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Purpose: The consensus for the clinical implementation of arterial spin labeling (ASL) perfusion imaging recommends a segmented 3D Gradient and Spin-Echo (GRASE) readout for optimal signal-to-noise-ratio (SNR). The correction of the associated susceptibility-induced geometric distortions has been shown to improve diagnostic precision, but its impact on ASL data has not been systematically assessed and it is not consistently part of pre-processing pipelines. Here, we investigate the effects of susceptibility-induced distortion correction on perfusion imaging by pseudo-continuous ASL (pCASL) with a segmented 3D GRASE readout. Methods: Data acquired from 28 women using pCASL with 3D GRASE at 3T was analyzed using three pre-processing options: without distortion correction, with distortion correction, and with spatial smoothing (without distortion correction) matched to control for blurring effects induced by distortion correction. Maps of temporal SNR (tSNR) and relative perfusion were analyzed in eight regions-of-interest (ROIs) across the brain. Results: Distortion correction significantly affected tSNR and relative perfusion across the brain. Increases in tSNR were like those produced by matched spatial smoothing in most ROIs, indicating that they were likely due to blurring effects. However, that was not the case in the frontal and temporal lobes, where we also found increased relative perfusion with distortion correction even compared with matched spatial smoothing. These effects were found in both controls and patients, with no interactions with the participant group. Conclusion: Correction of susceptibility-induced distortions significantly impacts ASL perfusion imaging using a segmented 3D GRASE readout, and this step should therefore be considered in ASL pre-processing pipelines. This is of special importance in clinical studies, reporting perfusion across ROIs defined on relatively undistorted images and when conducting group analyses requiring the alignment of images across different subjects.

Studying the placenta can provide information about the mechanistic pathways of pregnancy disease. However, analyzing placental tissues and manipulating placental function in real-time during pregnancy is not feasible. The ex vivo placental perfusion model allows observing important aspects of the physiology and pathology of the placenta, while maintaining its viability and functional integrity, and without causing harm to mother or fetus. In this review, we describe and compare setups for this technically complex model and summarize outcomes from various published studies. We hope that our review will encourage wider use of ex vivo placental perfusion, which in turn would generate more knowledge to improve pregnancy outcomes.

Donation after circulatory death (DCD) has emerged as attainable strategy to tackle the issue of organ shortage, expanding the donor pool. The DCD concept has been applied to the multiple declinations of circulatory arrest, as per the Modified Maastricht Classification. Notwithstanding, whichever the scenario, DCD donors experience a variable warm ischemia time whose correlation with graft dysfunction is ascertained. This applies to both “controlled” (cDCD) donors (i.e., the timespan from the withdrawal of life-sustaining therapies to the onset of in-situ perfusion), and “uncontrolled” DCD (uDCD) (i.e., the low-flow period during cardiopulmonary resuscitation – CPR). This sums up to the no-flow time from cardiac arrest to the start of CPR for uDCD donors, and to the no-touch period for both uDCDs and cDCDs. Static and hypothermic storage may not be appropriate for DCD grafts. In order to overcome this ischemic insult, extracorporeal membrane oxygenation devices are adopted to guarantee the in-situ grafts preservation by means of techniques such as the normothermic regional perfusion (NRP) which consists in a selective abdominal perfusion obtained via the endovascular or surgical occlusion of the thoracic aorta. The maintenance of an adequate pump flood throughout NRP is therefore a sine qua non to accomplish the DCD donation. The issue of insufficient pump flow during NRP is prevalent and clinically significant but its management remains technically challenging and not standardized. Hereby we propose a systematic algorithmic approach to address this relevant occurrence.

Ex vivo normothermic perfusion (EVNP) is increasingly recognised as a viability tool to increase organ utilisation in deceased donor transplantation. We report the use of EVNP to assess graft perfusion quality following indication nephrectomy and back-bench arterial reconstruction in a case of renal artery stenosis, unamenable to endovascular treatment. Once explanted, it was not possible to effectively cold perfuse the graft through the main renal artery or collaterals. An arterial reconstruction was performed with patch angioplasty using the largest collateral creating a single common stem. EVNP was used to assess organ perfusion and, therefore, viability. Excellent global perfusion was evident alongside urine production, demonstrating that the arterial reconstruction was satisfactory. A patient with end-stage renal disease was consented with particular attention to the uncertainty of the underlying donor disease process and long-term outcome of the reconstruction. Primary function was achieved and recipient estimated glomerular filtration rate (eGFR) remains stable at 58 mL/min/1.73 m² at 6 months.

Purpose: The consensus for the clinical implementation of arterial spin labeling (ASL) perfusion imaging recommends a segmented 3D Gradient and Spin-Echo (GRASE) readout for optimal signal-to-noise-ratio (SNR). The correction of the associated susceptibility-induced geometric distortions has been shown to improve diagnostic precision, but its impact on ASL data has not been systematically assessed and it is not consistently part of pre-processing pipelines. Here, we investigate the effects of susceptibility-induced distortion correction on perfusion imaging by pseudo-continuous ASL (pCASL) with a segmented 3D GRASE readout. Methods: Data acquired from 28 women using pCASL with 3D GRASE at 3T was analyzed using three pre-processing options: without distortion correction, with distortion correction, and with spatial smoothing (without distortion correction) matched to control for blurring effects induced by distortion correction. Maps of temporal SNR (tSNR) and relative perfusion were analyzed in eight regions-of-interest (ROIs) across the brain. Results: Distortion correction significantly affected tSNR and relative perfusion across the brain. Increases in tSNR were like those produced by matched spatial smoothing in most ROIs, indicating that they were likely due to blurring effects. However, that was not the case in the frontal and temporal lobes, where we also found increased relative perfusion with distortion correction even compared with matched spatial smoothing. These effects were found in both controls and patients, with no interactions with the participant group. Conclusion: Correction of susceptibility-induced distortions significantly impacts ASL perfusion imaging using a segmented 3D GRASE readout, and this step should therefore be considered in ASL pre-processing pipelines. This is of special importance in clinical studies, reporting perfusion across ROIs defined on relatively undistorted images and when conducting group analyses requiring the alignment of images across different subjects.

Older donors have the potential to close the gap between demand and supply in solid organs transplantation. Utilizing older organs, at the same time, has been associated with worse short- and long-term outcomes. Here, we introduce potential mechanisms on how treatments during machine perfusion (MP) may safely improve the utilization of older organs.Consequences of ischemia reperfusion injury (IRI), a process of acute, sterile inflammation leading to organ injury are more prominent in older organs. Of relevance, organ age and IRI seem to act synergistically, leading to an increase of damage associated molecular patterns that trigger innate and adaptive immune responses. While cold storage has traditionally been considered the standard of care in organ preservation, accumulating data support that both hypothermic and normothermic MP improve organ quality, particularly in older organs. Furthermore, MP provides the opportunity to assess the quality of organs while adding therapeutic agents. Experimental data have already demonstrated the potential of applying treatments during MP. New experimental show that the depletion of senescent cells that accumulate in old organs improves organ quality and transplant outcomes.As the importance of expanding the donor pool is increasing, MP and novel treatments bear the potential to assess and regenerate older organs, narrowing the gap between demand and supply.

