Real-time Blood Flow Imaging Research Articles

Constructing a Transient Ischemia Attack Model Utilizing Flexible Spatial Targeting Photothrombosis with Real-Time Blood Flow Imaging Feedback.

Transient ischemic attack (TIA) is an early warning sign of stroke and death, necessitating suitable animal models due to the associated clinical diagnostic challenges. In this study, we developed a TIA model using flexible spatially targeted photothrombosis combined with real-time blood flow imaging feedback. By modulating the excitation light using wavefront technology, we precisely created a square light spot (50 × 250 µm), targeted at the distal middle cerebral artery (dMCA). The use of laser speckle contrast imaging (LSCI) provided real-time feedback on the ischemia, while the excitation light was ceased upon reaching complete occlusion. Our results demonstrated that the photothrombus formed in the dMCA and spontaneously recanalized within 10 min (416.8 ± 96.4 s), with no sensorimotor deficits or infarction 24 h post-TIA. During the acute phase, ischemic spreading depression occurred in the ipsilateral dorsal cortex, leading to more severe ischemia and collateral circulation establishment synchronized with the onset of dMCA narrowing. Post-reperfusion, the thrombi were primarily in the sensorimotor and visual cortex, disappearing within 24 h. The blood flow changes in the dMCA were more indicative of cortical ischemic conditions than diameter changes. Our method successfully establishes a photochemical TIA model based on the dMCA, allowing for the dynamic observation and control of thrombus formation and recanalization and enabling real-time monitoring of the impacts on cerebral blood flow during the acute phase of TIA.

ADMNet: Adaptive-Weighting Dual Mapping for Online Tracking With Respiratory Motion Estimation in Contrast-Enhanced Ultrasound.

Lesion localization and tracking are critical for accurate, automated medical imaging analysis. Contrast-enhanced ultrasound (CEUS) significantly enriches traditional B-mode ultrasound with contrast agents to provide high-resolution, real-time images of blood flow in tissues and organs. However, many trackers, designed primarily for natural RGB or B-mode ultrasound images, underutilize the extensive data from dual-screen enhanced images and fail to account for respiratory motion, thus facing challenges in achieving accurate target tracking. To address the existing challenges, we propose an adaptive-weighted dual mapping (ADMNet), an online tracking framework tailored for CEUS. Firstly, we introduced a novel Multimodal Atrous Attention Fusion (MAAF) module, innovatively designed to adapt the weightage between B-mode and enhanced images in dual-screen CEUS, reflecting the clinician's dynamic focus shifts between screens. Secondly, we proposed a Respiratory Motion Compensation (RMC) module to correct motion trajectory interferences due to respiratory motion, effectively leveraging temporal information. We utilized two newly established CEUS datasets, totaling 35,082 frames, to benchmark the ADMNet against various advanced B-mode ultrasound trackers. Our extensive experiments revealed that ADMNet achieves new state-of-the-art performance in CEUS tracking. Ablation studies and visualizations further underline the effectiveness of MAAF and RMC modules, demonstrating the promising potential of ADMNet in clinical CEUS tracing, thus providing novel research avenues in this field.

Effect of vascular structure on laser speckle contrast imaging

Laser speckle contrast imaging (LSCI) is a powerful tool for non-invasive, real-time imaging of blood flow in tissue. However, the effect of tissue geometry on the form of the electric field autocorrelation function and speckle contrast values is yet to be investigated. In this paper, we present an ultrafast forward model for simulating a speckle contrast image with the ability to rapidly update the image for a desired illumination pattern and flow perturbation. We demonstrate the first simulated speckle contrast image and compare it against experimental results. We simulate three mouse-specific cerebral cortex decorrelation time images and implement three different schemes for analyzing the effects of homogenization of vascular structure on correlation decay times. Our results indicate that dissolving structure and assuming homogeneous geometry creates up to ∼ 10x shift in the correlation function decay times and alters its form compared with the case for which the exact geometry is simulated. These effects are more pronounced for point illumination and detection imaging schemes, highlighting the significance of accurate modeling of the three-dimensional vascular geometry for accurate blood flow estimates.

Prospective Study Comparing Clinical vs Indocyanine Green Fluorescence-Based Assessment of Line of Transection in Robotic Rectal Cancer Surgery-Indian Study.

