Computationally Efficient IMplicit Training Strategy for UNrolled NEtworks (IMUNNE): A preliminary analysis using accelerated real-time cardiac cine MRI.

OBJECTIVE: Highly-undersampled, dynamic MRI reconstruction, particularly in multi-coil scenarios, is a challenging inverse problem. Unrolled networks achieve state-of-the-art performance in MRI reconstruction but suffer from long training times and extensive GPU memory cost. METHODS: In this work, we propose a novel training strategy for IMplicit UNrolled NEtworks (IMUNNE) for highly-undersampled, multi-coil dynamic MRI reconstruction. It formulates the MRI reconstruction problem as an implicit fixed-point equation and leverages gradient approximation for backpropagation, enabling training of deep architectures with fixed memory cost. This study represents the first application of implicit network theory in the context of real-time cine MRI. The proposed method is evaluated using a prospectively undersampled, real-time cine dataset using radial k-space sampling, comprising balanced steady-state free precession (b-SSFP) readouts. Experiments include a hyperparameter search, head-to-head comparisons with a complex U-Net (CU-Net) and an alternating unrolled network (Alt-UN), and an analysis of robustness under noise perturbations; peak signal-to-noise ratio, structural similarity index, normalized root mean-square error, spatio-temporal entropic difference, and a blur metric were used. RESULTS: IMUNNE produced significantly and slightly better image quality compared to CU-Net and Alt-UN, respectively. Compared with Alt-UN, IMUNNE significantly reduced training and inference times, making it a promising approach for highly-accelerated, multi-coil real-time cine MRI reconstruction. CONCLUSION: IMUNNE strategy successfully applies unrolled networks to image reconstruction of highly-accelerated, real-time radial cine MRI. SIGNIFICANCE: Implicit training enables rapid, high-quality, and cost-effective CMR exams by reducing training and inference times and lowering memory cost associated with advanced reconstruction methods.

Identification of retinal oligomeric, citrullinated, and other tau isoforms in early and advanced AD and relations to disease status.

This study investigates various pathological tau isoforms in the retina of individuals with early and advanced Alzheimer's disease (AD), exploring their connection with disease status. Retinal cross-sections from predefined superior-temporal and inferior-temporal subregions and corresponding brains from neuropathologically confirmed AD patients with a clinical diagnosis of either mild cognitive impairment (MCI) or dementia (n = 45) were compared with retinas from age- and sex-matched individuals with normal cognition (n = 30) and non-AD dementia (n = 4). Retinal tau isoforms, including tau tangles, paired helical filament of tau (PHF-tau), oligomeric-tau (Oligo-tau), hyperphosphorylated-tau (p-tau), and citrullinated-tau (Cit-tau), were stereologically analyzed by immunohistochemistry and Nanostring GeoMx digital spatial profiling, and correlated with clinical and neuropathological outcomes. Our data indicated significant increases in various AD-related pretangle tau isoforms, especially p-tau (AT8, 2.9-fold, pS396-tau, 2.6-fold), Cit-tau at arginine residue 209 (CitR209-tau; 4.1-fold), and Oligo-tau (T22+, 9.2-fold), as well as pretangle and mature tau tangle forms like MC-1-positive (1.8-fold) and PHF-tau (2.3-fold), in AD compared to control retinas. MCI retinas also exhibited substantial increases in Oligo-tau (5.2-fold), CitR209-tau (3.5-fold), and pS396-tau (2.2-fold). Nanostring GeoMx analysis confirmed elevated retinal p-tau at epitopes: Ser214 (2.3-fold), Ser396 (2.6-fold), Ser404 (2.4-fold), and Thr231 (1.8-fold), particularly in MCI patients. Strong associations were found between retinal tau isoforms versus brain pathology and cognitive status: a) retinal Oligo-tau vs. Braak stage, neurofibrillary tangles (NFTs), and CDR cognitive scores (ρ = 0.63-0.71), b) retinal PHF-tau vs. neuropil threads (NTs) and ABC scores (ρ = 0.69-0.71), and c) retinal pS396-tau vs. NTs, NFTs, and ABC scores (ρ = 0.67-0.74). Notably, retinal Oligo-tau strongly correlated with retinal Aß42 and arterial Aß40 forms (r = 0.76-0.86). Overall, this study identifies and quantifies diverse retinal tau isoforms in MCI and AD patients, underscoring their link to brain pathology and cognition. These findings advocate for further exploration of retinal tauopathy biomarkers to facilitate AD detection and monitoring via noninvasive retinal imaging.