Shortage of healthy donors’ organs has appeared as one of the main challenges for organ transplantation. This study focuses on the novel endovascular device development to increase the number of available organs from cardiac death donors. The primary objective of this study is the design validation of a newly developed stent graft for the abdominal organ perfusion with cardiac blood flow isolation. In this paper, the effectiveness of the device design has been validated via the assessment of the device performance both in vitro and in vivo. The radial force of stent structure was first numerically analyzed using finite element method, then was quantified experimentally. The blood perfusion parameters were investigated to demonstrate their effect on the blood delivered to the abdominal organs, maintaining the organs healthy for donation. In vitro flow leakage was measured using a 3-D printing-based silicone aortic model to evaluate the isolation between cardiac flow and perfusion flow with minimum values. Following the design validation process, a functional prototype stent graft has been successfully fabricated using optimized laser welding conditions and subsequent joining processes. In vivo porcine study results have demonstrated smooth delivery and successful placement of the device showing complete cardiac flow separation isolating abdominal regions only with the oxygenated blood flow.

Aim-\ud \ud To identify if the proportion of poor blood flow (blue) within an LDI (Laser doppler Imaging) image of a burn independently correlates with healing time.\ud \ud Methods-\ud \ud Patient age, gender, burn type, and burn surface area were collected from the IBID (International Burn Injury Database). All LDI images were copied from the MoorLDI2-BI- Laser Doppler (MLDI) Scanner, onto Adobe Photoshop® version 2020 for pixel counting analysis and calculation of % TBSA (Total Body Surface Area) blue. Multiple linear regression analysis determined if there was a proportional relationship of each parameter (age, gender, % TBSA Blue and comorbidities) with healing time.\ud \ud Results-\ud \ud 110 patients with 197 burns were scanned with MLDI. Median age was 5 years (IQR 1–6). Median burn surface area was 1.5% (IQR 1–2.4). 56.4% of patients were male and patients were scanned an average of 2.68 days (SD±1.37) following burn injury. Number of physical comorbidities and age were found to have a statistically significant relationship with healing time (p = 0.03, p = 0.002). Gender and %TBSA blue did not have a statistically significant relationship with healing time (p = 0.07 and p = 0.058 respectively). There was a statistically significant difference in the mean healing time between burns with and without blue (3.43 weeks vs. 2.80 weeks, p = 0.0001). % TBSA Blue was more than four times higher in the operated group (0.48% vs. 0.11%) and was shown to have a statistically significant relationship with decision to operate (p = 0.027). Positive predictive value for the presence of blue on operative rate was 71.6%. Age, gender and number of comorbidities did not have a statistically significant influence on operative rate (p = 0.07, p = 0.50 and p = 0.49).\ud \ud Conclusion-\ud \ud % TBSA blue was not found to be a reliable individual indicator of burn healing time, but the presence of blue within an LDI image, advanced patient age and increased number of comorbidities did have a statistically significant relationship with healing time. This suggests their standardised inclusion into management decisions regarding intermediate depth burns is warranted.

Background Depiction of bypass blood flow in patients who received extracranial–intracranial (EC–IC) bypass surgery is important for patient care. Purpose To develop a vessel-encoded arterial spin labeling (VE-ASL) method using surgical staples as a magnetic resonance (MR)-conditional product in patients who received EC–IC bypass surgery. Material and Methods Pseudo-continuous labeling was used for VE-ASL acquisition with a 3-T MR unit. First, an experimental study was conducted to determine the appropriate number of surgical staples to obtain a spatially sufficient saturation effect. Thereafter, four healthy normal volunteers underwent a VE-ASL study to confirm the sufficiency of the saturation effect to the right or left common carotid artery. Finally, VE-ASL scanning was performed in seven patients after EC–IC bypass surgery to confirm the ability of VE-ASL to visualize the territorial bypass perfusion. All qualitative evaluation was performed by two neuroradiologists using a 3-point grading system (2 = good, 1 = moderate, 0 = poor). Results A quantity of 200 staples was found to be appropriate for VE-ASL scanning. In healthy volunteers, one neuroradiologist rated the images of all four cases as good, while the other rated three cases as good and one case as moderate. For the seven patients after EC–IC bypass surgery, one neuroradiologist rated all seven cases as good, and the other rated six cases as good and one case as moderate. Conclusion VE-ASL using surgical staples might be useful for the evaluation of territorial bypass perfusion in patients after EC–IC bypass surgery.

Metabolism management plays an essential role in extracorporeal technologies. There are different metabolic management devices integrated to extracorporeal devices; the most commonly used and accepted metabolic target in adult patients is indexed oxygen delivery (280 mL/min/m2) and cardiac index (2.4 L/min/m2), which can be managed independently or according to other metabolic parameters. Extracorporeal membrane oxygenation (ECMO) is a temporary form of life support providing a prolonged biventricular circulatory and pulmonary support for patients experiencing both pulmonary and cardiac failure unresponsive to conventional therapy. The goal-directed perfusion initiative during cardiopulmonary bypass (CPB) reduced the incidence of acute kidney injury after cardiac surgery. On the basis of the available literature, the identified goals to achieve during CPB include maintenance of oxygen delivery > 300 mL O2/min/m2 and reduction in vasopressor use. ECMO and CPB are conceptually similar but differ in many aspects and finality; in particular, they differ in the scientific evidence for metabolic management nadirs. As for CPB, predictive target parameters have been found and consolidated, particularly in terms of acute renal injury and the prevention of anaerobic metabolism, while for ECMO management, a blurred path remains. In this context, we review the strategies for optimal goal-directed therapy during CPB and ECMO, trying to transfer the knowledge and experience from daily cardiac surgery to veno-arterial ECMO.

BACKGROUND: The shortage of donor organs for transplantation remains a worldwide problem. The utilization of suboptimal deceased donors enlarges the pool of potential organs, yet consequently, clinicians face the difficult decision of whether these sub-optimal organs are of sufficient quality for transplantation. Novel technologies could play a pivotal role in making pre-transplant organ assessment more objective and reliable.METHODS: Ex vivo normothermic machine perfusion (NMP) at temperatures around 35-37°C allows organ quality assessment in a near-physiological environment. Advanced magnetic resonance imaging (MRI) techniques convey unique information about an organ's structural and functional integrity. The concept of applying magnetic resonance imaging during renal normothermic machine perfusion is novel in both renal and radiological research and we have developed the first MRI-compatible NMP setup for human-sized kidneys.RESULTS: We were able to obtain a detailed and real-time view of ongoing processes inside renal grafts during ex vivo perfusion. This new technique can visualize structural abnormalities, quantify regional flow distribution, renal metabolism, and local oxygen availability, and track the distribution of ex vivo administered cellular therapy.CONCLUSION: This platform allows for advanced pre-transplant organ assessment, provides a new realistic tool for studies into renal physiology and metabolism, and may facilitate therapeutic tracing of pharmacological and cellular interventions to an isolated kidney.

