Lack of association between cognitive impairment and systemic inflammation in asymptomatic carotid stenosis.

BACKGROUND: Asymptomatic carotid atherosclerotic stenosis (ACAS) is associated with cognitive impairment. Systemic inflammation occurs in patients with systemic atherosclerosis and is also associated with cognitive impairment. The goal of this study was to determine if cognitive impairment in patients with ACAS is the result of systemic inflammation. METHODS: A cross-sectional analysis of 104 patients (63 patients with ACAS, 41 controls) with cognitive function and inflammatory biomarker assessments was performed. Venous blood was assayed for proinflammatory biomarkers (IL-1ß, IL-6, IL-6R, IL-8, IL-17, tumor necrosis factor-α, matrix metalloproteinase [MMP]-1, MMP-2, MMP-7, MMP-9, vascular cell adhesion molecule, and high-sensitivity C-reactive protein). The patients also underwent comprehensive cognitive testing to compute five domain-specific cognitive scores per patient. We first assessed the associations between carotid stenosis and cognitive function, and between carotid stenosis and systemic inflammation in separate regression models. We then determined whether cognitive impairments persisted in patients with carotid stenosis after accounting for inflammation by adjusting for inflammatory biomarker levels in a combined model. RESULTS: Patients with ACAS and control patients differed in age, race, coronary artery disease prevalence, and education. Stenosis patients had worse cognitive scores in two domains: learning and memory (P = .05) and motor and processing speed (P = .002). Despite adjusting for inflammatory biomarker levels, patients with ACAS still demonstrated deficits in the domains of learning and memory and motor and processing speed. CONCLUSIONS: Although systemic atherosclerosis-induced inflammation is a well-recognized cause for cognitive impairment, our data suggest that it is not the primary underlying mechanism behind cognitive impairments seen in ACAS. Cognitive impairments in learning and memory and motor and processing speed seen in patients with ACAS persist after adjusting for systemic inflammation. Thus, alternative mechanisms should be explored to account for the observed functional impairments.

Computed tomography angiographic biomarkers help identify vulnerable carotid artery plaque.

OBJECTIVE: The current risk assessment for patients with carotid atherosclerosis relies primarily on measuring the degree of stenosis. More reliable risk stratification could improve patient selection for targeted treatment. We have developed and validated a model to predict for major adverse neurologic events (MANE; stroke, transient ischemic attack, amaurosis fugax) that incorporates a combination of plaque morphology, patient demographics, and patient clinical information. METHODS: We enrolled 221 patients with asymptomatic carotid stenosis of any severity who had undergone computed tomography angiography at baseline and ≥6 months later. The images were analyzed for carotid plaque morphology (plaque geometry and tissue composition). The data were partitioned into training and validation cohorts. Of the 221 patients, 190 had complete records available and were included in the present analysis. The training cohort was used to develop the best model for predicting MANE, incorporating the patient and plaque features. First, single-variable correlation and unsupervised clustering were performed. Next, several multivariable models were implemented for the response variable of MANE. The best model was selected by optimizing the area under the receiver operating characteristic curve (AUC) and Cohen's kappa statistic. The model was validated using the sequestered data to demonstrate generalizability. RESULTS: A total of 62 patients had experienced a MANE during follow-up. Unsupervised clustering of the patient and plaque features identified single-variable predictors of MANE. Multivariable predictive modeling showed that a combination of the plaque features at baseline (matrix, intraplaque hemorrhage [IPH], wall thickness, plaque burden) with the clinical features (age, body mass index, lipid levels) best predicted for MANE (AUC, 0.79), In contrast, the percent diameter stenosis performed the worst (AUC, 0.55). The strongest single variable for discriminating between patients with and without MANE was IPH, and the most predictive model was produced when IPH was considered with wall remodeling. The selected model also performed well for the validation dataset (AUC, 0.64) and maintained superiority compared with percent diameter stenosis (AUC, 0.49). CONCLUSIONS: A composite of plaque geometry, plaque tissue composition, patient demographics, and clinical information predicted for MANE better than did the traditionally used degree of stenosis alone for those with carotid atherosclerosis. Implementing this predictive model in the clinical setting could help identify patients at high risk of MANE.

Revascularization for asymptomatic carotid artery stenosis improves balance and mobility.