In Vivo Mapping of Myocardial Injury Outside the Infarct Zone: Tissue at an Intermediate Pathological State.

BACKGROUND: The goal was to determine the feasibility of mapping the injured-but-not-infarcted myocardium using 99mTc-duramycin in the postischemic heart, with spatial information for its characterization as a pathophysiologically intermediate tissue, which is neither normal nor infarcted. METHODS AND RESULTS: Coronary occlusion was conducted in Sprague Dawley rats with preconditioning and 30-minute ligation. In vivo single-photon emission computed tomography was acquired after 3 hours (n=6) using 99mTc-duramycin, a phosphatidylethanolamine-specific radiopharmaceutical. The 99mTc-duramycin+ areas were compared with infarct and area-at-risk (n=8). Cardiomyocytes and endothelial cells were isolated for gene expression profiling. Cardiac function was measured with echocardiography (n=6) at 4 weeks. In vivo imaging with 99mTc-duramycin identified the infarct (3.9±2.4% of the left ventricle and an extensive area 23.7±2.2% of the left ventricle) with diffuse signal outside the infarct, which is pathologically between normal and infarcted (apoptosis 1.8±1.6, 8.9±4.2, 13.6±3.8%; VCAM-1 [vascular cell adhesion molecule 1] 3.2±0.8, 9.8±4.1, 15.9±4.2/mm2; tyrosine hydroxylase 14.9±2.8, 8.6±4.4, 5.6±2.2/mm2), with heterogeneous changes including scattered micronecrosis, wavy myofibrils, hydropic change, and glycogen accumulation. The 99mTc-duramycin+ tissue is quantitatively smaller than the area-at-risk (26.7% versus 34.4% of the left ventricle, P=0.008). Compared with infarct, gene expression in the 99mTc-duramycin+-noninfarct tissue indicated a greater prosurvival ratio (BCL2/BAX [B-cell lymphoma 2/BCL2-associated X] 7.8 versus 5.7 [cardiomyocytes], 3.7 versus 3.2 [endothelial]), and an upregulation of ion channels in electrophysiology. There was decreased contractility at 4 weeks (regional fractional shortening -8.6%, P<0.05; circumferential strain -52.9%, P<0.05). CONCLUSIONS: The injured-but-not-infarcted tissue, being an intermediate zone between normal and infarct, is mapped in vivo using phosphatidylethanolamine-based imaging. The intermediate zone contributes significantly to cardiac dysfunction.

Gender differences in diet quality and the association between diet quality and BMI: an analysis in young Australian adults who completed the Healthy Eating Quiz.

BACKGROUND: Many young adults report poor diet quality. However, research evaluating whether young adult males and females differ in diet quality is limited. Additionally, although diet quality has a known inverse association with body mass index (BMI), it is unclear whether this association is observed in young adults and whether it varies by gender. The present study aimed to evaluate gender differences in diet quality in young adults, as well as the associations between diet quality and BMI. METHODS: Data collected via the Healthy Eating Quiz (HEQ) in respondents aged 18-35 years between July 2019 and December 2021 were analysed, including demographics, and diet quality calculated using the Australian Recommended Food Score (ARFS). Differences in characteristics were analysed using a two-sample t-test, chi-squared and one-way analysis of covariance. Linear regressions were performed to estimate associations between diet quality and BMI. An interaction term was included in the model to test differences between genders. RESULTS: The respondents (n = 28,969) were predominantly female (70.8%) with a mean ± SD age of 25.9 ± 5.0 years and BMI of 24.6 ± 5.2 kg/m2. The mean ± SD ARFS was significantly different between females and males (33.1 ± 8.6 vs. 31.4 ± 9.3 points out of 70; p < 0.001). Diet quality had a small, significant inverse association with BMI in both genders. The interaction effect between diet quality score and gender in predicting BMI was significant (p < 0.001), suggesting the impact of diet quality on BMI varies by gender, with lower diet quality more strongly associated with higher BMI in females compared to males. CONCLUSION: Interventions that target young adults are needed to improve diet quality and its potential contribution to BMI status. As a result of the small observed effect sizes, caution should be applied in interpreting these findings.

