Publications

BACKGROUND: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging enables imaging of scar/fibrosis and is a cornerstone of most CMR imaging protocols. CMR imaging can benefit from image acceleration; however, image acceleration in LGE remains challenging due to its limited signal-to-noise ratio. In this study, we sought to evaluate a rapid 2D LGE imaging protocol using a generative artificial intelligence (AI) algorithm with inline reconstruction.

METHODS: A generative AI-based image enhancement was used to improve the sharpness of 2D LGE images acquired with low spatial resolution in the phase-encode direction. The generative AI model is an image enhancement technique built on the enhanced super-resolution generative adversarial network. The model was trained using balanced steady-state free-precession cine images, readily used for LGE without additional training. The model was implemented inline, allowing the reconstruction of images on the scanner console. We prospectively enrolled 100 patients (55 ± 14 years, 72 males) referred for clinical CMR at 3T. We collected three sets of LGE images in each subject, with in-plane spatial resolutions of 1.5×1.5-3-6 mm2. The generative AI model enhanced in-plane resolution to 1.5×1.5 mm2 from the low-resolution counterparts. Images were compared using a blur metric, quantifying the perceived image sharpness (0 = sharpest, 1=blurriest). LGE image sharpness (using a 5-point scale) was assessed by three independent readers.

RESULTS: The scan times for the three imaging sets were 15±3, 9±2, and 6±1seconds, with inline generative AI-based images reconstructed time of  37 ms. The generative-AI-based model improved visual image sharpness, resulting in lower blur metric than low-resolution counterparts (AI-enhanced from 1.5×3 mm2 resolution: 0.3±0.03 vs. 0.35±0.03, P<0.01). Meanwhile, AI-enhanced images from 1.5×3 mm2 resolution and original LGE images showed similar blur metric (0.30±0.03 vs. 0.31±0.03, P=1.0) Additionally, there was an overall 18% improvement in image sharpness between AI-enhanced images from 1.5×3 mm2 resolution and original LGE images in the subjective blurriness score (P<0.01).

CONCLUSIONS: Generative AI-based model enhances the image quality of 2D LGE images while reducing the scan time and preserving imaging sharpness. Further evaluation in a large cohort is needed to assess the clinical utility of AI-enhanced LGE images for scar evaluation, as this proof-of-concept study does not provide evidence of an impact on diagnosis.

BACKGROUND: Prenatal per- and polyfluoroalkyl substance (PFAS) exposures are associated with adverse offspring health outcomes, yet the underlying pathological mechanisms are unclear. Cord blood metabolomics can identify potentially important pathways associated with prenatal PFAS exposures, providing mechanistic insights that may help explain PFAS' long-term health effects.

METHODS: The study included 590 mother-infant dyads from the Boston Birth Cohort. We measured PFAS in maternal plasma samples collected 24-72 h after delivery and metabolites in cord plasma samples. We used metabolome-wide association studies and pathway enrichment analyses to identify metabolites and pathways associated with individual PFAS, and quantile-based g-computation models to examine associations of metabolites with the PFAS mixture. We used False Discovery Rate to account for multiple comparisons.

RESULTS: We found that 331 metabolites and 18 pathways were associated with ≥ 1 PFAS, and 38 metabolites were associated with the PFAS mixture, predominantly amino acids and lipids. Amino acids such as alanine and lysine and their pathways, crucial to energy generation, biosynthesis, and bone health, were associated with PFAS and may explain PFAS' effects on fetal growth restriction. Carnitines and carnitine shuttle pathway, associated with 7 PFAS and the PFAS mixture, are involved in mitochondrial fatty acid β-oxidation, which may predispose higher risks of fetal and child growth restriction and cardiovascular diseases. Lipids, such as glycerophospholipids and their related pathway, can contribute to insulin resistance and diabetes by modulating transporters on cell membranes, participating in β-cell signaling pathways, and inducing oxidative damage. Neurotransmission-related metabolites and pathways associated with PFAS, including cofactors, precursors, and neurotransmitters, may explain the PFAS' effects on child neurodevelopment. We observed stronger associations between prenatal PFAS exposures and metabolites in males.

CONCLUSIONS: This prospective birth cohort study contributes to the limited literature on potential metabolomic perturbations for prenatal PFAS exposures. Future studies are needed to replicate our findings and link prenatal PFAS associated metabolomic perturbations to long-term child health outcomes.

