Papers by patricia desmond
Schizophrenia
Brain iron is central to dopaminergic neurotransmission, a key component in schizophrenia patholo... more Brain iron is central to dopaminergic neurotransmission, a key component in schizophrenia pathology. Iron can also generate oxidative stress, which is one proposed mechanism for gray matter volume reduction in schizophrenia. The role of brain iron in schizophrenia and its potential link to oxidative stress has not been previously examined. In this study, we used 7-Tesla MRI quantitative susceptibility mapping (QSM), magnetic resonance spectroscopy (MRS), and structural T1 imaging in 12 individuals with chronic schizophrenia and 14 healthy age-matched controls. In schizophrenia, there were higher QSM values in bilateral putamen and higher concentrations of phosphocreatine and lactate in caudal anterior cingulate cortex (caCC). Network-based correlation analysis of QSM across corticostriatal pathways as well as the correlation between QSM, MRS, and volume, showed distinct patterns between groups. This study introduces increased iron in the putamen in schizophrenia in addition to netwo...
Epilepsia
ObjectiveRecent work has shown that people with common epilepsies have characteristic patterns of... more ObjectiveRecent work has shown that people with common epilepsies have characteristic patterns of cortical thinning, and that these changes may be progressive over time. Leveraging a large multicenter cross‐sectional cohort, we investigated whether regional morphometric changes occur in a sequential manner, and whether these changes in people with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE‐HS) correlate with clinical features.MethodsWe extracted regional measures of cortical thickness, surface area, and subcortical brain volumes from T1‐weighted (T1W) magnetic resonance imaging (MRI) scans collected by the ENIGMA‐Epilepsy consortium, comprising 804 people with MTLE‐HS and 1625 healthy controls from 25 centers. Features with a moderate case–control effect size (Cohen d ≥ .5) were used to train an event‐based model (EBM), which estimates a sequence of disease‐specific biomarker changes from cross‐sectional data and assigns a biomarker‐based fine‐grained disease stag...
Neuroradiology, 2022
Purpose Development of a freely available stroke population–specific anatomical CT/MRI atlas with... more Purpose Development of a freely available stroke population–specific anatomical CT/MRI atlas with a reliable normalisation pipeline for clinical CT. Methods By reviewing CT scans in suspected stroke patients and filtering the AIBL MRI database, respectively, we collected 50 normal-for-age CT and MRI scans to build a standard-resolution CT template and a high-resolution MRI template. The latter was manually segmented into anatomical brain regions. We then developed and validated a MRI to CT registration pipeline to align the MRI atlas onto the CT template. Finally, we developed a CT-to-CT-normalisation pipeline and tested its reliability by calculating Dice coefficient (Dice) and Average Hausdorff Distance (AHD) for predefined areas in 100 CT scans from ischaemic stroke patients. Results The resulting CT/MRI templates were age and sex matched to a general stroke population (median age 71.9 years (62.1–80.2), 60% male). Specifically, this accounts for relevant structural changes relat...
Drug-resistant focal epilepsy is often caused by focal cortical dysplasias (FCDs). The distributi... more Drug-resistant focal epilepsy is often caused by focal cortical dysplasias (FCDs). The distribution of these lesions across the cerebral cortex and the impact of lesion location on clinical presentation and surgical outcome are largely unknown. We created a neuroimaging cohort of patients with individually mapped FCDs to determine factors associated with lesion location and predictors of postsurgical outcome.The Multi-centre Epilepsy Lesion Detection (MELD) project collated a retrospective cohort of 580 patients with epilepsy attributed to FCD from 20 epilepsy centres worldwide. MRI-based maps of individual FCDs with accompanying demographic, clinical and surgical information were collected. We mapped the distribution of FCDs, examined for associations between clinical factors and lesion location, and developed a predictive model of postsurgical seizure freedom.FCDs were non-uniformly distributed, concentrating in the superior frontal sulcus, frontal pole and temporal pole. Epilepsy...
Brain, 2021
Temporal lobe epilepsy, a common drug-resistant epilepsy in adults, is primarily a limbic network... more Temporal lobe epilepsy, a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter structural alterations in temporal lobe epilepsy relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry; or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multisite ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 temporal lobe epilepsy patients and 1418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in temporal lobe epilepsy, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity calculated using 207 healthy controls obtained from Human C...
The Lancet, 2020
Background Patients who have had a stroke with unknown time of onset have been previously exclude... more 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 patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. Findings Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1•49 [95% CI 1•10-2•03]; p=0•011), with low heterogeneity across studies (I²=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1•38 [95% CI 1•05-1•80]; p=0•019), and a higher odds of independent outcome (adjusted OR 1•50 [1•06-2•12]; p=0•022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0•76 [0•52-1•11]; p=0•15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2•06 [1•03-4•09]; p=0•040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5•58 [1•22-25•50]; p=0•024). Interpretation In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death.
