Methods in 'Stroke Prevention in the Wisconsin Native American Population'.

Native American individuals are more frequently affected by cerebrovascular diseases including stroke and vascular cognitive decline. The aim of this study is to determine stroke risk factors that are most prevalent in Wisconsin Native Americans and to examine how education at the community and individual level as well as intensive health wellness coaching may influence modification of stroke risk factors. Additionally, we will investigate the role novel stroke biomarkers may play in stroke risk in this population. This paper details the aims and methods employed in the "Stroke Prevention in the Wisconsin Native American Population" (clinicaltrials.gov identifier: NCT04382963) study including participant health assessments, clinical ultrasound exam of the carotid arteries, cognitive testing battery and structure and execution of the coaching program.

Transcranial Color-Coded Doppler Cerebral Hemodynamics Following Aerobic Exercise Training: Outcomes From a Pilot Randomized Clinical Trial.

Introduction: An active lifestyle with regular exercise is thought to decrease or delay the onset of Alzheimer dementia through increasing blood flow to the brain. We examined the mean flow velocity (MFV) and pulsatility index (PI) in the middle cerebral arteries of individuals randomized into two groups-a Usual Physical Activity (UPA) group and an Enhanced Physical Activity (EPA) exercise intervention group-to determine if exercise training is related to changes in cerebral blood flow. Methods: We examined 23 participants, randomized into a UPA group (n=12) and an EPA group (n=11), with transcranial color-coded Doppler (TCCD) and cardiorespiratory fitness (VO2peak, mL/kg/min) testing at baseline and following a 26-week intervention. TCCD was used to measure MFV and PI. Participants in the EPA group completed supervised aerobic exercise training for 26 weeks. Kendall's tau b correlation was used to examine relationships between variables. The Wilcoxon Rank Sum tests were used to examine changes between the UPA and EPA groups. Results: There was no significant change in MFV or PI in the UPA group or the EPA group (p-values >0.05) between baseline and 26 weeks; the change between the UPA and EPA groups was also not significant (p=0.603). There was no evidence of an association between change in VO2peak and change in MFV or PI (all p-values >0.05). Participants in the EPA group significantly increased their VO2peak compared to the UPA group (p=0.027). Conclusion: This study did not demonstrate evidence of a significant change in the MFV in the middle cerebral arteries or evidence of a significant change in the PI between UPA and EPA groups. Future studies should be performed in larger cohorts and should consider use of personalized exercise programs to maximize understanding of how cerebrovascular hemodynamics change in structure and function with exercise for adults at risk for Alzheimer dementia.

Effects of ultrasound technology advances on measurement of carotid intima-media thickness: A review.

In this review, we describe how technological advances in ultrasound imaging related to transducer construction and image processing fundamentally alter generation of ultrasound images to produce better quality images with higher resolution. However, carotid intima-media thickness (IMT) measurements made from images acquired on modern ultrasound systems are not comparable to historical population nomograms that were used to determine wall thickness thresholds that inform atherosclerotic cardiovascular disease risk. Because it is nearly impossible to replicate instrumentation settings that were used to create the reference carotid IMT nomograms and to place an individual's carotid IMT value in or above a clinically relevant percentile, carotid IMT measurements have a very limited role in clinical medicine, but remain a useful research tool when instrumentation, presets, image acquisition, and measurements can be standardized. In addition to new validation studies, it would be useful for the ultrasound imaging community to reach a consensus regarding technical aspects of ultrasound imaging acquisition, processing, and display for blood vessels so standard presets and imaging approaches could reliably yield the same measurements.

Carotid Plaque Strain Indices Were Correlated With Cognitive Performance in a Cohort With Advanced Atherosclerosis, and Traditional Doppler Measures Showed no Association.

