Point-of-Care Bedside Brain Magnetic Resonance Imaging is Safe in Extracorporeal Membrane Oxygenation Patients With Swan Ganz Catheters: A Phantom Experiment and Single Center Experience.

INTRODUCTION: More than 1.2 million pulmonary artery catheters (PACs) are used in cardiac patients per annum within the United States. However, it is contraindicated in traditional 1.5 and 3T magnetic resonance imaging (MRI) scans. We aimed to test preclinical and clinical safety of using this imaging modality given the potential utility of needing it in the clinical setting. METHODS: We conducted two phantom experiments to ensure that the electromagnetic field power deposition associated with bare and jacketed PACs was safe and within the acceptable limit established by the Food and Drug Administration. The primary end points were the safety and feasibility of performing Point-of-Care (POC) MRI without imaging-related adverse events. We performed a preclinical computational electromagnetic simulation and evaluated these findings in nine patients with PACs on veno-arterial extracorporeal membrane oxygenation. RESULTS: The phantom experiments showed that the baseline point specific absorption rate through the head averaged 0.4 W/kg. In both the bare and jacketed catheters, the highest net specific absorption rates were at the neck entry point and tip but were negligible and unlikely to cause any heat-related tissue or catheter damage. In nine patients (median age 66, interquartile range 42-72 y) with veno-arterial extracorporeal membrane oxygenation due to cardiogenic shock and PACs placed for close hemodynamic monitoring, POC MRI was safe and feasible with good diagnostic imaging quality. CONCLUSIONS: Adult ECMO patients with PACs can safely undergo point-of-care low-field (64 mT) brain MRI within a reasonable timeframe in an intensive care unit setting to assess for acute brain injury that might otherwise be missed with conventional head computed tomography.

Brain injury plasma biomarkers in patients on veno-arterial extracorporeal membrane oxygenation: A pilot prospective observational study.

INTRODUCTION: Early diagnosis of acute brain injury (ABI) is critical for patients on veno-arterial extracorporeal membrane oxygenation (V-A ECMO) to guide anticoagulation strategy; however, neurological assessment in ECMO is often limited by patient sedation. METHODS: In this pilot study of adults from June 2018 to May 2019, plasma samples of glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL), and tubulin associated unit (Tau) were collected daily after V-A ECMO cannulation and measured using a multiplex platform. Primary outcomes were occurrence of ABI, assessed clinically, and neurologic outcome, assessed by modified Rankin Scale (mRS). RESULTS: Of 20 consented patients (median age = 48.5°years; 55% female), 8 (40%) had ABI and 15 (75%) had unfavorable neurologic outcome at discharge. 10 (50%) patients were centrally cannulated. Median duration on ECMO was 4.5°days (IQR: 2.5-9.5). Peak GFAP, NFL, and Tau levels were higher in patients with ABI vs. without (AUC = 0.77; 0.85; 0.57, respectively) and in patients with unfavorable vs. favorable neurologic outcomes (AUC = 0.64; 0.59; 0.73, respectively). GFAP elevated first, NFL elevated to the highest degree, and Tau showed limited change regardless of ABI. CONCLUSION: Further studies are warranted to determine how plasma biomarkers may facilitate early detection of ABIs in V-A ECMO to assist timely clinical decision-making.

Detection of Acute Brain Injury in Intensive Care Unit Patients on ECMO Support Using Ultra-Low-Field Portable MRI: A Retrospective Analysis Compared to Head CT.

Early detection of acute brain injury (ABI) is critical to intensive care unit (ICU) patient management and intervention to decrease major complications. Head CT (HCT) is the standard of care for the assessment of ABI in ICU patients; however, it has limited sensitivity compared to MRI. We retrospectively compared the ability of ultra-low-field portable MR (ULF-pMR) and head HCT, acquired within 24 h of each other, to detect ABI in ICU patients supported on extracorporeal membrane oxygenation (ECMO). A total of 17 adult patients (median age 55 years; 47% male) were included in the analysis. Of the 17 patients assessed, ABI was not observed on either ULF-pMR or HCT in eight patients (47%). ABI was observed in the remaining nine patients with a total of 10 events (8 ischemic, 2 hemorrhagic). Of the eight ischemic events, ULF-pMR observed all eight, while HCT only observed four events. Regarding hemorrhagic stroke, ULF-pMR observed only one of them, while HCT observed both. ULF-pMR outperformed HCT for the detection of ABI, especially ischemic injury, and may offer diagnostic advantages for ICU patients. The lack of sensitivity to hemorrhage may improve with modification of the imaging acquisition program.

Clinical Use of Bedside Portable Low-field Brain Magnetic Resonance Imaging in Patients on ECMO: The Results from Multicenter SAFE MRI ECMO Study.

