Cardiac MRI evaluation of aortic biophysical properties in paediatric Turner syndrome.

BACKGROUND: Aortopathy in Turner syndrome is associated with aortic dilation, and the risk of dissection is increased when the aortic size index is ≥ 2-2.5 cm/m2. We evaluated the aortic biophysical properties in paediatric Turner syndrome using cardiac MRI to determine their relationship to aortic size index. METHODS: Turner syndrome patients underwent cardiac MRI to evaluate ventricular function, aortic dimensions, and biophysical properties (aortic stiffness index, compliance, distensibility, pulse wave velocity, and aortic and left ventricular elastance). Spearman correlation examined correlations between these properties and aortic size index. Data was compared to 10 controls. RESULTS: Of 25 Turner syndrome patients, median age 14.7 years (interquartile range: 11.0-16.8), height z score -2.7 (interquartile range: -2.92 - -1.54), 24% had a bicuspid aortic valve. Turner syndrome had increased diastolic blood pressure (p < 0.001) and decreased left ventricular end-diastolic (p < 0.001) and end-systolic (p = 0.002) volumes compared to controls. Median aortic size index was 1.81 cm/m2 (interquartile range: 1.45-2.1) and 7 had an aortic size index > 2 cm/m2. Aortic and left ventricular elastance were greater in Turner syndrome compared to controls (both p < 0.001). Increased aortic size index correlated with increased aortic elastance (r = 0.5, p = 0.01) and left ventricular elastance (r = 0.59, p = 0.002) but not aortic compliance. Higher ascending aortic areas were associated with increased aortic compliance (r = 0.44, p = 0.03) and left ventricular elastance (r = 0.49, p = 0.01). CONCLUSION: Paediatric Turner syndrome with similar aortic size index to controls showed MRI evidence of abnormal aortic biophysical properties. These findings point to an underlying aortopathy and provide additional parameters that may aid in determining risk factors for aortic dissection.

Analysis of left ventricle regional myocardial motion for cardiac radioablation: Left ventricular motion analysis.

PURPOSE: Left ventricle (LV) regional myocardial displacement due to cardiac motion was assessed using cardiovascular magnetic resonance (CMR) cine images to establish region-specific margins for cardiac radioablation treatments. METHODS: CMR breath-hold cine images and LV myocardial tissue contour points were analyzed for 200 subjects, including controls (n = 50) and heart failure (HF) patients with preserved ejection fraction (HFpEF, n = 50), mid-range ejection fraction (HFmrEF, n = 50), and reduced ejection fraction (HFrEF, n = 50). Contour points were divided into segments according to the 17-segment model. For each patient, contour point displacements were determined for the long-axis (all 17 segments) and short-axis (segments 1-12) directions. Mean overall, tangential (longitudinal or circumferential), and normal (radial) displacements were calculated for the 17 segments and for each segment level. RESULTS: The greatest overall motion was observed in the control group-long axis: 4.5 ± 1.2 mm (segment 13 [apical anterior] epicardium) to 13.8 ± 3.0 mm (segment 6 [basal anterolateral] endocardium), short axis: 4.3 ± 0.8 mm (segment 9 [mid inferoseptal] epicardium) to 11.5 ± 2.3 mm (segment 1 [basal anterior] endocardium). HF patients exhibited lesser motion, with the smallest overall displacements observed in the HFrEF group-long axis: 4.3 ± 1.7 mm (segment 13 [apical anterior] epicardium) to 10.6 ± 3.4 mm (segment 6 [basal anterolateral] endocardium), short axis: 3.9 ± 1.3 mm (segment 8 [mid anteroseptal] epicardium) to 7.4 ± 2.8 mm (segment 1 [basal anterior] endocardium). CONCLUSIONS: This analysis provides an estimate of epicardial and endocardial displacement for the 17 segments of the LV for patients with normal and impaired LV function. This reference data can be used to establish treatment planning margin guidelines for cardiac radioablation. Smaller margins may be used for patients with higher degree of impaired heart function, depending on the LV segment.

