skip to main content

Title: In vivo assessment of mitral valve leaflet remodelling following myocardial infarction
Abstract

Each year, more than 40,000 people undergo mitral valve (MV) repair surgery domestically to treat regurgitation caused by myocardial infarction (MI). Although continual MV tissue remodelling following repair is believed to be a major contributor to regurgitation recurrence, the effects of the post-MI state on MV remodelling remain poorly understood. This lack of understanding limits our ability to predict the remodelling of the MV both post-MI and post-surgery to facilitate surgical planning. As a necessary first step, the present study was undertaken to noninvasively quantify the effects of MI on MV remodelling in terms of leaflet geometry and deformation. MI was induced in eight adult Dorset sheep, and real-time three-dimensional echocardiographic (rt-3DE) scans were collected pre-MI as well as at 0, 4, and 8 weeks post-MI. A previously validated image-based morphing pipeline was used to register corresponding open- and closed-state scans and extract local in-plane strains throughout the leaflet surface at systole. We determined that MI inducedpermanentchanges in leaflet dimensions in the diastolic configuration, which increased with time to 4 weeks, then stabilised. MI substantially affected the systolicshapeof the MV, and therange of stretchexperienced by the MV leaflet at peak systole was substantially reduced when referred to the current time-point. more » Interestingly, when we referred the leaflet strains to the pre-MI configuration, the systolic strains remained very similar throughout the post-MI period. Overall, we observed that post-MI ventricular remodeling induced permanent changes in the MV leaflet shape. This predominantly affected the MV’s diastolic configuration, leading in turn to a significant decrease in the range of stretch experienced by the leaflet when referenced to the current diastolic configuration. These findings are consistent with our previous work that demonstrated increased plastic (i.e. non-recoverable) leaflet deformations post-MI, that was completely accounted for by the associated changes in collagen fiber structure. Moreover, we demonstrated through noninvasive methods that the state of the MV leaflet can elucidate the progression and extent of MV adaptation following MI and is thus highly relevant to the design of current and novel patient specific minimally invasive surgical repair strategies.

« less
Authors:
; ; ; ; ;
Publication Date:
NSF-PAR ID:
10377149
Journal Name:
Scientific Reports
Volume:
12
Issue:
1
ISSN:
2045-2322
Publisher:
Nature Publishing Group
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract

    In two-thirds of intensive care unit (ICU) patients and 90% of surgical patients, arterial blood pressure (ABP) is monitored non-invasively but intermittently using a blood pressure cuff. Since even a few minutes of hypotension increases the risk of mortality and morbidity, for the remaining (high-risk) patients ABP is measured continuously using invasive devices, and derived values are extracted from the recorded waveforms. However, since invasive monitoring is associated with major complications (infection, bleeding, thrombosis), the ideal ABP monitor should be both non-invasive and continuous. With large volumes of high-fidelity physiological waveforms, it may be possible today to impute a physiological waveform from other available signals. Currently, the state-of-the-art approaches for ABP imputation only aim at intermittent systolic and diastolic blood pressure imputation, and there is no method that imputes the continuous ABP waveform. Here, we developed a novel approach to impute the continuous ABP waveform non-invasively using two continuously-monitored waveforms that are currently part of the standard-of-care, the electrocardiogram (ECG) and photo-plethysmogram (PPG), by adapting a deep learning architecture designed for image segmentation. Using over 150,000 min of data collected at two separate health systems from 463 patients, we demonstrate that our model provides a highly accurate prediction of themore »continuous ABP waveform (root mean square error 5.823 (95% CI 5.806–5.840) mmHg), as well as the derived systolic (mean difference 2.398 ± 5.623 mmHg) and diastolic blood pressure (mean difference − 2.497 ± 3.785 mmHg) compared to arterial line measurements. Our approach can potentially be used to measure blood pressure continuously and non-invasively for all patients in the acute care setting, without the need for any additional instrumentation beyond the current standard-of-care.

    « less
  2. Photoacoustic imaging is a promising technique to provide guidance during multiple surgeries and procedures. One challenge with this technique is that major blood vessels in the liver are difficult to differentiate from surrounding tissue within current safety limits, which only exist for human skin and eyes. In this paper, we investigate the safety of raising this limit for liver tissue excited with a 750 nm laser wavelength and approximately 30 mJ laser energy (corresponding to approximately 150 mJ/cm2fluence). Laparotomies were performed on six swine to empirically investigate potential laser-related liver damage. Laser energy was applied for temporal durations of 1 minute, 10 minutes, and 20 minutes. Lasered liver lobes were excised either immediately after laser application (3 swine) or six weeks after surgery (3 swine). Cell damage was assessed using liver damage blood biomarkers and histopathology analyses of 41 tissue samples total. The biomarkers were generally normal over a 6 week post-surgicalin vivostudy period. Histopathology revealed no cell death, although additional pathology was present (i.e., hemorrhage, inflammation, fibrosis) due to handling, sample resection, and fibrous adhesions as a result of the laparotomy. These results support a new protocol for studying laser-related liver damage, indicating the potential to raise the safetymore »limit for liver photoacoustic imaging to approximately 150 mJ/cm2with a laser wavelength of 750 nm and for imaging durations up to 10 minutes without causing cell death. This investigation and protocol may be applied to other tissues and extended to additional wavelengths and energies, which is overall promising for introducing new tissue-specific laser safety limits for photoacoustic-guided surgery.

