Quantification Of Tissue Perfusion Research Articles

EFSUMB Technical Review - Update 2023: Dynamic Contrast-Enhanced Ultrasound (DCE-CEUS) for the Quantification of Tumor Perfusion.

Dynamic contrast-enhanced ultrasound (DCE-US) is a technique to quantify tissue perfusion based on phase-specific enhancement after the injection of microbubble contrast agents for diagnostic ultrasound. The guidelines of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) published in 2004 and updated in 2008, 2011, and 2020 focused on the use of contrast-enhanced ultrasound (CEUS), including essential technical requirements, training, investigational procedures and steps, guidance regarding image interpretation, established and recommended clinical indications, and safety considerations. However, the quantification of phase-specific enhancement patterns acquired with ultrasound contrast agents (UCAs) is not discussed here. The purpose of this EFSUMB Technical Review is to further establish a basis for the standardization of DCE-US focusing on treatment monitoring in oncology. It provides some recommendations and descriptions as to how to quantify dynamic ultrasound contrast enhancement, and technical explanations for the analysis of time-intensity curves (TICs). This update of the 2012 EFSUMB introduction to DCE-US includes clinical aspects for data collection, analysis, and interpretation that have emerged from recent studies. The current study not only aims to support future work in this research field but also to facilitate a transition to clinical routine use of DCE-US.

Real-time quantification of bowel perfusion using Laparoscopic Laser Speckle Contrast Imaging (LSCI) in a porcine model

Background/purposeReal-time quantification of tissue perfusion can improve intraoperative surgical decision making. Here we demonstrate the utility of Laser Speckle Contrast Imaging as an intra-operative tool that quantifies real-time regional differences in intestinal perfusion and distinguishes ischemic changes resulting from arterial/venous obstruction.MethodsPorcine models (n = 3) consisted of selectively devascularized small bowel loops that were used to measure the perfusion responses under conditions of control/no vascular occlusion, arterial inflow occlusion, and venous outflow occlusion using laser speckle imaging and indocyanine green fluoroscopy. Laser Speckle was also used to assess perfusion differences between small bowel antimesenteric-antimesenteric and mesenteric-mesenteric anastomoses. Perfusion quantification was measured in relative perfusion units calculated from the laser speckle perfusion heatmap.ResultsLaser Speckle distinguished between visually identified perfused, watershed, and ischemic intestinal segments with both color heatmap and quantification (p < .00001). It detected a continuous gradient of relative intestinal perfusion as a function of distance from the stapled ischemic bowel edge. Strong positive linear correlation between relative perfusion units and changes in mean arterial pressure resulting from both arterial (R2 = .96/.79) and venous pressure changes (R2 = .86/.96) was observed. Furthermore, Laser Speckle showed that the antimesenteric anastomosis had a higher perfusion than mesenteric anastomosis (p < 0.01).ConclusionsLaser Speckle Contrast Imaging provides objective, quantifiable tissue perfusion information in both color heatmap and relative numerical units. Laser Speckle can detect spatial/temporal differences in perfusion between antimesenteric and mesenteric borders of a bowel segment and precisely detect perfusion changes induced by progressive arterial/venous occlusions in real-time.

Techniques Providing Endpoints for Revascularization in Chronic Limb-Threatening Ischemia.

It is frequently difficult to estimate the revascularization endpoint in patients with chronic limb-threatening ischemia where there may be extensive multifocal multiarterial disease. There have been attempts to identify an endpoint for revascularization procedures, but none has become the standard of care. An ideal indicator of an endpoint can objectively quantify tissue perfusion, predict wound healing, and is easily and efficiently used intraprocedurally to assist real-time decision making on whether adequate perfusion has been reached. Candidate techniques to evaluate endpoints post-revascularization are discussed here.