Identification of retinal tau oligomers, citrullinated tau, and other tau isoforms in early and advanced AD and relations to disease status.

Importance: This study identifies and quantifies diverse pathological tau isoforms in the retina of both early and advanced-stage Alzheimer's disease (AD) and determines their relationship with disease status. Objective: A case-control study was conducted to investigate the accumulation of retinal neurofibrillary tangles (NFTs), paired helical filament (PHF)-tau, oligomeric tau (oligo-tau), hyperphosphorylated tau (p-tau), and citrullinated tau (Cit-tau) in relation to the respective brain pathology and cognitive dysfunction in mild cognitively impaired (MCI) and AD dementia patients versus normal cognition (NC) controls. Design setting and participants: Eyes and brains from donors diagnosed with AD, MCI (due to AD), and NC were collected (n=75 in total), along with clinical and neuropathological data. Brain and retinal cross-sections-in predefined superior-temporal and inferior-temporal (ST/IT) subregions-were subjected to histopathology analysis or Nanostring GeoMx digital spatial profiling. Main outcomes and measure: Retinal burden of NFTs (pretangles and mature tangles), PHF-tau, p-tau, oligo-tau, and Cit-tau was assessed in MCI and AD versus NC retinas. Pairwise correlations revealed associations between retinal and brain parameters and cognitive status. Results: Increased retinal NFTs (1.8-fold, p=0.0494), PHF-tau (2.3-fold, p<0.0001), oligo-tau (9.1-fold, p<0.0001), CitR 209 -tau (4.3-fold, p<0.0001), pSer202/Thr205-tau (AT8; 4.1-fold, p<0.0001), and pSer396-tau (2.8-fold, p=0.0015) were detected in AD patients. Retinas from MCI patients showed significant increases in NFTs (2.0-fold, p=0.0444), CitR 209 -tau (3.5-fold, p=0.0201), pSer396-tau (2.6-fold, p=0.0409), and, moreover, oligo-tau (5.8-fold, p=0.0045). Nanostring GeoMx quantification demonstrated upregulated retinal p-tau levels in MCI patients at phosphorylation sites of Ser214 (2.3-fold, p=0.0060), Ser396 (1.8-fold, p=0.0052), Ser404 (2.4-fold, p=0.0018), and Thr231 (3.3-fold, p=0.0028). Strong correlations were found between retinal tau forms to paired-brain pathology and cognitive status: a) retinal oligo-tau vs. Braak stage (r=0.60, P=0.0002), b) retinal PHF-tau vs. ABC average score (r=0.64, P=0.0043), c) retinal pSer396-tau vs. brain NFTs (r=0.68, P<0.0001), and d) retinal pSer202/Thr205-tau vs. MMSE scores (r= -0.77, P=0.0089). Conclusions and Relevance: This study reveals increases in immature and mature retinal tau isoforms in MCI and AD patients, highlighting their relationship with brain pathology and cognition. The data provide strong incentive to further explore retinal tauopathy markers that may be useful for early detection and monitoring of AD staging through noninvasive retinal imaging.

Ultra-rapid, Free-breathing, Real-time Cardiac Cine MRI Using GRASP Amplified with View Sharing and KWIC Filtering.

