Publications by authors named "Laurent Petit"

106 Publications

Functionnectome as a framework to analyse the contribution of brain circuits to fMRI.

Commun Biol 2021 Sep 2;4(1):1035. Epub 2021 Sep 2.

Groupe d'Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives-UMR 5293, CNRS, CEA, University of Bordeaux, Bordeaux, France.

In recent years, the field of functional neuroimaging has moved away from a pure localisationist approach of isolated functional brain regions to a more integrated view of these regions within functional networks. However, the methods used to investigate functional networks rely on local signals in grey matter and are limited in identifying anatomical circuitries supporting the interaction between brain regions. Mapping the brain circuits mediating the functional signal between brain regions would propel our understanding of the brain's functional signatures and dysfunctions. We developed a method to unravel the relationship between brain circuits and functions: The Functionnectome. The Functionnectome combines the functional signal from fMRI with white matter circuits' anatomy to unlock and chart the first maps of functional white matter. To showcase this method's versatility, we provide the first functional white matter maps revealing the joint contribution of connected areas to motor, working memory, and language functions. The Functionnectome comes with an open-source companion software and opens new avenues into studying functional networks by applying the method to already existing datasets and beyond task fMRI.
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http://dx.doi.org/10.1038/s42003-021-02530-2DOI Listing
September 2021

Novel characterization of the relationship between verbal list-learning outcomes and hippocampal subfields in healthy adults.

Hum Brain Mapp 2021 Aug 28. Epub 2021 Aug 28.

Université de Bordeaux - Neurocampus, CEA, CNRS, IMN UMR 5293, Bordeaux, France.

The relationship between hippocampal subfield volumetry and verbal list-learning test outcomes have mostly been studied in clinical and elderly populations, and remain controversial. For the first time, we characterized a relationship between verbal list-learning test outcomes and hippocampal subfield volumetry on two large separate datasets of 447 and 1,442 healthy young and middle-aged adults, and explored the processes that could explain this relationship. We observed a replicable positive linear correlation between verbal list-learning test free recall scores and CA1 volume, specific to verbal list learning as demonstrated by the hippocampal subfield volumetry independence from verbal intelligence. Learning meaningless items was also positively correlated with CA1 volume, pointing to the role of the test design rather than word meaning. Accordingly, we found that association-based mnemonics mediated the relationship between verbal list-learning test outcomes and CA1 volume. This mediation suggests that integrating items into associative representations during verbal list-learning tests explains CA1 volume variations: this new explanation is consistent with the associative functions of the human CA1.
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http://dx.doi.org/10.1002/hbm.25614DOI Listing
August 2021

Tractography dissection variability: What happens when 42 groups dissect 14 white matter bundles on the same dataset?

Neuroimage 2021 Aug 22;243:118502. Epub 2021 Aug 22.

Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Madrid, Spain.

White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation. In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human whole-brain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols for each fiber pathway. Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects. In order to foster the use of tractography bundle dissection in routine clinical settings, and as a fundamental analytical tool, future endeavors must aim to resolve and reduce this heterogeneity. Although external validation is needed to verify the anatomical accuracy of bundle dissections, reducing heterogeneity is a step towards reproducible research and may be achieved through the use of standard nomenclature and definitions of white matter bundles and well-chosen constraints and decisions in the dissection process.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118502DOI Listing
August 2021

Age-Related Variations in Regional White Matter Volumetry and Microstructure During the Post-adolescence Period: A Cross-Sectional Study of a Cohort of 1,713 University Students.

Front Syst Neurosci 2021 3;15:692152. Epub 2021 Aug 3.

Groupe d'Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives, UMR 5293, Université de Bordeaux, Bordeaux, France.

Human brain white matter undergoes a protracted maturation that continues well into adulthood. Recent advances in diffusion-weighted imaging (DWI) methods allow detailed characterizations of the microstructural architecture of white matter, and they are increasingly utilized to study white matter changes during development and aging. However, relatively little is known about the late maturational changes in the microstructural architecture of white matter during post-adolescence. Here we report on regional changes in white matter volume and microstructure in young adults undergoing university-level education. As part of the MRi-Share multi-modal brain MRI database, multi-shell, high angular resolution DWI data were acquired in a unique sample of 1,713 university students aged 18-26. We assessed the age and sex dependence of diffusion metrics derived from diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) in the white matter regions as defined in the John Hopkins University (JHU) white matter labels atlas. We demonstrate that while regional white matter volume is relatively stable over the age range of our sample, the white matter microstructural properties show clear age-related variations. Globally, it is characterized by a robust increase in neurite density index (NDI), and to a lesser extent, orientation dispersion index (ODI). These changes are accompanied by a decrease in diffusivity. In contrast, there is minimal age-related variation in fractional anisotropy. There are regional variations in these microstructural changes: some tracts, most notably cingulum bundles, show a strong age-related increase in NDI coupled with decreases in radial and mean diffusivity, while others, mainly cortico-spinal projection tracts, primarily show an ODI increase and axial diffusivity decrease. These age-related variations are not different between males and females, but males show higher NDI and ODI and lower diffusivity than females across many tracts. These findings emphasize the complexity of changes in white matter structure occurring in this critical period of late maturation in early adulthood.
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http://dx.doi.org/10.3389/fnsys.2021.692152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369154PMC
August 2021

The MRi-Share database: brain imaging in a cross-sectional cohort of 1870 university students.

