Pascal Sati

Pascal Sati
National Institutes of Health | NIH · National Institutes of Health (NIH)

PhD

About

111
Publications
16,420
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3,489
Citations
Additional affiliations
November 2009 - present
National Institutes of Health
Position
  • Researcher

Publications

Publications (111)
Article
Background: The central vein sign (CVS) is a proposed MRI biomarker of multiple sclerosis (MS). The impact of gadolinium-based contrast agent (GBCA) administration on CVS evaluation remains poorly investigated. Objective: To assess the effect of GBCA use on CVS detection and on the diagnostic performance of the CVS for MS, using a 3-T FLAIR* sequen...
Article
Background: The "central vein sign" (CVS), a linear hypointensity on T2*-weighted imaging corresponding to a central vein/venule, is associated with multiple sclerosis (MS) lesions. The effect of lesion-size exclusion criteria on MS diagnostic accuracy has not been extensively studied. Objective: Investigate the optimal lesion-size exclusion cri...
Article
Full-text available
Objectives: Neuropathological studies have shown that multiple sclerosis (MS) lesions are heterogeneous in terms of myelin/axon damage and repair as well as iron content. However, it remains a challenge to identify specific chronic lesion types, especially remyelinated lesions, in vivo in patients with MS. Methods: We performed 3 studies: (1) a...
Preprint
Background/Purpose Multicenter study designs involving a variety of MRI scanners have become increasingly common. However, these present the issue of biases in image-based measures due to scanner or site differences. To assess these biases, we imaged 11 volunteers with multiple sclerosis (MS) with scan and rescan data at 4 sites. Materials and Met...
Preprint
Manually segmenting multiple sclerosis (MS) cortical lesions (CL) is extremely time-consuming, and past studies have shown only moderate inter-rater reliability. To accelerate this task, we developed a deep learning-based framework (CLAIMS: Cortical Lesion Artificial Intelligence-based assessment in Multiple Sclerosis) for the automated detection a...
Article
Full-text available
Background and objectives: The central vein sign (CVS), a central linear hypointensity within lesions on T2*-weighted imaging, has been established as a sensitive and specific biomarker for the diagnosis of multiple sclerosis (MS). However, the CVS has not yet been comprehensively studied in newly developing MS lesions. We aimed to identify the CV...
Article
Manually segmenting multiple sclerosis (MS) cortical lesions (CL) is extremely time‐consuming, and past studies have shown only moderate inter‐rater reliability. To accelerate this task, we developed a deep learning‐based framework (CLAIMS: Cortical Lesion Artificial Intelligence‐based assessment in Multiple Sclerosis) for the automated detection a...
Article
Background Dramatic improvements in visualization of cortical (especially subpial) multiple sclerosis (MS) lesions allow assessment of impact on clinical course. Objective Characterize cortical lesions by 7 tesla (T) T 2 * -/T 1 -weighted magnetic resonance imaging (MRI); determine relationship with other MS pathology and contribution to disabilit...
Preprint
Full-text available
The current multiple sclerosis (MS) diagnostic criteria lack specificity, and this may lead to misdiagnosis, which remains an issue in present-day clinical practice. In addition, conventional biomarkers only moderately correlate with MS disease progression. Recently, advanced MS lesional imaging biomarkers such as cortical lesions (CL), the central...
Preprint
Remyelination is crucial for recovery from inflammatory demyelination in multiple sclerosis (MS). Investigating remyelination in vivo using magnetic resonance imaging (MRI) is difficult in MS, where collecting serial short-interval scans is challenging. Using experimental autoimmune encephalomyelitis (EAE) in common marmosets, a model of MS that re...
Article
Full-text available
The specificity and implementation of current MRI-based diagnostic criteria for multiple sclerosis (MS) are imperfect. Approximately 1 in 5 of individuals diagnosed with MS are eventually determined not to have the disease, with overreliance on MRI findings a major cause of MS misdiagnosis. The central vein sign (CVS), a proposed MRI biomarker for...
