New methods for deep tissue imaging

Microscopes play vital role biological science and medicine. For single photon microscopies, the scattering of photons makes regions of interest located a few hundred microns beneath the surface inaccessible. Multi-photon microscopes are widely used for minimally invasive in vivo brain imaging due to their increased imaging depth. However, multi-photon microscopes are hampered by limited dynamic range, preventing weak sample features from being detected in the presence of strong features, or preventing the capture of unpredictable bursts in sample strength. In the first part of the thesis, I present a solution to vastly improve the dynamic range of a multi-photon microscope while limiting potential photodamage. Benefits are shown in both structural and in-vivo functional mouse brain imaging applications. In the second section of the thesis work, I explore a completely different approach towards deep tissue imaging by changing the type of radiation from light to ultrasound. Inspired by an optical phase contrast technique invented in the lab, I developed an unprecedented ultrasound imaging system that can visualize the ultrasound phase contrast in the sample. The ultrasound phase contrast technique is able to visualize local sound speed variations instead of local reflectivity. Compared with existing sound speed tomography systems, our technique eliminates the cumbersome sound speed reconstruction process. The research work in this section contains three parts. In the first part, we designed a low-cost single element scanning system as proof of concept. In the second part, we implemented the ultrasound phase contrast imaging system on a commercial linear phased transducer array and an imaging apparatus designed for samples with finite thickness. In the third part, we studied the feasibility of ultrasound phase contrast imaging in arbitrarily thick tissue. We presented a complete workflow of theoretical study, simulation, prototyping and experimental testing for all three parts.2020-02-28T00:00:00

An investigation of forecasting methods for a purchasing decision support system. A real-world case study of modelling, forecasting and decision support for purchasing decisions in the rental industry.

This research designs a purchasing decision support system (PDSS) to assist real-world decision makings on whether to purchase or to sub-hire for equipment shortfalls problem, and to avoid shortage loss for rental business. Research methodology includes an extensive literature review on decision support systems, rental industry, and forecasting methods. A case study was conducted in a rental company to learn the real world problem and to develop the research topics. A data converter is developed to recover the missing data and transform data sets to the accumulative usage data for the forecasting model. Simulations on a number of forecasting methods was carried out to select the best method for the research data based on the lowest forecasting errors. A hybrid forecasting approach is proposed by adding company revenue data as a parameter, in addition to the selected regression model to further reduce the forecasting error. Using the forecasted equipment usage, a two stage PDSS model was constructed and integrated to the forecasting model and data converter. This research fills the gap between decision support system and rental industry. The PDSS now assists the rental company on equipments buy or hire decisions. A hybrid forecasting method has been introduced to improve the forecasting accuracy significantly. A dada converter is designed to efficiently resolve data missing and data format problems, which is very common in real world

Neuronal imaging with ultrahigh dynamic range multiphoton microscopy

Multiphoton microscopes are hampered by limited dynamic range, preventing weak sample features from being detected in the presence of strong features, or preventing the capture of unpredictable bursts in sample strength. We present a digital electronic add-on technique that vastly improves the dynamic range of a multiphoton microscope while limiting potential photodamage. The add-on provides real-time negative feedback to regulate the laser power delivered to the sample, and a log representation of the sample strength to accommodate ultrahigh dynamic range without loss of information. No microscope hardware modifications are required, making the technique readily compatible with commercial instruments. Benefits are shown in both structural and in-vivo functional mouse brain imaging applications.R21 EY027549 - NEI NIH HH

High-risk subtype: Clinical manifestations and molecular characteristics of submandibular gland adenoid cystic carcinoma