Brain Struct Funct 2021 Sep 20;226(7):2057-2085. Epub 2021 Jul 20.

Groupe d'Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives, UMR5293, Université de Bordeaux, Bordeaux, France.

We report on MRi-Share, a multi-modal brain MRI database acquired in a unique sample of 1870 young healthy adults, aged 18-35 years, while undergoing university-level education. MRi-Share contains structural (T1 and FLAIR), diffusion (multispectral), susceptibility-weighted (SWI), and resting-state functional imaging modalities. Here, we described the contents of these different neuroimaging datasets and the processing pipelines used to derive brain phenotypes, as well as how quality control was assessed. In addition, we present preliminary results on associations of some of these brain image-derived phenotypes at the whole brain level with both age and sex, in the subsample of 1722 individuals aged less than 26 years. We demonstrate that the post-adolescence period is characterized by changes in both structural and microstructural brain phenotypes. Grey matter cortical thickness, surface area and volume were found to decrease with age, while white matter volume shows increase. Diffusivity, either radial or axial, was found to robustly decrease with age whereas fractional anisotropy only slightly increased. As for the neurite orientation dispersion and densities, both were found to increase with age. The isotropic volume fraction also showed a slight increase with age. These preliminary findings emphasize the complexity of changes in brain structure and function occurring in this critical period at the interface of late maturation and early ageing.
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http://dx.doi.org/10.1007/s00429-021-02334-4DOI Listing
September 2021

Reply to the letter to the Editor.

Brain Struct Funct 2021 Nov 20;226(8):2479-2480. Epub 2021 Jul 20.

Department of Neurosurgery, Structural and Functional Connectivity Lab Project, "Santa Chiara" Hospital, Azienda Provinciale Per I Servizi Sanitari (APSS), Trento, Italy.

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http://dx.doi.org/10.1007/s00429-021-02344-2DOI Listing
November 2021

Ability of neutrophil-to-lymphocyte ratio to predict secondary neurological impairment in patients with mild to moderate head injury. A retrospective study.

Am J Emerg Med 2021 Jun 19;50:46-50. Epub 2021 Jun 19.

Emergency Department, CHU Pellegrin, 33000 Bordeaux, France. Electronic address:

Background: The main objective was to assess the performance of the neutrophil-lymphocyte ratio (NLR) for early prediction of delayed neurological impairment and cerebral contusion worsening in patients with mild-to-moderate traumatic brain injury (TBI).

Methods: Over a 3-year period, every adult patient triaged to our level 1 trauma center with brain contusion and Glasgow Coma Scale (GCS) of 10 or greater were retrospectively included. The main study outcome was the occurrence of delayed clinical deterioration, defined as a GCS < 10 and/or a secondary need for mechanical ventilation, within 5 days after TBI. The performance of NLR for prediction of delayed clinical deterioration was assessed by receiver operating characteristic (ROC) curve.

Results: Overall, 115 patients were included and 16 (14%) presented a delayed clinical deterioration. Overall, the NLR at ED admission was higher in patients who developed a delayed clinical deterioration (18 [12-29] vs 8 [5-13], p = 0.0003). The area under the ROC curves for NLR at ED admission in predicting delayed clinical deterioration was 0.79 [0.65-0.93] and NLR > 15 was found to be independently associated with the occurrence of delayed clinical deterioration (adjusted OR = 10.1 [95%CI: 2.3-45.6]).

Conclusion: The NLR at ED admission was independently associated with the occurrence of delayed clinical deterioration, although limited by a poor discriminative value by itself. Further studies are needed to test the predictive value of composite scoring systems including NLR for prevention of under-triage of patients with mild-to-moderate TBI.
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http://dx.doi.org/10.1016/j.ajem.2021.06.030DOI Listing
June 2021

Filtering in tractography using autoencoders (FINTA).

Med Image Anal 2021 08 7;72:102126. Epub 2021 Jun 7.

Videos & Images Theory and Analytics Laboratory (VITAL), Department of Computer Science, Université de Sherbrooke, 2500, boul. de l'Université, Sherbrooke, Québec J1K 2R1, Canada.

Current brain white matter fiber tracking techniques show a number of problems, including: generating large proportions of streamlines that do not accurately describe the underlying anatomy; extracting streamlines that are not supported by the underlying diffusion signal; and under-representing some fiber populations, among others. In this paper, we describe a novel autoencoder-based learning method to filter streamlines from diffusion MRI tractography, and hence, to obtain more reliable tractograms. Our method, dubbed FINTA (Filtering in Tractography using Autoencoders) uses raw, unlabeled tractograms to train the autoencoder, and to learn a robust representation of brain streamlines. Such an embedding is then used to filter undesired streamline samples using a nearest neighbor algorithm. Our experiments on both synthetic and in vivo human brain diffusion MRI tractography data obtain accuracy scores exceeding the 90% threshold on the test set. Results reveal that FINTA has a superior filtering performance compared to conventional, anatomy-based methods, and the RecoBundles state-of-the-art method. Additionally, we demonstrate that FINTA can be applied to partial tractograms without requiring changes to the framework. We also show that the proposed method generalizes well across different tracking methods and datasets, and shortens significantly the computation time for large (>1 M streamlines) tractograms. Together, this work brings forward a new deep learning framework in tractography based on autoencoders, which offers a flexible and powerful method for white matter filtering and bundling that could enhance tractometry and connectivity analyses.
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http://dx.doi.org/10.1016/j.media.2021.102126DOI Listing
August 2021

The inferior fronto-occipital fascicle: a century of controversies from anatomy theaters to operative neurosurgery.