At the moment, many researchers are using in vitro techniques to investigate chemokine-driven leukocyte adhesion/recruitment, for example, by using a transwell or flow chamber system. Here we describe a more physiologically relevant, sophisticated, and highly flexible method to study leukocyte adhesion ex vivo in fresh murine carotid arteries under arterial flow conditions. This model mimics an in vivo situation and allows the combination of leukocytes and arteries isolated from different donors in one experiment, generating information on both vascular and leukocyte adhesive properties of both donors. This method provides a versatile, highly physiologically relevant model to investigate leukocyte adhesion.

Autoimmune pancreatitis (AIP) is a pancreatic phenotype of IgG4-related systemic disease. Since its first description in the literature, characteristic imaging features have gradually become known to many clinicians encompassing various specialties in the past quarter century. CT and MRI have been the workhorses for imaging diagnosis of AIP. Typical features include sausage-like swelling of the focal or entire pancreas, duct-penetrating sign, a capsule-like rim of the affected lesions, and homogeneous delayed enhancement or enhanced duct sign after contrast administration, as well as characteristic combined findings reflecting coexisting pathologies in the other organs as a systemic disease. In this review, recent and future developments in CT and MRI that may help diagnose AIP are discussed, including restricted diffusion and perfusion and increased elasticity measured using MR.

Purpose Characteristic features of amyloid-PET (A), tau-PET (T), and FDG-PET (N) can serve for the A/T/N classification of neurodegenerative diseases. Recent studies showed that the early, perfusion-weighted phases of amyloid- or tau-PET recordings serve to detect cerebrometabolic deficits equally to FDG-PET, therefore providing a surrogate of neuronal injury. As such, two channels of diagnostic information can be obtained in the setting of a single PET scan. However, there has hitherto been no comparison of early-phase amyloid- and tau-PET as surrogates for deficits in perfusion/metabolism. Therefore, we undertook to compare [18F]flutemetamol-amyloid-PET and [18F]PI-2620 tau-PET as “one-stop shop” dual purpose tracers for the detection of neurodegenerative disease. Methods We obtained early-phase PET recordings with [18F]PI-2620 (0.5–2.5 min p.i.) and [18F]flutemetamol (0–10 min p.i.) in 64 patients with suspected neurodegenerative disease. We contrasted global mean normalized images (SUVr) in the patients with a normal cohort of 15 volunteers without evidence of increased pathology to β-amyloid- and tau-PET examinations. Regional group differences of tracer uptake (z-scores) of 246 Brainnetome volumes of interest were calculated for both tracers, and the correlations of the z-scores were evaluated using Pearson’s correlation coefficient. Lobar compartments, regions with significant neuronal injury (z-scores Results The z-scores of perfusion-weighted images of both tracers showed high correlations across the brain, especially in the frontal and parietal lobes, which were the brain regions with pronounced perfusion deficit in the patient group (R = 0.83 ± 0.08; range, 0.61–0.95). Z-scores of individual patients correlated well by region (R = 0.57 ± 0.15; range, 0.16–0.90), notably when significant perfusion deficits were present (R = 0.66 ± 0.15; range, 0.28–0.90). Conclusion The early perfusion phases of [18F]PI-2620 tau- and [18F]flutemetamol-amyloid-PET are roughly equivalent indices of perfusion defect indicative of regional and lobar neuronal injury in patients with various neurodegenerative diseases. As such, either tracer may serve for two diagnostic channels by assessment of amyloid/tau status and neuronal activity.

Although appealing from a reconstructive standpoint, the incorporation of the overlying skin in a serratus anterior muscle flap has not yet seen widespread use, due to considerations with its blood supply. In the present study, a systematic review of the literature has been performed, evaluating studies that investigated the vascular anatomy and variations of serratus anterior myocutaneous flap. The anatomy of the cutaneous blood supply, the size of the cutaneous territory, the design of the skin paddle and the reconstructive goals were analyzed. The results showed that the main blood supply originates from the intramuscular anastomoses between intercostal artery perforators and the serratus artery branch in the form of choke vessels. Complementary perfusion from true intramuscular vessel anastomoses or from direct serratus artery cutaneous perforators could contribute to the skin blood supply but only in 25% of the cases. The design of the flap is elliptical with its long axis over the harvested muscle slips and maximum width is approximately 6-8 cm. Α myocutaneous serratus anterior flap could be applied in a variety of reconstructive fields, most commonly for head and neck defects. A delay procedure would considerably enhance the perfusion of the cutaneous component and improve the overall viability of the flap.

Evidence suggests that hearts that are perfused under ex-situ conditions lose normal coronary vasomotor tone and experience contractile failure over a few hours. We aimed to evaluate the effect of different coronary perfusion strategies during ex situ heart perfusion on cardiac function and coronary vascular tone.Porcine hearts (n = 6 each group) were perfused in working mode for 6 hours with either constant aortic diastolic pressure (40 mmHg) or constant coronary flow rate (500 mL/min). Functional and metabolic parameters, cytokine profiles, cardiac and vascular injury, coronary artery function and oxidative stress were compared between groups.Constant coronary flow perfusion demonstrated better functional preservation and less edema formation (Cardiac index: flow control = 8.33 vs pressure control = 6.46 mL·minA strategy of controlled coronary flow during ex situ heart perfusion provides superior functional preservation and less edema formation, together with less myocardial damage, leukocyte, platelet, endothelial activation, and oxidative stress. There was loss of coronary autoregulation and decrease of coronary vascular resistance during ESHP irrespective of coronary flow control strategy. Inflammation and oxidative stress state in the coronary vasculature may play a role.

Pregnancy pathologies including gestational diabetes, intrauterine fetal growth restriction, and pre-eclampsia are common and significantly increase the risk of poor pregnancy outcomes. Research to better understand the pathophysiology and improve diagnosis and treatment is therefore crucial. The ex vivo placenta perfusion model offers a unique system to study pregnancy pathology without the risk of harm to mother or fetus. The presence of a maternal and fetal circulation and intact villus tree, facilitates investigations into maternal-fetal transfer, altered hemodynamics and vascular reactivity in the human placenta. It also provides a platform to test novel therapeutic agents. Here we review the key studies which have utilized the ex vivo placenta perfusion model to study different aspects of such pregnancy pathologies.

BACKGROUND: In recent years, indocyanine green angiography (ICG-A) has been used increasingly to assist tissue perfusion assessments during plastic and reconstructive surgery procedures, but no guidelines exist regarding its use. We sought to identify areas of consensus and non-consensus among international experts on the use of ICG-A for tissue-perfusion assessments during plastic and reconstructive surgery.METHODS: A two-round, online Delphi survey was conducted of 22 international experts from four continents asking them to vote on 79 statements divided into five modules: module 1 = patient preparation and contraindications (n = 11 statements); module 2 = ICG administration and camera settings (n = 17); module 3 = other factors impacting perfusion assessments (n = 10); module 4 = specific indications, including trauma debridement (n = 9), mastectomy skin flaps (n = 6), and free flap reconstruction (n = 8); and module 5 = general advantages and disadvantages, training, insurance coverage issues, and future directions (n = 18). Consensus was defined as ≥70% inter-voter agreement.RESULTS: Consensus was reached on 73/79 statements, including the overall value, advantages, and limitations of ICG-A in numerous surgical settings; also, on the dose (0.05 mg/kg) and timing of ICG administration (∼20-60 seconds preassessment) and best camera angle (61-90o) and target-to-tissue distance (20-30 cm). However, consensus also was reached that camera angle and distance can vary, depending on the make of camera, and that further research is necessary to technically optimize this imaging tool. The experts also agreed that ambient light, patient body temperature, and vasopressor use impact perfusion assessments.CONCLUSION: ICG-A aids perfusion assessments during plastic and reconstructive surgery and should no longer be considered experimental. It has become an important surgical tool.

