Histopathological dimensions differ between aganglionic and ganglionic bowel wall in children with Hirschsprung's disease.

BACKGROUND: In the validation of new imaging technology for children with Hirschsprung's disease (HSCR), basic anatomical parameters of the bowel wall must be established specifically for this patient group. AIM: To explore differences in histoanatomical layers of bowel wall, comparing ganglionic and aganglionic bowel walls, and to examine if the bowel wall thickness is linked to patient weight. METHODS: This was an observational study of bowel specimens from children weighing 0-10 kg, operated on consecutively during 2018-2020. Ganglionic and aganglionic bowel walls were measured in digitalized microscopy images from 10 sites per trans-sectional specimen and compared regarding the thickness of their histoanatomical layers. RESULTS: Bowel walls were measured in 21 children. Full bowel wall thickness did not differ between aganglionic and ganglionic bowel (2.20 vs 2.04; p = 0.802) while weight at surgery correlated positively with both ganglionic and aganglionic bowel wall thickness (r = 0.688 and 0.849, respectively), and age at surgery with ganglionic bowel wall thickness (r = 0.517). In aganglionic segments, the muscularis externa layer was thicker compared to that in ganglionosis (0.45 vs 0.31 mm, p = 0.012) whereas the muscularis interna was thinner (0.45 vs 0.62 mm, p < 0.001). A diagnostic index was identified whereby a lower ratio of muscularis interna/externa thickness followed by a thinner muscularis interna differed between aganglionic and ganglionic bowel in all specimens. CONCLUSION: Thicknesses of the bowel wall's muscle layers differ between aganglionic and ganglionic bowel walls in children with HSCR. These findings support a diagnostic index that could be validated for transfer to instant diagnostic imaging techniques. LEVEL OF EVIDENCE: Diagnostic: 3.

Novel Evidence Concerning Lacrimal Sac Movement Using Ultra-High-Frequency Ultrasound Examinations of Lacrimal Drainage Systems.

PURPOSE: Current hypothesis regarding the mechanism of active tear drainage is based on studies performed ex vivo or under nonphysiological conditions. Novel ultra-high-frequency ultrasound has the advantage of generating images with superior resolution, enabling measurements of low flow in small vessels, and the tracking of tissue motion in real time. The purpose of this study was to investigate the lacrimal drainage system and active drainage using this modality. METHODS: The upper lacrimal drainage system was investigated with 40-70 MHz ultrasound in 22 eyes in 13 patients. Irrigation confirmed a lacrimal obstruction in 10 eyes. Motion tracking was used to map movement of the lateral lacrimal sac wall and to measure flow when possible. RESULTS: The anatomy of the upper lacrimal drainage system was mapped in vivo, including the proximal canaliculi, which have not previously been imaged. The lacrimal sac lumen is slit shaped in its resting state but is distended when irrigated or if a nasolacrimal duct obstruction is present. Thus, the healthy lacrimal sac is not a cavity, and the medial retinaculum does not act against a stretched structure. Motion tracking visualized the "lacrimal pump," showing that the direction of motion of the lateral lacrimal sac wall is mainly in the sagittal plane during blinking. CONCLUSIONS: Ultra-high-frequency ultrasound allows detailed physiological monitoring of the upper lacrimal drainage system in vivo. Our findings suggest that current theories of active tear drainage need to be reappraised.

Spectral Signatures in the Different Layers of the Human Eyelid by Photoacoustic Imaging.