J Neurosurg Sci 2021 May 3. Epub 2021 May 3.

Division of Neurosurgery, Structural and Functional Connectivity Lab, S. Chiara Hospital, Trento, Italy.

Introduction: Since its first description in the early 19th century, the inferior frontooccipital fascicle (IFOF) and its anatomo-functional features were neglected in the neuroscientific literature for the last century. In the last decade, the rapid development of in vivo imaging for the reconstruction of white matter (WM) connectivity (i.e., tractography) and the consequent interest in more traditional ex vivo methods (postmortem dissection) have allowed a renewed debate about course, termination territories, anatomical relationships, and functional roles of this fascicle.

Evidence Acquisition: We reviewed the main current knowledge concerning the structural and functional anatomy of the IFOF and possible implications in neurosurgical practice.

Evidence Synthesis: The IFOF connects the occipital cortex, the temporo-basal areas, the superior parietal lobule, and the pre-cuneus to the frontal lobe, passing through the ventral third of subinsular WM of the external capsule. This wide distribution of cortical terminations provides multimodal integration between several functional networks, including language, non-verbal semantic processing, object identification, visuo-spatial processing and planning, reading, facial expression recognition, memory and conceptualization, emotional and neuropsychological behavior. This anatomo-functional organization has important implication also in neurosurgical practice, especially when approaching the frontal, insular, temporo-parieto-occipital regions and the ventricular system.

Conclusions: The IFOF is the most extensive associative bundle of the human connectome. Its multi-layer organization reflects important implications in many aspects of brain functional processing. Accurate awareness of IFOF functional anatomy and integration between multimodal datasets coming from different sources has crucial implications for both neuroscientific knowledge and quality of neurosurgical treatments.
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http://dx.doi.org/10.23736/S0390-5616.21.05360-1DOI Listing
May 2021

Hodology of the superior longitudinal system of the human brain: a historical perspective, the current controversies, and a proposal.

Brain Struct Funct 2021 Jun 21;226(5):1363-1384. Epub 2021 Apr 21.

Groupe d'Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives, UMR 5293, CNRS, CEA, University of Bordeaux, Centre Broca Nouvelle-Aquitaine - 3ème étage - 146 rue Léo Saignat, CS 61292, 33076, Bordeaux Cedex, France.

The description of human white matter pathways experienced a tremendous improvement, thanks to the advancement of neuroimaging and dissection techniques. The downside of this progress is the production of redundant and conflicting literature, bound by specific studies' methods and aims. The Superior Longitudinal System (SLS), encompassing the arcuate (AF) and the superior longitudinal fasciculi (SLF), becomes an illustrative example of this fundamental issue, being one of the most studied white matter association pathways of the brain. Herein, we provide a complete illustration of this white matter fiber system's current definition, from its early descriptions in the nineteenth century to its most recent characterizations. We propose a review of both in vivo diffusion magnetic resonance imaging-based tractography and anatomical dissection studies, enclosing all the information available up to date. Based on these findings, we reconstruct the wiring diagram of the SLS, highlighting a substantial variability in the description of its cortical sites of termination and the taxonomy and partonomy that characterize the system. We aim to level up discrepancies in the literature by proposing a parallel across the various nomenclature. Consistent with the topographical arrangement already documented for commissural and projection pathways, we suggest approaching the SLS organization as an orderly and continuous wiring diagram, respecting a medio-lateral palisading topography between the different frontal, parietal, occipital, and temporal gyri rather than in terms of individualized fascicles. A better and complete description of the fine organization of white matter association pathways' connectivity is fundamental for a better understanding of brain function and their clinical and neurosurgical applications.
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http://dx.doi.org/10.1007/s00429-021-02265-0DOI Listing
June 2021

Are third-generation cephalosporins still an option for empirical antibiotic therapy in critically ill trauma patients with early ventilator or hospital-acquired pneumonia?

Anaesth Crit Care Pain Med 2021 04 18;40(2):100833. Epub 2021 Mar 18.

Anaesthesiology and Critical Care Department, CHU Pellegrin, 33000 Bordeaux, France. Electronic address:

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http://dx.doi.org/10.1016/j.accpm.2021.100833DOI Listing
April 2021

Hierarchical Microstructure Informed Tractography.

Brain Connect 2021 03 28;11(2):75-88. Epub 2021 Jan 28.

Department of Computer Science, University of Verona, Verona, Italy.

