Tissue Tracer Research Articles

Behaviour of 7.62x39mm tracer and API bullets in soft tissue.

Some bullets, called tracer and API bullets, contain a pyrotechnical charge. The charge in the bottom of a tracer bullet burns in flight and enables the shooter or an observer to see the bullet's trajectory. An Armor Piercing Incendiary (API) bullet contains a hard core and a pyrotechnical charge that ignites on impact with a hard target. These bullets are designed to both pierce armor and ignite combustible materials. Both tracer and API bullets are quintessentially military ammunition, but some 7.62x39mm caliber variants are occasionally used in crimes. This fact triggered a study on the behavior of these bullets in soft tissue. Two different types of tracer bullets and two different types of API bullets were tested. The tracer bullets behaved similarly in a soft tissue simulant, in terms of energy transfer and deflection. These bullets deflected more from their original trajectory than the tested API bullets and the full metal jacket (FMJ) bullets that were tested as a reference. The two types of API bullets behaved completely different in the soft tissue simulant, especially in terms of energy transfer. One type yawed very late in the simulant and stayed intact, transferring little kinetic energy. The other type yawed early and disintegrated in the simulant, transferring much more of its kinetic energy, causing massive tissue (simulant) disruption. The difference in bullet behaviour was caused by a small but important difference in bullet design with the two types of API bullets.

Noninvasive measurement of tracer extraction efficiency in tissue, illustrated with Tc-99m-MAG3.

The aim of this study is to develop a noninvasive technique for measuring tissue tracer extraction efficiency ( E ) and illustrate it for Tc-99m-mercaptoacetyltriglycine (MAG3) and kidney. E was measured in 10 patients with normal MAG3 renography. E is the ratio of tissue clearance-to-blood flow ( Ki/F ). For single-photon tracers, attenuation constants are unknown, so Ki and F cannot be separately measured. However, by deriving attenuation-uncorrected Ki' and F' from the same regions of interests (ROIs), these constants cancel out, giving E . Using a lung ROI for blood activity, F was measured from first-pass and Ki' from Gjedde-Patlak-Rutland (GPR) analysis up to 130 s. Because of interference from right ventricle, a left ventricular ROI (LV) is unsuitable for F' but was used in GPR analysis, making an adjustment for the ratio of respective blood pool signals arising from lung and LV ROIs in early frames (60-90 s). A lung ROI underestimates F' by 4% at normal LV function. Chest wall interstitial activity ( I ), which does not affect F' , amounted to 53 and 30% of the lung and LV signals at 20 min, and 12 and 6% at 130 s, resulting in underestimations of Ki of 4 and 2%, respectively. Ignoring these opposing errors, E based on lung ROI for left and right kidneys was 43.5 (SD 8)% and 47.3 (9)%, and based on LV ROI for GPR analysis was 44.5 (10.9)% and 48.3 (10.6)%. E can be measured by combining blood flow from first-pass with clearance from GPR analysis, and has potential value both clinically and in clinical research.

99mTc/123I Dual-Radionuclide Correction for Self-Scatter, Down-Scatter, and Tailing Effect for a CZT SPECT with Varying Tracer Distributions.

SPECT systems distinguish radionuclides by using multiple energy windows. For CZT detectors, the energy spectrum has a low energy tail leading to additional crosstalk between the radionuclides. Previous work developed models to correct the scatter and crosstalk for CZT-based dedicated cardiac systems with similar 99mTc/123I tracer distributions. These models estimate the primary and scatter components by solving a set of equations employing the MLEM approach. A penalty term is applied to ensure convergence. The present work estimates the penalty term for any 99mTc/123I activity level. An iterative approach incorporating Monte Carlo into the iterative image reconstruction loops was developed to estimate the penalty terms. We used SIMIND and XCAT phantoms in this study. Distribution of tracers in the myocardial tissue and blood pool were varied to simulate a dynamic acquisition. Evaluations of the estimated and the real penalty terms were performed using simulations and large animal data. The myocardium to blood pool ratio was calculated using ROIs in the myocardial tissue and the blood pool for quantitative analysis. All corrected images yielded a good agreement with the gold standard images. In conclusion, we developed a CZT crosstalk correction method for quantitative imaging of 99mTc/123I activity levels by dynamically estimating the penalty terms.