ObjectiveAdenoid cystic carcinoma of the head and neck mainly occurs in the major salivary glands, of which the parotid gland and submandibular gland are the most common. The purpose of this study was to clarify the site-specific differences in prognosis and molecular expression characteristics of the patients and to achieve stratified risk management of the clinical prognosis.MaterialsBy performing a single-centre retrospective analysis combined with analyses of the Surveillance, Epidemiology, and End Results (SEER) database, cBioPortal and GEO databases, the clinical prognostic characteristics and the differences in molecular expression patterns of ACC in the submandibular gland and parotid gland were analysed. Cox regression analysis, the chi-square test, Fisher’s test and the log-rank test were used to compare the significance of differences.ResultsCompared with patients with parotid gland ACC, the submandibular gland ACC is more likely to have metastases in the cervical lymph node (21.7% vs. 3.3%) and shows a higher rate of distant metastasis within 1 year after the primary site diagnosis (47.8% vs. 23.3%), a worse overall prognosis, more frequent mutations of MYB/MYBL1 (50% vs. 25%) and abnormal upregulation of the phosphatidylinositol-3 kinase (PI3K) pathway.ConclusionsSubmandibular gland ACC is associated with site-specific early cervical lymph node metastasis and hidden distant metastasis, along with rapid progression and a poor prognosis. A high MYB/MYBL1 mutation rate and abnormal upregulation of the PI3K pathway with MYB involvement were identified

Platelet-rich plasma loaded with antibiotics as an affiliated treatment for infected bone defect by combining wound healing property and antibacterial activity

To be faced with an infected bone defect and the need to accelerate bone union while controlling infection is a welcome challenge for orthopedists. Platelet-rich plasma (PRP) has been applied in tissue defects given their composition of growth factors however the weak antibacterial effects have limited the use of PRP in the clinical setting. Therefore, the aim of this study was to explore the feasibility of using PRP in a local antibiotic delivery system (PADS) with the characteristics of promoting wound healing of bone infection. PADS was prepared with the addition of antibiotics or no antibiotics as control after PRP was prepared by a two-step centrifugation procedure. Antibacterial tests showed zones of inhibition produced by antibiotics were not significantly different with antibiotics combined with PRP. HPLC analysis demonstrated that about 60% of the total vancomycin (VAN) and ceftazidime (CAZ) dose were released within 10 min, then the release rate gradually decreased. However, 90% clindamycin was released within 10 min. Interestingly, above 10 times the minimum inhibitory concentration was presented after 72 h. Additionally, ELISA and morphology studies of PADS indicated that loaded antibiotics could reduce the PRP-released growth factor concentration and disturb the structure of platelet-fibrin beams and fibrin network in a dose-dependent manner. Fortunately, the lower dose of antibiotics maintained their anti-microbial effect, meanwhile growth factors released from PADS, the structure of platelet-fibrin beams, fibrin network remained unaffected. In addition, a patient experiencing infected bone defect receiving this PADS treatment achieved union within the 15-month follow-up. Therefore, this novel PADS approach might represent a potential therapy for patients who have sustained infected bone defects

Interobserver variability in target volume delineation in definitive radiotherapy for thoracic esophageal cancer: a multi-center study from China

Abstract Purpose To investigate the interobserver variability (IOV) in target volume delineation of definitive radiotherapy for thoracic esophageal cancer (TEC) among cancer centers in China, and ultimately improve contouring consistency as much as possible to lay the foundation for multi-center prospective studies. Methods Sixteen cancer centers throughout China participated in this study. In Phase 1, three suitable cases with upper, middle, and lower TEC were chosen, and participants were asked to contour a group of gross tumor volume (GTV-T), nodal gross tumor volume (GTV-N) and clinical target volume (CTV) for each case based on their routine experience. In Phase 2, the same clinicians were instructed to follow a contouring protocol to re-contour another group of target volume. The variation of the target volume was analyzed and quantified using dice similarity coefficient (DSC). Results Sixteen clinicians provided routine volumes, whereas ten provided both routine and protocol volumes for each case. The IOV of routine GTV-N was the most striking in all cases, with the smallest DSC of 0.37 (95% CI 0.32–0.42), followed by CTV, whereas GTV-T showed high consistency. After following the protocol, the smallest DSC of GTV-N was improved to 0.64 (95% CI 0.45–0.83, P = 0.005) but the DSC of GTV-T and CTV remained constant in most cases. Conclusion Variability in target volume delineation was observed, but it could be significantly reduced and controlled using mandatory interventions