Tractography uses diffusion magnetic resonance imaging to noninvasively infer the macroscopic pathways of white matter fibers and it is the only available technique to probe the structural connectivity of the brain. However, despite this unique and compelling ability and its wide range of possible neurological applications, tractography is still limited, lacks anatomical precision, and suffers from a serious sensitivity/specificity trade-off. For this reason, in the past few years, tractography postprocessing techniques have emerged and proved effective for improving the quality of the reconstructions. Among them, the Convex Optimization Modeling for Microstructure Informed Tractography formulation allows incorporating the anatomical prior that fibers are naturally organized in fascicles, and has obtained exceptional results in increasing the accuracy of the estimated tractograms. We propose an extension to this idea and introduce a multilevel grouping of the streamlines to capture the white matter arrangement in fascicles and subfascicles. We tested our proposed formulation in synthetic and data. Our experiments show that using multiple levels allows considering information about the white matter organization more adequately and helps to improve further the accuracy of the resulting tractograms. This new formulation represents a further important step toward a more accurate structural connectivity estimation.
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http://dx.doi.org/10.1089/brain.2020.0907DOI Listing
March 2021

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

Nat Commun 2020 12 8;11(1):6285. Epub 2020 Dec 8.

University of Alabama at Birmingham School of Medicine, Birmingham, AL, 35233, USA.

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.
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http://dx.doi.org/10.1038/s41467-020-19111-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722866PMC
December 2020

Performance of the Kleihauer Betke test in the prediction of neonatal anemia.

J Matern Fetal Neonatal Med 2020 Oct 26:1-7. Epub 2020 Oct 26.

Nantes University Hospital, Nantes, France.

Objectives: The aim of this study was to correlate antenatal Kleihauer (KT) test results with fetal hemoglobin at birth to find a threshold for predicting severe fetal anemia. The secondary objectives were to assess the impact of KT on obstetric management and to study the correlation between the middle cerebral artery peack systolic velocity and fetal anemia.

Results: One thousand forty-six KT were positive over the 10-year period, but only 147 were included from 88 patients, of which 17 fetuses were anemic. Demographic and obstetric characteristics were similar between anemic and non-anemic groups. As regards new-born, there was a higher risk of prematurity among anemic as long as a lower birth rate in accordance. While a negative correlation was observed between KT and hemoglobin at birth, no KT upper threshold could be found that was both sensitive and specific. In addition, there was no case of fetal anemia when KT was repeated, even though it increased. KT showed little usefulness in obstetrics management to help improving neonatal care for anemia. Conversely, the MCA PSV demonstrated good performance in this matter and the ROC curve area was 0.91 (figure).

Discussion: Feto-maternal hemorrhage is a rare but grave pathology which could lead to anemia. The most common clinical sign is reduced fetal movement and it was the main indication to perform a KT. Cardiotocography patterns suggestive of anemia are sinusoidal, micro-oscillatory and non-reactive monitoring. Ultrasound features were polyhydramnios, hydrop fetalis and increased MCA peack systolic velocity. KT was correlated with MCA PSV and with hemoglobin level at birth. However, the latter showed a better diagnostic performance. MCA PSV measurement is a powerful test to screen for fetal anemia, and should be part of the regular training of obstetricians. Indeed, this technic gives immediate and reliable results, while those of KT are delayed.

Conclusion: The KT should not be used as a tool to screen for fetal anemia but rather as a test to explain a fetal anemia. However, the MCA PSV is reliable in this matter and give immediate result, thus obstetrician should be trained to routinely perform it.
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http://dx.doi.org/10.1080/14767058.2020.1837768DOI Listing
October 2020

May the neutrophil-to-lymphocyte ratio at admission predict the occurrence and the severity of ARDS after blunt chest trauma patients? A retrospective study.

Am J Emerg Med 2021 01 24;39:137-142. Epub 2020 Sep 24.

Anesthesiology and Critical Care Department, CHU Pellegrin, 33000 Bordeaux, France. Electronic address:

Introduction: In blunt chest trauma patients, the activation of inflammatory response is thought to be one of the pathophysiological pathways leading to delayed acute respiratory distress syndrome(ARDS). The main objective of the study was to assess the performance of the neutrophil-lymphocyte ratio(NLR) for prediction of delayed ARDS. The secondary objective was to compare NLR in patients with traumarelated focal and non-focal ARDS.

Methods: Over a 2-year period, every adult patient triaged to our level 1 trauma center with multiple rib fractures and PaO 2 /FiO 2 ratio > 200 at admission were retrospectively included. The NLR was recorded at admission in the Emergency Department(ED). The main study outcome was the occurrence of moderate to severe ARDS within 5 days after admission according to Berlin criteria. Two phenotypes (focal and non-focal ARDS) were determined based on the closest chest CT regarding the ARDS onset.

Results: 216 patients were included and 42(19%) underwent moderate to severe ARDS within 5 days after ED admission (focal, N = 26 [12%] and non-focal, N = 16 [7%]). The NLR at ED admission was not statistically different between patients who developed or not a delayed ARDS (14 ± 13 vs. 11 ± 8,p = 0.095), although patients with non-focal ARDS presented higher NLR ratio than focal ARDS (21 ± 18 p < 0.0001). The AUC for NLR at ED in predicting delayed ARDS was 0.53.

Conclusion: In blunt chest trauma patients, the NLR at ED admission was unable to predict delayed ARDS over the five first days post-injury. Although not clinically relevant, the NLR was higher in patients with non focal ARDS.
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http://dx.doi.org/10.1016/j.ajem.2020.09.050DOI Listing
January 2021

Brain connections derived from diffusion MRI tractography can be highly anatomically accurate-if we know where white matter pathways start, where they end, and where they do not go.