PURPOSE: Hypertension (HTN) is common and represents a major modifiable risk factor for ischemic heart disease in older adults. While home blood pressure monitoring (HBPM) is important in HTN management, patterns of HBPM engagement in older adults undergoing mobile health cardiac rehabilitation (mHealth-CR) are unknown. We aimed to identify patterns of adherence to HBPM in a cohort of older adults undergoing mHealth-CR to optimize HBPM use in the future.

METHODS: We used interim data from the ongoing Rehabilitation using Mobile Health for Older Adults with Ischemic Heart Disease in the Home Setting (RESILIENT) randomized trial, in which intervention arm participants (adults ≥ 65 years with ischemic heart disease) were instructed to monitor blood pressure (BP) at least weekly. Engagement groups were determined by latent class analysis and compared using ANOVA or Chi-Square tests. Longitudinal mixed effect modeling determined the associations between weekly HBPM and baseline covariates including uncontrolled HTN, obesity, diabetes, depression, alcohol, and tobacco use.

RESULTS: Of the 111 participants, the mean age was 71.9 ± 5.6 years, and 83% had HTN. Over the 12-week study, mean HBPM engagement was 2.3 ± 2.3 d/wk. We observed 3 distinct patterns of engagement: high engagement (22%), gradual decline (10%), and sustained baseline engagement (68%). HBPM adherence decreased in two of the engagement groups over time. Of the covariates tested, only depression was associated with weekly HBPM after adjusting for relevant covariates (OR 9.09, P  = .03).

CONCLUSIONS: In this older adult cohort undergoing mHealth-CR, we found three main engagement groups with declining engagement over time in two of the three groups. These patterns can inform future mHealth-CR interventions.

OBJECTIVE: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating illness with symptoms such as post-exertional malaise and cognitive dysfunction that can be challenging for patients to manage independently. Randomized controlled trials (RCTs) have examined mind-body and psychological approaches that teach patients coping skills for mitigating ME/CFS symptoms, including emerging literature on Qigong or Tai Chi instruction programs. This systematic review aims to summarize the characteristics of these trials and highlight potential areas for future optimization and refinement.

METHODS: Ovid MEDLINE, Embase.com, Web of Science Core Collection, Cochrane CENTRAL, PsycINFO via Ovid, and ClinicalTrials.gov were searched in April 2023 using controlled vocabulary and keywords for the following eligibility criteria: Sample (ME/CFS), Design (RCT), Behavioral Intervention (mind-body or psychological interventions). Data extraction and reporting followed Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

RESULTS: "Qigong" and "Tai Chi" yielded 142 and 80 abstracts, respectively. Of the 222 abstracts, full texts were available for 5 RCTs of Qigong (k = 5; N = 481). Notably, no trials of Tai Chi utilized a randomized control design. Among the 5 Qigong RCTs, the publication range was from 2012 to 2023. Details regarding intervention components and effects were summarized. Qigong intervention sessions (median = 12, mode = 10, 12) tended to last between 1-2 hours and occur across 5-12 weeks (median = 7, mode = 5). The Qigong interventions were all delivered in groups and incorporated at-home practice. Daily practice was a requirement (k = 4) or an advisement (k = 1). Patient-reported outcomes suggest an emerging evidence base for diffuse benefits on physical and emotional health outcomes.

CONCLUSIONS: Qigong interventions are promising, yet relatively understudied, in improving ME/CFS symptom severity and frequency. Future trials must implement standardized eligibility criteria for ME/CFS history, integrate Qigong or Tai Chi with other empirically supported mind-body and psychological practices, and assess long-term resiliency outcomes relevant to ME/CFS survivorship.

INTRODUCTION: Fear of cancer recurrence (FCR) is prevalent and distressing among survivors of cancer. Evidence-based mind-body and cognitive-behavioral skills lack integration and testing in scalable formats.

OBJECTIVE: This pilot randomized controlled trial (NCT04876599) tested a synchronous, virtual mind-body group resiliency intervention for FCR (IN FOCUS).

METHOD: Adults with elevated FCR (FCR Inventory severity ≥ 16; 16-21 = elevated, 22-36 = clinically elevated) after completing primary treatment for non-metastatic cancer were randomly assigned (1:1) to eight weekly sessions of IN FOCUS or usual care (UC; synchronous, virtual community group support referral). Feasibility metrics included ≥ 70% retention per arm (primary outcome), ≥ 75% attendance in ≥ 6 sessions, ≥ 75% adherence to relaxation skills practice ≥ 3 days per week and by delivery fidelity (% content covered in video-recorded sessions). Acceptability was assessed quantitatively via ratings of enjoyableness, convenience, helpfulness, odds of future use, and satisfaction (benchmark ≥ 80% of ratings ≥ 4 on 1-5 Likert scale) and qualitatively via individual exit interviews. Linear mixed models explicated slopes in FCR (secondary) and resiliency (exploratory; Current Experiences Scale) from baseline to 2 months (primary endpoint) and 5 months using intention-to-treat.

