Ona Wu

• Massachusetts General Hospital

Importance Identifying anatomy causally involved in psychosis could inform therapeutic neuromodulation targets for schizophrenia. Objective To assess whether lesions that cause secondary psychosis have functional connections to a common brain circuit. Design, Setting, and Participants This case-control study mapped functional connections of publi...

Background The effects of intravenous alteplase in patients with prior antiplatelet therapy (APT) remain controversial. We aimed to assess the efficacy and safety of imaging-based intravenous alteplase in patients with unknown-onset stroke with prior APT. Methods Data from randomized controlled trials comparing alteplase with placebo/standard care...

Background Chronic emotional distress among cardiac arrest (CA) survivors and their caregivers is prevalent and worsens quality of life and recovery. Interventions to prevent chronic distress post-CA are needed. We developed Recovering Together after Cardiac Arrest (RT-CA), an intervention to increase resiliency in CA survivor-caregiver dyads (pair...

Introduction The effects of imaging-based intravenous thrombolysis on outcomes based on patient sex remain unclear. We aimed to investigate whether outcomes among patients with stroke with an unknown onset time and treated with imaging-based intravenous thrombolysis are influenced by their sex. Patients and Methods This study was a pooled analysis...

Background: Emotional distress in cardiac arrest survivors and their caregivers (dyads) is prevalent, persistent, and undermines clinical and quality of life outcomes. To date, there is an absence of interventions that address early distress to prevent chronicity. Aim: To inform psychosocial intervention content for new cardiac arrest survivor-care...

Objective To systematically evaluate which lesion‐based imaging features and methods allow for the best statistical prediction of poststroke deficits across independent datasets. Methods We utilized imaging and clinical data from three independent datasets of patients experiencing acute stroke (N1 = 109, N2 = 638, N3 = 794) to statistically predic...

Importance Identifying anatomy causally involved in psychosis could inform therapeutic neuromodulation targets for schizophrenia. Objective To assess whether lesions that cause secondary psychosis have functional connections to a common brain circuit. Design This case-control study mapped functional connections of published cases of lesions causi...

Leukoaraiosis is a neuroimaging marker of small-vessel disease that is characterized by high signal intensity on Fluid-Attenuated Inversion Recovery (FLAIR) MRI. There is increasing evidence from pathology and neuroimaging suggesting that the structural abnormalities which characterize leukoaraiosis are actually present within regions of normal-app...

Background: Stroke with unknown time of onset can be categorized into 2 groups; wake-up stroke (WUS) and unwitnessed stroke with an onset time unavailable for reasons other than wake-up (non-wake-up unwitnessed stroke, non-WUS). We aimed to assess potential differences in the efficacy and safety of intravenous thrombolysis (IVT) between these subg...

Introduction: Although prior antiplatelet therapy (APT) could potentially contribute to bleeding risk, the influence of prior APT on intravenous thrombolysis outcomes remains controversial. We sought to assess the efficacy and safety of intravenous thrombolysis for acute ischemic stroke in patients receiving prior APT Methods: Patients with an acut...

Deep learning has allowed for remarkable progress in many medical scenarios. Deep learning prediction models often require 105–107 examples. It is currently unknown whether deep learning can also enhance predictions of symptoms post-stroke in real-world samples of stroke patients that are often several magnitudes smaller. Such stroke outcome predic...

Introduction: Significant knowledge gaps remain in predicting neurological outcomes for comatose cardiac arrest survivors. Severe cerebral edema (SCE) development offers an objective imaging surrogate for neurologic injury. Aim: We have previously shown that deep learning (DL) algorithms can detect SCE on CT. We aim to determine whether our model w...

Futile recanalization hampers prognoses of ischemic stroke after successful mechanical thrombectomy, hypothetically through post-recanalization perfusion deficits, onset-to-groin delays and sex effects. Clinically, acute multiparametric imaging studies remain challenging. We assessed possible relationships between these factors and disease outcome...

Early prediction of the recovery of consciousness in comatose cardiac arrest patients remains challenging. We prospectively studied task-relevant fMRI responses in 19 comatose cardiac arrest patients and five healthy controls to assess the fMRI’s utility for neuroprognostication. Tasks involved instrumental music listening, forward and backward lan...