Determinants of Impaired Peak Oxygen Uptake in Breast Cancer Survivors: JACC: CardioOncology Primer.

•Exercise intolerance is common among breast cancer survivors.•Exercise intolerance in breast cancer survivors is related to cardiac, vascular, and skeletal muscle impairments.•Holistic rehabilitation or pharmacological therapies are needed to address these impairments.

Effect of lower body negative pressure on cardiac and cerebral function in postural orthostatic tachycardia syndrome: A pilot MRI assessment.

Postural orthostatic tachycardia syndrome (POTS) is characterized by an excessive heart rate (HR) response upon standing and symptoms indicative of inadequate cerebral perfusion. We tested the hypothesis that during lower body negative pressure (LBNP), individuals with POTS would have larger decreases in cardiac and cerebrovascular function measured using magnetic resonance (MR) imaging. Eleven patients with POTS and 10 healthy controls were studied at rest and during 20 min of -25 mmHg LBNP. Biventricular volumes, stroke volume (SV), cardiac output (Qc), and HR were determined by cardiac MR. Cerebral oxygen uptake (VO2 ) in the superior sagittal sinus was calculated from cerebral blood flow (CBF; MR phase contrast), venous O2 saturation (SvO2 ; susceptometry-based oximetry), and arterial O2 saturation (pulse oximeter). Regional cerebral perfusion was determined using arterial spin labelling. HR increased in response to LBNP (p < 0.001) with no group differences (HC: +9 ± 8 bpm; POTS: +13 ± 11 bpm; p = 0.35). Biventricular volumes, SV, and Qc decreased during LBNP (p < 0.001). CBF and SvO2 decreased with LBNP (p = 0.01 and 0.03, respectively) but not cerebral VO2 (effect of LBNP: p = 0.28; HC: -0.2 ± 3.7 mL/min; POTS: +1.1 ± 2.0 mL/min; p = 0.33 between groups). Regional cerebral perfusion decreased during LBNP (p < 0.001) but was not different between groups. These data suggest patients with POTS have preserved cardiac and cerebrovascular function.

Left ventricle segment-specific motion assessment for cardiac-gated radiosurgery.

Purpose.Cardiac radiosurgery is a non-invasive treatment modality for ventricular tachycardia, where a linear accelerator is used to irradiate the arrhythmogenic region within the heart. In this work, cardiac magnetic resonance (CMR) cine images were used to quantify left ventricle (LV) segment-specific motion during the cardiac cycle and to assess potential advantages of cardiac-gated radiosurgery.Methods.CMR breath-hold cine images and LV contour points were analyzed for 50 controls and 50 heart failure patients with reduced ejection fraction (HFrEF, EF < 40%). Contour points were divided into anatomic segments according to the 17-segment model, and each segment was treated as a hypothetical treatment target. The optimum treatment window (one fifth of the cardiac cycle) was determined where segment centroid motion was minimal, then the maximum centroid displacement and treatment area were determined for the full cardiac cycle and for the treatment window. Mean centroid displacement and treatment area reductions with cardiac gating were determined for each of the 17 segments.Results.Full motion segment centroid displacements ranged between 6-14 mm (controls) and 4-11 mm (HFrEF). Full motion treatment areas ranged between 129-715 mm2(controls) and 149-766 mm2(HFrEF). With gating, centroid displacements were reduced to 1 mm (controls and HFrEF), while treatment areas were reduced to 62-349 mm2(controls) and 83-393 mm2(HFrEF). Relative treatment area reduction ranged between 38%-53% (controls) and 26%-48% (HFrEF).Conclusion.This data demonstrates that cardiac cycle motion is an important component of overall target motion and varies depending on the anatomic cardiac segment. Accounting for cardiac cycle motion, through cardiac gating, has the potential to significantly reduce treatment volumes for cardiac radiosurgery.

