High Frame Research Articles

Abstract 4177: High-throughput in vivo monitoring of splenomegaly and tumor burden in a murine breast cancer model

Abstract Splenomegaly is a valuable parameter in mouse model cancer studies, as it can reflect the magnitude of cancer burden, hematopoietic activity, immune status, and can provide an indirect measure of cancer treatment efficacy. In liquid cancer models specifically (leukemia/lymphoma), spleen sizing is important as it is usually the only measure of in vivo tumor burden that can be assessed noninvasively without genetic labeling of tumor cells. Magnetic resonance imaging (MRI) and contrast-enhanced computed tomography (CT) are highly effective at evaluating spleen size in small animals. However, these techniques can impose limitations on large-cohort study designs due to high cost, long scan time, and ionizing radiation. Ultrasound is an alternative method with lower cost, high frame rate, and no ionization, but can suffer from poor inter-user variability, limited 2D field-of-view, and low throughput due to manual operation. In this work, we evaluated a novel 3D automated ultrasound scanner (Vega, Revvity, Inc.) for rapid assessment of splenomegaly in a murine cancer model. Female BALB/c mice (n=10) were implanted with 5e5 4T1 (ATCC) cells on the right flank. Mice were imaged at five timepoints over 25 days to track longitudinal progression of both spleen and tumor enlargement. Images were segmented manually in 3D using the “Slice Draw” and “Fill Between Slices” effects in SonoEQ v2.0.1 (Revvity, Inc.) to quantify tissue volume. After the final timepoint, mice were euthanized, and spleen weight was measured ex vivo. An additional cohort of age-matched mice without tumors (n=7) were imaged at the final timepoint to serve as controls. Imaging revealed a substantial enlargement of the spleen over time, from 30 ± 3 mm3 to 545 ± 105 mm3, representing an 18-fold increase. In the same time span, tumor volume grew to 1966 ± 87 mm3. Correlation analysis demonstrated good agreement between ultrasound volumes and ex vivo spleen weights (R² = 0.90). The results in this study demonstrate that noninvasive, nonlabelled quantification of murine spleen size with automated ultrasound is feasible, robust, and fast. The average time to acquire the spleen image for each mouse was less than 30 seconds. Future studies will apply this workflow in liquid cancer models, as well as explore using machine learning approaches to automatically segment spleen borders for faster data analysis. Citation Format: Craig McMannus, Tomek J. Czernuszewicz, Ryan C. Gessner, Jeffrey D. Peterson. High-throughput in vivo monitoring of splenomegaly and tumor burden in a murine breast cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4177.

FFYOLO: A Lightweight Forest Fire Detection Model Based on YOLOv8

Forest is an important resource for human survival, and forest fires are a serious threat to forest protection. Therefore, the early detection of fire and smoke is particularly important. Based on the manually set feature extraction method, the detection accuracy of the machine learning forest fire detection method is limited, and it is unable to deal with complex scenes. Meanwhile, most deep learning methods are difficult to deploy due to high computational costs. To address these issues, this paper proposes a lightweight forest fire detection model based on YOLOv8 (FFYOLO). Firstly, in order to better extract the features of fire and smoke, a channel prior dilatation attention module (CPDA) is proposed. Secondly, the mixed-classification detection head (MCDH), a new detection head, is designed. Furthermore, MPDIoU is introduced to enhance the regression and classification accuracy of the model. Then, in the Neck section, a lightweight GSConv module is applied to reduce parameters while maintaining model accuracy. Finally, the knowledge distillation strategy is used during training stage to enhance the generalization ability of the model and reduce the false detection. Experimental outcomes demonstrate that, in comparison to the original model, FFYOLO realizes an mAP0.5 of 88.8% on a custom forest fire dataset, which is 3.4% better than the original model, with 25.3% lower parameters and 9.3% higher frames per second (FPS).

