, Churilov, Leonid, Guha, Prodipta, Beharry, James, Mitchell, Peter J., Kleinig, Timothy J., Yassi, Nawaf, Thijs, Vincent, Wu, Teddy Y., Brown, Helen, Dewey, Helen M., Wijeratne, Tissa, Yan, Bernard, Sharma, Gagan, Desmond, Patricia M., Parsons, Mark W., Donnan, Geoffrey A., Davis, Stephen M., Campbell, Bruce C.V., Dowling, Richard, Bush, Steven, Scroop, Rebecca, Brooks, Mark, Asadi, Hamed, Ang, Timothy, Miteff, Ferdinand, Levi, Christopher, Zhao, Henry, Ng, Felix, Alemseged, Fana, Rice, Henry, de Villiers, Laetitia, Redmond, Kendal, and Leggett, David

Published
2023
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5. Reduced Severity of Tissue Injury Within the Infarct May Partially Mediate the Benefit of Reperfusion in Ischemic Stroke.

Author

Ng, Felix C., Churilov, Leonid, Yassi, Nawaf, Kleinig, Timothy J., Thijs, Vincent, Wu, Teddy Y., Shah, Darshan G., Dewey, Helen M., Sharma, Gagan, Desmond, Patricia M., Yan, Bernard, Parsons, Mark W., Donnan, Geoffrey A., Davis, Stephen M., Mitchell, Peter J., Leigh, Richard, Campbell, Bruce C.V., and EXTEND-IA TNK Part 1 and 2 Investigators

Published
2022
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6. Microvascular Dysfunction in Blood-Brain Barrier Disruption and Hypoperfusion Within the Infarct Posttreatment Are Associated With Cerebral Edema.

Author

Ng, Felix C., Churilov, Leonid, Yassi, Nawaf, Kleinig, Timothy J., Thijs, Vincent, Wu, Teddy Y., Shah, Darshan G., Dewey, Helen M., Sharma, Gargan MCA, Desmond, Patricia M., Yan, Bernard DMedSci, Parsons, Mark W., Donnan, Geoffrey A., Davis, Stephen M., Mitchell, Peter J. MMed, Leigh, Richard, Campbell, Bruce C.V., Sharma, Gargan, Yan, Bernard, and Mitchell, Peter J

Published
2022
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7. Safety and Efficacy of Tenecteplase in Older Patients With Large Vessel Occlusion: A Pooled Analysis of the EXTEND-IA TNK Trials.

Author

Yogendrakumar, Vignan, Churilov, Leonid, Mitchell, Peter J. MMed, Kleinig, Timothy J., Yassi, Nawaf, Thijs, Vincent, Wu, Teddy Y., Shah, Darshan G., Ng, Felix C., Dewey, Helen M., Wijeratne, Tissa, Yan, Bernard DMedSc, Desmond, Patricia M., Parsons, Mark W., Donnan, Geoffrey Alan, Davis, Stephen M., Campbell, Bruce C.V., Mitchell, Peter J, Yan, Bernard, and EXTEND-IA TNK Investigators

Published
2022
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10. Microvascular Dysfunction in Blood-Brain Barrier Disruption and Hypoperfusion Within the Infarct Posttreatment Are Associated With Cerebral Edema

Author

Ng, Felix C., Churilov, Leonid, Yassi, Nawaf, Kleinig, Timothy J., Thijs, Vincent, Wu, Teddy Y., Shah, Darshan G., Dewey, Helen M., Sharma, Gargan, Desmond, Patricia M., Yan, Bernard, Parsons, Mark W., Donnan, Geoffrey A., Davis, Stephen M., Mitchell, Peter J., Leigh, Richard, and Campbell, Bruce C.V.

Published
2022
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11. Safety and Efficacy of Tenecteplase in Older Patients With Large Vessel Occlusion

Author

Yogendrakumar, Vignan, Churilov, Leonid, Mitchell, Peter J., Kleinig, Timothy J., Yassi, Nawaf, Thijs, Vincent, Wu, Teddy Y., Shah, Darshan G., Ng, Felix C., Dewey, Helen M., Wijeratne, Tissa, Yan, Bernard, Desmond, Patricia M., Parsons, Mark W., Donnan, Geoffrey Alan, Davis, Stephen M., Campbell, Bruce C.V., Dowling, Richard, Bush, Steven, Scroop, Rebecca, Simpson, Marion, Brooks, Mark, Asadi, Hamed, Ang, Timothy, Miteff, Ferdinand, Levi, Christopher, Zhao, Henry, Alemseged, Fana, Salvaris, Patrick, GarciaEsperon, Carlos, Bailey, Peter, Rice, Henry, de Villiers, Laetitia, Choi, Philip, Brown, Helen, Redmond, Kendal, Leggett, David, Fink, John, Collecutt, Wayne, Kraemer, Thomas, Cordato, Dennis, Muller, Claire, Coulthard, Alan, Mitchell, Ken, Clouston, John, Mahady, Kate, Field, Deborah, O’Brien, Bill, Clissold, Benjamin, Clissold, Anna, Cloud, Geoffrey, Bolitho, Leslie, Bonavia, Luke, Bhattacharya, Arup, Wright, Alistair, Mamun, Abul, O’Rourke, Fintan, Worthington, John, Wong, Andrew, Ma, Henry, Phan, Thanh, Chong, Winston, Chandra, Ronil, Slater, Lee-Anne, Krause, Martin, Harrington, Timothy, Faulder, Kenneth, Steinfort, Brendan, Bladin, Christopher, and Sharma, Gagan