Reference Values for Water-Specific T1 of the Liver at 3 T: T2*-Compensation and the Confounding Effects of Fat.

BACKGROUND: T1 mapping of the liver is confounded by the presence of fat. Multiparametric T1 mapping combines fat-water separation with T1-weighting to enable imaging of water-specific T1 (T1Water ), proton density fat fraction (PDFF), and T2* values. However, normative T1Water values in the liver and its dependence on age/sex is unknown. PURPOSE: Determine normative values for T1Water in the liver with comparison to MOLLI and evaluate a T2*-compensation approach to reduce T1 variability. STUDY TYPE: Prospective observational; phantoms. POPULATIONS: One hundred twenty-four controls (56 male, 18-75 years), 50 patients at-risk for liver disease (18 male, 30-76 years). FIELD STRENGTH/SEQUENCE: 2.89 T; Saturation-recovery chemical-shift encoded T1 Mapping (SR-CSE); MOLLI. ASSESSMENT: SR-CSE provided T1Water measurements, PDFF and T2* values in the liver across three slices in 6 seconds. These were compared with MOLLI T1 values. A new T2*-compensation approach to reduce T1 variability was evaluated test/re-test reproducibility. STATISTICAL TESTS: Linear regression, ANCOVA, t-test, Bland and Altman, intraclass correlation coefficient (ICC). P < 0.05 was considered statistically significant. RESULTS: Liver T1 values were significantly higher in healthy females (F) than males (M) for both SR-CSE (F-973 ± 78 msec, M-930 ± 72 msec) and MOLLI (F-802 ± 55 msec, M-759 ± 69 msec). T1 values were negatively correlated with age, with similar sex- and age-dependencies observed in T2*. The T2*-compensation model reduced the variability of T1 values by half and removed sex- and age-differences (SR-CSE: F-946 ± 36 msec, M-941 ± 43 msec; MOLLI: F-775 ± 35 msec, M-770 ± 35 msec). At-risk participants had elevated PDFF and T1 values, which became more distinct from the healthy cohort after T2*-compensation. MOLLI systematically underestimated liver T1 values by ~170 msec with an additional positive T1-bias from fat content (~11 msec/1% in PDFF). Reproducibility ICC values were ≥0.96 for all parameters. DATA CONCLUSION: Liver T1Water values were lower in males and decreased with age, as observed for SR-CSE and MOLLI acquisitions. MOLLI underestimated liver T1 with an additional large positive fat-modulated T1 bias. T2*-compensation removed sex- and age-dependence in liver T1, reduced the range of healthy values and increased T1 group differences between healthy and at-risk groups. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Dynamic changes in lung water density and volume following supine body positioning.

PURPOSE: Measure the changes in relative lung water density (rLWD), lung volume, and total lung water content as a function of time after supine body positioning. METHODS: An efficient ultrashort-TE pulse sequence with a yarnball k-space trajectory was used to measure water density-weighted lung images for 25 min following supine body positioning (free breathing, 74-s acquisitions, 3D images at functional residual capacity, 18 time points) in 9 healthy volunteers. Global and regional (10 chest-to-back positions) rLWD, lung volume, and total lung water volume were measured in all subjects at all time points. Volume changes were validated with a nitrogen washout study in 3 participants. RESULTS: Global rLWD increased significantly (p = 0.001) from 31.8 ± 5.5% to 34.8 ± 6.8%, while lung volumes decreased significantly (p < 0.001) from 2390 ± 620 mL to 2130 ± 630 mL over the same 25-min interval. Total lung water volume decreased slightly from 730 ± 125 mL to 706 ± 126 mL (p = 0.028). There was a significant chest-to-back gradient in rLWD (20.7 ± 4.6% to 39.9 ± 6.1%) at all time points with absolute increases of 1.8 ± 1.2% at the chest and 5.4 ± 1.9% at the back. Nitrogen washout studies yielded a similar reduction in lung volume (12.5 ± 0.9%) and time course following supine positioning. CONCLUSION: Lung volumes during tidal breathing decrease significantly over tens of minutes following supine body positioning, with corresponding increases in lung water density (9.2 ± 4.4% relative increase). The total volume of lung water is slightly reduced over this interval (3.3 ± 4.0% relative change). Evaluation of rLWD should take time after supine positioning, and more generally, all sources of lung volume changes should be taken into consideration to avoid significant bias.