Purpose To achieve ultra-high temporal resolution (approximately 20 msec) in free-breathing, real-time cardiac cine MRI using golden-angle radial sparse parallel (GRASP) reconstruction amplified with view sharing (VS) and k-space-weighted image contrast (KWIC) filtering. Materials and Methods Fourteen pediatric patients with congenital heart disease (mean age [SD], 9 years ± 2; 13 male) and 10 adult patients with arrhythmia (mean age, 62 years ± 8; nine male) who underwent both standard breath-hold cine and free-breathing real-time cine using GRASP were retrospectively identified. To achieve high temporal resolution, each time frame was reconstructed using six radial spokes, corresponding to acceleration factors ranging from 24 to 32. To compensate for loss in spatial resolution resulting from over-regularization in GRASP, VS and KWIC filtering were incorporated. The blur metric, visual image quality scores, and biventricular parameters were compared between clinical and real-time cine images. Results In pediatric patients, the incorporation of VS and KWIC into GRASP (ie, GRASP + VS + KWIC) produced significantly (P < .05) sharper x-y-t (blur metric: 0.36 ± 0.03, 0.41 ± 0.03, 0.48 ± 0.03, respectively) and x-y-f (blur metric: 0.28 ± 0.02, 0.31 ± 0.03, 0.37 ± 0.03, respectively) component images compared with GRASP + VS and conventional GRASP. Only the noise score differed significantly between GRASP + VS + KWIC and clinical cine; all visual scores were above the clinically acceptable (3.0) cutoff point. Biventricular volumetric parameters strongly correlated (R2 > 0.85) between clinical and real-time cine images reconstructed with GRASP + VS + KWIC and were in good agreement (relative error < 6% for all parameters). In adult patients, the visual scores of all categories were significantly lower (P < .05) for clinical cine compared with real-time cine with GRASP + VS + KWIC, except for noise (P = .08). Conclusion Incorporating VS and KWIC filtering into GRASP reconstruction enables ultra-high temporal resolution (approximately 20 msec) without significant loss in spatial resolution. Keywords: Cine, View Sharing, k-Space-weighted Image Contrast Filtering, Radial k-Space, Pediatrics, Arrhythmia, GRASP, Compressed Sensing, Real-Time, Free-Breathing Supplemental material is available for this article. © RSNA, 2024.

SCMR expert consensus statement for cardiovascular magnetic resonance of patients with a cardiac implantable electronic device.

Cardiovascular magnetic resonance (CMR) is a proven imaging modality for informing diagnosis and prognosis, guiding therapeutic decisions, and risk stratifying surgical intervention. Patients with a cardiac implantable electronic device (CIED) would be expected to derive particular benefit from CMR given high prevalence of cardiomyopathy and arrhythmia. While several guidelines have been published over the last 16 years, it is important to recognize that both the CIED and CMR technologies, as well as our knowledge in MR safety, have evolved rapidly during that period. Given increasing utilization of CIED over the past decades, there is an unmet need to establish a consensus statement that integrates latest evidence concerning MR safety and CIED and CMR technologies. While experienced centers currently perform CMR in CIED patients, broad availability of CMR in this population is lacking, partially due to limited availability of resources for programming devices and appropriate monitoring, but also related to knowledge gaps regarding the risk-benefit ratio of CMR in this growing population. To address the knowledge gaps, this SCMR Expert Consensus Statement integrates consensus guidelines, primary data, and opinions from experts across disparate fields towards the shared goal of informing evidenced-based decision-making regarding the risk-benefit ratio of CMR for patients with CIEDs.

Incorporation of view sharing and KWIC filtering into GRASP-Pro improves spatial resolution of single-shot, multi-TI, late gadolinium enhancement MRI.