Background and Objectives Epileptiform activity and burst suppression are neurophysiology signatures reflective of severe brain injury following cardiac arrest. We aimed to delineate the evolution of coma neurophysiology features ensembles associated with recovery from coma after cardiac arrest. Methods Adult subjects in acute coma following cardi...

Importance: It remains unclear why lesions in some locations cause epilepsy while others do not. Identifying the brain regions or networks associated with epilepsy by mapping these lesions could inform prognosis and guide interventions. Objective: To assess whether lesion locations associated with epilepsy map to specific brain regions and netwo...

American-style football (ASF) players experience repetitive head impacts which may result in chronic traumatic encephalopathy neuropathologic change (CTE-NC). At present, a definitive diagnosis of CTE-NC requires the identification of localized hyperphosphorylated Tau (p-Tau) after death via immunohistochemistry. Some studies suggest that positron...

Background There is increasing evidence from pathology and neuroimaging suggesting that the structural abnormalities which characterize leukoaraiosis are present within regions of normal-appearing white matter. In this study, we aimed to verify whether signal intensity on FLAIR imaging in normal-appearing white matter is related to the leukoaraiosi...

Background: The unknown onset stroke can be categorized into two groups; wake-up stroke (WUS) and non-wake-up unwitnessed stroke with a time of onset unavailable due to aphasia, impaired consciousness, or cognitive impairment (non-wake-up unknown onset stroke, non-WUS). We aimed to assess the differences in efficacy and safety of intravenous thromb...

Introduction: Predicting individual outcomes post-stroke with the highest possible accuracy is a crucial steppingstone in the realization of precision medicine. We here evaluated various types of lesion information in their capacity to predict stroke severity in a large cohort of patients with acute ischemic stroke. Methods: A total of 1,075 patien...

Introduction: Deep learning (DL) has allowed for substantial progress in many, often machine vision-focused medical scenarios. Since DL models typically require 10 ⁵ -10 ⁷ examples, it is currently unknown whether DL can also enhance predictions of outcomes post-stroke in real-world samples of stroke patients that are several magnitudes smaller. We...

Introduction Deep learning has allowed for remarkable progress in many medical scenarios. Since deep learning prediction models often require 105-107 examples, it is currently unknown whether deep learning can also enhance predictions of symptoms post-stroke in real-world samples of stroke patients that are often several magnitudes smaller. Such st...

This study aimed to investigate the influence of stroke lesions in predefined highly interconnected (rich-club) brain regions on functional outcome post-stroke, determine their spatial specificity and explore the effects of biological sex on their relevance. We analyzed MRI data recorded at index stroke and ~3-months modified Rankin Scale (mRS) dat...

Background and Objectives While chronological age is one of the most influential determinants of post-stroke outcomes, little is known of the impact of neuroimaging-derived biological “brain age”. We hypothesized that radiomics analyses of T2-FLAIR images texture would provide brain age estimates and that advanced brain age of stroke patients will...

Introduction: Previous studies have shown that lower gray:white matter ratio (GWR) is associated with poor outcomes in patients initially comatose after cardiac arrest. However, those studies focused on survival, a measure that may be confounded by withdrawal of life-sustaining therapy (WLST) decisions. We assessed the association of GWR with sever...

Background purpose A substantial number of patients with acute ischemic stroke (AIS) experience multiple acute lesions (MAL). We here aimed to scrutinize MAL in a large radiologically deep-phenotyped cohort. Materials and methods Analyses relied upon imaging and clinical data from the international MRI-GENIE study. Imaging data comprised both Flui...

Background Although chronic kidney disease (CKD) is associated with worse stroke outcomes, data regarding the influence of CKD on intravenous thrombolysis outcomes are scarce. We sought to assess the efficacy and safety of intravenous thrombolysis for acute ischemic stroke with unknown onset time in patients with CKD. Methods Patients with an acut...

Objective To examine potential genetic relationships between migraine and the two distinct phenotypes posterior circulation ischemic stroke (PCiS) and anterior circulation ischemic stroke (ACiS), we generated migraine polygenic risk scores (PRSs) and compared these between PCiS and ACiS, and separately vs. non-stroke control subjects. Methods Acut...