Sex-based Differences in the Phenotypic Expression and Prognosis of Idiopathic Non-ischemic Cardiomyopathy: A Cardiovascular Magnetic Resonance Study.

AIMS: We sought to characterize sex-related differences in CMR-based cardiovascular phenotypes and prognosis in patients with idiopathic non-ischemic cardiomyopathy (NICM). METHODS AND RESULTS: Patients with NICM enrolled in the Cardiovascular Imaging Registry of Calgary (CIROC) between 2015 and 2021 were identified. Z-score values for chamber volumes and function were calculated as standard deviation from mean values of 157 sex-matched healthy volunteers, ensuring reported differences were independent of known sex-dependencies. Patients were followed for the composite outcome of all-cause mortality, heart failure admission, or ventricular arrhythmia.A total of 747 patients were studied, 531 (71%) males. By Z-score values, females showed significantly higher left ventricular (LV) ejection fraction (EF; median difference 1 SD) and right ventricular (RV) EF (difference 0.6 SD) with greater LV mass (difference 2.1 SD; p-value<0.01 for all) versus males despite similar chamber volumes. Females had a significantly lower prevalence of mid-wall striae (MWS) fibrosis (23% versus 36%; p-value<0.001). Over a median follow-up of 4.7 years, 173 patients (23%) developed the composite outcome, with equal distribution in males and females. LV EF and MWS were significant independent predictors of the outcome (respective HR [95% CI] 0.97 [0.95-0.99] and 1.6 [1.2-2.3]; p-value=0.003 and 0.005). There was no association of sex with the outcome. CONCLUSIONS: In a large contemporary cohort, NICM was uniquely expressed in females versus males. Despite similar chamber dilation, females demonstrated greater concentric remodelling, lower reductions in bi-ventricular function, and a lower burden of replacement fibrosis. Overall, their prognosis remained similar to male patients with NICM.

Bruch's Membrane Calcification in Pseudoxanthoma Elasticum: Comparing Histopathology and Clinical Imaging.

Purpose: To investigate the histology of Bruch's membrane (BM) calcification in pseudoxanthoma elasticum (PXE) and correlate this to clinical retinal imaging. Design: Experimental study with clinicopathological correlation. Subjects and Controls: Six postmortem eyes from 4 PXE patients and 1 comparison eye from an anonymous donor without PXE. One of the eyes had a multimodal clinical image set for comparison. Methods: Calcification was labeled with OsteSense 680RD, a fluorescent dye specific for hydroxyapatite, and visualized with confocal microscopy. Scanning electron microscopy coupled with energy-dispersive x-ray spectroscopy (SEM-EDX) and time-of-flight secondary ion mass spectrometry (TOF-SIMs) were used to analyze the elemental and ionic composition of different anatomical locations. Findings on cadaver tissues were compared with clinical imaging of 1 PXE patient. Main Outcome Measures: The characteristics and topographical distribution of hydroxyapatite in BM in eyes with PXE were compared with the clinical manifestations of the disease. Results: Analyses of whole-mount and sectioned PXE eyes revealed an extensive, confluent OsteoSense labeling in the central and midperipheral BM, transitioning to a speckled labeling in the midperiphery. These areas corresponded to hyperreflective and isoreflective zones on clinical imaging. Scanning electron microscopy coupled with energy-dispersive x-ray spectroscopy and TOF-SIMs analyses identified these calcifications as hydroxyapatite in BM of PXE eyes. The confluent fluorescent appearance originates from heavily calcified fibrous structures of both the collagen and the elastic layers of BM. Calcification was also detected in an aged comparison eye, but this was markedly different from PXE eyes and presented as small snowflake-like deposits in the posterior pole. Conclusions: Pseudoxanthoma elasticum eyes show extensive hydroxyapatite deposition in the inner and outer collagenous and elastic BM layers in the macula with a gradual change toward the midperiphery, which seems to correlate with the clinical phenotype. The snowflake-like calcification in BM of an aged comparison eye differed markedly from the extensive calcification in PXE. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A Review on the Role of Exercise Training to Prevent a Decline in Cardiorespiratory Fitness and Cardiac Function in Breast Cancer Survivors.

