Context-aware deep learning enables high-efficacy localization of high concentration microbubbles for super-resolution ultrasound localization microscopy.

Ultrasound localization microscopy (ULM) enables deep tissue microvascular imaging by localizing and tracking intravenously injected microbubbles circulating in the bloodstream. However, conventional localization techniques require spatially isolated microbubbles, resulting in prolonged imaging time to obtain detailed microvascular maps. Here, we introduce LOcalization with Context Awareness (LOCA)-ULM, a deep learning-based microbubble simulation and localization pipeline designed to enhance localization performance in high microbubble concentrations. In silico, LOCA-ULM enhanced microbubble detection accuracy to 97.8% and reduced the missing rate to 23.8%, outperforming conventional and deep learning-based localization methods up to 17.4% in accuracy and 37.6% in missing rate reduction. In in vivo rat brain imaging, LOCA-ULM revealed dense cerebrovascular networks and spatially adjacent microvessels undetected by conventional ULM. We further demonstrate the superior localization performance of LOCA-ULM in functional ULM (fULM) where LOCA-ULM significantly increased the functional imaging sensitivity of fULM to hemodynamic responses invoked by whisker stimulations in the rat brain.

Computational Fractal-Based Analysis of Brain Tumor Microvascular Networks.

Brain parenchyma microvasculature is set in disarray in the presence of tumors, and malignant brain tumors are among the most vascularized neoplasms in humans. As microvessels can be easily identified in histologic specimens, quantification of microvascularity can be used alone or in combination with other histological features to increase the understanding of the dynamic behavior, diagnosis, and prognosis of brain tumors. Different brain tumors, and even subtypes of the same tumor, show specific microvascular patterns, as a kind of "microvascular fingerprint," which is particular to each histotype. Reliable morphometric parameters are required for the qualitative and quantitative characterization of the neoplastic angioarchitecture, although the lack of standardization of a technique able to quantify the microvascular patterns in an objective way has limited the "morphometric approach" in neuro-oncology.In this chapter, we focus on the importance of computational-based morphometrics, for the objective description of tumoral microvascular fingerprinting. By also introducing the concept of "angio-space," which is the tumoral space occupied by the microvessels, we here present fractal analysis as the most reliable computational tool able to offer objective parameters for the description of the microvascular networks.The spectrum of different angioarchitectural configurations can be quantified by means of Euclidean and fractal-based parameters in a multiparametric analysis, aimed to offer surrogate biomarkers of cancer. Such parameters are here described from the methodological point of view (i.e., feature extraction) as well as from the clinical perspective (i.e., relation to underlying physiology), in order to offer new computational parameters to the clinicians with the final goal of improving diagnostic and prognostic power of patients affected by brain tumors.

Dual-exposure temporal laser speckle imaging for simultaneously accessing microvascular blood perfusion and angiography.

Laser speckle contrast imaging (LSCI) has gained significant attention in the biomedical field for its ability to map the spatio-temporal dynamics of blood perfusion in vivo. However, LSCI faces difficulties in accurately resolving blood perfusion in microvessels. Although the transmissive detecting geometry can improve the spatial resolution of tissue imaging, ballistic photons directly transmitting forward through tissue without scattering will cause misestimating in the flow speed by LSCI because of the lack of a quantitative theoretical model of transmissvie LSCI. Here, we develop a model of temporal LSCI which accounts for the effect of nonscattered light on estimating decorrelation time. Based on this model, we further propose a dual-exposure temporal laser speckle imaging method (dEtLSCI) to correct the overestimation of background speed when performing traditional transmissive LSCI, and reconstruct microvascular angiography using the scattered component extracted from total transmitted light. Experimental results demonstrated that our new method opens an opportunity for LSCI to simultaneously resolve the blood vessels morphology and blood flow speed at microvascular level in various contexts, ranging from the drug-induced vascular response to angiogenesis and the blood perfusion monitoring during tumor growth.

Pattern recognition of microcirculation with super-resolution ultrasound imaging provides markers for early tumor response to anti-angiogenic therapy.