Article
Full-text available
Objective To noninvasively assess myelin status in chronic white matter lesions of multiple sclerosis (MS), we developed and evaluated a simple classification scheme based on T1 relaxation time maps derived from 7-tesla postmortem and in vivo MRI. Methods Using the MP2RAGE MRI sequence, we classified 36 lesions from 4 postmortem MS brains as “long...
Article
Full-text available
Background and Purpose The presence of a paramagnetic rim around a white matter lesion has recently been shown to be a hallmark of a particular pathological type of multiple sclerosis lesion. Increased prevalence of these paramagnetic rim lesions is associated with a more severe disease course in MS, but manual identification is time-consuming. We...
Article
Full-text available
Objective To assess whether chronic white matter inflammation in multiple sclerosis (MS) patients - as detected in-vivo by paramagnetic rim MRI lesions (PRL) - is associated with higher serum neurofilament light chain (sNfL) levels, a marker of neuro-axonal damage. Methods In 118 MS patients with no gadolinium-enhancing lesions or recent relapses,...
Article
Full-text available
Quantitative MRI provides biophysical measures of the microstructural integrity of the CNS, which can be compared across CNS regions, patients, and centres. In patients with multiple sclerosis, quantitative MRI techniques such as relaxometry, myelin imaging, magnetization transfer, diffusion MRI, quantitative susceptibility mapping, and perfusion M...
Article
Full-text available
Objective The central vein sign (CVS) and “paramagnetic rim lesions” (PRL) are emerging imaging biomarkers in multiple sclerosis (MS) reflecting perivenular demyelination and chronic, smoldering inflammation. The objective of this study was to assess relationships between cognitive impairment (CI) and the CVS and PRL in radiologically isolated synd...
Article
Full-text available
Damage to the myelin sheath and the neuroaxonal unit is a cardinal feature of multiple sclerosis; however, a detailed characterization of the interaction between myelin and axon damage in vivo remains challenging. We applied myelin water and multi-shell diffusion imaging to quantify the relative damage to myelin and axons (i) among different lesion...
Article
Background: Cortical lesions are common in multiple sclerosis (MS). T2*-weighted (T2*w) imaging at 7 T is relatively sensitive for cortical lesions, but quality is often compromised by motion and main magnetic field (B0) fluctuations. Purpose: The aim of this study was to determine whether motion and B0 correction with a navigator-guided gradien...
Article
Background: Misdiagnosis of multiple sclerosis (MS) is common and often occurs due to misattribution of non-MS magnetic resonance imaging (MRI) lesions to MS demyelination. A recently developed MRI biomarker, the central vein sign (CVS), has demonstrated high specificity for MS lesions and may thus help prevent misdiagnosis. Objective: This study e...
Article
Cortical lesions are a primary driver of disability in multiple sclerosis (MS). However, noninvasive detection of cortical lesions with in vivo magnetic resonance imaging (MRI) remains challenging. Experimental autoimmune encephalomyelitis (EAE) in the common marmoset is a relevant animal model of MS for investigating the pathophysiological mechani...
Preprint
Full-text available
Background and Purpose The presence of a paramagnetic rim around a white matter lesion has recently been shown to be a hallmark of a particular pathological type of multiple sclerosis (MS) lesion. Increased prevalence of these paramagnetic rim lesions (PRLs) is associated with a more severe disease course in MS. The identification of these lesions...
Chapter
The automated detection of cortical lesions (CLs) in patients with multiple sclerosis (MS) is a challenging task that, despite its clinical relevance, has received very little attention. Accurate detection of the small and scarce lesions requires specialized sequences and high or ultra-high field MRI. For supervised training based on multimodal str...
Article
In multiple sclerosis (MS), a subset of chronic active white matter lesions are identifiable on MRI by their paramagnetic rims, and increasing evidence supports their association with clinical disease severity. Here we study their potential role in differential diagnosis, screening an international multicenter clinical research‐based sample of 438...
Preprint
Full-text available
The automated detection of cortical lesions (CLs) in patients with multiple sclerosis (MS) is a challenging task that, despite its clinical relevance, has received very little attention. Accurate detection of the small and scarce lesions requires specialized sequences and high or ultra-high field MRI. For supervised training based on multimodal str...
