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PURPOSE: Conventional contrast-enhanced MRI is currently the primary imaging technique used to evaluate radiation treatment response in meningiomas. However, newer perfusion-weighted MRI techniques, such as 3D pseudocontinuous arterial spin labeling (3D pCASL) MRI, capture physiologic information beyond the structural information provided by conventional MRI and may provide additional complementary treatment response information. The purpose of this study is to assess 3D pCASL for the evaluation of radiation-treated meningiomas. METHODS: Twenty patients with meningioma treated with surgical resection followed by radiation, or by radiation alone, were included in this retrospective single-institution study. Patients were evaluated with 3D pCASL and conventional contrast-enhanced MRI before and after radiation (median follow up 6.5 months). Maximum pre- and post-radiation ASL normalized cerebral blood flow (ASL-nCBF) was measured within each meningioma and radiation-treated meningioma (or residual resected and radiated meningioma), and the contrast-enhancing area was measured for each meningioma. Wilcoxon signed-rank tests were used to compare pre- and post-radiation ASL-nCBF and pre- and post-radiation area. RESULTS: All treated meningiomas demonstrated decreased ASL-nCBF following radiation (p

High-molecular-weight linear polymers (HMWLPs) have earned the name "drag-reducing polymers" because of their ability to reduce drag in turbulent flows. Recently, these polymers have become popular in bioengineering applications. This study investigated whether the addition of HMWLP in a venoarterial extracorporeal circulation (ECC) model could improve microvascular perfusion and oxygenation. Golden Syrian hamsters were instrumented with a dorsal skinfold window chamber and subjected to ECC using a circuit comprised of a peristaltic pump and a bubble trap. The circuit was primed with lactated Ringer solution (LR) containing either 5 ppm of polyethylene glycol (PEG) with a low molecular weight of 500 kDa (PEG500k) or 5 ppm of PEG with a high molecular weight of 3,500 kDa (PEG3500k). After 90 min of ECC at 15% of the animal's cardiac output, the results showed that the addition of PEG3500k to LR improved microvascular blood flow in arterioles and venules acutely (2 h after ECC), whereas functional capillary density showed improvement up to 24 h after ECC. Similarly, PEG3500k improved venular hemoglobin O2 saturation on the following day after ECC. The serum and various excised organs all displayed reduced inflammation with the addition of PEG3500k, and several of these organs also had a reduction in markers of damage with the HMWLPs compared to LR alone. These promising results suggest that the addition of small amounts of PEG3500k can help mitigate the loss of microcirculatory function and reduce the inflammatory response from ECC procedures.NEW & NOTEWORTHY High-molecular-weight linear polymers have gained traction in bioengineering applications. The addition of PEG3500k to lactated Ringer solution (LR) improved microvascular blood flow in arterioles and venules acutely after extracorporeal circulation (ECC) in a hamster model and improved functional capillary density up to 24 h after ECC. PEG3500k improved venular hemoglobin O2 saturation and oxygen delivery acutely after ECC and reduced inflammation in various organs compared to LR alone.

Stroke alters blood flow to the brain resulting in damaged tissue and cell death. Moreover, the disruption of cerebral blood flow (perfusion) can be observed in areas surrounding and distal to the lesion. These structurally preserved but suboptimally perfused regions may also affect recovery. Thus, to better understand aphasia recovery, the relationship between cerebral perfusion and language needs to be systematically examined. In the current study, we aimed to evaluate (i) how stroke affects perfusion outside of lesioned areas in chronic aphasia and (ii) how perfusion in specific cortical areas and perilesional tissue relates to language outcomes in aphasia. We analysed perfusion data from a large sample of participants with chronic aphasia due to left hemisphere stroke (n = 43) and age-matched healthy controls (n = 25). We used anatomically defined regions of interest that covered the frontal, parietal, and temporal areas of the perisylvian cortex in both hemispheres, areas typically known to support language, along with several control regions not implicated in language processing. For the aphasia group, we also looked at three regions of interest in the perilesional tissue. We compared perfusion levels between the two groups and investigated the relationship between perfusion levels and language subtest scores while controlling for demographic and lesion variables. First, we observed that perfusion levels outside the lesioned areas were significantly reduced in frontal and parietal regions in the left hemisphere in people with aphasia compared to the control group, while no differences were observed for the right hemisphere regions. Second, we found that perfusion in the left temporal lobe (and most strongly in the posterior part of both superior and middle temporal gyri) and inferior parietal areas (supramarginal gyrus) was significantly related to residual expressive and receptive language abilities. In contrast, perfusion in the frontal regions did not show such a relationship; no relationship with language was also observed for perfusion levels in control areas and all right hemisphere regions. Third, perilesional perfusion was only marginally related to language production abilities. Cumulatively, the current findings demonstrate that blood flow is reduced beyond the lesion site in chronic aphasia and that hypoperfused neural tissue in critical temporoparietal language areas has a negative impact on behavioural outcomes. These results, using perfusion imaging, underscore the critical and general role that left hemisphere posterior temporal regions play in various expressive and receptive language abilities. Overall, the study highlights the importance of exploring perfusion measures in stroke.

Introduction: Subjective surgeon interpretation of near-infrared perfusion video is limited by low inter-observer agreement and poor correlation to clinical outcomes. In contrast, quantification of indocyanine green fluorescence video (Q-ICG) correlates with histologic level of perfusion as well as clinical outcomes. Measuring dye volume over time, however, has limitations, such as it is not on-demand, has poor spatial resolution, and is not easily repeatable. Laser speckle contrast imaging quantification (Q-LSCI) is a real-time, dye-free alternative, but further validation is needed. We hypothesize that Q-LSCI will distinguish ischemic tissue and correlate over a range of perfusion levels equivalent to Q-ICG. Methods: Nine sections of intestine in three swine were devascularized. Pairs of indocyanine green fluorescence imaging and laser speckle contrast imaging video were quantified within perfused, watershed, and ischemic regions. Q-ICG used normalized peak inflow slope. Q-LSCI methods were laser speckle perfusion units (LSPU), the base unit of laser speckle imaging, relative perfusion units (RPU), a previously described methodology which utilizes an internal control, and zero-lag normalized cross-correlation (X-Corr), to investigate if the signal deviations convey accurate perfusion information. We determine the ability to distinguish ischemic regions and correlation to Q-ICG over a perfusion gradient. Results: All modalities distinguished ischemic from perfused regions of interest; Q-ICG values of 0.028 and 0.155 (p < 0.001); RPU values of 0.15 and 0.68 (p < 0.001); and X-corr values of 0.73 and 0.24 (p < 0.001). Over a range of perfusion levels, RPU had the best correlation with Q-ICG (r = 0.79, p < 0.001) compared with LSPU (r = 0.74, p < 0.001) and X-Corr (r = 0.46, p < 0.001). Conclusion: These results demonstrate that Q-LSCI discriminates ischemic from perfused tissue and represents similar perfusion information over a broad range of perfusion levels comparable to clinically validated Q-ICG. This suggests that Q-LSCI might offer clinically predictive real-time dye-free quantification of tissue perfusion. Further work should include validation in histologic studies and human clinical trials. [ABSTRACT FROM AUTHOR]

Objectives: del Nido cardioplegia is utilized for myocardial protection in adult patients undergoing cardiac surgery; however, no standardized re-dosing protocol exists. We describe perfusion characteristics and clinical outcomes in adult cardiac surgery patients who were re-dosed with del Nido cardioplegia. Methods: Chart review was performed for adult patients undergoing cardiac surgery (specific inclusion/exclusion criteria below) who received exactly two doses of del Nido cardioplegia from 2012 to 2019; n = 542 patients. The main outcome was a composite endpoint comprised of operative mortality, myocardial infarction, post-operative cardiac support device (CSD), and postoperative decrease in ejection fraction (EF), which was analyzed via multivariable logistic regression (MVLR). A secondary analysis evaluated postoperative vasoactive-inotropic scores (VIS) via gamma log link regression (GLLR) as a more physiologic indication of myocardial recovery. Results: MVLR demonstrated that increased total cardiopulmonary bypass (CPB) time was associated with a positive composite outcome (p <.001), whereas time between doses (p =.237) and the volume of each dose was not (p =.626). GLLR also demonstrated that prolonged CBP, decreased EF, congestive heart failure at time of surgery, and low hematocrit at the start of the surgery were all associated with higher VIS. Conclusions: In this retrospective study, variations in re-dosing strategy for del Nido cardioplegia do not affect postoperative outcomes and increased CPB time is associated with increased operative mortality, myocardial infarction, need for post-operative CSDs, and reduced postoperative EF, and increased VIS, irrespective of the re-dosing strategy. Further studies are warranted to to identify additional patient and operative characteristics that predispose to complications. [ABSTRACT FROM AUTHOR]