ObjectiveTools 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.MethodsTen 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.ResultsThere 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).ConclusionsThe 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.

In the US, only 23% of lungs offered for transplantation are transplanted. Ex vivo lung perfusion (EVLP) allows for evaluation of additional donor lungs; its adoption has been limited by resources and expertise. Dedicated facilities with a centralized lung evaluation system (CLES) could expand access to EVLP.In this unblinded, nonrandomized, traditional feasibility study, 7 US transplant centers referred lungs declined for standard transplantation to a dedicated EVLP facility, which utilized a CLES. EVLP was remotely monitored by the transplant teams. CLES lungs were matched with contemporaneous conventional static cold-preserved controls at each center.A total of 115 recipients were enrolled, and 66 received allografts from 63 donors after EVLP at the dedicated CLES facility. Forty-nine contemporaneous patients served as controls. Primary graft dysfunction grade 3 at 72 hours (PGD3-72 hours) was higher in the CLES group with 16 (24%) vs 2 (4%) in the control (common RD 95% CI, 0.07-0.32; p = 0.0009). All recipients survived to 30 days and 1-year survival was similar for both groups (92% controls vs 89% CLES; common RD 95% CI, -0.14-0.08; p = 0.58). Total preservation time, hospital and ICU lengths of stay, and time to first extubation were longer in the CLES group.Remote ex vivo perfusion of lung allografts declined for conventional transplantation at a dedicated CLES facility is feasible and resulted in additional transplants. Recipients of allografts assessed with a CLES had a higher rate of PGD3-72 hours, but similar 30-day and 1-year outcomes compared to conventional lung recipients. (NCT02234128).

Although microdialysis is a common in vivo sampling technique, a detailed characterization of the performance of a microdialysis probe used for sampling ethanol molecules has not been conducted. In this work, experimental and computational investigations were carried out to quantitatively study ethanol diffusion characteristics for home-made and commercially available probes. Probe efficiency, i.e. recovery rate (defined as the ethanol concentration in the dialysate to that in the external medium surrounding the probe) was used to characterize the performance. The recovery rate was measured at different perfusion flow rates (0.1, 0.2, 0.5, 1, 1.5, 2 μL/min) and external ethanol concentrations (1, 2.5, 5, 10, 20 mM) with controlled environmental conditions. Effect of temperature was also investigated at 19, 37 and 47 °C. The results show that reducing the flow rate from 2 to 0.1 μL/min at least triples the recovery rate for the home-made probes, and it remains nearly unchanged when varying external ethanol concentration. The performance for two commercial microdialysis probes with different membrane materials and configurations were also determined and have similar recovery rates. Through computational modeling, the diffusion coefficient of ethanol in the semipermeable membrane of the home-made probe was determined by fitting the experimental data, and it was found to be 9 × 10

Objectives: New temperature management concepts of moderate and mild hypothermic circulatory arrest during aortic arch surgery have gained weight over profound cooling. Comparisons of all temperature levels have rarely been performed. We performed direct and indirect comparisons of deep hypothermic circulatory arrest (DHCA) (≤20°C), moderate hypothermic circulatory arrest (MHCA) (20.1–25°C), and mild hypothermic circulatory arrest (mild HCA) (≥25.1°C) in a network meta-analysis. Methods: The literature was systematically searched for all papers published through February 2022 reporting on clinical outcomes after aortic arch surgery utilizing DHCA, MHCA and mild HCA. The primary outcome was operative mortality. The secondary outcomes were postoperative stroke and acute kidney failure (AKI). Results: A total of 34 studies were included, with a total of 12,370 patients. DHCA was associated with significantly higher postoperative incidence of stroke when compared with MHCA (odds ratio [OR], 1.46, 95% confidence interval [CI], 1.19–1.78) and mild HCA: (OR, 1.50, 95% CI, 1.14–1.98). Furthermore, DHCA and MHCA were associated with higher operative mortality when compared with mild HCA (OR 1.71, 95% CI, 1.23–2.39 and OR 1.50, 95% CI, 1.12–2.00, respectively). Separate analysis of randomized and propensity score matched studies showed sustained increased risk of stroke with DHCA in contrast to MHCA and mild HCA (OR, 1.61, 95% CI, 1.18–2.20, p value =.0029 and OR, 1.74, 95% CI, 1.09–2.77, p value =.019). Conclusions: In the included studies, the moderate to mild hypothermia strategies were associated with decreased operative mortality and the risk of postoperative stroke. Large-scale prospective studies are warranted to further explore appropriate temperature management for the treatment of aortic arch pathologies.

The American Transplant Congress 2022, which took place between June 4th and June 8th of 2022, was a hybrid meeting with in-person attendance in Boston-MA and a real-time virtual experience via an online platform. First, we identified abstracts discussing machine perfusion preservation for all organs, a hot topic and approach that may develop into the new gold standard of organ preservation in the near future. A total of 39 abstracts on organ machine preservation were presented at the meeting. Next, we selected abstracts which focus on advances including new approaches to organ preservation, promising biomarkers, ex-situ treatment including cellular therapies, and novel research areas. Here, we summarized the latest developments on machine perfusion preservation in both experimental and clinical studies.

Ex vivo lung perfusion (EVLP), is a platform that allows simultaneous testing and treatment of the lungs. However, use of EVLP is costly and requires access to lab animals and accompanying facilities. To increase the use of EVLP for research, we developed a method to perform EVLP using abattoir procured lungs. Furthermore, we were also able to significantly decrease costs.Six pair of lungs were procured from abattoir sheep. The lungs were then flushed and stored in ice for 3 h. A low-flow (20% of cardiac output) approach, a tidal volume of 6 ml/kg bodyweight and total perfusion time of 3 h were chosen. Perfusion fluids and circuits were self-made. Lung biopsies, perfusate collection, respiratory values, circulatory pressures were recorded and hourly blood gas analyses were performed.Mean pOSheep lungs, acquired from an abattoir, can be ex vivo perfused under similar conditions as lab animal lungs with similar results regarding e.g., oxygenation and ATP restoration. Furthermore, costs can be significantly reduced by making use of this abattoir model. By increasing accessibility and lowering costs for experiments using lung perfusion, more results may be achieved in the field of lung diseases.

