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1. Serum Glial Fibrillary Acidic Protein and Neurofilament Light Chain Levels Reflect Different Mechanisms of Disease Progression under B-Cell Depleting Treatment in Multiple Sclerosis.

Author

Benkert, Pascal, Maleska Maceski, Aleksandra, Schaedelin, Sabine, Oechtering, Johanna, Zadic, Amar, Vilchez Gomez, Juan, Melie-Garcia, Lester, Cagol, Alessandro, Galbusera, Riccardo, Subramaniam, Suvitha, Lorscheider, Johannes, Galli, Edoardo, Mueller, Jannis, Fischer-Barnicol, Bettina, Achtnichts, Lutz, Findling, Oliver, Lalive, Patrice, Bridel, Claire, Uginet, Marjolaine, Müller, Stefanie, Pot, Caroline, Mathias, Amandine, Du Pasquier, Renaud, Salmen, Anke, Hoepner, Robert, Chan, Andrew, Disanto, Giulio, Zecca, Chiara, DSouza, Marcus, Hemkens, Lars, Yaldizli, Özgür, Derfuss, Tobias, Roth, Patrick, Gobbi, Claudio, Brassat, David, Tackenberg, Björn, Pedotti, Rosetta, Raposo, Catarina, Oksenberg, Jorge, Wiendl, Heinz, Berger, Klaus, Hermesdorf, Marco, Piehl, Fredrik, Conen, David, Buser, Andreas, Kappos, Ludwig, Khalil, Michael, Granziera, Cristina, Abdelhak, Ahmed, Leppert, David, Willemse, Eline, and Kuhle, Jens

Abstract

OBJECTIVE: To investigate the longitudinal dynamics of serum glial fibrillary acidic protein (sGFAP) and serum neurofilament light chain (sNfL) levels in people with multiple sclerosis (pwMS) under B-cell depleting therapy (BCDT) and their capacity to prognosticate future progression independent of relapse activity (PIRA) events. METHODS: A total of 362 pwMS (1,480 samples) starting BCDT in the Swiss Multiple Sclerosis (MS) Cohort were included. sGFAP levels in 2,861 control persons (4,943 samples) provided normative data to calculate adjusted Z scores. RESULTS: Elevated sGFAP levels (Z score >1) at 1 year were associated with a higher hazard for PIRA (hazard ratio [HR]: 1.80 [95% CI: 1.17-2.78]; p = 0.0079) than elevated sNfL levels (HR, 1.45 [0.95-2.24], p = 0.0886) in a combined model. Independent of PIRA events, sGFAP levels longitudinally increased by 0.49 Z score units per 10 years follow-up (estimate, 0.49 [0.29, 0.69], p

Published
2024

3. 3D external shape analysis and barycentremetry can provide early signs of progression in adolescent idiopathic scoliosis

Author

Langlais, Tristan, Vergari, Claudio, Mainard, Nicolas, du Cluzel, Xavier, Baudoux, Matthieu, Gajny, Laurent, Abelin-Genevois, Kariman, Bernard, Jean Claude, Hu, Zongshan, Cheng, Jack Chun Yiu, Chu, Winnie Chiu Wing, Assi, Ayman, Karam, Mohamad, Ghanem, Ismat, Bassani, Tito, Galbusera, Fabio, Sconfienza, Luca Maria, Brayda-Bruno, Marco, Courtois, Isabelle, Ebermeyer, Eric, Vialle, Raphael, Dubousset, Jean, and Skalli, Wafa

Published
2024
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4. Is the information provided by large language models valid in educating patients about adolescent idiopathic scoliosis? An evaluation of content, clarity, and empathy: The perspective of the European Spine Study Group

Author

Lang, Siegmund, Vitale, Jacopo, Galbusera, Fabio, Fekete, Tamás, Boissiere, Louis, Charles, Yann Philippe, Yucekul, Altug, Yilgor, Caglar, Núñez-Pereira, Susana, Haddad, Sleiman, Gomez-Rice, Alejandro, Mehta, Jwalant, Pizones, Javier, Pellisé, Ferran, Obeid, Ibrahim, Alanay, Ahmet, Kleinstück, Frank, and Loibl, Markus

Published
2024
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7. Hardware Density Reduction To Avoid Proximal Junction Failure In Adult Spine Surgery: In Silico Case Studies and Virtual Cohort