Purpose: This case report describes a patient with a pelvic kidney associated with an aortoiliac aneurysm amenable to open repair. Methods: We chose the selective cold renal perfusion to preserve renal function. Results: Other techniques such as transient or permanent extra-anatomic bypass, extracorporeal circulation and proximal aortic double clamping are also described in this report. Conclusions: Choosing the renal perfusion technique depended on the anatomical evaluations of the kidney and the renal artery location during the preoperative period. [ABSTRACT FROM AUTHOR]

This article discusses the use of CZT SPECT systems in brain imaging applications. CZT-based detectors offer advantages such as higher contrast, energy resolution, and spatial resolution compared to traditional scintillation crystals. Preliminary studies have shown that CZT SPECT systems can reduce acquisition time without compromising image quality. CZT SPECT is particularly useful in brain perfusion imaging and dopaminergic imaging. It also has potential applications in theranostics for brain tumors. Efforts are being made to standardize protocols and collect data to further improve diagnostic accuracy and patient management. [Extracted from the article]

Contemporary quality control methods are often insufficient in predicting clinical outcomes after revascularization in lower extremity arterial disease (LEAD) patients. This study evaluates the potential of near-infrared fluorescence imaging with indocyanine green to predict the clinical outcome following revascularization. Near-infrared fluorescence imaging was performed before and within 5 days following the revascularization procedure. Clinical improvement was defined as substantial improvement of pain free walking distance, reduction of rest- and/or nocturnal pain, or tendency toward wound healing. Time-intensity curves and 8 perfusion parameters were extracted from the dorsum of the treated foot. The quantified postinterventional perfusion improvement was compared within the clinical outcome groups. Successful near-infrared fluorescence imaging was performed in 72 patients (76 limbs, 52.6% claudication, 47.4% chronic limb-threatening ischemia) including 40 endovascular- and 36 surgical/hybrid revascularizations. Clinical improvement was observed in 61 patients. All perfusion parameters showed a significant postinterventional difference in the clinical improvement group (P -values <.001), while no significant differences were seen in the group without clinical improvement (P -values.168–.929). Four parameters demonstrated significant differences in percentage improvement comparing the outcome groups (P -values within.002–.006). Near-infrared fluorescence imaging has promising additional value besides clinical parameters for predicting the clinical outcome of revascularized LEAD patients. [ABSTRACT FROM AUTHOR]

Midodrine is an oral vasopressor option that allows for discontinuation of intravenous vasopressors for patients with cardiovascular conditions. It does not have a US Food and Drug Administration-labeled indication for use in children, and there is a paucity of literature in patients ≤6 years of age. This case series describes 2 infants with complex congenital heart diseases initiated on midodrine for augmentation of systolic (SBP) or diastolic blood pressure (DBP) to increase coronary perfusion. Case 1 was initiated on midodrine on hospital day 19 at a dose of 0.5 mg (0.17 mg/kg) enterally every 8 hours that was eventually increased to 1 mg (0.33 mg/kg) every 8 hours. Case 2 was initiated on midodrine on hospital day 15 at a dose of 2.5 mg (0.49 mg/kg) enterally every 8 hours, and this was decreased to 1.25 mg (0.25 mg/kg) every 8 hours due to high SBP. Both patients were discharged home on midodrine; other than the initially high SBP for Case 2, no other adverse drug events were noted. While midodrine was effective based on clinical response in these two infants, additional studies are needed due to the lack of safety and efficacy in children <6 years of age. [ABSTRACT FROM AUTHOR]

Background: Neuromonitoring devices are often used in traumatic brain injury. The objective of this report is to raise awareness concerning variations in optimal cerebral perfusion pressure (CPPopt) determination using exploratory information provided by two neuromonitoring monitors that are part of research programs (Moberg CNS Monitor and RAUMED NeuroSmart LogO). Methods: We connected both monitors simultaneously to a parenchymal intracranial pressure catheter and recorded the pressure reactivity index (PRx) and the derived CPPopt estimates for a patient with a severe traumatic brain injury. These estimates were available at the bedside and were updated at each minute. Results: Using the Bland and Altman method, we found a mean variation of − 3.8 (95% confidence internal from − 8.5 to 0.9) mm Hg between the CPPopt estimates provided by the two monitors (limits of agreement from − 26.6 to 19.1 mm Hg). The PRx and CPPopt trends provided by the two monitors were similar over time, but CPPopt trends differed when PRx values were around zero. Also, almost half of the CPPopt estimates differed by more than 10 mm Hg. Conclusions: These wide variations recorded in the same patient are worrisome and reiterate the importance of understanding and standardizing the methodology and algorithms behind commercial neuromonitoring devices prior to incorporating them in clinical use. [ABSTRACT FROM AUTHOR]

MRI evaluation of the diabetic foot is still a challenge not only from an interpretative but also from a technical point of view. The incorporation of advanced sequences such as diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) MRI into standard protocols for diabetic foot assessment could aid radiologists in differentiating between neuropathic osteoarthropathy (Charcot's foot) and osteomyelitis. This distinction is crucial as both conditions can coexist in diabetic patients, and they require markedly different clinical management and have distinct prognoses. Over the past decade, several studies have explored the effectiveness of DWI and dynamic contrast-enhanced MRI (DCE-MRI) in distinguishing between septic and reactive bone marrow, as well as soft tissue involvement in diabetic patients, yielding promising results. DWI, without the need for exogenous contrast, can provide insights into the cellularity of bone marrow and soft tissues. DCE-MRI allows for a more precise evaluation of soft tissue and bone marrow perfusion compared to conventional post-gadolinium imaging. The data obtained from these sequences will complement the traditional MRI approach in assessing the diabetic foot. The objective of this review is to familiarize readers with the fundamental concepts of DWI and DCE-MRI, including technical adjustments and practical tips for image interpretation in diabetic foot cases. [ABSTRACT FROM AUTHOR]

The myocardium and vascular system are influenced by the neurological, paracrine and endocrine systems to control blood pressure in health. Blood pressure control is crucial to maintain adequate organ perfusion and function. In disease, the homeostatic mechanisms that control these systems are dysregulated, which can lead to organ failure. Therefore, understanding the means of manipulating these systems using anaesthesia is important. The central nervous system, cardiac muscle and vascular smooth muscle all have physiological processes which can be targeted to reduce the stress response associated with their derangement. This article reviews the different pharmacological means of altering cardiac function and blood vessel calibre to improve organ perfusion. [ABSTRACT FROM AUTHOR]

In this research, we aim to investigate the feasibility of a one-stop CT energy spectrum perfusion imaging technique for chemotherapy efficacy assessment of lung cancer patients by obtaining both functional imaging parameters of energy spectrum and perfusion in one scan. From November 2018 to February 2020, a group of 23 patients with pathologically confirmed lung cancer were chosen to undergo CT energy spectrum scans both before and after treatment. The post-treatment CT perfusion data was acquired one week after the second conventional chemotherapy session. Out of the 23 patients, 15 were in the chemotherapy effective group and the remaining 8 were in the ineffective group. The reason for this group was according to recist criteria. Arterial phase iodine concentration (icap) and intravenous phase iodine concentration (icpp) of the lesions were measured, and standardized iodine base values (nic) were calculated. The maximum diameter of the tumor before and after treatment was compared to the perfusion parameters and energy spectrum parameters before and after chemotherapy in the effective group and the invalid group was compared by two tests that p<0.05. The differences between the maximum diameter of the tumor before and after chemotherapy. 2 of the 15 patients in the effective group had liquefied necrotic areas in their lesions. One-stop ct energy-spectrum perfusion imaging can show the disease progression from a functional perspective and assess the efficacy early according to the changes in perfusion parameters and energy-spectrum parameters after lung cancer treatment. [ABSTRACT FROM AUTHOR]

Pressure ulcer is considered a common and costly problem in the care of patients. Prevention and management of pressure ulcer are very important due to the high cost of treatment and the adverse consequences of pressure ulcer. This study aimed to evaluate the effect of implementing “aSSKINg” model in reducing pressure ulcer risk. This study used a before- and afterintervention quasi-experimental design. This study was performed on 60 patients who were not randomly selected and assigned in to control and study group. The data collection tool was a 3-part sheet (Braden scale, skin health assessment, and Pressure ulcer assessment). The incidence of pressure ulcer was 19 (60.0%) in the control group versus 9 (30.0%) in the study group with statistical significant differences. The most common site of pressure ulcer was coccyx (6 [31.6%]) in the control group and Heel (3 [33.3%]) in the study group. The application of “aSSKINg” model in the patients with pressure ulcers is effective in reducing the incidence and severity of pressure ulcers. [ABSTRACT FROM AUTHOR]