While single-shot late gadolinium enhancement (LGE) is useful for imaging patients with arrhythmia and/or dyspnea, it produces low spatial resolution. One approach to improve spatial resolution is to accelerate data acquisition using compressed sensing (CS). Our previous work described a single-shot, multi-inversion time (TI) LGE pulse sequence using radial k-space sampling and CS, but over-regularization resulted in significant image blurring that muted the benefits of data acceleration. The purpose of the present study was to improve the spatial resolution of the single-shot, multi-TI LGE pulse sequence by incorporating view sharing (VS) and k-space weighted contrast (KWIC) filtering into a GRASP-Pro reconstruction. In 24 patients (mean age = 61 ± 16 years; 9/15 females/males), we compared the performance of our improved multi-TI LGE and standard multi-TI LGE, where clinical standard LGE was used as a reference. Two clinical raters independently graded multi-TI images and clinical LGE images visually on a five-point Likert scale (1, nondiagnostic; 3, clinically acceptable; 5, best) for three categories: the conspicuity of myocardium or scar, artifact, and noise. The summed visual score (SVS) was defined as the sum of the three scores. Myocardial scar volume was quantified using the full-width at half-maximum method. The SVS was not significantly different between clinical breath-holding LGE (median 13.5, IQR 1.3) and multi-TI LGE (median 12.5, IQR 1.6) (P = 0.068). The myocardial scar volumes measured from clinical standard LGE and multi-TI LGE were strongly correlated (coefficient of determination, R2 = 0.99) and in good agreement (mean difference = 0.11%, lower limit of the agreement = -2.13%, upper limit of the agreement = 2.34%). The inter-rater agreement in myocardial scar volume quantification was strong (intraclass correlation coefficient = 0.79). The incorporation of VS and KWIC into GRASP-Pro improved spatial resolution. Our improved 25-fold accelerated, single-shot LGE sequence produces clinically acceptable image quality, multi-TI reconstruction, and accurate myocardial scar volume quantification.

Use of Atrial Fibrillation Electrograms and T1/T2 Magnetic Resonance Imaging to Define the Progressive Nature of Molecular and Structural Remodeling: A New Paradigm Underlying the Emergence of Persistent Atrial Fibrillation.

BACKGROUND: The temporal progression states of the molecular and structural substrate in atrial fibrillation (AF) are not well understood. We hypothesized that these can be detected by AF electrograms and magnetic resonance imaging parametric mapping. METHODS AND RESULTS: AF was induced in 43 dogs (25-35 kg, ≥1 year) by rapid atrial pacing (RAP) (3-33 weeks, 600 beats/min), and 4 controls were used. We performed high-resolution epicardial mapping (UnEmap, 6 atrial regions, both atria, 130 electrodes, distance 2.5 mm) and analyzed electrogram cycle length, dominant frequency, organization index, and peak-to-peak bipolar voltage. Implantable telemetry recordings were used to quantify parasympathetic nerve activity over RAP time. Magnetic resonance imaging native T1, postcontrast T1, T2 mapping, and extracellular volume fraction were assessed (1.5T, Siemens) at baseline and AF. In explanted atrial tissue, DNA oxidative damage (8-hydroxy-2'-deoxyguanosine staining) and percentage of fibrofatty tissue were quantified. Cycle length and organization index decreased (R=0.5, P<0.05; and R=0.5, P<0.05; respectively), and dominant frequency increased (R=0.3, P n.s.) until 80 days of RAP but not thereafter. In contrast, voltage continued to decrease throughout the duration of RAP (R=0.6, P<0.05). Parasympathetic nerve activity increased following RAP and plateaued at 80 days. Magnetic resonance imaging native T1 and T2 times increased with RAP days (R=0.5, P<0.05; R=0.6, P<0.05) in the posterior left atrium throughout RAP. Increased RAP days correlated with increasing 8-hydroxy-2'-deoxyguanosine levels and with fibrosis percentage (R=0.5, P<0.05 for both). CONCLUSIONS: A combination of AF electrogram characteristics and T1/T2 magnetic resonance imaging can detect early-stage AF remodeling (autonomic remodeling, oxidative stress) and advanced AF remodeling due to oxidative stress and fibrosis.

A bibliographic review of sustainability research output and investment in 10 leading public health journals across three time periods.