Published
2022
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13. From molecular to macro: the key role of the apical ligaments in uterovaginal support.

Author

Kieserman-Shmokler, Caroline, Swenson, Carolyn W., Chen, Luyun, Desmond, Lisa M., Ashton-Miller, James A., and DeLancey, John O.

Subjects
LIGAMENTS, PELVIC organ prolapse, UTERINE prolapse, MUSCLES, PELVIC floor, KINEMATICS, PHYSIOLOGY
Abstract

To explain the pathophysiology of pelvic organ prolapse, we must first understand the complexities of the normal support structures of the uterus and vagina. In this review, we focus on the apical ligaments, which include the cardinal and uterosacral ligaments. The aims of this review are the following: (1) to provide an overview of the anatomy and histology of the ligaments; (2) to summarize the imaging and biomechanical studies of the ligament properties and the way they relate to anterior and posterior vaginal wall prolapse; and (3) to synthesize these findings into a conceptual model for the progression of prolapse. [ABSTRACT FROM AUTHOR]

Published
2020
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14. Extending thrombolysis to 4·5–9 h and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data

Author

Campbell, Bruce C V, Ma, Henry, Ringleb, Peter A, Parsons, Mark W, Churilov, Leonid, Bendszus, Martin, Levi, Christopher R, Hsu, Chung, Kleinig, Timothy J, Fatar, Marc, Leys, Didier, Molina, Carlos, Wijeratne, Tissa, Curtze, Sami, Dewey, Helen M, Barber, P Alan, Butcher, Kenneth S, De Silva, Deidre A, Bladin, Christopher F, Yassi, Nawaf, Pfaff, Johannes A R, Sharma, Gagan, Bivard, Andrew, Desmond, Patricia M, Schwab, Stefan, Schellinger, Peter D, Yan, Bernard, Mitchell, Peter J, Serena, Joaquín, Toni, Danilo, Thijs, Vincent, Hacke, Werner, Davis, Stephen M, Donnan, Geoffrey A, Donnan, Geoffrey A., Davis, Stephen M., Ma, Henry, Campbell, Bruce C.V., Churilov, Leonid, Parsons, Mark W., Yan, Bernard, Mitchell, Peter J., Yassi, Nawaf, Sharma, Gagan, Desmond, Patricia M., Oxley, Thomas, Wu, Teddy Y., Shah, Darshan, Zhao, Henry, Rodrigues, Edrich, Salvaris, Patrick, Alemseged, Fana, Ng, Felix, Williams, Cameron, Ng, Jo-Lyn, Tu, Hans T-H., McDonald, Amy, Jackson, David, Tsoleridis, Jessica, McCoy, Rachael, Pesavento, Lauren, Weir, Louise, Bivard, Andrew, Kleinig, Timothy J., Patel, S., Harvey, J., Mahadevan, J., Cheong, E., Balabanski, Anna, Waters, Michael, Drew, Roy, Cranefield, Jennifer, Wijeratne, Tissa, Mackey, Elizabeth, Celestino, Sherisse, Low, Essie, Dewey, Helen M., Bladin, Christopher F., Loh, Poh Sien, Choi, Philip M., Coote, Skye, Frost, Tanya, Hogan, K., Ding, C., McModie, S., Zhang, W.W., Kyndt, Christopher, Moore, A., Ross, Z., Liu, J., Miteff, Ferdinand, Levi, Christopher R., Ang, Timothy, Spratt, Neil, Garcia-Esperon, Carlos, Kaauwai, Lara, Phan, Thanh G., Ly, John, Singhal, Shaloo, Clissold, Benjamin, Wong, Kitty, Krause, Martin, Day, Susan, Sturm, Jonathan, O'Brian, Bill, Grimley, Rohan, Thijs, Vincent, Simpson, Marion, Lee-Archer, Matthew, Brodtmann, Amy, Coulton, Bronwyn, Young, Dennis, Wong, Andrew A., Muller, Claire, Field, Deborah