Author

Rasouligandomani, Morteza, del Arco, Alex, Villa, Tomaso, La Barbera, Luigi, Pellise, Ferran, Ballester, Miguel Angel Gonzalez, Galbusera, Fabio, and Noailly, Jerome

Subjects
Physics - Medical Physics, Physics - Biological Physics
Abstract

Background: Proximal Junctional Failure (PJF) is a post-operative complication in adult spine surgery, often requiring reoperation. Osteotomy is often used in revision surgeries, leading to 34.8% complications. Hence, suboptimal decisions might be extending hardware without osteotomy, which yields to severe Global Alignment and Proportion (GAP) scores. High GAPs increase PJF risk, but Hardware Density Reduction (HDR) might limit it. Methods: Two clinical cases were evaluated: 1) Initially operated with hardware extended to T10, GAP 10; 2) PJF at T11 and hardware extended to T3, GAP 11. Two patient-personalized spine FE models were constructed through Statistical Shape Modelling (SSM) and mesh morphing. Intervertebral Disk (IVD) fiber strain, screw pull-out force, and rod stress were evaluated for the cases 1) and 2), also for 91 virtual HDR scenarios with different GAP scores, using Finite Element (FE) simulations. Different rod and bone material properties were also assessed. Results: HDR could decrease IVD fiber strain (-70% at most) and increase screw pull-out forces (+142% at most) for cases with Ti rod and normal bone. Cr-Co rod and osteopenia, and osteoporotic bones had high PJF risk. Trade-off analyses could determine the best configurations avoiding PJF. Virtual cohort study showed that GAP 12 and 13 could not avoid PJF in any HDR scenarios either with Ti or Cr-Co rods. HDR in a UIV T10 virtual patient with GAP 11 could not de-risk in case of Cr-Co rods. UIV T3 with GAP 13 could not benefit any HDR strategy, independently of rod properties. In contrast, Ti rods might allow HDR to de-risk GAP 12 patients with UIV T3. Conclusions: HDR could avoid PJF in the patients with medium high GAP scores, depending on the screw reduction pattern, and bone and rod material properties. Remarkably, HDR technique might avoid excessive spine surgeries and minimize the surgery cost.

Published
2024

8. Data Repository of Finite Element Models of Normal and Deformed Thoracolumbar Spine

Author

Rasouligandomani, Morteza, del Arco, Alex, Chemorion, Francis Kiptengwer, Bisotti, Marc-Antonio, Galbusera, Fabio, Noailly, Jerome, and Ballester, Miguel Angel Gonzalez

Subjects
Physics - Biological Physics, Quantitative Biology - Tissues and Organs
Abstract

Adult spine deformity (ASD) is prevalent and leads to a sagittal misalignment in the vertebral column. Computational methods, including Finite Element (FE) Models, have emerged as valuable tools for investigating the causes and treatment of ASD through biomechanical simulations. However, the process of generating personalized FE models is often complex and time-consuming. To address this challenge, we present a repository of FE models with diverse spine morphologies that statistically represent real geometries from a cohort of patients. These models are generated using EOS images, which are utilized to reconstruct 3D surface spine models. Subsequently, a Statistical Shape Model (SSM) is constructed, enabling the adaptation of a FE hexahedral mesh template for both the bone and soft tissues of the spine through mesh morphing. The SSM deformation fields facilitate the personalization of the mean hexahedral FE model based on sagittal balance measurements. Ultimately, this new hexahedral SSM tool offers a means to generate a virtual cohort of 16807 thoracolumbar FE spine models, which are openly shared in a public repository.

Published
2024

9. Multicenter external validation of prediction models for clinical outcomes after spinal fusion for lumbar degenerative disease

Author

Grob, Alexandra, Rohr, Jonas, Stumpo, Vittorio, Vieli, Moira, Ciobanu-Caraus, Olga, Ricciardi, Luca, Maldaner, Nicolai, Raco, Antonino, Miscusi, Massimo, Perna, Andrea, Proietti, Luca, Lofrese, Giorgio, Dughiero, Michele, Cultrera, Francesco, D’Andrea, Marcello, An, Seong Bae, Ha, Yoon, Amelot, Aymeric, Bedia Cadelo, Jorge, Viñuela-Prieto, Jose M., Gandía-González, Maria L., Girod, Pierre-Pascal, Lener, Sara, Kögl, Nikolaus, Abramovic, Anto, Laux, Christoph J., Farshad, Mazda, O’Riordan, Dave, Loibl, Markus, Galbusera, Fabio, Mannion, Anne F., Scerrati, Alba, De Bonis, Pasquale, Molliqaj, Granit, Tessitore, Enrico, Schröder, Marc L., Stienen, Martin N., Regli, Luca, Serra, Carlo, and Staartjes, Victor E.