Objectives: Long-term delivery, or sustainability, of evidence-based interventions is necessary for public health benefits to be realised. However, sustainment of effective interventions is poor. Understanding the evidence-base and identifying potential gaps is necessary to inform where future research efforts are most warranted. Study design: We undertook a repeat cross-sectional bibliographic review of research published in 10 public health journals across three time periods (2010, 2015 and 2020/2021). Methods: Studies were eligible if they were a data-based study or review article. Studies were assessed as to whether they focused on sustainability. The percentage of public health research studies assessing sustainability overall and by the three time periods was calculated. The association between time period and the proportion of sustainability articles was assessed using logistic regression. Descriptive statistics were used to summarise study characteristics overall and by time period. Results: 10,588 data-based articles were identified, of which 1.3 % (n = 136) focused on sustainability. There was a statistically significant association between time period and the proportion of sustainability research, with a slight increase across the three time periods: 0.3 % (95 % CI: 0.1 %, 0.7 %) in 2010, 1.4 % (95 % CI: 1.0 %, 1.9 %) in 2015 and 1.6 % (95 % CI: 1.3 %, 1.9 %) in 2020/2021. Most research was descriptive/epidemiological (n = 69, 51 %), few focused on measurement (n = 2, 1.5 %) and none on cost effectiveness. Only one intervention study assessed the effect of specific sustainability strategies. Conclusions: This bibliographic review highlights the need for more public health research on sustainability, particularly in the areas of measurement, sustainability interventions, and cost effectiveness.

Deep learning-enabled analysis of medical images identifies cardiac sphericity as an early marker of cardiomyopathy and related outcomes.

BACKGROUND: Quantification of chamber size and systolic function is a fundamental component of cardiac imaging. However, the human heart is a complex structure with significant uncharacterized phenotypic variation beyond traditional metrics of size and function. Examining variation in cardiac shape can add to our ability to understand cardiovascular risk and pathophysiology. METHODS: We measured the left ventricle (LV) sphericity index (short axis length/long axis length) using deep learning-enabled image segmentation of cardiac magnetic resonance imaging data from the UK Biobank. Subjects with abnormal LV size or systolic function were excluded. The relationship between LV sphericity and cardiomyopathy was assessed using Cox analyses, genome-wide association studies, and two-sample Mendelian randomization. FINDINGS: In a cohort of 38,897 subjects, we show that a one standard deviation increase in sphericity index is associated with a 47% increased incidence of cardiomyopathy (hazard ratio [HR]: 1.47, 95% confidence interval [CI]: 1.10-1.98, p = 0.01) and a 20% increased incidence of atrial fibrillation (HR: 1.20, 95% CI: 1.11-1.28, p < 0.001), independent of clinical factors and traditional magnetic resonance imaging (MRI) measurements. We identify four loci associated with sphericity at genome-wide significance, and Mendelian randomization supports non-ischemic cardiomyopathy as causal for LV sphericity. CONCLUSIONS: Variation in LV sphericity in otherwise normal hearts predicts risk for cardiomyopathy and related outcomes and is caused by non-ischemic cardiomyopathy. FUNDING: This study was supported by grants K99-HL157421 (D.O.) and KL2TR003143 (S.L.C.) from the National Institutes of Health.

Quantification of left atrial function by the area-length method overestimates left atrial emptying fraction.

PURPOSE: The biplane area-length method is commonly used in cardiac magnetic resonance (CMR) to assess left atrial (LA) volume (LAV) and function. Associations between left atrial emptying fraction (LAEF) and clinical outcomes have been reported. However, only limited data are available on the calculation of LAEF using the biplane method compared to 3D assessment. This study aimed to compare volumetric and functional LA parameters obtained from the biplane method with 3D assessment in a large, multiethnic cohort. METHOD: 158 participants of MESA (Multi-Ethnic Study of Atherosclerosis) underwent CMR that included standard two- and four-chamber steady-state free precession (SSFP) cine imaging for the biplane method. For 3D-based assessment, short-axis SSFP cine series covering the entire LA were obtained, followed by manual delineation of LA contours to create a time-resolved 3D LAV dataset. Paired t-tests and Bland-Altman plots were used to analyze the data. RESULTS: Standard volumetric assessment showed that LAVmin (bias: -8.35 mL, p < 0.001), LAVmax (bias: -9.38 mL, p < 0.001) and LAVpreA (bias: -10.27 mL, p < 0.001) were significantly smaller using the biplane method compared to 3D assessment. Additionally, the biplane method reported significantly higher LAEFtotal (bias: 7.22 %, p < 0.001), LAEFactive (bias: 6.08 %, p < 0.001), and LAEFpassive (bias: 4.51 %, p < 0.001) with wide limits of agreement. CONCLUSIONS: LA volumes were underestimated using the biplane method compared to 3D assessment, while LAEF parameters were overestimated. These findings demonstrate a lack of precision using the biplane method for LAEF assessment. Our results support the usage of 3D assessment in specific settings when LA volumetric and functional parameters are in focus.