Characterization of real-time cine MR imaging distortion on 0.35 T MRgRT with concentric cine imaging QA phantom

Objective. Real-time MRgRT uses 2D-cine imaging for target tracking and motion evaluation. Rotation of gantry induced B 0 off-resonance, resulting in image artifacts and imaging isocenter-shift precluding MR-guided arc therapy. Standard MRI phantoms designed for higher resolution images face challenges when low-resolution cine imaging is needed to achieve high frame rates. This work aimed to examine the spatial accuracy including geometric distortion and isocenter shift in real-time during gantry rotation on a 0.35 T MR-Linac using the concentric Cine imaging quality assurance (QA) phantom and its associated image analysis software. Approach. The Cine imaging QA phantom consists of two concentric shells of low-T1 mineral oil and a central alignment structure. The phantom was scanned on three different MRI systems; 0.55 T Siemens Free.Max, 1.5 T Philips Ingenia, and 0.35 T ViewRay MRIdian MR-Linac using 2D balanced steady-state free precession (bSSFP) imaging sequence. In addition, bSSFP cine MRI with the banding artifact correction was tested on 0.35 T ViewRay MR-Linac. Images from the MR-Linac were acquired with the Linac gantry stationary and rotating from gantry 300°→ 0° and vice versa. Three orthogonal image planes were scanned excluding the 1.5 T Philips Ingenia, where only the axial plane was scanned. The image analysis software calculated the distortion values as well as the isocenter position for each cine frame. Main results. The geometric distortion of cine imaging on MRIs and MR-Linac at gantry stationary are within 1 mm while the substantial geometric distortion of 2 and 2.2 mm were observed on 0.35 T MR-Linac while rotating the gantry clockwise (300°→ 0°) and counterclockwise 0°→ 300° respectively. The average imaging isocenter shift was 0.1 mm for both MRIs and the static gantry and imaging isocenter shift of ≤1.5 mm was observed during the gantry rotation. The imaging isocenter shift decreased by 1 ± 0.2 mm clockwise and counterclockwise with B 0 compensation. Significance. The concentric Cine imaging QA phantom and its associated software effectively demonstrate the image distortion on real-time cine imaging on regular MRIs and 0.35 T MR-Linac. The results of significant geometric distortion with a rotating gantry in the MR-Linac system require further investigation to alleviate the extent of the image distortion.

Fast volumetric multifocus structured illumination microscopy of subcellular dynamics in living cells.

Studying the nanoscale dynamics of subcellular structures is possible with 2D structured illumination microscopy (SIM). The method allows for acquisition with improved resolution over typical widefield. For 3D samples, the acquisition speed is inherently limited by the need to acquire sequential two-dimensional planes to create a volume. Here, we present a development of multifocus SIM designed to provide high volumetric frame rate by using fast synchronized electro-optical components. We demonstrate the high volumetric imaging capacity of the microscope by recording the dynamics of microtubule and endoplasmatic reticulum in living cells at up to 2.3 super resolution volumes per second for a total volume of 30 × 30 × 1.8 µm3.

Three Dimensional Reconstruction of Two-step Moving Objects based on Phase-shifting Profilometry

In recent years, 3D object reconstruction based on phase-shifting profilometry has gradually received attention and been widely applied. Domestic and foreign scholars have been continuously researching and exploring the accuracy and speed of three-dimensional measurement, and gradually developing towards dynamic measurement. Most dynamic measurements require projecting multiple stripe patterns to obtain sufficient object phase information, and the more stripes there are, the greater the phase error caused by motion. This article proposes the use of increasing the sampling fringe pattern during the projection period of a fringe pattern to achieve high frame rate dynamic 3D object reconstruction. By combining the intensity values of ambient light; Finally, the phase information of the object is extracted by tracking the motion information obtained from the moving object. This article demonstrates the feasibility of this method through simulation experiments and improves the frame rate of 3D reconstruction of moving objects.

A prototype scintillator real-time beam monitor for ultra-high dose rate radiotherapy.