Determination of tissue tracer transit of Technetium-99m-mercaptoacetyltriglycine diuretic renography in infants with suspected ureteropelvic junction obstruction - A multicenter prospective observational study

There is an ongoing controversy regarding management of ureteropelvic junction obstruction in infants, with a shift towards a non-operative approach. However, precise predictors of outcome are lacking. Recent studies postulated a high prognostic value of Technetium-99m-mercaptoacetyltriglycine tissue tracer transit with regard to the development of an impaired differential renal function and its potential improvement following pyeloplasty. To evaluate the prognostic value of Technetium-99m-mercaptoacetyltriglycine tissue tracer transit for the occurrence of changes in differential renal function in infants with suspected unilateral ureteropelvic junction obstruction in a prospective observational multicenter study. Infants below 3 months of age with a unilateral isolated hydronephrosis≥grade 3 received ultrasound and Technetium-99m-mercaptoacetyltriglycine diuretic renography at two different time points (timepoint 1 and timepoint 2). Data were analyzed at local centers and at the study center and were collected in an internet-based database system. Tissue tracer transit was determined for each diuretic renography, inter-observer variation for tissue tracer transit and standard parameters for judgement of differential renal function development were assessed. Thirty-seven patients were analyzed. Median age was 11 weeks (7-15) at timepoint 1 and 26 weeks (19-33) at timepoint 2. A delayed tissue tracer transit at timepoint 1 was not associated with deterioration of differential renal function at timepoint 2 in both, locally (10/37 cases) and centrally (4/37) analyzed cases. However, sensitivity and specificity were poor. The intraclass correlation coefficient comparing local and central findings of tissue tracer transit and renal drainage demonstrated poor or fair agreement. Analysis of standard parameters for differential renal function development revealed a prognostic value only for the dichotomized anteroposterior renal pelvic diameter (APD, p=0.03, 95%-CI 1.2-22.2). Regarding the primary endpoint of our study, we could not confirm the hypothesis that delayed tissue tracer transit reliably predicts a subsequent decline in differential renal function in the cohort of patients studied. Whether the low age of the patients, technical problems in the correct assessment of tissue tracer transit by the investigator in early infancy, the study design, or the parameter itself played a role is debated. In the presented setting tissue tracer transit was not useful as a predictive parameter for deterioration of differential renal function in infants with suspected unilateral ureteropelvic junction obstruction. Sensitivity and specificity of tissue tracer transit were not sufficient for risk stratification. Improved utility of tissue tracer transit as a marker might be achieved using a different study setting.

Molecular imaging of alphaVbeta3 integrin for evaluation of myocardial injury after acute myocardial infarction

Abstract Background 68Ga-NODAGA-RGD is a positron emission tomography (PET) tracer targeting αvβ3 integrin that is upregulated during angiogenesis. αvβ3 integrin expression increases early after acute myocardial infarction (AMI), and has been proposed as a marker of myocardial repair. Purpose We prospectively evaluated the uptake of 68Ga-NODAGA-RGD and its association to left ventricular function after human AMI. Methods Thirty patients underwent PET at 7.7±3.8 days after primary percutaneous coronary intervention for ST-elevation AMI. Resting myocardial perfusion was evaluated using 15O-water PET followed by evaluation of 68Ga-NODAGA-RGD uptake 60–75 minutes after injection of 179 MBq of tracer. Left ventricular function was evaluated by transthoracic echocardiography on the day of PET, and at 6-month follow-up. The definition of the ischemic area at risk and remote myocardial segments was based on the culprit coronary arterial segments in invasive angiography. 68Ga-NODAGA-RGD images were co-registered with perfusion images and uptake was measured as the standardized uptake value in the segment with the highest uptake (SUVmax) in ischemic area at risk, and the mean standardized uptake value (SUVmean) in remote segments. In addition, we calculated 68Ga-NODAGA-RGD uptake corrected to the mean myocardial blood flow (MBF) in the area at risk (SUVmax/MBFmean) to account for reduced distribution of tracer in non-viable tissue. Results Mean age of patients was 64±9 years, and 90% were males. Uptake of 68Ga-NODAGA-RGD was low in the remote myocardium, but focally increased in the ischemic area at risk (Figure 1). SUVmax in the ischemic area at risk was higher than SUVmean of the remote myocardium (0.73±0.16 vs. 0.51±0.11, p<0.001). 68Ga-NODAGA-RGD SUVmax did not correlate with MBF in the area at risk. Univariable predictors of 68Ga-NODAGA-RGD SUVmax in the area at risk included peak Troponin T (p<0.001), peak pro-BNP (p<0.001), low global longitudinal strain (p=0.01), and low regional longitudinal strain in the area at risk (p=0.02). In multivariable analysis, peak pro-BNP independently predicted SUVmax in the area at risk (p<0.001). At follow-up, left ventricular ejection fraction increased by 1.6±6.9% and global longitudinal strain by 0.5±3.2%. In univariable analysis, SUVmax and SUVmax/MBFmean in the area at risk predicted improvement of global longitudinal strain at 6 months after AMI (p=0.04 and p<0.001, respectively). Conclusion 68Ga-NODAGA-RGD uptake shows increased αvβ3 integrin expression in the ischemic area at risk early after reperfused AMI that is associated with the extent of myocardial injury, both regional and global systolic dysfunction, and increased left ventricular filling pressure. Increased 68Ga-NODAGA-RGD uptake in ischemic myocardium at risk predicts left ventricular function improvement at 6 months after AMI. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Academy of Finland, Finnish Foundation for Cardiovascular Research

