Perfusion Agent Research Articles

Assessment of resting myocardial blood flow in regions of known transmural scar to confirm accuracy and precision of 3D cardiac positron emission tomography

BackgroundComposite invasive and non-invasive data consistently demonstrate that resting myocardial blood flow (rMBF) in regions of known transmural myocardial scar (TMS) converge on a value of ~ 0.30 mL/min/g or lower. This value has been confirmed using the 3 most common myocardial perfusion agents (13N, 15O-H2O and 82Rb) incorporating various kinetic models on older 2D positron emission tomography (PET) systems. Thus, rMBF in regions of TMS can serve as a reference “truth” to evaluate low-end accuracy of various PET systems and software packages (SWPs). Using 82Rb on a contemporary 3D-PET-CT system, we sought to determine whether currently available SWP can accurately and precisely measure rMBF in regions of known TMS.ResultsMedian rMBF (in mL/min/g) and COV in regions of TMS were 0.71 [IQR 0.52–1.02] and 0.16 with 4DM; 0.41 [0.34–0.54] and 0.10 with 4DM-FVD; 0.66 [0.51–0.85] and 0.11 with Cedars; 0.51 [0.43–0.61] and 0.08 with Emory-Votaw; 0.37 [0.30–0.42], 0.07 with Emory-Ottawa, and 0.26 [0.23–0.32], COV 0.07 with HeartSee.ConclusionsSWPs varied widely in low end accuracy based on measurement of rMBF in regions of known TMS. 3D PET using 82Rb and HeartSee software accurately (0.26 mL/min/g, consistent with established values) and precisely (COV = 0.07) quantified rMBF in regions of TMS. The Emory-Ottawa software yielded the next-best accuracy (0.37 mL/min/g), though rMBF was higher than established gold-standard values in ~ 5% of the resting scans. 4DM, 4DM-FDV, Cedars and Emory-Votaw SWP consistently resulted values higher than the established gold standard (0.71, 0.41, 0.66, 0.51 mL/min/g, respectively), with higher interscan variability (0.16, 0.11, 0.11, and 0.09, respectively).Trial registration: clinicaltrial.gov, NCT05286593, Registered December 28, 2021, https://clinicaltrials.gov/ct2/show/NCT05286593.

Cisplatin exhibits superiority over MMC as a perfusion agent in a peritoneal mesothelioma patient specific organoid HIPEC platform

Peritoneal mesothelioma (PM) is a rare malignancy with poor prognosis, representing about 10–15% of all mesothelioma cases. Herein we apply PM patient-derived tumor organoids (PTOs) in elucidating personalized HIPEC responses to bypass rarity of disease in generating preclinical data. Specimens were obtained from PM patients undergoing cytoreductive surgery with HIPEC. PTOs were fabricated with tumor cells suspended in ECM-hydrogel and treated with HIPEC regimen parameters. Viability and characterization analyses were performed post-treatment. Treatment efficacy was defined as ≥ 50% viability reduction and p < 0.05 compared to controls. From October 2020 to November 2022, 17 tumors from 7 patients were biofabricated into organoids, with 16/17 (94.1%) sites undergoing comparative 37° and 42° treatments with cisplatin and mitomycin C (MMC). Hyperthermic cisplatin and MMC enhanced cytotoxicity which reduced treatment viability by 25% and 22%, respectively, compared to normothermia. Heated cisplatin displayed the greatest cytotoxicity, with efficacy in 12/16 (75%) tumors and an average viability of 38% (5–68%). Heated MMC demonstrated efficacy in 7/16 (43.8%) tumors with an average treatment viability of 51% (17–92.3%). PTOs fabricated from distinct anatomic sites exhibited site-specific variability in treatment responses. PM PTOs exhibit patient and anatomic location treatment responses suggestive of underlying disease clonality. In PM organoids cisplatin is superior to MMC in HIPEC.

Parahydrogen-Polarized Fumarate for Preclinical in Vivo Metabolic Magnetic Resonance Imaging.