OBJECTIVE: Balance and mobility function worsen with age, more so for those with underlying chronic diseases. We recently found that asymptomatic carotid artery stenosis (ACAS) restricts blood flow to the brain and might also contribute to balance and mobility impairment. In the present study, we tested the hypothesis that ACAS is a modifiable risk factor for balance and mobility impairment. Our goal was to assess the effect of restoring blood flow to the brain by carotid revascularization on the balance and mobility of patients with high-grade ACAS (≥70% diameter-reducing stenosis). METHODS: Twenty adults (age, 67.0 ± 9.4 years) undergoing carotid endarterectomy for high-grade stenosis were enrolled. Balance and mobility assessments were performed before and 6 weeks after revascularization. These included the Short Physical Performance Battery, the Berg Balance Scale, the Four Square Step Test, the Dynamic Gait Index (DGI), the Timed Up and Go test, gait speed, the Mini-Balance Evaluation Systems Test (Mini-BESTest), and the Walking While Talking complex test. RESULTS: Consistent with our previous findings, patients demonstrated reduced scores on the Short Physical Performance Battery, Berg Balance Scale, DGI, and Timed Up and Go test and in gait speed. Depending on the outcome measure, 25% to 90% of the patients had scored in the impaired range at baseline. After surgery, significant improvements were observed in the outcome measures that combined walking with dynamic movements, including the DGI (P = .02) and Mini-BESTest (P = .002). The proportion of patients with Mini-BESTest scores indicating a high fall risk had decreased significantly from 90% (n = 18) at baseline to 40% (n = 8) after surgery (P = .02). We used Pearson's correlations to examine the relationship between balance and mobility before surgery and the change after surgery. Patients with lower baseline DGI and Mini-BESTest scores demonstrated the most improvement after surgery (r = -0.59, P = .006; and r = -0.70, P = .001, respectively). CONCLUSIONS: Carotid revascularization improved patients' balance and mobility, especially for measures that combine walking and dynamic movements. The greatest improvements were observed for the patients who had been most impaired at baseline.

Asymptomatic carotid artery stenosis is associated with cerebral hypoperfusion.

OBJECTIVE: We have shown that almost 50% of patients with asymptomatic carotid stenosis (ACS) will demonstrate cognitive impairment. Recent evidence has suggested that cerebral hypoperfusion is an important cause of cognitive impairment. Carotid stenosis can restrict blood flow to the brain, with consequent cerebral hypoperfusion. In contrast, cross-hemispheric collateral compensation through the Circle of Willis, and cerebrovascular vasodilation can also mitigate the effects of flow restriction. It is, therefore, critical to develop a clinically relevant measure of net brain perfusion in patients with ACS that could help in risk stratification and in determining the appropriate treatment. To determine whether ACS results in cerebral hypoperfusion, we developed a novel approach to quantify interhemispheric cerebral perfusion differences, measured as the time to peak (TTP) and mean transit time (MTT) delays using perfusion-weighted magnetic resonance imaging (PWI) of the whole brain. To evaluate the utility of using clinical duplex ultrasonography (DUS) to infer brain perfusion, we also assessed the relationship between the PWI findings and ultrasound-based peak systolic velocity (PSV). METHODS: Structural and PWI of the brain and magnetic resonance angiography of the carotid arteries were performed in 20 patients with ≥70% ACS. DUS provided the PSV, and magnetic resonance angiography provided plaque geometric measures at the stenosis. Volumetric perfusion maps of the entire brain from PWI were analyzed to obtain the mean interhemispheric differences for the TTP and MTT delays. In addition, the proportion of brain volume that demonstrated a delay in TTP and MTT was also measured. These proportions were measured for increasing severity of perfusion delays (0.5, 1.0, and 2.0 seconds). Finally, perfusion asymmetries on PWI were correlated with the PSV and stenosis features on DUS using Pearson's correlation coefficients. RESULTS: Of the 20 patients, 18 had unilateral stenosis (8 right and 10 left) and 2 had bilateral stenoses. The interhemispheric (left-right) TTP delays measured for the whole brain volume identified impaired perfusion in the hemisphere ipsilateral to the stenosis in 16 of the 18 patients. More than 45% of the patients had had ischemia in at least one half of their brain volume, with a TTP delay >0.5 second. The TTP and MTT delays showed strong correlations with PSV. In contrast, the correlations with the percentage of stenosis were weaker. The correlations for the PSV were strongest with the perfusion deficits (TTP and MTT delays) measured for the whole brain using our proposed algorithm (r = 0.80 and r = 0.74, respectively) rather than when measured on a single magnetic resonance angiography slice as performed in current clinical protocols (r = 0.31 and r = 0.58, respectively). CONCLUSIONS: Interhemispheric TTP and MTT delay measured for the whole brain using PWI has provided a new tool for assessing cerebral perfusion deficits in patients with ACS. Carotid stenosis was associated with a detectable reduction in ipsilateral brain perfusion compared with the opposite hemisphere in >80% of patients. The PSV measured at the carotid stenosis using ultrasonography correlated with TTP and MTT delays and might serve as a clinically useful surrogate to brain hypoperfusion in these patients.