Article
Full-text available
Magnetic resonance imaging (MRI) is the most important paraclinical tool for assessing drug response in multiple sclerosis (MS) clinical trials. As such, MRI has also been widely used in preclinical research to investigate drug efficacy and pathogenic aspects in MS animal models. Keeping track of all published preclinical imaging studies, and possi...
Article
Individuals with radiologically isolated syndrome (RIS) have incidental magnetic resonance imaging (MRI) abnormalities suggestive of multiple sclerosis (MS).¹ Recent studies using susceptibility-based imaging have shown that a subgroup of chronic MS white matter lesions (WMLs) have a rim of paramagnetic susceptibility-associated signal loss at the...
Article
The central vein sign (CVS) is an efficient imaging biomarker for multiple sclerosis (MS) diagnosis, but its application in clinical routine is limited by inter‐rater variability and the expenditure of time associated with manual assessment. We describe a deep learning‐based prototype for automated assessment of the CVS in white matter MS lesions u...
Poster
Full-text available
The presence of a central vein in MS white matter lesions has been extensively described using MRI. This finding has been further refined with a more formal definition of a central vein sign (CVS) and has been found to be present in a majority of white matter lesions in MS patients, with significantly lower numbers in other conditions with white ma...
Article
Background and purpose: Multiple sclerosis lesions develop around small veins that are radiologically described as the so-called central vein sign. With 7T MR imaging and magnetic susceptibility-based sequences, the central vein sign has been observed in 80%-100% of MS lesions in patients' brains. However, a lower proportion ∼50% has been reported...
Article
Background The central vein sign (CVS) has been shown to help in the differential diagnosis of multiple sclerosis (MS), but most prior studies are retrospective. Objectives To prospectively assess the diagnostic predictive value of the CVS in diagnostically difficult cases. Methods In this prospective multicenter study, 51 patients with suspected...
Article
Full-text available
Inflammatory destruction of iron-rich myelin is characteristic of multiple sclerosis (MS). Although iron is needed for oligodendrocytes to produce myelin during development, its deposition has also been linked to neurodegeneration and inflammation, including in MS. We report perivascular iron deposition in multiple sclerosis lesions that was mirror...
Article
Importance In multiple sclerosis (MS), chronic active lesions, which previously could only be detected at autopsy, can now be identified on susceptibility-based magnetic resonance imaging (MRI) in vivo as non–gadolinium-enhancing lesions with paramagnetic rims. Pathologically, they feature smoldering inflammatory demyelination at the edge, remyelin...
Article
Background and purpose: Radiologically isolated syndrome describes asymptomatic individuals with incidental radiologic abnormalities suggestive of multiple sclerosis. Recent studies have demonstrated that >40% of white matter lesions in MS (and often substantially more) have visible central veins on MR imaging. This "central vein sign" reflects pe...
Article
This paper presents an open-source pipeline to train neural networks to segment structures of interest from MRI data. The pipeline is tailored towards homogeneous datasets and requires relatively low amounts of manual segmentations (few dozen, or less depending on the homogeneity of the dataset). Two use-case scenarios for segmenting the spinal cor...
Presentation
Full-text available
In this work, we developed a semi-automatic cloud-based workflow for evaluating the clinical value of the central vein sign for MS diagnosis using FLAIR* in a multicenter setting. This novel workflow is a powerful tool that has the potential to significantly accelerate clinical research imaging studies in MS.
Article
Objectives: The aim of this study was to develop a new automated segmentation method of white matter (WM) and cortical multiple sclerosis (MS) lesions visible on magnetization-prepared 2 inversion-contrast rapid gradient echo (MP2RAGE) images acquired at 7 T MRI. Materials and methods: The proposed prototype (MSLAST [Multiple Sclerosis Lesion An...
Article
Accumulating evidence corroborates the role of the “central vein sign” in the radiological diagnosis of multiple sclerosis (MS). Here, we report human MRI‐pathological data that inflammation‐dependent intracerebral remodeling of the vessel wall is directly associated with the prominence of intralesional veins on susceptibility‐based MRI. In adult m...