BACKGROUND AND OBJECTIVES: The eyelids are susceptible to a number of skin cancers, which are challenging to excise radically without sacrificing excessive healthy tissue. Photoacoustic (PA) imaging is an emerging non-invasive biomedical imaging modality that could potentially be used for intraoperative micrographic control of the surgical margins of eyelid tumors. In this study, non-cancerous human eyelid tissue was characterized using PA as a first step in the development of this technique. STUDY DESIGN/MATERIALS AND METHODS: Twelve full-thickness samples from nine patients were analyzed ex vivo using PA imaging. Two-dimensional PA images were acquired using 59 wavelengths in the range of 680-970 nm to obtain the spectral signatures of the skin, orbicularis oculi muscle, and the tarsal plate. Three-dimensional images were obtained by scanning the tissues using a linear stepping motor. Spectral unmixing was performed to visualize the chromophore distribution. RESULTS: The resulting PA spectra could be used to differentiate between the orbicularis oculi muscle and the other two structures (P < 0.05). The signals from the skin and the tarsal plate were more similar in appearance, probably due to similarities in their molecular composition. Spectral unmixing provided a clear visualization of the overall architecture of the eyelids. CONCLUSIONS: PA imaging can be used to differentiate between the orbicularis oculi muscle and the eyelid skin and tarsal plate. The main structures of human eyelids could be visualized in three dimensions using PA imaging. This technique could potentially be used to examine eyelid tumors intraoperatively in the future. However, further studies on tumors in vivo are needed before considering such clinical use. Lasers Surg Med. © 2019 Wiley Periodicals, Inc.

The heme and radical scavenger α1-microglobulin (A1M) confers early protection of the immature brain following preterm intraventricular hemorrhage.

BACKGROUND: Germinal matrix intraventricular hemorrhage (GM-IVH) is associated with cerebro-cerebellar damage in very preterm infants, leading to neurodevelopmental impairment. Penetration, from the intraventricular space, of extravasated red blood cells and extracellular hemoglobin (Hb), to the periventricular parenchyma and the cerebellum has been shown to be causal in the development of brain injury following GM-IVH. Furthermore, the damage has been described to be associated with the cytotoxic nature of extracellular Hb-metabolites. To date, there is no therapy available to prevent infants from developing either hydrocephalus or serious neurological disability. Mechanisms previously described to cause brain damage following GM-IVH, i.e., oxidative stress and Hb-metabolite toxicity, suggest that the free radical and heme scavenger α1-microglobulin (A1M) may constitute a potential neuroprotective intervention. METHODS: Using a preterm rabbit pup model of IVH, where IVH was induced shortly after birth in pups delivered by cesarean section at E29 (3 days prior to term), we investigated the brain distribution of recombinant A1M (rA1M) following intracerebroventricular (i.c.v.) administration at 24 h post-IVH induction. Further, short-term functional protection of i.c.v.-administered human A1M (hA1M) following IVH in the preterm rabbit pup model was evaluated. RESULTS: Following i.c.v. administration, rA1M was distributed in periventricular white matter regions, throughout the fore- and midbrain and extending to the cerebellum. The regional distribution of rA1M was accompanied by a high co-existence of positive staining for extracellular Hb. Administration of i.c.v.-injected hA1M was associated with decreased structural tissue and mitochondrial damage and with reduced mRNA expression for proinflammatory and inflammatory signaling-related genes induced by IVH in periventricular brain tissue. CONCLUSIONS: The results of this study indicate that rA1M/hA1M is a potential candidate for neuroprotective treatment following preterm IVH.

Scatterer size estimation using the center frequency assessed from ultrasound time domain data.

Scatterer size estimation is useful when characterizing tissue using ultrasound. In all previous studies on scatterer size, the estimations are performed in the frequency domain and are thus subjected to a trade off in time-frequency resolution. This study focused on the feasibility of estimating scatterer size in the time domain using only the ultrasound center frequency, assuming a Gaussian-shaped pulse. A model for frequency normalization was derived and the frequency-dependent attenuation was compensated. Five phantoms with well-defined sizes of spherical glass beads were made and scanned with two different linear array transducers with variable center frequencies. A strong correlation (r = 0.99, p < 10-19) between the backscattered center frequency and the product between the wave number and scatterer radius was demonstrated. On average the scatterer diameter was underestimated by 6% ± 24%. These results suggest that estimation of scatterer size is possible using only the center frequency assessed in the time domain.

Altered expression of aquaporin 1 and 5 in the choroid plexus following preterm intraventricular hemorrhage.