Protein-Coated Aryl Modified Gold Nanoparticles for Cellular Uptake Study by Osteosarcoma Cancer Cells.

Gold nanoparticles coated with proteins have shown extraordinary biocompatibility which advanced to several nanomedicine engineering applications. We synthesized protein-coated gold nanoparticles using green and chemical reduction routes for cellular uptake study. In the current work, we coated gold-aryl nanoparticles of the type AuNPs-C6H4-4-COOH with bovine serum albumin (BSA), collagen, zein, and lysozyme proteins. Both routes were carried out without phase-transfer catalysts or extraneous stabilizing agents. High crystallinity of the AuNPs synthesized by the green route can be seen in transmission electron microscopy images. Osteosarcoma cancer cells are malignant bone tumors with abnormal cellular functions. Studies using MG-63 cells will provide mechanistic suggestions on the details of the amplification in tumors. We studied the cellular uptake of the bioconjugates by MG-63 osteosarcoma cells using laser confocal fluorescence microscopy (LCFM) and flow cytometry. In the LCFM study, BSA-AuNPs were uptaken most efficiently of all protein-coated gold nanoparticles synthesized by the green route. Lysozyme-AuNPs synthesized by the chemical reduction method were mostly efficiently internalized by MG-63 cells among all AuNPs. Zein- and lysozyme-coated AuNPs, though of relatively small size, prepared by the green method were not efficiently uptaken by MG-63. The two nanoparticles are negatively charged, and zein is also a hydrophobic coat. The difference in hydrophobicity and charge might have affected the internalization. All of those coated nanoparticles that were efficiently uptaken can potentially be used as diagnostic and therapeutic agents for osteosarcoma.

Paradoxical effects of the epigenetic modifiers 5-aza-deoxycytidine and suberoylanilide hydroxamic acid on adipogenesis.

Adipogenesis is an important biological process that is linked to obesity and metabolic disorders. On the other hand, fat regeneration is crucial as a restorative approach following mastectomy or severe burn injury. Furthermore, optimizing an in-vitro model of adipogenesis, which would help in understanding the possible effects and/or side effects of fat-soluble drugs and anti-obesity remedies, in addition to the developmental studies. Epigenetic is an important factor that is involved in cellular differentiation and commitment. This study aimed at investigating the effect of DNA methylation and histone deactylases inhibitors, 5-Aza-deoxycytidine (5-Aza-dC) and Suberoylanilide hydroxamic acid (SAHA), on the adipogenic differentiation process. The two modifiers were applied according to our previously published protocol, followed by three cycles of a classical, two-step adipogenesis protocol. The cells pretreated with SAHA showed enhanced expression of the many adipogenic genes, including peroxisome proliferator-activated receptor-γ as well as the accumulation of intracytoplasmic fat as shown by oil red and Nile red staining and the secretion of adipokines, such as MCP-1 and IP-10. On contrary, 5-Aza-dC inhibited all these markers. In conclusion, adding the reported step with SAHA to the differentiation protocols could have an impact on the progress of the in-vitro fat regenerative approach. The possible role of 5-Aza-dC in the inhibition of adipogenesis can be of clinical interest and will need further characterization in the future.

Quantitative assessment of carotid plaque morphology (geometry and tissue composition) using computed tomography angiography.