Brain Struct Funct 2020 Nov 20;225(8):2387-2402. Epub 2020 Aug 20.

Sherbrooke Connectivity Imaging Laboratory (SCIL), Universite de Sherbrooke, Sherbrooke, Canada.

MR Tractography, which is based on MRI measures of water diffusivity, is currently the only method available for noninvasive reconstruction of fiber pathways in the brain. However, it has several fundamental limitations that call into question its accuracy in many applications. Therefore, there has been intense interest in defining and mitigating the intrinsic limitations of the method. Recent studies have reported that tractography is inherently limited in its ability to accurately reconstruct the connections of the brain, when based on voxel-averaged estimates of local fiber orientation alone. Several validation studies have confirmed that tractography techniques are plagued by both false-positive and false-negative connections. However, these validation studies which quantify sensitivity and specificity, particularly in animal models, have not utilized prior anatomical knowledge, as is done in the human literature, for virtual dissection of white matter pathways, instead assessing tractography implemented in a relatively unconstrained manner. Thus, they represent a worse-case scenario for bundle-segmentation techniques and may not be indicative of the anatomical accuracy in the process of bundle segmentation, where streamline filtering using inclusion and exclusion regions-of-interest is common. With this in mind, the aim of the current study is to investigate and quantify the upper bounds of accuracy using current tractography methods. Making use of the same dataset utilized in two seminal validation papers, we show that prior anatomical knowledge in the form of manually placed or template-driven constraints can significantly improve the anatomical accuracy of estimated brain connections. Thus, we show that it is possible to achieve a high sensitivity and high specificity simultaneously, and conclude that current tractography algorithms, in combination with anatomically driven constraints, can result in reconstructions which very accurately reflect the ground truth white matter connections.
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http://dx.doi.org/10.1007/s00429-020-02129-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554161PMC
November 2020

A new method for accurate in vivo mapping of human brain connections using microstructural and anatomical information.

Sci Adv 2020 Jul 29;6(31):eaba8245. Epub 2020 Jul 29.

Department of Computer Science, University of Verona, Verona, Italy.

Diffusion magnetic resonance imaging is a noninvasive imaging modality that has been extensively used in the literature to study the neuronal architecture of the brain in a wide range of neurological conditions using tractography. However, recent studies highlighted that the anatomical accuracy of the reconstructions is inherently limited and challenged its appropriateness. Several solutions have been proposed to tackle this issue, but none of them proved effective to overcome this fundamental limitation. In this work, we present a novel processing framework to inject into the reconstruction problem basic prior knowledge about brain anatomy and its organization and evaluate its effectiveness using both simulated and real human brain data. Our results indicate that our proposed method dramatically increases the accuracy of the estimated brain networks and, thus, represents a major step forward for the study of connectivity.
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http://dx.doi.org/10.1126/sciadv.aba8245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399649PMC
July 2020

Characterization of acute kidney injury in critically ill patients with severe coronavirus disease 2019.

Clin Kidney J 2020 Jun 6;13(3):354-361. Epub 2020 Jun 6.

Service de Médecine Intensive Réanimation, Hôpital Pellegrin et Hôpital Saint André, CHU de Bordeaux, Bordeaux, France.

Background: Coronavirus disease 2019 (COVID-19)-associated acute kidney injury (AKI) frequency, severity and characterization in critically ill patients has not been reported.

Methods: Single-centre cohort performed from 3 March 2020 to 14 April 2020 in four intensive care units in Bordeaux University Hospital, France. All patients with COVID-19 and pulmonary severity criteria were included. AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. A systematic urinary analysis was performed. The incidence, severity, clinical presentation, biological characterization (transient versus persistent AKI; proteinuria, haematuria and glycosuria) and short-term outcomes were evaluated.

Results: Seventy-one patients were included, with basal serum creatinine (SCr) of 69 ± 21 µmol/L. At admission, AKI was present in 8/71 (11%) patients. Median [interquartile range (IQR)] follow-up was 17 (12-23) days. AKI developed in a total of 57/71 (80%) patients, with 35% Stage 1, 35% Stage 2 and 30% Stage 3 AKI; 10/57 (18%) required renal replacement therapy (RRT). Transient AKI was present in only 4/55 (7%) patients and persistent AKI was observed in 51/55 (93%). Patients with persistent AKI developed a median (IQR) urine protein/creatinine of 82 (54-140) (mg/mmol) with an albuminuria/proteinuria ratio of 0.23 ± 20, indicating predominant tubulointerstitial injury. Only two (4%) patients had glycosuria. At Day 7 after onset of AKI, six (11%) patients remained dependent on RRT, nine (16%) had SCr >200 µmol/L and four (7%) had died. Day 7 and Day 14 renal recovery occurred in 28% and 52%, respectively.

Conclusion: Severe COVID-19-associated AKI is frequent, persistent, severe and characterized by an almost exclusive tubulointerstitial injury without glycosuria.
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http://dx.doi.org/10.1093/ckj/sfaa099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314187PMC
June 2020

May the initial CT scan predict the occurrence of delayed hemothorax in blunt chest trauma patients?

Eur J Trauma Emerg Surg 2021 Feb 21;47(1):71-78. Epub 2020 May 21.

