-
European Radiology Experimental Jul 2023Critical limb ischemia is associated with high mortality and major amputations. Intra-arterial digital subtraction angiography (IADSA) has been the reference standard...
Critical limb ischemia is associated with high mortality and major amputations. Intra-arterial digital subtraction angiography (IADSA) has been the reference standard but has some shortcomings including the two-dimensional projection and the lack of tissue perfusion information. The aim of this exploratory study is to examine four-dimensional computed tomography (4DCT) angiography and perfusion imaging using low-volume intra-arterial contrast injections for an improved anatomic and hemodynamic assessment in patients with foot ulcers. Three patients underwent a low-volume (2 mL) intra-arterial contrast-enhanced 4DCT examination combined with a diagnostic IADSA. An automated assessment of blood flow and tissue perfusion from the 4DCT data was performed. Vascular structures and corresponding blood flows were successfully assessed and correlated well with the IADSA results. Perfusion values of the affected tissue were significantly higher compared to the unaffected tissue. The proposed 4DCT protocol combined with the minimal usage of contrast agent (2 mL) provides superior images compared to IADSA as three phases (arterial, perfusion, and venous) are captured. The obtained parameters could allow for an improved diagnosis of critical limb ischemia as both the proximal vasculature and the extent of the perfusion deficit in the microvasculature can be assessed.Relevance statementIntra-arterial 4DCT allows for assessing three phases (arterial, perfusion and venous) using minimal contrast (2 mL). This method could lead to an improved diagnosis of critical limb ischemia as both proximal vasculature and the extent of the perfusion deficit are assessed.Trial registrationISRCTN, ISRCTN95737449. Registered 14 March 2023-retrospectively registered, https://www.isrctn.com/ISRCTN95737449 Key points• Three phases (arterial, perfusion, and venous) are obtained from 2 mL intra-arterial 4DCT.• The obtained hemodynamic parameters correlated well with the IADSA findings.• 4DCT surpassed IADSA in terms of assessment of venous blood flow and inflammatory hyperperfusion.• The assessment of tissue perfusion could lead to optimizing the revascularization strategy.
Topics: Humans; Diabetic Foot; Four-Dimensional Computed Tomography; Chronic Limb-Threatening Ischemia; Hemodynamics; Perfusion; Diabetes Mellitus
PubMed: 37491549
DOI: 10.1186/s41747-023-00352-x -
Cells Oct 2023Despite the high prevalence of acute kidney injury (AKI), the therapeutic approaches for AKI are disappointing. This deficiency stems from the poor understanding of the...
Despite the high prevalence of acute kidney injury (AKI), the therapeutic approaches for AKI are disappointing. This deficiency stems from the poor understanding of the pathogenesis of AKI. Recent studies demonstrate that αMUPA, alpha murine urokinase-type plasminogen activator (uPA) transgenic mice, display a cardioprotective pathway following myocardial ischemia. We hypothesize that these mice also possess protective renal pathways. Male and female αMUPA mice and their wild type were subjected to 30 min of bilateral ischemic AKI. Blood samples and kidneys were harvested 48 h following AKI for biomarkers of kidney function, renal injury, inflammatory response, and intracellular pathways sensing or responding to AKI. αMUPA mice, especially females, exhibited attenuated renal damage in response to AKI, as was evident from lower SCr and BUN, normal renal histology, and attenuated expression of NGAL and KIM-1. Notably, αMUPA females did not show a significant change in renal inflammatory and fibrotic markers following AKI as compared with wild-type (WT) mice and αMUPA males. Moreover, αMUPA female mice exhibited the lowest levels of renal apoptotic and autophagy markers during normal conditions and following AKI. αMUPA mice, especially the females, showed remarkable expression of PGC1α and eNOS following AKI. Furthermore, MUPA mice showed a significant elevation in renal leptin expression before and following AKI. Pretreatment of αMUPA with leptin-neutralizing antibodies prior to AKI abolished their resistance to AKI. Collectively, the kidneys of αMUPA mice, especially those of females, are less susceptible to ischemic I/R injury compared to WT mice, and this is due to nephroprotective actions mediated by the upregulation of leptin, eNOS, ACE2, and PGC1α along with impaired inflammatory, fibrotic, and autophagy processes.