Published
2024
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13. Assessment of malalignment at early stage in adolescent idiopathic scoliosis: a longitudinal cohort study

Author

Langlais, Tristan, Vergari, Claudio, Rougereau, Gregoire, Gaume, Mathilde, Gajny, Laurent, Abelin-Genevois, Kariman, Bernard, Jean Claude, Hu, Zongshan, Cheng, Jack Chun Yiu, Chu, Winnie Chiu Wing, Assi, Ayman, Karam, Mohamad, Ghanem, Ismat, Bassani, Tito, Galbusera, Fabio, Sconfienza, Luca Maria, Brayda-Bruno, Marco, Courtois, Isabelle, Ebermeyer, Eric, Vialle, Raphael, Dubousset, Jean, and Skalli, Wafa

Published
2024
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19. Intelligence-Based Spine Care Model: A New Era of Research and Clinical Decision-Making

Author

Mallow, G Michael, Siyaji, Zakariah K, Galbusera, Fabio, Espinoza-Orías, Alejandro A, Giers, Morgan, Lundberg, Hannah, Ames, Christopher, Karppinen, Jaro, Louie, Philip K, Phillips, Frank M, Pourzal, Robin, Schwab, Joseph, Sciubba, Daniel M, Wang, Jeffrey C, Wilke, Hans-Joachim, Williams, Frances MK, Mohiuddin, Shoeb A, Makhni, Melvin C, Shepard, Nicholas A, An, Howard S, and Samartzis, Dino

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, artificial, intelligence, machine, learning, computation, data, science, precision, personalized, spine, pain, disc, degeneration, low back pain, tumor, deformity, Clinical sciences
Published
2021

20. Association between sagittal alignment and loads at the adjacent segment in the fused spine: a combined clinical and musculoskeletal modeling study of 205 patients with adult spinal deformity

Author

Ignasiak, Dominika, Behm, Pascal, Mannion, Anne F., Galbusera, Fabio, Kleinstück, Frank, Fekete, Tamás F., Haschtmann, Daniel, Jeszenszky, Dezsö, Zimmermann, Laura, Richner-Wunderlin, Sarah, Vila-Casademunt, Alba, Pellisé, Ferran, Obeid, Ibrahim, Pizones, Javier, Sánchez Pérez-Grueso, Francisco J., Karaman, Muhammed Ilkay, Alanay, Ahmet, Yilgor, Çaglar, Ferguson, Stephen J., and Loibl, Markus

Published
2023
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21. GAMER MRI: Gated-attention mechanism ranking of multi-contrast MRI in brain pathology

Author

Lu, Po-Jui, Yoo, Youngjin, Rahmanzadeh, Reza, Galbusera, Riccardo, Weigel, Matthias, Ceccaldi, Pascal, Nguyen, Thanh D, Spincemaille, Pascal, Wang, Yi, Daducci, Alessandro, La Rosa, Francesco, Bach Cuadra, Meritxell, Sandkühler, Robin, Nael, Kambiz, Doshi, Amish, Fayad, Zahi A, Kuhle, Jens, Kappos, Ludwig, Odry, Benjamin, Cattin, Philippe, Gibson, Eli, and Granziera, Cristina

Subjects
Biomedical and Clinical Sciences, Biological Psychology, Clinical and Health Psychology, Neurosciences, Psychology, Clinical Research, Neurodegenerative, Biomedical Imaging, Multiple Sclerosis, Brain Disorders, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Neurological, Stroke, Brain, Brain Ischemia, Diffusion Magnetic Resonance Imaging, Humans, Magnetic Resonance Imaging, Deep learning, Attention mechanism, Relative importance order, Multiple sclerosis, Quantitative MRI, Biological psychology, Clinical and health psychology
Abstract