Objective To examine whether high white matter hyperintensity (WMH) burden is associated with greater stroke severity and worse functional outcomes in lesion pattern-specific ways. Methods MR neuroimaging and National Institutes of Health Stroke Scale data at index stroke, as well as modified Rankin Scale (mRS) at 3-6 months post-stroke were obtai...

Background A substantial number of patients with acute ischemic stroke (AIS) experience multiple acute lesions (MAL). However, the spatial distribution and clinical implications of such MAL are incompletely understood. Methods Analyses relied upon imaging and clinical data of patients with AIS from the international MRI-GENIE study. Initially, we...

This study aimed to investigate the influence of stroke lesions in pre-defined highly interconnected (rich club) brain regions on functional outcome post-stroke, determine their spatial specificity and explore the effects of biological sex on their relevance. We analyzed MRI data recorded at index stroke and ∼3-months modified Rankin Scale (mRS) da...

Introduction Bien que l’âge chronologique soit l'un des facteurs pronostiques les plus déterminants après un AVC ischémique, l'impact de l’âge cérébral, un biomarqueur personnalisé de santé cérébrale, reste inconnu. Nous formulons l'hypothèse que l'analyse radiomique de l'imagerie T2-FLAIR peut déterminer l’âge cérébral et qu'un âge cérébral avancé...

Stroke represents a considerable burden of disease for both men and women. However, a growing body of literature suggests clinically relevant sex differences in the underlying causes, presentations and outcomes of acute ischaemic stroke. In a recent study, we reported sex divergences in lesion topographies: specific to women, acute stroke severity...

Introduction: Our prior meta-analysis reported that imaging-based intravenous thrombolysis (IVT) was safe and effective for patients who have had a stroke with an unknown onset time. The aim of this study is to investigate whether sex differences exist in clinical outcomes among this population. Methods: This is a pooled analysis of individual pati...

Introduction: About ~10% of acute ischemic stroke (AIS) patients experience multiple acute lesions (MAL). However, the spatial distribution and clinical implications of such MAL are incompletely understood. Here, we scrutinized MAL in a large, radiologically deep-phenotyped cohort of AIS patients. Methods: We analyzed imaging and clinical data of 2...

Background Studies of neurologic outcomes have found conflicting results regarding differences between patients with substance-related cardiac arrests (SRCA) and non-SRCA. We investigate the effects of SRCA on severe cerebral edema development, a neuroimaging intermediate endpoint for neurologic injury. Methods 327 out-of-hospital comatose cardiac...

Introduction: Understanding the relations between lesions and outcomes is a particularly promising avenue to support tailored stroke care. We here employed a novel Bayesian framework integrating lesion location and functional lesion connectivity, i.e., lesion network mapping data, aiming to augment the prediction of stroke severity and the interpre...

Objective: Most cardiac arrest patients who are successfully resuscitated are initially comatose due to hypoxic-ischemic brain injury. Quantitative electroencephalography (EEG) provides valuable prognostic information. However, prior approaches largely rely on snapshots of the EEG, without taking advantage of temporal information. Methods: We pr...

Introduction: Previous studies have shown that women have poorer neurological outcomes than men following out-of-hospital cardiac arrest (OHCA). However, those studies focused on survival, a measure that may be confounded by withdrawal of life-sustaining therapy (WLST) decisions. We sought to assess sex differences in severe cerebral edema developm...

Objective To examine whether high white matter hyperintensity (WMH) burden is associated with greater stroke severity and worse functional outcomes in lesion pattern-specific ways. Methods MR neuroimaging and National Institutes of Health Stroke Scale data at index stroke, as well as modified Rankin Scale (mRS) at 3-6 months post-stroke were obtain...

Several clinical trials have demonstrated that advanced neuroimaging can select patients for recanalization therapy in an extended time window. The favorable functional outcomes and safety profile of these studies have led to the incorporation of neuroimaging in endovascular treatment guidelines, and most recently, also extended to decision making...

Background: Few MRA-based studies have systematically evaluated the prevalence and laterality of a fetal configuration of the posterior cerebral artery (FTP) in ischemic stroke populations versus other populations. This common variant is important in the setting of acute stroke and secondary prevention decisions. Objective: To determine the prev...