Surgical and Trauma Intensive Care Unit, Anesthesiology and Critical Care Department, Hôpital Pellegrin, CHU Bordeaux, Place Amélie Raba Léon, 33076, Bordeaux Cedex, France.

Purpose: To assess the impact of delayed hemothorax on outcomes in blunt chest trauma patients without life-threatening condition at admission and characterize the predictive value of predefined anatomical factors for delayed hemothorax.

Methods: In a single-centre retrospective study, every spontaneous breathing patient admitted for a blunt chest trauma without significant pleural effusion at ICU admission was included. A multivariable regression model was used to determine the covariate-adjusted odd of secondary respiratory complications in patients with delayed hemothorax ≥ 500 ml. The characteristics of rib fractures (number, location and displacement) were integrated into a logistic regression model to determine variables associated with delayed hemothorax in multivariate analysis.

Results: Over the study period, 109 patients were included and the rate of delayed hemothorax ≥ 500 ml was 36%. Patients with delayed hemothorax had higher rates of pulmonary infections (OR 4.8 [1.6-16.4]) but no statistical association between delayed hemothorax and secondary respiratory failure (OR 2.0 [0.4-9.4]). A posterior location and a displaced rib fracture were independent predictors of delayed hemothorax (OR 3.4 [1.3-8.6] and OR 2.3 [1.1-5.1], respectively). At least one displaced rib fracture was more specific of delayed hemothorax than the commonly used threshold of three or more rib fractures (81.3 vs. 51.5%).

Conclusion: Delayed hemothorax is a frequent complication associated with increased risk of pulmonary infection. The posterior location and the displacement of at least one rib fracture in the initial CT scan were independent risk factors for predicting the occurrence of delayed hemothorax.
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http://dx.doi.org/10.1007/s00068-020-01391-4DOI Listing
February 2021

Age-Related Changes of Peak Width Skeletonized Mean Diffusivity (PSMD) Across the Adult Lifespan: A Multi-Cohort Study.

Front Psychiatry 2020 4;11:342. Epub 2020 May 4.

Institute of Neurodegenerative Diseases (IMN), CNRS, CEA, Bordeaux, France.

Parameters of water diffusion in white matter derived from diffusion-weighted imaging (DWI), such as fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, AD, and RD), and more recently, peak width of skeletonized mean diffusivity (PSMD), have been proposed as potential markers of normal and pathological brain ageing. However, their relative evolution over the entire adult lifespan in healthy individuals remains partly unknown during early and late adulthood, and particularly for the PSMD index. Here, we gathered and analyzed cross-sectional diffusion tensor imaging (DTI) data from 10 population-based cohort studies in order to establish the time course of white matter water diffusion phenotypes from post-adolescence to late adulthood. DTI data were obtained from a total of 20,005 individuals aged 18.1 to 92.6 years and analyzed with the same pipeline for computing skeletonized DTI metrics from DTI maps. For each individual, MD, AD, RD, and FA mean values were computed over their FA volume skeleton, PSMD being calculated as the 90% peak width of the MD values distribution across the FA skeleton. Mean values of each DTI metric were found to strongly vary across cohorts, most likely due to major differences in DWI acquisition protocols as well as pre-processing and DTI model fitting. However, age effects on each DTI metric were found to be highly consistent across cohorts. RD, MD, and AD variations with age exhibited the same U-shape pattern, first slowly decreasing during post-adolescence until the age of 30, 40, and 50 years, respectively, then progressively increasing until late life. FA showed a reverse profile, initially increasing then continuously decreasing, slowly until the 70s, then sharply declining thereafter. By contrast, PSMD constantly increased, first slowly until the 60s, then more sharply. These results demonstrate that, in the general population, age affects PSMD in a manner different from that of other DTI metrics. The constant increase in PSMD throughout the entire adult life, including during post-adolescence, indicates that PSMD could be an early marker of the ageing process.
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http://dx.doi.org/10.3389/fpsyt.2020.00342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212692PMC
May 2020

Salt wasting syndrome in brain trauma patients: a pathophysiologic approach using sodium balance and urinary biochemical analysis.

BMC Neurol 2020 May 16;20(1):190. Epub 2020 May 16.

Anesthesiology and Critical Care Department, CHU Bordeaux, 33000, Bordeaux, France.

Background: To explore the underlying mechanisms leading to the occurrence of hyponatremia and enhanced urinary sodium excretion in brain trauma patients using sodium balance and urinary biochemical analysis.

Methods: We conducted a retrospective analysis of a local database prospectively collected in 60 brain trauma patients without chronic renal dysfunction. Metabolic and hemodynamic parameters were averaged over three consecutive periods over the first seven days after admission. The main outcome investigated in this study was the occurrence of at least one episode of hyponatremia.

Results: Over the study period, there was a prompt decrease in sodium balance (163 ± 193 vs. -12 ± 154 mmol/day, p < 0.0001) and free water clearance (- 0.7 ± 0.7 vs. -1.8 ± 2.3 ml/min, p < 0.0001). The area under the ROC curves for sodium balance in predicting the occurrence of hyponatremia during the next period was 0.81 [95% CI: 0.64-0.97]. Variables associated with averaged urinary sodium excretion were sodium intake (R = 0.26, p < 0.0001) and fractional excretion of urate (R = 0.15, p = 0.009). Urinary sodium excretion was also higher in patients with sustained augmented renal clearance over the study period (318 ± 106 vs. 255 ± 135 mmol/day, p = 0.034).