PURPOSE: Improvements in diagnosis and treatment mean that the long-term health of breast cancer survivors (BCS) is increasingly dictated by cardiovascular comorbidities. This is partly a consequence of exposure to cardiotoxic therapies, which result in cardiac dysfunction and decreased cardiorespiratory fitness (CRF). Exercise training (ExT) is a key therapeutic strategy for secondary prevention and increasing CRF in adults with established cardiovascular disease. Exercise-based cardio-oncology rehabilitation (CORE) has been proposed as an emerging strategy to address CRF and cardiac impairment in BCS. This review aims to (1) provide an overview of the impact of breast cancer therapy on CRF; (2) provide an up-to-date summary of the effects of ExT on CRF and cardiac function in BCS undergoing cardiotoxic therapy; and (3) discuss how traditional ExT approaches can be adapted for BCS undergoing therapy. REVIEW METHODS: A literature review was performed based on an intensive literature search for systematic reviews and meta-analyses, randomized and non-randomized controlled trials and single-arm trials investigating the impact of exercise training or cardiac rehabilitation on CRF and/or cardiac function in BCS who are undergoing or have completed cardiotoxic cancer therapy. SUMMARY: Overall, current evidence suggests that ExT induces clinically meaningful benefits for CRF in BCS during and after therapy. There is also emerging evidence that ExT can improve peak exercise measures of cardiac function; however, there is a need for further research to understand how to adapt these effective ExT approaches into clinical CORE-based settings.

Integration of longitudinal and circumferential strain predicts volumetric change across the cardiac cycle and differentiates patients along the heart failure continuum.

BACKGROUND: Left ventricular (LV) circumferential and longitudinal strain provide important insight into LV mechanics and function, each contributing to volumetric changes throughout the cardiac cycle. We sought to explore this strain-volume relationship in more detail, by mathematically integrating circumferential and longitudinal strain and strain rate to predict LV volume and volumetric rates of change. METHODS: Cardiac magnetic resonance (CMR) imaging from 229 participants from the Alberta HEART Study (46 healthy controls, 77 individuals at risk for developing heart failure [HF], 70 patients with diagnosed HF with preserved ejection fraction [HFpEF], and 36 patients with diagnosed HF with reduced ejection fraction [HFrEF]) were evaluated. LV volume was assessed by the method of disks and strain/strain rate were assessed by CMR feature tracking. RESULTS: Integrating endocardial circumferential and longitudinal strain provided a close approximation of LV ejection fraction (EFStrain), when compared to gold-standard volumetric assessment (EFVolume: r = 0.94, P < 0.0001). Likewise, integrating circumferential and longitudinal strain rate provided a close approximation of peak ejection and peak filling rates (PERStrain and PFRStrain, respectively) compared to their gold-standard volume-time equivalents (PERVolume, r = 0.73, P < 0.0001 and PFRVolume, r = 0.78, P < 0.0001, respectively). Moreover, each integrated strain measure differentiated patients across the HF continuum (all P < 0.01), with the HFrEF group having worse EFStrain, PERStrain, and PFRStrain compared to all other groups, and HFpEF having less favorable EFStrain and PFRStrain compared to both at-risk and control groups. CONCLUSIONS: The data herein establish the theoretical framework for integrating discrete strain components into volumetric measurements across the cardiac cycle, and highlight the potential benefit of this approach for differentiating patients along the heart failure continuum.