We present a versatile method for the preparation of hyperpolarized [1-13C]fumarate as a contrast agent for preclinical in vivo MRI, using parahydrogen-induced polarization (PHIP). To benchmark this process, we compared a prototype PHIP polarizer to a state-of-the-art dissolution dynamic nuclear polarization (d-DNP) system. We found comparable polarization, volume, and concentration levels of the prepared solutions, while the preparation effort is significantly lower for the PHIP process, which can provide a preclinical dose every 10 min, opposed to around 90 min for d-DNP systems. With our approach, a 100 mM [1-13C]-fumarate solution of volumes up to 3 mL with 13-20% 13C-hyperpolarization after purification can be produced. The purified solution has a physiological pH, while the catalyst, the reaction side products, and the precursor material concentrations are reduced to nontoxic levels, as confirmed in a panel of cytotoxicity studies. The in vivo usage of the hyperpolarized fumarate as a perfusion agent in healthy mice and the metabolic conversion of fumarate to malate in tumor-bearing mice developing regions with necrotic cell death is demonstrated. Furthermore, we present a one-step synthesis to produce the 13C-labeled precursor for the hydrogenation reaction with high yield, starting from 13CO2 as a cost-effective source for 13C-labeled compounds.

Agglomerated serum albumin adsorbed protocatechuic acid coated superparamagnetic iron oxide nanoparticles as a theranostic agent

Iron oxide nanoparticles have been one of the most widely used nanomaterials in biomedical applications. However, the incomplete understanding of the toxicity mechanisms limits their use in diagnosis and treatment processes. Many parameters are associated with their toxicity such as size, surface modification, solubility, concentration and immunogenicity. Further research needs to be done to address toxicity-related concerns and to increase its effectiveness in various applications. Herein, colloidally stable nanoparticles were prepared by coating magnetic iron oxide nanoparticles (MIONPs) with protocatechuic acid (PCA) which served as a stabilizer and a linkage for a further functional layer. A new perfusion agent with magnetic imaging capability was produced by the adsorption of biocompatible passivating agent macro-aggregated albumin (MAA) on the PCA-coated MIONPs. PCA-coated MIONPs were investigated using infrared spectroscopy, thermogravimetric analysis and dynamic light scattering while adsorption of MAA was analysed by transmission electron microscopy, Fourier-transform infrared spectroscopy and x-ray diffraction methods. Magnetic measurements of samples indicated that all samples showed superparamagnetic behaviour. Cytotoxicity results revealed that the adsorption of MAA onto PCA-coated MIONPs provided an advantage by diminishing their toxicity against the L929 mouse fibroblast cell line compared to bare Fe3O4.

Exposure to Neoadjuvant Oxaliplatin-Containing Chemotherapy, Does it Effect Intraperitoneal Hyperthermic Chemotherapy Perfusion?

Patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) are commonly exposed to oxaliplatin neoadjuvant chemotherapy (NAT) regimens. The impact of systemic exposure to oxaliplatin prior to HIPEC with oxaliplatin is unknown. We conducted a retrospective review of our institutional registry of CRS/HIPEC cases who received oxaliplatin-containing NAT, and compared patients who underwent HIPEC with oxaliplatin versus cases perfused with mitomycin C. The primary outcome was survival, defined by overall survival (OS) and disease-free survival (DFS). Subgroup analysis was performed based on primary tumor etiology and completeness of cytoreduction. A total of 333 cases satisfied the selection criteria-159 appendiceal primaries (all high-grade disease) and 174 colorectal cases. Thirty-one cases (9.3%) underwent HIPEC with oxaliplatin, with the remaining 302 cases (90.7%) receiving mitomycin C. Both cohorts were identical in regard to baseline characteristics, and both groups were alike in regard to NAT regimens and oxaliplatin exposure. There was no difference in survival outcomes. OS times were 2.9 (±2.8) and 2.8 ( ± 3.6) years for oxaliplatin and mitomycin C perfusions, respectively (p=0.94), and the 5-year OS rates were also similar at 9.7 and 18.5% (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.14-1.67, p=0.24) for oxaliplatin and mitomycin cases, respectively. Likewise, DFS findings were similar, with survival of 2.5 (± 4.5) and 1.8 (± 2.4) years for oxaliplatin and mitomycin perfusions, respectively (p=0.21). There was no difference in 5-year DFS rates, at 10.5 and 7.8% (OR 1.39, 95% CI 0.30-6.56, p=0.68) for oxaliplatin and mitomycin C, respectively. Subgroup analysis found minimal discordant findings from the main results. This analysis found no discernable association with NAT oxaliplatin exposure in regard to survival outcomes following CRS/HIPEC stratified out by perfusion agent.