OBJECTIVES: Traditional Doppler measures have been used to predict cognitive performance in patients with carotid atherosclerosis. Novel measures, such as carotid plaque strain indices (CPSIs), have shown associations with cognitive performance. We hypothesized that lower mean middle cerebral artery (MCA) velocities, higher bulb-internal carotid artery (ICA) velocities, the MCA pulsatility index (PI), and CPSIs would be associated with poorer cognitive performance in individuals with advanced atherosclerosis. METHODS: Neurocognitive testing, carotid ultrasound imaging, transcranial Doppler imaging, and carotid strain imaging were performed on 40 patients scheduled for carotid endarterectomy. Kendall tau correlations were used to examine relationships between cognitive tests and the surgical-side maximum peak systolic velocity (PSV; from the bulb, proximal, mid, or distal ICA), mean MCA velocity and PI, and maximum CPSIs (axial, lateral, and shear strain indices used to characterize plaque deformations with arterial pulsation). Cognitive measures included age-adjusted indices of verbal fluency, verbal and visual learning/memory, psychomotor speed, auditory attention/working memory, visuospatial construction, and mental flexibility. RESULTS: Participants had a median age of 71.0 (interquartile range, 9.75) years; 26 were male (65%), and 14 were female (35%). Traditional Doppler parameters, PSV, mean MCA velocity, and MCA PI did not predict cognitive performance (all P > .05). Maximum CPSIs were significantly associated with cognitive performance (P < .05). CONCLUSIONS: Traditional velocity measurements of the maximum bulb-ICA PSV, mean MCA velocity, and PI were not associated with cognitive performance in patients with advanced atherosclerotic disease; however, maximum CPSIs were associated with cognitive performance. These findings suggest that cognition may be associated with unstable plaque rather than blood flow.

Deep Learning for Carotid Plaque Segmentation using a Dilated U-Net Architecture.

Carotid plaque segmentation in ultrasound longitudinal B-mode images using deep learning is presented in this work. We report on 101 severely stenotic carotid plaque patients. A standard U-Net is compared with a dilated U-Net architecture in which the dilated convolution layers were used in the bottleneck. Both a fully automatic and a semi-automatic approach with a bounding box was implemented. The performance degradation in plaque segmentation due to errors in the bounding box is quantified. We found that the bounding box significantly improved the performance of the networks with U-Net Dice coefficients of 0.48 for automatic and 0.83 for semi-automatic segmentation of plaque. Similar results were also obtained for the dilated U-Net with Dice coefficients of 0.55 for automatic and 0.84 for semi-automatic when compared to manual segmentations of the same plaque by an experienced sonographer. A 5% error in the bounding box in both dimensions reduced the Dice coefficient to 0.79 and 0.80 for U-Net and dilated U-Net respectively.

Brachial Artery Echogenicity and Grayscale Texture Changes in HIV-Infected Individuals Receiving Low-Dose Methotrexate.

Objective- We evaluated the biological effects of low-dose methotrexate on 3 novel brachial artery grayscale ultrasound measures that may indicate subclinical arterial injury. Approach and Results- Exploratory analysis from a clinical trial of people with HIV infection at increased cardiovascular disease risk who were randomly assigned to low-dose methotrexate (target dose 15 mg/wk) or placebo. Brachial artery ultrasound grayscale median, gray level difference statistic texture-contrast (GLDS-CON), and gray level texture entropy were measured at baseline and after 24 weeks of intervention. Findings from the intention-to-treat (N=148) and adequately-dosed (N=118) populations were consistent, so the adequately-dosed population results are presented. Participants were a median (Q1, Q3) age of 54 (50, 60) years. After 24 weeks, the low-dose methotrexate intervention was associated with a 25.4% (-18.1, 58.6; P=0.007) increase in GLDS-CON compared with 1.3% (-29.1, 44.7; P=0.97) with placebo ( P=0.05) and a 0.10 u (-0.06, 0.23; P=0.026) increase in entropy compared with 0.02 u (-0.11, 0.14; P=0.54) with placebo ( P=0.14). At week 24, changes in CD4+ T cells correlated inversely with changes in GLDS-CON (ρ=-0.20; P=0.031), and entropy (ρ=-0.21; P=0.023). Changes in D-dimer levels, but no other inflammatory biomarkers, also correlated inversely with changes in GLDS-CON (ρ=-0.23; P=0.014) and entropy (ρ=-0.26; P=0.005). Conclusions- Brachial artery GLDS-CON and entropy increased after 24 weeks of low-dose methotrexate, though the latter was not significantly different from placebo. Grayscale changes were associated with decreases in CD4+ T-cell and D-dimer concentrations and may indicate favorable arterial structure changes.