OBJECTIVE: Quantification of carotid plaque morphology (geometry and tissue composition) may help stratify risk for future stroke and assess plaque progression or regression in response to medical risk factor modification. We assessed the feasibility and reliability of morphologic measurements of carotid plaques using computed tomography angiography (CTA) and determined the minimum detectable change in plaque features by this approach. METHODS: CTA images of both carotid arteries in 50 patients were analyzed by two observers using a semiautomatic image analysis program, yielding 93 observations per user (seven arteries were excluded because of prior stenting). One observer repeated the analyses 4 weeks later. Measurements included total plaque volume; percentage stenosis (by diameter and area); and tissue composition for calcium, lipid-rich necrotic core (LRNC), and intraplaque hemorrhage (IPH). Reliability of measurements was assessed by intraclass and interclass correlation and Bland-Altman plots. Dice similarity coefficient (DSC) and modified Hausdorff distance (MHD) assessed reliability of geometric shape measurements. We additionally computed the minimum amount of change in these features detectable by our approach. RESULTS: The cohort was 51% male (mean age, 70.1 years), and 56% had a prior stroke. The mean (± standard deviation) plaque volume was 837.3 ± 431.3 mm3, stenosis diameter was 44.5% ± 25.6%, and stenosis area was 58.1% ± 29.0%. These measurements showed high reliability. Intraclass correlation coefficients for plaque volume, percentage stenosis by diameter, and percentage stenosis by area were 0.96, 0.87, and 0.83, respectively; interclass correlation coefficients were 0.88, 0.84, and 0.78. Intraclass correlations for tissue composition were 0.99, 0.96, and 0.86 (calcium, LRNC, and IPH, respectively), and interclass correlations were 0.99, 0.92, and 0.92. Shape measurements showed high intraobserver (DSC, 0.95 ± 0.04; MHD, 0.16 ± 0.10 mm) and interobserver (DSC, 0.94 ± 0.05; MHD, 0.19 ± 0.12 mm) luminal agreement. This approach can detect a change of at least 3.9% in total plaque volume, 1.2 mm3 in calcium, 4.3 mm3 in LRNC, and 8.6 mm3 in IPH with the same observer repeating measurements and 9.9% in plaque volume, 1.9 mm3 in calcium, 7.9 mm3 in LRNC, and 6.8 mm3 in IPH for two different observers. CONCLUSIONS: Carotid plaque geometry (total volume, diameter stenosis, and area stenosis) and tissue composition (calcium, LRNC, and IPH) are measured reliably from clinical CTA images using a semiautomatic image analysis program. The minimum change in plaque volume detectable is ∼4% if the same observer makes both measurements and ∼10% for different observers. Small changes in plaque composition can also be detected reliably. This approach can facilitate longitudinal studies for identifying high-risk plaque features and for quantifying plaque progression or regression after treatment.

Noninvasive characterization of carotid plaque strain.

OBJECTIVE: Current risk stratification of internal carotid artery plaques based on diameter-reducing percentage stenosis may be unreliable because ischemic stroke results from plaque disruption with atheroembolization. Biomechanical forces acting on the plaque may render it vulnerable to rupture. The feasibility of ultrasound-based quantification of plaque displacement and strain induced by hemodynamic forces and their relationship to high-risk plaques have not been determined. We studied the feasibility and reliability of carotid plaque strain measurement from clinical B-mode ultrasound images and the relationship of strain to high-risk plaque morphology. METHODS: We analyzed carotid ultrasound B-mode cine loops obtained in patients with asymptomatic ≥50% stenosis during routine clinical scanning. Optical flow methods were used to quantify plaque motion and shear strain during the cardiac cycle. The magnitude (maximum absolute shear strain rate [MASSR]) and variability (entropy of shear strain rate [ESSR] and variance of shear strain rate [VSSR]) of strain were combined into a composite shear strain index (SSI), which was assessed for interscan repeatability and correlated with plaque echolucency. RESULTS: Nineteen patients (mean age, 70 years) constituting 36 plaques underwent imaging; 37% of patients (n = 7) showed high strain (SSI ≥0.5; MASSR, 2.2; ESSR, 39.7; VSSR, 0.03) in their plaques; the remaining clustered into a low-strain group (SSI <0.5; MASSR, 0.58; ESSR, 21.2; VSSR, 0.002). The area of echolucent morphology was greater in high-strain plaques vs low-strain plaques (28% vs 17%; P = .018). Strain measurements showed low variability on Bland-Altman plots with cluster assignment agreement of 76% on repeated scanning. Two patients developed a stroke during 2 years of follow-up; both demonstrated high SSI (≥0.5) at baseline. CONCLUSIONS: Carotid plaque strain is reliably computed from routine B-mode imaging using clinical ultrasound machines. High plaque strain correlates with known high-risk echolucent morphology. Strain measurement can complement identification of patients at high risk for plaque disruption and stroke.