Rationale: Cancer treatment outcome is traditionally evaluated by tumor volume change in clinics, while tumor microvascular heterogeneity reflecting tumor response has not been fully explored due to technical limitations. Methods: We introduce a new paradigm in super-resolution ultrasound imaging, termed pattern recognition of microcirculation (PARM), which identifies both hemodynamic and morphological patterns of tumor microcirculation hidden in spatio-temporal space trajectories of microbubbles. Results: PARM demonstrates the ability to distinguish different local blood flow velocities separated by a distance of 24 µm. Compared with traditional vascular parameters, PARM-derived heterogeneity parameters prove to be more sensitive to microvascular changes following anti-angiogenic therapy. Particularly, PARM-identified "sentinel" microvasculature, exhibiting evident structural changes as early as 24 hours after treatment initiation, correlates significantly with subsequent tumor volume changes (|r| > 0.9, P < 0.05). This provides prognostic insight into tumor response much earlier than clinical criteria. Conclusions: The ability of PARM to noninvasively quantify tumor vascular heterogeneity at the microvascular level may shed new light on early-stage assessment of cancer therapy.

The value of varying diffusion curvature MRI for assessing the microvascular invasion of hepatocellular carcinoma.

PURPOSE: Varying diffusion curvature (VDC) MRI is an emerging diffusion-weighted imaging (DWI) technique that can capture non-Gaussian diffusion behavior and reflect tissue heterogeneity. However, its clinical utility has hardly been evaluated. We aimed to investigate the value of the VDC technique in noninvasively assessing microvascular invasion (MVI) in hepatocellular carcinoma (HCC). METHODS: 74 patients with HCCs, including 39 MVI-positive and 35 MVI-negative HCCs were included into this prospective study. Quantitative metrics between subgroups, clinical risk factors, as well as diagnostic performance were evaluated. The power analysis was also carried out to determine the statistical power. RESULTS: MVI-positive HCCs exhibited significantly higher VDC-derived structural heterogeneity measure, D1 (0.680 ± 0.100 × 10-3 vs 0.572 ± 0.148 × 10-3 mm2/s, p = 0.001) and lower apparent diffusion coefficient (ADC) (1.350 ± 0.166 × 10-3 vs 1.471 ± 0.322 × 10-3 mm2/s, p = 0.0495) compared to MVI-negative HCCs. No statistical significance was observed for VDC-derived diffusion coefficient, D0 between the subgroups (p = 0.562). Tumor size (odds ratio (OR) = 1.242) and alpha-fetoprotein (AFP) (OR = 2.527) were identified as risk factors for MVI. A predictive nomogram was constructed based on D1, ADC, tumor size, and AFP, which exhibited the highest diagnostic accuracy (AUC = 0.817), followed by D1 (AUC = 0.753) and ADC (AUC = 0.647). The diagnostic performance of the nomogram-based model was also validated by the calibration curve and decision curve. CONCLUSION: VDC can aid in the noninvasive and preoperative diagnosis of HCC with MVI, which may result in the clinical benefit in terms of prognostic prediction and clinical decision-making.

Using a combination of superb microvascular imaging and other auxiliary ultrasound techniques to increase the accuracy of gray-scale ultrasound for breast masses.

BACKGROUND: Breast ultrasound is highly sensitive, but its specificity is not as high for detecting malignant lesions. Auxiliary modalities like elastography, Color and Power Doppler ultrasound are used as adjuncts to yield both a high sensitivity and specificity. Superb microvascular imaging (SMI) is a newer modality with more accuracy for detecting breast lesions. In this study, our goal was to investigate the role of SMI as an adjunct to ultrasound and find a suitable combination model for the evaluation of breast masses. METHODS: In this cross-sectional study, 132 women with 172 breast masses who underwent ultrasound-guided biopsy were included.. The ultrasound features of the lesion, the strain ratio in strain elastography, the number of vessels for each lesion, their morphology and distribution in Doppler and Power Doppler ultrasound and SMI were recorded for each lesion. A vascular score and a vascular ratio were defined. RESULTS: In the histologic examination, 31 lesions (18%) were malignant and 141 lesions (82%) were benign. The vascular score was more accurate than the vascular ratio in all three modalities. The predictive ability of strain ratio was higher than Doppler and Power Doppler ultrasound and SMI. Adding SMI alone to ultrasound increased the specificity from 46.10% to 61.2% and the accuracy from 55.80% to 70.11%. In the combination of ultrasound with other modalities, the best was the combination of ultrasound, strain elastography, and SMI; which yielded a specificity and sensitivity of 100% and 74.4%, respectively. CONCLUSION: Adding SMI and STE modalities as adjuncts to ultrasound lowers the chance of missing malignant lesions and reduces unnecessary biopsies of breast lesions. A study with a larger sample size using this combination model to evaluate the accuracy with greater precision is recommended.