Anastomotic leakage continues to be the most feared postoperative complications in rectal surgery with negative impact on both short- and long-term outcomes. Fortunately, new surgical strategies have helped to offset this complication and improve surgical outcomes. Traditionally, perfusion is assessed by intraoperative visual judgment by the surgeon. These subjective methods lack predictive accuracy resulting in either excess or insufficient colonic resection. Indocyanine green (ICG) fluorescence has shown promise in identifying the adequacy of perfusion. After injection of ICG, the system projected high-resolution near-infrared real-time images of blood flow in mesentery and bowel wall. This novel imaging method is used intraoperatively for taking real-time informed decisions. We conducted a single institutional prospective study to identify the feasibility of ICG identification of vascularity of anastomotic site and its impact on the change of plan of surgical management in robotic rectal cancer surgery. Between September 2017 and April 2019, fifty patients undergoing robotic rectal cancer surgery were included in the study. The aim was to analyze the feasibility and clinical benefit of intraoperative near-infrared fluorescence imaging in determining the line of transection in comparison with the traditional method. Line of proximal transection of the bowel subjectively assessed by the surgical team was marked point B and that after ICG injection was marked point A if moved proximally and point C if moved distally. The vascular anatomy was clearly identified with no intraoperative or injection-related adverse effects. Of the 50 patients, the line of transaction remained the same in 6 patients (12%). Based on the fluorescence imaging, the surgical team opted for further proximal change of the transection line up to an "adequate" fluorescent portion in 3 patients (6%) and distally in 41 patients (82%). ICG-based infrared image-guided localization gives a real-time image of colon vascularity possibly affecting anastomotic leak. The ICG fluorescence imaging system is a simple, safe, and useful technique, performed within a short time, and it enables visual evaluation of the blood flow in the intestinal tract prior to anastomosis. Larger studies are needed before this can become the standard of care.

642 The Use of Laser Speckle Contrast Imaging in Assessing Depth and Progression of Burn Wounds

Abstract Introduction The ability of laser speckle contrast imaging (LSCI) to provide real-time images of blood flow makes this modality appealing in the assessment of burn wounds, particularly for clinicians making treatment decisions based on burn wound depth and presumed progression. Here we present 2 preclinical studies that used LSCI to assess wound progress, both immediately and months after injury. Methods LSCI images were taken 10-40cm away from the wound and captured with a 1388x1038-pixel CCD camera. In the first study, LSCI images were captured prior to and immediately following creation of superficial partial-thickness (SPTB, 10s), deep partial-thickness (DPTB, 15s), and full-thickness burns (FTB, 20s), and on post-burn day (PBD) 1, 2, and 3. In the second study, LSCI images were obtained before and after DPTB creation and on PBD 7, 14, 21, 28, 60, 90, and 120. Results 92 wounds from 9 swine were included. Speckle data was normalized to control sites and converted to percentages ([speckle wound/speckle control] x 100), producing speckle percentage of control (SPOC) which quantifies the relative decrease or increase in speckle output (vascularity). SPOC was significantly decreased for all burn times on PBD 0, 1, and 2. By PBD 3, only DPTB and FTB remained diminished (p=0.028 and p=0.005, respectively), and FTB SPOC was significantly less than the SPTB (p=0.015). In the second study, SPOC showed an increase post-debridement on PBD 7, noted as post-debridement day (PDD) 0. SPOC continued to increase significantly to a peak at PDD 7 (p< 0.0001) and remained elevated until PDD 28. By PDD 60, SPOC was no longer significantly increased. Conclusions LSCI is a reliable method for analyzing burn depth and wound progression in the preclinical setting. LSCI data shows an immediate decrease in vascularity at all burn depths immediately following burn creation, followed by a peak in vascularity on PDD 7, with a trend back to normal by PDD 60. Applicability of Research to Practice The correlation of wound bed vascularity based on LSCI to known data on burn depth and progression suggests that LSCI could be a useful measurement tool in the clinical setting for the provider determining wound viability.

From coloured stars to colour flow imaging – or when is ‘Doppler’ not Doppler?

