Publications by authors named "Manus Donahue"

Background And Purpose: Anatomical imaging is a hallmark for visualizing chronic and acute infarcts but provides incomplete information on stroke risk. Respiratory hypercapnic gas challenges show promise for non-invasively assessing hemodynamic function and mapping cerebrovascular reserve capacity, an indicator of how near parenchyma is to exhausting autoregulatory capacity. However, limited safety information exists for this method in high-risk patients with flow-limiting stenosis.

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Magnetic resonance imaging (MRI) sequences commonly used in simultaneous electroencephalogram (EEG)-MRI studies include blood oxygenation level-dependent (BOLD) and anatomical T-weighted MRI. Safety and electrode heating profiles for these sequences have been well-characterized. However, recent improvements in EEG design may allow for additional sequences to be performed with similar expectations of heating safety, which would expand the EEG-MRI infrastructure for quantitative physiological studies.

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Objective: Both direct and indirect surgical revascularization techniques are commonly applied for the treatment of moyamoya disease and syndrome; however, responses can be heterogeneous and efficacy in the context of ischemic disease is not yet formally known from randomized clinical trials. Here, a prospective, longitudinal interventional study was performed to test the hypothesis that presenting 1) parenchymal cerebrovascular reactivity (CVR) and 2) CVR response times portend hemodynamic improvements after direct and indirect revascularization.

Methods: Catheter angiography and hypercapnic blood oxygenation-weighted 3-T MRI (spatial resolution 3.

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Background: Central synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), involve alpha-synuclein accumulation and dopaminergic cell loss in the substantia nigra (SN) and locus coeruleus (LC). Pure autonomic failure (PAF), a peripheral synucleinopathy, often precedes central synucleinopathies.

Objectives: To assess early brain involvement in PAF using neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and fluorodopa-positron emission tomography (FDOPA-PET), and to determine whether PAF patients with a high likelihood ratio (LR) for conversion to a central synucleinopathy exhibit reduced NM-MRI contrast in the LC and SN compared with controls and low-LR patients.

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Moyamoya is a non-atherosclerotic intracranial steno-occlusive condition that places patients at high risk for ischaemic stroke. Randomized trials of surgical revascularization demonstrating efficacy in ischaemic moyamoya have not been performed, and as such, biomarkers of parenchymal haemodynamic impairment are needed to assist with triage and evaluate post-surgical response. In this prospective study, we test the hypothesis that parenchymal cerebrovascular reactivity (CVR) metrics in response to a fixed-inspired 5% carbon dioxide challenge correlate with recent focal ischaemic symptoms.

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Background And Objectives: Sickle cell disease (SCD) is a hemoglobinopathy resulting in hemoglobin-S production, hemolytic anemia, and elevated stroke risk. Treatments include oral hydroxyurea, blood transfusions, and hematopoietic stem cell transplantation (HSCT). Our objective was to evaluate the neurologic relevance of these therapies by characterizing how treatment-induced changes in hemoglobin (Hb) affect brain health biomarkers.

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Patients with sickle cell disease (SCD) are at elevated risk of silent cerebral infarcts and strokes; however, they frequently lack established stroke risk factors (eg, macrovascular arterial steno-occlusion) and the mechanisms underlying such events are incompletely characterized. This study evaluated cerebral hemometabolism with respect to imaging markers of vascular shunting in 143 participants with SCD, including 73 pediatric (aged 6-17 years) and 70 adult (aged 18-40 years) participants using 3-Tesla brain magnetic resonance imaging (MRI). Vascular shunting was assessed in each patient using a previously published ordinal venous hyperintensity score (VHS) of 0, 1, or 2 on cerebral blood flow-weighted MRI.

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Objective: Paramagnetic rim lesions (PRLs) are a biomarker of chronic active lesions (CALs), and an important driver of neurological disability in multiple sclerosis (MS). The reason subtending some acute lesions evolvement into CALs is not known. Here we ask whether a relatively lower oxygen content is linked to CALs.

