Multidimensional Analysis of the Adult Human Heart in Health and Disease Using Hierarchical Phase-Contrast Tomography.

Background Current clinical imaging modalities such as CT and MRI provide resolution adequate to diagnose cardiovascular diseases but cannot depict detailed structural features in the heart across length scales. Hierarchical phase-contrast tomography (HiP-CT) uses fourth-generation synchrotron sources with improved x-ray brilliance and high energies to provide micron-resolution imaging of intact adult organs with unprecedented detail. Purpose To evaluate the capability of HiP-CT to depict the macro- to microanatomy of structurally normal and abnormal adult human hearts ex vivo. Materials and Methods Between February 2021 and September 2023, two adult human donor hearts were obtained, fixed in formalin, and prepared using a mixture of crushed agar in a 70% ethanol solution. One heart was from a 63-year-old White male without known cardiac disease, and the other was from an 87-year-old White female with a history of multiple known cardiovascular pathologies including ischemic heart disease, hypertension, and atrial fibrillation. Nondestructive ex vivo imaging of these hearts without exogenous contrast agent was performed using HiP-CT at the European Synchrotron Radiation Facility. Results HiP-CT demonstrated the capacity for high-spatial-resolution, multiscale cardiac imaging ex vivo, revealing histologic-level detail of the myocardium, valves, coronary arteries, and cardiac conduction system across length scales. Virtual sectioning of the cardiac conduction system provided information on fatty infiltration, vascular supply, and pathways between the cardiac nodes and adjacent structures. HiP-CT achieved resolutions ranging from gross (isotropic voxels of approximately 20 µm) to microscopic (approximately 6.4-µm voxel size) to cellular (approximately 2.3-µm voxel size) in scale. The potential for quantitative assessment of features in health and disease was demonstrated. Conclusion HiP-CT provided high-spatial-resolution, three-dimensional images of structurally normal and diseased ex vivo adult human hearts. Whole-heart image volumes were obtained with isotropic voxels of approximately 20 µm, and local regions of interest were obtained with resolution down to 2.3-6.4 µm without the need for sectioning, destructive techniques, or exogenous contrast agents. Published under a CC BY 4.0 license Supplemental material is available for this article. See also the editorial by Bluemke and Pourmorteza in this issue.

Subjective Cognitive Decline in a Registry Sample: Relation to Psychiatric History, Loneliness, and Personality.

BACKGROUND: With the increasing focus on prevention of Alzheimer's disease, there is need for characterization of preclinical populations. Local participant registries offer an opportunity to facilitate research engagement via remote data collection, inform recruitment, and characterize preclinical samples, including individuals with subjective cognitive decline. OBJECTIVES: We sought to characterize subjective cognitive decline in a registry sample, as related to psychiatric history and related variables, including personality and loneliness, quality of life, and factors related to dementia risk (e.g., family history of dementia). DESIGN, SETTING, PARTICIPANTS: Participants were 366 individuals (mean age=67.2 (range 50-88), 65% female, 94% white, 97% non-Hispanic or Latino, 82% with at least a bachelor's degree) with no reported history of mild cognitive impairment or dementia. All participants had expressed interest in research, primarily via community outreach events and prior research involvement. Data was collected via electronic surveys, distributed using REDCap. Electronic questionnaires included questions on demographic variables, subjective cognitive decline, quality of life, loneliness, and personality. RESULTS: There was a high prevalence of risk factors for dementia in the registry sample (68% with family history of dementia, 31% with subjective cognitive decline). Subjective cognitive decline was more common in women and associated with history of depression, but not with family history of dementia. Subjective cognitive decline was also associated with lower conscientiousness and lower emotional stability, as well as higher loneliness and lower quality of life. Among participants who endorsed a psychiatric history, most reported onset more than 10 years prior, rather than within the last 10 years. CONCLUSIONS: Subjective cognitive decline in a registry sample may be more strongly associated with longstanding psychiatric and personality variables, rather than family history of dementia, adding to the literature on characterization of subjective cognitive decline across different settings. These findings highlight the acceptability of remote data collection and the potential of registries to inform recruitment by characterizing registrants, which may help to stratify dementia risk and match participants to eligible trials.