Objective Electroencephalography (EEG) is an important tool for neurological outcome prediction after cardiac arrest. However, the complexity of continuous EEG data limits timely and accurate interpretation by clinicians. We develop a deep neural network (DNN) model to leverage complex EEG trends for early and accurate assessment of cardiac arrest...

While chronological age is one of the most influential determinants of post-stroke outcomes, little is known of the impact of neuroimaging-derived biological brain age. We here first examine whether radiomics analysis of the texture of brain T2-FLAIR MRI images can be used to predict brain age in stroke patients. We then assess the clinical determi...

Objective: To personalize the prognostication of post-stroke outcome using MRI-detected cerebrovascular pathology, we sought to investigate the association between the excessive white matter hyperintensity (WMH) burden unaccounted for by the traditional stroke risk profile of individual patients and their long-term functional outcomes after a strok...

Objective Neuroimaging measurements of brain structural integrity are thought to be surrogates for brain health, but precise assessments require dedicated advanced image acquisitions. By means of quantitatively describing conventional images, radiomic analyses hold potential for evaluating brain health. We sought to: (1) evaluate radiomics to asses...

Acute ischemic stroke affects men and women differently. In particular, women are often reported to experience higher acute stroke severity than men. We derived a low-dimensional representation of anatomical stroke lesions and designed a Bayesian hierarchical modeling framework tailored to estimate possible sex differences in lesion patterns linked...

The brain regions responsible for hallucinations remain unclear. We studied 89 brain lesions causing hallucinations using a recently validated technique termed lesion network mapping. We found that hallucinations occurred following lesions to a variety of different brain regions, but these lesion locations fell within a single functionally connecte...

The aim of the current study was to explore the whole-brain dynamic functional connectivity patterns in acute ischemic stroke (AIS) patients and their relation to short and long-term stroke severity. We investigated resting-state functional MRI-based dynamic functional connectivity of 41 AIS patients two to five days after symptom onset. Re-occurri...

Introduction: MRI-detected white matter hyperintensity (WMH) burden is linked to the overall brain health and incident stroke outcomes. However, data are limited as to whether specific acute stroke lesion patterns purport greater stroke severity in patients with extensive pre-existing WMH. In this analysis, we sought to investigate lesion pattern-s...

Introduction: As a radiographic signature of end-stage small vessel disease, white matter hyperintensity (WMH) burden impacts recovery and outcomes after acute ischemic stroke (AIS). In this study, we sought to investigate the effect of WMH volume (WMHv) on stroke severity and functional outcomes independent of the infarct size and topography. Meth...

Introduction Neuroimaging measurements of brain structural integrity are thought to be surrogates for brain health, but precise assessments require dedicated advanced image acquisitions. By means of describing the texture of conventional images beyond what meets the naked eye, radiomic analyses hold potential for evaluating brain health. We sought...

Introduction: The incidence of substance-related cardiac arrests (SRCA) has increased due to the opioid epidemic. Previous studies have shown that SRCA present differently than non-SRCA. Weinvestigated differences in the clinical courses between the two groups for patients who were initially comatose post-resuscitation. Methods: Data from out-of-ho...

Background Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. Methods We did a systematic review and meta-analysis of individual pati...

White matter hyperintensities of presumed vascular origin (WMH) are a prevalent form of cerebral small-vessel disease and an important risk factor for post-stroke cognitive dysfunction. Despite this prevalence, it is not well understood how WMH contributes to post-stroke cognitive dysfunction. Preliminary findings suggest that increasing WMH volume...

Acute ischemic stroke affects men and women differently in many ways. In particular, women are oftentimes reported to experience a higher acute stroke severity than men. Here, we derived a low-dimensional representation of anatomical stroke lesions and designed a sex-aware Bayesian hierarchical modelling framework for a large-scale, well phenotyped...

BACKGROUND Although mania is characteristic of bipolar disorder, it can also occur following focal brain damage. Such cases may provide unique insight into brain regions responsible for mania symptoms and identify therapeutic targets. METHODS Lesion locations associated with mania were identified using a systematic literature search (n = 41) and ma...

Objective: To determine whether brain volume is associated with functional outcome after acute ischemic stroke (AIS). Methods: We analyzed cross-sectional data of the multi-site, international hospital-based MRI-GENetics Interface Exploration (MRI-GENIE) study (July 1, 2014- March 16, 2019) with clinical brain magnetic resonance imaging (MRI) obtai...