FLASH Radiotherapy (RT) is an emergent cancer RT modality where an entire therapeutic dose is delivered at more than 1000 times higher dose rate than conventional RT. For clinical trials to be conducted safely, a precise and fast beam monitor that can generate out-of-tolerance beam interrupts is required. This paper describes the overall concept and provides results from a prototype ultra-fast, scintillator-based beam monitor for both proton and electron beam FLASH applications. A FLASH Beam Scintillator Monitor (FBSM) is being developed that employs a novel proprietary scintillator material. The FBSM has capabilities that conventional RT detector technologies are unable to simultaneously provide: (1) large area coverage; (2) a low mass profile; (3) a linear response over a broad dynamic range; (4) radiation hardness; (5) real-time analysis to provide an IEC-compliant fast beam-interrupt signal based on true two-dimensional beam imaging, radiation dosimetry and excellent spatial resolution. The FBSM uses a proprietary low mass, less than 0.5mm water equivalent, non-hygroscopic, radiation tolerant scintillator material (designated HM: hybrid material) that is viewed by high frame rate CMOS cameras. Folded optics using mirrors enable a thin monitor profile of ∼10cm. A field programmable gate array (FPGA) data acquisition system generates real-time analysis on a time scale appropriate to the FLASH RT beam modality: 100-1000Hz for pulsed electrons and 10-20kHz for quasi-continuous scanning proton pencil beams. An ion beam monitor served as the initial development platform for this work and was tested in low energy heavy-ion beams (86Kr+26 and protons). A prototype FBSM was fabricated and then tested in various radiation beams that included FLASH level dose per pulse electron beams, and a hospital RT clinic with electron beams. Results presented in this report include image quality, response linearity, radiation hardness, spatial resolution, and real-time data processing. The HM scintillator was found to be highly radiation damage resistant. It exhibited a small 0.025%/kGy signal decrease from a 216 kGy cumulative dose resulting from continuous exposure for 15 min at a FLASH compatible dose rate of 237Gy/s. Measurements of the signal amplitude versus beam fluence demonstrate linear response of the FBSM at FLASH compatible dose rates of >40Gy/s. Comparison with commercial Gafchromic film indicates that the FBSM produces a high resolution 2D beam image and can reproduce a nearly identical beam profile, including primary beam tails. The spatial resolution was measured at 35-40µm. Tests of the firmware beta version show successful operation at 20000Hz frame rate or 50 µs/frame, where the real-time analysis of the beam parameters is achieved in less than 1 µs. The FBSM is designed to provide real-time beam profile monitoring over a large active area without significantly degrading the beam quality. A prototype device has been staged in particle beams at currents of single particles up to FLASH level dose rates, using both continuous ion beams and pulsed electron beams. Using a novel scintillator, beam profiling has been demonstrated for currents extending from single particles to 10 nA currents. Radiation damage is minimal and even under FLASH conditions would require ≥50 kGy of accumulated exposure in a single spot to result in a 1% decrease in signal output. Beam imaging is comparable to radiochromic films, and provides immediate images without hours of processing. Real-time data processing, taking less than 50 µs (combined data transfer and analysis times), has been implemented in firmware for 20kHz frame rates for continuous proton beams.

Increasing abdominal aortic aneurysm curvature visibility using 3D dual probe bistatic ultrasound imaging combined with probe translation