Changes in carotid artery structure with smoking cessation.

Carotid artery grayscale ultrasound echogenicity and texture features predict cardiovascular disease events. We evaluated the longitudinal effects of smoking cessation on four grayscale ultrasound measures. This was a secondary analysis of data from 188 age, sex, and body mass index (BMI)-matched smokers (94 eventual abstainers [EA], 94 continued smokers [CS]) from a smoking cessation trial that had carotid ultrasound examinations at baseline and after 3 years. General linear models that included time, smoking group (EA or CS), and a time*smoking interaction term were used to examine the impact of smoking abstinence on carotid artery grayscale marker values at year 3. Participants were mean (SD) 50.3 (11.4) years old (57% female, 86% white). The baseline grayscale median value (GSM) was inversely correlated with age, BMI, insulin resistance, and smoking pack-years (r = -0.20 to -0.30, p < 0.007 for all). There was a significant time*smoking status interaction for predicting GSM at year 3: GSM decreased significantly in the EA group compared to the CS group (-3.63 [13.00] vs CS 0.39 [12.06] units; p = 0.029). BMI increased more in the EA than the CS group (2.42 [3.00] vs CS 0.35 [2.57] kg/m2; p < 0.001). After adjusting for changes in BMI, the time*smoking status interaction no longer was significant (p = 0.138). From baseline to year 3, contrast increased similarly in both groups. Entropy and angular second moment did not change significantly in either group. Changes in carotid ultrasound echogenicity and grayscale texture features during a smoking cessation attempt are modest and mostly related to weight gain. Clinicaltrials.gov Identifier: NCT01553084.

Brachial artery intima-media thickness and grayscale texture changes in patients with peripheral artery disease receiving supervised exercise training in the PROPEL randomized clinical trial.

We performed an exploratory analysis to evaluate the effects of a treadmill exercise program on brachial artery (BA) intima-media thickness (IMT) and three BA grayscale ultrasound measures that may indicate subclinical arterial injury. Data were from a clinical trial in individuals with peripheral artery disease who were randomly assigned to treadmill exercise training or attention control. B-mode ultrasonography was performed at baseline and after 26 weeks. BA IMT, grayscale median (GSM), entropy, and gray-level difference statistic-contrast (GLDS-CON) were measured by a single reader. The 184 participants were (mean (SD)) 66.7 (8.2) years old and had an ankle-brachial index of 0.70 (0.18). Exercise training was associated with a 0.01 (0.06) mm ( p = 0.025) reduction in BA IMT compared to 0.00 (0.05) mm ( p = 0.807) in the control group (between-group p = 0.061). BA GSM, entropy, and GLDS-CON did not change significantly with exercise. Improvements in the 6-minute walk distance correlated with increases in resting BA blood flow ( r = 0.23, p = 0.032), flow-mediated dilation ( r = 0.24, p = 0.022), diameter ( r = 0.29, p = 0.005), entropy ( r = 0.21, p = 0.047), and GLDS-CON ( r = 0.22, p = 0.041). In a post hoc analysis, BA IMT improved significantly with treadmill exercise training but did not change with attention control; however, the between-group difference did not reach statistical significance. With exercise, improvements in the 6-minute walk distance were associated with improved endothelial function, increased resting blood flow, and BA dilation, as well as higher grayscale entropy and GLDS-CON, indicating that lower extremity exercise is associated with salutary changes in upper-extremity arterial wall structure and function. ClinicalTrials.gov Identifier: NCT01408901.

Carotid artery displacement and cardiovascular disease risk in the Multi-Ethnic Study of Atherosclerosis.