Tissue-growth-based synthetic tree generation and perfusion simulation

Biological tissues receive oxygen and nutrients from blood vessels by developing an indispensable supply and demand relationship with the blood vessels. We implemented a synthetic tree generation algorithm by considering the interactions between the tissues and blood vessels. We first segment major arteries using medical image data and synthetic trees are generated originating from these segmented arteries. They grow into extensive networks of small vessels to fill the supplied tissues and satisfy the metabolic demand of them. Further, the algorithm is optimized to be executed in parallel without affecting the generated tree volumes. The generated vascular trees are used to simulate blood perfusion in the tissues by performing multiscale blood flow simulations. One-dimensional blood flow equations were used to solve for blood flow and pressure in the generated vascular trees and Darcy flow equations were solved for blood perfusion in the tissues using a porous model assumption. Both equations are coupled at terminal segments explicitly. The proposed methods were applied to idealized models with different tree resolutions and metabolic demands for validation. The methods demonstrated that realistic synthetic trees were generated with significantly less computational expense compared to that of a constrained constructive optimization method. The methods were then applied to cerebrovascular arteries supplying a human brain and coronary arteries supplying the left and right ventricles to demonstrate the capabilities of the proposed methods. The proposed methods can be utilized to quantify tissue perfusion and predict areas prone to ischemia in patient-specific geometries.

Arterial spin labeling magnetic resonance imaging quantifies tissue perfusion around foot ulcers.

Tools that quantify tissue perfusion of the foot are deficient, contributing to the uncertainty in predicting ulcer healing potential. This pilot study aims to quantify peri-wound foot perfusion at various tissue depths using a novel application of pseudo-continuous arterial spin labeling magnetic resonance imaging. Ten diabetic patients with neuropathic wounds and 20 healthy volunteers without wounds were recruited. Wounds were graded according to the Wound, Ischemia, Foot Infection (WIfI) system. All subjects underwent a noncontrasted ASL MRI of the foot for perfusion measurements. For healthy volunteers, perfusion was compared at rest and during sustained toe flexion between four regions: lateral plantar, medial plantar, lateral calcaneal, and medial calcaneal. Evaluations of diabetic volunteers compared perfusion between four zones: wound, near border, far border, and remote. Remote zone perfusion in diabetics was compared with perfusion in the plantar foot of healthy volunteers. There were 11 wounds, which were located over the metatarsal heads in five, the stump of a transmetatarsal amputation in three, the heel in two, and the mid foot in one. The median WIfI stage was 2. One patient had a WIfI ischemia grade of 1; the remaining patients' grades were 0. The mean ankle-brachial index was 1.0± 0.3. There were two patients with a WIfI foot infection grade of 1; the remaining patients' grades were 0. In healthy volunteers, plantar foot perfusion with sustained toe flexion was 43.9± 1.7mL/100g/min and significantly higher than perfusion at rest (27.3± 2.7mL/100g/min; P< .001). In diabetic patients, perfusion at the wound, near border, far border, and remote regions was 96.1± 10.7, 92.7± 9.4, 73.4± 8.2, and 62.8± 2.7mL/100g/min. Although this perfusion pattern persisted throughout the depth of the wound, perfusion decreased with tissue depth. In the near border, perfusion at 20% of the wound depth was 124.0± 35.6mL/100g/min and 69.9± 10.1mL/100g/min at 100% (P= .006). Lastly, remote perfusion in diabetics was 2.3 times the plantar perfusion in healthy volunteers (27.3± 2.7mL/100g/min; P< .001). The pattern of resting tissue perfusion around nonischemic diabetic foot ulcers was successfully quantified with arterial spin labeling magnetic resonance imaging. Diabetic patients with wounds were hyperemic compared withhealthy volunteers. There was a 1.5-fold increase in peri-wound tissue perfusion relative to the rest of the foot. This study is the first step in developing a tool to assess the perfusion deficit in ischemic wounds.

Correction of overexposure in laser speckle contrast imaging.

Laser speckle contrast imaging (LSCI) is a method to visualize and quantify tissue perfusion and blood flow. A common flaw in LSCI variants is their sensitivity to the optical setup parameters and that they operate well only on statistics of undistorted laser speckle patterns. The signal saturation of the sensors makes the contrast calculation misleading; hence the illumination level must be well controlled. We describe the theoretical explanation for the saturation-caused degradation. We introduce a linear extrapolation method to eliminate the overexposure induced error up to an extent of 60-70% saturated pixel count. This, depending on the contrast value and use case, enables to use 3-8 times higher external illumination level with no deterioration of the contrast calculation and thus the measured blood flow index. Our method enables a higher signal-to-noise ratio in darker areas by allowing the use of higher illumination, utilizing a larger portion of the dynamic range of the sensors, and making the illumination level setting less cumbersome.