ASO Visual Abstract: Switching Perfusion Agents for Repeat Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy, Surgical Dogma or Evidence-Based Practice?

ASO Visual Abstract: Switching Perfusion Agents for Repeat Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy, Surgical Dogma or Evidence-Based Practice?

Switching Perfusion Agents for Repeat Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy: Surgical Dogma or Evidence-Based Practice?

A common practice is to switch chemotherapy perfusion agents for repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). However, there is a paucity of objective benefit with this practice. A retrospective review of our institutional registry involving repeat CRS-HIPEC cases was conducted, comparing cases that underwent a perfusion agent switch versus those cases with no switch. The primary outcome of this study was survival, measured by overall survival (OS) and disease-free survival (DFS). A subgroup analysis was performed on the basis of primary etiology. A total of 101 cases met selection criteria. Mitomycin C was used as the index perfusion agent in 84% of cases, while oxaliplatin was utilized in the remaining 16% of cases. In total, 66 cases underwent a perfusion switch, with 35 cases using the same agent. Analysis revealed no survival benefit with HIPEC perfusion switch. For OS, there were similar mean survival times of 5.2 (± 4.1) years and 5.1 (± 3.6) years for cases with perfusion switch and no perfusion switch, respectively (P = 0.985). The 5-year OS rates were also similar at 61.4% and 53.3% for switch and non-switch cases, respectively [odds ratio (OR) 0.41, 95% confidence interval (CI) 0.54-3.56, P = 0.49]. Mean DFS was 4.0 (± 4.2) years and 3.6 (± 3.8) years for switch and non-switch cases, respectively (P = 0.74). The 5-year DFS rates had a greater difference with statistical trend, with rates of 53% versus 28% for switch and non-switch cases, respectively (OR 2.91, 95% CI 0.86-9.86, P = 0.081). Subgroup analysis had a similar trend to the main results. The study findings revealed no survival benefit with switching perfusion agents. Analysis suggests that the practice of perfusion switch is ineffective.

Weak lesion feature extraction by dual-branch separation and enhancement network for safe hemorrhagic transformation prediction.

Hemorrhagic transformation (HT) is regarded as a safety endpoint of arterial ischemic stroke acute treatment and secondary prevention trials (Hutchinson and Beslow, 2019). Accurate HT prediction dramatically reduces the death rate from misdiagnosis. At present, HT predictions almost all rely on contrast images with perfusion agents, which is time-consuming and labor-intensive, causing secondary brain damage and high cost. Almost all machine learning algorithms cannot use non-contrast CT for HT prediction because of huge challenges. In this study, a Dual-branch Separation and Enhancement Network (DBSE-Net) is proposed for weak feature extraction and safe HT prediction without perfusion agents. DBSE-Net innovatively uses a dual-branch separation and fusion mechanism to achieve weak feature adaptive extraction. In the DBSE-Net's encoder submodules, Brain Compression Assessment Branch (BCAB) and Infarct Assessment Branch (IAB) are proposed to apply lightweight encoding structures with different receptive fields, which are adapted to the lesion area's characteristics. With the help of DBSE-Net's keyframe selection algorithm and area guidance knowledge, DBSE-Net removes redundant information and clearly describes the severity of lesions. In summary, DBSE-Net integrates global and local features to obtain multi-scale and multi-category brain status information, enhancing the weak features of non-contrast CT and realizes accurate HT prediction. Experimental Result: Among all 144 intracranial stroke patients diagnosed by doctors as having no HT risk, DBSE-Net identified 73 high-risk HT patients (88 HT cases in total). The result illustrates that DBSE-Net helps doctors secondary diagnose the HT risk of intracranial stroke patients and becomes a potential tool to prevent doctors from false HT risk diagnosis.