K., Vallat, W., Maxwell, Vanessa, Bailey, Peter, Sabet, Arman, Mishra, Sachin, Tan, Meng, George, K., Barber, P. Alan, Zhao, L., Meretoja, Atte, Curtze, Sami, Tatlisumak, Turgut, Sibolt, G., Tiainen, M., Koivu, M., Aarnio, K., Virta, J., Kasari, O., Eirola, S., Sun, M.C., Chen, T.C., Chuang, C.S., Chen, Y.Y., Lin, C.M., Ho, S.C., Hsiao, P.M., Tsai, C.H., Huang, W.S., Yang, Y.W., Huang, H.Y., Wang, W.C., Liu, C.H., Lu, M.K., Lu, C.H., Kung, W.L., Jiang, S.K., Wu, Y.H., Huang, S.C., Tseng, C.H., Tseng, L.T., Guo, Y.C., Lin, D., Hsu, C.T., Kuan, C.W., Hsu, J.P., Tsai, H.T., Suzuki, M., Sun, Y., Chen, H.F., Lu, C.J., Lin, C.H., Huang, C.C., Chu, H.J., Lee, C.Y., Chang, W.H., Lo, Y.C., Hsu, Y.T., Chen, C.H., Sung, P.S., Ysai, C.L., Jeng, J.S., Tang, S.C., Tsai, L.K., Yeh, S.J., Lee, Y.C., Wang, Y.T., Chung, T.C., Hu, C.J., Chan, L., Chiou, Y.W., Lien, L.M., Yeh, H.L., Yeh, J.H., Chen, W.H., Lau, C.L., Chang, A., Lee, I.Y., Huang, M.Y., Lee, J.T., Peng, G.S., Lim, J.C., Hsu, Y.D., Lin, C.C., Cheng, C.A., Yen, C.H., Yang, F.C., Hsu, C.H., Sung, Y.F., Tsai, C.K., Tsai, C.L., Hsiao, P.M., Lee, A., Hankey, Graeme, Blacker, David, Gerraty, Richard, Chen, C-I., Hsu, C-S., Cowley, Elise, McCoy, Rachael, Sallaberger, Michele, Snow, Barry, Kolbe, John, Stark, Richard, King, John, Macdonnell, Richard, Attia, John, D'Este, Catherine, Bernhardt, Julie, Carey, Leeanne, Cadilhac, Dominique, Anderson, Craig, Howells, David, Barber, A., Connelly, Alan, Macleod, Malcolm, O'Collins, Victoria, Wilson, W., Macaulay, L., Bendszus, Martin, Bluhmki, Erich, Eschenfelder, Christoph, Hacke, Werner, Molina, Carlos, Leys, Didier, Ringleb, Peter, Schellinger, Peter, Schwab, Stefan, Toni, Danilo, Wahlgren, Nils, Wardlaw, Joanna, Oppenheim, Catherine, Lees, Kennedy R., Kaste, Markku, von Kummer, Rüdiger, Chatellier, Gilles, Laage, Rico, Nuñez, Xavier, Ehrenkrona, Christina, Svenson, Ann-Sofie, Cove, Lynda, Niederkorn, Kurt, Gruber, Franz, Kapeller, Peter, Mikulik, Robert, Mas, Jean-Louis, Berrouschot, Jörg, Sobesky, Jan, Köhrmann, Martin, Steiner, Thorsten, Kessler, Christof, Fatar, Marc, Dziewas, Rainer, Poli, Sven, Althaus-Knaurer, Katharina, Bovi, Paolo, Rodriguez, Alain L., Arenillas, Juan F., Muir, Keith, Veltkamp, Roland, Dixit, Anand, Muddegowda, Girish, Kala, Lalit, De Silva, Deidre A., Butcher, Kenneth S., Byrnes, G., Peeters, Andre, Chalk, J.B., Fink, John N., Kimber, Thomas E., Schultz, David, Hand, Peter J., Frayne, Judith, Tress, Brian M., McNeil, John, Burns, R., Johnston, C., and Williams, M.

Abstract

Stroke thrombolysis with alteplase is currently recommended 0–4·5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4·5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis.

Published
2019
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16. Association of Reperfusion After Thrombolysis With Clinical Outcome Across the 4.5- to 9-Hours and Wake-up Stroke Time Window: A Meta-Analysis of the EXTEND and EPITHET Randomized Clinical Trials

Author

Campbell, Bruce C. V., Ma, Henry, Parsons, Mark W., Churilov, Leonid, Yassi, Nawaf, Kleinig, Timothy J., Hsu, Chung Y., Dewey, Helen M., Butcher, Kenneth S., Yan, Bernard, Desmond, Patricia M., Wijeratne, Tissa, Curtze, Sami, Barber, P. Alan, De Silva, Deidre A., Thijs, Vincent, Levi, Christopher R., Bladin, Christopher F., Sharma, Gagan, Bivard, Andrew, Donnan, Geoffrey A., and Davis, Stephen M.