Cardio-oncology and Cancer Rehabilitation: Is an Integrated Approach Possible?

With significant improvements in the understanding of cancer biology, improved detection, and the use of novel adjuvant therapies, each year more Canadians are surviving a cancer diagnosis. Despite their effectiveness these therapies often result in short- and long-term deleterious effects to major organ systems, particularly cardiovascular. Cardio-oncology is an emerging field of study with the aim to improve cardiovascular health across the oncology disease spectrum. International guidelines distinguish "cardio-oncology" rehabilitation from "cancer" rehabilitation, but how this is navigated is currently unknown. How such care should be assessed and integrated acutely or in the longer term remains unknown. Accordingly, the aim of this article is to consider the cancer patient's needs beyond the scope of cardio-oncology rehabilitation to holistically integrate cancer rehabilitation across the disease trajectory.

Two-Photon Excited Fluorescence Lifetime Imaging of Tetracycline-Labeled Retinal Calcification.

Deposition of calcium-containing minerals such as hydroxyapatite and whitlockite in the subretinal pigment epithelial (sub-RPE) space of the retina is linked to the development of and progression to the end-stage of age-related macular degeneration (AMD). AMD is the most common eye disease causing blindness amongst the elderly in developed countries; early diagnosis is desirable, particularly to begin treatment where available. Calcification in the sub-RPE space is also directly linked to other diseases such as Pseudoxanthoma elasticum (PXE). We found that these mineral deposits could be imaged by fluorescence using tetracycline antibiotics as specific stains. Binding of tetracyclines to the minerals was accompanied by increases in fluorescence intensity and fluorescence lifetime. The lifetimes for tetracyclines differed substantially from the known background lifetime of the existing natural retinal fluorophores, suggesting that calcification could be visualized by lifetime imaging. However, the excitation wavelengths used to excite these lifetime changes were generally shorter than those approved for retinal imaging. Here, we show that tetracycline-stained drusen in post mortem human retinas may be imaged by fluorescence lifetime contrast using multiphoton (infrared) excitation. For this pilot study, ten eyes from six anonymous deceased donors (3 female, 3 male, mean age 83.7 years, range 79-97 years) were obtained with informed consent from the Maryland State Anatomy Board with ethical oversight and approval by the Institutional Review Board.

Safety and efficacy of a kaolin-impregnated hemostatic gauze in cardiac surgery: A randomized trial.

Objective: A kaolin-based nonresorbable hemostatic gauze, QuikClot Control+, has demonstrated effective hemostasis and safety when used for severe/life-threatening (grade 3/4) internal organ space bleeding. We evaluated the efficacy and safety of this gauze for mild to moderate (grade 1-2) bleeding in cardiac surgery compared with control gauze. Methods: This was a randomized, controlled, single-blinded study of patients who underwent cardiac surgery between June 2020 and September 2021 across 7 sites with 231 subjects randomized 2:1 to QuikClot Control+ or control. The primary efficacy end point was hemostasis rate (ie, subjects achieving grade 0 bleed) through up to 10 minutes of bleeding site application, assessed using a semiquantitative validated bleeding severity scale tool. The secondary efficacy end point was the proportion of subjects achieving hemostasis at 5 and 10 minutes. Adverse events, assessed up to 30 days postsurgery, were compared between arms. Results: The predominant procedure was coronary artery bypass grafting, and 69.7% and 29.4% were sternal edge and surgical site (suture line)/other bleeds, respectively. Of the QuikClot Control+ subjects, 121 of 153 (79.1%) achieved hemostasis within 5 minutes, compared with 45 of 78 (58.4%) controls (P < .001). At 10 minutes, 137 of 153 patients (89.8%) achieved hemostasis compared with 52 of 78 controls (68.4%) (P < .001). At 5 and 10 minutes, hemostasis was achieved in 20.7% and 21.4% more QuikClot Control+ subjects, respectively, compared with controls (P < .001). There were no significant differences in safety or adverse events between treatment arms. Conclusions: QuikClot Control+ demonstrated superior performance in achieving hemostasis for mild to moderate cardiac surgery bleeding compared with control gauze. The proportion of subjects achieving hemostasis was more than 20% higher in QuikClot Control+ subjects at both timepoints compared with controls, with no significant difference in safety outcomes.