Background: Magnetic resonance imaging (MRI) serves as a cornerstone in defining stroke phenotype and etiological subtype through examination of ischemic stroke lesion appearance and is therefore an essential tool in linking genetic traits and stroke. Building on baseline MRI examinations from the centralized and structured radiological assessments...

Background and Purpose To explore the whole-brain dynamic functional network connectivity patterns in acute ischemic stroke (AIS) patients and their relation to stroke severity in the short and long term. Methods We investigated large-scale dynamic functional network connectivity of 41 AIS patients two to five days after symptom onset. Re-occurring...

Objective To examine etiologic stroke subtypes and vascular risk factor profiles and their association with white matter hyperintensity (WMH) burden in patients hospitalized for acute ischemic stroke (AIS). Methods For the MRI Genetics Interface Exploration (MRI-GENIE) study, we systematically assembled brain imaging and phenotypic data for 3,301...

Objective To determine whether brain volume is associated with functional outcome after acute ischemic stroke (AIS). Patients and Methods This study was conducted between July 1, 2014, and March 16, 2019. We analyzed cross-sectional data of the multisite, international hospital-based MRI-Genetics Interface Exploration study with clinical brain mag...

Registration is a core component of many imaging pipelines. In case of clinical scans, with lower resolution and sometimes substantial motion artifacts, registration can produce poor results. Visual assessment of registration quality in large clinical datasets is inefficient. In this work, we propose to automatically assess the quality of registrat...

Selected patients with large vessel occlusions (LVO) can benefit from thrombectomy up to 24 hours after onset. Identifying patients who might benefit from late intervention after transfer from community hospitals to thrombectomy-capable centers would be valuable. We searched for presentation biomarkers to identify such patients. Frequent MR imaging...

Background: Early outcome prediction after acute ischemic stroke (AIS) is critical to guide care and rehabilitation strategies. Pre-existing chronic structural injury to cerebral white matter (WM), including ischemic WM hyperintensity (WMH) and microstructural changes within the normal-appearing WM (NAWM), is known to impede post-stroke recovery. Q...

Background: Fundamental advances in stroke care will require pooling imaging phenotype data from multiple centers, to complement the current aggregation of genomic, environmental, and clinical information. Sharing clinically acquired MRI data from multiple hospitals is challenging due to inherent heterogeneity of clinical data, where the same MRI s...

Background White matter hyperintensity of presumed vascular origin is a risk factor for poor stroke outcomes. In patients with acute ischemic stroke, however, the in vivo mechanisms of white matter microstructural injury are less clear. Aims To characterize the directional diffusivity components in normal-appearing white matter and white matter hy...

Chronic white matter structural injury is a risk factor for poor long-term outcomes after acute ischemic stroke (AIS). However, it is unclear how white matter structural injury predisposes to poor outcomes after AIS. To explore this question, in 42 AIS patients with moderate to severe white matter hyperintensity (WMH) burden, we characterized WMH a...

Background: For cardiac arrest survivors who are initially comatose after restoration of spontaneous circulation, the extent of brain injury and expected recovery are crucial for management decisions. Advanced diffusion imaging approaches may provide additional insight into microstructural integrity and potential for arousal recovery (AR). Methods:...

Objective Posterior circulation ischemic stroke (PCiS) constitutes 20–30% of ischemic stroke cases. Detailed information about differences between PCiS and anterior circulation ischemic stroke (ACiS) remains scarce. Such information might guide clinical decision making and prevention strategies. We studied risk factors and ischemic stroke subtypes...

Background and Purpose— The ability to model long-term functional outcomes after acute ischemic stroke represents a major clinical challenge. One approach to potentially improve prediction modeling involves the analysis of connectomics. The field of connectomics represents the brain’s connectivity as a graph, whose topological properties have helpe...

Objective: To determine whether the rich-club organization, essential for information transport in the human connectome, is an important biomarker of functional outcome after acute ischemic stroke (AIS). Methods: Consecutive AIS patients (N = 344) with acute brain magnetic resonance imaging (MRI) (<48 h) were eligible for this study. Each patient u...