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Histopathologic studies report higher concentrations of multiple sclerosis white matter lesions in watershed areas of the brain, suggesting that areas with relatively lower oxygen levels may be more vulnerable to disease. However, it is unknown at what point in the disease course lesion predilection for watershed territories begins. Accordingly, we studied a cohort of people with newly diagnosed disease and asked whether (1) white matter lesions disproportionally localize to watershed-regions and (2) the degree of microstructural injury in watershed-lesions is more severe.

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Intravenous arachnoid granulations (AGs) are protrusions of the arachnoid membrane into the venous lumen and function as contributors to the cerebrospinal fluid (CSF) flow circuit. Patients with Parkinson disease (PD) often present with accumulation of alpha synuclein. Previous works have provided evidence for neurofluid circulation dysfunction in neurodegenerative diseases associated with changes in CSF egress, which may have implications regarding AG morphology.

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Sickle cell disease (SCD) is the most common genetic blood disorder, characterized by red cell hemolysis, anemia, and corresponding increased compensatory cerebral blood flow (CBF). SCD patients are at high risk for cerebral infarcts and CBF quantification is likely critical to assess infarct risk. Infarcts primarily localize to white matter (WM), yet arterial spin labeling (ASL) MRI, the most common non-invasive CBF approach, has poor WM CBF sensitivity owing to low WM CBF and long WM bolus arrival time (BAT).

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Background: Parkinson's disease is characterized by dopamine-responsive symptoms as well as aggregation of α-synuclein protofibrils. New diagnostic methods assess α-synuclein aggregation characteristics from cerebrospinal fluid (CSF) and recent pathophysiologic mechanisms suggest that CSF circulation disruptions may precipitate α-synuclein retention. Here, diffusion-weighted MRI with low-to-intermediate diffusion-weightings was applied to test the hypothesis that CSF motion is reduced in Parkinson's disease relative to healthy participants.

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Background And Objectives: Previously we demonstrated that 90% of infarcts in children with sickle cell anemia occur in the border zone regions of cerebral blood flow (CBF). We tested the hypothesis that adults with sickle cell disease (SCD) have silent cerebral infarcts (SCIs) in the border zone regions, with a secondary hypothesis that older age and traditional stroke risk factors would be associated with infarct occurrence in regions outside the border zones.

Methods: Adults with SCD 18-50 years of age were enrolled in a cross-sectional study at 2 centers and completed a 3T brain MRI.

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Background: Moyamoya disease (MMD) is a non-atherosclerotic intracranial steno-occlusive condition placing patients at high risk for ischemic stroke. Direct and indirect surgical revascularization can improve blood flow in MMD; however, randomized trials demonstrating efficacy have not been performed and biomarkers of parenchymal hemodynamic impairment are needed to triage patients for interventions and evaluate post-surgical efficacy. We test the hypothesis that hypercapnia-induced maximum cerebrovascular reactivity (CVR ) and the more novel indicator cerebrovascular reactivity (CVR) response time (CVR ), both assessed from time-regression analyses of non-invasive hypercapnic imaging, correlate with recent focal ischemic symptoms.

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Background: The choroid plexus functions as the blood-cerebrospinal fluid (CSF) barrier, plays an important role in CSF production and circulation, and has gained increased attention in light of the recent elucidation of CSF circulation dysfunction in neurodegenerative conditions. However, methods for routinely quantifying choroid plexus volume are suboptimal and require technical improvements and validation. Here, we propose three deep learning models that can segment the choroid plexus from commonly-acquired anatomical MRI data and report performance metrics and changes across the adult lifespan.

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Background: Peri-sinus structures such as arachnoid granulations (AG) and the parasagittal dural (PSD) space have gained much recent attention as sites of cerebral spinal fluid (CSF) egress and neuroimmune surveillance. Neurofluid circulation dysfunction may manifest as morphological changes in these structures, however, automated quantification of these structures is not possible and rather characterization often requires exogenous contrast agents and manual delineation.

Methods: We propose a deep learning architecture to automatically delineate the peri-sinus space (e.