Abstract

IMPORTANCE: Intravenous alteplase reduces disability after ischemic stroke in patients 4.5 to 9 hours after onset and with wake-up onset stroke selected using perfusion imaging mismatch. However, whether the benefit is consistent across the 4.5- to 6-hours, 6- to 9-hours, and wake-up stroke epochs is uncertain. OBJECTIVE: To examine the association of reperfusion with reduced disability, including by onset-to-randomization time strata in the Extending the Time for Thrombolysis in Emergency Neurological Deficits (EXTEND) and Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) randomized clinical trials. DESIGN, SETTING, AND PARTICIPANTS: Individual patient meta-analysis of randomized clinical trials performed from August 2001 to June 2018 with 3-month follow-up. Patients had acute ischemic stroke with 4.5-to 9-hours poststroke onset or with wake-up stroke were randomized to alteplase or placebo after perfusion mismatch imaging. Analysis began July 2019 and ended May 2020. EXPOSURES: Reperfusion was defined as more than 90% reduction in time to maximum of more than 6 seconds’ lesion volume at 24- to 72-hour follow-up. MAIN OUTCOMES AND MEASURES: Ordinal logistic regression adjusted for baseline age and National Institutes of Health Stroke Scale score was used to analyze functional improvement in day 90 modified Rankin Scale score overall, including a reperfusion × time-to-randomization multiplicative interaction term, and in the 4.5- to 6-hours, 6- to 9-hours, and wake-up time strata. Symptomatic hemorrhage was defined as large parenchymal hematoma with a National Institutes of Health Stroke Scale score increase of 4 points or more. RESULTS: Reperfusion was assessable in 270 of 295 patients (92%), 68 of 133 (51%) in the alteplase group, and 38 of 137 (28%) in the placebo reperfused group (P < .001). The median (interquartile range) age was 76 (66-81) years in the reperfusion group vs 74 (64.5-81.0) years in the group with no reperfusion. The median (interquartile range) baseline National Institutes of Health Stroke Scale score was 10 (7-15) in the reperfusion group vs 12 (8.0-17.5) in the no reperfusion group. Overall, reperfusion was associated with improved functional outcome (common odds ratio, 7.7; 95% CI, 4.6-12.8; P < .001). Reperfusion was associated with significantly improved functional outcome in each of the 4.5- to 6-hours, 6- to 9-hours, and wake-up time strata, with no evidence of association between time to randomization and beneficial effect of reperfusion (P = .63). Symptomatic hemorrhage, assessed in all 294 patients, occurred in 3 of 51 (5.9%) in the 4.5- to 6-hours group, 2 of 28 (7.1%) in the 6- to 9-hours group, and 4 of 73 (5.5%) in the wake-up stroke in patients treated with alteplase (Fisher P = .91). CONCLUSIONS AND RELEVANCE: Strong benefits of reperfusion in all time strata without differential risk in symptomatic hemorrhage support the consistent treatment effect of alteplase in perfusion mismatch–selected patients throughout the 4.5- to 9-hours and wake-up stroke time window.

Published
2021
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17. Noncontrast Magnetic Resonance Angiography in the Era of Nephrogenic Systemic Fibrosis and Gadolinium Deposition

Author

Lim, Ruth P., Hecht, Elizabeth M., and Desmond, Patricia M.

Abstract

Gadolinium-based contrast agents for clinical magnetic resonance imaging are overall safe. However, the discovery of nephrogenic systemic fibrosis in patients with severe renal impairment and gadolinium deposition in patients receiving contrast have generated developments in contrast-free imaging of the vasculature, that is, noncontrast magnetic resonance angiography. This article presents an update on noncontrast magnetic resonance angiography techniques, with comparison to other imaging alternatives. Potential benefits and challenges to implementation, and evidence to date for various clinical applications are discussed.

Published
2021
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18. Melbourne Mobile Stroke Unit and Reperfusion Therapy

Author

Zhao, Henry, Coote, Skye, Easton, Damien, Langenberg, Francesca, Stephenson, Michael, Smith, Karen, Bernard, Stephen, Cadilhac, Dominique A., Kim, Joosup, Bladin, Christopher F., Churilov, Leonid, Crompton, Douglas E., Dewey, Helen M., Sanders, Lauren M., Wijeratne, Tissa, Cloud, Geoffrey, Brooks, Duncan M., Asadi, Hamed, Thijs, Vincent, Chandra, Ronil V., Ma, Henry, Desmond, Patricia M., Dowling, Richard J., Mitchell, Peter J., Yassi, Nawaf, Yan, Bernard, Campbell, Bruce C.V., Parsons, Mark W., Donnan, Geoffrey A., and Davis, Stephen M.

Abstract

Supplemental Digital Content is available in the text.