Drugs that induce reversible slowing of metabolic and physiological processes would have great value for organ preservation, especially for organs with high susceptibility to hypoxia- reperfusion injury, such as the heart. Using whole-organism screening of metabolism, mobility, and development in Xenopus, we identified an existing drug, SNC80, that rapidly and reversibly slows biochemical and metabolic activities while preserving cell and tissue viability. Although SNC80 was developed as a delta opioid receptor activator, we discovered that its ability to slow metabolism is independent of its opioid modulating activity as a novel SNC80 analog (WB3) with almost 1000 times less delta opioid receptor binding activity is equally active. Metabolic suppression was also achieved using SNC80 in microfluidic human organs-on-chips, as well as in explanted whole porcine hearts and limbs, demonstrating the cross-species relevance of this approach and potential clinical relevance for surgical transplantation. Pharmacological induction of physiological slowing in combi- nation with organ perfusion transport systems may offer a new therapeutic approach for tissue and organ preservation for transplantation, trauma management, and enhancing patient survival in remote and low- resource locations. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion Endothelial dysfunction is a pathophysiological change preceding many cardiovascular events. Measuring improvements of endothelial function is challenging when function is already optimal, which may be remediated using a physiological challenge. This study aimed to determine whether imaging assessments can detect microvascular effects of a mixed meal tolerance test (MMTT).Twenty healthy volunteers (age ≥45 and ≤70 years) underwent two MMTTs at the beginning (Day 1) and end (Day 84) of a twelve‐week period. Imaging methods included laser speckle contrast imaging (LSCI) combined with post‐occlusive reactive hyperaemia (PORH) and local thermal hyperaemia (LTH) challenges, passive leg movement ultrasonography (PLM), and sidestream dark field microscopy (SDFM). Measurements were conducted pre‐MMTT and at 5 timepoints post‐MMTT for PLM and SDFM and 3 timepoints post‐MMTT for PORH and LTH.No consistent effects of the MMTT were detected on LSCI LTH, PLM and SDFM endpoints. LSCI PORH maximum perfusion was significantly suppressed 46, 136, and 300 min post‐MMTT administration on Day 1, while residual perfusion decreased significantly 46 and 136 min post‐MMTT on Day 1. However, when repeated on Day 84, PORH endpoints were not significantly affected by the MMTT.SDFM, PLM and LSCI LTH endpoints displayed high intra‐subject variability and did not detect consistent effects of MMTT. LSCI PORH endpoints displayed the lowest intra‐subject variability of all assessed endpoints and were affected by the MMTT on Day 1, but not on Day 84. Further standardization of methods or more robust challenges to affect vascular endpoints may be needed. [ABSTRACT FROM AUTHOR]

Background and purpose: Imaging with conventional MRI plays a pivotal role in characterization of skull base bone-intrinsic lesions, yet some lesions are very challenging. The purpose of this study is to evaluate the role of diffusion and perfusion by T2* dynamic susceptibility contrast (DSC) in characterization of such lesions. Results: Lesions showed mostly correlated with approach: Chordomas had low perfusion and intermediate to high perfusion, while chondrosarcoma had ADC value > 1.6 × 10–3/cm2 and more perfused. Metastases had variable ADC values usually intermediate with high perfusion. Plasmacytomas had similar features yet with characteristic conventional morphology and single number. Lymphoma (primary bony) had high perfusion and lowest diffusion ADC (= 04–0.7 × 10–3/cm2). Giant cell tumors and hemangiopericytomas had lowest perfusion. Conclusion: The proposed imaging approach showed very good results and high accuracy in differentiation of skull base bony lesions. [ABSTRACT FROM AUTHOR]

Postoperative tissue flap vitality monitoring enables early detection of clinical complications, allowing for intervention. Timely re-operation can prevent the need for extensive correction procedures, thus reducing healthcare costs and hospitalization time. Statistics show that monitoring can increase the success rate of flap survival to 95% or higher. However, despite the significant progress in monitoring techniques, major and minor complications, leading to the loss of the flap, still occur. This clinical application review aims to provide a comprehensive overview of the recent advancements and findings in flap surgery reconstructions, transplants, and systems for their postoperative assessment. The literature from the years 1925 to 2024 has been reviewed to capture previous and current solutions for monitoring flap vitality. Clinically acclaimed methods and experimental techniques were classified and reviewed from a technical and clinical standpoint. Physical examination, metabolism change, ultrasound method, and electromagnetic (EM) radiation-based measurement methods were carefully evaluated from the perspective of their considered applications. Guidelines aiding engineers in the future design and development process of monitoring systems were proposed. This paper provides a comprehensive overview of the monitoring techniques used in postoperative flap vitality monitoring. It also gives an overview of each approach and potential ways for future development. [ABSTRACT FROM AUTHOR]

We previously reported that normothermic ex vivo kidney perfusion (NEVKP) is superior in terms of organ protection compared to static cold storage (SCS), which is still the standard method of organ preservation, but the mechanisms are incompletely understood. We used a large animal kidney autotransplant model to evaluate mitochondrial function during organ preservation and after kidney transplantation, utilizing live cells extracted from fresh kidney tissue. Male porcine kidneys stored under normothermic perfusion showed preserved mitochondrial function and higher ATP levels compared to kidneys stored at 4 °C (SCS). Mitochondrial respiration and ATP levels were further enhanced when AP39, a mitochondria-targeted hydrogen sulfide donor, was administered during warm perfusion. Correspondingly, the combination of NEVKP and AP39 was associated with decreased oxidative stress and inflammation, and with improved graft function after transplantation. In conclusion, our findings suggest that the organ-protective effects of normothermic perfusion are mediated by maintenance of mitochondrial function and enhanced by AP39 administration. Activation of mitochondrial function through the combination of AP39 and normothermic perfusion could represent a new therapeutic strategy for long-term renal preservation. The authors previously reported that normothermic ex vivo kidney perfusion is superior to static cold storage in terms of organ protection, but the detailed mechanism was unclear. Here the authors show that the organ-protective effects of normothermic perfusion are mediated by maintenance of mitochondrial function and enhanced by administration of AP39, a mitochondria-targeted hydrogen sulfide donor. [ABSTRACT FROM AUTHOR]

Background: Ictal brain perfusion SPECT provides higher sensitivity for the identification of the epileptic seizure onset zone (SOZ) than interictal SPECT. However, ictal SPECT is demanding due to the unpredictable waiting period for the next seizure to allow for ictal tracer injection. Thus, starting with an interictal scan and skipping the ictal scan if the interictal scan provides a SOZ candidate with high confidence could be an efficient approach. The current study estimated the rate of high-confidence SOZ candidates and the false lateralization rate among them for interictal and ictal SPECT. Methods: 177 patients (48% females, median age 38y, interquartile range 27–48y) with ictal and interictal SPECT acquired with 99mTc-HMPAO (n = 141) or -ECD (n = 36) were included retrospectively. The vast majority of the patients was suspected to have temporal lobe epilepsy. Visual interpretation of the SPECT data was performed independently by 3 readers in 3 settings: "interictal only" (interictal SPECT and statistical hypoperfusion map), "ictal only" (ictal SPECT and hyperperfusion map), and "full" setting (side-by-side interpretation of ictal and interictal SPECT including statistical maps and SISCOM analysis). The readers lateralized the SOZ (right, left, none) and characterized their confidence using a 5-score. A case was considered "lateralizing with high confidence" if all readers lateralized to the same hemisphere with at least 4 of 5 confidence points. Lateralization of the SOZ in the "full" setting was used as reference standard. Results: The proportion of "lateralizing with high confidence" cases was 4.5/31.6/38.4% in the "interictal only"/"ictal only"/"full" setting. One (12.5%) of the 8 cases that were "lateralizing with high confidence" in the "interictal only" setting lateralized to the wrong hemisphere. Among the 56 cases that were "lateralizing with high confidence" in the "ictal only" setting, 54 (96.4%) were also lateralizing in the "full" setting, all to the same hemisphere. Conclusions: Starting brain perfusion SPECT in the presurgical evaluation of epilepsy with an interictal scan to skip the ictal scan in case of a high-confidence interictal SOZ candidate is not a useful approach. In contrast, starting with an ictal scan to skip the interictal scan in case of a high-confidence ictal SOZ candidate can be recommended. [ABSTRACT FROM AUTHOR]