Radiolabeling, biological distribution, docking and ADME studies of 99mTc-Ros as a promising natural tumor tracer

Rosmarinic acid (Ros) is one of phenolic metabolites with powerful potency as an anticancer agent, with different mechanisms to diminish the cancer cells. This current study represents radiolabeling of Ros with 99mTc using SnCl2 in pH4 for 15 min at 60 °C, The yield up to 92.2%. Biological evaluation in normal and cancer mice revealed the localization of the tracer in tumor tissue. Furthermore, docking and ADME (Absorption, Distribution, Metabolism, and Excretion) studies were performed, The resulted data clarifies the use of Ros as a promissing natural tracer.

Traffic pollution tracers in the lymphatic system tissue of children-possible link to chronic tonsillitis development: pilot study.

The origin of metal elements in tonsillar tissues of children patients was investigated in order to establish the link between environmental pollution and tonsilitis diagnosis. The children lived either in a polluted, industrial region (Moravian-Silesian Region, North-East Czechia) or a clean, predominantly agricultural region (South Bohemian Region, South-East Czechia). Simultaneously, the distance of the address of the patients to the closest main road was assessed. The elemental content of the present particulate matter in the tonsil samples, coming from indicated tonsillectomies, was analysed using scanning electron microscopy equipped with an X-ray microprobe. No significant association of the elemental composition and the region was found using both bivariate and multivariate methods; however, an association with the distance to the closest main road was found. The study presents a novel assessment of the tonsillar tissues and supports the link between environmental factors (traffic-related particulate pollution) and the onset of chronic, idiopathic diseases in children, which has been debated recently.

Non-Invasive Imaging Technique for the Estimation of Drug Delivery in Tumors

Non-Invasive Imaging Technique for the Estimation of Drug Delivery in Tumors

Complementary imaging of ultrasound and PET/CT: A new opportunity?

To evaluate the effectiveness of complementary imaging of high-resolution ultrasound including CEUS with PET/CT for tissue characterization and tumor detection. 100 patients were examined with PET/CT and US/CEUS between January 2018 until February 2020. All patients underwent PET/CT followed by selective US/CEUS within 4 weeks. Comparison regarding concordant or diverging findings in PET/CT and US. Analysis of the differences concerning the lesions number of found by PET/CT and US/CEUS or the possibility of a secured diagnosis following ultrasound causing therapeutic changes. Diverging findings regarding the number of liver lesions in PET/CT and CEUS were found in 35 out of 64 patients (54%). Regarding renal lesions, a more definite diagnosis following ultrasound, causing a change of therapeutic approach, was achieved in 89%. Concordant results in PET/CT and US were found in 83% of patients with splenic and nodal findings. In 78% of patients with increased musculoskeletal or soft tissue tracer uptake, US was able to make a secured diagnosis with therapeutic changes. The present results indicate a strong benefit of complementary imaging of PET/CT and selective, high-resolution ultrasound especially in patients with liver, renal and musculoskeletal or soft tissue findings.