Semiautomatic quantification of carotid plaque volume with three-dimensional ultrasound imaging.

OBJECTIVE: Vessel wall volume (VWV) assessed by three-dimensional duplex ultrasound (3DUS) imaging provides a more comprehensive measure of plaque burden than conventional two-dimensional measures of diameter stenosis. We previously demonstrated that manual outlining of the arterial lumen-intima boundary and outer wall boundary can be performed reliably on images obtained with a commercially available 3D-DUS transducer. Manual segmentation, however, is time consuming (∼45 minutes), limiting its clinical translation. We have developed a semiautomatic algorithm (manual selection of the carotid bifurcation image with subsequent automatic plaque outlining) to outline carotid plaques on 3DUS data sets. In this study, we investigated the accuracy, reproducibility, reliability, and time taken by this algorithm. METHODS: 3DUS data sets from 30 patients with asymptomatic ≥50% carotid stenosis underwent manual outlining of lumen-intima boundary and outer wall boundary to measure VWV. Two observers implemented a semiautomatic segmentation algorithm. The algorithm's accuracy was compared with manual outlining using the Pearson correlation coefficient. The Dice similarity coefficient (DSC) and modified-Hausdorff distance (MHD) were used to quantify the geometric similarity of the outlines. We also compared results after an intermediate stage of the algorithm vs the complete algorithm. Reproducibility and the least amount of detectable change in plaque volume were computed for each method. Intraobserver and interobserver metrics for each method were computed using the intraclass correlation coefficient (ICC), coefficient of variability (CV), minimum detectable change (MDC), and standard error of measurement (SEM) of the VWV. RESULTS: Plaque volume estimates obtained from the semiautomatic algorithm were accurate compared with manual outlining. The Pearson correlation coefficient was 0.76 (P < .001), and measurements were geometrically similar (DSC, 0.85; MHD, 0.48 mm). The algorithm was more reproducible and reliable and could detect smaller changes in plaque volume on repeat imaging (low interobserver variability: ICC, 0.9; CV, 8.22%; MDC, 5.57%; SEM, 1.45%; DSC, 0.88; MHD, 0.43 mm). Intraobserver variability was even lower (ICC, 0.9; CV, 8%; MDC, 3.62%; SEM, 1.31%; DSC, 0.89; MHD, 0.37 mm). Plaque volume estimates at the intermediate stage of the algorithm matched results from the full algorithm (Pearson correlation coefficient, 0.76; DSC, 0.84; MHD, 0.52 mm). The intermediate approach, however, was less reliable than the full algorithm (interobserver: ICC, 0.81; CV, 11.7%; MDC, 9.58%; SEM, 3.46%; DSC, 0.88; MHD, 0.42 mm; intraobserver: ICC, 0.87; CV, 8.6%; MDC, 4.55%; SEM, 1.64%; DSC, 0.89; MHD, 0.38 mm). The full algorithm required ∼14 minutes to implement. However, a quick (7 minutes) and accurate assessment of VWV can be obtained by running only the intermediate stage of the algorithm, although with a loss in repeatability and reliability. CONCLUSIONS: We present a unique algorithm to perform semiautomatic quantification of carotid plaque volume using 3DUS imaging. It is quick (mean time, 14 minutes), accurate, repeatable, and implementable in a clinical environment and in longitudinal studies tracking plaque progression. It reliably detects plaque volume changes as low as 4% to 6% with 95% confidence.

Asymptomatic carotid stenosis is associated with cognitive impairment.