Conclusion: The decreased vascular volume resulting from a negative sodium balance is a major precipitating factor of hyponatremia in brain trauma patients. Predisposing factors for enhanced urinary sodium excretion were high sodium intake, high fractional excretion of urate and augmented renal clearance over the first seven days after ICU admission.
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http://dx.doi.org/10.1186/s12883-020-01771-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229604PMC
May 2020

Rib fracture displacement is a strong predictor for long-term opioid requirement in blunt chest trauma patients.

Injury 2020 07 7;51(7):1686-1688. Epub 2020 May 7.

Anesthesiology and Critical Care Department, CHU Bordeaux, 33000 Bordeaux, France; Univ. Bordeaux Segalen, 33000 Bordeaux, France.

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http://dx.doi.org/10.1016/j.injury.2020.05.003DOI Listing
July 2020

Population Pharmacokinetic Study of the Suitability of Standard Dosing Regimens of Amikacin in Critically Ill Patients with Open-Abdomen and Negative-Pressure Wound Therapy.

Antimicrob Agents Chemother 2020 03 24;64(4). Epub 2020 Mar 24.

Anesthesiology and Critical Care Department, CHU Bordeaux, Bordeaux, France.

The aim was to assess the appropriateness of recommended regimens for empirical MIC coverage in critically ill patients with open-abdomen and negative-pressure therapy (OA/NPT). Over a 5-year period, every critically ill patient who received amikacin and who underwent therapeutic drug monitoring (TDM) while being treated by OA/NPT was retrospectively included. A population pharmacokinetic (PK) modeling was performed considering the effect of 10 covariates (age, sex, total body weight [TBW], adapted body weight [ABW], body surface area [BSA], modified sepsis-related organ failure assessment [SOFA] score, vasopressor use, creatinine clearance [CL], fluid balance, and amount of fluids collected by the NPT over the sampling day) in patients who underwent continuous renal replacement therapy (CRRT) or did not receive CRRT. Monte Carlo simulations were employed to determine the fractional target attainment (FTA) for the PK/pharmacodynamic [PD] targets (maximum concentration of drug [ ]/MIC ratio of ≥8 and a ratio of the area under the concentration-time curve from 0 to 24 h [AUC]/MIC of ≥75). Seventy critically ill patients treated by OA/NPT (contributing 179 concentration values) were included. Amikacin PK concentrations were best described by a two-compartment model with linear elimination and proportional residual error, with CL and ABW as significant covariates for volume of distribution () and CL for CL. The reported ) in non-CRRT and CRRT patients was 35.8 and 40.2 liters, respectively. In Monte Carlo simulations, ABW-adjusted doses between 25 and 35 mg/kg were needed to reach an FTA of >85% for various renal functions. Despite an increased and a wide interindividual variability, desirable PK/PD targets may be achieved using an ABW-based loading dose of 25 to 30 mg/kg. When less susceptible pathogens are targeted, higher dosing regimens are probably needed in patients with augmented renal clearance (ARC). Further studies are needed to assess the effect of OA/NPT on the PK parameters of antimicrobial agents.
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http://dx.doi.org/10.1128/AAC.02098-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179257PMC
March 2020

Tractostorm: The what, why, and how of tractography dissection reproducibility.

Hum Brain Mapp 2020 05 10;41(7):1859-1874. Epub 2020 Jan 10.

Sherbrooke Connectivity Imaging Laboratory (SCIL), Université de Sherbrooke, Sherbrooke, Canada.

Investigative studies of white matter (WM) brain structures using diffusion MRI (dMRI) tractography frequently require manual WM bundle segmentation, often called "virtual dissection." Human errors and personal decisions make these manual segmentations hard to reproduce, which have not yet been quantified by the dMRI community. It is our opinion that if the field of dMRI tractography wants to be taken seriously as a widespread clinical tool, it is imperative to harmonize WM bundle segmentations and develop protocols aimed to be used in clinical settings. The EADC-ADNI Harmonized Hippocampal Protocol achieved such standardization through a series of steps that must be reproduced for every WM bundle. This article is an observation of the problematic. A specific bundle segmentation protocol was used in order to provide a real-life example, but the contribution of this article is to discuss the need for reproducibility and standardized protocol, as for any measurement tool. This study required the participation of 11 experts and 13 nonexperts in neuroanatomy and "virtual dissection" across various laboratories and hospitals. Intra-rater agreement (Dice score) was approximately 0.77, while inter-rater was approximately 0.65. The protocol provided to participants was not necessarily optimal, but its design mimics, in essence, what will be required in future protocols. Reporting tractometry results such as average fractional anisotropy, volume or streamline count of a particular bundle without a sufficient reproducibility score could make the analysis and interpretations more difficult. Coordinated efforts by the diffusion MRI tractography community are needed to quantify and account for reproducibility of WM bundle extraction protocols in this era of open and collaborative science.
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http://dx.doi.org/10.1002/hbm.24917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267902PMC
May 2020

Increased β-Lactams dosing regimens improve clinical outcome in critically ill patients with augmented renal clearance treated for a first episode of hospital or ventilator-acquired pneumonia: a before and after study.