Application of Nano-Carbon Tracing Technology in Thyroid Cancer and Its Relationship with Cytotoxic T Lymphocyte Antigen 4 Gene Polymorphism.

The most common malignant tumor of the human endocrine system is thyroid cancer, most used surgical treatment for thyroid cancer is total thyroidectomy with central lymph node dissection. However, surgery and thorough lymph node dissection can easily damage the parathyroid glands and cause corresponding surgery. Symptoms such as permanent hyperparathyroidism, nano-carbon is a common type of new lymphoid tissue tracer, it is mainly used to trace lymphoid tissue in tumor surgery. With the continuous advancement of surgical technology, more and more scholars have used nano-carbon to trace lymphoid tissue during thyroid cancer surgery, and have achieved good results. The results of this study show that thyroid cancer surgery with nano-carbon to negatively develop the parathyroid glands significantly reduces the incidence of serum PTH and blood calcium decline, and largely protects the parathyroid glands. Practice has also shown that the use of nano-carbon tracers is more thorough in lymph node dissection than thyroid cancer surgery without nano-carbon tracers.

Regional binding of tau and amyloid PET tracers in Down syndrome autopsy brain tissue

IntroductionTau pathology is a major age-related event in Down syndrome with Alzheimer’s disease (DS-AD). Although recently, several different Tau PET tracers have been developed as biomarkers for AD, these tracers showed different binding properties in Alzheimer disease and other non-AD tauopathies. They have not been yet investigated in tissue obtained postmortem for DS-AD cases. Here, we evaluated the binding characteristics of two Tau PET tracers (3H-MK6240 and 3H-THK5117) and one amyloid (3H-PIB) ligand in the medial frontal gyrus (MFG) and hippocampus (HIPP) in tissue from adults with DS-AD and DS cases with mild cognitive impairment (MCI) compared to sporadic AD.MethodsTau and amyloid autoradiography were performed on paraffin-embedded sections. To confirm respective ligand targets, adjacent sections were immunoreacted for phospho-Tau (AT8) and stained for amyloid staining using Amylo-Glo.ResultsThe two Tau tracers showed a significant correlation with each other and with AT8, suggesting that both tracers were binding to Tau deposits. 3H-MK6240 Tau binding correlated with AT8 immunostaining but to a lesser degree than the 3H-THK5117 tracer, suggesting differences in binding sites between the two Tau tracers. 3H-THK5117, 3H-MK6240 and 3H-PIB displayed dense laminar binding in the HIPP and MFG in adult DS brains. A regional difference in Tau binding between adult DS and AD was observed suggesting differential regional Tau deposition in adult DS compared to AD, with higher THK binding density in the MFG in adult with DS compared to AD. No significant correlation was found between 3H-PIB and Amylo-Glo staining in adult DS brains suggesting that the amyloid PIB tracer binds to additional sites.ConclusionsThis study provides new insights into the regional binding distribution of a first-generation and a second-generation Tau tracer in limbic and neocortical regions in adults with DS, as well as regional differences in Tau binding in adult with DS vs. those with AD. These findings provide new information about the binding properties of two Tau radiotracers for the detection of Tau pathology in adults with DS in vivo and provide valuable data regarding Tau vs. amyloid binding in adult DS compared to AD.

Feasibility of commonly used fluorescent dyes and viral tracers in aqueous and solvent-based tissue clearing