Frontiers in Aging Neuroscience, 2020
White matter (WM) microstructure is a sensitive marker to distinguish individuals at risk of Alzh... more White matter (WM) microstructure is a sensitive marker to distinguish individuals at risk of Alzheimer's disease. The association of objective physical fitness (PF) measures and WM microstructure has not been explored and mixed results reported with physical activity (PA). Longitudinal studies of WM with PA and PF measures have had limited investigation. This study explored the relationship between objective PF measures over 24-months with "normal-appearing" WM microstructure. Data acquired on magnetic resonance imaging was used to measure "normal-appearing" WM microstructure at baseline and 24-months. Clinical variables such as cognitive and blood-based measures were collected longitudinally. Also, as part of the randomized controlled trial of a PA, extensive measures of PA and fitness were obtained over the 24 months. Bilateral corticospinal tracts (CST) and the corpus callosum showed a significant association between PF performance over 24-months and baseline WM microstructural measures. There was no significant longitudinal effect of the intervention or PF performance over 24-months. Baseline WM microstructural measures were significantly associated with PF performance over 24-months in this cohort of participants with vascular risk factors and at risk of Alzheimer's disease with distinctive patterns for each PF test.
SUMMARYEpilepsy is increasingly conceptualized as a network disorder. In this cross-sectional meg... more SUMMARYEpilepsy is increasingly conceptualized as a network disorder. In this cross-sectional mega-analysis, we integrated neuroimaging and connectome analysis to identify network associations with atrophy patterns in 1,021 adults with epilepsy compared to 1,564 healthy controls from 19 international sites. In temporal lobe epilepsy, areas of atrophy co-localized with highly interconnected cortical hub regions, whereas idiopathic generalized epilepsy showed preferential subcortical hub involvement. These morphological abnormalities were anchored to the connectivity profiles of distinct disease epicenters, pointing to temporo-limbic cortices in temporal lobe epilepsy and fronto-central cortices in idiopathic generalized epilepsy. Indices of progressive atrophy further revealed a strong influence of connectome architecture on disease progression in temporal lobe, but not idiopathic generalized, epilepsy. Our findings were reproduced across individual sites and single patients, and wer...
Human Brain Mapping, 2020
Epilepsy is a common and serious neurological disorder, with many different constituent condition... more Epilepsy is a common and serious neurological disorder, with many different constituent conditions characterized by their electro clinical, imaging, and genetic features. MRI has been fundamental in advancing our understanding of brain processes in the epilepsies. Smaller‐scale studies have identified many interesting imaging phenomena, with implications both for understanding pathophysiology and improving clinical care. Through the infrastructure and concepts now well‐established by the ENIGMA Consortium, ENIGMA‐Epilepsy was established to strengthen epilepsy neuroscience by greatly increasing sample sizes, leveraging ideas and methods established in other ENIGMA projects, and generating a body of collaborating scientists and clinicians to drive forward robust research. Here we review published, current, and future projects, that include structural MRI, diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI), and that employ advanced methods including structural c...
Journal of Neuroimaging, 2019
ABSTRACTBACKGROUND AND PURPOSEQuantitative susceptibility mapping (QSM) of the brain has become h... more ABSTRACTBACKGROUND AND PURPOSEQuantitative susceptibility mapping (QSM) of the brain has become highly reproducible and has applications in an expanding array of diseases. To translate QSM from bench to bedside, it is important to automate its reconstruction immediately after data acquisition. In this work, a server system that automatically reconstructs QSM and exchange images with the scanner using the DICOM standard is demonstrated using a multi‐site, multi‐vendor reproducibility study and a large, single‐site, multi‐scanner image quality review study in a clinical environment.METHODSA single healthy subject was scanned with a 3D multi‐echo gradient echo sequence at nine sites around the world using scanners from three manufacturers. A high‐resolution (HiRes, .5 × .5 × 1 mm3 reconstructed) and standard‐resolution (StdRes, .5 × .5 × 3 mm3) protocol was performed. ROI analysis of various white matter and gray matter regions was performed to investigate reproducibility across sites....
The two cardinal pathologies of Alzheimer’s disease (AD) develop according to distinct anatomical... more The two cardinal pathologies of Alzheimer’s disease (AD) develop according to distinct anatomical trajectories. Cerebral tau-related pathology first accumulates in the mesial temporal region, while amyloid-related pathology first appears in neocortex. The eventual distributions of these pathologies reflect their anatomical origins. An implication is that the cardinal pathologies might exert preferential effects on the structurofunctional brain changes observed in AD. We investigated this hypothesis in 39 patients with dementia of the Alzheimer’s type. Interrelationships were analysed between cerebrospinal fluid (CSF) biomarkers of the cardinal pathologies, volumetric brain changes using magnetic resonance imaging, and brain metabolism using [18F]-FDG-PET. Amyloid-related pathology was preferentially associated with structurofunctional changes in the precuneus and lateral temporal regions. Tau-related pathology was not associated with changes in these regions. These findings support ...