High frame rate ultrasound (US) imaging techniques in 3D are promising tools for capturing abdominal aortic aneurysms (AAAs) over time, however, with the limited number of channel-to-element connections current footprints are small, which limits the field of view. Moreover, the maximal steering angle of the ultrasound beams in transmit and the maximal receptance angle in receive are insufficient for capturing the curvy shape of the AAA. Therefore, an approach is needed towards large arrays. In this study, high frame rate bistatic 3D US data (17 Hz) were acquired with two synchronized matrix arrays positioned at different locations (multi-aperture imaging) using a translation stage to simulate what a larger array with limited channel-to-element connections can potentially achieve. Acquisitions were performed along an AAA shaped phantom with different probe tilting angles (0 up to ± 30°). The performance of different multi-aperture configurations was quantified using the generalized contrast-to-noise ratio of the wall and lumen (gCNR). Furthermore, a parametric model of the multi-aperture system was used to estimate in which AAA wall regions the contrast is expected to be high. This was evaluated for AAAs with increasing diameters and curvature. With an eight-aperture 0° probe angle configuration a 69 % increase in field of view was measured in the longitudinal direction compared to the field of view of a single aperture configuration. When increasing the number of apertures from two to eight, the gCNR improved for the upper wall and lower wall by 35 % and 13 % (monostatic) and by 36 % and 13 % (bistatic). Contrast improvements up to 22 % (upper wall) and 12 % (lower wall) are achieved with tilted probe configurations compared to non-tilted configurations. Moreover, with bistatic imaging with tilted probe configurations gCNR improvements up to 4 % (upper wall) and 7 % (lower wall) are achieved compared to monostatic imaging. Furthermore, imaging with a larger inter-probe distance improved the gCNR for a ± 15° probe angle configuration. The gCNR has an expected pattern over time, where the contrast is lower when there is more wall motion (systole) and higher when motion is reduced (diastole). Furthermore, a higher frame rate (45 Hz) yields a lower gCNR, because fewer compound angles are used. The results of the parametric model suggest that a flat array is suitable for imaging AAA shapes with limited curvature, but that it is not suitable for imaging larger AAA shapes with more curvature. According to the model, tilted multi-aperture configurations combined with bistatic imaging can achieve a larger region with high contrast compared to non-tilted configurations. The findings of the model are in agreement with experimental findings. To conclude, this study demonstrates the vast improvements in field of view and AAA wall visibility that a large, sparsely populated 3D array can potentially achieve when imaging AAAs compared to single or dual aperture imaging. In the future, larger arrays, less thermal noise, more steering, and more channel-to-element connections combined with carefully chosen orientations of (sub-) apertures will likely advance 3D imaging of AAAs.

Miniaturized acoustic concentrators for ultrafast 3D ultrasound imaging

Ultrafast 3D ultrasound imaging is a rapidly growing research field that enables real-time imaging at a high frame rate and in a non-invasive manner. Currently, to achieve ultrafast 3D ultrasound, plane or diverging waves from virtual sources are used. These virtual sources can be considered as focal points during emission, allowing for improved transmission of ultrasonic energy. However, they have limitations in terms of transmitted energy, complex electronics, and timing issues, which impact the quality of the resulting images. To address this, a study was conducted to design and experiment with new miniaturized ultrasound transmitters based on cylindrical waveguides with tapered sections. These transmitters, with a diameter of approximately 100 μm, can replace the virtual sources. A numerical study based on 2D axisymmetric Finite Element Modeling (FEM) is first performed to model the transmission and reflection of longitudinal ultrasonic waves through various cylindrical rods. The results demonstrated that the transmission depends on the diameter ratio, frequency and longitudinal mode order (L0, L1, L2, etc.). An experimental study is then conducted on a stainless steel waveguide instrumented with 6mm piezo discs. The mechanical energy, estimated using Laser Doppler Vibrometer is transmitted through a 150 μm diameter rod, allowing mechananical focusing in the frequency range between 0.5 and 5 MHz. The application of this method to separate emission/reception transducers is then demonstrated for 3D ultrafast imaging.

Three-dimensional coherence beamforming using row-column arrays and matrix arrays

Much advancement in 3D ultrasound imaging has been achieved in recent years, allowing for its implementation in many research capacities. Translation of 3D imaging to a clinical setting has been hindered by small fields of view, expensive equipment and poor image quality. For ultrafast imaging, these challenges are accentuated by the need for a small number of transmission events. The row-column array is an emerging technology which can produce large field-of-view 3D ultrasound images, however, they can produce major artefacts when operated at high frame rates. Here we present some techniques which have been developed to improve the image quality and reduce the artifact level of row-column arrays by exploiting the incoherence of the transmission schemes. Presented will be the Row-Column specific Frame Multiply and Sum beamforming along with a technique for implementing Acoustic Sub-Aperture Processing which improves signal-to-noise ratio whilst also increasing the effective frame rate. Additional coherence-based algorithms, which have previously been developed for 2D imaging, are implemented and presented here for 3D imaging using a matrix array probe. All of the above algorithms have been optimised for super-resolution but should improve all types of 3D ultrasound imaging.