Purpose: Early detection of acute brain injury (ABI) is critical for improving survival for patients with extracorporeal membrane oxygenation (ECMO) support. We aimed to evaluate the safety of ultra-low-field portable MRI (ULF-pMRI) and the frequency and types of ABI observed during ECMO support. Methods: We conducted a multicenter prospective observational study (NCT05469139) at two academic tertiary centers (August 2022-November 2023). Primary outcomes were safety and validation of ULF-pMRI in ECMO, defined as exam completion without adverse events (AEs); secondary outcomes were ABI frequency and type. Results: ULF-pMRI was performed in 50 patients with 34 (68%) on venoarterial (VA)-ECMO (11 central; 23 peripheral) and 16 (32%) with venovenous (VV)-ECMO (9 single lumen; 7 double lumen). All patients were imaged successfully with ULF-pMRI, demonstrating discernible intracranial pathologies with good quality. AEs occurred in 3 (6%) patients (2 minor; 1 serious) without causing significant clinical issues.ABI was observed in ULF-pMRI scans for 22 patients (44%): ischemic stroke (36%), intracranial hemorrhage (6%), and hypoxic-ischemic brain injury (4%). Of 18 patients with both ULF-pMRI and head CT (HCT) within 24 hours, ABI was observed in 9 patients with 10 events: 8 ischemic (8 observed on ULF-oMRI, 4 on HCT) and 2 hemorrhagic (1 observed on ULF-pMRI, 2 on HCT). Conclusions: ULF-pMRI was shown to be safe and valid in ECMO patients across different ECMO cannulation strategies. The incidence of ABI was high, and ULF-pMRI may more sensitive to ischemic ABI than HCT. ULF-pMRI may benefit both clinical care and future studies of ECMO-associated ABI.

Brain Frontal-Lobe Misery Perfusion in COVID-19 ICU Survivors: An MRI Pilot Study.

Post-acute COVID-19 syndrome (PCS) is highly prevalent. Critically ill patients requiring intensive care unit (ICU) admission are at a higher risk of developing PCS. The mechanisms underlying PCS are still under investigation and may involve microvascular damage in the brain. Cerebral misery perfusion, characterized by reduced cerebral blood flow (CBF) and elevated oxygen extraction fraction (OEF) in affected brain areas, has been demonstrated in cerebrovascular diseases such as carotid occlusion and stroke. This pilot study aimed to examine whether COVID-19 ICU survivors exhibited regional misery perfusion, indicating cerebral microvascular damage. In total, 7 COVID-19 ICU survivors (4 female, 20-77 years old) and 19 age- and sex-matched healthy controls (12 female, 22-77 years old) were studied. The average interval between ICU admission and the MRI scan was 118.6 ± 30.3 days. The regional OEF was measured using a recently developed technique, accelerated T2-relaxation-under-phase-contrast MRI, while the regional CBF was assessed using pseudo-continuous arterial spin labeling. COVID-19 ICU survivors exhibited elevated OEF (ß = 5.21 ± 2.48%, p = 0.047) and reduced relative CBF (ß = -0.083 ± 0.025, p = 0.003) in the frontal lobe compared to healthy controls. In conclusion, misery perfusion was observed in the frontal lobe of COVID-19 ICU survivors, suggesting microvascular damage in this critical brain area for high-level cognitive functions that are known to manifest deficits in PCS. Physiological biomarkers such as OEF and CBF may provide new tools to improve the understanding and treatment of PCS.

Long-Term Neuropsychiatric, Neurocognitive, and Functional Outcomes of Patients Receiving ECMO: A Systematic Review and Meta-Analysis