Objective: To determine whether ascending arousal network (AAn) connectivity is reduced in patients presenting with traumatic coma. Methods: We performed high-angular-resolution diffusion imaging in 16 patients with acute severe traumatic brain injury who were comatose on admission and in 16 matched controls. We used probabilistic tractography t...

Background and purpose Functional outcomes after ischaemic stroke are worse in women, despite adjusting for differences in comorbidities and treatment approaches. White matter microvascular integrity represents one risk factor for poor long-term functional outcomes after ischaemic stroke. The aim of the study is to characterise sex-specific differe...

Objectives: To assess whether plasma biomarkers of oxidative stress predict diffusion-perfusion mismatch in patients with acute ischemic stroke (AIS). Methods: We measured plasma levels of oxidative stress biomarkers such as F2-isoprostanes (F2-isoPs), total and perchloric acid Oxygen Radical Absorbance Capacity (ORACTOT and ORACPCA), urinary le...

Human memory is thought to depend on a circuit of connected brain regions, but this hypothesis has not been directly tested. We derive a human memory circuit using 53 case reports of strokes causing amnesia and a map of the human connectome (n = 1000). This circuit is reproducible across discovery (n = 27) and replication (n = 26) cohorts and speci...

Registration is a core component of many imaging pipelines. In case of clinical scans, with lower resolution and sometimes substantial motion artifacts, registration can produce poor results. Visual assessment of registration quality in large clinical datasets is inefficient. In this work, we propose to automatically assess the quality of registrat...

Background and Purpose— We evaluated deep learning algorithms’ segmentation of acute ischemic lesions on heterogeneous multi-center clinical diffusion-weighted magnetic resonance imaging (MRI) data sets and explored the potential role of this tool for phenotyping acute ischemic stroke. Methods— Ischemic stroke data sets from the MRI-GENIE (MRI-Gen...

Background and purpose: Accurate automated infarct segmentation is needed for acute ischemic stroke studies relying on infarct volumes as an imaging phenotype or biomarker that require large numbers of subjects. This study investigated whether an ensemble of convolutional neural networks trained on multiparametric DWI maps outperforms single netwo...

White matter hyperintensity (WMH) burden is a critically important cerebrovascular phenotype linked to prediction of diagnosis and prognosis of diseases, such as acute ischemic stroke (AIS). However, current approaches to its quantification on clinical MRI often rely on time intensive manual delineation of the disease on T2 fluid attenuated inverse...

Objective: Radiologic predictors of posttraumatic amnesia (PTA) duration are lacking. We hypothesized that the number and distribution of traumatic microbleeds (TMBs) detected by gradient recalled echo (GRE) magnetic resonance imaging (MRI) predicts PTA duration. Setting: Academic, tertiary medical center. Participants: Adults with traumatic b...

Background The ability to model long-term functional outcomes after acute ischemic stroke (AIS) represents a major clinical challenge. One approach to potentially improve prediction modeling involves the analysis of connectomics. The field of connectomics represents the brain’s connectivity as a graph, whose topological properties have helped uncov...

Purpose: White matter hyperintensity (WMH) is a common phenotype across a variety of neurological diseases, particularly prevalent in stroke patients; however, vascular territory dependent variation in WMH burden has not yet been identified. Here, we sought to investigate the spatial specificity of WMH burden in patients with acute ischemic stroke...

Objective: The role of heparin in acute ischemic stroke is controversial. We investigated the effect of heparin on ischemic lesion growth. Methods: Data were analyzed on nonthrombolyzed ischemic stroke patients in whom diffusion-weighted imaging (DWI)/perfusion-weighted imaging (PWI) MRI was performed less than 12 hours of last known well and sh...

White matter hyperintensity (WMH) burden is a critically important cerebrovascular phenotype linked to prediction of diagnosis and prognosis of diseases, such as acute ischemic stroke (AIS). However, current approaches to its quantification on clinical MRI often rely on time intensive manual delineation of the disease on T2 fluid attenuated inverse...

Objective: To determine whether the rich-club organization, essential for information transport in the human connectome, is an important biomarker of functional outcome after acute ischemic stroke (AIS). Methods: Consecutive AIS patients (N=344) with acute brain magnetic resonance imaging (MRI) (<48 hours) were eligible for this study. Each patient...