RESULTS: From July 2021 to March 2022, 64 survivors enrolled (25-73 years old, M = 7 years since diagnosis). IN FOCUS was feasible and acceptable (91% retention; attendance median = 7 sessions, 97% relaxation practice adherence, 95% content fully covered; 82% of acceptability ratings ≥ 4). Interviews (n = 59) revealed benefits in both arms. By 2 months, compared to UC, IN FOCUS reduced FCR to a medium-to-large effect (Mdiff = -2.4; 95% CI = -4.2, -0.7; d = 0.66). By 5 months, FCR effects had attenuated (Mdiff = -0.16, 95% CI -1.97, 1.65; d = -0.04), although levels of resiliency had increased with a medium-to-large effect (Mdiff = 10.0; 95% CI = 4.9, 15.1; d = 0.78).

CONCLUSIONS: For survivors of non-metastatic cancer, a synchronous, virtual mind-body resiliency program for FCR is feasible, acceptable, and seemingly beneficial compared to a community group referral.

BACKGROUND: Although the pathogenesis of delirium is poorly understood, increasing evidence supports a role for inflammation. Previously, individual inflammatory biomarkers have been associated with delirium. Aggregating biomarkers into an index may provide more information than individual biomarkers in predicting certain health outcomes (e.g., mortality); however, inflammatory indices have not yet been examined in delirium.

METHODS: Four inflammatory markers, C-reactive protein, Interleukin-6, Soluble Tumor Necrosis Factor Alpha Receptor-1, and Chitinase-3 Like Protein-1 (CHI3L1), were measured preoperatively (PREOP) and on postoperative day 2 (POD2) in 548 adults aged 70+ undergoing major noncardiac surgery (mean age 76.7 [standard deviation 5.2], 58% female, 24% delirium). From these markers, four inflammatory indices were considered: 1) quartile summary score, 2) weighted summary score (WSS), 3) principal component score, 4) a well-established inflammatory (LASSO-derived) index associated with mortality. Delirium was assessed using the Confusion Assessment Method (CAM), supplemented by chart review. Generalized linear models (GLM) with a log-link term were used to determine the association between each inflammatory index and delirium incidence.

RESULTS: Among the inflammatory indices, WSS demonstrated the strongest association with delirium: participants in WSS quartile (Q)4 had a higher risk of delirium vs. participants in Q1, after clinical variable adjustment (relative risk [RR], 95% confidence interval [CI] for PREOP: 3.07, 1.80-5.22; and POD2: 2.65, 1.63-4.30). WSS was more strongly associated with delirium than the strongest associated individual inflammatory marker (PREOP CHI3L1 [RR 2.45, 95% CI 1.53-3.92]; POD2 interleukin-6 [RR 2.39, 95% CI 1.50-3.82]).

CONCLUSIONS: A multi-protein inflammatory index using WSS provides a slight advantage over individual inflammatory markers in their association with delirium.

BACKGROUND: Delirium commonly occurs in older adults following surgery; although its pathophysiology is not fully understood, underlying neurodegeneration is a risk factor.

OBJECTIVE: Examine the association of preoperative levels of markers of neuronal damage, neurofilament light (NfL) and phosphorylated tau (p-tau)181, with postoperative delirium.

METHODS: Preoperative CSF and plasma were obtained from 158 patients undergoing hip fracture repair and enrolled in the clinical trial "A STrategy to Reduce the Incidence of Postoperative Delirium in Elderly Patients" (STRIDE). Delirium diagnosis was adjudicated by a consensus panel. The association of plasma and CSF NfL and p-tau181 levels with delirium incidence and severity were examined for the overall cohort and for the subgroup (n=134) of patients without dementia.

RESULTS: Patients who developed delirium were older, had lower Mini-Mental State Exam (MMSE) score, higher Clinical Dementia Rating (CDR) and Geriatric Depression Scale (GDS) scores at baseline; the overall incidence of delirium was 37.6% and 31.1% for the subgroup without dementia. Plasma and CSF p-tau181 levels were not associated with delirium incidence or severity. CSF NfL levels were significantly associated with delirium severity, but not with incidence in the overall cohort. In the subgroup of patients without dementia, CSF NfL levels were significantly associated with increased odds of delirium incidence (OR 4.74, 95% CI 1.21-18.59, p=0.03) adjusted for age, sex, and CDR.