Assessment of Beat-To-Beat Variability in Left Atrial Hemodynamics Using Real Time Phase Contrast MRI in Patients With Atrial Fibrillation.

BACKGROUND: Hemodynamic assessment of left atrial (LA) flow using phase contrast MRI provides insight into thromboembolic risk in atrial fibrillation (AF). However, conventional flow imaging techniques are averaged over many heartbeats. PURPOSE: To evaluate beat-to-beat variability and LA hemodynamics in patients with AF using real time phase contrast (RTPC) MRI. STUDY TYPE: Prospective. SUBJECTS: Thirty-five patients with history of AF (68 ± 10 years, nine female), 10 healthy controls (57 ± 19 years, four female). FIELD STRENGTH/SEQUENCE: 5T, 2D RTPC with through-plane velocity-encoded gradient echo sequence and 4D flow MRI with three-directional velocity-encoded gradient echo sequence. ASSESSMENT: RTPC was continuously acquired for a mid-LA slice in all subjects. 4D flow data were interpolated at the RTPC location and normally projected for comparison with RTPC. RR intervals extracted from RTPC were used to calculate heart rate variability (HRV = interquartile range over median × 100%). Patients were classified into low (<9.7%) and high (>9.7%) HRV groups. LA peak/mean velocity and stasis (%velocities < 5.8 cm/sec) were calculated from segmented 2D images. Variability in RTPC flow metrics was quantified by coefficient of variation (CV) over all cycles. STATISTICAL TESTS: Pearson's correlation coefficient (r), Bland-Altman analysis, Kruskal-Wallis test. A P value < 0.05 was considered statistically significant. RESULTS: RTPC and 4D flow measurements were strongly/significantly correlated for all hemodynamic parameters (R2  = 0.75-0.83) in controls. Twenty-four patients had low HRV (mean = 4 ± 2%) and 11 patients had high HRV (27 ± 9%). In patients, increased HRV was significantly correlated with CV of peak velocity (r = 0.67), mean velocity (r = 0.51), and stasis (r = 0.41). A stepwise decrease in peak/mean velocity and increase in stasis was observed when comparing controls vs. low HRV vs. high HRV groups. Mean velocity and stasis differences were significant for control vs. high HRV groups. CONCLUSIONS: RTPC may be suitable for assessing the impact of HRV on hemodynamics and provide insight for AF management in highly arrhythmic patients. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

RNA editing of microtubule-associated protein tau circular RNAs promotes their translation and tau tangle formation.

Aggregation of the microtubule-associated protein tau characterizes tauopathies, including Alzheimer's disease and frontotemporal lobar degeneration (FTLD-Tau). Gene expression regulation of tau is complex and incompletely understood. Here we report that the human tau gene (MAPT) generates two circular RNAs (circRNAs) through backsplicing of exon 12 to either exon 7 (12→7 circRNA) or exon 10 (12→10 circRNA). Both circRNAs lack stop codons. The 12→7 circRNA contains one start codon and is translated in a rolling circle, generating a protein consisting of multimers of the microtubule-binding repeats R1-R4. For the 12→10 circRNA, a start codon can be introduced by two FTLD-Tau mutations, generating a protein consisting of multimers of the microtubule-binding repeats R2-R4, suggesting that mutations causing FTLD may act in part through tau circRNAs. Adenosine to inosine RNA editing dramatically increases translation of circRNAs and, in the 12→10 circRNA, RNA editing generates a translational start codon by changing AUA to AUI. Circular tau proteins self-aggregate and promote aggregation of linear tau proteins. Our data indicate that adenosine to inosine RNA editing initiates translation of human circular tau RNAs, which may contribute to tauopathies.

Arrhythmic sudden death survival prediction using deep learning analysis of scarring in the heart.

