Ultrasound velocimetry has been widely used for blood flow imaging. However, the flow measurements are constrained to resolve the in-plane 2D flow components when using a 1D transducer array. In this work, an ultrasound speckle decorrelation analysis-based velocimetry (3C-vUS) is proposed for 3D velocity components measurement using a 1D transducer array. The 3C-vUS theory is first derived and validated with numerical simulations and phantom experiments. The in vivo testing results show that 3C-vUS can accurately measure the blood flow 3D-velocity-components of the human carotid artery at arbitrary probe-to-vessel angles throughout the cardiac cycle. With such capability, the 3C-vUS will alleviate the requirement of operators and promote disease screening for blood flow-related disorders.

BACKGROUND: Extracting phenotype-representative flow patterns and their associated numerical metrics is a bottleneck in the clinical translation of advanced cardiac flow imaging modalities. We hypothesized that reduced-order models (ROMs) are a suitable strategy for deriving simple and interpretable clinical metrics of intraventricular flow suitable for further assessments. Combined with machine learning (ML) flow-based ROMs could provide new insight to help diagnose and risk-stratify patients.
METHODS: We analyzed 2D color-Doppler echocardiograms of 81 non-ischemic dilated cardiomyopathy (DCM) patients, 51 hypertrophic cardiomyopathy (HCM) patients, and 77 normal volunteers (Control). We applied proper orthogonal decomposition (POD) to build patient-specific and cohort-specific ROMs of LV flow. Each ROM aggregates a low number of components representing a spatially dependent velocity map modulated along the cardiac cycle by a time-dependent coefficient. We tested three classifiers using deliberately simple ML analyses of these ROMs with varying supervision levels. In supervised models, hyperparameter grid search was used to derive the ROMs that maximize classification power. The classifiers were blinded to LV chamber geometry and function. We ran vector flow mapping on the color-Doppler sequences to help visualize flow patterns and interpret the ML results.
RESULTS: POD-based ROMs stably represented each cohort through 10-fold cross-validation. The principal POD mode captured >80 % of the flow kinetic energy (KE) in all cohorts and represented the LV filling/emptying jets. Mode 2 represented the diastolic vortex and its KE contribution ranged from <1 % (HCM) to 13 % (DCM). Semi-unsupervised classification using patient-specific ROMs revealed that the KE ratio of these two principal modes, the vortex-to-jet (V2J) energy ratio, is a simple, interpretable metric that discriminates DCM, HCM, and Control patients. Receiver operating characteristic curves using V2J as classifier had areas under the curve of 0.81, 0.91, and 0.95 for distinguishing HCM vs. Control, DCM vs. Control, and DCM vs. HCM, respectively.
CONCLUSIONS: Modal decomposition of cardiac flow can be used to create ROMs of normal and pathological flow patterns, uncovering simple interpretable flow metrics with power to discriminate disease states, and particularly suitable for further processing using ML.

UNASSIGNED: Intraoperative monitoring of blood flow (BF) remains vital to guiding surgical decisions. Here, we report the use of SurgeON™ Blood Flow Monitor (BFM), a prototype system that attaches to surgical microscopes and implements laser speckle contrast imaging (LSCI) to noninvasively obtain and present vascular BF information in real-time within the microscope\'s eyepiece.
UNASSIGNED: The ability of SurgeON BFM to monitor BF status during reversible vascular occlusion procedures was investigated in two large animal models: occlusion of saphenous veins in six NZW rabbit hindlimbs and clipping of middle cerebral artery (MCA) branches in four Dorset sheep brain hemispheres. SurgeON BFM acquired, presented, and stored LSCI-based blood flow velocity index (BFVi) data and performed indocyanine green video angiography (ICG-VA) for corroboration.
UNASSIGNED: Stored BFVi data were analyzed for each phase: pre-occlusion (baseline), with the vessel occluded (occlusion), and after reversal of occlusion (re-perfusion). In saphenous veins, BFVi relative to baseline reduced to 5.2±3.7 % during occlusion and returned to 102.9±14.9 % during re-perfusion. Unlike ICG-VA, SurgeON BFM was able to monitor reduced BFVi and characterize re-perfusion robustly during five serial occlusion procedures conducted 2-5 min apart on the same vessel. Across four sheep MCA vessels, BFVi reduced to 18.6±7.7 % and returned to 120.1±27.8 % of baseline during occlusion and re-perfusion phases, respectively.
UNASSIGNED: SurgeON BFM can noninvasively monitor vascular occlusion status and provide intuitive visualization of BF information in real-time to an operating surgeon. This technology may find application in vascular, plastic, and neurovascular surgery.