Parallel- and micro-beamforming challenges in real-time, high-frame-rate, ultrasound imaging

Delay-and-sum beamforming for classic (line-by-line) ultrasound imaging is usually performed in real-time by FPGAs and GPUs. However, when a high-frame-rate (HFR) has to be achieved, beamforming becomes challenging. Here, the echoes following the transmission of multi-line focused beams, plane waves, or diverging waves, must be simultaneously beamformed along multiple view lines. Such parallel beamforming is feasible online when the scanner is endowed with high flexibility and processing power. This talk will show how the FPGAs of the ULA-OP 256, a hardware-based open scanner, were efficiently utilized to enable parallel beamforming at high speed. The talk will also discuss how the data transfer between the scanner boards impacts the frame rate, which actually achieved 4400 frames per second through a new communication topology. The talk will also examine the image quality deterioration emerging when HFR imaging sequences are implemented in probes equipped with a microbeamformer (uB) that was designed for focused beam transmission. Simulations show how the transmitted beamwidth and uB size impact the image contrast and resolution, taking into account that the uB ASIC cannot handle multiple sets of delays and apodization weights after each transmit event. Technological improvements needed in the next generation uBs will be finally discussed.

Acoustic emissions based estimation of the temporal changes in microbubble radius during ultrasonic excitation

Our ability to study microbubble dynamics in vivo and link them to distinct mechano-biological effects hinges on our ability to accurately estimate the temporal changes in MB radius during ultrasonic excitation. Here, we hypothesize that real-time passive cavitation detection (PCD) monitoring combined with linear acoustic wave propagation theory can accurately estimate stable MB radius dynamics under in vivo conditions. To test our hypothesis, we employed numerical simulations, based on Rayleigh–Plesset modeling, followed by experimental validation, using calibrated PCDs with concurrent optical imaging of MB dynamics using high frame rate microscopy. Our method termed linear acoustic wave propagation and superposition (LAWPS) algorithm, combines Fourier series expansion with Euler’s relationship to estimate the acoustic emission (AE) from single MB, which is considered as a monopole source (i.e., R0 + ΔR < λ). LAWPS algorithm, which is independent of MB properties and, thus, can be linearly reversed to calculate MB oscillation radius from AE, was able to accurately capture the radiated pressure generated from a Rayleigh–Plesset MB modeling. Crucially, inverse LAWPS algorithm onto AE generated by Vokurka et al. resulted in the original MB model. Experimental observation using monodisperse MBs was able to accurately estimate the temporal changes in MB radius during 0.5 MHz ultrasonic excitation

Resolving soft X-ray photons with a high-rate hybrid pixel detector

Due to their high frame rates and dynamic range, large area coverage, and high signal-to-noise ratio, hybrid silicon pixel detectors are an established standard for photon science applications at X-ray energies between 2 keV and 20 keV. These properties also make hybrid detectors interesting for experiments with soft X-rays between 200 eV and 2 keV. In this energy range, however, standard hybrid detectors are limited by the quantum efficiency of the sensor and the noise of the readout electronics. These limitations can be overcome by utilizing inverse Low-Gain Avalanche Diode (iLGAD) sensors with an optimized X-ray entrance window. We have developed and characterized a prototype soft X-ray iLGAD sensor bonded to the charge integrating 75 µm pixel JUNGFRAU chip. Cooled to −22°C, the system multiplication factor of the signal generated by an impinging photon is ≥ 11. With this gain, the effective equivalent noise charge of the system is ≤5.5 electrons root-mean-square at a 5 µs integration time. We show that by cooling the system below −50°C, single photon resolution at 200 eV becomes feasible with a signal-to-noise ratio better than 5.