Novel technology permits quantification of common carotid artery (CCA) displacement, which is traditionally ignored. We evaluated associations with CCA displacement and cardiovascular disease (CVD) risk and events in a large, multi-ethnic cohort. Right CCA longitudinal displacement (LD), transverse displacement (TD), and grayscale median (GSM) were evaluated using ultrasound speckle-tracking and texture analysis software in 2050 participants. Regression analyses were used to define relationships between CCA LD, TD, GSM, and CVD risk factors. Cox proportional hazards models were used to assess relationships between LD, TD, and incident CVD events. Participants were mean (SD) 64 (10) years old. There were 791 cases with a CVD event over a 12-year median follow-up. The mean LD was 0.29 (0.20) mm. In multivariable models including age, sex, race/ethnicity, heart rate, and CVD risk factors, LD was associated positively with active smoking (ß = 0.08, p < 0.001) and inversely with black (ß = -0.08, p < 0.001), Chinese (ß = -0.05, p < 0.001), and Hispanic (ß = -0.04, p < 0.05) race/ethnicities relative to white individuals, heart rate (ß = -0.03/10 beats/min, p < 0.001), and diastolic blood pressure (ß = -0.01/5 mmHg, p < 0.05). In fully adjusted models, LD and TD were associated with GSM (p < 0.01), but neither predicted incident CVD events (LD: hazard ratio (HR) 0.77 [0.48 to 1.24], p = 0.3; TD: HR 1.12 [0.8 to 1.57], p = 0.5). CCA LD and TD are associated with race/ethnicity and CVD risk factors but not incident CVD events. LD and TD are not measures of arterial stiffness but their association with GSM suggests that lower LD and TD may be related to structural changes within the carotid arterial wall.

Influence of Ultrasound System and Gain on Grayscale Median Values.

OBJECTIVES: The purpose of this study was to determine the reliability of grayscale median (GSM) measurements across different ultrasound (US) systems and effects of gain on GSM values. METHODS: Two vessels in a grayscale vascular phantom were imaged with 7 US systems at 3 gain settings. Two human participants were imaged at 3 gain settings. Each image was normalized, standardized, and segmented by expert and novice readers using grayscale analysis software. The concordance correlation coefficient (CCC) assessed agreement of GSM values for each system across gain settings and vessels and between readers. The intraclass correlation coefficient (ICC) assessed system-level reader concordance across gain settings and vessels. A general linear mixed model for repeated measures was used to assess within- and between-system mean GSM values. RESULTS: Grayscale median measurements performed on images from the same US system yielded excellent (CCC) (95% confidence intervals): 0.85 (0.75, 0.92) to 0.96 (0.92, 0.98). ICC per system were 0.94 to 0.98 for the expert reader and 0.85 to 0.95 for the novice reader. Gain adjustments above and below an optimal setting contributed to significantly different intrasystem GSM values on 4 of 7 systems in the near zone and 5 of 7 systems in the far zone (P < .05). Intersystem GSM values differed on 5 of 7 systems (P < .05). Images from the human participants showed differences in GSM values at optimum gain values ± 10 dB/%. CONCLUSIONS: Grayscale median measurements are highly reproducible when obtained from the same US system with similar gain settings. Grayscale median values differ significantly across gain values and between systems. Researchers should consider the impact of US system and gain settings on GSM values when working to minimize system- and operator-dependent factors.

Lagrangian carotid strain imaging indices normalized to blood pressure for vulnerable plaque.

OBJECTIVE: Ultrasound Lagrangian carotid strain imaging (LCSI) utilizes physiological deformation caused by arterial pressure variations to generate strain tensor maps of the vessel walls and plaques. LCSI has been criticized for the lack of normalization of magnitude-based strain indices to physiological stimuli, namely blood pressure. We evaluated the impact of normalization of magnitude-based strain indices to blood pressure measured immediately after the acquisition of radiofrequency (RF) data loops for LCSI. MATERIALS AND METHODS: A complete clinical ultrasound examination along with RF data loops for LCSI was performed on 50 patients (30 males and 20 females) who presented with >60% carotid stenosis and were scheduled for carotid endarterectomy. Cognition was assessed using the 60-minute neuropsychological test protocol. RESULTS: For axial strains correlation of maximum accumulated strain indices (MASI), cognition scores were -0.46 for non-normalized and -0.45, -0.49, -0.37, and -0.48 for systolic, diastolic, pulse pressure, and mean arterial pressure normalized data, respectively. The corresponding area under the curve (AUC) values for classifiers designed using maximum likelihood estimation of a binormal distribution with a median-split of the executive function cognition scores were 0.73, 0.70, 0.71, 0.70, and 0.71, respectively. CONCLUSIONS: No significant differences in the AUC estimates were obtained between normalized and non-normalized magnitude-based strain indices.