BACKGROUND AND OBJECTIVES: Despite the common occurrence of neurologic complications during extracorporeal membrane oxygenation (ECMO) support, data on long-term neuropsychiatric, neurocognitive, and functional outcomes are sparse. We aimed to determine the prevalence of long-term neuropsychiatric symptoms, neurocognitive and functional impairment, and favorable neurologic outcomes in adult patients who receive ECMO. METHODS: PubMed, Embase, Cochrane, Web of Science, and Scopus were searched for text related to ECMO and neuropsychiatric, neurocognitive, and functional outcomes from inception to May 3, 2023. Our primary outcome was the prevalence of neuropsychiatric symptoms (pain/discomfort, anxiety, depression, posttraumatic stress disorder [PTSD], and sleep disturbance) at long-term (≥6 months) follow-up. Our secondary outcomes were the prevalence of neurocognitive impairment (memory, attention, and reasoning), functional impairment (daily activities, physical activity/mobility, and personal/self-care), and favorable neurologic outcomes (Cerebral Performance Category ≤2, modified Rankin scale ≤3, or Glasgow Outcome Scale ≥4). This study was registered in PROSPERO (CRD42023420565). RESULTS: We included 59 studies with 3,280 patients (median age 54 years, 69% male). The cohort consisted of 86% venoarterial (VA)-ECMO (n = 2,819) and 14% venovenous (VV)-ECMO (n = 461) patients. More than 10 tools were used to assess neuropsychiatric and neurocognitive outcomes, indicating a lack of standardization in assessment methodologies. The overall prevalence of neuropsychiatric symptoms was 41% (95% CI 33%-49%): pain/discomfort (52%, 95% CI 42%-63%), sleep disturbance (37%, 95% CI 0%-98%), anxiety (36%, 95% CI 27%-46%), depression (31%, 95% CI 22%-40%), and PTSD (18%, 95% CI 9%-29%). The prevalence of neurocognitive impairment was 38% (95% CI 13%-65%). The prevalence of functional impairment was 52% (95% CI 40%-64%): daily activities (54%, 95% CI 41%-66%), mobility (41%, 95% CI 28%-54%), and self-care (21%, 95% CI 13%-31%). The prevalence of neuropsychiatric symptoms in VV-ECMO patients was higher than that in VA-ECMO patients (55% [95% CI 34%-75%] vs 32% [95% CI 23%-41%], p = 0.01), though the prevalence of neurocognitive and functional impairment was not different between the groups. The prevalence of favorable neurologic outcomes was not different at various follow-ups: 3 months (23%, 95% CI 12%-36%), 6 months (25%, 95% CI 16%-35%), and ≥1 year (28%, 95% CI 21%-36%, p = 0.68). DISCUSSION: A substantial proportion of ECMO patients seemed to experience neuropsychiatric symptoms and neurocognitive and functional impairments at long-term follow-up. Considerable heterogeneity in methodology for gauging these outcomes exists, warranting the need for standardization. Multicenter prospective observational studies are indicated to further investigate risk factors for these outcomes in ECMO-supported patients.

Blood-brain barrier breakdown in COVID-19 ICU survivors: an MRI pilot study.

Objectives: Coronavirus disease 2019 (COVID-19) results in severe inflammation at the acute stage. Chronic neuroinflammation and abnormal immunological response have been suggested to be the contributors to neuro-long-COVID, but direct evidence has been scarce. This study aims to determine the integrity of the blood-brain barrier (BBB) in COVID-19 intensive care unit (ICU) survivors using a novel MRI technique. Methods: COVID-19 ICU survivors (n=7) and age and sex-matched control participants (n=17) were recruited from June 2021 to March 2023. None of the control participants were hospitalized due to COVID-19 infection. The COVID-19 ICU survivors were studied at 98.6 ± 14.9 days after their discharge from ICU. A non-invasive MRI technique was used to assess the BBB permeability to water molecules, in terms of permeability surface area-product (PS) in the units of mL/100 g/min. Results: PS was significantly higher in COVID-19 ICU survivors (p=0.038) when compared to the controls, with values of 153.1 ± 20.9 mL/100 g/min and 132.5 ± 20.7 mL/100 g/min, respectively. In contrast, there were no significant differences in whole-brain cerebral blood flow (p=0.649) or brain volume (p=0.471) between the groups. Conclusions: There is preliminary evidence of a chronic BBB breakdown in COVID-19 survivors who had a severe acute infection, suggesting a plausible contributor to neurological long-COVID symptoms.

Hypoxic-Ischemic Brain Injury in ECMO: Pathophysiology, Neuromonitoring, and Therapeutic Opportunities.

Extracorporeal membrane oxygenation (ECMO), in conjunction with its life-saving benefits, carries a significant risk of acute brain injury (ABI). Hypoxic-ischemic brain injury (HIBI) is one of the most common types of ABI in ECMO patients. Various risk factors, such as history of hypertension, high day 1 lactate level, low pH, cannulation technique, large peri-cannulation PaCO2 drop (∆PaCO2), and early low pulse pressure, have been associated with the development of HIBI in ECMO patients. The pathogenic mechanisms of HIBI in ECMO are complex and multifactorial, attributing to the underlying pathology requiring initiation of ECMO and the risk of HIBI associated with ECMO itself. HIBI is likely to occur in the peri-cannulation or peri-decannulation time secondary to underlying refractory cardiopulmonary failure before or after ECMO. Current therapeutics target pathological mechanisms, cerebral hypoxia and ischemia, by employing targeted temperature management in the case of extracorporeal cardiopulmonary resuscitation (eCPR), and optimizing cerebral O2 saturations and cerebral perfusion. This review describes the pathophysiology, neuromonitoring, and therapeutic techniques to improve neurological outcomes in ECMO patients in order to prevent and minimize the morbidity of HIBI. Further studies aimed at standardizing the most relevant neuromonitoring techniques, optimizing cerebral perfusion, and minimizing the severity of HIBI once it occurs will improve long-term neurological outcomes in ECMO patients.