Published
2020
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19. Utility of icobrain for brain volumetry in multiple sclerosis clinical practice

Author

Nguyen, Ai-Lan, Sormani, Maria Pia, Horakova, Dana, Havrdova, Eva H, Barnett, Michael H, De Stefano, Nicola, Battaglini, Marco, Vaneckova, Manuela, Lui, Elaine, Gaillard, Frank, Desmond, Patricia M, Prime, Hayden, Datta, Mineesh, Van der Walt, Anneke, Jokubaitis, Vilija G, Podevyn, Femke, Zivadinov, Robert, Weinstock-Guttman, Bianca, D'hooghe, Marie B, Nagels, Guy, Van Pesch, Vincent, Laureys, Guy, Van Hijfte, Liesbeth, Lechner-Scott, Jeannette, Patti, Francesco, Cristiano, Edgardo, Rojas, Juan I, Sima, Diana M, Van Hecke, Wim, Kalincik, Tomas, and Butzkueven, Helmut

Abstract

•In this real-world clinical MS setting, using icobrain for analysis of brain atrophy and our quality control criteria, we found comparable variance on brain volume changes for same-scanner and different-scanner MRI pairs•A higher number of different-scanner MRI pairs did not pass quality control and had poorer alignment similarity•Applying strict selection criteria for volumetric analyses in real-world settings, and longitudinal imaging within scanners, remain imperative to reduce brain atrophy variability

Published
2024
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24. MRI correlates of general intelligence in neurotypical adults.

Author

Malpas, Charles B., Genc, Sila, Saling, Michael M., Velakoulis, Dennis, Desmond, Patricia M., and O’Brien, Terence J.

Abstract

There is growing interest in the neurobiological substrate of general intelligence. Psychometric estimates of general intelligence are reduced in a range of neurological disorders, leading to practical application as sensitive, but non-specific, markers of cerebral disorder. This study examined estimates of general intelligence in neurotypical adults using diffusion tensor imaging and resting-state functional connectivity analysis. General intelligence was related to white matter organisation across multiple brain regions, confirming previous work in older healthy adults. We also found that variation in general intelligence was related to a large functional sub-network involving all cortical lobes of the brain. These findings confirm that individual variance in general intelligence is related to diffusely represented brain networks. [ABSTRACT FROM AUTHOR]

Published
2016
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25. Examining the structural correlates of amyloid‐beta in people with DLB.

Author

Gajamange, Sanuji, Yassi, Nawaf, Chin, Kai Sin, Desmond, Patricia M., Villemagne, Victor L., Rowe, Christopher C., and Watson, Rosie

Abstract

Background: Dementia with Lewy bodies (DLB) is a neurodegenerative disorder characterized pathologically by the deposition of alpha synuclein. Many patients with DLB also have brain compatible with Alzheimer’s disease (namely Amyloid‐β and tau), which can lead to challenges with clinical diagnosis and management. In this study we aim to understand the influence of Aβ on brain atrophy in DLB patients. Method: 19 participants with probable DLB underwent 3T MRI T1‐weighted (voxel size=0.8x0.8x0.8mm3, TR=2400ms, TE=2.31ms) and β‐amyloid (Aβ) PET (radiotracer 18F‐NAV4694) imaging. Participants were grouped into Aβ negative (n=10; age=71.6±5.8 years) and Aβ positive (n=9; age=75.1±4.3 years) with a threshold of 50 centiloid units to identify neuropathological change (Amadoru et al. 2020). Brain volume measures (regional subcortical grey matter and global white and grey matter) were segmented from T1‐weighted images with FreeSurfer (Fischl et al. 2002, Fischl 2012). Given previous literature suggesting prominence of thalamic structural changes in DLB, we also specifically analysed changes in the thalamus by segmenting the thalamus into 25 nuclei, which were then grouped into six regions (anterior, lateral, ventral, intralaminar, medial and posterior) (Watson et al. 2017, Iglesias et al. 2018). All brain volumes were expressed as fractions of intracranial volume to account for differences in head size. Group comparison analyses were not controlled for age and sex as both these covariates did not statistically differ between groups. Result: Brain volume differed significantly between Aβ‐ and Aβ+ DLB patients in the left thalamus (Aβ‐:4.39±0.37x103, Aβ+:4.07±0.19x103, p=0.03) and right thalamus (Aβ‐:4.17±0.34x103, Aβ+:3.84±0.22 x103, p=0.03). Specifically, the ventral (LEFT; Aβ‐:1.78±0.15, Aβ+:1.63±0.14, p=0.03. RIGHT; Aβ‐:1.83±0.15, Aβ+:1.65±0.12, p=0.01) and posterior (LEFT; Aβ‐:1.30±0.12, Aβ+:1.17±0.10, p=0.04. RIGHT; Aβ‐:1.42±0.14, Aβ+:1.21±0.12, p=0.003) regions were significantly reduced in Aβ+ compared to Aβ‐ DLB patients. Conclusion: We demonstrated significant thalamic atrophy in Aβ+ patients compared to Aβ‐ DLB patients. We did not observe significant differences in grey matter and hippocampal volume between patient groups. This study showed that AD‐related processes in DLB patients are associated with thalamic atrophy, specifically in the ventral and posterior regions. Future studies would benefit a larger DLB cohort to further understand the association between AD‐related pathology and the regional thalamic correlates of clinical function. [ABSTRACT FROM AUTHOR]

Published
2021
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26. Effect of Surface Chemistry on the Fluorescence of Detonation Nanodiamonds

Author

Reineck, Philipp, Lau, Desmond W. M., Wilson, Emma R., Fox, Kate, Field, Matthew R., Deeleepojananan, Cholaphan, Mochalin, Vadym N., and Gibson, Brant C.