Rapid Quantification of Tissue Perfusion Properties with a Two-Stage Look-Up Table

Tissue perfusion properties reveal crucial information pertinent to clinical diagnosis and treatment. Multispectral spatial frequency domain imaging (SFDI) is an emerging imaging technique that has been widely used to quantify tissue perfusion properties. However, slow processing speed limits its usefulness in real-time imaging applications. In this study, we present a two-stage look-up table (LUT) approach that accurately and rapidly quantifies optical (absorption and reduced scattering maps) and perfusion (total hemoglobin and oxygen saturation maps) properties using stage-1 and stage-2 LUTs, respectively, based on reflectance images at 660 and 850 nm. The two-stage LUT can be implemented on both CPU and GPU computing platforms. Quantifying tissue perfusion properties using the simulated diffuse reflectance images, we achieved a quantification speed of 266, 174, and 74 frames per second for three image sizes 512 × 512, 1024 × 1024, and 2048 × 2048 pixels, respectively. Quantification of tissue perfusion properties was highly accurate with only 3.5% and 2.5% error for total hemoglobin and oxygen saturation quantification, respectively. The two-stage LUT has the potential to be integrated with dual-sensor cameras to enable real-time quantification of tissue hemodynamics.

A Review of Clinical Applications for Super-resolution Ultrasound Localization Microscopy.

Microvascular structure and hemodynamics are important indicators for the diagnosis and assessment of many diseases and pathologies. The structural and functional imaging of tissue microvasculature in vivo is a clinically significant objective for the development of many imaging modalities. Contrast-enhanced ultrasound (CEUS) is a popular clinical tool for characterizing tissue microvasculature, due to the moderate cost, wide accessibility, and absence of ionizing radiation of ultrasound. However, in practice, it remains challenging to demonstrate microvasculature using CEUS, due to the resolution limit of conventional ultrasound imaging. In addition, the quantification of tissue perfusion by CEUS remains hindered by high operator-dependency and poor reproducibility. Inspired by super-resolution optical microscopy, super-resolution ultrasound localization microscopy (ULM) was recently developed. ULM uses the same ultrasound contrast agent (i.e. microbubbles) in CEUS. However, different from CEUS, ULM uses the location of the microbubbles to construct images, instead of using the backscattering intensity of microbubbles. Hence, ULM overcomes the classic compromise between imaging resolution and penetration, allowing for the visualization of capillary-scale microvasculature deep within tissues. To date, many in vivo ULM results have been reported, including both animal (kidney, brain, spinal cord, xenografted tumor, and ear) and human studies (prostate, tibialis anterior muscle, and breast cancer tumors). Furthermore, a variety of useful biomarkers have been derived from using ULM for different preclinical and clinical applications. Due to the high spatial resolution and accurate blood flow speed estimation (approximately 1 mm/s to several cm/s), ULM presents as an enticing alternative to CEUS for characterizing tissue microvasculature in vivo. This review summarizes the principles and present applications of CEUS and ULM, and discusses areas where ULM can potentially provide a better alternative to CEUS in clinical practice and areas where ULM may not be a better alternative. The objective of the study is to provide clinicians with an up-to-date review of ULM technology, and a practical guide for implementing ULM in clinical research and practice.

Quantifying tissue perfusion after peripheral endovascular procedures: Novel tissue perfusion endpoints to improve outcomes.

Peripheral artery disease (PAD) is a flow-limiting condition caused by narrowing of the peripheral arteries typically due to atherosclerosis. It affects almost 200 million people globally with patients either being asymptomatic or presenting with claudication or critical or acute limb ischemia. PAD-affected patients display increased mortality rates, rendering their management critical. Endovascular interventions have proven crucial in PAD treatment and decreasing mortality and have significantly increased over the past years. However, for the functional assessment of the outcomes of revascularization procedures for the treatment of PAD, the same tests that have been used over the past decades are still being employed. Those only allow an indirect evaluation, while an objective quantification of limb perfusion is not feasible. Standard intraarterial angiography only demonstrates post-intervention vessel patency, hence is unable to accurately estimate actual limb perfusion and is incapable of quantifying treatment outcome. Therefore, there is a significant necessity for real-time objectively measurable procedural outcomes of limb perfusion that will allow vascular experts to intraoperatively quantify and assess outcomes, thus optimizing treatment, obviating misinterpretation, and providing significantly improved clinical results. The purpose of this review is to familiarize readers with the currently available perfusion-assessment methods and to evaluate possible prospects.