In 1842 Christian Doppler wrote a paper entitled ‘On the Coloured Light of the Double Stars’ in which he sort to explain why some stars appear bluish and some reddish. His theory was that when a star is approaching an observer the wavelength of its light will be shorter and the star thus appears to be blue, whilst when a star is receding from an observer the wavelengths of its light will be longer and it would appear to be red. Doppler was actually wrong on a number of counts as to the explanation for the colour of stars (as will be explained during the talk) although his theory was correct. It is therefore perhaps slightly ironic that Doppler's theory is now widely used in astronomy to measure the speed with which stars are receding from the earth. Doppler's theory was challenged by the young Dutch scientist Christophorus Buys-Ballot, who believed that Doppler's theory could not explain the colours of double stars and set out to prove experimentally, using sound rather that light, that the Doppler effect did not exist. He carried out a number of experiments involving horn players travelling on the Amsterdam-Utrecht railway line, but instead of disproving the Doppler effect, showed that Doppler's theory was correct. The possibility of using the Doppler effect for measuring blood flow was introduced by Shigeo Satomura and colleagues in a number of papers published between 1955 and 1960, and a major advance took place around 1969 when Peter Wells, Pierre Peronneau, and Donald Baker independently described Pulsed ‘Doppler’ units which enabled blood flow signals from specific ranges to be acquired. Further important advances took place around 1982 when Kasai and Namekawa introduced real-time blood flow imaging. Curiously enough, however, whilst continuous wave Doppler units rely on the Doppler shift on the back-scattered ultrasound to measure blood flow velocity, instruments which use pulsed waves do not (and could not for reasons that will once again be explained during the talk) measure the Doppler shift on individual pulses, but rather measure the relative phase-shifts of returning signals with respect to a master oscillator in each inter-pulse interval. Fortunately for most practical purposes the resulting signal is equivalent to a Doppler shift signal. In summary, this talk will explain why the apparent colour of stars could not be due to the Doppler effect, and why pulsed ‘Doppler’ devices cannot detect Doppler frequency shifts.

Laser speckle imaging to improve clinical outcomes for patients with trigeminal neuralgia undergoing radiofrequency thermocoagulation.

Percutaneous treatments for trigeminal neuralgia are safe, simple, and effective for achieving good pain control. Procedural risks could be minimized by using noninvasive imaging techniques to improve the placement of the radiofrequency thermocoagulation probe into the trigeminal ganglion. Positioning of a probe is crucial to maximize pain relief and to minimize unwanted side effects, such as denervation in unaffected areas. This investigation examined the use of laser speckle imaging during probe placement in an animal model. This preclinical safety study used nonhuman primates, Macaca nemestrina (pigtail monkeys), to examine whether real-time imaging of blood flow in the face during the positioning of a coagulation probe could monitor the location and guide the positioning of the probe within the trigeminal ganglion. Data from 6 experiments in 3 pigtail monkeys support the hypothesis that laser imaging is safe and improves the accuracy of probe placement. Noninvasive laser speckle imaging can be performed safely in nonhuman primates. Because improved probe placement may reduce morbidity associated with percutaneous rhizotomies, efficacy trials of laser speckle imaging should be conducted in humans.

Induction and imaging of photothrombotic stroke in conscious and freely moving rats.

In experimental stroke research, anesthesia is common and serves as a major reason for translational failure. Real-time cerebral blood flow (CBF) monitoring during stroke onset can provide important information for the prediction of brain injury; however, this is difficult to achieve in clinical practice due to various technical problems. We created a photothrombotic focal ischemic stroke model utilizing our self-developed miniature headstage in conscious and freely moving rats. In this model, a high spatiotemporal resolution imager using laser speckle contrast imaging technology was integrated to acquire real-time two-dimensional CBF information during thrombosis. The feasibility, stability, and reliability of the system were tested in terms of CBF, behavior, and T2-weighted magnetic resonance imaging (MRI) findings. After completion of occlusion, the CBF in the targeted cortex of the stroke group was reduced to 16 ± 9% of the baseline value. The mean infarct volume measured by MRI 24 h postmodeling was 77 ± 11 mm3 and correlated well with CBF (R2 = 0.74). This rodent model of focal cerebral ischemia and real-time blood flow imaging opens the possibility of performing various fundamental and translational studies on stroke without the influence of anesthetics.