Background: MR perfusion is a standard marker to distinguish progression and therapy-associated changes after surgery and radiochemotherapy for glioblastoma. TRAMs (Treatment Response Assessment Maps) were introduced, which are intended to facilitate the differentiation of vital tumor cells and radiation necrosis by means of late (20–90 min) contrast clearance and enhancement. The differences of MR perfusion and late-enhancement are not fully understood yet. Methods: We have implemented and established a fully automated creation of rapid wash-out (15–20 min interval) maps in our clinic. We included patients with glioblastoma, CNS lymphoma or brain metastases who underwent our MR protocol with MR perfusion and rapid wash-out between 01/01/2024 and 30/06/2024. Since both wash-out and hyperperfusion are intended to depict the active tumor area, this study involves a quantitative and qualitative comparison of both methods. For this purpose, we volumetrically measured rCBV (relative cerebral blood volume) maps and rapid wash-out maps separately (two raters). Additionally, we rated the agreement between both maps on a Likert scale (0–10). Results: Thirty-two patients were included in the study: 15 with glioblastoma, 7 with CNS lymphomas and 10 with brain metastasis. We calculated 36 rapid wash-out maps (9 initial diagnosis, 27 follow-up). Visual agreement of MR perfusion with rapid wash-out by rating were found in 44 ± 40% for initial diagnosis, and 75 ± 31% for follow-up. We found a strong correlation (Pearson coefficient 0.92, p < 0.001) between the measured volumes of MR perfusion and rapid wash-out. The measured volumes of MR perfusion and rapid wash-out did not differ significantly. Small lesions were often not detected by MR perfusion. Nevertheless, the measured volumes showed no significant differences in this small cohort. Conclusions: Rapid wash-out calculation is a simple tool that provides new information and, when used in conjunction with MR perfusion, may increase diagnostic accuracy. The method shows promising results, particularly in the evaluation of small lesions. [ABSTRACT FROM AUTHOR]

Therapeutic oligonucleotides (ONs) are typically manufactured via solid-phase synthesis, characterized by limited scalability and huge environmental footprint, limiting their availability. Biomanufactured ONs have the potential to reduce the immunogenic side-effects, and to improve the sustainability of their chemical counterparts. Rhodovulum sulfidophilum was demonstrated a valuable host for the extracellular production of recombinant ONs. However, low viable cell densities and product titer were reported so far. In this work, perfusion cell cultures were established for the intensification of ON biomanufacturing. First, the perfusion conditions were simulated in 50 mL spin tubes, selected as a scale-down model of the process, with the aim of optimizing the medium composition and process parameters. This optimization stage led to an increase in the cell density by 44 % compared to the reference medium formulation. In addition, tests at increasing perfusion rates were conducted until achieving the maximum viable cell density (VCD max), allowing the determination of the minimum cell-specific perfusion rate (CSPR min) required to sustain the cell culture. Intriguingly, we discovered in this system also a maximum CSPR, above which growth inhibition starts. By leveraging this process optimization, we show for the first time the conduction of perfusion cultures of R. sulfidophilum in bench-scale bioreactors. This process development pipeline allowed stable cultures for more than 20 days and the continuous biomanufacturing of ONs, testifying the great potential of perfusion processes. • Medium composition and design space defined for perfusion cultures of Rhodovulum sulfidophilum. • Process scaled up to a 2 L bioreactor with ATF and effect of perfusion rate investigated. • Stable perfusion cultures for >20 days, with cell densities lager than in fed-batch. • Oligonucleotides continuously harvested, with titers 2 orders of magnitudes larger than literature. • First report on continuous biomanufacturing of oligonucleotides. [ABSTRACT FROM AUTHOR]

The peripheral perfusion index (PI) is derived from pulse oximetry and is defined as the ratio of the pulse wave of the pulsatile portion (arteries) to the non-pulsatile portion (venous and other tissues). A growing number of clinical studies have supported the use of PI in various clinical scenarios, such as guiding hemodynamic management and serving as an indicator of outcome and organ function. In this review, we will introduce and discuss this traditional but neglected indicator of the peripheral microcirculatory perfusion. Further clinical trials are required to clarify the normal and critical values of PI for different monitoring devices in various clinical conditions, to establish different standards of PI-guided strategies, and to determine the effect of PI-guided therapy on outcome. [ABSTRACT FROM AUTHOR]

The paper-based culture platform developed by Whitesides readily incorporates tissue-like structures into laboratories with established workflows that rely on monolayer cultures. Cell-laden hydrogels are deposited in these porous scaffolds with micropipettes; these scaffolds support the thin gel slabs, allowing them to be evaluated individually or stacked into thick constructs. The paper-based culture platform has inspired many basic and translational studies, each exploring how readily accessible materials can generate complex structures that mimic aspects of tissues in vivo. Many of these examples have relied on static culture conditions, which result in diffusion-limited environments and cells experiencing pericellular hypoxia. Perfusion-based systems can alleviate pericellular hypoxia and other cell stresses by continually exposing the cells to fresh medium. These perfusion systems are common in microfluidic and organ-on-chip devices supporting cells as monolayer cultures or as 3D constructs. Here, we introduce a continuous flow delivery system, which uses parts readily produced with 3D printing to provide a self-contained culture platform in which cells in paper or other scaffolds are exposed to fresh (flowing) medium. We demonstrate the utility of this device with examples of cells maintained in single cell-laden scaffolds, stacks of cell-laden scaffolds, and scaffolds that contain monolayers of endothelial cells. These demonstrations highlight some possible experimental questions that can be enabled with readily accessible culture materials and a perfusion-based device that can be readily fabricated. [ABSTRACT FROM AUTHOR]

Introduction Continuous extracorporeal perfusion (ECP), or machine perfusion, holds promise for prolonged skeletal muscle preservation in limb ischemia-reperfusion injury. This study aimed to extend the amputation-to-replantation time window from currently 6 hours to 33 hours using a 24-hour ECP approach. Materials and Methods Six large white pigs underwent surgical forelimb amputation under general anesthesia. After amputation, limbs were kept for 9 hours at room temperature and then perfused by 24-hour ECP with a modified histidine-tryptophan-ketoglutarate (HTK) solution. After ECP, limbs were orthotopically replanted and perfused in vivo for 12 hours. Clinical data, blood, and tissue samples were collected and analyzed. Results All 6 forelimbs could be successfully replanted and in vivo reperfused for 12 hours after 9 hours of room temperature ischemia followed by 24 hours ECP. Adequate limb perfusion was observed after replantation as shown by thermography and laser Doppler imaging. All pigs survived without severe organ failure, and no significant increase in inflammatory cytokines was found. Macroscopy and histology showed marked interstitial muscular edema of the limbs, whereas myofiber necrosis was not evident, implying the preservation of muscular integrity. Conclusions The use of a 24-hour ECP has successfully extended limb preservation to 33 hours. The modified histidine-tryptophan-ketoglutarate perfusate demonstrated its ability for muscle protection. This innovative approach not only facilitates limb replantation after combat injuries, surmounting geographical barriers, but also broadens the prospects for well-matched limb allotransplants across countries and continents. [ABSTRACT FROM AUTHOR]

Background and Purpose Methods Results Conclusions Ischemic strokes due to isolated posterior cerebral artery (PCA) occlusions represent 5% of all strokes but have significant impacts on patients’ quality of life, primarily due to visual deficits and thalamic involvement. Current guidelines for acute PCA occlusion management are sparse, and the prognostic value of perfusion imaging parameters remains underexplored.We conducted a retrospective analysis of 32 patients with isolated PCA occlusions treated at Johns Hopkins Medical Institutions between January 2017 and March 2023. Patients underwent pretreatment perfusion imaging, with perfusion parameters analyzed using RAPID software. The primary outcome was short‐term clinical outcome as measured by the National Institutes of Health Stroke Scale (NIHSS) at discharge.The median age of the cohort was 70 years, with 34% female and 66% male. Significant correlations were found between NIHSS at discharge and various perfusion parameters, including time‐to‐maximum (Tmax) >6 seconds (ρ = .55, p = .004), Tmax >8 seconds (ρ = .59, p = .002), Tmax >10 seconds (ρ = .6, p = .001), mismatch volume (ρ = .51, p = .008), and cerebral blood volume (CBV) < 34% (ρ = .59, p = .002).Tmax and CBV volumes significantly correlated with discharge NIHSS with marginal superiority of Tmax >10 seconds and CBV <42% volumes. These findings suggest that CT and MR perfusion imaging can play a crucial role in the acute management of PCA strokes, though larger, standardized studies are needed to validate these results and refine imaging thresholds specific to posterior circulation infarcts. [ABSTRACT FROM AUTHOR]