Contrast-Enhanced Ultrasound of the Indeterminate Renal Mass, From the AJR "How We Do It" Special Series.

Contrast-enhanced ultrasound (CEUS) is distinguished from CT and MRI by the use of microbubble ultrasound contrast agents (UCAs) with intravascular blood pool distribution. When performing CEUS, low-intensity ultrasound allows real-time tissue subtraction imaging, whereas high-intensity ultrasound leads to microbubble destruction, enabling visualization of the contrast inflow pattern. CEUS has exceptional contrast resolution that enables the detection of even minimal blood flow, achieving very high NPV for ruling out vascular perfusion and providing high frame rates in the evaluation of tissue perfusion dynamics. UCAs undergo hepatic metabolism and pulmonary clearance, ensuring safety in patients with renal impairment. CEUS excels in distinguishing solid from cystic renal masses, with higher sensitivity than CT or MRI for detection of lesion enhancement. CEUS can aid the further characterization of both solid and cystic lesions and may have particular applications in the surveillance of cystic masses and surveillance after renal cell carcinoma ablation. This review describes the use of CEUS to help characterize indeterminate renal masses, based on the authors' institutional experience. The article highlights key differences between CEUS and CT or MRI, and provides practical insights for performing and interpreting CEUS of renal masses.

NeuroIGN: Explainable Multimodal Image-Guided System for Precise Brain Tumor Surgery.

Precise neurosurgical guidance is critical for successful brain surgeries and plays a vital role in all phases of image-guided neurosurgery (IGN). Neuronavigation software enables real-time tracking of surgical tools, ensuring their presentation with high precision in relation to a virtual patient model. Therefore, this work focuses on the development of a novel multimodal IGN system, leveraging deep learning and explainable AI to enhance brain tumor surgery outcomes. The study establishes the clinical and technical requirements of the system for brain tumor surgeries. NeuroIGN adopts a modular architecture, including brain tumor segmentation, patient registration, and explainable output prediction, and integrates open-source packages into an interactive neuronavigational display. The NeuroIGN system components underwent validation and evaluation in both laboratory and simulated operating room (OR) settings. Experimental results demonstrated its accuracy in tumor segmentation and the success of ExplainAI in increasing the trust of medical professionals in deep learning. The proposed system was successfully assembled and set up within 11min in a pre-clinical OR setting with a tracking accuracy of 0.5 (± 0.1) mm. NeuroIGN was also evaluated as highly useful, with a high frame rate (19 FPS) and real-time ultrasound imaging capabilities. In conclusion, this paper describes not only the development of an open-source multimodal IGN system but also demonstrates the innovative application of deep learning and explainable AI algorithms in enhancing neuronavigation for brain tumor surgeries. By seamlessly integrating pre- and intra-operative patient image data with cutting-edge interventional devices, our experiments underscore the potential for deep learning models to improve the surgical treatment of brain tumors and long-term post-operative outcomes.

Real‐Time Polygonal Lighting of Iridescence Effect using Precomputed Monomial‐Gaussians

AbstractThe real world consists of mass phenomena, such as iridescence on thin film and metal oxide layers, that is only explicable by wave optics. Existing research can reproduce such effects with simple point lights or low‐frequency environmental lighting. However, it remains a difficult task to efficiently rendering these effects when near‐field, high‐frequency area lights are involved. This paper presents a high‐fidelity, real‐time rendering algorithm for the iridescence effect under polygonal lights. We introduce a novel set of spherical functions, Monomial‐Gaussians, to accurately fit iridescent materials' reflectance. With a precomputed lookup table, the Monomial‐Gaussians are easily integrated over spherical polygons in linear time. Importance sampling of Monomial‐Gaussians is also supported to efficiently reduce Monte‐Carlo error. Our approach produces accurate renderings of the iridescence effect while still preserving high frame rates.