    « less
  3. Coronary artery disease (CAD), or atherosclerosis, is responsible for nearly a third of all American deaths annually. Detection of plaques and differentiation of plaque stage remains a complicating factor for treatment. Classification of plaque before significant blockage or rupture could inform clinical decisions and prevent mortality. Current detection methods are either nonspecific, slow, or require the use of potentially harmful contrast agents. Recent advances in hyperspectral imaging could be used to detect changes in the autofluorescence of arteries associated with vessel remodeling and subsequent plaque formation and could detect and classify existing lesions. Here, we present data comparing spectral image characteristics of a mouse model designed to undergo vessel remodeling. C57Bl/6 mice underwent ligation of three of four caudal branches of the left common carotid artery (left external carotid, internal carotid, and occipital artery) with the superior thyroid artery left intact under IACUC approved protocol. Vessels were harvested at a variety of timepoints to compare degrees of remodeling, including 4 weeks and 5 months post-surgery. Immediately following harvest, vessels were prepared by longitudinal opening to expose the luminal surface to a 20X objective. A custom inverted microscope (TE-2000, Nikon Instruments) with a Xe arc lamp and thin film tunable filtermore »arrary (Versachrome, Semrock, Inc.) were used to achieve spectral imaging. Excitation scans utilized wavelengths between 340 nm and 550 nm in 5 nm increments. Hyperspectral data were generated and analyzed with custom Matlab scripts and visualized in ENVI. Preliminary data suggest consistent spectral features associated with control and remodeled vessels. © (2019) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.« less
  4. Routine blood pressure (BP) measurement in pregnancy is commonly performed using automated oscillometric devices. Since no wireless oscillometric BP device has been validated in preeclamptic populations, a simple approach for capturing readings from such devices is needed, especially in low-resource settings where transmission of BP data from the field to central locations is an important mechanism for triage. To this end, a total of 8192 BP readings were captured from the Liquid Crystal Display (LCD) screen of a standard Omron M7 self-inflating BP cuff using a cellphone camera. A cohort of 49 lay midwives captured these data from 1697 pregnant women carrying singletons between 6 weeks and 40 weeks gestational age in rural Guatemala during routine screening. Images exhibited a wide variability in their appearance due to variations in orientation and parallax; environmental factors such as lighting, shadows; and image acquisition factors such as motion blur and problems with focus. Images were independently labeled for readability and quality by three annotators (BP range: 34–203 mm Hg) and disagreements were resolved. Methods to preprocess and automatically segment the LCD images into diastolic BP, systolic BP and heart rate using a contour-based technique were developed. A deep convolutional neural network was thenmore »trained to convert the LCD images into numerical values using a multi-digit recognition approach. On readable low- and high-quality images, this proposed approach achieved a 91% classification accuracy and mean absolute error of 3.19 mm Hg for systolic BP and 91% accuracy and mean absolute error of 0.94 mm Hg for diastolic BP. These error values are within the FDA guidelines for BP monitoring when poor quality images are excluded. The performance of the proposed approach was shown to be greatly superior to state-of-the-art open-source tools (Tesseract and the Google Vision API). The algorithm was developed such that it could be deployed on a phone and work without connectivity to a network.« less
  5. Diastolic dysfunction is a common pathology occurring in about one third of patients affected by heart failure. This condition may not be associated with a marked decrease in cardiac output or systemic pressure and therefore is more difficult to diagnose than its systolic counterpart. Compromised relaxation or increased stiffness of the left ventricle induces an increase in the upstream pulmonary pressures, and is classified as secondary or group II pulmonary hypertension (2018 Nice classification). This may result in an increase in the right ventricular afterload leading to right ventricular failure. Elevated pulmonary pressures are therefore an important clinical indicator of diastolic heart failure (sometimes referred to as heart failure with preserved ejection fraction, HFpEF), showing significant correlation with associated mortality. However, accurate measurements of this quantity are typically obtained through invasive catheterization and after the onset of symptoms. In this study, we use the hemodynamic consistency of a differential-algebraic circulation model to predict pulmonary pressures in adult patients from other, possibly non-invasive, clinical data. We investigate several aspects of the problem, including the ability of model outputs to represent a sufficiently wide pathologic spectrum, the identifiability of the model's parameters, and the accuracy of the predicted pulmonary pressures. We alsomore »find that a classifier using the assimilated model parameters as features is free from the problem of missing data and is able to detect pulmonary hypertension with sufficiently high accuracy. For a cohort of 82 patients suffering from various degrees of heart failure severity, we show that systolic, diastolic, and wedge pulmonary pressures can be estimated on average within 8, 6, and 6 mmHg, respectively. We also show that, in general, increased data availability leads to improved predictions.« less