To evaluate muscle perfusion in patients with peripheral artery disease (PAD) before and after percutaneous transluminal angioplasty (PTA) of the limb by means of MR arterial spin labeling (ASL) and intravoxel incoherent motion (IVIM) under the resting state.Twenty-eight patients with lower extremity PAD were enrolled. Skeletal muscles in lower extremities were examined at rest by using ASL and IVIM at 3.0 T. Imaging metrics, including blood flow (BF), perfusion fraction f, diffusion coefficient D, and pseudodiffusion coefficient DABI was significantly improved after PTA (P 0.001). For ASL and IVIM imaging, significant changes were noted in ASL-BF and IVIM-D values in the lateral, soleus, and gastrocnemius muscle groups (all P 0.0125) when comparing pre- and postoperative measurements. Changes in ASL-BF and IVIM-f values in the anterior muscle group, and in IVIM-DMultiparametric MR techniques including ASL and IVIM can detect the perfusion changes of lower limb tissue before and after PTA in patients with PAD under resting state.

Modular automation is a flexible and reliable option to build the foundation of a new or evolving process or to introduce automation to a process that is already established. Herein the authors demonstrate that modular automation provides both high-quality and high-yield T-cell products.Cells from three individual donors collected on an automated continuous flow centrifugation system were successfully expanded in a functionally closed, automated, perfusion-based hollow fiber bioreactor. These cells were then prepared for cryopreservation in an automated closed-system device that maintains temperature and aliquots a mixed cell product and cryoprotectant into product bags. Cell product bags were thawed and expanded in flasks. Samples taken throughout this manufacturing process were analyzed for cell phenotype, exhaustion markers and functionality. The proportion of CD4+ and CD8+ T cells was maintained through each step, from pre-expansion and post-expansion to immediately after thaw and 24 h after thaw.Interestingly, phenotypic markers such as CD45RO, CD45RA and CCR7 evolved throughout the process and stem-like memory T cells emerged as the predominant phenotype in the clinically relevant 24-h post-thaw sample.Modular automation supported the generation of stem-like memory T cells that were not terminally exhausted and were able to produce effector cytokines upon restimulation.

The human amniotic membrane contains the cellular parts obligatory for cell integration and tissue remodeling and has high tensile strength and persistence. We theorized that such material could function as a scaffold to improve the survival of ischemic tissue in random skin flaps. Male Albino Wistar rats (n = 30) were randomly assigned to three groups, each receiving a different model of AM on dorsal paravertebral areas: saline, amniotic membrane sheet, and micronized amniotic membrane. Digital photographs were taken, and the survival area was examined after one week. Histological analysis of skin flap tissue was performed, and the expression rate of vascular endothelial growth factor and apoptotic protein was examined. The survival percentage increased over time in all groups; however, one week after the implanted AM was increased survival in both experimental groups, with significantly greater than in the group control. In the experimental groups, there was a more regular arrangement of collagen and improved epithelialization in the flap tissue, also an increased number of inflammatory cells was observed in the control group. Additionally, VEGF and apoptotic protein expression, respectively, were significantly lower and greater in the control group than in the experimental groups. These results show that micronized membrane is an excellent scaffold for promoting flap survival.

This article describes fabrication of a customizable bioreactor, which comprises a perfusion system and coverslip-based tissue culture chamber that allow centimeter-scale vascularized or otherwise canalized tissue constructs to be maintained in weeks long static and/or perfusion culture at an exceptionally low cost, with intermittent live imaging and media sampling capabilities. The perfusion system includes a reusable polydimethylsiloxane (PDMS) lid generated from a three-dimensional (3D)-printed poly-lactic acid (PLA) mold and several lengths of perfusion tubing. The coverslip tissue culture chamber includes PDMS components built with 3D-printed PLA molds, as well as 3D-printed PLA frames and glass coverslips that house perfusable hydrogel constructs. As proof of concept, we fabricated a vascularized hydrogel construct, which was subjected to static and perfusion tissue culture, as well as flow studies using fluorescent beads and widefield fluorescent microscopy. This system can be readily reproduced, promoting the advancement of tissue engineering and regenerative medicine research.

This study proposes a computational fluid dynamics model of a human placenta's independent exchange unit (placentome) to assess the effect that the inner villi distribution and decidual veins (DVs) location and number, have on the oxygen uptake.The internal placentome porosity distribution was altered in symmetric morphology, while asymmetry was introduced by varying the location and number of DVs. The DV asymmetry was introduced by either displacing them circumferentially, thereby changing the angle between them, or by adding DVs in the inlet cross-section. The results were analyzed by the changes in the normalized oxygen mass fraction and the oxygen uptake.Oxygenated blood was shown to be delivered deeper into the placentome when the area of non-homogeneous porosity was larger. The largest oxygen uptake was achieved in the asymmetric model with the smallest angle distance between the DVs, where a 10% decrease relative to the farthest case was obtained. Placing DVs adjacent to the spiral artery opening enhanced the drainage of oxygenated blood.This study demonstrates the importance of the local porosity distribution for the proper perfusion of the intervillous space and proposes a novel approach to improve our understanding of the role of the DVs in placental oxygen uptake.

The aim of this study was to investigate the tissue perfusion status and circadian rhythm in moderately premature infants. As a prospective study, from July 2019 to October 2019, the haemodynamic stability of moderate to late preterm, including such indicators as perfusion index (PI), blood pressure (systolic/diastolic) (BP), heart rate (HR), respiratory rate (RR), oxygen saturation (SpO2) and body temperature were monitored in the morning and at night within eight days after birth. There was no difference of statistical significance between PI values in the morning and at night (P>0.05). The HR from days six to eight after birth was higher than days one to three (P

Background: SpO2 is a widely used estimation of oxygen saturation owing to its convenient usage and low cost. However, SpO2 determination under low perfusion condition is severely affected by noise.Methods: In this paper, an autocorrelation modeling method for the oxygen saturation measurement during low perfusion is presented. The proposed method mainly contains two steps: calculating the autocorrelation of the photoplethysmography (PPG) signals and modeling for the parameter calculation. The autocorrelation of the PPG signals can suppress the noise and extract pulse waves from low perfusion signals. The model can realize the calculation of SpO2 with the autocorrelation signals. Results: Experiments showed that the new method had a good accuracy and stability under low perfusion condition (perfusion index (PI)

PURPOSE: SSFS is an underdiagnosed complication of craniectomized patients, which mainly presents with headache, motor weakness, and cognitive impairments. In these patients, cranioplasty improves these symptoms. Furthermore, patients without a classical SSFS have been shown to improve their neurological functions after reconstructive surgery. Amongst the many different pathophysiological theories proposed, the changes of CBP caused by the cranial defect might have a role in the neurological deficiencies. We have studied CBP in twelve cortical areas of both hemispheres, using 99mTc-HMPAO SPECT-CT before and after cranioplasty.METHODS: Twenty-eight craniectomized patients subject to reconstructive surgery were studied with 99mTc- HMPAO in three different times, before cranioplasty, a week after, and three months later. The images were processed with quantification software comparing CBP of 24 cortical areas with a reference area , and with a database of normal individuals. A mixed effects model was used to determine the signification of CBP changes in the cortex regions of both the damaged and undamaged brain hemispheres.RESULTS: CBP increased significantly in both hemispheres after cranioplasty both in ratio (β=0.019 p-value=0,030 first post-surgical SPECT-CT and β=0.021 p-value=0,015 in the second study, vs. pre-surgical) and Z-score (β=0.220 p-value=0,026 and β=0.279 p-value=0,005 respectively). Nine of twelve areas of the damaged side had a significant lower CBP ratio and Z-score than the undamaged. Posterior cingulate showed an increased CBP ratio (p-value=0,034) and Z-score(p-value0,028) in the first post-surgical SPECT-CT.CONCLUSION: CBP changes significantly in specific cortical areas after cranioplasty, which might explain the clinical improvements observed. Posterior cingulate changes might explain some improvements in attention impairments described. 99mTc-HMPAO SPECT-CT might be a valid tool to assess CBP changes in these patients and could have a role in the management of craniectomized individuals.CLINICAL TRIAL REGISTRATIONNot applicable