UNASSIGNED: To investigate the accuracy of high-framerate echo particle image velocimetry (ePIV) and computational fluid dynamics (CFD) for determining velocity vectors in femoral bifurcation models through comparison with optical particle image velocimetry (oPIV).
UNASSIGNED: Separate femoral bifurcation models were built for oPIV and ePIV measurements of a non-stenosed (control) and a 75%-area stenosed common femoral artery. A flow loop was used to create triphasic pulsatile flow. In-plane velocity vectors were measured with oPIV and ePIV. Flow was simulated with CFD using boundary conditions from ePIV and additional duplex-ultrasound (DUS) measurements. Mean differences and 95%-limits of agreement (1.96*SD) of the velocity magnitudes in space and time were compared, and the similarity of vector complexity (VC) and time-averaged wall shear stress (TAWSS) was assessed.
UNASSIGNED: Similar flow features were observed between modalities with velocities up to 110 and 330  cm/s in the control and the stenosed model, respectively. Relative to oPIV, ePIV and CFD-ePIV showed negligible mean differences in velocity (<3  cm/s), with limits of agreement of ±25  cm/s (control) and ±34  cm/s (stenosed). CFD-DUS overestimated velocities with limits of agreements of 13±40 and 16.1±55  cm/s for the control and stenosed model, respectively. VC showed good agreement, whereas TAWSS showed similar trends but with higher values for ePIV, CFD-DUS, and CFD-ePIV compared to oPIV.
UNASSIGNED: EPIV and CFD-ePIV can accurately measure complex flow features in the femoral bifurcation and around a stenosis. CFD-DUS showed larger deviations in velocities making it a less robust technique for hemodynamical assessment. The applied ePIV and CFD techniques enable two- and three-dimensional assessment of local hemodynamics with high spatiotemporal resolution and thereby overcome key limitations of current clinical modalities making them an attractive and cost-effective alternative for hemodynamical assessment in clinical practice.

Functional ultrasound (fUS) flow imaging provides a non-invasive method for the in vivo study of cerebral blood flow and neural activity. This study used functional flow imaging to investigate rat brain\'s response to ultrasound and colored-light stimuli. Male Long-Evan rats were exposed to direct full-field strobe flashes light and ultrasound stimulation to their retinas, while brain activity was measured using high-frequency ultrasound imaging. Our study found that light stimuli, particularly blue light, elicited strong responses in the visual cortex and lateral geniculate nucleus (LGN), as evidenced by changes in cerebral blood volume (CBV). In contrast, ultrasound stimulation elicited responses undetectable with fUS flow imaging, although these were observable when directly measuring the brain\'s electrical signals. These findings suggest that fUS flow imaging can effectively differentiate neural responses to visual stimuli, with potential applications in understanding visual processing and developing new diagnostic tools.

AVM surgery is challenging due to progressive and often unforeseeable flow changes during its resection which involve both the AVM and the surrounding brain tissue. Hence, accurate monitoring of blood flow is crucial to minimize complications and improve outcomes. The following case report illustrates the usefulness of complimentary non-invasive tools that can provide real time blood flow assessment. We present a case demonstrating the application of laser speckle contrast imaging (LSCI) in evaluating vessel flow dynamics during AVM surgery. A 30-year-old female presented with sudden headaches, nausea, vomiting, and vertigo. Emergency imaging revealed a ruptured cerebellar AVM necessitating surgical intervention. LSCI was integrated into the surgical workflow, providing continuous visualization of relative cerebral blood flow (rCBF) of vessels surrounding the AVM. Before AVM resection, LSCI measurements revealed the arterialized vasculature supplying the AVM nidus; measurements after AVM resection showed significant hemodynamic changes including normal flow in the initially arterialized AVM draining veins and adjacent arterial branches. LSCI also detected blood flow alterations during temporary occlusion, enabling assessment of downstream vascular regions. In conclusion, we provide an example supporting the utility of LSCI for real-time hemodynamic monitoring during AVM resection surgery. LSCI offers non-invasive, continuous, and immediate blood flow information, complementing conventional imaging methods like indocyanine green angiography. Additionally, our findings suggest that LSCI has the potential to provide a non-invasive means of identifying the specific superficial vessel branches or cortical areas that receive blood supply from a particular vessel.

UNASSIGNED: Extracting explainable flow metrics is a bottleneck to the clinical translation of advanced cardiac flow imaging modalities. We hypothesized that reduced-order models (ROMs) of intraventricular flow are a suitable strategy for deriving simple and interpretable clinical metrics suitable for further assessments. Combined with machine learning (ML) flow-based ROMs could provide new insight to help diagnose and risk-stratify patients.
UNASSIGNED: We analyzed 2D color-Doppler echocardiograms of 81 non-ischemic dilated cardiomyopathy (DCM) patients, 51 hypertrophic cardiomyopathy (HCM) patients, and 77 normal volunteers (Control). We applied proper orthogonal decomposition (POD) to build patient-specific and cohort-specific ROMs of LV flow. Each ROM aggregates a low number of components representing a spatially dependent velocity map modulated along the cardiac cycle by a time-dependent coefficient. We tested three classifiers using deliberately simple ML analyses of these ROMs with varying supervision levels. In supervised models, hyperparameter gridsearch was used to derive the ROMs that maximize classification power. The classifiers were blinded to LV chamber geometry and function. We ran vector flow mapping on the color-Doppler sequences to help visualize flow patterns and interpret the ML results.
UNASSIGNED: POD-based ROMs stably represented each cohort through 10-fold cross-validation. The principal POD mode captured >80% of the flow kinetic energy (KE) in all cohorts and represented the LV filling/emptying jets. Mode 2 represented the diastolic vortex and its KE contribution ranged from <1% (HCM) to 13% (DCM). Semi-unsupervised classification using patient-specific ROMs revealed that the KE ratio of these two principal modes, the vortex-to-jet (V2J) energy ratio, is a simple, interpretable metric that discriminates DCM, HCM, and Control patients. Receiver operating characteristic curves using V2J as classifier had areas under the curve of 0.81, 0.91, and 0.95 for distinguishing HCM vs. Control, DCM vs. Control, and DCM vs. HCM, respectively.
UNASSIGNED: Modal decomposition of cardiac flow can be used to create ROMs of normal and pathological flow patterns, uncovering simple interpretable flow metrics with power to discriminate disease states, and particularly suitable for further processing using ML.