Topics: Mice; Male; Female; Animals; Mice, Transgenic; Leptin; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Kidney; Acute Kidney Injury; Reperfusion Injury; Ischemia; Reperfusion
PubMed: 37887341
DOI: 10.3390/cells12202497 -
BMC Neurology Oct 2023Magnetic resonance imaging (MRI) and CT perfusion may provide diagnostic information for intravenous tissue-type plasminogen activator (IV t-PA) administration in acute... (Observational Study)
Observational Study
OBJECTIVE
Magnetic resonance imaging (MRI) and CT perfusion may provide diagnostic information for intravenous tissue-type plasminogen activator (IV t-PA) administration in acute ischemic stroke (AIS) patients. We aimed to compare the clinical features and perfusion deficits of diffusion weighted imaging (DWI)-negative and DWI-positive AIS patients.
METHODS
This retrospective and observational study included thrombolysis-treated AIS patients undergoing multimodel CT imaging before treatment and DWI after treatment between 2021 and 2022. Two experienced neuroradiologists blindly and independently examined the images to identify perfusion deficits in AIS patients. The patients were divided into DWI-positive and DWI-negative groups based on visible hyperintense lesions on DWI. A modified Rankin scale (mRS) score of ≤ 2 indicated good functional outcomes at discharge. Sensitivity analysis was conducted to determine whether CT perfusion was an independent predictor of positive DWI imaging on follow-up.
RESULTS
This study included 151 patients, of whom 35 (23.2%) patients were DWI-negative on follow-up. These DWI-negative patients were less likely to have a medical history of atrial fibrillation; they had lower triglyceride levels, a shorter admission time, lower National Institutes of Health Stroke Scale (NIHSS) scores after IV t-PA and lower mRS scores at discharge, and had better functional outcomes. A total of 37.1% of DWI-positive and 25.7% of DWI-negative patients had vascular stenosis (P = 0.215). A total of 47.4% of DWI-positive and 37.1% of DWI-negative patients had CT perfusion deficits (P = 0.284). A total of 73.5% of patients with normal CT perfusion had positive DWI, while 19.1% of patients with perfusion deficits had negative DWI. The sensitivity and specificity of NCCT were 14.8% and 97.1% (Kappa = 0.061, P = 0.074), CTP was 47.4% and 62.9% for predicting DWI lesion (Kappa = 0.069, P = 0.284).
CONCLUSIONS
About 23.2% of AIS patients who received intravenous thrombolysis treatment did not have a relevant DWI-MRI lesion on follow-up. Over one-third of patients in the DWI-MRI negative group showed CT perfusion deficits, with a sensitivity of 47.4% for predicting DWI lesions in non-mechanical thrombectomy patients.
Topics: Humans; Stroke; Ischemic Stroke; Brain Ischemia; Retrospective Studies; Treatment Outcome; Tissue Plasminogen Activator; Diffusion Magnetic Resonance Imaging; Thrombolytic Therapy; Perfusion; Fibrinolytic Agents
PubMed: 37865726
DOI: 10.1186/s12883-023-03427-9 -
Frontiers in Bioscience (Landmark... Aug 2023Cerebral ischemia-reperfusion injury (CIR) following a stroke results in secondary damage and is a leading cause of adult disability. The present study aimed to identify...
BACKGROUND
Cerebral ischemia-reperfusion injury (CIR) following a stroke results in secondary damage and is a leading cause of adult disability. The present study aimed to identify hub genes and networks in CIR to explore potential therapeutic agents for its treatment.
METHODS
Differentially expressed genes based on the GSE23163 dataset were identified, and weighted gene co-expression network analysis was performed to explore co-expression modules associated with CIR. Hub genes were identified by intersecting immune gene profiles, differentially expressed genes, and modular genes. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and transcription factor-microRNA-gene regulatory network analyses were then conducted in selected crucial modules. Subsequently, their expression levels in animal models were verified using real-time quantitative polymerase chain reaction and Western blotting. Finally, potential drug molecules were screened for, and molecular docking simulations were performed to identify potential therapeutic targets.
RESULTS
Seven hub genes-namely, , , , , , , and -were identified. Furthermore, we established a protein interaction network using the STRING database and found that the core genes selected through the cytohubba plugin remained consistent. Animal experiments showed that at the transcriptional level, all seven genes showed significant differences ( < 0.001, fold change vs sham, 5-200). At the translational level, however, only , , , , and showed significant differences, while and did not. Nifedipine, with the highest predicted score, was identified as a therapeutic agent and successfully docked with the protein encoded by the hub genes.
CONCLUSIONS
The expression of , , , , and was significantly different in CIR tissues compared to normal tissues both at the transcriptional and translational levels. Systems biology approaches indicated that these could be possible CIR marker genes, providing a stepping stone for further experimental studies.