Abstract

Detonation nanodiamonds (DNDs) have unique physical and chemical properties that make them invaluable in many applications. However, DNDs are generally assumed to show weak fluorescence, if any, unless chemically modified with organic molecules. We demonstrate that detonation nanodiamonds exhibit significant and excitation-wavelength-dependent fluorescence from the visible to the near-infrared spectral region above 800 nm, even without the engraftment of organic molecules to their surfaces. We show that this fluorescence depends on the surface functionality of the DND particles. The investigated functionalized DNDs, produced from the same purified DND as well as the as-received polyfunctional starting material, are hydrogen, hydroxyl, carboxyl, ethylenediamine, and octadecylamine-terminated. All DNDs are investigated in solution and on a silicon wafer substrate and compared to fluorescent high-pressure high-temperature nanodiamonds. The brightest fluorescence is observed from octadecylamine-functionalized particles and is more than 100 times brighter than the least fluorescent particles, carboxylated DNDs. The majority of photons emitted by all particle types likely originates from non-diamond carbon. However, we locally find bright and photostable fluorescence from nitrogen-vacancy centers in diamond in hydrogenated, hydroxylated, and carboxylated detonation nanodiamonds. Our results contribute to understanding the effects of surface chemistry on the fluorescence of DNDs and enable the exploration of the fluorescent properties of DNDs for applications in theranostics as nontoxic fluorescent labels, sensors, nanoscale tracers, and many others where chemically stable and brightly fluorescent nanoparticles with tailorable surface chemistry are needed.

Published
2017
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28. Simultaneous Multiple Intracerebral Hemorrhages (SMICH)

Author

Wu, Teddy Y., Yassi, Nawaf, Shah, Darshan G., Ma, Minmin, Sharma, Gagan, Putaala, Jukka, Strbian, Daniel, Campbell, Bruce C.V., Yan, Bernard, Tatlisumak, Turgut, Desmond, Patricia M., Davis, Stephen M., and Meretoja, Atte

Abstract

Supplemental Digital Content is available in the text.

Published
2017
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31. Amyloid angiopathy may contribute to white‐matter hyperintensities in Alzheimer's disease: Development of new models and analysis methods: Novel imaging analysis.

Author

Xia, Ying, Fazlollahi, Amir, Yates, Paul A., Yassi, Nawaf, Desmond, Patricia M., Salvado, Olivier, Villemagne, Victor L.L., Rowe, Christopher C., Fripp, Jurgen, Masters, Colin L., and Raniga, Parnesh

Abstract

Background: Cerebral amyloid angiopathy (CAA) is characterised by the accumulation of amyloid‐b (Aβ) in cerebral vessels and is often coexistent with Alzheimer's disease (AD). However, the overlap between CAA and AD and the contribution of CAA pathology to cerebrovascular lesions are not well understood. We hypothesize that in subjects with high Aβ load, the presence of imaging markers of CAA would be associated with greater white matter hyperintensities (WMH) burden. Method: Data used in the preparation of this article was obtained from the Australian Imaging Biomarkers and Lifestyle flagship study of ageing (AIBL). See www.aibl.csiro.au. We analysed MRI (SWI and FLAIR) and 11C‐PiB‐PET data from 98 cognitively normal (CN), 34 mild‐cognitive impairment (MCI) and 38 AD participants. Subjects were classified as being Aβ+ if their Aβ load was above 20 centiloid. SWI images were manually read for lobar microbleeds (LMB) and superficial siderosis. Subjects were classified as probable‐CAA (PCAA, 2 or more LMB or siderosis), possible‐CAA (SCAA, single LMB or siderosis) or non‐CAA (NCAA) based on the modified Boston criteria. Subjects classified as SCAA (n = 24) were excluded from further analysis since literature shows this group to be heterogenous and having low incidence of CAA pathology. WMH were automatically quantified on FLAIR. Group comparisons of WMH load were made using Kruskal Wallis rank test. A GLM was performed comparing WMH (log10 transformed) and CAA/ Aβ+ classification with age, intracranial volume, gender, APOE‐ε4 genotype and use of anti‐platelet or anticoagulant medication modelled as covariates. Result: Significantly higher WMH volume was observed in PCAA (n = 17) than NCAA (n = 129) (p‐value = 0.021, d = 0.36). When amyloid status was considered, PCAA/Aβ+ (n = 15) subjects had a significantly higher WMH load than NCAA/Aβ+ (n = 57) subjects (p‐value = 0.012, d = 0.57) and NCAA/Aβ‐ (n = 72) subjects (p‐value = 0.0006, d = 0.76) (Figure 1). PCAA/Aβ‐ (n = 2) were removed from further analysis. GLM results showed a significant association of WMH with PCAA/Aβ+ as compared to NCAA/Aβ+ (p‐value = 0.02, beta = 0.322 [0.056,0.588]). Conclusion: Our findings suggest that CAA may contribute to WMH burden in subjects with high Aβ load. Further studies are required to validate our observations and characterise the contributions of CAA compared to small vessel disease associated with traditional risk factors towards the phenotype of AD. [ABSTRACT FROM AUTHOR]

Published
2020
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41. Brain imaging in transient ischemic attack – redefining TIA.