Objective: To study the compatibility of traditional tracers and viral tracers with tissue clearing technology and to provide guidance in choosing suitable tracing methods for a specific tissue clearing technique. Method: Experiment 1: In this study, two different types of representative tracers, namely fluorescent dye tracers (Fluoro-Gold and Fluoro-Ruby) and viral tracers carrying fluorescent proteins (rAAV9-hSyn-mCherry-WPRE-pA and rAAV9-hSyn-EGFP-WPRE-pA), were selected to trace the cerebrospinal tract of the animals by microinjection. Furthermore, we presented the signal changes after using the three representative transparentizing methods, which included FRUIT (aqueous tissue clearing), 3DISCO (solvent-based tissue clearing), and uDISCO (solvent-based tissue clearing), were compared after slicing. Experiment 2: Based on the research mentioned above, Fluoro-Ruby was microinjected unilaterally into the primary motor cortex of rats, directly tracing the pyramidal tract to the spinal cord. Then, the entire brain and spinal cord were collected for tissue transparency using the 3DISCO method, after which three-dimensional imaging was performed using optical microscopic imaging equipment. Results: Experiment 1 indicated that Fluoro-Gold and Fluoro-Ruby displayed better compatibility with the three transparent methods. The viral tracer exhibited higher compatibility with the FRUIT method, while its compatibility with 3DISCO and uDISCO was low. Furthermore, GFP was quenched more quickly and seriously than cherry protein under the same experimental conditions. Experiment 2: The Fluoro-Ruby tag displayed the presence of long-distance axons. For microscopic imaging, light sheet microscopy and two-photon microscopy were both used to identify the signals of tracers in transparent tissue. Results: Both Fluoro-Gold and Fluoro-Ruby displayed excellent compatibility with tissue clearing technology, which, with dehydration and delipidation at its core, lead to quenching of fluorescence proteins, while exhibiting poor compatibility with viral tracers. In combination with tissue clearing technology and optical microscopy, the anterograde tracer Fluoro-Ruby could stereoscopically display the complete neural conduction pathway.

Comparative Study Regarding the Properties of Methylene Blue and Proflavine and Their Optimal Concentrations for In Vitro and In Vivo Applications.

Methylene blue and proflavine are fluorescent dyes used to stain nucleic acid from the molecular level to the tissue level. Already clinically used for sentinel node mapping, detection of neuroendocrine tumors, methemoglobinemia, septic shock, ifosfamide-induced encephalopathy, and photodynamic inactivation of RNA viruses, the antimicrobial, anti-inflammatory, and antioxidant effect of methylene blue has been demonstrated in different in vitro and in vivo studies. Proflavine was used as a disinfectant and bacteriostatic agent against many gram-positive bacteria, as well as a urinary antiseptic involved in highlighting cell nuclei. At the tissue level, the anti-inflammatory effects of methylene blue protect against pulmonary, renal, cardiac, pancreatic, ischemic-reperfusion lesions, and fevers. First used for their antiseptic and antiviral activity, respectively, methylene blue and proflavine turned out to be excellent dyes for diagnostic and treatment purposes. In vitro and in vivo studies demonstrated that both dyes are efficient as perfusion and tissue tracers and permitted to evaluate the minimal efficient concentration in different species, as well as their pharmacokinetics and toxicity. This review aims to identify the optimal concentrations of methylene blue and proflavine that can be used for in vivo experiments to highlight the vascularization of the skin in the case of a perforasome (both as a tissue tracer and in vascular mapping), as well as their effects on tissues. This review is intended to be a comparative and critical presentation of the possible applications of methylene blue (MB) and proflavine (PRO) in the surgical field, and the relevant biomedical findings from specialized literature to date are discussed as well.

Validation of automated whole-body analysis of metabolic and morphological parameters from an integrated FDG-PET/MRI acquisition

Automated quantification of tissue morphology and tracer uptake in PET/MR images could streamline the analysis compared to traditional manual methods. To validate a single atlas image segmentation approach for automated assessment of tissue volume, fat content (FF) and glucose uptake (GU) from whole-body [18F]FDG-PET/MR images. Twelve subjects underwent whole-body [18F]FDG-PET/MRI during hyperinsulinemic-euglycemic clamp. Automated analysis of tissue volumes, FF and GU were achieved using image registration to a single atlas image with reference segmentations of 18 volume of interests (VOIs). Manual segmentations by an experienced radiologist were used as reference. Quantification accuracy was assessed with Dice scores, group comparisons and correlations. VOI Dice scores ranged from 0.93 to 0.32. Muscles, brain, VAT and liver showed the highest scores. Pancreas, large and small intestines demonstrated lower segmentation accuracy and poor correlations. Estimated tissue volumes differed significantly in 8 cases. Tissue FFs were often slightly but significantly overestimated. Satisfactory agreements were observed in most tissue GUs. Automated tissue identification and characterization using a single atlas segmentation performs well compared to manual segmentation in most tissues and will be valuable in future studies. In certain tissues, alternative quantification methods or improvements to the current approach is needed.