BACKGROUND: Cerebrovascular risk factors (eg, hypertension, coronary artery disease) and stroke can lead to vascular cognitive impairment. The Asymptomatic Carotid Stenosis and Cognitive Function study evaluated the isolated impact of asymptomatic carotid stenosis (no prior ipsilateral or contralateral stroke or transient ischemic attack) on cognitive function. Cerebrovascular hemodynamic and carotid plaque characteristics were analyzed to elucidate potential mechanisms affecting cognition. METHODS: There were 82 patients with ≥50% asymptomatic carotid stenosis and 62 controls without stenosis but matched for vascular comorbidities who underwent neurologic, National Institutes of Health Stroke Scale, and comprehensive neuropsychological examination. Overall cognitive function and five domain-specific scores were computed. Duplex ultrasound with Doppler waveform and B-mode imaging defined the degree of stenosis, least luminal diameter, plaque area, and plaque gray-scale median. Breath-holding index (BHI) and microembolization were measured using transcranial Doppler. We assessed cognitive differences between stenosis patients and control patients and of stenosis patients with low vs high BHI and correlated cognitive function with microembolic counts and plaque characteristics. RESULTS: Stenosis and control patients did not differ in vascular risk factors, education, estimated intelligence, or depressive symptoms. Stenosis patients had worse composite cognitive scores (P = .02; Cohen's d = 0.43) and domain-specific scores for learning/memory (P = .02; d = 0.42) and motor/processing speed (P = .01; d = 0.65), whereas scores for executive function were numerically lower (P = .08). Approximately 49.4% of all stenosis patients were impaired in at least two cognitive domains. Precisely 50% of stenosis patients demonstrated a reduced BHI. Stenosis patients with reduced BHI performed worse on the overall composite cognitive score (t = -2.1; P = .02; d = 0.53) and tests for learning/memory (t = -2.7; P = .01; d = 0.66). Cognitive function did not correlate with measures of plaque burden (degree of stenosis, least luminal diameter, and plaque area) or with plaque gray-scale median. CONCLUSIONS: Asymptomatic carotid stenosis is associated with cognitive impairment independent of known vascular risk factors for vascular cognitive impairment. Approximately 49.4% of these patients demonstrate impairment in at least two neuropsychological domains. The deficit is driven primarily by reduced motor/processing speed and learning/memory and is mild to moderate in severity. The mechanism for impairment is likely to be hemodynamic as evidenced by reduced cerebrovascular reserve and the likely result of hypoperfusion from a pressure drop across the stenosis in the presence of inadequate collateralization.

Disseminated blastomycosis with an intracranial fungoma in an immunocompetent patient: illustrative case.

BACKGROUND: Blastomyces dermatitidis is a fungus endemic to central and southern North America. While infection most commonly results in pneumonia, a small number of infections progress to systemic disease, which may include intracranial lesions. Progression to systemic disease is most common in immunocompromised patients, such as those with human immunodeficiency virus. OBSERVATIONS: The authors present a 44-year-old immunocompetent male who presented following a tonic-clonic seizure. Initial workup revealed a 19-mm enhancing intracranial mass. There was avid uptake of fluorescein sodium, and an en bloc resection of the mass was performed. Histopathology revealed B. dermatitidis. Medical management included amphotericin B and azole therapy. Postoperative recovery was uneventful, and no focal neurological deficits were appreciated. LESSONS: This case highlights the neurosurgical management of a rare intracranial fungal manifestation in an immunocompetent patient. A literature review was also performed to better understand the role of neurosurgery in fungal infections. There were limited cases of intracranial Blastomyces reported in immunocompetent patients, and neurosurgical management varied (no intervention, biopsy, resection) and was underreported. Too few cases are reported to suggest neurosurgical intervention for blastomycosis improves outcomes. Medical management was relatively standard with azole and amphotericin therapy.

Limited-View and Sparse Photoacoustic Tomography for Neuroimaging with Deep Learning.

Photoacoustic tomography (PAT) is a non-ionizing imaging modality capable of acquiring high contrast and resolution images of optical absorption at depths greater than traditional optical imaging techniques. Practical considerations with instrumentation and geometry limit the number of available acoustic sensors and their "view" of the imaging target, which result in image reconstruction artifacts degrading image quality. Iterative reconstruction methods can be used to reduce artifacts but are computationally expensive. In this work, we propose a novel deep learning approach termed pixel-wise deep learning (Pixel-DL) that first employs pixel-wise interpolation governed by the physics of photoacoustic wave propagation and then uses a convolution neural network to reconstruct an image. Simulated photoacoustic data from synthetic, mouse-brain, lung, and fundus vasculature phantoms were used for training and testing. Results demonstrated that Pixel-DL achieved comparable or better performance to iterative methods and consistently outperformed other CNN-based approaches for correcting artifacts. Pixel-DL is a computationally efficient approach that enables for real-time PAT rendering and improved image reconstruction quality for limited-view and sparse PAT.

Fully Dense UNet for 2-D Sparse Photoacoustic Tomography Artifact Removal.