Magnetic Resonance Imaging of Aerosol Deposition.

Nuclear magnetic resonance imaging (MRI) uses non-ionizing radiation and offers a host of contrast mechanisms with the potential to quantify aerosol deposition. This chapter introduces the physics of MRI, its use in lung imaging, and more specifically, the methods that are used for the detection of regional distributions of inhaled particles. The most common implementation of MRI is based on imaging of hydrogen atoms (1H) in water. The regional deposition of aerosol particles can be measured by the perturbation of the acquired 1H signals via labeling of the aerosol with contrast agents. Existing in vitro human and in vivo animal model measurements of regional aerosol deposition in the respiratory tract are described, demonstrating the capability of MRI to assess aerosol deposition in the lung.

Fluorescence Lifetime Imaging of Human Sub-RPE Calcification In Vitro Following Chlortetracycline Infusion.

We have shown that all sub-retinal pigment epithelial (sub-RPE) deposits examined contain calcium phosphate minerals: hydroxyapatite (HAP), whitlockite (Wht), or both. These typically take the form of ca. 1 µm diameter spherules or >10 µm nodules and appear to be involved in the development and progression of age-related macular degeneration (AMD). Thus, these minerals may serve as useful biomarkers the for early detection and monitoring of sub-RPE changes in AMD. We demonstrated that HAP deposits could be imaged in vitro by fluorescence lifetime imaging microscopy (FLIM) in flat-mounted retinas using legacy tetracycline antibiotics as selective sensors for HAP. As the contrast on a FLIM image is based on the difference in fluorescence lifetime and not intensity of the tetracycline-stained HAP, distinguishing tissue autofluorescence from the background is significantly improved. The focus of the present pilot study was to assess whether vascular perfusion of the well tolerated and characterized chlortetracycline (widely used as an orally bioavailable antibiotic) can fluorescently label retinal HAP using human cadavers. We found that the tetracycline delivered through the peripheral circulation can indeed selectively label sub-RPE deposits opening the possibility for its use for ophthalmic monitoring of a range of diseases in which deposit formation is reported, such as AMD and Alzheimer disease (AD).

Implementation of weekday time-restricted eating to improve metabolic health in breast cancer survivors with overweight/obesity.

OBJECTIVE: This study aimed to evaluate the implementation of telephone-based delivery of weekday-only time-restricted eating (TRE), its preliminary efficacy for metabolic outcomes, and concurrent lifestyle changes. METHODS: Twenty-two breast cancer survivors aged 60+ years with overweight/obesity completed an 8-week feasibility study of 12 to 8 p.m. weekday-only ad libitum TRE. The intervention was delivered by one registered dietitian call, twice-daily automated text messages asking about eating start and stop times, and three support phone calls. Magnetic resonance imaging, venipuncture, and 3 days of diet records and accelerometry were performed at baseline and after intervention. RESULTS: Participants had a mean age of 66 (SD 5) years with BMI of 31.8 (4.8) kg/m2 . Intervention implementation was successful, including excellent adherence (98%), participant acceptability, and a low symptom profile and cost ($63/participant). There were no significant changes in individual components of metabolic syndrome, lipid profile, or hemoglobin A1c , despite clinically relevant changes occurring within individual participants. Magnetic resonance imaging-derived hepatic steatosis and thigh myosteatosis did not change. Dietary intake changes included reduced energy (-22%) and protein (-0.2 g/kg). Physical activity and sleep did not change. CONCLUSIONS: Eight weeks of telephone-delivered weekday TRE is a feasible, acceptable, low-symptom, and low-cost intervention. Future studies may consider a longer intervention length for more consistent metabolic improvements and counseling to enhance protein intake.