90449 Can Ultrasound detect changes to spinal cord blood flow before and after injury?

ABSTRACT IMPACT: To track recovery and mitigate additional spinal cord injury (avoiding further paralysis), we are assessing the applicability of an implantable ultrasound device that can monitor the tissue health postoperatively. OBJECTIVES/GOALS: To date, no method has been developed that monitors spinal cord perfusion rate (mL/min/g) or pressure (mmHg) successfully after the surgery. Our goal is to design, construct, and validate (in animal models) a novel sensor that quantifies postoperative tissue perfusion in patients with SCI at the site of and downstream from the injury. METHODS/STUDY POPULATION: A sample size of 10 animals will allow us to test our hypothesis to track tissue perfusion before and after the SCI using ultrasound. After prepping and scrubbing the animal, the skin will be incised with a blade, bony structures will be removed and the spinal cord will be revealed. A 25-g weight will then be dropped from a height of 15 cm, and the animal will be observed for contraction of the lower extremities, a sign that the cord was damaged. Using Doppler ultrasound settings available on commercial transducers, we will investigate the acceptable frequency, as well as proper Doppler mode with and without contrast agents, and with and without elastography (stiffness mapping of the tissue). A range of frequencies will be tested (5 -25 MHz). RESULTS/ANTICIPATED RESULTS: It is expected that at frequencies 12 MHz and above, our radiologist collaborators would be able to easily detect the blood flow. It is also expected that the injury will have a noticeable effect on the changes of this detected blood flow. We aim to present figures demonstrating ultrasound image qualities obtained at various frequencies. We expect three such figures: one for gray scale ultrasound imaging, one for color Doppler and finally, one for spectral Doppler, which is the one mostly used to quantify blood flow. DISCUSSION/SIGNIFICANCE OF FINDINGS: To monitor recovery and mitigate secondary injury in patients with traumatic SCI, there is a need to monitor tissue perfusion intra-operatively. To address this need, we will design, construct, and validate a novel sensor that will postoperatively quantify tissue perfusion for the SCI patients at the site of the injury.

Evaluation of Lung Quality by Near-Infrared Fluorescent Imaging during Ex Vivo Lung Perfusion

Improved real-time assessment of donor lung quality during Ex Vivo Lung Perfusion (EVLP) could enhance safe utilization of lungs for transplantation. Near-infrared (NIR) fluorescent imaging with indocyanine green (ICG) has been used in various clinical intraoperative applications to evaluate tissue perfusion. We investigated the feasibility of NIR imaging during EVLP and aimed to detect and quantify lung perfusion and permeability. Pig lungs with extended 24-hour cold ischemia (n=4) and human lungs rejected from clinical transplantation (n=2) were assessed with NIR imaging during EVLP. Serial NIR imaging was performed with SPY Elite imaging system after ICG (0.3, 0.6 or 1.0 mg) administration through pulmonary artery (Fig A). Tissue perfusion was quantified using SPYQ analysis software, and tissue ICG accumulation was correlated with lung damage. Strong NIR signal was detected immediately after ICG administration with 0.6 mg (pig lungs) or 1.0 mg (human lungs) doses resulting in optimal fluorescence for tissue perfusion evaluation. In contrast to the transient kinetics and fast liver metabolism during clinical in vivo ICG administration, a single ICG dose during EVLP resulted in stable NIR signal for over 10 hours. Perfusion quantification of pig lungs with extended cold preservation revealed peripheral areas with compromised tissue perfusion that gradually recovered over time with recruitment of additional pulmonary vascular beds (Fig B). ICG accumulation was detected in sites with damage and increased vascular permeability in pig and human lungs (Fig C and D). NIR imaging with a clinically-approved intravascularly-delivered ICG fluorescent probe can dynamically quantify tissue perfusion and detect damage-induced vascular permeability. This novel and promising imaging modality could be used during EVLP to assess lung quality, or to determine effects of therapeutics that target tissue perfusion and vascular permeability.

Comparison of the ViOptix Intra.Ox Near Infrared Tissue Spectrometer and Indocyanine Green Angiography in a Porcine Bowel Model.