Photoacoustic imaging is an emerging imaging modality that is based upon the photoacoustic effect. In photoacoustic tomography (PAT), the induced acoustic pressure waves are measured by an array of detectors and used to reconstruct an image of the initial pressure distribution. A common challenge faced in PAT is that the measured acoustic waves can only be sparsely sampled. Reconstructing sparsely sampled data using standard methods results in severe artifacts that obscure information within the image. We propose a modified convolutional neural network (CNN) architecture termed fully dense UNet (FD-UNet) for removing artifacts from two-dimensional PAT images reconstructed from sparse data and compare the proposed CNN with the standard UNet in terms of reconstructed image quality.

Assessment of Interhemispheric Cerebral Perfusion Deficit in Carotid Artery Stenosis.

Asymptomatic carotid stenosis patients manifest compromised cognitive performance compared to controls. Cerebral perfusion deficit could be an important contributor to cognitive impairment. The relationship between carotid stenosis and cerebral perfusion deficit is not established. If established, this could lead to a more informed selection of ACS patients likely to benefit from carotid revascularization. Perfusion-weighted MR imaging (PWI) is a clinically viable non-invasive technique to quantify cerebral perfusion. However, its impact is limited due to lack of efficient clinical tools to analyze PWI data in different brain regions for characterizing interhemispheric perfusion asymmetry. Development of automated approaches to characterize clinically relevant perfusion deficits is therefore required. Moreover, there is no established evidence of association between perfusion deficit and stenosis severity. In this paper, we propose an approach to quantify interhemispheric perfusion differences in different brain regions using clinical data. Our proposed metrics, based on the PWI mean transit time, for characterizing difference between ipsilateral and contralateral hemispheres demonstrate a very strong relationship with Doppler ultrasound based peak systolic velocity measured at stenosis. Our approach also highlights dependence of perfusion asymmetry on effective collateralization through the cerebral vasculature. In future studies, we plan to extend this method to a larger cohort and refine the methods for validating novel biomarker for risk-stratification of carotid stenosis.

Sparsity Analysis of a Sonomyographic Muscle-Computer Interface.

OBJECTIVE: Sonomyography has been shown to be a promising method for decoding volitional motor intent from analysis of ultrasound images of the forearm musculature. The objectives of this paper are to determine the optimal location for ultrasound transducer placement on the anterior forearm for imaging maximum muscle deformations during different hand motions, and to investigate the effect of using a sparse set of ultrasound scanlines for motion classification for ultrasound-based muscle-computer interfaces (MCIs). METHODS: The optimal placement of the ultrasound transducer along the forearm was identified using freehand three-dimensional reconstructions of the muscle thickness during rest and motion completion. Based on the ultrasound images acquired from the optimally placed transducer, classification accuracy with equally spaced scanlines across the cross-sectional field of view was determined. Furthermore, the unique contribution of each scanline to class discrimination using Fisher criterion (FC) and mutual information (MI) with respect to motion discriminability was determined. RESULTS: Experiments with five able-bodied subjects show that the maximum muscle deformation occurred between 40%-50% of the forearm length for multiple degrees-of-freedom. The average classification accuracy was 94% ± 6% with the entire 128-scanline image and 94% ± 5% with four equally spaced scanlines. However, no significant improvement in classification accuracy was observed with optimal scanline selection using FC and MI. CONCLUSION: For an optimally placed transducer, a small subset of ultrasound scanlines can be used instead of a full imaging array without sacrificing performance in terms of classification accuracy for multiple degrees-of-freedom. SIGNIFICANCE: The selection of a small subset of transducer elements can enable the reduction of computation, and simplification of the instrumentation and power consumption of wearable sonomyographic MCIs, particularly for rehabilitation and gesture recognition applications.

National Trends in General Surgery Resident Exposure to Complex Oncology-Relevant Cases.