Dosymmetric estimates of 99mTc (MAA) and 133Xe in newborn lungs using Cristy-Eckerman / Segars representations

Using the Cristy-Eckerman (C-E) / Segars anatomical representations and the MIRD formalism, the Absorbed doses in lungs of newborn patients scanned with radiopharmaceuticals 133Xe (ventilation) and 99mTc (MAA) (perfusion) are estimated. These representations are phantoms used in Monte Carlo calculations to determine specific absorbed fractions, which, associated with the pharmaceutical residence time, determine the absorbed dose. Concerns about the dosimetric impact of using these ventilation / perfusion agents, as well as the use of different phantoms, were explored in newborn patients. When the lungs were scanned with 99mTc (MAA), the relative difference in total dose between the C-E / Segars anatomical representations was 1.0%. When the lungs were scanned with 133Xe, the relative difference in total dose between the anthropomorphic representations of C-E / Segars was 0.5%. Regardless of the radiopharmaceutical used for the pulmonary studies of a newborn patient, the substitution of the C-E representation for that of Segars does not reflect very significant changes in the calculation of the absorbed dose in the lungs, where the greatest dosimetric contribution is its self-dose, which is supplied mainly by the electrons produced during the 99mTc and 133Xe decay.

Application value of new nano-drug carrier in biphasic 3D-pCASL in the evaluation of cerebral perfusion blood flow in symptomatic and asymptomatic unilateral middle cerebral artery subtotal occlusion

We investigate the use of superparamagnetic iron oxide nanoparticles as a contrast agent for the cerebral perfusion of unilateral middle cerebral artery (MCA) subtotal occlusion by magnetic resonance three-dimensional pseudo-continuous arterial spin-labelled imaging (3D-pCASL) dual-phase scanning technology for the application value of blood flow to evaluate the difference of cerebral perfusion between symptomatic and asymptomatic patients. We found through research that the biphasic 3D-pCASL technology can accurately detect cerebral perfusion blood flow in patients with subtotal middle cerebral artery occlusion. Asymptomatic patients have higher cerebral perfusion than symptomatic patients with collateral circulation superparamagnetic iron oxide nanoparticles. Phase (PLD) equal to 1.5 s is more sensitive than 2.5 s, and PLD = 2.5 s can accurately reflect secondary collateral circulation's compensation status.

Post-ISCHEMIA Trial Era: Reconsideration of the Role of Nuclear Cardiology in Patients with Chronic Coronary Artery Disease.

The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial has had a great impact on the management of chronic coronary artery disease (CAD). One of the implications of this trial is the importance of close patient follow-up. To improve patient prognosis, evaluation of the residual extent of ischemia after treatment may be important because several studies have shown a close relationship between residual ischemia and cardiac events. For this assessment, myocardial perfusion single-photon emission computed tomography (MPS) has been utilized and is almost the only modality. Among the participants in the ISCHEMIA trial, more than 10% were excluded due to the absence of obstructive CAD. The pathophysiology of ischemia without non-obstructive coronary artery disease (INOCA) is gaining recognition; however, diagnosis is difficult, except for the assessment of myocardial flow reserve (MFR). Myocardial perfusion positron emission tomography (PET) is the most common modality for noninvasive evaluation of MFR; however, its availability in Japan is limited. For a breakthrough in this situation, a novel gamma camera with a cadmium zinc telluride (CZT) semiconductor might be one of the solutions that enables the evaluation of MFR with a commercially available perfusion tracer, similar to PET. Another solution is a novel PET tracer with a longer half-life. Clinical trials with 18F labeled perfusion agents have been initiated in Japan, and in a few years, delivery of this perfusion tracer will result in more frequent and easier assessment of MFR.