IntroductionDuring the last decade, a multitude of novel quantitative and semiquantitative MRI techniques have provided new information about the pathophysiology of neurological diseases. Yet, selection of the most relevant contrasts for a given pathology remains challenging. In this work, we developed and validated a method, Gated-Attention MEchanism Ranking of multi-contrast MRI in brain pathology (GAMER MRI), to rank the relative importance of MR measures in the classification of well understood ischemic stroke lesions. Subsequently, we applied this method to the classification of multiple sclerosis (MS) lesions, where the relative importance of MR measures is less understood.MethodsGAMER MRI was developed based on the gated attention mechanism, which computes attention weights (AWs) as proxies of importance of hidden features in the classification. In the first two experiments, we used Trace-weighted (Trace), apparent diffusion coefficient (ADC), Fluid-Attenuated Inversion Recovery (FLAIR), and T1-weighted (T1w) images acquired in 904 acute/subacute ischemic stroke patients and in 6,230 healthy controls and patients with other brain pathologies to assess if GAMER MRI could produce clinically meaningful importance orders in two different classification scenarios. In the first experiment, GAMER MRI with a pretrained convolutional neural network (CNN) was used in conjunction with Trace, ADC, and FLAIR to distinguish patients with ischemic stroke from those with other pathologies and healthy controls. In the second experiment, GAMER MRI with a patch-based CNN used Trace, ADC and T1w to differentiate acute ischemic stroke lesions from healthy tissue. The last experiment explored the performance of patch-based CNN with GAMER MRI in ranking the importance of quantitative MRI measures to distinguish two groups of lesions with different pathological characteristics and unknown quantitative MR features. Specifically, GAMER MRI was applied to assess the relative importance of the myelin water fraction (MWF), quantitative susceptibility mapping (QSM), T1 relaxometry map (qT1), and neurite density index (NDI) in distinguishing 750 juxtacortical lesions from 242 periventricular lesions in 47 MS patients. Pair-wise permutation t-tests were used to evaluate the differences between the AWs obtained for each quantitative measure.ResultsIn the first experiment, we achieved a mean test AUC of 0.881 and the obtained AWs of FLAIR and the sum of AWs of Trace and ADC were 0.11 and 0.89, respectively, as expected based on previous knowledge. In the second experiment, we achieved a mean test F1 score of 0.895 and a mean AW of Trace = 0.49, of ADC = 0.28, and of T1w = 0.23, thereby confirming the findings of the first experiment. In the third experiment, MS lesion classification achieved test balanced accuracy = 0.777, sensitivity = 0.739, and specificity = 0.814. The mean AWs of T1map, MWF, NDI, and QSM were 0.29, 0.26, 0.24, and 0.22 (p

Published
2021

22. Spinal Compressive Forces in Adolescent Idiopathic Scoliosis With and Without Carrying Loads: A Musculoskeletal Modeling Study

Author

Schmid, Stefan, Burkhart, Katelyn A., Allaire, Brett T., Grindle, Daniel, Bassani, Tito, Galbusera, Fabio, and Anderson, Dennis E.

Subjects
Physics - Medical Physics, Physics - Biological Physics, Quantitative Biology - Quantitative Methods, Quantitative Biology - Tissues and Organs
Abstract

The pathogenesis of adolescent idiopathic scoliosis (AIS) remains poorly understood and biomechanical data are limited. A deeper insight into spinal loading could provide valuable information for the improvement of current treatment strategies. This work therefore aimed at using subject-specific musculoskeletal full-body models of patients with AIS to predict segmental compressive forces around the curve apex and to investigate how these forces are affected by simulated load carrying. Models were created based on spatially calibrated biplanar radiographic images from 24 patients with mild to moderate AIS and validated by comparing predictions of paravertebral muscle activity with reported values from in vivo studies. Spinal compressive forces were predicted during unloaded upright standing as well as upright standing with external loads of 10%, 15% and 20% of body weight (BW) applied to the scapulae to simulate carrying a backpack in the regular way, in front of the body and over both shoulders. The validation studies showed higher convex muscle activity, which was comparable to the literature. The implementation of spinal deformity resulted in a 10% increase of compressive force at the curve apex during unloaded upright standing. Apical compressive forces further increased by 50-62%, 77-94% and 103-128% for 10%, 15% and 20% BW loads, respectively. Moreover, load-dependent compressive force increases were the lowest in the regular backpack and the highest in the frontpack and convex conditions. The predictions indicated increased segmental compressive forces during unloaded standing, which could be ascribed to the scoliotic deformation. When carrying loads, compressive forces further increased depending on the carrying mode and the weight of the load. These results can be used as a basis for further studies investigating segmental loading in AIS patients during functional activities.