Echogenicity of the carotid arterial wall in active smokers.

This pilot study evaluated associations between carotid wall echogenicity, cardiovascular disease (CVD) risk factors, and three markers of smoking heaviness in a cohort of active smokers. Common carotid artery (CCA) grayscale median (GSM) values were measured from sonographic images. Univariable correlations and exploratory multivariable models were used to determine associations between CCA GSM, CVD risk factors, and measures of smoking heaviness. CCA GSM was measured in 162 smokers and was correlated inversely with cigarettes smoked/day (r=-0.16, p=0.048), pack-years (r=-0.204, p=0.009), CVD risk factors such as age, male sex, waist circumference, and low-density lipoprotein cholesterol (all p≤0.03) and positively with high-density lipoprotein cholesterol (p<0.001). Associations between CCA GSM and smoking heaviness markers were not statistically significant after adjustment for traditional risk factors. The results from this pilot study demonstrate the feasibility of measuring the GSM value of the CCA far wall and its association with measures of smoking heaviness and traditional CVD risk factors among current smokers.

Assessing an isiZulu questionnaire with educators in primary schools in Pietermaritzburg to establish a baseline of knowledge of Autism Spectrum Disorder.

BACKGROUND: Autism Spectrum Disorder (ASD) is a significant childhood disorder and has a growing prevalence rate across the world. It has been identified in children from a wide range of racial groups, ethnicities and socio-economic groups, making it a globally relevant disorder. However, a lack of research on ASD in Africa makes it difficult to determine the prevalence rate, presentation and level of knowledge regarding the disorder locally. Therefore, assessing knowledge of ASD amongst professionals is a useful starting point for research in countries where research on ASD is limited. Educators in particular are a vital resource due to the likelihood of their early identification of developmental delays in children of school going age. Awareness studies reveal that professionals have poor awareness of ASD and therefore what educators in South Africa know about ASD needs to be established. METHODS: This study translated the Knowledge about Childhood Autism among Health Workers (KCAHW) questionnaire that was originally designed by Bakare and colleagues (Clinical Practice and Epidemiology in Mental Health 4:17, 2008). The isiZulu KCAHW questionnaire was then used to investigate the level of knowledge of ASD amongst educators in Edendale, Pietermaritzburg, South Africa. Fifty (50) educators consented to complete the questionnaire and the data was analysed using the statistical programme SPSS. RESULTS: The results suggested that educators have an adequate baseline knowledge of ASD but their knowledge was found to be lacking in specific detail. The mean total score for the educator sample was 13.08 (out of a possible 19) which suggested that educators in Edendale, Pietermaritzburg knew 68% of the symptoms covered in the questionnaire. CONCLUSIONS: The isiZulu KCAHW questionnaire appears to be a useful measure for use in the South African context. It provided significant information regarding educator knowledge of ASD in Edendale, Pietermaritzburg. However, the analysis also showed that whilst the educators had an adequate general knowledge of ASD, they lacked specific insight into the disorder, particularly with regards to etiology and age of onset. Furthermore, the results showed that there is an opportunity for further research and interventions to develop knowledge of ASD within the local context in South Africa.

The search for a timely diagnosis: parents' experiences of their child being diagnosed with an Autistic Spectrum Disorder.