Dimension-based quantification of aging-associated cerebral microvasculature determined by optical coherence tomography and two-photon microscopy.

Cerebral microvascular health is a key biomarker for the study of natural aging and associated neurological diseases. Our aim is to quantify aging-associated change of microvasculature at diverse dimensions in mice brain. We used optical coherence tomography (OCT) and two-photon microscopy (TPM) to obtain nonaged and aged C57BL/6J mice cerebral microvascular images in vivo. Our results indicated that artery & vein, arteriole & venule, and capillary from nonaged and aged mice showed significant differences in density, diameter, complexity, perimeter, and tortuosity. OCT angiography and TPM provided the comprehensive quantification for arteriole and venule via compensating the limitation of each modality alone. We further demonstrated that arteriole and venule at specific dimensions exhibited negative correlations in most quantification analyses between nonaged and aged mice, which indicated that TPM and OCT were able to offer complementary vascular information to study the change of cerebral blood vessels in aging.

Characterizing differences in retinal and choroidal microvasculature and structure in individuals with Huntington's Disease compared to healthy controls: A cross-sectional prospective study.

OBJECTIVE: To characterize retinal and choroidal microvascular and structural changes in patients who are gene positive for mutant huntingtin protein (mHtt) with symptoms of Huntington's Disease (HD). METHODS: This study is a cross-sectional comparison of patients who are gene positive for mHtt and exhibit symptoms of HD, either motor manifest or prodromal (HD group), and cognitively normal individuals without a family history of HD (control group). HD patients were diagnosed by Duke movement disorder neurologists based on the Unified Huntington's Disease Rating Scale (UHDRS). Fovea and optic nerve centered OCT and OCTA images were captured using Zeiss Cirrus HD-5000 with AngioPlex. Outcome metrics included central subfield thickness (CST), peripapillary retinal nerve fiber layer (pRNFL) thickness, ganglion cell-inner plexiform layer (GCIPL) thickness, and choroidal vascularity index (CVI) on OCT, and foveal avascular zone (FAZ) area, vessel density (VD), perfusion density (PD), capillary perfusion density (CPD), and capillary flux index (CFI) on OCTA. Generalized estimating equation (GEE) models were used to account for inter-eye correlation. RESULTS: Forty-four eyes of 23 patients in the HD group and 77 eyes of 39 patients in the control group were analyzed. Average GCIPL thickness and FAZ area were decreased in the HD group compared to controls (p = 0.001, p < 0.001). No other imaging metrics were significantly different between groups. CONCLUSIONS: Patients in the HD group had decreased GCIPL thickness and smaller FAZ area, highlighting the potential use of retinal biomarkers in detecting neurodegenerative changes in HD.

Quantitative evaluation of choroidal and retinal microvasculature post-alcohol consumption: A pilot study.

PURPOSE: The aim of this study was to assess the impact of acute, heavy alcohol consumption on the ocular microvasculature, providing insight into the largely unexplored response of microvascular structures to excessive drinking. METHODS: Healthy volunteers in this prospective pilot study were tasked with consuming spirits, wine, and water at different times. Alcohol intake was measured according to body weight (g/kg). The ocular microvascular parameters primarily including choroidal volume (CV) and choroidal vessel volume (CVV) reflecting arteriolovenularity, and choroidal capillary density (CCD) reflecting capillary, were evaluated using swept-source optical coherence tomography angiography at baseline and 0.5-, 1-, 2-, and 3-hour post-consumption. RESULTS: A total of 34 eyes underwent 170 successful examinations in this study. After consuming spirits or wine, we observed significant decreases in CV and CVV values (all P < 0.01 for 0.5-, 1-, 2-, and 3-hour post-consumption), along with significant increase in CCD (P < 0.05 at 0.5-, 1-, 2-hour post-spirits consumption and 1-hour post-wine consumption). The most pronounced changes occurred 1-hour after spirits or wine consumption (all P < 0.001 in both univariate and multivariate model). However, post-consumption changes in the ocular microvasculature showed no significant differences between spirits and wine (P > 0.05). Additionally, no significant differences were observed in any parameters after water intake (all P > 0.05). CONCLUSIONS: Excessive alcohol consumption leads to ocular arteriolovenular vasoconstriction and capillary vasodilation, most evident 1-hour post-consumption of spirits and wine. Our research provides insight into alcohol's immediate ocular microvascular effects, hinting at systemic microvascular effects.