This study aims to directly compare measurements of tissue oxygenation obtained using the Intra.Ox (Vioptix Inc., Fremont, CA) near infrared spectrometer with the perfusion assessment of the indocyanine green (ICG)-based SPY Elite imaging system (Stryker Co., Kalamazoo, MI) in a porcine bowel model. Two live minipigs underwent laparotomy and isolation of a 30-cm segment of a large bowel. Standardized oximetry measurements were taken along the segment of bowel immediately before, after, and serially for 30 minutes following transection. A 0.5 mg/kg dose of ICG was then injected intravenously and the SPY Elite system was used to visualize and quantify tissue perfusion. Pearson's correlation coefficients were calculated using the outcomes. Transected and ligated bowel yielded mean Intra.Ox measurements of 61% oxygenation at the proximal base of the limb and 27.8% at the distal edges. Analysis of the relative ICG fluorescence using the SPY Elite's proprietary software yielded perfusion estimates of 64.8% proximally and 6.8% distally. Intra.Ox and SPY Elite measurements demonstrate a Pearson product-moment correlation of 0.929. Repeat measurements at 15-mm intervals along the tissue yielded decreasing Intra.Ox measurements along the length of the flap that correlate to SPY Elite measurements (r = 0.645). Both the Intra.Ox and the SPY detected clinically relevant changes in bowel oxygenation following transection and ligation. The use of intravenous ICG dye did not appear to affect measurements of tissue oxygenation obtained using the Intra.Ox.

P.871 “The woman who saw little spiders with red feet”- hypnagogic and hypnopompic hallucinations related to serotonin-norepinephrine reuptake inhibitors intake

Reducing anastomotic leak (AL) continues to be a main focus in colorectal research. Several new technologies have been developed with an aim to reduce this fluorescence angiography (FA) with indocyanine green (ICG) in colorectal surgery is now a well-established technique. By using FA we are able to have a visual representation of perfusion which aids intraoperative decision making. The main impact is change in the level of bowel transection at the proximal side of an anastomosis. Previous studies have shown that routine FA use is safe and reproducible. Recent results from randomized control trials and meta-analyses show that FA use reduces the rate of anastomotic leak. The main limitation of FA is its lack of ability to quantify perfusion. Novel technologies are being developed that will quantify tissue perfusion and oxygenation. Overall, FA is a safe technique and we would advocate its routine use.

Quantitative methods in sonography

B‑mode and color Doppler ultrasound are standard radiological methods to quantify tissue echo texture and tissue perfusion. Microstructure and composition of tissue influence echo texture parameters and acoustic parameters, such as speed of sound, attenuation and backscatter and quantitative color Doppler image parameters are influenced by the hemodynamics in depictable vessels. Dynamic contrast-enhanced ultrasound enables quantification of tissue perfusion and ultrasound elastography assists in assessing tissue stiffness. B‑mode texture analysis, analysis of high-frequency echo signals and quantitative color Doppler image analysis are able to contribute to the assessment of tissue microstructure but have so far not been implemented clinically due to their complexity. Dynamic contrast-enhanced ultrasound and ultrasound elastography have proven to be robust under clinical conditions.

P3395Arrival time at hyperemia of below the ankle as a determinant factor for limb salvage: evaluation by 2 dimension perfusion angiography

Abstract Background In patients with critical limb ischemia, it is desirable to obtain enough skin perfusion pressure (SPP) levels through revascularization. 2D-perfusion angiography is an emerging technology for the quantification of tissue perfusion consisted of 6 parameters calculated by time-density curve of digital subtraction angiography (DSA). Purpose We evaluated the feasibility of 2D-perfusion angiography for below the knee (BTK) endovascular therapy (EVT). We aimed to clarify which angiographical parameters of lower limb are related to SPP after EVT. Methods Consecutive 33 limbs (mean age 74.5 years, men 55%), which successfully underwent EVT for isolated BTK lesions, were enrolled in this study. We excluded Rutherford 6 limbs with severe gangrene or tissue loss, consequently 26 limbs were Rutherford 4 or 5 critical limb ischemia. We treated total 47 lesions, including 26 chronic total occlusive lesions. 5Fr guiding sheath was advanced to popliteal artery. DSA images were obtained by mechanical contrast infusion. We quantified indexed blood flow on below the ankle area by using 2D-perfusion angiography, and examined 6 parameters [arrival time (AT), time to peak (TTP), wash-in rate, width, area under the curve and mean transit time (MTT)] from acquired DSA. Hyperemia was induced by 20mg papaverine intra-arterial infusion through the guiding sheath. Results The parameters except wash-in rate were significantly shortened after hyperemia induced by intra-arterial papaverine infusion below the ankle region. Dorsal and plantar SPP were significantly correlated with hyperemic AT, hyperemic wash-in rate and AT ratio (hyperemic/rest) of lower ankle regions after EVT. However, only AT ratio was independently associated with dorsal SPP in multivariate analysis (P=0.032). A receiver operating characteristic curve showed hyperemic AT &lt;4.5 seconds and AT ratio &lt;0.49 predicted to obtain SPP levels &gt;50 mmHg after EVT with the area under the curve of 0.71 (95% confidence interval, 0.52–0.90) and 0.73 (95% confidence interval, 0.55–0.90), respectively. Representative Case of 2D-perfusion Conclusion Hyperemic AT &lt;4.5 seconds and AT ratio &lt;0.49 of lower ankle regions may be essential to obtain the sufficient levels of SPP for limb salvage after BTK intervention. 2D perfusion angiography technique at hyperemic condition is feasible and has the potential to monitor lower limb tissue perfusion through EVT and to optimize the interventional treatment.