Intraventricular hemorrhage (IVH) with posthemorrhagic ventricular dilatation (PHVD) is a common cause of hydrocephalus in infants. Dysregulation of cerebrospinal fluid (CSF) production by the choroid plexus may contribute to the development of PHVD. The aquaporins (AQPs), transmural water transporting proteins, are believed to contribute to CSF production. The aim of the study was to characterize the expression and localization of AQP1, 4 and 5 in the choroid plexus following preterm IVH. Using a preterm rabbit pup model, the mRNA expression, protein level and localization of AQP1, 4 and 5 were investigated in the choroid plexus at 24 and 72 h following IVH with PHVD. Further, AQP1, 4 and 5 expression were characterized in primary human plexus epithelial cells exposed to CSF from preterm human infants with IVH and to hemoglobin metabolites. IVH with PHVD in the immature brain caused a downregulation of AQP1 mRNA, the key AQP in CSF production, but an upregulation of AQP1 protein level with apical epithelial cell localization. Notably, AQP5 was expressed in the choroid plexus with upregulated mRNA expression and protein levels during PHVD with apical epithelial cell localization. Analysis of human choroid plexus epithelial cells in vitro, following exposure to posthemorrhagic CSF and to hemin, displayed results concordant with those observed in vivo, i.e. downregulation of AQP1 mRNA and upregulation of AQP5 mRNA expression. AQP4 was neither detectable in vivo nor in vitro. The changes observed in AQP1 and AQP5 expression in the choroid plexus suggest an adaptive response following IVH with possible functional implications for the development of PHVD.

Extracellular hemoglobin - mediator of inflammation and cell death in the choroid plexus following preterm intraventricular hemorrhage.

BACKGROUND: Intraventricular hemorrhage (IVH) with post-hemorrhagic ventricular dilatation (PHVD) is a major cause of neurodevelopmental impairment and mortality in preterm infants. The mechanisms leading to PHVD and brain damage remain largely unknown. The choroid plexus and the ependyma, which constitute an essential part of the blood-brain barrier (BBB), are the first structures to encounter the damaging effects of extravasated blood. The breakdown of the BBB is a critical upstream event leading to brain damage following IVH. In this study we investigated the impact of hemorrhage and hemoglobin (Hb) metabolites on the choroid plexus epithelium. METHODS: Using a preterm rabbit pup model of IVH, the structural and functional integrity, cellular, inflammatory and oxidative response of the choroid plexus, at 24 and 72 hours following IVH + PHVD, were investigated. In order to further characterize cellular and molecular mechanisms, primary human choroid plexus epithelial cells were exposed to cerebrospinal fluid (CSF) from preterm infants with IVH as well as to Hb-metabolites. Finally, the blocking effects of the Hb-scavenger haptoglobin (Hp) were investigated both in vivo and in vitro. RESULTS: Following IVH + PHVD, an up-regulation of mRNA for the receptor-related genes TLR-4, IL1R1, FAS, the transcription factor NF-Κß and for the pro-inflammatory and chemotactic effector molecules, IL-1ß, TNFα, MCP-1, IL-8, and IL-6 was observed in the choroid plexus at 24 and 72 hours. This was associated with structural disintegration, caspase activation and cell death in the choroid plexus epithelium. In vitro characterization of choroid plexus epithelial cells, following exposure to hemorrhagic CSF and to the Hb-metabolites metHb and heme, displayed apoptotic and necrotic cell death and an up-regulation of receptor-related and inflammatory effector molecules similar to that observed in vivo following IVH + PHVD. Intraventricular injection of the Hb-scavenger Hp in vivo and co-incubation with Hp in vitro reversed or reduced the cellular activation, inflammatory response, structural damage and cell death. CONCLUSION: Hb-metabolites are important causal initiators of cell death following IVH and removal or scavenging of Hb-metabolites may present an efficient means to reduce the damage to the immature brain following IVH.

Increased diameter and stiffness of elastic but not muscular arteries in men with abdominal aortic aneurysm.