Correlation of the macular microvasculature to the axial length in pediatric patients with high axial refractive errors.

AIMS: To compare the vascular density (VD) of the macular superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC), and the foveal avascular zone (FAZ) among high hyperopic, high myopic, and emmetropic children using optical coherence tomography angiography (OCTA). METHODS: This was a cross sectional comparative study of otherwise healthy children with different refractive errors. Patients were recruited from Cairo University Children's Hospital. OCTA imaging was performed using the RTVue XR Avanti device with AngioVue software. Both the 3 × 3 and 6 × 6 mm macular scans were utilized. Automated measurements were obtained from the built-in machine software. Axial length (AL) measurements were done using Lenstar LS 900 optical biometer. RESULTS: Ninety eyes from 51 healthy children were included. Among high myopes, there was significant thinning of the parafovea (p < 0.001). SCP-VD was also lower in high myopes in all areas except the fovea (all p < 0.001). The DCP-VD was significantly lower in high myopes in the parafovea and perifovea. High hyperopes had lower subfoveal CC-VD. Despite high myopes showing a significantly lower OCTA signal strength, linear regression analysis revealed that AL was an independent and significant predictor for the FAZ-area, as well as parafoveal and perifoveal SCP and DCP-VD. CONCLUSION: High myopia results in a reduction of VD in both the SCP and DCP, which can be non-invasively detected and monitored using OCTA. While lower VD may, in part, be attributed to lower OCTA image quality, our findings demonstrate that AL independently and significantly predicts macular vascular parameters on OCTA in children.

Deep segmentation of OCTA for evaluation and association of changes of retinal microvasculature with Alzheimer's disease and mild cognitive impairment.

BACKGROUND: Optical coherence tomography angiography (OCTA) enables fast and non-invasive high-resolution imaging of retinal microvasculature and is suggested as a potential tool in the early detection of retinal microvascular changes in Alzheimer's Disease (AD). We developed a standardised OCTA analysis framework and compared their extracted parameters among controls and AD/mild cognitive impairment (MCI) in a cross-section study. METHODS: We defined and extracted geometrical parameters of retinal microvasculature at different retinal layers and in the foveal avascular zone (FAZ) from segmented OCTA images obtained using well-validated state-of-the-art deep learning models. We studied these parameters in 158 subjects (62 healthy control, 55 AD and 41 MCI) using logistic regression to determine their potential in predicting the status of our subjects. RESULTS: In the AD group, there was a significant decrease in vessel area and length densities in the inner vascular complexes (IVC) compared with controls. The number of vascular bifurcations in AD is also significantly lower than that of healthy people. The MCI group demonstrated a decrease in vascular area, length densities, vascular fractal dimension and the number of bifurcations in both the superficial vascular complexes (SVC) and the IVC compared with controls. A larger vascular tortuosity in the IVC, and a larger roundness of FAZ in the SVC, can also be observed in MCI compared with controls. CONCLUSION: Our study demonstrates the applicability of OCTA for the diagnosis of AD and MCI, and provides a standard tool for future clinical service and research. Biomarkers from retinal OCTA images can provide useful information for clinical decision-making and diagnosis of AD and MCI.

Optical coherence tomography angiography analysis of choroidal microvasculature in various forms of diabetic macular edema.