Dosimetry of radiopharmaceuticals used in adult patients with suspected pulmonary embolism

The absorbed dose of radiopharmaceuticals is estimated in adults with suspected pulmonary embolism explored by ventilation/perfusion studies. For pulmonary ventilation studies 81mKr, 133Xe, 99mTc (Technegas)-aerosol and 99mTc (DTPA)-aerosol are used. For perfusion agents, 99mTc(MAA), 99mTc (MSA) (macroaggregates and albumin microspheres) are used. For the dose calculation, the MIRD methodology and the anthropomorphic representation of the biokinetic organs of Cristy-Eckerman are used. In ventilation/perfusion studies, the lowest dose absorbed by the lungs with suspected embolism is due to 81mKr/ 99mTc (MSA), and the highest dose is due to 99mTc (Technegas)/99mTc (MAA) calculated for activities of 150 MBq for perfusion agents and 40 MBq for ventilation agents.

Delayed genital necrosis after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with Mitomycin-C

IntroductionGenital necrosis (GN) is a rare complication of cytoreductive surgery with hyperthermic intraoperative chemotherapy (CRS/HIPEC) which can be confused with necrotizing fasciitis. We present an analysis of GN after CRS/HIPEC to define its natural history. MethodsWe identified patients with GN after CRS/HIPEC at two peritoneal surface malignancy institutions. Patient demographic, surgical, and postoperative data were extracted from prospective databases. ResultsOf 1597 CRS/HIPECs performed, 13 patients (0.8%) had GN. The median age was 57 years (IQR: 49–64) and 77% (n = 10) were male. Mitomycin-C was the perfusion agent in all cases of GN (100%). The median time to GN onset after CRS/HIPEC was 64 days (IQR: 60–108) and 2 (15%) patients were receiving systemic chemotherapy at the time of GN onset. Symptoms included severe pain (100%), edema (100%), labial or scrotal skin ulceration (92%), signs of infection (39%), and fever (15%). Seven (54%) patients had thrombocytosis >400 ∗109/L, whereas coagulation tests were within normal reference range in 100% cases. All patients initially underwent conservative treatment, with antibiotic therapy administered in 62% (n = 8). Surgical debridement was performed in 9 (70%) cases with median time after GN onset of 57 (IQR: 8–180). ConclusionGN is a debilitating complication after CRS/HIPEC with delayed onset and a protracted clinical course. Optimal treatment results could be achieved with initial conservative management until complete lesion demarcation followed by surgical debridement. The pathophysiology of GN is unclear, and we call for other researchers attention to better understand the complication and prevention.

Original Method for Evaluating Endothelial Vasomotor Function of Isolated Vessel in Experiment.

We describe a method for experimental assessment of endothelial dysfunction in an isolated using extracorporeal machine perfusion and vasoactive substrates agents (norepinephrine and acetylcholine). Quantitative assessment of endothelial vasomotor dysfunction was proposed, based on registration of changes in volumetric perfusate flow rate through the isolated vessel. Functional activity of the isolated aorta endothelium and total content of stable NO degradation products in blood plasma were studied in outbred white male rats after subtotal liver resection. Impaired vasodilation ability of the aorta and increased content of NO degradation products in blood plasma observed after surgery indicate the development of vasomotor endothelial dysfunction associated with oxidative stress, cholemia, and endotoxemia.

Cardiac PET-CT: A Brief Review of Indications and Feasibility in the Indian Scenario

AbstractCardiac positron emission tomography (PET) is a functional imaging modality with the predominant indications being an assessment of myocardial perfusion and viability using short-lived positron emitters. PET procedures are used for perfusion assessment only when single-photon emission computed tomography is equivocal. Perfusion agents are ultra short-lived and have limited availability in our country, that is, only at centers with onsite cyclotron. Viability assessment with fluorodeoxyglucose (FDG) is widely performed in many centers across the country due to the availability of FDG. The other important indication is in the detection of inflammatory myocarditis, the most common being cardiac sarcoidosis done with special dietary instructions and FDG as a tracer. This indication is widely used for early detection of myocardial inflammation which would be reversible if treated early. It is also used in the assessment of treatment response. Newer tracer 68 Ga Dotapeptide is also used in this application.