Integrating Cardiac MRI Imaging and Multidisciplinary Clinical Care is Associated With Improved Outcomes in Patients With Fabry Disease.

Given the inherent complexities of Fabry disease (FD) and evolving landscape of cardiovascular clinical management, there is no established ideal clinical care model for these patients. We identified clinical factors predictive of increased risk of major adverse cardiac events (MACE) in patients with FD targeted to improve clinical outcomes. Ninety-five patients studied over a median follow-up time of 6.3 years, and 26 patients reached the composite endpoint with a high prevalence of heart failure and cerebrovascular events and no cardiac-related mortality. Patients with MACE had worse health-related quality of life scores. Hypertrophy and presence of myocardial fibrosis increase risk of MACE by 4-5 times, and dyslipidemia increases risk of MACE by 3 times. Early Fabry-specific treatment and close monitoring of comorbidities reduce cardiac complications and mortality. These findings highlight the importance of comprehensive multidisciplinary management to help improve outcomes in FD patients.

Rationale and design of IMPACT-women: a randomised controlled trial of the effect of time-restricted eating, healthy eating and reduced sedentary behaviour on metabolic health during chemotherapy for early-stage breast cancer.

Metabolic dysfunction and excess accumulation of adipose tissue are detrimental side effects from breast cancer treatment. Diet and physical activity are important treatments for metabolic abnormalities, yet patient compliance can be challenging during chemotherapy treatment. Time-restricted eating (TRE) is a feasible dietary pattern where eating is restricted to 8 h/d with water-only fasting for the remaining 16 h. The purpose of this study is to evaluate the effect of a multimodal intervention consisting of TRE, healthy eating, and reduced sedentary time during chemotherapy treatment for early-stage (I-III) breast cancer on accumulation of visceral fat (primary outcome), other fat deposition locations, metabolic syndrome and cardiovascular disease risk (secondary outcomes) compared with usual care. The study will be a two-site, two-arm, parallel-group superiority randomised control trial enrolling 130 women scheduled for chemotherapy for early-stage breast cancer. The intervention will be delivered by telephone, including 30-60-minute calls with a registered dietitian who will provide instructions on TRE, education and counselling on healthy eating, and goal setting for reducing sedentary time. The comparison group will receive usual cancer and supportive care including a single group-based nutrition class and healthy eating and physical activity guidelines. MRI, blood draws and assessment of blood pressure will be performed at baseline, after chemotherapy (primary end point), and 2-year follow-up. If our intervention is successful in attenuating the effect of chemotherapy on visceral fat accumulation and cardiometabolic dysfunction, it has the potential to reduce risk of cardiometabolic disease and related mortality among breast cancer survivors.

Ratiometric Zinc Biosensor Based on Bioluminescence Resonance Energy Transfer: Trace Metal Ion Determination with Tunable Response.

Determination of metal ions such as zinc in solution remains an important task in analytical and biological chemistry. We describe a novel zinc ion biosensing approach using a carbonic anhydrase-Oplophorus luciferase fusion protein that employs bioluminescence resonance energy transfer (BRET) to transduce the level of free zinc as a ratio of emission intensities in the blue and orange portions of the spectrum. In addition to high sensitivity (below nanomolar levels) and selectivity, this approach allows both quantitative determination of "free" zinc ion (also termed "mobile" or "labile") using bioluminescence ratios and determination of the presence of the ion above a threshold simply by the change in color of bioluminescence, without an instrument. The carbonic anhydrase metal ion sensing platform offers well-established flexibility in sensitivity, selectivity, and response kinetics. Finally, bioluminescence labeling has proven an effective approach for molecular imaging in vivo since no exciting light is required; the expressible nature of this sensor offers the prospect of imaging zinc fluxes in vivo.