Background & Aims: To evaluate, if high frame rate (HiFR) contrast-enhanced ultrasound (CEUS) and external perfusion analysis (VueBox®)can give answers on liver tumour diagnostics. Methods: A multifrequency probe (C1-6 /Resona R9) and 1-2.4 ml ultrasound contrast medium were used for CEUS up to 5-6 min. Independent analysis of DICOM-CINE files was performed, correlated to follow-up, computed tomography, magnetic resonance imaging, or histopathology. Results: In 110 patients the difference between marginal peak enhancement (PE) of malignant and benign leasions was significant. In the peripheral area, the AUCs were lower in malignant lesions (144.8±139.3) than in benign lesions (123.6±119.8). The mean transit time (mTT) was shorter in malignant lesions in the center. In the liver parenchyma, however, the mTT was significantly longer in malignant lesions (141.6±107.9s) than in benign lesions (128.8±138.6 s). The rise time (RT) was significantly shorter central (66.5±30.9s) and peripheral (72.8±35.1s) in malignant lesions than in benign lesions (114.33±159.58s). The wash in rate (WiR) in benign lesions was 848.3±2,563.7 rU in the center. Wash-out rate (WoR) in the center, peripheral and in the liver parenchyma showed a significantly lower wash-out in the malignant lesions. Conclusions: HiFR CEUS with perfusion analysis enables the assessment of focal, diffuse and postinterventional liver changes. [ABSTRACT FROM AUTHOR]

Introduction: Three-dimensional fractional moving blood volume (3D-FMBV) may provide superior noninvasive measurement of feto-placental perfusion compared to current methods. This study investigated the feasibility and repeatability of producing 3D-FMBV measurements of the placenta, fetal liver, kidney, and brain in a single ultrasound consultation. Methods: The placenta, fetal liver, kidney, and brain were scanned in triplicate using 3D power Doppler ultrasound (3D-PDU) in 48 women ≥22 weeks of gestation with healthy fetuses. 3D-FMBV was calculated by two analyzers. Feasibility was assessed as the percentage of cases where 3D-FMBV could be evaluated; repeatability (intraobserver and interobserver) using two-way mixed measure intraclass correlation coefficients (ICCs). Results: 3D-FMBV was calculated for 100% of scanned organs. Intraobserver ICCs (95% CI) were good to excellent; 0.93 (0.88–0.96) and 0.87 (0.78–0.92) for placenta, 0.95 (0.92–0.97) and 0.98 (0.96–0.99) for fetal liver, 0.96 (0.94–0.98) and 0.91 (0.85–0.95) for fetal kidney, and 0.98 (0.97–0.99) and 0.97 (0.95–0.98) for fetal brain. Interobserver ICCs (95% CI) were 0.50 (0.08–0.73), 0.92 (0.85–0.96), 0.89 (0.78–0.94), and 0.71 (0.46–0.85) for placenta, fetal liver, kidney, and brain. Conclusion: Feto-placental perfusion assessment with 3D-FMBV is highly reliable in healthy pregnancies ≥22 weeks of gestation and can be feasibly calculated in four feto-placental vascular beds in a single ultrasound consultation. Plain Language Summary: Throughout pregnancy the placenta provides the fetus with nutrients and oxygen. If blood flow to the fetus is impaired (i.e., in placental disease), the fetus adapts by directing more blood to its brain and less to peripheral organs, called "brain-sparing." This has consequences including impaired growth, stillbirth, and chronic adulthood disease. Brain-sparing is currently detected by measuring how pulsatile blood flow is in the fetal brain and placental vessels. However, in many cases, brain-sparing is detected too late for interventions to be implemented, or not at all. Three-dimensional fractional moving blood volume (3D-FMBV) is a new noninvasive technique that may be able to earlier detect brain-sparing by measuring blood flow in whole fetal organs. If successful, this technique could be used to define normal blood flow ranges in different organs throughout pregnancy, allowing for early detection, intervention, and optimization of fetal outcomes. To do this, it must first be practical to take 3D-FMBV measurements in a single ultrasound consultation (and not be too time intensive) and produce reliable measurements between patients. Our study found that it is practical to measure blood flow in four organs; placenta, fetal liver, kidney, and brain, in a single ultrasound consult, taking a median 10 min and 12 s for scanning and 41 min and 59 s for offline analysis. We were able to calculate 3D-FMBV for all organs scanned. Following our proposed protocol for scanning and analysis, 3D-FMBV measurements can be reliably calculated to a good to excellent degree by the same observer and between observers. [ABSTRACT FROM AUTHOR]

Background: We tested whether gene polymorphisms for angiotensin-converting enzyme (ACE, rs1799752) and tenascin-C (TNC, rs2104772) are associated with variability in fatigue resistance and metabolic strain during static lumbar exercise through interactions with chronic nonspecific lower back pain and habitual physical exercise levels (PA). Methods: Forty-eight patients and matched controls performed an isometric endurance test for lumbar extensors. Metabolic strain to longissimus muscle (oxygen saturation, lactate) and cardiovascular system (muscle hemoglobin, blood pressure) and holding time were monitored. Subjects were genotyped for rs1799752 (II, ID, DD) and rs2104772 (AA, AT, TT). Associations of variance with group, genotype, and PA were analyzed under a 5% false discovery rate. Results: The holding time was lower in patients than in controls (150.9 vs. 188.6 s). This difference was associated with both genotypes, as patients with DD-rs1799752-genotype (p = 0.007) and TT-rs2104772-genotype (p = 0.041) showed lower fatigue resistance. Muscle deoxygenation during exercise varied in positive association with the rs2104772-genotype and PA (p = 0.010, η2 = 0.236). Mean arterial blood pressure (p = 0.028, η2 = 0.108) and recovery of hemoglobin concentration (p = 0.003, η2 = 0.907) demonstrated complex group x rs2104772 interactions. Conclusions: Polymorphisms rs1799752 and rs2104772 influence back pain-related variability in lumbar fatigue resistance. rs2104772 was linked to cardiovascular strain during isometric exercise and recovery via muscle perfusion. [ABSTRACT FROM AUTHOR]

OBJECTIVES Historically, the perfusion-guided sequence suggests to first transplant the side with lowest lung perfusion. This sequence is thought to limit right ventricular afterload and prevent acute heart failure after first pneumonectomy. As a paradigm shift, we adopted the right-first implantation sequence, irrespective of lung perfusion. The right donor lung generally accommodates a larger proportion of the cardiac output. We hypothesized that the right-first sequence reduces the likelihood of oedema formation in the firstly transplanted graft during second-lung implantation. Our objective was to compare the perfusion-guided and right-first sequence for intraoperative extracorporeal membrane oxygenation (ECMO) need and primary graft dysfunction (PGD). METHODS A retrospective single-centre cohort study (2008–2021) including double-lung transplant cases (N  = 696) started without ECMO was performed. Primary end-points were intraoperative ECMO cannulation and PGD grade 3 (PGD3) at 72 h. Secondary end-points were patient and chronic lung allograft dysfunction-free survival. In cases with native left lung perfusion ≤50% propensity score adjusted comparison of the perfusion-guided and right-first sequence was performed. RESULTS When left lung perfusion was ≤50%, right-first implantation was done in 219 and left-first in 189 cases. Intraoperative escalation to ECMO support was observed in 10.96% of right-first versus 19.05% of left-first cases (odds ratio 0.448; 95% confidence interval 0.229–0.0.878; P  = 0.0193). PGD3 at 72 h was observed in 8.02% of right-first versus 15.64% of left-first cases (0.566; 0.263–1.217; P  = 0.1452). Right-first implantation did not affect patient or chronic lung allograft dysfunction-free survival. CONCLUSIONS The right-first implantation sequence in off-pump double-lung transplantation reduces need for intraoperative ECMO cannulation with a trend towards less PGD grade 3. [ABSTRACT FROM AUTHOR]

Background: Predicting the viability of the skin flaps after mastectomy is of high importance and significance in immediate breast reconstruction. Numerous methods have been used and are readily available. This review aims to describe and compare the current preferred perfusion assessment tools. Methods: Four major scientific databases—Web of Science, PubMed, Embase, and Scopus—were consulted to retrieve reviews, meta-analyses, clinical trials, experimental studies, and case reports focused on skin flap perfusion assessment following mastectomy. English-language articles published within the last 10 years were included. The most recent search was conducted on 31 July 2024. Results: A summary focused on the relevant information of all included studies was drafted, and the results of the studies have been synthetized and compared. A total of 58 studies have been included in this review. Conclusion: Indocyanine green angiography (ICG-A) is the preferred and most-used method of evaluating perfusion, especially in high-risk patients, while new technologies show promising results and might be of great interest in the future. Perfusion assessment tools complement and should not replace clinical evaluation. [ABSTRACT FROM AUTHOR]