Blood flow dynamics after laser therapy of port wine stain birthmarks

During laser therapy of port wine stain (PWS) birthmarks, regions of perfusion may persist. We hypothesize that such regions are not readily observable even when laser surgery is performed by highly experienced clinicians. The objective of this study was to use objective feedback to assess the acute vascular response to laser therapy. A clinic-friendly laser speckle imaging (LSI) instrument was developed to provide the clinician with real-time images of blood flow during laser therapy. Images were acquired from patients undergoing laser therapy of PWS birthmarks at Scripps Clinic and the Beckman Laser Institute and Medical Clinic. Blood flow maps were extracted from the acquired imaging data. Histogram-based analysis was applied in grading the degree of heterogeneity present in the blood flow maps after laser therapy. Collectively, two types of patient responses were observed in response to laser exposure: (1) an immediate increase in perfusion within minutes after laser therapy; and (2) an overall decrease in blood perfusion approximately 1 hour after laser therapy, with distinct regions of persistent perfusion apparent in the majority of post-treatment blood-flow images. A comparison of blood flow in PWS and adjacent normal skin demonstrated that PWS blood flow can be greater than, or sometimes equivalent to, that of normal skin. In general, a decrease in skin perfusion is observed during pulsed laser therapy of PWS birthmarks. However, a heterogeneous perfusion map was frequently observed. These regions of persistent perfusion may be due to incomplete photocoagulation of the targeted vessels. We hypothesize that immediate retreatment of these regions identified with LSI, will result in enhanced removal of the PWS vasculature. Lasers Surg. Med. 41:563-571, 2009. (c) 2009 Wiley-Liss, Inc.

B-Flow Imaging of the Hepatic Vasculature: Correlation with Color Doppler Sonography

B-flow imaging is a non-Doppler technology that provides real-time imaging of blood flow during gray-scale sonography. The utility of B-flow imaging is reflected in numerous publications that describe normal and pathologic findings in the carotid arteries and hemodialysis fistulas. However, there is a paucity of articles describing B-flow imaging of the abdominopelvic viscera. The purpose of this article is to illustrate a spectrum of findings encountered during noninvasive flow evaluation of the hepatic vasculature, correlating the Doppler sonography and B-flow imaging findings. Color and spectral Doppler sonography are invaluable for noninvasive evaluation of the hepatic vasculature. However, a number of pitfalls and artifacts have been described that can cause important pathologic findings to be overlooked or can suggest incorrect diagnoses. In our experience, B-flow imaging often correctly displays normal and pathological vascular structures for which Doppler sonographic findings have been misleading or erroneous.

Noninvasive Methods for Determining Lesion Depth From Vesicant Exposure

Before sulfur mustard (HD) injuries can be effectively treated, assessment of lesion depth must occur. Accurate depth assessment is important because it dictates how aggressive treatment needs to be to minimize or prevent cosmetic and functional deficits. Depth of injury typically is assessed by physical examination. Diagnosing very superficial and very deep lesions is relatively easy for the experienced burn surgeon. Lesions of intermediate depth, however, are often problematic in determining the need for grafting. This study was a preliminary evaluation of two noninvasive bioengineering methodologies, laser Doppler perfusion imaging (LDPI) and indocyanine green fluorescence imaging (ICGFI), to determine their ability to accurately diagnose depth of sulfur mustard lesions in a weanling swine model. Histological evaluation was used to assess the accuracy of the imaging techniques in determining burn depth. Six female weanling swine (8-12 kg) were exposed to 400 microl of neat sulfur mustard on six ventral sites for 2, 8, 30, or 60 minutes. This exposure regimen produced lesions of varying depths from superficial to deep dermal. Evaluations of lesion depth using the bioengineering techniques were conducted at 24, 48, and 72 hours after exposure. After euthanasia at 72 hours after exposure, skin biopsies were taken from each site and processed for routine hematoxylin and eosin histological evaluation to determine the true depth of the lesion. Results demonstrated that LDPI and ICGFI were useful tools to characterize skin perfusion and provided a good estimate of HD lesion depth. Traditional LDPI and the novel prototype ICGFI instrumentation used in this study produced images of blood flow through skin lesions, which provided a useful assessment of burn depth. LDPI and ICGFI accurately predicted the need for aggressive treatment (30- and 60-minute HD lesions) and nonaggressive treatment (2- and 8-minute HD lesions) for the lesions generated in this study. Histological evaluation confirmed the accuracy of the assessment. The ICGFI instrument offers several advantages over LDPI including real-time blood flow imaging, low cost, small size, portability, and not requiring the patient to be repositioned. A negative, however, is the need for intravenous dye injection. Although this would not be an issue in a hospital, it may be problematic in a mass casualty field setting. Additional experiments are required to determine the exposure time necessary to produce a graded series of partial-thickness HD lesions and to optimize instrumental parameters. The data generated in this follow-on study will allow for a full assessment of the potential LDPI and ICGFI hold for predicting the need for aggressive treatment after HD exposure. The lasting message is that objective imaging techniques can augment the visual judgment of burn depth.