Tissue Oxygenation Sensor and an ActiveIn VitroPhantom for Sensor Validation

A free flap is a tissue reconstruction procedure where healthy tissue is harvested to cover up vital structures after wound debridement. Microvascular anastomoses are carried out to join the arteries and veins of the flap with recipient vessels near the target site. Continuous monitoring is required to identify the flap failure and enable early intervention to salvage the flap. Although there are medical instruments that can assist surgeons in monitoring flap viability, high upfront costs and time-consuming data interpretation have hindered the use of such technologies in practice. Surgeons still rely largely on the clinical examination to monitor flaps after operations. This paper presents a low-cost, low-power (6.6 mW), and miniaturized Hamlyn StO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> (tissue oxygen saturation) sensor that can be embodied as a plaster and attached to a flap for real-time monitoring. Similar to the design of oxygen saturation (SpO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> /SaO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> ) sensors, the Hamlyn StO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> sensor was designed based on photoplethysmography (PPG), but with a different target of quantifying tissue perfusion rather than capturing pulsatile flow. To understand the spectral response to oxygenation/deoxygenation and vascular flow, an active in vitro silicone phantom was developed. The new sensor was validated using the silicone phantom and compared with a commercially available photospectroscopy and laser Doppler machine (O2C, LEA, Germany). In addition, in vivo experiments were conducted using a brachial pressure cuff forearm ischemia model. The experiment results have shown a high correlation between the proposed sensor and the O2C machine (r = 0.672 and p <; 0.001), demonstrating the potential value of the of the proposed low-cost sensor in post-operative free flap monitoring.

A multi-model framework to estimate perfusion parameters using contrast-enhanced ultrasound imaging.

Contrast-enhanced ultrasound imaging has expanded the diagnostic potential of ultrasound by enabling real-time imaging and quantification of tissue perfusion. Several perfusion models andcurve fitting methods have been developed to quantify the temporal behavior of tracer signal and standardize perfusion quantification. While the least-squares approach has traditionally been applied for curve fitting, it can be inadequate for noisy and complex data. Moreover, previous research suggests that certain perfusion models may be more relevant depending on the organ or tissue imaged. We propose a multi-model framework to select the most appropriate perfusion model and curve fitting method for each diagnostic application. Our multi-model approach uses a system identification method, which estimates perfusion parameters from the model with the best fit to a given time-intensity curve. We compared current perfusion quantification methods that use a single perfusion model and curve fitting method and our proposed multi-model framework on bolus 3D dynamic contrast-enhanced ultrasound (DCE-US) invivo images obtained in mice implanted with a colon cancer, as well as on simulation data. The quality of fit in estimating perfusion parameters was evaluated using the Spearman correlation coefficient, the coefficient of determination (R2 ), and the normalized root-mean-square error (NRMSE) to ensure that the multi-model framework finds the best perfusion model and curve fitting algorithm. Our multi-model framework outperforms conventional single perfusion model approaches with least-squares optimization, providing more robust perfusion parameter estimation. R2 and NRMSE are 0.98 and 0.18, respectively, for our proposed method. By comparison, the performance of the traditional approach is much more dependent upon the selection of the appropriate model. The R2 and NRMSE are 0.91 and 0.31, respectively. The proposed multi-model framework for perfusion modeling outperforms the current approach of single perfusion modeling using least-squares optimization and more robustly estimates perfusion parameters when using empiric data labeled by an expert as the gold standard. Our technique is minimally sensitive to issues affecting the accuracy of perfusion parameter estimation, including rise time, noise, region of interest size, and frame rate. This framework could be of key utility in modeling different perfusion systems in different tissues and organs.

