Depth of cervical plexus block and phrenic nerve blockade: a randomized trial

Background and objectivesCervical plexus blocks are commonly used to facilitate carotid endarterectomy (CEA) in the awake patient. These blocks can be divided into superficial, intermediate, and deep blocks by their relation to the fasciae of the neck. We hypothesized that the depth of block would have a significant impact on phrenic nerve blockade and consequently hemi-diaphragmatic motion.MethodsWe enrolled 45 patients in an observer blinded randomized controlled trial, scheduled for elective, awake CEA. Patients received either deep, intermediate, or superficial cervical plexus blocks, using 20 mL of 0.5% ropivacaine mixed with an MRI contrast agent. Before and after placement of the block, transabdominal ultrasound measurements of diaphragmatic movement were performed. Patients underwent MRI of the neck to evaluate spread of the injectate, as well as lung function measurements. The primary outcome was ipsilateral difference of hemi-diaphragmatic motion during forced inspiration between study groups.ResultsPostoperatively, forced inspiration movement of the ipsilateral diaphragm (4.34±1.06, 3.86±1.24, 2.04±1.20 (mean in cm±SD for superficial, intermediate and deep, respectively)) was statistically different between block groups (p<0.001). Differences were also seen during normal inspiration. Lung function, oxygen saturation, complication rates, and patient satisfaction did not differ. MRI studies indicated pronounced permeation across the superficial fascia, but nevertheless easily distinguishable spread of injectate within the targeted compartments.ConclusionsWe studied the characteristics and side effects of cervical plexus blocks by depth of injection. Diaphragmatic dysfunction was most pronounced in the deep cervical plexus block group.Trial registration numberEudraCT 2017-001300-30.

Nanosized T1 MRI Contrast Agent Based on a Polyamidoamine as Multidentate Gd Ligand

A linear polyamidoamine (PAA) named BAC-EDDS, containing metal chelating repeat units composed of two tert-amines and four carboxylic groups, has been prepared by the aza-Michael polyaddition of ethylendiaminodisuccinic (EDDS) with 2,2-bis(acrylamido)acetic acid (BAC). It was characterized by size exclusion chromatography (SEC), FTIR, UV–Vis and NMR spectroscopies. The pKa values of the ionizable groups of the repeat unit were estimated by potentiometric titration, using a purposely synthesized molecular ligand (Agly-EDDS) mimicking the structure of the BAC-EDDS repeat unit. Dynamic light scattering (DLS) and ζ-potential analyses revealed the propensity of BAC-EDDS to form stable nanoaggregates with a diameter of approximately 150 nm at pH 5 and a net negative charge at physiological pH, in line with an isoelectric point <2. BAC-EDDS stably chelated Gd (III) ions with a molar ratio of 0.5:1 Gd (III)/repeat unit. The stability constant of the molecular model Gd-Agly-EDDS (log K = 17.43) was determined as well, by simulating the potentiometric titration through the use of Hyperquad software. In order to comprehend the efficiency of Gd-BAC-EDDS in contrasting magnetic resonance images, the nuclear longitudinal (r1) and transverse (r2) relaxivities as a function of the externally applied static magnetic field were investigated and compared to the ones of commercial contrast agents. Furthermore, a model derived from the Solomon–Bloembergen–Morgan theory for the field dependence of the NMR relaxivity curves was applied and allowed us to evaluate the rotational correlation time of the complex (τ = 0.66 ns). This relatively high value is due to the dimensions of Gd-BAC-EDDS, and the associated rotational motion causes a peak in the longitudinal relaxivity at ca. 75 MHz, which is close to the frequencies used in clinics. The good performances of Gd-BAC-EDDS as a contrast agent were also confirmed through in vitro magnetic resonance imaging experiments with a 0.2 T magnetic field.

Multimodal Imaging Technology Effectively Monitors HER2 Expression in Tumors Using Trastuzumab-Coupled Organic Nanoparticles in Patient-Derived Xenograft Mice Models

Trastuzumab is a monoclonal antibody targeting human epidermal growth factor 2 (HER2), which has been successfully used in the treatment of patients with breast cancer and gastric cancer; however, problems concerning its cardiotoxicity, drug resistance, and unpredictable efficacy still remain. Herein, we constructed novel organic dopamine–melanin nanoparticles (dMNs) as a carrier and then surface-loaded them with trastuzumab to construct a multifunctional nanoprobe named Her-PEG-dMNPs. We used micro-PET/CT and PET/MRI multimodality imaging to evaluate the retention effect of the nanoprobe in HER2 expression in gastric cancer patient-derived xenograft (PDX) mice models after labeling of the radionuclides 64Cu or 124I and MRI contrast agent Mn2+. The nanoprobes can specifically target the HER2-expressing SKOV-3 cells in vitro (3.61 ± 0.74 vs. 1.24 ± 0.43 for 2 h, P = 0.002). In vivo, micro-PET/CT and PET/MRI showed that the 124I-labeled nanoprobe had greater contrast and retention effect in PDX models than unloaded dMNPs as carrier (1.63 ± 0.07 vs. 0.90 ± 0.04 at 24 h, P = 0.002), a similarity found in 64Cu-labeled Her-PEG-dMNPs. Because 124I has a longer half-life and matches the pharmacokinetics of the nanoparticles, we focused on the further evaluation of 124I-Her-PEG-dMNPs. Furthermore, immunohistochemistry staining confirmed the overexpression of HER2 in the animal model. This study developed and validated novel HER2-specific multimodality imaging nanoprobes for quantifying HER2 expression in mice. Through the strong retention effect of the tumor site, it can be used for the promotion of monoclonal antibody treatment effect and process monitoring.

Preparation of Magnetic Resonance Nano Contrast Agent and Its Adoption in Diagnosis of Breast Cancer

This study aimed to explore the value of preoperative mammography in the differential diagnosis of benign and malignant tumors of nipple discharge. A biocompatible T1 contrast agent KMnF3 nanoparticle was first developed in the research, and then RGD-coupled KMnF3 nanoparticles were further synthesized as a highly sensitive tumor-targeted magnetic resonance imaging (MRI) contrast agent. While the nanoparticle was characterized physically, cytotoxicity test and MRI test in breast cancer mice were performed, and the excised tumors were subjected to immunostaining and tumor electron microscope section processing. At the same time, 60 patients with nipple discharge were screened to participate in the research, and the prepared MRI nano contrast agent was used for the differential diagnosis of breast benign/malignant tumors of nipple discharge. In the experiment, the synthetic nanoparticles were tested by Fourier transformed infrared (FTIR), which proved that the designed RGDtu/KMnF3 nanoparticles were successfully synthesized. The quantitative analysis of the synthesized nanoparticles showed that the relaxation efficiency reached 23.12 mM−1s−1, and there was no obvious toxicity. After staining, the microscope showed that the tumor was proliferating. After intravenous injection of low-dose RGDtu/KMnF3 contrast agent, nanoparticles were found in the tumor tissue. It was found that the synthesized nanoparticles enhanced the contrast of tumors with a volume of less than 50 mm3 by observing tumor slices. The imaging of the patient’s breast showed that the X-ray classification of galactography based on this contrast agent was statistically significant in distinguishing benign/malignant lesions of nipple discharge (X2 = 58.700, P < 0.01).