Author

Pavlovic, Aleksandra M., Barras, Christen D., Hand, Peter J., Tress, Brian M., Desmond, Patricia M., and Davis, Stephen M.

Subjects
DIFFUSION magnetic resonance imaging, TRANSIENT ischemic attack, BIOMARKERS, BRAIN imaging, CEREBROVASCULAR disease risk factors, MAGNETIC resonance imaging of the brain
Abstract

Abstract: Transient ischemic attack (TIA) has recently been redefined to incorporate the latest clinical and neuroimaging information that has shed new light on TIA pathophysiology. Patients suffering from TIA are at a substantial risk of subsequent stroke, but quantifying this risk is difficult as TIA patients are a heterogeneous population and there are multiple TIA mimics. Clinical scores for prediction of stroke risk are principally based on patient history and potentially understate actual risk. Magnetic resonance imaging (MRI), in particular diffusion-weighted imaging (DWI) performed in the first days following TIA, reveals relevant focal ischemic abnormalities in 21–68% of patients. These lesions predict stroke recurrence, functional dependence and subsequent vascular events. Adding imaging information to clinical scores improves prediction of stroke risk following TIA. Alongside clinical judgement, use of MRI has the potential to change the management of TIA patients and is the imaging modality of choice for this condition. [ABSTRACT FROM AUTHOR]

Published
2010
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42. Regional very low cerebral blood volume predicts hemorrhagic transformation better than diffusion-weighted imaging volume and thresholded apparent diffusion coefficient in acute ischemic stroke.

Author

Campbell BC, Christensen S, Butcher KS, Gordon I, Parsons MW, Desmond PM, Barber PA, Levi CR, Bladin CF, De Silva DA, Donnan GA, Davis SM, EPITHET Investigators, Campbell, Bruce C V, Christensen, Søren, Butcher, Kenneth S, Gordon, Ian, Parsons, Mark W, Desmond, Patricia M, and Barber, P Alan

Published
2010
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43. Diagnosing acute lacunar infarction using CT perfusion.

Author

Cao, Wenjie, Yassi, Nawaf, Sharma, Gagan, Yan, Bernard, Desmond, Patricia M., Davis, Stephen M., and Campbell, Bruce C.V.

Abstract

The value of CT perfusion (CTP) in detecting acute lacunar infarcts (LACI) has not been well established. We tested the sensitivity of CTP for LACI. CTP maps of consecutive stroke patients from 2009–2013 were examined. MRI diffusion imaging was used to identify those with LACI. Two stroke neurologists independently evaluated the CTP maps for evidence of a perfusion lesion in a deep perforating artery territory. Cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT) and time to maximum (Tmax) maps were first examined in isolation and then in combination. Inter-observer agreement was measured using Cohen’s κ. The lesions identified were later confirmed against the diffusion MRI reference and the sensitivity and specificity of CTP maps calculated. A total of 63 patient scans were analysed. There were 32 patients with MRI-confirmed LACI within the coverage of CTP; 18 in the striatum, 10 thalamic, and four in the corona radiata. Another 31 patients had normal MRI. Inter-rater agreement was good (κ = 0.83). Sensitivity (blinded consensus) was highest for MTT (56.2%) compared to Tmax (25%, p < 0.001), CBV (9.3%, p = 0.021) and CBF (43.7%, p < 0.001). MTT maps enable detection of a significant proportion of LACI using CTP. [ABSTRACT FROM AUTHOR]

Published
2016
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44. Density and shape as CT predictors of intracerebral hemorrhage growth.

Author

Barras CD, Tress BM, Christensen S, MacGregor L, Collins M, Desmond PM, Skolnick BE, Mayer SA, Broderick JP, Diringer MN, Steiner T, Davis SM, Recombinant Activated Factor VII Intracerebral Hemorrhage Trial Investigators, Barras, Christen D, Tress, Brian M, Christensen, Soren, MacGregor, Lachlan, Collins, Marnie, Desmond, Patricia M, and Skolnick, Brett E

Published
2009
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45. Psychosocial Perspectives on Postamputation Rehabilitation: A Review of Disease, Trauma, and War Related Literature.