Simultaneous Metabolic and Perfusion Imaging Using Hyperpolarized 13C MRI Can Evaluate Early and Dose-Dependent Response to Radiation Therapy in a Prostate Cancer Mouse Model

To investigate use of a novel imaging approach, hyperpolarized (HP) 13C magnetic resonance imaging (MRI) for simultaneous metabolism and perfusion assessment, to evaluate early and dose-dependent response to radiation therapy (RT) in a prostate cancer mouse model. Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice (n = 18) underwent single-fraction RT (4-14 Gy steep dose across the tumor) and were imaged serially at pre-RT baseline and 1, 4, and 7 days after RT using HP 13C MRI with combined [1-13C]pyruvate (metabolic active agent) and [13C]urea (perfusion agent), coupled with conventional multiparametric 1H MRI including T2-weighted, dynamic contrast-enhanced, and diffusion-weighted imaging. Tumor tissues were collected 4 and 7 days after RT for biological correlative studies. We found a significant decrease in HP pyruvate-to-lactate conversion in tumors responding to RT, with concomitant significant increases in HP pyruvate-to-alanine conversion and HP urea signal; the opposite changes were observed in tumors resistant to RT. Moreover, HP lactate change was dependent on radiation dose; tumor regions treated with higher radiation doses (10-14 Gy) exhibited a greater decrease in HP lactate signal than low-dose regions (4-7 Gy) as early as 1 day post-RT, consistent with lactate dehydrogenase enzyme activity and expression data. We also found that HP [13C]urea MRI provided assessments of tumor perfusion similar to those provided by 1H dynamic contrast-enhanced MRI in this animal model. However, apparent diffusion coefficien , a conventional 1H MRI functional biomarker, did not exhibit statistically significant changes within 7 days after RT. These results demonstrate the ability of HP 13C MRI to monitor radiation-induced physiologic changes in a timely and dose-dependent manner, providing the basic science premise for further clinical investigation and translation.

Imaging probes for non-invasive tumoral detection and functional monitoring of cancer multidrug resistance.

Aim: Several cationic radiotracers originally developed as myocardial perfusion agents have shown potential for both early detection of cancer and non-invasive monitoring of multiple drug resistance (MDR) by single photon emission computed tomography. We have introduced two cationic complexes, 99mTc-DMEOP [di-methoxy-tris-pyrazolyl-99mTc-(CO)3] and 99mTc-TMEOP [tri-methoxy-tris-pyrazolyl-99mTc-(CO)3], which showed excellent preclinical results as cardiac imaging probes, namely a persistent heart uptake with rapid blood and liver clearance. This study aimed at the evaluation of their usefulness for tumoral detection and functional assessment of MDR.Methods: The uptake and efflux kinetics of 99mTc-DMEOP and 99mTc-TMEOP were evaluated in human prostate, lung, and breast cancer cell lines, including drug-resistant cell lines that are known to overexpress the MDR P-glycoprotein (Pgp). The effects of MDR modulators were also studied. In vivo studies were performed in xenografted tumor models, and the MDR phenotype of the tumors was confirmed by Western blot.Results: The uptake kinetics of both complexes in human cancer cell lines is comparable with the one found for 99mTc-Sestamibi, increasing over time. The uptake of 99mTc-TMEOP is greatly reduced in cells overexpressing Pgp and increased in the presence of a Pgp modulator. In nude mice, the tumor uptake of 99mTc-TMEOP was higher in the MCF-7 xenografts compared with the MCF7 Pgp tumors.Conclusion: The uptake kinetics of both complexes in human cancer cell lines is comparable with the one found for 99mTc-Sestamibi, increasing over time. The uptake of 99mTc-TMEOP is greatly reduced in cells overexpressing Pgp, and increased in the presence of a Pgp modulator. In nude mice, the tumor uptake of 99mTc-TMEOP was higher in the MCF-7 xenografts compared with the MCF7 Pgp tumors.