Published
2019
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30. Synchronous diversification of Sulawesis iconic artiodactyls driven by recent geological events.

Author

Frantz, Laurent, Rudzinski, Anna, Nugraha, Abang, Evin, Allowen, Burton, James, Hulme-Beaman, Ardern, Linderholm, Anna, Barnett, Ross, Vega, Rodrigo, Irving-Pease, Evan, Haile, James, Allen, Richard, Leus, Kristin, Shephard, Jill, Hillyer, Mia, Gillemot, Sarah, van den Hurk, Jeroen, Ogle, Sharron, Atofanei, Cristina, Thomas, Mark, Johansson, Friederike, Mustari, Abdul, Williams, John, Mohamad, Kusdiantoro, Damayanti, Chandramaya, Wiryadi, Ita, Obbles, Dagmar, Mona, Stephano, Day, Hally, Yasin, Muhammad, Meker, Stefan, Evans, Ben, von Rintelen, Thomas, Ho, Simon, Searle, Jeremy, Kitchener, Andrew, Macdonald, Alastair, Shaw, Darren, Hall, Robert, Galbusera, Peter, Larson, Greger, and Mcguire, Jimmy

Subjects
Wallacea, biogeography, evolution, geology, Animals, Base Sequence, Buffaloes, DNA, Mitochondrial, Genetic Speciation, Geography, Geological Phenomena, Indonesia, Islands, Microsatellite Repeats, Phylogeny, Phylogeography, Swine
Abstract

The high degree of endemism on Sulawesi has previously been suggested to have vicariant origins, dating back to 40 Ma. Recent studies, however, suggest that much of Sulawesis fauna assembled over the last 15 Myr. Here, we test the hypothesis that more recent uplift of previously submerged portions of land on Sulawesi promoted diversification and that much of its faunal assemblage is much younger than the island itself. To do so, we combined palaeogeographical reconstructions with genetic and morphometric datasets derived from Sulawesis three largest mammals: the babirusa, anoa and Sulawesi warty pig. Our results indicate that although these species most likely colonized the area that is now Sulawesi at different times (14 Ma to 2-3 Ma), they experienced an almost synchronous expansion from the central part of the island. Geological reconstructions indicate that this area was above sea level for most of the last 4 Myr, unlike most parts of the island. We conclude that emergence of land on Sulawesi (approx. 1-2 Myr) may have allowed species to expand synchronously. Altogether, our results indicate that the establishment of the highly endemic faunal assemblage on Sulawesi was driven by geological events over the last few million years.

Published
2018

32. D-aspartate oxidase gene duplication induces social recognition memory deficit in mice and intellectual disabilities in humans

Author

Lombardo, Barbara, Pagani, Marco, De Rosa, Arianna, Nunziato, Marcella, Migliarini, Sara, Garofalo, Martina, Terrile, Marta, D’Argenio, Valeria, Galbusera, Alberto, Nuzzo, Tommaso, Ranieri, Annaluisa, Vitale, Andrea, Leggiero, Eleonora, Di Maio, Anna, Barsotti, Noemi, Borello, Ugo, Napolitano, Francesco, Mandarino, Alessandra, Carotenuto, Marco, Heresco-Levy, Uriel, Pasqualetti, Massimo, Malatesta, Paolo, Gozzi, Alessandro, Errico, Francesco, Salvatore, Francesco, Pastore, Lucio, and Usiello, Alessandro

Published
2022
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36. Effect of curve location on the severity index for adolescent idiopathic scoliosis: a longitudinal cohort study

Author

Vergari, Claudio, Skalli, Wafa, Abelin-Genevois, Kariman, Bernard, Jean Claude, Hu, Zongshan, Cheng, Jack Chun Yiu, Chu, Winnie Chiu Wing, Assi, Ayman, Karam, Mohammad, Ghanem, Ismat, Bassani, Tito, Galbusera, Fabio, Sconfienza, Luca Maria, Brayda-Bruno, Marco, Courtois, Isabelle, Ebermeyer, Eric, Vialle, Raphael, Langlais, Tristan, and Dubousset, Jean

Published
2021
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