Background: Selective antegrade cerebral perfusion (SACP) is adopted as an alternative to deep hypothermic circulatory arrest (DHCA) during aortic arch surgery. However, there is still no preclinical evidence to support the use of SACP associated with moderate hypothermia (28–30°C) instead of DHCA (18–20°C). The present study aims to develop a reliable and reproducible preclinical model of cardiopulmonary bypass (CPB) with SACP applicable for assessing the best temperature management. Materials and methods: A central cannulation through the right jugular vein and the left carotid artery was performed, and CPB was instituted. Animals were randomized into two groups: normothermic circulatory arrest without or with cerebral perfusion (NCA vs SACP). EEG monitoring was maintained during CPB. After 10 min of circulatory arrest, rats underwent 60 min of reperfusion. After that, animals were sacrificed, and brains were collected for histology and molecular biology analysis. Results: Power spectral analysis of the EEG signal showed decreased activity in both cortical regions and lateral thalamus in all rats during the circulatory arrest. Only SACP determined complete recovery of brain activity and higher power spectral signal compared to NCA (p < 0.05). Histological damage scores and western blot analysis of inflammatory and apoptotic proteins like caspase-3 and Poly-ADP ribose polymerase (PARP) were significantly lower in SACP compared to NCA. Vascular endothelial growth factor (VEGF) and RNA binding protein 3 (RBM3) involved in cell-protection mechanisms were higher in SACP, showing better neuroprotection (p < 0.05). Conclusions: SACP by cannulation of the left carotid artery guarantees good perfusion of the whole brain in this rat model of CPB with circulatory arrest. The present model of SACP is reliable, repeatable, and not expensive, and it could be used in the future to achieve preclinical evidence for the best temperature management and to define the best cerebral protection strategy during circulatory arrest. [ABSTRACT FROM AUTHOR]

Introduction: Adult and pediatric ECMO procedures have been increasingly established as conventional life-saving modalities in critical care services across the world. Since 2017, a multidisciplinary team of program advisors for our perfusion education program have aimed to increase cardiovascular perfusion (CVP) student ECMO exposure and improve clinical decision-making. In this QI intervention, the use of 3D computer-based simulation was assessed in establishing a standardized process to improve the diagnosis and treatment of adult ECMO complications among first year CVP students. Methods: The Califia 3D Patient Simulator was incorporated into the curriculum for first year CVP students (n = 26) along with traditional lecture for the adult ECMO complication laboratory session. Pre-class knowledge assessments using de-identified polling software were compared to post-class assessments following the first assigned learning activity. Assessments from students that received simulation before lecture (SIM, n = 15) were compared to students receiving lecture before simulation (LEC, n = 11). User experience questionnaires (UEQ) consisting of 26 questions for six scales of simulation instruction were administered to measure the comprehensive impression of the student experience. Results: Overall median [IQR] pre- and -post knowledge assessment scores were 74% [11] and 84% [11], respectively (p = 0.01). There were no significant differences in pre-class assessment scores between the SIM and LEC groups (74.0% and 74.0%, respectively, p = 0.959). The LEC group achieved higher median post-assessment scores than the SIM group (84% vs 79%, p = 0.032). Among the 26 UEQ survey scales, 23 were positively evaluated (>0.8), and three were a neutral evaluation (−0.8 to 0.8). Cronbach Alpha-Coefficients of >0.78 were measured for attractiveness, perspicuity, efficacy, and stimulation. The coefficient for dependability was 0.37. 25 (96.2%) students indicated that 3D simulation was beneficial to improving ECMO clinical decision-making. Conclusions: In this QI intervention, the implementation of computer-based 3D simulation following lecture was perceived by learners to help improve the diagnosis and treatment of ECMO-related complications. [ABSTRACT FROM AUTHOR]

Objectives: Acknowledging lacking of consensus exist in total aortic arch (TAA) surgery for acute type A aortic dissection (AAD), this study aimed to investigate the neurologic injury rate between bilateral and unilateral cerebrum perfusion on the specific population. Methods: A total of 595 AAD patients other than Marfan syndrome receiving TAA surgery since March 2013 to March 2022 were included. Among them, 276 received unilateral cerebral perfusion (via right axillary artery, RCP) and 319 for bilateral cerebral perfusion (BCP). The primary outcome was neurologic injury rate. Secondary outcomes were 30-day mortality, serum inflammation response (high sensitivity C reaction protein, hs-CRP; Interleukin-6, IL-6; cold-inducible RNA binding protein, CIRBP) and neuroprotection (RNA-binding motif 3, RBM3) indexes. Results: The BCP group reported a significantly lower permanent neurologic deficits [odds ratio: 0.481, Confidence interval (CI): 0.296–0.782, p = 0.003] and 30-day mortality (odds ratio: 0.353, CI: 0.194–0.640, p < 0.001) than those received RCP treatment. There were also lower inflammation cytokines (hr-CRP: 114 ± 17 vs. 101 ± 16 mg/L; IL-6: 130 [103,170] vs. 81 [69,99] pg/ml; CIRBP: 1076 [889, 1296] vs. 854 [774, 991] pg/ml, all p < 0.001), but a higher neuroprotective cytokine (RBM3: 4381 ± 1362 vs 2445 ± 1008 pg/mL, p < 0.001) at 24 h after procedure in BCP group. Meanwhile, BCP resulted in a significantly lower Acute Physiology, Age and Chronic Health Evaluation (APACHE) Ⅱscore (18 ± 6 vs 17 ± 6, p < 0.001) and short stay in intensive care unit (4 [3,5] vs. 3 [2,3] days, p < 0.001) and hospital (16 ± 4 vs 14 ± 3 days, p < 0.001). Conclusions: This present study indicated that BCP compared with RCP was associated with lower permanent neurologic deficits and 30-day mortality in AAD patients other than Marfan syndrome receiving TAA surgery. [ABSTRACT FROM AUTHOR]

In progressive supranuclear palsy (PSP), subcortical tau and cortical perfusion can be assessed using the tracer [18F]PI-2620. We investigated if subcortical tau (globus pallidus internus, dentate nucleus) and frontal/limbic perfusion correlate in a cohort of 32 PSP patients. Tau in subcortical regions showed significant negative correlation with perfusion in limbic cortex. Perfusion in frontal regions was negatively associated with tau in both subcortical regions, but the significance threshold was only passed for the dentate nucleus. A reason could be a diaschisis-like phenomenon; that is, subcortical tau could lead to reduced connectivity to frontal regions and, thereby, to decreased perfusion. Plain Language Summary: In a study of 32 patients with progressive supranuclear palsy (PSP), we used a molecular imaging tracer called [18F]PI-2620 to measure two things: the presence of a protein called tau in deep brain areas (specifically, the globus pallidus internus and dentate nucleus) and the function of the brain's cortex by assessing blood flow (perfusion). We found that higher amounts of tau in these deep brain areas were associated with reduced blood flow in the limbic cortex, which is involved in emotion regulation. Also, the frontal areas of the brain showed reduced blood flow related to tau in these deep brain regions. However, this connection was statistically significant only for the dentate nucleus. This study suggests that the buildup of tau protein in deeper brain areas can disrupt function in parts of the brain's cortex, highlighting the damaging role of tau in PSP. [ABSTRACT FROM AUTHOR]

A limited understanding of tendon cell biology in healthy and pathological conditions has impeded the development of effective treatments, necessitating in vitro biomimetic models for studying tendon events. We established a dynamic culture using fibrin scaffolds, bioengineered with tendon stem/progenitor cells (hTSPCs) from healthy or diseased human biopsies and perfused with 20 ng/mL of human transforming growth factor-β1 for 21 days. Both cell types showed long-term viability and upregulated Scleraxis (SCX-A) and Tenomodulin (TNMD) gene expressions, indicating tenogenic activity. However, diseased hTSPCs underexpressed collagen type I and III (COL1A1 and COL3A1) genes and exhibited lower SCX-A and TNMD protein levels, but increased type I collagen production, with a type I/type III collagen ratio > 1.5 by day 14, matching healthy cells. Diseased hTSPCs also showed constant high levels of pro-inflammatory cytokines, such as IL-8 and IL-6. This biomimetic environment is a valuable tool for studying tenogenic and inflammatory events in healthy and diseased tendon cells and identifying new therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: The possibility of keeping liver grafts viable and functioning until transplantation has been explored since the 1950s. However, the current modalities of Normothermic Machine Perfusion (NMP) have shown several limitations, such as the inability to correct electrolytes and pH derangements efficiently. Combining NMP with continuous kidney replacement therapy (CKRT) might provide a promising new model to overcome these issues. Methods: An NMP that covers the organ perfusion, oxygenation, carbon dioxide removal, and thermal balance was connected to a CKRT circuit to ensure physiological hydro-electrolytes, acid–base balance, and catabolite removal from the perfusate. Results: The integration of NMP and CKRT maintains a neoplastic liver in a perfusion system with physiological perfusate for 100 h. CKRT re-established and maintained the hydro-electrolyte and acid–base status throughout the 100 h of perfusion. Significant limitations were the need for frequent monitoring of electrolytes and acid–base disorders and the loss of low molecular weight nutrients, which have to be replenished by manual infusion into the system. Conclusions: This novel CKRT-NMP integrated system may represent a practical and versatile model to support organs' perfusion and extend preservation times. Further experiments are needed to fix monitoring and adjusting processes. [ABSTRACT FROM AUTHOR]