It has been proposed that formation of abdominal aortic aneurysm (AAA) is part of a systemic arterial dilatative disease. However, arteries in the upper extremities are scarcely studied and it remains unclear whether both muscular and elastic arteries are affected by the proposed systemic arterial dilatation. The aim of this study was to investigate the diameter and stiffness of muscular and elastic arteries in arterial branches originating from the aortic arch. Twenty-six men with AAA (69 ± 4 yr) and 57 men without AAA (70 ± 5 yr) were included in the study. Ultrasound was used to examine the distal and proximal brachial artery, axillary artery, and common carotid artery (CCA), and measurement of diameter and diameter change was performed with wall-tracking software. Blood pressure measurements were used to calculate local arterial wall stiffness indices. The AAA cohort presented larger arterial diameters in the CCA and axillary artery after adjustment for body surface area (P = 0.002, respectively), whereas the brachial artery diameters were unchanged. Indices of increased stiffness in CCA (e.g., lower distensibility, P = 0.003) were seen in subjects with AAA after adjustments for body mass index and mean arterial blood pressure. This study supports the theory of a systemic arterial dilating diathesis in peripheral elastic, but not in muscular, arteries. Peripheral elastic arteries also exhibited increased stiffness, in analogy with findings in the aorta in AAA.NEW & NOTEWORTHY We present data partially supporting the notion of abdominal aortic aneurysm being a systemic vascular disease with focal manifestation in the abdominal aorta, from two well-defined groups recruited from a regional screening program. We show that elastic arteries distal from the aorta exhibit vascular alterations without aneurysmal formation in subjects with AAA compared with controls while muscular arteries seem unaffected.

Optical tuning of copolymer-in-oil tissue-mimicking materials for multispectral photoacoustic imaging.

Objective. The availability of tissue-mimicking materials (TMMs) for manufacturing high-quality phantoms is crucial for standardization, evaluating novel quantitative approaches, and clinically translating new imaging modalities, such as photoacoustic imaging (PAI). Recently, a gel comprising the copolymer styrene-ethylene/butylene-styrene (SEBS) in mineral oil has shown significant potential as TMM due to its optical and acoustic properties akin to soft tissue. We propose using artists' oil-based inks dissolved and diluted in balsam turpentine to tune the optical properties.Approach. A TMM was fabricated by mixing a SEBS copolymer and mineral oil, supplemented with additives to tune its optical absorption and scattering properties independently. A systematic investigation of the tuning accuracies and relationships between concentrations of oil-based pigments and optical absorption properties of the TMM across visible and near-infrared wavelengths using collimated transmission spectroscopy was conducted. The photoacoustic spectrum of various oil-based inks was studied to analyze the effect of increasing concentration and depth.Main results. Artists' oil-based inks dissolved in turpentine proved effective as additives to tune the optical absorption properties of mineral oil SEBS-gel with high accuracy. The TMMs demonstrated long-term stability and suitability for producing phantoms with desired optical absorption properties for PAI studies.Significance. The findings, including tuning of optical absorption and spectral shape, suggest that this TMM facilitates the development of more sophisticated phantoms of arbitrary shapes. This approach holds promise for advancing the development of PAI, including investigation of the spectral coloring effect. In addition, it can potentially aid in the development and clinical translation of ultrasound optical tomography.

Hemoglobin induces inflammation after preterm intraventricular hemorrhage by methemoglobin formation.