OBJECTIVE: This study aimed to describe the experiences of a group of South African parents whose children had received Autistic Spectrum Disorder (ASD) diagnoses. METHOD: A qualitative approach involving semi-structured interviews with a sample of eight parents (seven mothers and one father) of ASD children was used. RESULTS: These interviews highlighted key issues in the area of ASD in South Africa, including: a lack of knowledge amongst professionals, an unwillingness to diagnose, and lack of available support and facilities. Many of the parents in the sample reported significant difficulties in obtaining an ASD diagnosis. These findings are discussed in the light of the importance of early intervention in South Africa. CONCLUSIONS: Practitioners appear to be reluctant to diagnose and label children with ASD at an early age. This reluctance results in lost opportunities for early intervention and years of uncertainty and distress for families. Access to resources for diagnosis and intervention for children with ASD in South Africa appears to be limited to a few families. For this select population, many difficulties and much dissatisfaction with diagnostic processes remain. The study recommends enhancing awareness of ASD to facilitate early identification, and to strengthen the support offered to parents of children with ASD.

Lumen segmentation using a Mask R-CNN in carotid arteries with stenotic atherosclerotic plaque.

In patients at high risk for ischemic stroke, clinical carotid ultrasound is often used to grade stenosis, determine plaque burden and assess stroke risk. Analysis currently requires a trained sonographer to manually identify vessel and plaque regions, which is time and labor intensive. We present a method for automatically determining bounding boxes and lumen segmentation using a Mask R-CNN network trained on sonographer assisted ground-truth carotid lumen segmentations. Automatic lumen segmentation also lays the groundwork for developing methods for accurate plaque segmentation, and wall thickness measurements in cases with no plaque. Different training schemes are used to identify the Mask R-CNN model with the highest accuracy. Utilizing a single-channel B-mode training input, our model produces a mean bounding box intersection over union (IoU) of 0.81 and a mean lumen segmentation IoU of 0.75. However, we encountered errors in prediction when the jugular vein is the most prominently visualized vessel in the B-mode image. This was due to the fact that our dataset has limited instances of B-mode images with both the jugular vein and carotid artery where the vein is dominantly visualized. Additional training datasets are anticipated to mitigate this issue.

Sexual dimorphism during integrative endocrine and immune responses to ionizing radiation in mice.

Exposure to cosmic ionizing radiation is an innate risk of the spaceflight environment that can cause DNA damage and altered cellular function. In astronauts, longitudinal monitoring of physiological systems and interactions between these systems are important to consider for mitigation strategies. In addition, assessments of sex-specific biological responses in the unique environment of spaceflight are vital to support future exploration missions that include both females and males. Here we assessed sex-specific, multi-system immune and endocrine responses to simulated cosmic radiation. For this, 24-week-old, male and female C57Bl/6J mice were exposed to simplified five-ion, space-relevant galactic cosmic ray (GCRsim) radiation at 15 and 50 cGy, to simulate predicted radiation exposures that would be experienced during lunar and Martian missions, respectively. Blood and adrenal tissues were collected at 3- and 14-days post-irradiation for analysis of immune and endocrine biosignatures and pathways. Sexually dimorphic adrenal gland weights and morphology, differential total RNA expression with corresponding gene ontology, and unique immune phenotypes were altered by GCRsim. In brief, this study offers new insights into sexually dimorphic immune and endocrine kinetics following simulated cosmic radiation exposure and highlights the necessity for personalized translational approaches for astronauts during exploration missions.

The Impact of Microgravity on Immunological States.

As we explore other planetary bodies, astronauts will face unique environmental and physiological challenges. The human immune system has evolved under Earth's gravitational force. Consequently, in the microgravity environment of space, immune function is altered. This can pose problematic consequences for astronauts on deep space missions where medical intervention will be limited. Studying the unique environment of microgravity has its challenges, yet current research has uncovered immunological states that are probable during exploration missions. As microgravity-induced immune states are uncovered, novel countermeasure developments and personalized mitigation programs can be designed to improve astronaut health. This can also benefit immune-related monitoring programs for disorders on Earth. This is a comprehensive review, including gaps in knowledge, of simulated and spaceflight microgravity studies in human and rodent models.

In Vivo Adaptive Bayesian Regularized Lagrangian Carotid Strain Imaging for Murine Carotid Arteries and Its Associations With Histological Findings.