CONCLUSIONS: CSF NfL was significantly associated with delirium incidence and severity in patients without dementia undergoing hip fracture repair. Results confirm prior studies suggesting NfL as an important marker of delirium risk and supports an association between pre-existing axonal injury and delirium. These results highlight delirium vulnerability in older hip fracture patients, even when clinical dementia is not identified.

BACKGROUND: Concussions are common, particularly among young adults, and often are associated with persistent, debilitating, and hard-to-treat symptoms. Anxiety and concussion symptoms often amplify each other, and growing evidence indicates that anxiety plays a key role in symptoms persistence after concussion. Targeting anxiety early after concussion may be a promising means of helping prevent persistent concussion symptoms in this population. We developed the Toolkit for Optimal Recovery after Concussion (TOR-C), the first mind-body program tailored for young adults with a recent concussion and anxiety, aiming to prevent persistent concussion symptoms.

OBJECTIVE: This study aims to conduct an open pilot of TOR-C to test preliminary feasibility, signal of change in measures, and treatment perceptions.

METHODS: Five young adults (aged 18-24 years) attended 4 weekly one-on-one live video sessions with a clinician. Participants completed questionnaires measuring treatment targets (ie, pain catastrophizing, mindfulness, fear avoidance, limiting behaviors, and all-or-nothing behaviors) and outcomes (ie, postconcussive symptoms, physical function, anxiety, depression, and pain) at baseline, immediately following the intervention, and 3 months after intervention completion. At the conclusion of the program, participants attended a qualitative interview and provided feedback about the program to help optimize study content and procedures.

RESULTS: Feasibility markers were excellent for credibility and expectancy (5/5, 100% of participants scored above the credibility and expectancy scale midpoint), client satisfaction (4/5, 80% of participants scored above the Client Satisfaction Questionnaire midpoint), therapist adherence (97% adherence), acceptability of treatment (5/5, 100% of participants attended 3 or more sessions), adherence to homework (87% home practice completion), and feasibility of assessments (no measures fully missing). The feasibility of recruitment was good (5/7, 71% of eligible participants agreed to participate). There were preliminary signals of improvements from pre-post comparisons in treatment targets (d=0.72-2.20) and outcomes (d=0.41-1.38), which were sustained after 3 months (d=0.38-2.74 and d=0.71-1.63 respectively). Exit interviews indicated overall positive perceptions of skills and highlighted barriers (eg, busyness) and facilitators (eg, accountability) to engagement.

CONCLUSIONS: TOR-C shows preliminary feasibility, is associated with a signal of improvement in treatment targets and outcomes, and has the potential to support recovery from concussion. The quantitative findings along with the qualitative feedback obtained from the exit interviews will help optimize TOR-C in preparation for an upcoming randomized controlled trial of TOR-C versus an active control condition of health education for concussion recovery.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/25746.

BACKGROUND: Evidence is lacking on the relative contributions of specific lifestyle factors and their overall contribution to prevention of hypertension, in particular early-onset hypertension.

METHODS: This prospective cohort study included participants of the Nurses' Health Study (NHS, N = 52,780 women, aged 40-67 in 1986), the NHS II (N = 83,871 women, aged 27-46 in 1991), and the Health Professionals Follow-up Study (HPFS, N = 31,269 men, aged 40-75 in 1986), who were free from hypertension, cardiovascular disease and cancer at baseline. Four modifiable lifestyles were evaluated based on hypertension guidelines: BMI, moderate-to-vigorous physical activity, Dietary Approaches to Stop Hypertension (DASH) score, and alcohol intake. Primary outcome was incident self-reported diagnosis of hypertension with 27-31 years of follow-up.

RESULTS: Each lifestyle factor was associated with incident hypertension in dose-dependent manners across the cohorts, with BMI having the strongest associations. On average, adhering to BMI <25 kg/m2 was associated with 20.3 [18.5, 22.0], 25.0 [23.2, 26.8], and 18.6 [16.7, 20.7] months longer periods free from hypertension during 25-year follow-up in each cohort respectively. BMI accounted for approximately 20 % of incident hypertension in NHS and HPFS, and 35 % of early-onset hypertension (age < 55 y). Moderate-to-vigorous physical activity and diet accounted for 10-15 % of incident hypertension in women, and the contributions were greater for early-onset hypertension.

CONCLUSION: Healthy weight during adulthood was most substantially associated with incident hypertension among lifestyle factors, but diet, physical activity, and alcohol intake were also related to the risk across all ages, and hypertension-free periods, with stronger associations in early-onset hypertension.