Topics: Animals; Molecular Docking Simulation; Reperfusion; Reperfusion Injury; Computational Biology; Biomarkers; Brain Ischemia
PubMed: 37664920
DOI: 10.31083/j.fbl2808179 -
Brazilian Journal of Cardiovascular... Oct 2023
Topics: Humans; Perfusion; Surveys and Questionnaires; Delivery of Health Care
PubMed: 37797244
DOI: 10.21470/1678-9741-2022-0474 -
Biologicals : Journal of the... Nov 2023In the current transition to intensified upstream processing, the risks of adopting traditional single-use systems for high-titer, long-duration perfusion cultures, have...
In the current transition to intensified upstream processing, the risks of adopting traditional single-use systems for high-titer, long-duration perfusion cultures, have thus far not been considered. This case study uses the Failure Modes and Effects Analysis (FMEA) method to evaluate the risks associated with implementing upstream single-use technology. The simulated model process was used to compare the risk level of single-use technology for a traditional fed-batch cell culture with that for perfusion culture, under the same annual protein production conditions. To provide a reasonable source of potential risk for FMEA, all single-use upstream operations for both fed-batch and perfusion processes were investigated using an analytical method developed to quantify the impact of process parameters and operating conditions on single-use system specifications and to ensure objectivity. Many of the risks and their levels, were similar in long-duration perfusion cultures and fed-batch cultures. However, differences were observed for high-risk components such as daily sampling and installation. The result of this analysis indicates that the reasons for risk are different for fed-batch cultures and perfusion cultures such as larger bioreactors in fed-batch and longer runs in perfusion, respectively. This risk assessment method could identify additional control measures and be part of a holistic contamination control strategy and help visualize their effectiveness.
Topics: Animals; Cricetinae; Biological Products; Bioreactors; Batch Cell Culture Techniques; Antibodies, Monoclonal; Perfusion; Cricetulus
PubMed: 37793309
DOI: 10.1016/j.biologicals.2023.101713 -
Tomography (Ann Arbor, Mich.) Nov 2023The number of scholarly articles continues to rise. The continuous increase in scientific output poses a challenge for researchers, who must devote considerable time to... (Review)
Review
The number of scholarly articles continues to rise. The continuous increase in scientific output poses a challenge for researchers, who must devote considerable time to collecting and analyzing these results. The topic modeling approach emerges as a novel response to this need. Considering the swift advancements in computed tomography perfusion (CTP), we deem it essential to launch an initiative focused on topic modeling. We conducted a comprehensive search of the Scopus database from 1 January 2000 to 16 August 2023, to identify relevant articles about CTP. Using the BERTopic model, we derived a group of topics along with their respective representative articles. For the 2020s, linear regression models were used to identify and interpret trending topics. From the most to the least prevalent, the topics that were identified include "Tumor Vascularity", "Stroke Assessment", "Myocardial Perfusion", "Intracerebral Hemorrhage", "Imaging Optimization", "Reperfusion Therapy", "Postprocessing", "Carotid Artery Disease", "Seizures", "Hemorrhagic Transformation", "Artificial Intelligence", and "Moyamoya Disease". The model provided insights into the trends of the current decade, highlighting "Postprocessing" and "Artificial Intelligence" as the most trending topics.
Topics: Humans; Tomography, X-Ray Computed; Stroke; Magnetic Resonance Imaging; Perfusion
PubMed: 37987344
DOI: 10.3390/tomography9060158 -
Proceedings of the National Academy of... Mar 2024We present a comprehensive study on the non-invasive measurement of hippocampal perfusion. Using high-resolution 7 tesla arterial spin labeling (ASL) data, we generated...
We present a comprehensive study on the non-invasive measurement of hippocampal perfusion. Using high-resolution 7 tesla arterial spin labeling (ASL) data, we generated robust perfusion maps and observed significant variations in perfusion among hippocampal subfields, with CA1 exhibiting the lowest perfusion levels. Notably, these perfusion differences were robust and already detectable with 50 perfusion-weighted images per subject, acquired in 5 min. To understand the underlying factors, we examined the influence of image quality metrics, various tissue microstructure and morphometric properties, macrovasculature, and cytoarchitecture. We observed higher perfusion in regions located closer to arteries, demonstrating the influence of vascular proximity on hippocampal perfusion. Moreover, ex vivo cytoarchitectonic features based on neuronal density differences appeared to correlate stronger with hippocampal perfusion than morphometric measures like gray matter thickness. These findings emphasize the interplay between microvasculature, macrovasculature, and metabolic demand in shaping hippocampal perfusion. Our study expands the current understanding of hippocampal physiology and its relevance to neurological disorders. By providing in vivo evidence of perfusion differences between hippocampal subfields, our findings have implications for diagnosis and potential therapeutic interventions. In conclusion, our study provides a valuable resource for extensively characterizing hippocampal perfusion.