Background. Septic shock is a common clinical critical disease with high mortality, hemodynamic instability, and easy to be complicated with multiple organ failure. The rapid progress of the patient’s condition poses a serious threat to patient’s safety. Aim. To investigate the relationship between the dynamic monitoring of microcirculation perfusion parameters and blood lactic acid level and the prognosis of patients with infection shock in ICU. Methods. A total of 104 patients with septic shock admitted to ICU of Affiliated Hai’an Hospital of Nantong University from February 2018 to June 2021 were selected for clinical research. According to the survival situation of patients after 28 days of treatment, they were divided into the death group (n = 48) and the survival group (n = 56). The central venous-arterial carbon dioxide partial pressure difference (Pcv-aCO2), the ratio of central venous-arterial carbon dioxide partial pressure difference to arterial central venous oxygen content difference (Pcv-aCO2/Ca-cvO2), and blood lactic acid level were retrospectively analyzed and compared between the two groups on the first, third, and seventh days after admission to ICU. The odds ratio (OR) of three indexes affecting the prognosis of patients with septic shock was analyzed by univariate and multivariate mathematical models, and the value of three indexes in predicting the prognosis of patients was analyzed by receiver operating curve (ROC). Results. Pcv-aCO2 and lactic acid in the death group were higher than those in the survival group on the 1st, 3rd, and 7th day of ICU stay ( P P P

To improve image quality and resolution of dynamic susceptibility contrast perfusion weighted imaging (DSC-PWI) by developing acquisition and reconstruction methods exploiting the temporal regularity property of DSC-PWI signal.A novel regularized reconstruction is proposed that recovers DSC-PWI series from interleaved segmented spiral k-space acquisition using higher order temporal smoothness (HOTS) properties of the DSC-PWI signal. The HOTS regularization is designed to tackle representational insufficiency of the standard first-order temporal regularizations for supporting higher accelerations. The higher accelerations allow for k-space coverage with shorter spiral interleaves resulting in improved acquisition point spread function, and acquisition of images at multiple TEs for more accurate DSC-PWI analysis.The methods were evaluated in simulated and in-vivo studies. HOTS regularization provided increasingly more accurate models for DSC-PWI than the standard first-order methods with either quadratic or robust norms at the expense of increased noise. HOTS DSC-PWI optimized for noise and accuracy demonstrated significant advantages over both spiral DSC-PWI without temporal regularization and traditional echo-planar DSC-PWI, improving resolution and mitigating image artifacts associated with long readout, including blurring and geometric distortions. In context of multi-echo DSC-PWI, the novel methods allowed ∼4.3× decrease of voxel volume, providing 2× number of TEs compared to the previously published results.Proposed HOTS reconstruction combined with dynamic spiral sampling represents a valid mechanism for improving image quality and resolution of DSC-PWI significantly beyond those available with established fast imaging techniques.

Cells grown in chemically defined medium are sensitive to shear force, potentially resulting in decreased cell growth. We optimized the perfusion process for HEK293 cell-based recombinant adenovirus-vectored zoster vaccine (Ad-HER) production with chemically defined medium.We first studied the pseudo-continuous strategies in shake flasks as a mimic of the bioreactor equipped with perfusion systems. Using design of experiment (DoE) in shake flasks, we obtained the regression models between Ad-HER titer/virus input-output ratio and three production process parameters: time of infection (TOI), multiplicity of infection (MOI), and virus production pH (pH). We then confirmed the effect of Pluronic F68 (PF-68) at 3.0 g/L on HEK293 cell growth and Ad-HER production in shake flasks and a 2 L benchtop bioreactor.The optimized process was scale-up to a 2 L benchtop bioreactor with the PATFP perfusion system, which yielded cell density of 7.4 × 10This optimization strategy could be used to develop a robust process with stable cell culture performance and adenovirus titer. Increasing PF-68 concentration in chemically defined medium could protect cells from shear stress generated by perfusion system.

This study aimed to evaluate the effect of radial artery cannulation on hand perfusion in patients with normal modified Allen's test undergoing cardiac surgeries using cardiopulmonary bypass (CPB).Prospective follow-up study.Single institution, Assiut University Cardiothoracic Hospital.Forty-nine patients who underwent cardiac surgeries using cardiopulmonary bypass were enrolled.Cannulation of radial artery in the dominant hand using a 20-gauge catheter.The primary outcomes were the mean peripheral perfusion index (PPI)60 seconds (mean PPIIn adult patients undergoing cardiac surgeries using CPB, even with normal modified Allen's test, radial artery cannulation may affect the perfusion of the dominant hand, especially at low arterial blood pressure or low core body temperature. Since the PPI is one of the noninvasive methods used for intraoperative assessment of the peripheral perfusion, the authors recommend the use of the noncannulated hand for this purpose to not misguide this assessment.

Here we report the perfusion culture of a multi-layered tissue composed of HepG2 cells (a human hepatoma line) in a pressure-driven microphysiological system (PD-MPS), which we developed previously as a multi-throughput perfusion culture platform. The perfusion culture of multi-layered tissue model was constructed by inserting a modified commercially available permeable membrane insert into the PD-MPS. HepG2 cells were layered on the membrane, and culture medium was perfused both through and below the membrane. The seeded density (number of cells/cm

Given the increasing graft shortage, the transplant community is forced to use so called marginal liver grafts with a higher susceptibility to ischemia-reperfusion injury. This exposes the recipient to a higher risk of graft failure and post-transplant complications. While static cold storage remains the gold standard in low-risk transplant scenarios, dynamic preservation strategies may allow to improve outcomes after transplantation of marginal liver grafts. Two dynamic preservation strategies, end-ischemic hypothermic oxygenated perfusion (HOPE) and continuous normothermic machine perfusion (cNMP), have been evaluated in randomized clinical trials. The results show improved preservation of liver grafts after cNMP and reduction of post-transplant biliary complications after HOPE. In comparison to cNMP, HOPE has the advantage of requiring less logistics and expertise with the possibility to return to default static cold storage. Both strategies allow to assess graft viability prior to transplantation and may thus contribute to optimizing graft selection and reducing discard rates. The use of dynamic preservation is rapidly increasing in France and results from a national randomized trial on the use of HOPE in marginal grafts will soon be available. Future applications should focus on controlled donation after circulatory death liver grafts, split grafts and graft treatment during perfusion. The final aim of dynamic liver graft preservation is to improve post-transplant outcomes, increase the number of transplanted grafts and allow expansion of transplant indications.