BACKGROUND: Cerebral intraventricular hemorrhage (IVH) is a major cause of severe neurodevelopmental impairment in preterm infants. To date, no therapy is available that prevents infants from developing serious neurological disability following IVH. Thus, to develop treatment strategies for IVH, it is essential to characterize the initial sequence of molecular events that leads to brain damage. In this study, we investigated extracellular hemoglobin (Hb) as a causal initiator of inflammation in preterm IVH. METHODS: Using a preterm rabbit pup model, we investigated the molecular mechanisms and events following IVH. We also characterized the concentrations of cell-free Hb metabolites and pro-inflammatory mediators in the cerebrospinal fluid (CSF) of preterm human infants and rabbit pups. Finally, Hb metabolites were evaluated as causal initiators of inflammation in primary rabbit astrocyte cell cultures. RESULTS: Following IVH in preterm rabbit pups, the intraventricular CSF concentration of cell-free methemoglobin (metHb) increased from 24 to 72 hours and was strongly correlated with the concentration of TNFα at 72 hours (r2 = 0.896, P <0.001). Also, the mRNA expression of TNFα, IL-1ß, and Toll-like receptor-4 and TNFα protein levels were significantly increased in periventricular tissue at 72 hours, which was accompanied by extensive astrocyte activation (that is, glial fibrillary acidic protein (GFAP)staining). Furthermore, exposure of primary rabbit astrocyte cell cultures to metHb caused a dose-dependent increase in TNFα mRNA and protein levels, which was not observed following exposure to oxyhemoglobin (oxyHb) or hemin. Finally, a positive correlation (r2 = 0.237, P <0.03) between metHb and TNFα concentrations was observed in the CSF of preterm human infants following IVH. CONCLUSIONS: Following preterm IVH, increased metHb formation in the intraventricular space induces expression of pro-inflammatory cytokines. Thus, the formation of metHb might be a crucial initial event in the development of brain damage following preterm IVH. Accordingly, removal, scavenging, or neutralization of Hb could present a therapeutic opportunity and plausible approach to decreasing the damage in the immature brain following preterm IVH.

Response of the carotid artery longitudinal motion to submaximal physical activity in healthy humans-Marked changes already at low workload.

The longitudinal motion of the arterial wall, that is, the displacement of the arterial wall along the artery, parallel to blood flow, is still largely unexplored. The magnitude and nature of putative changes in longitudinal motion of the arterial wall in response to physical activity in humans remain unknown. The aim of this study was therefore to study the longitudinal motion of the carotid artery wall during physical activity in healthy humans. Using in-house developed non-invasive ultrasonic methods, the longitudinal motion of the intima-media complex and the diameter changes of the right common carotid artery (CCA) in 40 healthy volunteers (20 volunteers aged 22-35 years; 20 volunteers aged 55-68 years) were assessed at rest and during submaximal supine bicycle exercise. In a subset of the subjects (n = 18) also intramural shear strain were analyzed. The longitudinal motion of the intima-media complex underwent marked changes in response to physical activity, already at low workload; with most evident a marked increase of the first antegrade displacement (p < 0.001) in early systole. Likewise, the corresponding shear strain also increased significantly (p = 0.004). The increase in longitudinal motion showed significant correlation to increase in blood pressure, but not to blood flow velocity or wall shear stress. In conclusion, physical activity markedly influences the longitudinal motion of the carotid artery wall in healthy humans already at low load. A possible "cushioning" function as well as possible implications for the function of the vasa vasorum, endothelium, and smooth muscle cells and extracellular matrix of the media, are discussed.

Design of a Pediatric Rectal Ultrasound Probe Intended for Ultra-High Frequency Ultrasound Diagnostics.

It has been shown that ultra-high frequency (UHF) ultrasound applied to the external bowel wall can delineate the histo-anatomic layers in detail and distinguish normal bowel from aganglionosis. This would potentially reduce or lessen the need for biopsies that are currently mandatory for the diagnosis of Hirschsprung's disease. However, to our knowledge, no suitable rectal probes for such a use are on the market. The aim was to define the specifications of an UHF transrectal ultrasound probe (50 MHz center frequency) suitable for use in infants. Probe requirements according to patient anatomy, clinicians' requests, and biomedical engineering UHF prerequisites were collected within an expert group. Suitable probes on the market and in clinical use were reviewed. The requirements were transferred into the sketching of potential UHF ultrasound transrectal probes followed by their 3D prototype printing. Two prototypes were created and tested by five pediatric surgeons. The larger and straight 8 mm head and shaft probe was preferred as it facilitated stability, ease of anal insertion, and possible UHF technique including 128 piezoelectric elements in a linear array. We hereby present the procedure and considerations behind the development of a proposed new UHF transrectal pediatric probe. Such a device can open new possibilities for the diagnostics of pediatric anorectal conditions.