Quantitative fluorescence endoscopy: an innovative endoscopy approach to evaluate neoadjuvant treatment response in locally advanced rectal cancer

Quantitative fluorescence endoscopy (QFE) is a new technique that can visualise and quantify fluorescently tagged tumour tissue. In 25 patients with locally advanced rectal cancer (LARC), we evaluated QFE targeting...

PET imaging during hypoglycaemia to study adipose tissue metabolism.

BackgroundDisturbances in adipose tissue glucose uptake may play a role in the pathogenesis of type 2 diabetes, yet its examination by 2‐deoxy‐2‐[18F]fluorodeoxyglucose ([18F]FDG) PET/CT is challenged by relatively low uptake kinetics. We tested the hypothesis that performing [18F]FDG PET/CT during a hypoglycaemic clamp would improve adipose tissue tracer uptake to allow specific comparison of adipose tissue glucose handling between people with or without type 2 diabetes.DesignWe enrolled participants with or without diabetes who were at least overweight, to undergo a hyperinsulinaemic hypoglycaemic clamp or a hyperinsulinaemic euglycaemic clamp (n = 5 per group). Tracer uptake was quantified using [18F]FDG PET/CT.ResultsHypoglycaemic clamping increased [18F]FDG uptake in visceral adipose tissue of healthy participants (P = 0.002). During hypoglycaemia, glucose uptake in visceral adipose tissue of type 2 diabetic participants was lower as compared to healthy participants (P < 0.0005). No significant differences were observed in skeletal muscle, liver or pancreas.ConclusionsThe present findings indicate that [18F]FDG PET/CT during a hypoglycaemic clamp provides a promising new research tool to evaluate adipose tissue glucose metabolism. Using this method, we observed a specific impairment in visceral adipose tissue [18F]FDG uptake in type 2 diabetes, suggesting a previously underestimated role for adipose tissue glucose handling in type 2 diabetes.

CMKLR1-targeting peptide tracers for PET/MR imaging of breast cancer.

Background: Molecular targeting remains to be a promising approach in oncology. Overexpression of G protein-coupled receptors (GPCRs) in human cancer is offering a powerful opportunity for tumor-selective imaging and treatment employing nuclear medicine. We utilized novel chemerin-based peptide conjugates for chemokine-like receptor 1 (CMKLR1) targeting in a breast cancer xenograft model.Methods: By conjugation with the chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), we obtained a family of five highly specific, high-affinity tracers for hybrid positron emission tomography/magnetic resonance (PET/MR) imaging. A xenograft model with target-positive DU4475 and negative A549 tumors in immunodeficient nude mice enabled CMKLR1-specific imaging in vivo. We acquired small animal PET/MR images, assessed biodistribution by ex vivo measurements and investigated the tracer specificity by blocking experiments.Results: Five CMKLR1-targeting peptide tracers demonstrated high biological activity and affinity in vitro with EC50 and IC50 values below 2 nM. Our target-positive (DU4475) and target-negative (A549) xenograft model could be validated by ex vivo analysis of CMKLR1 expression and binding. After preliminary PET imaging, the three most promising tracers [68Ga]Ga-DOTA-AHX-CG34, [68Ga]Ga-DOTA-KCap-CG34 and [68Ga]Ga-DOTA-ADX-CG34 with best tumor uptake were further analyzed. Hybrid PET/MR imaging along with concomitant biodistribution studies revealed distinct CMKLR1-specific uptake (5.1% IA/g, 3.3% IA/g and 6.2% IA/g 1 h post-injection) of our targeted tracers in DU4475 tumor tissue. In addition, tumor uptake was blocked by excess of unlabeled peptide (6.4-fold, 5.5-fold and 3.4-fold 1 h post-injection), further confirming CMKLR1 specificity. Out of five tracers, we identified these three tracers with moderate, balanced hydrophilicity to be the most potent in receptor-mediated tumor targeting.Conclusion: We demonstrated the applicability of 68Ga-labeled peptide tracers by visualizing CMKLR1-positive breast cancer xenografts in PET/MR imaging, paving the way for developing them into theranostics for tumor treatment.