INTRODUCTION: Optical coherence tomography angiography (OCTA) research in diabetic macular edema (DME) has focused on the retinal microvasculature with little attention to the choroid. The goal of this study was to analyze the association between quantitative choroidal OCTA parameters and various forms of DME observed on optical coherence tomography. METHODS: We conducted a retrospective study of 61 eyes of 53 patients with DME. DME was classified as early or advanced, and as sponge-like diffuse retinal thickening (DRT), cystoid macular edema (CME) or serous retinal detachment (SRD). Quantitative OCTA parameters (vessel density [VD] in the superficial capillary plexus [SCP], middle capillary plexus [MCP], deep capillary plexus [DCP] and choriocapillaris [CC]) were recorded. RESULTS: The VD in the CC and SCP was significantly higher in patients with early DME compared to patients with advanced DME (P value<0.01). CC VD was lower in subjects with SRD compared to DRT and CME (P value<0.001). Moreover, it was lower in CME compared to DRT (P value<0.05). No statistical differences were found between VD in the MCP and DCP (P value>0.05). Furthermore, CC VD was lower in patients with increased retinal thickness, disruption of the ellipsoid zone (EZ) or external limiting membrane (ELM), and disorganization of the inner retinal layers (DRIL) (P value<0.05). CONCLUSION: CC ischemia plays an important role in the pathogenesis of DME. We demonstrated a decrease in CC VD in patients with severe DME, SRD, retinal thickening, EZ and/or ELM disruption and DRIL.

Synchronous Intravital Imaging and Cavitation Monitoring of Antivascular Focused Ultrasound in Tumor Microvasculature Using Monodisperse Low Boiling Point Nanodroplets.

Focused ultrasound-stimulated microbubbles can induce blood flow shutdown and ischemic necrosis at higher pressures in an approach termed antivascular ultrasound. Combined with conventional therapies of chemotherapy, immunotherapy, and radiation therapy, this approach has demonstrated tumor growth inhibition and profound synergistic antitumor effects. However, the lower cavitation threshold of microbubbles can potentially yield off-target damage that the polydispersity of clinical agent may further exacerbate. Here we investigate the use of a monodisperse nanodroplet formulation for achieving antivascular effects in tumors. We first develop stable low boiling point monodisperse lipid nanodroplets and examine them as an alternative agent to mediate antivascular ultrasound. With synchronous intravital imaging and ultrasound monitoring of focused ultrasound-stimulated nanodroplets in tumor microvasculature, we show that nanodroplets can trigger blood flow shutdown and do so with a sharper pressure threshold and with fewer additional events than conventionally used microbubbles. We further leverage the smaller size and prolonged pharmacokinetic profile of nanodroplets to allow for potential passive accumulation in tumor tissue prior to antivascular ultrasound, which may be a means by which to promote selective tumor targeting. We find that vascular shutdown is accompanied by inertial cavitation and complex-order sub- and ultraharmonic acoustic signatures, presenting an opportunity for effective feedback control of antivascular ultrasound.

Broad Elevation Projection Super-Resolution Ultrasound (BEP-SRUS) Imaging With a 1-D Unfocused Linear Array.

Super-resolution ultrasound (SRUS) through localizing spatially isolated microbubbles (MBs) has been demonstrated to overcome the wave diffraction limit and reveal the microvascular structure and flow information at the microscopic scale. However, 3-D SRUS imaging remains a challenge due to the fabrication and computational complexity of 2-D matrix array probes. Inspired by X-ray radiography which can present information within a volume in a single projection image with much simpler hardware than X-ray computerized tomography (CT), this study investigates the feasibility of broad elevation projection super-resolution (BEP-SR) ultrasound using a 1-D unfocused linear array. Both simulation and in vitro experiments were conducted on 3-D microvessel phantoms. In vivo demonstration was done on the Rabbit kidney. Data from a 1-D linear array with and without an elevational focus were synthesized by summing up row signals acquired from a 2-D matrix array with and without delays. A full 3-D reconstruction was also generated as the reference, using the same data of the 2-D matrix array but without summing row signals. Results show that using an unfocused 1-D array probe, BEP-SR can capture significantly more information within a volume in both vascular structure and flow velocity than the conventional 1-D elevational-focused probe. Compared with the 2-D projection image of the full 3-D SRUS results using the 2-D array probe with the same aperture size, the 2-D projection SRUS image of BEP-SR has similar volume coverage, using 32 folds fewer independent elements. This study demonstrates BEP-SR's ability of high-resolution imaging of microvascular structures and flow velocity within a 3-D volume at significantly reduced costs. The proposed BEP method could significantly benefit the clinical translation of the SRUS imaging technique by making it more affordable and repeatable.