Ultrasonography monitoring with Superb Microvascular Imaging during cerebrovascular surgery

IntroductionUltrasonography (US) is used as a real-time dynamic imaging modality during neurosurgery. A novel Doppler US technique, Superb Microvascular Imaging (SMI), can be used to visualize low-velocity flow of small vessels at high resolution with high frame rates. We visualized vessel flow using this US SMI technique and contrast agent during cerebrovascular surgery. MethodsForty-three patients with an unruptured cerebral aneurysm (control), ischemic and hemorrhagic moyamoya disease, carotid artery stenosis, hemangioblastoma, severe stenosis of the middle cerebral artery, venous angioma, and intracerebral hemorrhage (ICH) underwent neurosurgery with US SMI monitoring using a contrast agent. The diameter, length, and number of penetrating vessels were analyzed in patients with an unruptured cerebral aneurysm (control), moyamoya disease, and ICH. ResultsDiameter and length of cerebral penetrating vessels were significantly increased in patients with moyamoya disease and ICH compared to control patients. The number of penetrating vessels was increased in moyamoya disease patients compared to control and ICH patients. In hemorrhagic moyamoya disease, flow in the penetrating vessels originated from a deep periventricular point and extended to the cerebral surface. Pulsatile cerebral aneurysms during clipping surgery and carotid artery stenosis during carotid endarterectomy were easily identified by SMI. Drastically increased vessel flow in patients with a hemangioblastoma or a venous angioma was observed. ConclusionUsing the US SMI technique and contrast agent, we obtained useful flow information of the vascular disease structure and intracerebral deep small vessels during cerebrovascular surgery. Further quantitative analysis will be informative and helpful for cerebrovascular surgery.

Quantitative pulsatility measurements using 3D dynamic ultrasound localization microscopy

A rise in blood flow velocity variations (i.e. pulsatility) in the brain, caused by the stiffening of upstream arteries, is associated with cognitive impairment and neurodegenerative diseases. The study of this phenomenon requires brain-wide pulsatility measurements, with large penetration depth and high spatiotemporal resolution. The development of dynamic ultrasound localization microscopy (DULM), based on ULM, has enabled pulsatility measurements in the rodent brain in 2D. However, 2D imaging accesses only one slice of the brain and measures only 2D-projected and hence biased velocities . Herein, we present 3D DULM: using a single ultrasound scanner at high frame rate (1000–2000 Hz), this method can produce dynamic maps of microbubbles flowing in the bloodstream and extract quantitative pulsatility measurements in the cat brain with craniotomy and in the mouse brain through the skull, showing a wide range of flow hemodynamics in both large and small vessels. We highlighted a decrease in pulsatility along the vascular tree in the cat brain, which could be mapped with ultrasound down to a few tens of micrometers for the first time. We also performed an intra-animal validation of the method by showing consistent measurements between the two sides of the Willis circle in the mouse brain. Our study provides the first step towards a new biomarker that would allow the detection of dynamic abnormalities in microvessels in the brain, which could be linked to early signs of neurodegenerative diseases.

Quantum Efficiency Measurement and Modeling of Silicon Sensors Optimized for Soft X-ray Detection

Hybrid pixel detectors have become indispensable at synchrotron and X-ray free-electron laser facilities thanks to their large dynamic range, high frame rate, low noise, and large area. However, at energies below 3 keV, the detector performance is often limited because of the poor quantum efficiency of the sensor and the difficulty in achieving single-photon resolution due to the low signal-to-noise ratio. In this paper, we address the quantum efficiency of silicon sensors by refining the design of the entrance window, mainly by passivating the silicon surface and optimizing the dopant profile of the n+ region. We present the measurement of the quantum efficiency in the soft X-ray energy range for silicon sensors with several process variations in the fabrication of planar sensors with thin entrance windows. The quantum efficiency for 250 eV photons is increased from almost 0.5% for a standard sensor to up to 62% as a consequence of these developments, comparable to the quantum efficiency of backside-illuminated scientific CMOS sensors. Finally, we discuss the influence of the various process parameters on quantum efficiency and present a strategy for further improvement.