Aging is associated with inspiratory muscle dysfunction; however, the impact of aging on diaphragm blood flow (BF) regulation, and whether sex differences exist, is unknown. We tested the hypotheses in young animals that diaphragm BF and vascular conductance (VC) would be greater in females and that aging would decrease the diaphragm's ability to increase BF with contractions. Young (4–6 mo) and old (22–24 mo) Fischer 344 rats were divided into four groups: young female (YF, n = 7), young male (YM, n = 8), old female (OF, n = 9), and old male (OM, n = 9). Diaphragm BF (mL/min/100 g) and VC (mL/mmHg/min/100 g) were determined, via fluorescent microspheres, at rest and during 1 Hz contractions. In YF versus OF, aging blunted the increase in medial costal diaphragm BF (44 ± 5% vs. 16 ± 12%; P < 0.05) and VC (43 ± 7% vs. 21 ± 12%; P < 0.05). Similarly, in YM versus OM, aging blunted the increase in medial costal diaphragm BF (43 ± 6% vs. 24 ± 12%; P < 0.05) and VC (50 ± 6% vs. 34 ± 10%; P < 0.05). In female rats, age increased dorsal costal diaphragm BF, whereas in male rats, age increased crural diaphragm BF (P < 0.05). Compared with age-matched females, dorsal costal diaphragm BF was lower in YM and OM (P < 0.05). In conclusion, aging results in an inability to augment medial costal diaphragm BF and alters regional diaphragm BF distribution in response to muscular contractions. Furthermore, sex differences in regional diaphragm BF are present in young and old animals. NEW & NOTEWORTHY: This is the first study, to our knowledge, to demonstrate that old age impairs the hyperemic response and alters blood flow distribution in the diaphragm of both female and male rats. In addition, this investigation provides novel evidence of sex differences in regional diaphragm blood flow distribution with contractions. The data presented herein suggest that aging compromises diaphragm vascular function and provides a potential mechanism for the diaphragm contractile dysfunction associated with old age. [ABSTRACT FROM AUTHOR]

Ultrasound imaging is inexpensive, portable, and widely available. The development of a real-time transcutaneous spinal cord perfusion monitoring system would allow more precise targeting of mean arterial pressure goals following acute spinal cord injury (SCI). There has been no prior demonstration of successful real-time cord perfusion monitoring in humans. Four adult patients who had undergone posterior cervical decompression and instrumentation at a single center were enrolled into this prospective feasibility study. All participants had undergone cervical laminectomies spanning ≥2 contiguous levels ≥2 months prior to inclusion with no history of SCI. The first 2 underwent transcutaneous ultrasound without contrast and the second 2 underwent contrast-enhanced ultrasound (CEUS) with intravenously injected microbubble contrast. Using noncontrast ultrasound with or without Doppler (n = 2), the dura, spinal cord, and vertebral bodies were apparent however ultrasonography was insufficient to discern intramedullary perfusion or clear white-gray matter differentiation. With application of microbubble contrast (n = 2), it was possible to quantify differential spinal cord perfusion within and between cross-sectional regions of the cord. Further, it was possible to quantify spinal cord hemodynamic perfusion using CEUS by measuring peak signal intensity and the time to peak signal intensity after microbubble contrast injection. Time-intensity curves were generated and area under the curves were calculated as a marker of tissue perfusion. CEUS is a viable platform for monitoring real-time cord perfusion in patients who have undergone prior cervical laminectomies. Further development has the potential to change clinical management acute SCI by tailoring treatments to measured tissue perfusion parameters. [ABSTRACT FROM AUTHOR]

Background: Normothermic machine perfusion (NMP) allows for the assessment and resuscitation of ex‐vivo human livers prior to transplantation. Commercially available NMP systems are closed circuits that accumulate metabolic waste and cytokines over time, potentially limiting organ preservation times. Dialysis has been proposed as a method to remove waste and excess fluid from such systems. This study aimed to demonstrate the utility of integrating dialysis into a commercially available system by quantifying solute removal. Methods: A dialysis filter was attached in parallel to a commercially available liver perfusion system. Three livers declined for transplantation were split before undergoing long‐term NMP with blood using the modified system. During perfusion, dialysate flow rates were set in the range of 100–600 mL/h for short periods of time. At each flow rate, perfusate and spent dialysate samples were collected and analyzed for solute clearance. Results: The addition of dialysis to a commercial NMP system removed water‐soluble waste and helped regulate electrolyte concentrations. Interleukin‐6 was successfully removed from the perfusate. Solute clearance was proportional to dialysate flow rate. A guide for our perfusion setup was created for the appropriate selection of dialysis flow rates and duration based on real‐time perfusate composition. Conclusions: Dialysis circuits can efficiently remove waste and regulate perfusate composition, and can be easily incorporated to improve the performance of commercially available systems. Quantification of the effect of dialysis on perfusate composition enables refined dialysis control to optimize electrolyte profiles and avoid the over‐ or under‐correction of key solutes. [ABSTRACT FROM AUTHOR]

Background: The global incidence of liver diseases is rising, yet there remains a dearth of precise research models to mimic these diseases. The use of normothermic machine perfusion (NMP) to study diseased livers recovered from liver transplantation (LT) recipients presents a promising avenue. Accordingly, we have developed a machine perfusion system tailored specifically for the human whole diseased livers and present our experience from the NMP of diseased livers. Methods: Six diseased livers recovered from LT recipients with different diagnoses were collected. The diseased livers were connected to the machine perfusion system that circulated tailored perfusate, providing oxygen and nutrients. The pressure and flow of the system were recorded, and blood gas analysis and laboratory tests of perfusate and bile were examined to analyze the function of the diseased livers. Liver tissues before and after NMP were collected for histological analysis. Results: Experiments showed that the system maintained the diseased livers in a physiological state, ensuring stable hemodynamics and a suitable partial pressure of oxygen and carbon dioxide. The results of blood gas analysis and laboratory tests demonstrated a restoration and sustenance of metabolism with minimal damage. Notably, a majority of the diseased livers exhibited bile production continuously, signifying their vivid functional integrity. The pathological characteristics remained stable before and after NMP. Conclusion: We successfully established the machine perfusion system tailored specifically for diseased human whole livers. Through the application of this system, we have developed a novel in vitro model that faithfully recapitulates the main features of human liver disease. This model holds immense promise as an advanced disease modeling platform, offering profound insights into liver diseases and potential implications for research and therapeutic development. [ABSTRACT FROM AUTHOR]

Background: The role of intraoperative near-infrared fluorescence angiography with indocyanine green in reducing anastomotic leakage (AL) has been demonstrated in colorectal surgery, however, its perfusion assessment mode, and efficacy in reducing anastomotic leakage after laparoscopic intersphincteric resection (LsISR) need to be further elucidated. Aim: Aim was to study near-infrared fluorescent angiography to help identify bowel ischemia to reduce AL after LsISR. Material and methods: A retrospective case-matched study was conducted in one referral center. A total of 556 consecutive patients with ultra-low rectal cancer including 140 patients with fluorescence angiography of epiploic appendages (FAEA)were enrolled. Perfusion assessment by FAEA in the monochrome fluorescence mode. Patients were divided into two groups based on perfusion assessment by FAEA. The primary endpoint was the AL rate within 6 months, and the secondary endpoint was the structural sequelae of anastomotic leakage (SSAL). Results: After matching, the study group (n = 109) and control group (n = 190) were well-balanced. The AL rate in the FAEA group was lower before (3.6% vs. 10.1%, P = 0.026) and after matching (3.7% vs. 10.5%, P = 0.036). Propensity scores matching analysis (OR 0.275, 95% CI 0.035–0.937, P 0.039), inverse probability of treatment weighting (OR 0.814, 95% CI 0.765–0.921, P 0.002), and regression analysis (OR 0.298, 95% CI 0.112–0.790, P = 0.015), showed that FAEA was an independent protector factor for AL. This technique can significantly shorten postoperative hospital stay [9 (6–13) vs. 10 (8–13), P = 0.024] and reduce the risk of SSAL (1.4% vs. 6.0%, P = 0.029). Conclusions: Perfusion assessment by FAEA can achieve better visualization in LsISR and reduce the incidence of AL, subsequently avoiding SSAL after LsISR. [ABSTRACT FROM AUTHOR]