Real-time in vivo color Doppler optical coherence tomography.

Color Doppler optical coherence tomography (CDOCT) is a functional extension of optical coherence tomography (OCT) that can image flow in turbid media. We have developed a CDOCT system capable of imaging flow in real time. Doppler processing of the analog signal is accomplished in hardware in the time domain using a novel autocorrelation technique. This Doppler processing method is compatible with a high speed OCT system capable of imaging in real time. Using this system, we demonstrate cross-sectional imaging of bidirectional flow with CDOCT at four frames per second in a tissue-simulating phantom consisting of intralipid solution flowing in glass capillaries. As a demonstration of real-time imaging of blood flow in vivo we imaged pulsatible blood flow in a rat femoral artery at eight frames per second. Issues of velocity sensitivity, imaging speed, and range of velocity measurement are discussed, as well as potential applications of real-time CDOCT.

Real time blood flow imaging by spiral scan phase velocity mapping.

The work describes the development of a novel sequence that uses rapid spiral k-space sampling, combined with phase velocity mapping, for real time flow velocity imaging. The performance of the technique is assessed on phantoms for both through-plane and in-plane flows. The flow measurements compared well with those measured using a bucket and stopwatch. One advantage of the technique is that flow related signal loss is minimal due to the early acquisition of the center of k-space data. Flow artifacts were observed for in-plane flow and these were understood with the aid of computer simulations. In vivo studies involved cine velocity mapping in normal volunteers; aortic blood flow waveforms acquired by spiral scanning in two cardiac cycles compared well with data from a conventional gradient-echo sequence. Potential applications of the method are demonstrated by studying the response of aortic flow to physical exercise and the real time monitoring of aortic flow during a valsalver maneuver.

Time domain formulation of pulse-Doppler ultrasound and blood velocity estimation by cross correlation

The Doppler effect is usually described as a frequency shift of the backscattered signals from moving targets with respect to the frequency transmitted. Recently, real-time blood flow imaging has become possible thanks to the development of a new velocity estimator based on phase-shift measurements of successive echoes. However, this method suffers from the well-known limitations of pulse-Doppler instruments. A new formulation is presented which describes the pulse-Doppler effect on the successive echoes from a cloud of moving targets as a progressive translation in time due to the displacement of the scatterers between two excitations. This approach allows us to generate efficiently computer-simulated data in order to evaluate accurately the various processing techniques. Furthermore, it leads to a novel class of velocity estimators in the time domain which measure the time shifts which are proportional to the local blood velocity. Among them, the cross correlation of the received rf signals turns out to be well suited. A local cross-correlation function is first calculated from a consecutive pair of range-gated echoes and the time shift is then determined by searching for the time position with the maximum correlation. The time-correlation technique is shown to provide accurate velocity profiles with broadband transducers. Moreover, the classical velocity limitation of pulse-Doppler is overcome because there is no ambiguity in measuring a time shift instead of a phase shift. These major advantages should make quantitative flow mapping possible and more reliable.

Time domain formulation of pulse-Doppler ultrasound and blood velocity estimation by cross correlation.

The Doppler effect is usually described as a frequency shift of the backscattered signals from moving targets with respect to the frequency transmitted. Recently, real-time blood flow imaging has become possible thanks to the development of a new velocity estimator based on phase-shift measurements of successive echoes. However, this method suffers from the well-known limitations of pulse-Doppler instruments. A new formulation is presented which describes the pulse-Doppler effect on the successive echoes from a cloud of moving targets as a progressive translation in time due to the displacement of the scatterers between two excitations. This approach allows us to generate efficiently computer-simulated data in order to evaluate accurately the various processing techniques. Furthermore, it leads to a novel class of velocity estimators in the time domain which measure the time shifts which are proportional to the local blood velocity. Among them, the cross correlation of the received rf signals turns out to be well suited. A local cross-correlation function is first calculated from a consecutive pair of range-gated echoes and the time shift is then determined by searching for the time position with the maximum correlation. The time-correlation technique is shown to provide accurate velocity profiles with broadband transducers. Moreover, the classical velocity limitation of pulse-Doppler is overcome because there is no ambiguity in measuring a time shift instead of a phase shift. These major advantages should make quantitative flow mapping possible and more reliable.