Topics: Perfusion; Arteries; Benchmarking; Hippocampus; Magnetic Resonance Imaging
PubMed: 38446857
DOI: 10.1073/pnas.2310044121 -
Scientific Reports Mar 2024Large volume soft tissue defects greatly impact patient quality of life and function while suitable repair options remain a challenge in reconstructive surgery....
Large volume soft tissue defects greatly impact patient quality of life and function while suitable repair options remain a challenge in reconstructive surgery. Engineered flaps could represent a clinically translatable option that may circumvent issues related to donor site morbidity and tissue availability. Herein, we describe the regeneration of vascularized porcine flaps, specifically of the omentum and tensor fascia lata (TFL) flaps, using a tissue engineering perfusion-decellularization and recellularization approach. Flaps were decellularized using a low concentration sodium dodecyl sulfate (SDS) detergent perfusion to generate an acellular scaffold with retained extracellular matrix (ECM) components while removing underlying cellular and nuclear contents. A perfusion-recellularization strategy allowed for seeding of acellular flaps with a co-culture of human umbilical vein endothelial cell (HUVEC) and mesenchymal stromal cells (MSC) onto the decellularized omentum and TFL flaps. Our recellularization technique demonstrated evidence of intravascular cell attachment, as well as markers of endothelial and mesenchymal phenotype. Altogether, our findings support the potential of using bioengineered porcine flaps as a novel, clinically-translatable strategy for future application in reconstructive surgery.
Topics: Humans; Swine; Animals; Quality of Life; Bioengineering; Biomedical Engineering; Perfusion; Surgical Flaps; Extracellular Matrix; Tissue Scaffolds; Tissue Engineering
PubMed: 38555385
DOI: 10.1038/s41598-024-58095-7 -
Computer Methods and Programs in... Oct 2023Hyperthermia treatment planning (HTP) tools can guide treatment delivery, particularly with locoregional radiative phased array systems. Uncertainties in tissue and...
INTRODUCTION
Hyperthermia treatment planning (HTP) tools can guide treatment delivery, particularly with locoregional radiative phased array systems. Uncertainties in tissue and perfusion property values presently lead to quantitative inaccuracy of HTP, leading to sub-optimal treatment. Assessment of these uncertainties would allow for better judgement of the reliability of treatment plans and improve their value for treatment guidance. However, systematically investigating the impact of all uncertainties on treatment plans is a complex, high-dimensional problem and too computationally expensive for traditional Monte Carlo approaches. This study aims to systematically quantify the treatment-plan impact of tissue property uncertainties by investigating their individual contribution to, and combined impact on predicted temperature distributions.
METHODS
A novel Polynomial Chaos Expansion (PCE)-based HTP uncertainty quantification was developed and applied for locoregional hyperthermia of modelled tumours in the pancreatic head, prostate, rectum, and cervix. Patient models were based on the Duke and Ella digital human models. Using Plan2Heat, treatment plans were created to optimise tumour temperature (represented by T90) for treatment using the Alba4D system. For all 25-34 modelled tissues, the impact of tissue property uncertainties was analysed individually i.e., electrical and thermal conductivity, permittivity, density, specific heat capacity and perfusion. Next, combined analyses were performed on the top 30 uncertainties with the largest impact.
RESULTS
Uncertainties in thermal conductivity and heat capacity were found to have negligible impact on the predicted temperature ( < 1 × 10 °C), density and permittivity uncertainties had a small impact (< 0.3 °C). Uncertainties in electrical conductivity and perfusion can lead to large variations in predicted temperature. However, variations in muscle properties result in the largest impact at locations that could limit treatment quality, with a standard deviation up to almost 6 °C (pancreas) and 3.5 °C (prostate) for perfusion and electrical conductivity, respectively. The combined influence of all significant uncertainties leads to large variations with a standard deviation up to 9.0, 3.6, 3.7 and 4.1 °C for the pancreatic, prostate, rectal and cervical cases, respectively.
CONCLUSION
Uncertainties in tissue and perfusion property values can have a large impact on predicted temperatures from hyperthermia treatment planning. PCE-based analysis helps to identify all major uncertainties, their impact and judge the reliability of treatment plans.
Topics: Male; Female; Humans; Hyperthermia, Induced; Uncertainty; Reproducibility of Results; Neoplasms; Perfusion
PubMed: 37339535
DOI: 10.1016/j.cmpb.2023.107675