Parapapillary choroidal microvasculature in retrobulbar optic neuritis: An optical coherence tomography angiography study.

PURPOSE: To compare superficial and deep vascular characteristics of the optic disc in retrobulbar optic neuritis using optical coherence tomography angiography (OCT-A). METHODS: Nineteen patients with unilateral non-infectious retrobulbar neuritis were included in the study. The contralateral eyes of each patient were served as controls. OCT-A scans of the optic discs were performed in a 4.5 × 4.5 mm rectangular area, while macular OCT-A scans were performed in a 6 × 6 mm rectangular area. Various parameters, including radial peripapillary capillary (RPC) density, peripapillary retinal nerve fibre layer (pRNFL) thickness, cup volume, rim area, disc area, cup-to-disc (c/d) area ratio, and vertical and horizontal c/d ratios were automatically obtained using the instrument software. The density for superficial capillary plexus (SCP) and deep capillary plexus (DCP) were assessed using macular OCT-A. Parapapillary choroidal microvascular (PPCMv) density was calculated using MATLAB software. RESULTS: Parafoveal inferior, perifoveal total and inferior SCP densities were significantly decreased in eyes with optic neuritis when compared with contralateral control eyes in OCT-A measurements (respectively, p = 0.027, p = 0.041, p = 0.045). The axial lengths, (p = 0.72), vertical and horizontal cup-disc ratios, and disc area, cup-disc areas, cup volumes, and pRNFL thicknesses between the groups were similar (for each, p>0.05). CONCLUSIONS: This study demonstrated for the first time that patients with retrobulbar optic neuritis had decreased SCP densities, though it did not cause any changes in PPCMv density.

Quantitative study of spatial and temporal variation in retinal capillary network perfusion in rat eye by in vivo confocal imaging.

Microvascular dysfunction is the underlying pathological process in many systemic diseases. However, investigation into its pathogenesis is impeded by the accessibility and complexity of the microvasculature within different organs, particularly for the central nervous system. The retina as an extension of the cerebrum provides a glimpse into the brain through which the microvasculature can be observed. Two major questions remain unanswered: How do the microvessels regulate spatial and temporal delivery to satisfy the varying cellular demands, and how can we quantify blood perfusion in the 3D capillary network? Here, quantitative measurements of red blood cell (RBC) speed in each vessel in the field were made in the in vivo rat retinal capillary network using an ultrafast confocal technique with fluorescently labelled RBCs. Retinal RBC speed and number were found to vary remarkably between microvessels ranging from 215 to 6641 microns per second with significant variations spatially and temporally. Overall, the RBC speed was significantly faster in the microvessels in the superficial retina than in the deep retina (estimated marginal means of 2405 ± 238.2 µm/s, 1641 ± 173.0 µm/s respectively). These observations point to a highly dynamic nature of microvasculature that is specific to its immediate cellular environment and is constantly changing.

Deep learning for fast super-resolution ultrasound microvessel imaging.

Objective. Ultrasound localization microscopy (ULM) enables microvascular reconstruction by localizing microbubbles (MBs). Although ULM can obtain microvascular images that are beyond the ultimate resolution of the ultrasound (US) diffraction limit, it requires long data processing time, and the imaging accuracy is susceptible to the density of MBs. Deep learning (DL)-based ULM is proposed to alleviate these limitations, which simulated MBs at low-resolution and mapped them to coordinates at high-resolution by centroid localization. However, traditional DL-based ULMs are imprecise and computationally complex. Also, the performance of DL is highly dependent on the training datasets, which are difficult to realistically simulate.Approach. A novel architecture called adaptive matching network (AM-Net) and a dataset generation method named multi-mapping (MMP) was proposed to overcome the above challenges. The imaging performance and processing time of the AM-Net have been assessed by simulation andin vivoexperiments.Main results. Simulation results show that at high density (20 MBs/frame), when compared to other DL-based ULM, AM-Net achieves higher localization accuracy in the lateral/axial direction.In vivoexperiment results show that the AM-Net can reconstruct ∼24.3µm diameter micro-vessels and separate two ∼28.3µm diameter micro-vessels. Furthermore, when processing a 128 × 128 pixels image in simulation experiments and an 896 × 1280 pixels imagein vivoexperiment, the processing time of AM-Net is ∼13 s and ∼33 s, respectively, which are 0.3-0.4 orders of magnitude faster than other DL-based ULM.Significance. We proposes a promising solution for ULM with low computing costs and high imaging performance.