OBJECTIVE: To evaluate trends in surgical resident exposure to complex oncologic procedures in order to determine whether additional fellowship training is necessary. DESIGN: An observational study of national Accreditation Council for Graduate Medical Education case log statistical reports was conducted to determine the average number of cases for selected oncology-relevant procedures completed during training. Linear regression and Cusick trend tests were used to assess temporal trends with the null hypothesis assuming an estimated slope of zero. Instrumental variable estimation was used to study the effect of duty-hour restrictions on oncologic cases per year. SETTING: United States general surgery residency training programs. PARTICIPANTS: Graduating surgical residents completing their training between 2000 and 2016. RESULTS: Across the study interval, mean case volume was 950.6 ± 29.7 (standard deviation) cases with 38.9 ± 3.1 complex oncologic cases per graduating resident. Decreasing trends were noted for average exposure to lymphadenectomies (-7.8 cases/decade; 95% confidence interval [CI] -8.8 to -6.8) and low rectal procedures (-0.9 cases/decade; 95% CI -1.2 to -0.6). There was no clinically important change in complex soft-tissue resections and foregut cases. A significant increase was seen in number of hepatopancreaticobiliary procedures (+3.9 cases/decade; 95% CI 3.1-4.7). Using instrumental variable estimation, there was a modest decline in cancer-relevant cases by 5.0 cases/decade (95% CI 4.5-5.6), while there was an increase in 38.5 total cases/decade (95% CI 10.4-66.7) associated with duty-hour restrictions. CONCLUSIONS: Case numbers for several complex oncologic procedures remain low, justifying a need for further fellowship training depending on individual resident experience.

Clinical viability of carotid plaque strain estimation using B-mode ultrasound image sequences.

It is estimated that approximately 30% of ischemic strokes are caused by rupture of plaque in the carotid artery. Development of techniques focusing on identifying plaques that are vulnerable to rupture is thus indispensable for stroke prevention. Recent studies have demonstrated that motion analysis of plaques from B-mode and RF ultrasound (US) image sequences can be used to estimate plaque strain. However, viability of these methods in a clinical setting, with variable acquisition protocols, has not been demonstrated yet. In this paper, we explore the viability of estimating plaque strain from B-mode US images of asymptomatic patients, acquired in a real clinical setting with different acquisition settings, frame rates, and operators. Our proposed strain measures, shear strain rate entropy and variance, combined with the recently reported maximum absolute shear strain rate, show that the plaques fall into two distinct clusters. Moreover, these clusters show good correlations with plaque echolucency and echogenicity. We conclude that B-mode US imaging is a viable tool for characterizing plaque dynamics in clinical environments. In future studies, we plan to implement this method on multi-center studies for longitudinal monitoring of plaque.

Gender differences in the symptoms of major depression in opposite-sex dizygotic twin pairs.

OBJECTIVE: Gender differences in the symptoms of major depression have received limited research attention. The aim of this study was to explore these differences in male-female twin pairs. METHOD: Telephone interviews were conducted to determine the lifetime history of major depression in 1,404 complete pairs of opposite-sex dizygotic twins identified through a population-based registry. From these, the authors selected 201 pairs in which both twins fulfilled the DSM-III-R criteria for lifetime major depression. Dichotomous symptom variables were analyzed by using McNemar's chi-square. For continuous variables, conditional logistic regression was used. RESULTS: Female twins reported experiencing significantly more fatigue, hypersomnia, and psychomotor retardation during the most severe major depressive episode, whereas male twins reported more insomnia and agitation. CONCLUSIONS: In this group of matched twins, gender differences in the symptoms of major depression were seen in the areas of sleep, psychomotor changes, and fatigue. Gender significantly modifies some clinical features of major depression.

Personality and comorbidity of common psychiatric disorders.

BACKGROUND: We know little about the degree to which comorbidity, socommonly seen among psychiatric disorders, arises from variation in normal personality. AIMS: To study the degree to which variation in normal personality accounts for the comorbidity of eight common psychiatric and substance use disorders. METHOD: Internalising disorders (major depression, generalised anxiety and panic disorders, phobias), externalising disorders (alcohol and drug dependence, antisocial personality and conduct disorders) and personality dimensions of neuroticism, extraversion and novelty seeking were assessed in 7588 participants from a population-based twin registry. The proportion of comorbidity explained by each personality dimension was calculated using structural equation modelling. RESULTS: Neuroticism accounted for the highest proportion of comorbidity within internalising disorders (20-45%) and between internalising and externalising disorders (19-88%). Variation in neuroticism and novelty seeking each accounted for a modest proportion (10-12% and 7-14%, respectively) of the comorbidity within externalising disorders. Extraversion contributed negligibly. CONCLUSIONS: High neuroticism appears to be a broad vulnerability factor for comorbid psychiatric disorders. Novelty seeking is modestly important for comorbid externalising disorders.