Author

Desmond, Deirdre M. and MacLachlan, Malcolm

Abstract

Interest in the psychosocial dimensions of adaptation to limb amputation has grown at a tremendous rate in recent decades as increasing emphasis is placed on understanding the complexity of the lived experience of amputation at personal, social, and cultural levels. The multidimensional nature of psychosocial adjustment and indeed the lack of a clear definition of "optimal" adaptation have stimulated investigation of a diverse range of indicators of psychosocial status. This burgeoning literature reflects considerable inconsistencies and ambiguities in terms of methodology and sampling, and evidences equivocal conclusions thus severely limiting generalizability. This review critically summarizes extant research on postamputation psychosocial well-being and determinants of psychosocial adaptation, including postamputation pain, health-related quality of life, depression and anxiety, coping responses, and the psychosocial dimensions of prosthetic provision. The primary objective is to clarify the state of knowledge in this domain and highlight issues of relevance for future research. [ABSTRACT FROM AUTHOR]

Published
2004

46. Incidence of cerebral microbleeds in preclinical Alzheimer disease

Author

Yates, Paul A., Desmond, Patricia M., Phal, Pramit M., Steward, Christopher, Szoeke, Cassandra, Salvado, Olivier, Ellis, Kathryn A., Martins, Ralph N., Masters, Colin L., Ames, David, Villemagne, Victor L., and Rowe, Christopher C.

Abstract

We sought to determine the incidence and associations of lobar microbleeds (LMBs) in a longitudinal cohort with 11C–Pittsburgh compound B (PiB) PET imaging.

Published
2014
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47. Prediction of Poststroke Hemorrhagic Transformation Using Computed Tomography Perfusion

Author

Yassi, Nawaf, Parsons, Mark W., Christensen, Søren, Sharma, Gagan, Bivard, Andrew, Donnan, Geoffrey A., Levi, Christopher R., Desmond, Patricia M., Davis, Stephen M., and Campbell, Bruce C.V.

Abstract

Intracerebral hemorrhage is a serious potential complication of stroke thrombolysis. We investigated the optimal computed tomography perfusion (CTP) parameter to predict cerebral parenchymal hematoma (PH) in acute ischemic stroke.

Published
2013
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48. The Effects of Alteplase 3 to 6 Hours After Stroke in the EPITHET–DEFUSE Combined Dataset

Author

Ogata, Toshiyasu, Christensen, Soren, Nagakane, Yoshinari, Ma, Henry, Campbell, Bruce C.V., Churilov, Leonid, Lansberg, Maarten G., Straka, Matus, Silva, Deidre A. De, Mlynash, Michael, Bammer, Roland, Olivot, Jean-Marc, Desmond, Patricia M., Albers, Gregory W., Davis, Stephen M., and Donnan, Geoffrey A.

Abstract

Two phase 2 studies of alteplase in acute ischemic stroke 3 to 6 hours after onset, Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET; a randomized, controlled, double-blinded trial), and Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study (DEFUSE; open-label, treatment only) using MR imaging-based outcomes have been conducted. We have pooled individual patient data from these to assess the response to alteplase. The primary hypothesis was that alteplase would significantly attenuate infarct growth compared with placebo in mismatch-selected patients using coregistration techniques.

Published
2013
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49. Comparison of Computed Tomography Perfusion and Magnetic Resonance Imaging Perfusion-Diffusion Mismatch in Ischemic Stroke

Author

Campbell, Bruce C.V., Christensen, Søren, Levi, Christopher R., Desmond, Patricia M., Donnan, Geoffrey A., Davis, Stephen M., and Parsons, Mark W.

Abstract

Perfusion imaging has the potential to select patients most likely to respond to thrombolysis. We tested the correspondence of computed tomography perfusion (CTP)-derived mismatch with contemporaneous perfusion-diffusion magnetic resonance imaging (MRI).

Published
2012
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50. Moving Beyond a Single Perfusion Threshold to Define Penumbra

Author

Nagakane, Yoshinari, Christensen, Soren, Ogata, Toshiyasu, Churilov, Leonid, Ma, Henry, Parsons, Mark W., Desmond, Patricia M., Levi, Christopher R., Butcher, Kenneth S., Davis, Stephen M., and Donnan, Geoffrey A.

Abstract

The mismatch lesion volumes defined by perfusion-weighted imaging exceeding diffusion-weighted imaging have been used as a marker of ischemic penumbral tissue. Defining the perfusion lesion by thresholding has shown promise as a practical tool; several positron emission tomography studies have indicated a more probabilistic relationship between perfusion and infarction. Here, we used a randomized controlled trial dataset of tissue-type plasminogen activator 3 to 6 hours after stroke to: (1) quantify the relationship between severity of hypoperfusion (measured by Tmax) and risk of infarction; (2) exploit this relationship to present a novel definition of mismatch based on infarct probabilities rather than dichotomies; and (3) examine the treatment response in the subgroup of patients with mismatch by the new definition.

Published
2012
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