Block matching serves as the foundation for ultrasound velocimetry techniques such as blood speckle tracking and echo-particle image velocimetry. Any spatial velocity gradients (SVGs) inside a block-matching pair will result in tracking error, due to both the finite block size and the ultrasound point-spread-function. We assess, using an in silico sinusoidal flow phantom, the effect of SVG magnitude and beam-to-flow angle on block-matching bias and precision. Secondarily we assess the effect that SVGs have on velocimetry bias when using angled plane-wave compounding.
The magnitude and angle of SVGs were varied by adjusting the wavelength and direction of a sinusoidal flow profile. Scatterers displaced by this flow profile were used for simulating ultrasound radio frequency data at discrete time points. After beamforming, the 2-D flow field was estimated using block matching. Two imaging sequences were tested, a single plane-wave and a three-angled plane-wave.
Smaller sinusoidal flow wavelengths resulted in increased bias and reduced precision, revealing an inverse relationship between sinusoidal flow wavelength and tracking error, with median errors ranging from 69%-90% for the smallest flow wavelengths (highest SVGs) down to 3%-5% for the largest (lowest SVGs). The SVG angle was also important, in which lateral SVGs (with axially oriented flows) resulted in significant speckle decorrelation and high tracking errors in regions with high SVGs. Conversely, axial SVGs (laterally oriented flow) experienced higher bias in the peak velocity regions of the flow profile. Coherent compounding resulted in higher velocity errors than using a single transmission for lateral SVGs but not for axial SVGs.
The highest SVGs that could be measured with ≤10% error was when the sinusoidal flow wavelength was less than 20 times the ultrasound pulse wavelength. The clinical significance is that the high SVGs present in high kinetic energy flows, such as severe carotid stenosis and aortic regurgitation, will limit the ability to accurately quantify the velocities in these flow structures.

Morphologically realistic flow phantoms are essential experimental tools for quantitative ultrasound-based microvessel imaging. As new quantitative flow imaging tools are developed, the need for more complex vessel-mimicking phantoms is indisputable. In this article, we propose a method for fabricating phantoms with sub-millimeter channels consisting of branches and curvatures in various shapes and sizes suitable for quantifying vessel morphological features. We used different tissue-mimicking materials (TMMs) compatible with ultrasound imaging as the base and metal wires of different diameters (0.15-1.25 mm) to create wall-less channels. The TMMs used are silicone rubber, plastisol, conventional gelatin, and medical gelatin. Mother channels in these phantoms were made in diameters of 1.25 mm or 0.3 mm and the daughter channels in diameters 0.3 mm or 0.15 mm. Bifurcations were created by soldering wires together at branch points. Quantitative parameters were assessed, and accuracy of measurements from the ground truth were determined. Channel diameters were seen to have increased (76-270%) compared to the initial state in the power Doppler images, partly due to blood mimicking fluid pressure. Amongst the microflow phantoms made from the different TMMs, the medical gelatin phantom was selected as the best option for microflow imaging, fulfilling the objective of being easy to fabricate with high transmittance while having a speed of sound and acoustic attenuation close to human tissue. A flow velocity of 0.85 ± 0.01 mm/s, comparable to physiological flow velocity was observed in the smallest diameter phantom (medical gelatin branch) presented here. We successfully constructed more complex geometries, including tortuous and multibranch channels using the medical gelatin as the TMM. We anticipate this will create new avenues for validating quantitative ultrasound microvessel imaging techniques.

The tubuloglomerular feedback (TGF) mechanism modulates renal hemodynamics and glomerular filtration rate in individual nephrons. Our study aimed to evaluate the TGF-induced vascular responses by inhibiting Na-K-2Cl co-transporters and sodium-glucose co-transporters in rats. We assessed cortical hemodynamics with high-resolution laser speckle contrast imaging, which enabled the evaluation of blood flow in individual microvessels and analysis of their dynamical patterns in the time-frequency domain. We demonstrated that a systemic administration of furosemide abolishes TGF-mediated hemodynamic responses. Furthermore, we showed that the local microcirculatory blood flow decreased, and the TGF-induced hemodynamic oscillations were sustained but weakened after inhibiting sodium-glucose co-transporters in Sprague-Dawley rats.