Role of Indocyanine Green in Fluorescence Imaging with Near-Infrared Light to Identify Sentinel Lymph Nodes, Lymphatic Vessels and Pathways Prior to Surgery - A Critical Evaluation of Options.

Modern surgical strategies aim to reduce trauma by using functional imaging to improve surgical outcomes. This reviews considers and evaluates the importance of the fluorescent dye indocyanine green (ICG) to visualize lymph nodes, lymphatic pathways and vessels and tissue borders in an interdisciplinary setting. The work is based on a selective search of the literature in PubMed, Scopus, and Google Scholar and the authorsʼ own clinical experience. Because of its simple, radiation-free and uncomplicated application, ICG has become an important clinical indicator in recent years. In oncologic surgery ICG is used extensively to identify sentinel lymph nodes with promising results. In some studies, the detection rates with ICG have been better than the rates obtained with established procedures. When ICG is used for visualization and the quantification of tissue perfusion, it can lead to fewer cases of anastomotic insufficiency or transplant necrosis. The use of ICG for the imaging of organ borders, flap plasty borders and postoperative vascularization has also been scientifically evaluated. Combining the easily applied ICG dye with technical options for intraoperative and interventional visualization has the potential to create new functional imaging procedures which, in future, could expand or even replace existing established surgical techniques, particularly the techniques used for sentinel lymph node and anastomosis imaging.

Repeatability of Contrast-Enhanced Ultrasonography of the Kidneys in Healthy Cats

Contrast-enhanced ultrasound can be used to image and quantify tissue perfusion. It holds great potential for the use in the diagnosis of various diffuse renal diseases in both human and veterinary medicine. Nevertheless, the technique is known to have an inherent relatively high variability, related to various factors associated with the patient, the contrast agent and machine settings. Therefore, the aim of this study was to assess week-to-week intra- and inter-cat variation of several perfusion parameters obtained with CEUS of both kidneys of 12 healthy cats. Repeatability was determined by calculating the coefficient of variation (CV). The contrast-enhanced ultrasound parameters with the lowest variation for the renal cortex were time-to-peak (CV 6.0%), rise time (CV 13%), fall time (CV 19%) and mean transit time (24%). Intensity-related parameters and parameters related to the slope of the time-intensity curve had a CV of >35%. Lower repeatability was present for perfusion parameters derived from the renal medulla compared with the renal cortex. Normalization to the inter-lobar artery does not cause a reduction in variation. In conclusion, time-related parameters for the cortex show a reasonable repeatability; whereas poor repeatability is present for intensity-related parameters and parameters related to in- and outflow of contrast agent. Poor repeatability is also present for all perfusion parameters for the renal medulla, except for time to peak, which has a good repeatability.

In-silico and in-vitro investigation of a photonic monitor for intestinal perfusion and oxygenation.

The quantification of visceral organ oxygenation after trauma-related systemic hypovolemia and shock is critical to enable effective resuscitation. In this work, a photoplethysmography-based (PPG) sensor was specifically designed for probing the perfusion and oxygenation condition of intestinal tissue with the ultimate goal to monitor patients post trauma to guide resuscitation. Through Monte Carlo modeling, suitable optofluidic phantoms were determined, the wavelength and separation distance for the sensor was optimized, and sensor performance for the quantification of tissue perfusion and oxygenation was tested on the in-vitro phantom. In particular, the Monte Carlo simulated both a standard block three-layer model and a more realistic model including villi. Measurements were collected on the designed three layer optofluidic phantom and the results taken with the small form factor PPG device showed a marked improvement when using shorter visible wavelengths over the more conventional longer visible wavelengths. Overall, in this work a Monte Carlo model was developed, an optofluidic phantom was built, and a small form factor PPG sensor was developed and characterized using the phantom for perfusion and oxygenation over the visible wavelength range. The results show promise that this small form factor PPG sensor could be used as a future guide to shock-related resuscitation.