Sudden cardiac death from arrhythmia is a major cause of mortality worldwide. Here, we develop a novel deep learning (DL) approach that blends neural networks and survival analysis to predict patient-specific survival curves from contrast-enhanced cardiac magnetic resonance images and clinical covariates for patients with ischemic heart disease. The DL-predicted survival curves offer accurate predictions at times up to 10 years and allow for estimation of uncertainty in predictions. The performance of this learning architecture was evaluated on multi-center internal validation data and tested on an independent test set, achieving concordance index of 0.83 and 0.74, and 10-year integrated Brier score of 0.12 and 0.14. We demonstrate that our DL approach with only raw cardiac images as input outperforms standard survival models constructed using clinical covariates. This technology has the potential to transform clinical decision-making by offering accurate and generalizable predictions of patient-specific survival probabilities of arrhythmic death over time.

Optimal saturation recovery time for minimizing the underestimation of arterial input function in quantitative cardiac perfusion MRI.

PURPOSE: The purpose of this study was to determine an optimal saturation-recovery time (TS) for minimizing the underestimation of arterial input function (AIF) in quantitative cardiac perfusion MRI without multiple gadolinium injections per subject. METHODS: We scanned 18 subjects (mean age = 59 ± 14 years, 9/9 males/females) to acquire resting perfusion data and 1 additional subject (age = 38 years, male) to obtain stress-rest perfusion data using a 5-fold accelerated pulse sequence with radial k-space sampling and applied k-space weighted image contrast (KWIC) filters on the same k-space data to retrospectively reconstruct five AIF images with effective TS ranging from 10 to 21.2 ms (2.8 ms steps). Undersampled images were reconstructed using a compressed sensing framework with temporal-total-variation and temporal-principal-component as 2 orthogonal sparsifying transforms. The image processing steps included, same motion correction across five different AIF images, signal normalization by the proton-density-weighted-image, signal-to-T1 conversion using a Bloch equation, T1 -to-gadolinium-concentration conversion assuming fast water exchange, T2 * correction to the AIF, and gadolinium-concentration to myocardial blood flow (MBF) conversion based on a Fermi model. RESULTS: Among five TS values, the shortest TS (10 ms) produced significantly (P < 0.05) higher peak AIF and lower resting MBF (13.73 mM, 0.73 mL g-1 min-1 ) than 12.8 ms (11.24 mM, 0.89 mL g-1 min-1 ), 15.6 ms (9.56 mM, 1.05 mL g-1 min-1 ), 18.4 ms (8.55 mM, 1.17 mL g-1 min-1 ), and 21.2 ms (7.95 mM, 1.27 mL g-1 min-1 ). Similarly, shorter TS reduced underestimation of AIF (or overestimation of MBF) for both during stress and at rest, but this effect was canceled in myocardial-perfusion-reserve (MPR). CONCLUSION: This study demonstrates that TS of 10 ms reduces the underestimation of AIF and, hence, the overestimation of MBF compared with longer TS values (12.8-21.2 ms).

A versatile approach for the synthesis of degradable polymers via controlled ring-opening metathesis copolymerization.

Norbornene derivatives (NBEs) are common monomers for living ring-opening metathesis polymerization and yield polymers with low dispersities and diverse functionalities. However, the all-carbon backbone of poly-NBEs is non-degradable. Here we report a method to synthesize degradable polymers by copolymerizing 2,3-dihydrofuran with NBEs. 2,3-Dihydrofuran rapidly reacts with Grubbs catalyst to form a thermodynamically stable Ru Fischer carbene-the only detectable active Ru species during copolymerization-and the addition of NBEs becomes rate determining. This reactivity attenuates the NBE homoaddition and allows uniform incorporation of acid-degradable enol ether linkages throughout the copolymers, which enables complete polymer degradation while maintaining the favourable characteristics of living ring-opening metathesis polymerization. Copolymerization of 2,3-dihydrofuran with NBEs gives low dispersity polymers with tunable solubility, glass transition temperature and mechanical properties. These polymers can be fully degraded into small molecule or oligomeric species under mildly acidic conditions. This method can be readily adapted to traditional ring-opening metathesis polymerization of widely used NBEs to synthesize easily degradable polymers with tunable properties for various applications and for environmental sustainability.