Article
Objective: To summarize current and emerging imaging techniques that can be used to assess neuroprotection and repair in multiple sclerosis (MS), and to provide a consensus opinion on the potential utility of each technique in clinical trial settings. Methods: Clinicians and scientists with expertise in the use of MRI in MS convened in Toronto,...
Article
Background:: Experimental autoimmune encephalomyelitis (EAE) in the common marmoset is a nonhuman primate model of multiple sclerosis (MS) that shares numerous clinical, radiological, and pathological features with MS. Among the clinical features are motor and sensory deficits that are highly suggestive of spinal cord (SC) damage. Objective:: To...
Article
Full-text available
This study explored whether autoregulatory shifts in cerebral blood volume induce susceptibility changes large enough to be depicted by quantitative susceptibility mapping. Eight healthy subjects underwent fast quantitative susceptibility mapping at 3T while lying down to slowly decrease mean arterial pressure. A linear relationship between mean ar...
Article
Full-text available
Pathogens, particularly human herpesviruses (HHVs), are implicated as triggers of disease onset/progression in multiple sclerosis (MS) and other neuroinflammatory disorders. However, the time between viral acquisition in childhood and disease onset in adulthood complicates the study of this association. Using nonhuman primates, we demonstrate that...
Article
Full-text available
Background and purpose: The central vein sign is a promising MR imaging diagnostic biomarker for multiple sclerosis. Recent studies have demonstrated that patients with MS have higher proportions of white matter lesions with the central vein sign compared with those with diseases that mimic MS on MR imaging. However, the clinical application of th...
Chapter
High resolution magnetic resonance (MR) images are desired in many clinical applications, yet acquiring such data with an adequate signal-to-noise ratio requires a long time, making them costly and susceptible to motion artifacts. A common way to partly achieve this goal is to acquire MR images with good in-plane resolution and poor through-plane r...
Conference Paper
The presence of a vein inside white matter lesions was recently proposed as an imaging biomarker that can help in the differential diagnosis of Multiple Sclerosis (MS), potentially reducing the challenging clinical-radiological gap. Here, we propose a prototype based on ensembling small 3D convolutional networks to classify perivenular (P+) and non...
Article
Recent advances in BOLD fMRI scan techniques have substantially improved spatial and temporal resolution, currently reaching to sub-millimeter and sub-second levels respectively. Unfortunately, there remain physiological barriers that prevent achieving this resolution in practice. BOLD contrast relies on the hemodynamic response to neuronal activit...
Article
Background and purpose: MR imaging-pathologic studies have reported that paramagnetic rims on 7T susceptibility-based MR imaging identify, in vivo, the subset of MS lesions with compartmentalized inflammation at the lesion edge and associated remyelination failure. Here, we assessed the reliability of detecting these rims on high-resolution 3T pha...
Article
Full-text available
Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system. Although it has been extensively studied, the proximate trigger of the immune response remains uncertain. Experimental autoimmune encephalomyelitis in the common marmoset recapitulates many radiological and pathological features of focal multiple sclerosis le...
Article
The long-standing relationship between ultra-high-field (7 T) MRI and multiple sclerosis (MS) has brought new insights to our understanding of lesion evolution and its associated pathology. With the recent FDA approval of a commercially available scanner, 7 T MRI is finally entering the clinic with great expectations about its potential added value...
Article
Full-text available
Background and purpose: Cortical lesions are common and often extensive in multiple sclerosis but are difficult to visualize by MRI, leaving important questions about their clinical implications and response to therapy unanswered. Our aim was to determine whether cortical lesions are better visualized using magnetization prepared 2 rapid acquisiti...
Article
Full-text available
Objectives: In multiple sclerosis (MS), MRI is a sensitive tool for detecting white matter lesions, but its diagnostic specificity is still suboptimal; ambiguous cases are frequent in clinical practice. Detection of perivenular lesions in the brain (the "central vein sign") improves the pathological specificity of MS diagnosis, but comprehensive e...