Evaluation of tumor microvasculature with 3D ultrasound localization microscopy based on 2D matrix array.

Evaluation of tumor microvascular morphology is of great significance in tumor diagnosis, therapeutic effect prediction, and surgical planning. Recently, two-dimensional ultrasound localization microscopy (2DULM) has demonstrated its superiority in the field of microvascular imaging. However, it suffers from planar dependence and is unintuitive. We propose a novel three-dimensional ultrasound localization microscopy (3DULM) to avoid these limitations. We investigated 3DULM based on a 2D array for tumor microvascular imaging. After intravenous injection of contrast agents, all elements of the 2D array transmit and receive signals to ensure a high and stable frame rate. Microbubble signal extraction, filtering, positioning, tracking, and other processing were used to obtain a 3D vascular map, flow velocity, and flow direction. To verify the effectiveness of 3DULM, it was validated on double helix tubes and rabbit VX2 tumors. Cisplatin was used to verify the ability of 3DULM to detect microvascular changes during tumor treatment. In vitro, the sizes measured by 3DULM at 3mm and 13mm were 178 and 182 , respectively. In the rabbit tumors, we acquired 9000 volumes to reveal vessels about 30 in diameter, which surpasses the diffraction limit of ultrasound in traditional ultrasound imaging, and the results matched with micro-angiography. In addition, there were significant changes in vascular density and curvature between the treatment and control groups. The effectiveness of 3DULM was verified in vitro and in vivo. Hence, 3DULM may have potential applications in tumor diagnosis, tumor treatment evaluation, surgical protocol guidance, and cardiovascular disease. 3D ultrasound localization microscopy is highly sensitive to microvascular changes; thus, it has clinical potential for tumor diagnosis and treatment evaluation. • 3D ultrasound localization microscopy is demonstrated on double helix tubes and rabbit VX2 tumors. • 3D ultrasound localization microscopy can reveal vessels about 30 in diameter-far smaller than traditional ultrasound. • This form of imaging has potential applications in tumor diagnosis, tumor treatment evaluation, surgical protocol guidance, and cardiovascular disease.

Evaluation of Turbulence Index and Flow Pattern for Atherosclerotic Carotid Stenosis: A High-Frame-Rate Vector Flow Imaging Study

ObjectiveThe emerging high-frame rate vector flow imaging (H-FRV Flow) provides a new way of hemodynamic evaluation for complex blood flow. This study aimed to explore quantitatively the characteristics of complex flow with turbulence (Tur) index and analyze flow pattern in atherosclerotic internal carotid artery stenosis (ICAS) using H-FRV Flow. MethodsThis study prospectively included 60 patients with ICAS. Tur values in different segments of stenosis and cardiac phases were compared. Meanwhile Spearman correlation analysis was performed between clinical plaque characteristics with turbulence grading by ln (Tur). Three complex flow patterns were qualitatively drawn on vector flow mode, and the detection rate of flow patterns in different stenosis groups and ulceration groups were compared. ResultsHighly disordered blood flow was observed in the stenosis (Tur (%) (M, QR) =12.5, 21.5) and distal segment (15.4, 27.2), particularly during systole (21.0, 30.7/ 33.3, 38.7, P<0.05). Spearman correlation analysis showed that stenosis rate was correlated with turbulence grading in the stenosis (ρ=0.65, P<0.05) and distal segment (ρ=0.79, P<0.05), and ulcer formation was correlated with turbulence grading in the stenosis segment (ρ=0.58, P<0.05). The overall detection rate of three flow patterns was higher respectively in the severe stenosis group (22/22) versus mild to moderate stenosis group (21/38) (P<0.001) and the ulcer group (21/23) versus non-ulcer group (23/37) (P<0.001). ConclusionH-FRV Flow was helpful for assess the severity and characteristics of flow turbulence. Lumen geometric factors could affect the flow turbulence and blood flow patterns around the plaque. This would provide important hemodynamic information for the detection of high-risk plaque.