Maternal circulating PlGF concentrations and placenta-related pregnancy complications: First results from the CoLab AngF Study.

INTRODUCTION: Circulating angiogenic factors are potential markers for preeclampsia, but heterogeneous studies have failed to identify precise predictive/diagnostic properties. The Global CoLaboratory is investigating how to merge published data of angiogenic factors for meta-analysis on an individual sample basis. OBJECTIVE: To amalgamate pregnancy angiogenic factor studies, investigate diagnostic and predictive properties of these markers in preeclampsia and placenta-related pregnancy complications, and to test if measures from disparate platforms can be standardised. This is the first report using PlGF measures to diagnose preeclampsia. METHODS: Data were derived from 15 cohorts, within and outside the CoLaboratory network. Women were classified as either case (confirmed diagnosis of preeclampsia at sampling) or non-case (no preeclampsia at sampling). Individual PlGF measurements from four different analytical platforms were used, along with transformations of the data (e.g. log-transformations, transformations to a baseline platform). Transformed measurements were standardised both for specific platforms and globally, stratifying on gestational age. Different statistical techniques were compared. RESULTS: The database currently contains 1442 cases and 11,512 non-cases, which were used to define an algorithm to merge PlGF measurements from different platforms. Non-case distributions were used to standardise case results. Diagnostic PlGF measurements in relation to preeclampsia will be presented and confirm feasibility. CONCLUSIONS: Future studies can extend this approach to other angiogenic factors, prediction as well as diagnosis and to other placenta-related disorders.

Qualitative interview study of communication between parents and children about maternal breast cancer.

OBJECTIVE: To examine parents' communication with their children about the diagnosis and initial treatment of breast cancer in the mother. DESIGN: Qualitative interview study within a cross-sectional cohort. SETTING: Two breast cancer treatment centers. PARTICIPANTS: 32 women with stage I or stage II breast cancer with 56 school-aged children. Main outcome measures Semistructured interview regarding timing and extent of communication with children about the diagnosis and initial treatment of the mother's illness, reasons for talking to children or withholding information, and help available and requested from health professionals. RESULTS: Women were most likely to begin talking to their children after their diagnosis had been confirmed by biopsy, but a few waited until after surgery or said nothing at all. Family discussion did not necessarily include mention of cancer. There was considerable consistency in the reasons given for either discussing or not discussing the diagnosis. The most common reason for not communicating was to avoid children's questions, particularly those about death. Although most women had helpful discussion with a physician concerning their illness, few were offered help with talking to their children; many would have liked help, particularly the opportunity for both parents to talk to a health professional with experience in understanding and talking to children. CONCLUSION: Parents diagnosed with cancer or other serious illnesses should be offered help to think about whether, what, and how to tell their children and about what children can understand, especially as they may well be struggling themselves to come to terms with their illness.

Qualitative interview study of communication between parents and children about maternal breast cancer.

OBJECTIVE: To examine parents' communication with their children about the diagnosis and initial treatment of breast cancer in the mother. DESIGN: Qualitative interview study within cross sectional cohort. SETTING: Two breast cancer treatment centres. PARTICIPANTS: 32 women with stage I or stage II breast cancer with a total of 56 school aged children. MAIN OUTCOME MEASURES: Semistructured interview regarding timing and extent of communication with children about the diagnosis and initial treatment of the mother's illness, reasons for talking to children or withholding information, and help available and requested from health professionals. RESULTS: Women were most likely to begin talking to their children after their diagnosis had been confirmed by biopsy, but a minority waited until after surgery or said nothing at all. Family discussion did not necessarily include mention of cancer. There was considerable consistency in the reasons given for either discussing or not discussing the diagnosis. The most common reason for not communicating was avoidance of children's questions and particularly those about death. While most mothers experienced helpful discussion with a doctor concerning their illness, few were offered help with talking to children; many would have liked help, particularly the opportunity for both parents to talk to a health professional with experience in understanding and talking to children. CONCLUSIONS: Parents diagnosed with cancer or other serious illnesses should be offered help to think about whether, what, and how to tell their children and about what children can understand, especially as they may well be struggling themselves to come to terms with their illness.