The impact of geometry, intramural friction, and pressure on the antegrade longitudinal motion of the arterial wall: A phantom and finite element study.

Longitudinal motion of the carotid arterial wall, as measured with ultrasound, has shown promise as an indicator of vascular health. The underlying mechanisms are however not fully understood. We have found, in in vivo studies, that blood pressure has a strong relation to the antegrade longitudinal displacement in early systole. Further, we have identified that a tapered geometry and the intramural friction in-between two parts of a vessel wall influence the longitudinal displacement. We therefore studied the interaction between pressure, vessel geometry and intramural friction, tapered and straight ultrasound phantoms in a paralleled hydraulic bench study and corresponding numerical models. Profound antegrade longitudinal motion was induced in the innermost part of both tapered phantoms and the numerical models, but to a lesser extent when intramural friction was increased in the simulations. Strong correlations (R = 0.82-0.96; p < 1e-3; k = 9.3-14 µm/mmHg) between longitudinal displacement and pulse pressure were found in six of seven regions of interest in tapered phantoms. The motion of the straight phantom and the corresponding numerical model was smaller, on average zero or close to zero. This study demonstrates that tapering of the lumen, low intramural friction, and pressure might be important conducive features to the antegrade longitudinal motion of the arterial wall in vivo.

A Computer Program for Assessing Histoanatomical Morphometrics in Ultra-High-Frequency Ultrasound Images of the Bowel Wall in Children: Development and Inter-Observer Variability.

Ultra-high-frequency ultrasound (UHFUS) has a reported potential to differentiate between aganglionic and ganglionic bowel wall, referred to as histoanatomical differences. A good correlation between histoanatomy and UHFUS of the bowel wall has been proven. In order to perform more precise and objective histoanatomical morphometrics, the main research objective of this study was to develop a computer program for the assessment and automatic calculation of the histoanatomical morphometrics of the bowel wall in UHFUS images. A computer program for UHFUS diagnostics was developed and presented. A user interface was developed in close collaboration between pediatric surgeons and biomedical engineers, to enable interaction with UHFUS images. Images from ex vivo bowel wall samples of 23 children with recto-sigmoid Hirschsprung's disease were inserted. The program calculated both thickness and amplitudes (image whiteness) within different histoanatomical bowel wall layers. Two observers assessed the images using the program and the inter-observer variability was evaluated. There was an excellent agreement between observers, with an intraclass correlation coefficient range of 0.970-0.998. Bland-Altman plots showed flat and narrow distributions. The mean differences ranged from 0.005 to 0.016 mm in thickness and 0 to 0.7 in amplitude units, corresponding to 1.1-3.6% and 0.0-0.8% from the overall mean. The computer program enables and ensures objective, accurate and time-efficient measurements of histoanatomical thicknesses and amplitudes in UHFUS images of the bowel wall. The program can potentially be used for several bowel wall conditions, accelerating research within UHFUS diagnostics.

Ultra-High Frequency Ultrasound Imaging of Bowel Wall in Hirschsprung's Disease-Correlation and Agreement Analyses of Histoanatomy.