Crit Care 2019 Nov 27;23(1):379. Epub 2019 Nov 27.

Anesthesiology and Critical Care Department, Hôpital Pellegrin, CHU Bordeaux, 33000, Bordeaux, France.

Background: Augmented renal clearance (ARC) is recognized as a leading cause of β-lactam subexposure when conventional dosing regimens are used. The main objective was to compare the clinical outcome of ARC patients treated by conventional or increased β-lactam dosing regimens for a first episode of hospital or ventilator-acquired pneumonia (HAP-VAP).

Methods: In this single-center, retrospective study, every ARC patient treated by β-lactam for a first episode of HAP-VAP was included during two 15-month periods, before (Control period) and after (Treatment period) the modification of a local antibiotic therapy protocol. ARC was defined by a 24-h measured creatinine clearance ≥ 150 ml/min. The primary endpoint was defined as a therapeutic failure of the antimicrobial therapy or a HAP-VAP relapse within 28 days. Inverse probability of treatment weight (IPTW) was derived from a propensity score model. Cox proportional hazard models were used to evaluate the association between treatment period and clinical outcome.

Results: During the study period, 177 patients were included (control period, N = 88; treatment period, N = 89). Therapeutic failure or HAP-VAP relapse was significantly lower in the treatment period (10 vs. 23%, p = 0.019). The IPTW-adjusted hazard ratio of poor clinical outcome in the treatment period was 0.35 (95% CI 0.15-0.81), p = 0.014. No antibiotic side effect was reported during the treatment period.

Conclusions: Higher than licensed dosing regimens of β-lactams may be safe and effective in reducing the rate of therapeutic failure and HAP-VAP recurrence in critically ill augmented renal clearance (ARC) patients.
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http://dx.doi.org/10.1186/s13054-019-2621-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881978PMC
November 2019

Piperacillin-tazobactam should be preferred to third-generation cephalosporins to treat wild-type inducible AmpC-producing Enterobacterales in critically ill patients with hospital or ventilator-acquired pneumonia.

J Crit Care 2020 04 13;56:6-11. Epub 2019 Nov 13.

Anesthesiology and Critical Care Department I, CHU Pellegrin, 33000 Bordeaux, France; Univ. Bordeaux Segalen, 33000 Bordeaux, France.

Purpose: To compare the rate of therapeutic failure in critically ill patients treated by third-generation cephalosporins (3GCs) or piperacillin-tazobactam (PTZ) for wild-type AmpC-producing Enterobacterales pulmonary infections.

Methods: Over a 4-year period, all adult patients treated for a wild-type AmpC-producing Enterobacterales pulmonary infection were retrospectively included. Two groups of patients were compared according to the definitive antibiotic therapy (3GCs or PTZ) considered after <48 h of empirical antibiotic therapy. The main outcome was the rate of therapeutic failure (impaired clinical response under treatment and/or a relapse of pulmonary infection). The secondary outcome was a secondary acquisition of 3GCs resistance.

Results: Over the study period, 244 patients were included; 56 (23%) experienced therapeutic failure. In the non-adjusted cohort, the rate of therapeutic failure and emergence of resistance were significantly higher in the 3GCs group (32 vs. 18%, p = .011 and 13 vs. 5%, p = .035, respectively). In the propensity score-matched population, the use of 3GCs was associated with higher rates of therapeutic failure (HR = 1.61 [1.27-2.07]). The secondary de-escalation to 3GCs after 48 h of PTZ as a first-line antibiotic therapy was not associated with increased rate of emergence of resistance.

Conclusion: Our study confirms that 3GCs should be avoided as first-line antibiotic therapy in wild-type AmpC-producing Enterobacterales pulmonary infections.
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http://dx.doi.org/10.1016/j.jcrc.2019.11.005DOI Listing
April 2020

Response: Commentary: The Nomenclature of Human White Matter Association Pathways: Proposal for a Systematic Taxonomic Anatomical Classification.

Front Neuroanat 2019 17;13:91. Epub 2019 Oct 17.

Groupe d'Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives-UMR 5293, CNRS, CEA University of Bordeaux, Bordeaux, France.

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http://dx.doi.org/10.3389/fnana.2019.00091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811495PMC
October 2019

Editorial: Organization of the White Matter Anatomy in the Human Brain.

Front Neuroanat 2019 18;13:85. Epub 2019 Sep 18.

Groupe d'Imagerie Neurofonctionnelle, Institut des Maladies Neurodégératives (IMN)-UMR5293-CNRS, CEA, Université de Bordeaux, Bordeaux, France.

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http://dx.doi.org/10.3389/fnana.2019.00085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759501PMC
September 2019

May levosimendan be safe and effective in refractory vasospasm despite adequate treatment with repeated angiography and milrinone infusion after subarachnoid haemorrhage?

Anaesth Crit Care Pain Med 2019 12 16;38(6):665-667. Epub 2019 Jul 16.

Anaesthesiology and Critical Care Department, University Hospital of Bordeaux, 33000 Bordeaux, France; University of Bordeaux-Segalen, 33000 Bordeaux, France.

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http://dx.doi.org/10.1016/j.accpm.2019.07.004DOI Listing
December 2019
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