Nitrido Technetium-99 m Core in Radiopharmaceutical Applications: Four Decades of Research

The knowledge on element 43 (Tc) of the periodic table, built over the years through the contributions given by the close relationship between chemistry and nuclear medicine, allowed the development of new and increasingly effective radiopharmaceuticals useful both as perfusion and target specific imaging agents for SPECT (single photon emission tomography). Among the manifold Tc-compounds, Tc(V) nitrido complexes played a relevant role in the search for new technetium-99m radiopharmaceuticals, providing efficient labeling procedures that can be conveniently exploited for the design and synthesis of agents, also incorporating small organic molecules or peptides having defined structural features. With this work, we present an overview of four decades of research on the chemistry and on the nuclear medicine applications of Tc(V) nitrido complexes.

Construction of digital three-dimensional reconstruction model of rabbit vascular network.

In order to study the construction of digital three-dimensional model of rabbit vascular network and provide a powerful basis for the model construction and image processing of human vascular network, in this study, rabbit abdominal and pelvic vessels are perfused with latex-bismuth oxide contrast agent. After that, the internal fibrous structure of the abdominal and pelvic vascular network in rabbits is studied by micro-computed tomography (Micro-CT). Angiography and post-processing software are performed. Firstly, six female rabbits are selected as the study subjects and are anesthetized by intraperitoneal injection of 12% chloral hydrate. After complete anesthesia, laparotomy is performed on the rabbits. The abdominal wall of the rabbit is cut longitudinally to expose the pelvic and abdominal cavity completely. The posterior peritoneum is found and opened. The catheter is inserted into the abdominal aorta and renal artery to complete the abdominal aorta and arterial intubation. Latex, bismuth oxide and potassium hydroxide are mixed in a ratio of 1:1:1 to form latex-bismuth oxide mixed solution as a mixed contrast agent for blood vessel perfusion. After the rabbit is perfused with mixed contrast medium, four organs, including bladder, uterus, small intestine and kidney, are selected as the research organs to construct the three-dimensional model of vascular network in this study. Finally, the above organs are scanned in vitro by micro-CT technology, and the original images of each organ are processed. Then, Mimics 17.0 software is used to build a digital three-dimensional model of the abdominal and pelvic vascular network in rabbits, obtain the information parameters of each network, and analyze the classification and diameter of blood vessels. The results show that the classification of bladder vascular network can only be divided into two levels, uterine vascular network can be divided into three levels, and small intestine and kidney vascular network can be divided into four levels. Therefore, the combination of micro-CT scanning and contrast agent can successfully construct a digital three-dimensional model of rabbit vascular network, which provides a new idea and method for the study of human abdominal and pelvic organs and physiological characteristics.

Preclinical imaging of epidermal growth factor receptor with ABY-029 in soft-tissue sarcoma for fluorescence-guided surgery and tumor detection.

Fluorescence-guided surgery using epidermal growth factor receptor (EGFR) targeting has been performed successfully in clinical trials using a variety of fluorescent agents. We investigate ABY-029 (anti-EGFR Affibody® molecule labeled with IRDye 800CW) compared with a small-molecule perfusion agent, IRDye 700DX carboxylate, in a panel of soft-tissue sarcomas with varying levels of EGFR expression and vascularization. Five xenograft soft-tissue sarcoma cell lines were implanted into immunosuppressed mice. ABY-029 and IRDye 700DX were each administered at 4.98 μM. Fluorescence from in vivo and ex vivo (fresh and formalin-fixed) fixed tissues were compared. The performance of three fluorescence imaging systems was assessed for ex vivo tissues. ABY-029 is retained longer within tumor tissue and achieves higher tumor-to-background ratios both in vivo and ex vivo than IRDye 700DX. ABY-029 fluorescence is less susceptible to formalin fixation than IRDye 700DX, but both agents have disproportional signal loss in a variety of tissues. The Pearl Impulse provides the highest contrast-to-noise ratio, but all systems have individual advantages. ABY-029 demonstrates promise to assist in wide local excision of soft-tissue sarcomas. Further clinical evaluation of in situ or freshly excised ex vivo tissues using fluorescence imaging systems is warranted.