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Article Synopsis
  • A 79-year-old woman with Alzheimer's participated in a Phase III trial for a drug called lecanemab, but was placed in the placebo group before later receiving the active drug during an extension phase.
  • After her third infusion, she experienced a seizure and MRI scans showed significant brain swelling and increased microhemorrhages.
  • Despite aggressive treatment, she worsened and died 5 days later, with autopsy results revealing severe cerebral amyloid-related inflammation and extensive brain damage linked to factors like the APOE4 gene.
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Background And Purpose: Choroid plexus (ChP) hyperemia has been observed in patients with intracranial vasculopathy and to reduce following successful surgical revascularization. This observation may be attributable to impaired vascular reserve of the ChP or other factors, such as the ChP responding to circulating markers of stress. We extend this work to test the hypothesis that vascular reserve of the ChP is unrelated to intracranial vasculopathy.

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Preliminary evidence from a series of 4 adults with sickle cell disease (SCD) suggests that hematopoietic stem cell transplant (HSCT) improves cerebral hemodynamics. HSCT largely normalizes cerebral hemodynamics in children with SCD. We tested the hypothesis in adults with SCD that cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) measured using magnetic resonance imaging, normalized to healthy values, comparing measurements from ∼1 month before to 12 to 24 months after HSCT (n = 11; age, 33.

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Impulsivity is a behavioral trait that is elevated in many neuropsychiatric disorders. Parkinson's disease (PD) patients can exhibit a specific pattern of reward-seeking impulsive-compulsive behaviors (ICBs), as well as more subtle changes to generalized trait impulsivity. Prior studies in healthy controls (HCs) suggest that trait impulsivity is regulated by D autoreceptors in mesocorticolimbic circuits.

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Article Synopsis
  • A national survey was conducted from 2016 to 2022 to examine the patient experience of women with lipedema, revealing a lack of existing data on this condition.
  • A total of 707 women with lipedema and 216 control participants reported significant symptoms such as leg swelling in heat, easy bruising, and altered gait, often beginning during puberty or pregnancy.
  • Most women with lipedema experienced minimal improvement with diet or exercise; common treatments included compression therapy, gastric bypass, and liposuction, indicating a need for further research on effective therapies.
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Hippocampal hyperactivity is a novel pharmacological target in the treatment of schizophrenia. We hypothesized that levetiracetam (LEV), a drug binding to the synaptic vesicle glycoprotein 2 A, normalizes hippocampal activity in persons with schizophrenia and can be measured using neuroimaging methods. Thirty healthy control participants and 30 patients with schizophrenia (28 treated with antipsychotic drugs), were randomly assigned to a double-blind, cross-over trial to receive a single administration of 500 mg oral LEV or placebo during two study visits.

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Background: The choroid plexus functions as the blood-cerebrospinal fluid barrier, plays an important role in neurofluid production and circulation, and has gained increased attention in light of the recent elucidation of neurofluid circulation dysfunction in neurodegenerative conditions. However, methods for routinely quantifying choroid plexus volume are suboptimal and require technical improvements and validation. Here, we propose three deep learning models that can segment the choroid plexus from commonly-acquired anatomical MRI data and report performance metrics and changes across the adult lifespan.

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Background: Parkinson's disease is characterized by dopamine-responsive symptoms as well as aggregation and accumulation of a-synuclein protofibrils. New diagnostic methods assess a-synuclein aggregation characteristics from cerebrospinal fluid and recent pathophysiologic mechanisms suggest that cerebrospinal fluid circulation disruptions may precipitate a-synuclein retention. Here, we test the hypothesis that cerebrospinal fluid motion at the level of the suprasellar cistern is reduced in Parkinson's disease relative to healthy participants and this reduction relates to choroid plexus perfusion.

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Purpose: Axillary lymph nodes (LNs) often present a reservoir for metastatic breast cancer, yet metastatic LN involvement cannot be discerned definitively using diagnostic imaging. This study investigated whether in vivo CEST may discriminate LNs with versus without metastatic involvement.

Methods: 3T MRI was performed in patients with breast cancer before clinically-indicated mastectomy or lumpectomy with LN removal, after which LN metastasic involvement was determined using histological evaluation.

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