Background: Anastomotic leakage (AL) is a dreaded complication following colorectal cancer surgery, impacting patient outcome and leads to increasing healthcare consumption as well as economic burden. Bowel perfusion is a significant modifiable factor for anastomotic healing and thus crucial for reducing AL. Aims: The study aimed to calculate a cut-off value for quantified laser speckle perfusion units (LSPUs) in order to differentiate between ischemic and well-perfused tissue and to assess inter-observer reliability. Methods: LSCI was performed using a porcine ischemic small bowel loop model with the PerfusiX-Imaging® system. An ischemic area, a well-perfused area, and watershed areas, were selected based on the LSCI colormap. Subsequently, local capillary lactate (LCL) levels were measured. A logarithmic curve estimation tested the correlation between LSPU and LCL levels. A cut-off value for LSPU and lactate was calculated, based on anatomically ischemic and well-perfused tissue. Inter-observer variability analysis was performed with 10 observers. Results: Directly after ligation of the mesenteric arteries, differences in LSPU values between ischemic and well-perfused tissue were significant (p < 0.001) and increased significantly throughout all following measurements. LCL levels were significantly different (p < 0.001) at both 60 and 120 min. Logarithmic curve estimation showed an R2 value of 0.56 between LSPU and LCL values. A LSPU cut-off value was determined at 69, with a sensitivity of 0.94 and specificity of 0.87. A LCL cut-off value of 3.8 mmol/L was found, with a sensitivity and specificity of 0.97 and 1.0, respectively. There was no difference in assessment between experienced and unexperienced observers. Cohen's Kappa values were moderate to good (0.52–0.66). Conclusion: Real-time quantification of LSPUs may be a feasible intraoperative method to assess tissue perfusion and a cut-off value could be determined with high sensitivity and specificity. Inter-observer variability was moderate to good, irrespective of prior experience with the technique. [ABSTRACT FROM AUTHOR]

Lipomatous soft tissue tumors (STT), ranging from benign lipomas to malignant liposarcomas, require accurate differentiation for timely treatment. Complementary to MRI, Contrast-enhanced ultrasound (CEUS) is emerging as a promising tool, providing insight into tumor microperfusion in real-time. This study aims to explore the potential of preoperative CEUS in differentiating benign lipomatous tumors from malignant liposarcoma subtypes. Eighty-seven patients with lipomatous STT scheduled for surgery were enrolled. Clinical and MRI assessments were conducted to obtain general tumor characteristics. CEUS was used for a standardized tumor perfusion evaluation. Perfusion analysis included peak enhancement, rise time, wash-in perfusion index, and wash-out rate, reflecting the perfusion kinetics. Histopathological results were obtained for every STT and compared to perfusion characteristics. In total, 48 lipoma, 23 ALT and 11 liposarcoma were identified. Significant differences in tumor microperfusion were demonstrated, with higher perfusion levels indicating higher malignancy (Peak enhancement [a.u.] of Lipoma: 145 ± 238; ALT: 268 ± 368; Liposarcoma: 3256 ± 4333; p (ALT vs. Liposarcoma) < 0.001). A perfusion-based identification of a benign lipoma or ALT versus sarcoma resulted in a positive predictive value of 93%. Patient-related factors (age, gender, BMI, ASA score, smoking status) had no significant impact on the CEUS-based perfusion parameters. Our study suggests CEUS as a capable non-invasive tool for improving preoperative assessment of lipomatous STT. It can assist in the distinction between benign and malignant STT, accelerating treatment decisions and enhancing patient outcomes. Significant correlations between CEUS-derived parameters and malignancy highlight its risk assessment potential. [ABSTRACT FROM AUTHOR]

Background Regarding the less-known effects of beta-blocker consumption on the diagnostic value of the myocardial perfusion scan with dipyridamole stress in coronary artery disease (CAD), we aimed to compare the findings of the scans done on the beta-blocker consumption course and after discontinuation of this medications. Materials and Methods Thirty patients with probably CAD and abnormal myocardial perfusion scans (presence of reversible defect), who had been treated with beta-blockers for at least 3 months, were studied. Dipyridamole stress phase of myocardial perfusion single-photon emission computed tomography (SPECT) was performed two times with an interval of about 1 week, once after discontinuation of all antianginal and anti-ischemic medications, statins, and beta-blockers for 72 hours prior to the study, and again after discontinuation of all these medications except for beta-blockers. Imaging was done with the same protocol, radiopharmaceutical dose, and imaging parameters. Summed stress score (SSS), summed stress rest, and summed difference scores (SDS), total perfusion deficit (TPD), severity, and extension of myocardial perfusion defects in three coronary artery territories were analyzed, using quantitative perfusion SPECT software. Results Most variables such as SSS, SDS, TPD, severity, and extension of defects showed a significant difference between the two conditions including beta-blocker consumption and after discontinuing beta-blocker consumption before stress imaging (p < 0.05). Moreover, in patients on treatment with metoprolol, all studied factors including SSS, SDS, TPD, severity, and extension of perfusion defects were significantly reduced when patients consumed beta-blockers before SPECT evaluation (p < 0.05). Conclusion Beta-blocker consumption can lead to a decrease in the severity and extent of myocardial perfusion defects and therefore probably a decrease in the sensitivity of myocardial scans. Discontinuation of beta-blocker prior to the dipyridamole myocardial perfusion scan can improve diagnostic accuracy. [ABSTRACT FROM AUTHOR]

In free flap reconstruction, improving flap tolerance to warm ischemia (WI) is fundamental. WI is the result of a venous or arterial thrombosis, which can only be addressed through surgical revision. No additional treatments have shown superior efficacy at salvaging free flaps after or during WI. Custom perfusion machines (PM), used to reduce the intensity of lesions of the flap stored in cold ischemia, have not been evaluated for WI flap salvage. This proof-of-concept study assessed whether the Lifeport® perfusion machine could improve the salvage procedure's success rates after one hour of venous WI. Five different groups were evaluated with four porcine latissimus dorsi free flaps included in each group. Depending on the group, the flaps were subjected to one hour of WI followed by revascularization, static hypothermic submersion, or dynamic Lifeport® perfusion. Additionally, two flap perfusion liquids were evaluated: KPS-1® and IGL-1®. Biopsies were performed before in vivo warm ischemia of the flap, after in vivo warm ischemia of the flap, and after one and two hours of preservation. Interstitial edema, muscular cell size and muscular diffuse necrosis were quantified by histological assessment. Static submersion did not demonstrate any efficacy for venous flap salvage. Dynamic perfusion on Lifeport® machine showed a significant improvement in tissue parameters. Thrombi and fibrine, present during the WI period, were no longer visible inside vessels and the perfusion machine flow evacuated the inflammatory cells and their substrates from the flap. The flap weights did not increase during perfusion time, confirming the benefits of the Lifeport® perfusion machine. Evaluating Lifeport® advantages on human free flap salvage is necessary to confirm the benefits for the tissue and to increase post-operative results after congestive free flap revision surgery. [ABSTRACT FROM AUTHOR]

The extent of perfusion of a deep inferior epigastric artery perforator (DIEP) flap is a primary concern for surgeons. This study aimed to determine whether the flap area or volume can be estimated using perforator and flap characteristics. Intraoperative flap perfusion was assessed using indocyanine green angiography in patients who underwent DIEP flap breast reconstruction between November 2018 and February 2023. The area perfused by a single dominant perforator was delineated on the surface of the flap and measured using the ImageJ software. Multiple linear regression analysis was conducted to estimate the 'perfusion ratio,' defined as the perfused area divided by the total flap area. Potential predictor variables included flap size (cm2), flap thickness (mm), perforator diameter (mm), perforator rows (medial/lateral), vertical location of perforator (at or above/below the umbilicus), and perforator eccentricity (vertical distance from upper flap margin to perforator, cm). In total, 101 patients were included in this analysis. The mean 'perfusion ratio' was 67.8% ± 11.5%, predicted by perforator diameter (p = 0.022) and vertical location below umbilicus (p < 0.001) with positive correlations and negatively correlated with flap thickness (p = 0.003) in the multivariable analysis. Both perfusion area and weight were predicted by perforator diameter, vertical location of perforator, flap size, and flap thickness (p < 0.001). The coefficient of determination (adjusted R2) for prediction of perfusion weight was higher than that for the perfusion area (75.5% vs. 69.4%). Flap volume, rather than area, is determined by a perforator of a given diameter and location. [ABSTRACT FROM AUTHOR]