OBJECTIVES: Non-invasive methods for monitoring arterial health and identifying early injury to optimize treatment for patients are desirable. The objective of this study was to demonstrate the use of an adaptive Bayesian regularized Lagrangian carotid strain imaging (ABR-LCSI) algorithm for monitoring of atherogenesis in a murine model and examine associations between the ultrasound strain measures and histology. METHODS: Ultrasound radiofrequency (RF) data were acquired from both the right and left common carotid artery (CCA) of 10 (5 male and 5 female) ApoE tm1Unc/J mice at 6, 16 and 24 wk. Lagrangian accumulated axial, lateral and shear strain images and three strain indices-maximum accumulated strain index (MASI), peak mean strain of full region of interest (ROI) index (PMSRI) and strain at peak axial displacement index (SPADI)-were estimated using the ABR-LCSI algorithm. Mice were euthanized (n = 2 at 6 and 16 wk, n = 6 at 24 wk) for histology examination. RESULTS: Sex-specific differences in strain indices of mice at 6, 16 and 24 wk were observed. For male mice, axial PMSRI and SPADI changed significantly from 6 to 24 wk (mean axial PMSRI at 6 wk = 14.10 ± 5.33% and that at 24 wk = -3.03 ± 5.61%, p < 0.001). For female mice, lateral MASI increased significantly from 6 to 24 wk (mean lateral MASI at 6 wk = 10.26 ± 3.13% and that at 24 wk = 16.42 ± 7.15%, p = 0.048). Both cohorts exhibited strong associations with ex vivo histological findings (male mice: correlation between number of elastin fibers and axial PMSRI: rs = 0.83, p = 0.01; female mice: correlation between shear MASI and plaque score: rs = 0.77, p = 0.009). CONCLUSION: The results indicate that ABR-LCSI can be used to measure arterial wall strain in a murine model and that changes in strain are associated with changes in arterial wall structure and plaque formation.

Changes in carotid artery texture by ultrasound and elastin features in a murine model.

Objective: In humans, arterial grayscale ultrasound texture features independently predict adverse cardiovascular disease (CVD) events and change with medical interventions. We performed this study to examine how grayscale ultrasound texture features and elastin fibers change in plaque-free segments of the arterial wall in a murine model prone to atherosclerosis. Methods: A total of 10 Apoetm1Unc/J mice (n = 5 male, n = 5 female) were imaged at 6, 16, and 24 weeks of age. Two mice were euthanized at 6 and 16 weeks and the remaining mice at 24 weeks. Texture features were extracted from the ultrasound images of the distal 1.0 mm of the common carotid artery wall, and elastin measures were extracted from histology images. Two-way analysis of variance was used to evaluate associations between week, sex, and grayscale texture features. Texture feature and elastin number comparisons between weeks were conducted using the sex-by-week two-way interaction contrasts. Sex-specific correlations between the number of elastin fibers and grayscale texture features were analyzed by conducting non-parametric Spearman's rank correlation analyses. Results: Arterial wall homogeneity changed significantly in male mice from 6 to 24 weeks, with a mean (SD) of 0.14 (0.03) units at 6 weeks and 0.18 (0.03) units at 24 weeks (p = 0.026). Spatial gray level dependence matrices-homogeneity (SGLD-HOM) also correlated with carotid artery plaque score (rs = 0.707, p = 0.033). Elastin fibers in the region of interest decreased from 6 to 24 weeks for both male and female mice, although only significantly in male mice. The mean (SD) number of elastin fibers for male mice was 5.32 (1.50) at 6 weeks and 3.59 (0.38) at 24 weeks (p = 0.023). For female mice, the mean (SD) number of elastin fibers was 3.98 (0.38) at 6 weeks and 3.46 (0.19) at 24 weeks (p = 0.051). Conclusion: Grayscale ultrasound texture features that are associated with increased risk for CVD events in humans were used in a murine model, and the grayscale texture feature SGLD-HOM was shown to change in male mice from 6 weeks to 24 weeks. Structural alterations of the arterial wall (change in elastin fiber number) were observed during this time and may differ by sex.