Conference Paper
7T MRI provides additional insights in Multiple Sclerosis (MS) due to improved signal-to-noise and contrast-to-noise ratios as well as improved spatial resolution, resulting in reduced partial volume effects. In this context, we have developed an in-house automated tool to perform automatic detection of MS lesions at 7T.
Article
Here, we report the existence of meningeal lymphatic vessels in human and nonhuman primates (common marmoset monkeys) and the feasibility of noninvasively imaging and mapping them in vivo with high-resolution, clinical MRI. On T2-FLAIR and T1-weighted black-blood imaging, lymphatic vessels enhance with gadobutrol, a gadolinium-based contrast agent...
Article
Full-text available
Here, we report the existence of meningeal lymphatic vessels in human and nonhuman primates (common marmoset monkeys) and the feasibility of noninvasively imaging and mapping them in vivo with high-resolution, clinical MRI. On T2-FLAIR and T1-weighted black-blood imaging, lymphatic vessels enhance with gadobutrol, a gadolinium-based contrast agent...
Article
Background: Cortical pathology in multiple sclerosis (MS) has been associated with prolonged and progressive disease. 7T magnetic resonance imaging (MRI) provides enhanced visualization of cortical lesions (CLs). Hence, we conducted a pilot study to explore whether CLs occur early in MS, as evidenced by pediatric-onset patients. Methods: A total...
Article
Background: Detection of a "central vein sign" (CVS) on FLAIR* magnetic resonance imaging (MRI) is highly specific and sensitive for multiple sclerosis (MS). We evaluated the specificity and sensitivity of simplified CVS algorithms for MS diagnosis. Methods: MRIs from 10 participants with MS without additional comorbidities for MRI white matter...
Article
Full-text available
Multiple sclerosis (MS) is a pathologically complex CNS disease: inflammation, demyelination, and neuroaxonal degeneration occur concurrently and may depend on one another. Current therapies are aimed at the immune-mediated, inflammatory destruction of myelin, whereas axonal degeneration is ongoing and not specifically targeted. Diffusion-weighted...
Conference Paper
Ultra-high-field Magnetic Resonance Imaging (7T MRI) has been shown to be a valuable tool to assess focal and diffuse pathology in multiple sclerosis (MS) patients, both in grey and in white matter. In this work, we developed and evaluated a method to automatically assess MS lesion load using magnetization-prepared two inversion-contrast rapid grad...
Conference Paper
MR imaging of the cortical structure in vivo is challenging, due to its complex microstructure and its heterogeneity across the brain. Hardware and software advances in MRI have enabled unprecedented spatial resolution in in vivo, thereby providing a precious window into cortical grey matter microstructure. Magnetization prepared 2 rapid gradient e...
Article
Full-text available
Objective To explore the potential of a post-processing technique combining FLAIR and T2* (FLAIR*) to distinguish between lesions caused by multiple sclerosis (MS) from cerebral small vessel disease (SVD) in a clinical setting. MethodsFLAIR and T2* head datasets acquired at 3T of 25 people with relapsing MS (pwRMS) and ten with pwSVD were used. Aft...
Article
Ultrahigh-field (≥7 T) magnetic resonance (MR) imaging is being used at many leading academic medical centers to study neurologic disorders. The improved spatial resolution and anatomic detail are due to the increase in signal-to-noise and contrast-to-noise ratio at higher magnetic field strengths. Ultrahigh-field MR imaging improves multiple scler...
Article
Full-text available
Magnetic resonance imaging (MRI) allows for the delineation between normal and abnormal tissue on a macroscopic scale, sampling an entire tissue volume three-dimensionally. While MRI is an extremely sensitive tool for detecting tissue abnormalities, association of signal changes with an underlying pathological process is usually not straightforward...
Article
Full-text available
Over the past few years, MRI has become an indispensable tool for diagnosing multiple sclerosis (MS). However, the current MRI criteria for MS diagnosis have imperfect sensitivity and specificity. The central vein sign (CVS) has recently been proposed as a novel MRI biomarker to improve the accuracy and speed of MS diagnosis. Evidence indicates tha...