In vivo structural and functional imaging of human nailbed microvasculature using photoacoustic microscopy.

Monitoring microvascular structure and function is of great significance for the diagnosis of many diseases. In this study, we demonstrate the feasibility of OR-PAM to nailbed microcirculation detection as a new, to the best of our knowledge, application scenario in humans. We propose a dual-wavelength optical-resolution photoacoustic microscopy (OR-PAM) with improved local-flexible coupling to image human nailbed microvasculature. Microchip lasers with 532 nm wavelength are employed as the pump sources. The 558 nm laser is generated from the 532 nm laser through the stimulated Raman scattering effect. The flowing water, circulated by a peristaltic pump, maintains the acoustic coupling between the ultrasonic transducer and the sample. These designs improve the sensitivity, practicality, and stability of the OR-PAM system for human in vivo experiments. The imaging of the mouse ear demonstrates the ability of our system to acquire structural and functional information. Then, the system is applied to image human nailbed microvasculature. The imaging results reveal that the superficial capillaries are arranged in a straight sagittal pattern, approximately parallel to the long axis of the finger. The arterial and venular limbs are distinguished according to their oxygen saturation differences. Additionally, the images successfully discover the capillary loops with single or multiple twists, the oxygen release at the end of the capillary loop, and the changes when the nailbed is abnormal.

Parapapillary choroidal microvasculature dropout in eyes with primary open-angle glaucoma.

The purpose of this study was to evaluate how various parameters are related to microvasculature dropout (MvD) area measured using optical coherence tomography angiography (OCTA). We measured the area of MvD in 55 patients with primary open-angle glaucoma (POAG). Using OCTA, MvD area and peripapillary choroidal atrophy (PPA) area were assessed in a 4.5 mm × 4.5 mm region. The following were examined: circumpapillary nerve fiber layer (cpRNFL) thickness, optic disc area, optic disc cupping area, optic disc rim area, Humphrey Field Analyzer (HFA) 24/10-2 mean deviation (MD), and pattern standard deviation (PSD). The relationship between MvD area and each parameter was evaluated using Spearman's rank correlation coefficient analysis. Mean MvD area and PPA area were 0.18 ± 0.17 mm2 and 1.13 ± 0.72 mm2, respectively. MvD area was significantly correlated with optic disc rim area (p = 0.0017), cpRNFL (p = 0.0027), HFA 24/10-2 MD, and PSD (p < 0.001). In eyes with POAG, MvD area indicates the severity of glaucoma, which might be associated with structural changes in the peripapillary vasculature around the optic disc.

Clinical and DCE-CT signs in predicting microvascular invasion in cHCC-ICC.

BACKGROUND: To predict the microvascular invasion (MVI) in patients with cHCC-ICC. METHODS: A retrospective analysis was conducted on 119 patients who underwent CT enhancement scanning (from September 2006 to August 2022). They were divided into MVI-positive and MVI-negative groups. RESULTS: The proportion of patients with CEA elevation was higher in the MVI-positive group than in the MVI-negative group, with a statistically significant difference (P = 0.02). The MVI-positive group had a higher rate of peritumoral enhancement in the arterial phase (P = 0.01) whereas the MVI-negative group had more oval and lobulated masses (P = 0.04). According to the multivariate analysis, the increase in CEA (OR = 10.15, 95% CI: 1.11, 92.48, p = 0.04), hepatic capsular withdrawal (OR = 4.55, 95% CI: 1.44, 14.34, p = 0.01) and peritumoral enhancement (OR = 6.34, 95% CI: 2.18, 18.40, p < 0.01) are independent risk factors for predicting MVI. When these three imaging signs are combined, the specificity of MVI prediction was 70.59% (series connection), and the sensitivity was 100% (parallel connection). CONCLUSIONS: Our multivariate analysis found that CEA elevation, liver capsule depression, and arterial phase peritumoral enhancement were independent risk factors for predicting MVI in cHCC-ICC.