Modeling of FMISO [F18] nanoparticle PET tracer in normal-cancerous tissue based on real clinical image

Hypoxia as one of the principal properties of tumor cells is a reaction to the deprivation of oxygen. The location of tumor cells could be identified by assessment of oxygen and nutrient level in human body. Positron emission tomography (PET) is a well-known non-invasive method that is able to measure hypoxia based on the FMISO (Fluoromisonidazole) tracer dynamic. This paper aims to study the PET tracer concentration through convection–diffusion-reaction equations in a real human capillary-like network. A non-uniform oxygen pressure along the capillary path and convection mechanism for FMISO transport are taken into account to accurately model the characteristics of the tracer. To this end, a multi-scale model consists of laminar blood flow through the capillary network, interstitial pressure, oxygen pressure, FMISO diffusion and FMISO convection transport in the extravascular region is developed. The present model considers both normal and tumor tissue regions in computational domain. The accuracy of numerical model is verified with the experimental results available in the literature. The convection and diffusion types of transport mechanism are employed in order to calculate the concentration of FMISO in the normal and tumor sub-domain. The influences of intravascular oxygen pressure, FMISO transport mechanisms, capillary density and different types of tissue on the FMISO concentration have been investigated. According to result (Table 4) the convection mechanism of FMISO molecules transportation is negligible, but it causes more accuracy of the proposed model. The approach of present study can be employed in order to investigate the effects of various parameters, such as tumor shape, on the dynamic behavior of different PET tracers, such as FDG, can be extended to different case study problems, such as drug delivery.

Predictors of Renal Functional Improvement After Pyeloplasty in Ureteropelvic Junction Obstruction: Clinical Value of Visually Assessed Renal Tissue Tracer Transit in 99mTc-mercaptoacetyltriglycine Renography

To determine the clinical value of visually assessed renal tissue transit time (TTT) in 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) renography for patients undergoing pyeloplasty. Medical records of 164 patients who underwent dismembered pyeloplasty were retrospectively reviewed. Baseline and postoperative renal ultrasonography and 99mTc-MAG3 renography were performed. Two urologists blinded to clinical data evaluated the renography and classified TTT as timely or delayed based on visualization of the tracer in the kidney pelvis between 2 and 10 minutes. Renal functional change after pyeloplasty was compared between patients in the timely and delayed groups. A total of 126 patients (median age, 9 months) were evaluated after excluding patients with bilateral ureteropelvic junction obstruction, a single functioning kidney, duplicated ureter, or <3 months of follow-up. There were no differences between 89 patients with timely TTT and 37 patients with delayed TTT in mean preoperative hydronephrosis grade (3.7 vs 3.8) and pelvic diameter (3.1 cm vs 3.4 cm). Although the pre- and postoperative mean values of differential renal function (DRF) were significantly higher in the timely group than in the delayed group (47.2% vs 38.3% and 47.9% vs 44.6%), DRF change was greater in the delayed group (6.3% vs 0.6%). In multivariate analysis, delayed TTT was the only significant predictor of >5% improvement in renal function after pyeloplasty. Delayed TTT in 99mTc-MAG3 renography was a significant predictor of renal functional improvement after pyeloplasty in ureteropelvic junction obstruction. Because substantial improvement of renal function is anticipated, we recommend immediate pyeloplasty in patients with delayed TTT and decreased DRF.

Determination of Evans blue as a blood–brain barrier integrity tracer in plasma and brain tissue by UHPLC/UV method

ABSTRACTBlood–brain barrier changes are an integral part of many neurodegenerative diseases. Evans blue is an intravital dye that binds to albumin and can therefore be used to monitor extravasation of this plasma protein across blood–brain barrier in animal models of neurodegeneration. To monitor extravasation of albumin across blood–brain barrier, we developed and validated an ultrahigh-performance liquid chromatography method for the analysis of Evans blue in rat plasma and brain samples. Analyte was separated on ACQUITY UPLC BEH C18 column (2.1 mm × 50 mm) using a 5-min gradient run and detected by a UV detector. The limits of quantification (LOQ) were 10 µg/mL in plasma and 0.5 µg/g in brain samples. The limits of detection (LOD) were 1 µg/mL in plasma and 0.015 µg/g in brain samples. The method showed excellent linearity with regression coefficients higher than 0.99. The accuracy was within the range of 91–105%. The inter-day precision was in the range of 1.3–8%. The benefits of using UPLC are selectivity, short analysis period, and thus, a very good sample throughput. Using this method, we analyzed albumin extravasation across blood–brain barrier in transgenic rat model for tauopathy SHR-72 and age-matched control animals.