Hirschsprung's disease (HD) is characterized by aganglionosis in the bowel wall, requiring resection. Ultra-high frequency ultrasound (UHFUS) imaging of the bowel wall has been suggested to be an instantaneous method of deciding resection length. The aim of this study was to validate UHFUS imaging of the bowel wall in children with HD by exploring the correlation and systematic differences between UHFUS and histopathology. Resected fresh bowel specimens of children 0-1 years old, operated on for rectosigmoid aganglionosis at a national HD center 2018-2021, were examined ex vivo with UHFUS center frequency 50 MHz. Aganglionosis and ganglionosis were confirmed by histopathological staining and immunohistochemistry. Histoanatomical layers of bowel wall in histopathological and UHFUS images, respectively, were outlined using MATLAB programs. Both histopathological and UHFUS images were available for 19 aganglionic and 18 ganglionic specimens. The thickness of muscularis interna correlated positively between histopathology and UHFUS in both aganglionosis (R = 0.651, p = 0.003) and ganglionosis (R = 0.534, p = 0.023). The muscularis interna was systematically thicker in histopathology than in UHFUS images in both aganglionosis (0.499 vs. 0.309 mm; p < 0.001) and ganglionosis (0.644 versus 0.556 mm; p = 0.003). Significant correlations and systematic differences between histopathological and UHFUS images support the hypothesis that UHFUS reproduces the histoanatomy of the bowel wall in HD accurately.

Breast Cancer Diagnosis Using Extended-Wavelength-Diffuse Reflectance Spectroscopy (EW-DRS)-Proof of Concept in Ex Vivo Breast Specimens Using Machine Learning.

This study aims to investigate the feasibility of using diffuse reflectance spectroscopy (DRS) to distinguish malignant breast tissue from adjacent healthy tissue, and to evaluate if an extended-wavelength range (450-1550 nm) has an advantage over the standard wavelength range (450-900 nm). Multivariate statistics and machine learning algorithms, either linear discriminant analysis (LDA) or support vector machine (SVM) are used to distinguish the two tissue types in breast specimens (total or partial mastectomy) from 23 female patients with primary breast cancer. EW-DRS has a sensitivity of 94% and specificity of 91% as compared to a sensitivity of 40% and specificity of 71% using the standard wavelength range. The results suggest that DRS can discriminate between malignant and healthy breast tissue, with improved outcomes using an extended wavelength. It is also possible to construct a simple analytical model to improve the diagnostic performance of the DRS technique.

Longitudinal displacement and intramural shear strain of the porcine carotid artery undergo profound changes in response to catecholamines.

The effects of catecholamines on longitudinal displacements and intramural shear strain of the arterial wall are unexplored. Therefore, the common carotid artery of five anaesthetized pigs was investigated using an in-house developed noninvasive ultrasonic technique. The study protocol included intravenous infusion of low-dose epinephrine (ß-adrenoceptor activation), as well as intravenous boluses of norepinephrine (α-adrenoceptor activation). Further, the effects of ß-blockade (metoprolol) were studied. There were significant positive correlations between pulse pressure and longitudinal displacement of the intima-media complex (r = 0.72; P < 0.001), as well as between pulse pressure and intramural shear strain (r = 0.48; P < 0.001). Following administration of norepinephrine, the longitudinal displacement of the intima-media complex and intramural shear strain profoundly increased (median 190%, range 102-296%, and median 141%, range 101-182%, respectively, compared with baseline), also when given during ß-blockade (median 228%, range 133-266%, and median 158%, range 152-235%, respectively). During infusion of low-dose epinephrine, the longitudinal displacement of the intima-media complex and intramural shear strain decreased (median 88%, range 69-122%, and median 69%, range 47-117%, respectively, compared with baseline). In conclusion, the present study shows, for the first time, that the longitudinal displacement and intramural shear strain of the porcine carotid artery undergo profound changes in response to catecholamines. Increase in longitudinal displacements seems to be strongly related to α-adrenoceptor activation. Thus metoprolol is insufficient to counteract a profound increase in longitudinal displacement and intramural shear strain following a surge of norepinephrine.

Mapping the architecture of the temporal artery with photoacoustic imaging for diagnosing giant cell arteritis.