Objective: This study investigates whether liver grafts donated after circulatory death (DCD) that are declined by the entire Eurotransplant region can be salvaged with abdominal normothermic regional perfusion (aNRP).Background: aNRP is increasingly used for DCD liver grafts because it prevents typical complications. However, it is unclear whether aNRP is capable to rescue pretransplant declined liver grafts by providing the opportunity to test function during donation.Methods: Donor livers from DCD donors, declined by all centers in the Eurotransplant region, were included for this study. The comparator cohort included standard DCD livers and livers donated after brain death, transplanted in the same time period.Results: After the withdrawal of life-sustaining treatment, 28 from the 43 donors had a circulatory death within 2 hours, in which case aNRP was initiated. Of these 28 cases, in 3 cases perfusion problems occurred, 5 grafts were declined based on liver assessment, and 20 liver grafts were transplanted. The main differences during aNRP between the transplanted grafts and the assessed nontransplanted grafts were alanine transaminase levels of 53 U/L (34–68 U/L) versus 367 U/L (318–488 U/L) (P=0.001) and bile production in 100% versus 50% of the grafts (P=0.024). The 12-month graft and patient survival were both 95%, similar to the comparator cohort. The incidence of ischemic cholangiopathy was 11%, which was lower than in the standard DCD cohort (18%).Conclusion: aNRP can safely select and thus is able to rescue DCD liver grafts that were deemed unsuitable for transplantation, while preventing primary nonfunction and minimizing ischemic cholangiopathy.

Radiation dose associated with computed tomography (CT) perfusion (CTP) may discourage its use despite its added diagnostic benefit in quantifying ischemic lesion volume. Sparse-view CT reduces scan dose by acquiring fewer X-ray projections per gantry rotation but is contaminated by streaking artifacts using filtered back projection (FBP). We investigated the achievable dose reduction by sparse-view CTP with FBP without affecting CTP lesion volume estimations.Thirty-eight consecutive patients with acute ischemic stroke and CTP were included in this simulation study. CTP projection data was simulated by forward projecting original reconstructions with 984 views and adding Gaussian noise. Full-view (984 views) and sparse-view (492, 328, 246, and 164 views) CTP studies were simulated by FBP of simulated projection data. Cerebral blood flow (CBF) and time-to-maximum of the impulse residue function (Tmax) maps were generated by deconvolution for each simulated CTP study. Ischemic volumes were measured by CBF30% relative to the contralateral hemisphere and Tmax6 s. Volume accuracy was evaluated with respect to the full-view CTP study by the Friedman test with post hoc multiplicity-adjusted pairwise tests and Bland-Altman analysis.Friedman and multiplicity-adjusted pairwise tests indicated that 164-view CBF30%, 246- and 164-view Tmax6 s volumes were significantly different to full-view volumes (p0.001). Mean difference ± standard deviation (sparse minus full-view lesion volume) ranged from -1.0 ± 2.8 ml to -4.1 ± 11.7 ml for CBF30% and -2.9 ± 3.8 ml to -12.5 ± 19.9 ml for Tmax6 s from 492 to 164 views, respectively.By ischemic volume accuracy, our study indicates that sparse-view CTP may allow dose reduction by up to a factor of 3.

Hypothermic Oxygenated Perfusion (HOPE) of the liver can reduce the incidence of early allograft dysfunction (EAD) and failure in extended criteria donors (ECD) grafts, although data from prospective studies are very limited. In this monocentric, open-label study, from December 2018 to January 2021, 110 patients undergoing transplantation of an ECD liver graft were randomized to receive a liver after HOPE or after static cold storage (SCS) alone. The primary endpoint was the incidence of EAD. The secondary endpoints included graft and patient survival, the EASE risk score, and the rate of graft or other graft-related complications. Patients in the HOPE group had a significantly lower rate of EAD (13% vs. 35%, p = .007) and were more frequently allocated to the intermediate or higher risk group according to the EASE score (2% vs. 11%, p = .05). The survival analysis confirmed that patients in the HOPE group were associated with higher graft survival one year after LT (p = .03, log-rank test). In addition, patients in the SCS group had a higher re-admission and overall complication rate at six months, in particular cardio-vascular adverse events (p = .04 and p = .03, respectively). HOPE of ECD grafts compared to the traditional SCS preservation method is associated with lower dysfunction rates and better graft survival.

Tumor angiogenesis is an essential factor for tumor growth and antiangiogenic therapy. To simulate the blood perfusion characteristics of human renal cell carcinoma (RCC) longitudinally in the process of tumor growth, multimodal ultrasound examination was performed on 40 orthotopic xenograft RCC mouse models. According to tumor maximum diameter ( d ), tumor growth progress was divided into 3 steps: d ≤ 5 mm, 5 mmd ≤ 10 mm, and d10 mm. Color Doppler flow imaging (CDFI), superb microvascular imaging (SMI), and contrast-enhanced ultrasound were administered to monitor tumor perfusion characteristics. The abundance of tumor vascularity on CDFI and SMI was divided into grades 0 to III in ascending order, and their distribution range was categorized into types I to IV. As a result, heterogeneous echogenicity and irregular shape were more common in tumors d10 mm than those d10 mm ( P0.001 for both). Tumor perfusion grade and type on both CDFI and SMI made statistic difference among different growth steps, with higher ratio of hypervascular characteristic in bigger ones (all P0.05). Tumor in the same growth step had a higher perfusion grade on SMI than that on CDFI ( P0.001). On contrast-enhanced ultrasound, heterogeneous enhancement was more common in those10 mm ( P0.001). It can be concluded that the blood perfusion characteristics of RCC keep on changing during its growth process. In addition, SMI is more sensitive in evaluating tumor perfusion than CDFI.

What is the central question of this study? Is the amount of inhaled nitric oxide (NO) used during a diffusing capacity for inhaled NO manoeuvre sufficient to reduce pulmonary artery systolic pressure (PASP)? What is the main finding and its importance? These findings suggest that a single breath of inhaled NO does not change PASP, and combined with previous correlational work, further validates the use of the diffusing capacity for NO manoeuvre as a technique to determine pulmonary capillary blood volume and membrane diffusing capacity.The measurement of diffusing capacity is an important pulmonary function test to evaluate gas exchange. Using both carbon monoxide and nitric oxide (NO), the diffusing capacity for nitric oxide (D

Targeted delivery and labeling of single living cells in heterogeneous cell populations are of great importance to understand the molecular biology and physiological functions of individual cells. However, it remains challenging to perfuse fluorescence markers into single living cells with high spatial and temporal resolution without interfering neighboring cells. Here, we report a single cell perfusion and fluorescence labeling strategy based on nanoscale glass nanopipettes. With the nanoscale tip hole of 100 nm, the use of nanopipettes allows special perfusion and high-resolution fluorescence labeling of different subcellular regions in single cells of interest. The dynamic of various fluorescent probes has been studied to exemplify the feasibility of nanopipette-dependent targeted delivery. According to experimental results, the cytoplasm labeling of Sulfo-Cyanine5 and fluorescein isothiocyanate is mainly based on the Brownian movement due to the dyes themselves and does not have a targeting ability, while the nucleus labeling of 4',6-diamidino-2-phenylindole (DAPI) is originated from the adsorption between DAPI and DNA in the nucleus. From the finite element simulation, the precise manipulation of intracellular delivery is realized by controlling the electro-osmotic flow inside the nanopipettes, and the different delivery modes between nontargeting dyes and nucleus-targeting dyes were compared, showcasing the valuable ability of nanopipette-based method for the analysis of specially defined subcellular regions and the potential applications for single cell surgery, subcellular manipulation, and gene delivery.