Annals of Neurology, 2019
This is the author manuscript accepted for publication and has undergone full peer review but has... more This is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as
Journal of Computer Assisted Tomography, 2015
Radiology, 1996
To determine the histopathologic findings of patellar tendinosis ("jumper's knee") demonstrated w... more To determine the histopathologic findings of patellar tendinosis ("jumper's knee") demonstrated with ultrasonography (US) and magnetic resonance (MR) imaging. MATERIALS AND METHODS: Twenty-four athletes (28 knees) with jumper's knee (23 men, one woman; mean age, 30.9 years) scheduled to undergo open tenotomy underwent US patellar tendon examination. 5eventeen patients (19 knees) also underwent MR imaging. Tissue was obtained for histopathologic examination in all 28 cases. Eleven age-, height-, and weight-matched athletes (22 knees) without previous knee symptoms served as control subjects for the US examination. Control material for histopathologic examination was obtained in 20 cadavers (39 knees). Data were analyzed with standard statistical methods. RESULTS: MR imaging and US both revealed an abnormal zone at the proximal patellar tendon attachment. Histopathologic examination revealed mucoid degeneration in all tendons in patients and in 8% (three of 39) of tendons in cadavers (P < .01). CONCLUSION: Jumper's knee is characterized by consistent changes at MR imaging, US, and histopathologic examination and is appropriately described as patellar tendinosis.
The New England journal of medicine, Jan 11, 2015
Background Trials of endovascular therapy for ischemic stroke have produced variable results. We ... more Background Trials of endovascular therapy for ischemic stroke have produced variable results. We conducted this study to test whether more advanced imaging selection, recently developed devices, and earlier intervention improve outcomes. Methods We randomly assigned patients with ischemic stroke who were receiving 0.9 mg of alteplase per kilogram of body weight less than 4.5 hours after the onset of ischemic stroke either to undergo endovascular thrombectomy with the Solitaire FR (Flow Restoration) stent retriever or to continue receiving alteplase alone. All the patients had occlusion of the internal carotid or middle cerebral artery and evidence of salvageable brain tissue and ischemic core of less than 70 ml on computed tomographic (CT) perfusion imaging. The coprimary outcomes were reperfusion at 24 hours and early neurologic improvement (≥8-point reduction on the National Institutes of Health Stroke Scale or a score of 0 or 1 at day 3). Secondary outcomes included the functiona...
Stroke, 2010
Background and Purpose— The Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) was a pros... more Background and Purpose— The Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) was a prospective, randomized, double-blinded, placebo-controlled, phase II trial of alteplase between 3 and 6 hours after stroke onset. The primary outcome of infarct growth attenuation on MRI with alteplase in mismatch patients was negative when mismatch volumes were assessed volumetrically, without coregistration, which underestimates mismatch volumes. We hypothesized that assessing the extent of mismatch by coregistration of perfusion and diffusion MRI maps may more accurately allow the effects of alteplase vs placebo to be evaluated. Methods— Patients were classified as having mismatch if perfusion-weighted imaging divided by coregistered diffusion-weighted imaging volume ratio was >1.2 and total coregistered mismatch volume was ≥10 mL. The primary outcome was a comparison of infarct growth in alteplase vs placebo patients with coregistered mismatch. Results— Of 99 patients with baseline d...
The Lancet, 2019
Background Stroke thrombolysis with alteplase is currently recommended 0-4•5 h after stroke onset... more Background Stroke thrombolysis with alteplase is currently recommended 0-4•5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4•5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis. Methods In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4•5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036. Findings We identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1•86, 95% CI 1•15-2•99, p=0•011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9•7, 95% CI 1•23-76•55, p=0•031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1•55, 0•81-2•96, p=0•66). Interpretation Patients with ischaemic stroke 4•5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis.
Journal of Clinical Neuroscience, 2014
Longitudinal changes in cerebral volume have been described in ischaemic stroke and may correlate... more Longitudinal changes in cerebral volume have been described in ischaemic stroke and may correlate with long-term outcome. We tested the hypothesis that baseline peri-infarct concentration of the neuronal metabolite N-acetylaspartic acid (NAA) correlates with subsequent cerebral volume change after stroke. Patients with supratentorial ischaemic stroke underwent 3 Tesla MRI within 1 week and at 1 and 3 months from onset. Structural imaging involved a T1-weighted axial magnetization prepared rapid gradient echo (1 mm slices, repetition time 1.9 s, echo time 2.82 ms). NAA estimation was performed at baseline using single-voxel spectroscopy (3 × 3 × 3 cm voxels, echo time 30 ms) with the voxel placed in the peri-infarct region determined by visual assessment of the diffusion-weighted image. Quantitative spectroscopic analysis was performed in LCmodel. Cerebral volume change was determined between the 1 and 3 month scans due to the effects of oedema on baseline scans. Grey and white matte...
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Papers by patricia desmond