Photoacoustic (PA) imaging is rapidly emerging as a promising clinical diagnostic tool. One of the main applications of PA imaging is to image vascular networks in humans. This relies on the signal obtained from oxygenated and deoxygenated hemoglobin, which limits imaging of the vessel wall itself. Giant cell arteritis (GCA) is a treatable, but potentially sight- and life-threatening disease, in which the artery wall is infiltrated by leukocytes. Early intervention can prevent complications making prompt diagnosis of importance. Temporal artery biopsy is the gold standard for diagnosing GCA. We present an approach to imaging the temporal artery using multispectral PA imaging. Employing minimally supervised spectral analysis, we produce histology-like images where the artery wall is clearly discernible from the lumen and further differentiate between PA spectra from biopsies diagnosed as GCA- and GCA+ in 77 patients.

Displacement Patterns in Magnetomotive Ultrasound Explored by Finite Element Analysis.

Magnetomotive ultrasound is an emerging technique that enables detection of magnetic nanoparticles. This has implications for ultrasound molecular imaging, and potentially addresses clinical needs regarding determination of metastatic infiltration of the lymphatic system. Contrast is achieved by a time-varying magnetic field that sets nanoparticle-laden regions in motion. This motion is governed by vector-valued mechanical and magnetic forces. Understanding how these forces contribute to observed displacement patterns is important for the interpretation of magnetomotive ultrasound images. Previous studies have captured motion adjacent to nanoparticle-laden regions that was attributed to diamagnetism. While diamagnetism could give rise to a force, it cannot fully account for the observed displacements in magnetomotive ultrasound. To isolate explanatory variables of the observed displacements, a finite element model is set up. Using this model, we explore potential causes of the unexplained motion by comparing numerical models with earlier experimental findings. The simulations reveal motion outside particle-laden regions that could be attributed to mechanical coupling and the principle of mass conservation. These factors produced a motion that counterbalanced the time-varying magnetic excitation, and whose extent and distribution was affected by boundary conditions as well as compressibility and stiffness of the surroundings. Our findings emphasize the importance of accounting for the vector-valued magnetic force in magnetomotive ultrasound imaging. In an axisymmetric geometry, that force can be represented by a simple scalar expression, an oversimplification that rapidly becomes inaccurate with distance from the symmetry axis. Additionally, it results in an underestimation of the vertical force component by up to 30%. We therefore recommend using the full vector-valued force to capture the magnetic interaction. This study enhances our understanding of how forces govern magnetic nanoparticle displacement in tissue, contributing to accurate analysis and interpretation of magnetomotive ultrasound imaging.

Photoacoustic imaging of periorbital skin cancer ex vivo: unique spectral signatures of malignant melanoma, basal, and squamous cell carcinoma.

Radical excision of periorbital skin tumors is difficult without sacrificing excessive healthy tissue. Photoacoustic (PA) imaging is an emerging non-invasive biomedical imagi--ng modality that has potential for intraoperative micrographic control of surgical margins. This is the first study to assess the feasibility of PA imaging for the detection of periocular skin cancer. Eleven patients underwent surgical excision of periocular skin cancer, one of which was a malignant melanoma (MM), eight were basal cell carcinomas (BCCs), and two squamous cell carcinomas (SCCs). Six tumors were located in the eyelid, and five in periocular skin. The excised samples, as well as healthy eyelid samples, were scanned with PA imaging postoperatively, using 59 wavelengths in the range 680-970 nm, to generate 3D multispectral images. Spectral unmixing was performed using endmember spectra for oxygenated and deoxygenated Hb, melanin, and collagen, to iden--tify the chromophore composition of tumors and healthy eyelid tissue. After PA scanning, the tumor samples were examined histopathologically using standard hematoxylin and eosin staining. The PA spectra of healthy eyelid tissue were dominated by melanin in the skin, oxygenated and deoxygenated hemoglobin in the orbicularis oculi muscle, and collagen in the tarsal plate. Multiwavelength 3D scanning provided spectral information on the three tumor types. The spectrum from the MM was primarily reconstructed by the endmember melanin, while the SCCs showed contributions primarily from melanin, but also HbR and collagen. BCCs showed contributions from all four endmembers with a predominance of HbO2 and HbR. PA imaging may be used to distinguish different kinds of periocular skin tumors, paving the way for future intraoperative micrographic control.