Liver transplantation has been demonstrated to be the best treatment for several liver diseases, while grafts are limited. This has caused an increase in waiting lists, making it necessary to find ways to expand the number of organs available for transplantation. Normothermic perfusion (NMP) of liver grafts has been established as an alternative to static cold storage (SCS), but only a small number of perfusion machines are commercially available.Using a customized ex situ machine perfusion, we compared the results between ex situ NMP and SCS preservation in a porcine liver transplant model.During NMP, lactate concentrations were 80% lower after the 3-h perfusion period, compared with SCS. Bile production had a 2.5-fold increase during the NMP period. After transplantation, aspartate transaminase (AST) and alanine transaminase (ALT) levels were 35% less in the NMP group, compared to the SCS group. In pathologic analyses of grafts after transplant, tissue oxidation did not change between groups, but the ischemia-reperfusion injury score was lower in the NMP group.NMP reduced hepatocellular damage and ischemia-reperfusion injury when compared to SCS using a customized perfusion machine. This could be an alternative for low-income countries to include machine perfusion in their therapeutic options.

Background Despite myocardial perfusion imaging (MPI) by cadmium-zinc-telluride (CZT) single-photon emission computed tomography (SPECT) camera is largely used in the diagnosis and risk stratification of patients with suspected or known coronary artery disease (CAD), no data are available on the prognostic value of a regional MPI evaluation. We evaluated the prognostic value of regional MPI by the CZT camera in predicting clinical outcomes at the vessel level in patients with available angiographic data. Methods and results Five hundred and forty-one subjects with suspected or known CAD referred to 99mTc-sestamibi gated CZT-SPECT cardiac imaging and with available angiographic data were studied. Both regional total perfusion deficit (TPD) and ischemic TPD (ITPD) were calculated separately for each vascular territory (left anterior descending, left circumflex, and right coronary artery). The outcome end points were cardiac death, target vessel-related myocardial infarction, or late coronary revascularization. The prevalence of CAD ≥ 50%, regional stress TPD, and regional ITPD was significantly higher in vessels with events as compared to those without (both P < 0.001). The receiver operating characteristics area under the curve for regional ITPD for the identification of vessel-related events was 0.81 (95% confidence interval 0.75–0.86). An ITPD value of 2.0% provided the best trade-off for identifying the vessel-related event. At multivariable analysis, both CAD ≥ 50% and ITPD ≥ 2.0% resulted in independent predictors of events. Conclusions Regional myocardial perfusion assessed by the CZT camera demonstrated good reliability in predicting vessel-related events in patients with suspected or known CAD.

Background: In patients with acute stroke who undergo endovascular thrombectomy, the relative prognostic power of computed tomography perfusion (CTP) parameters compared with multiphase CT angiogram (mCTA) is unknown. We aimed to compare the predictive accuracy of mCTA and CTP parameters on clinical outcomes. Methods: We included patients with acute ischemic stroke who had anterior circulation large vessel occlusion within 24 hours of onset in Melbourne Brain Centre at the Royal Melbourne Hospital. All patients underwent CTP for endovascular thrombectomy, and the mCTA collateral score was determined using CTP-reconstructed mCTA images. The primary outcome was 90-day functional outcomes defined by modified Rankin Scale. Multivariable logistic regression models analyzed associations between mCTA and CTP parameters and 90-day functional outcomes. The ability to discriminate 90 days-functional outcomes was compared between mCTA collateral score and CTP parameters using receiver operating curve analysis and C statistics. Results: One hundred and twenty patients were included. The median age was 69 years (interquartile range, 60–79), the median baseline National Institutes of Health Stroke Scale score was 14 (interquartile range, 9–19). The baseline ischemic core volume, defined by CTP-based relative cerebral blood flow P =0.015) and poor functional outcome (modified Rankin Scale score 5–6; odds ratio, 1.032 [1.007–1.056]; P =0.010) at 90 days in the analysis of multivariable regression. There was no significant association between the mCTA score and excellent functional outcome ( P =0.58) or poor functional outcome ( P =0.155). The relative cerebral blood flow Conclusions: The CTP-based ischemic core volume may provide better discrimination for 90-day functional outcomes for patients with acute stroke undergoing endovascular thrombectomy than the mCTA collateral score.

Ex-situ heart perfusion (ESHP) is commonly used for the reanimation and preservation of hearts following donation after circulatory determined death (DCD). The only commercially available existing ESHP device promotes perfusate lactate levels for assessment of heart viability. The reliability of this marker is yet to be confirmed for DCD heart transplantation.This is a single center, retrospective study examining DCD heart transplants from March 1, 2015 to June 30, 2020. Recipients were divided into 2 groups dependent upon their requirement for or absence of mechanical circulatory support post-transplant. Lactate profiles obtained during ESHP were analyzed. Hearts were procured using the direct procurement and perfusion (DPP) method.Fifty-one DCD heart transplant recipients were studied, of which 20 (39%) were dependent on mechanical circulatory support (MCS) following transplantation, (2% Ventricular Assist Device (VAD), 16% Extra Corporeal Membrane Oxygenation (ECMO) and 21% Intra-aortic balloon pumps (IABP). There was no difference in arterial lactate profiles on ESHP at any time point for those dependent upon MCS support (MCS) and those that were not (no MCS) post-transplant. After 3 hours of ESHP, the arterial lactate was5mmol/L in 80% upon MCS vs 62% no MCS, p = .30. There was also no difference in ESHP rising arterial lactate concentrations, (15% MCS vs 13% non MCS, p = 1.00).For DCD hearts transplants retrieved using the DPP technique, lactate profiles do not seem to be a reliable predictor of mechanical circulatory support requirement post-transplant.

Background The relationship between low oxygen delivery (DO2) on cardiopulmonary bypass and morbidity and mortality following cardiac surgery remains unexamined. Methods We reviewed patients undergoing Society of Thoracic Surgeons index procedures from March 2019 to July 2020, coincident with implementation of a new electronic perfusion record that provides for continuous recording of DO2 and flow parameters. Continuous perfusion variables were analyzed using area-over-the-curve (AOC) calculations below predefined thresholds (DO2 24 hours, stroke, sternal wound infection, and reoperation). Results Eight hundred thirty-four patients were included; 42.7% (356) underwent isolated coronary artery bypass grafting (CABG), whereas 57.3% underwent nonisolated CABG (eg, valvular or combined CABG/valvular operations). DO2 24 hours (P = .04), an effect again most pronounced in nonisolated-CABG cases (P = .002), as well as acute kidney injury Conclusions Low DO2 on bypass may be associated with morbidity/mortality following cardiac surgery, particularly in patients undergoing nonisolated CABG. These results underscore the importance of goal-directed perfusion strategies.