Deep learning-based segmentation of malignant pleural mesothelioma tumor on computed tomography scans: application to scans demonstrating pleural effusion

Tumor volume is a topic of interest for the prognostic assessment, treatment response evaluation, and staging of malignant pleural mesothelioma. Many mesothelioma patients present with, or develop, pleural fluid, which may complicate the segmentation of this disease. Deep convolutional neural networks (CNNs) of the two-dimensional U-Net architecture were trained for segmentation of tumor in the left and right hemithoraces, with the networks initialized through layers pretrained on ImageNet. Networks were trained on a dataset of 5230 axial sections from 154 CT scans of 126 mesothelioma patients. A test set of 94 CT sections from 34 patients, who all presented with both tumor and pleural effusion, in addition to a more general test set of 130 CT sections from 43 patients, were used to evaluate segmentation performance of the deep CNNs. The Dice similarity coefficient (DSC), average Hausdorff distance, and bias in predicted tumor area were calculated through comparisons with radiologist-provided tumor segmentations on the test sets. The present method achieved a median DSC of 0.690 on the tumor and effusion test set and achieved significantly higher performance on both test sets when compared with a previous deep learning-based segmentation method for mesothelioma

Left and right ventricle assessment with Cardiac CT: validation study vs. Cardiac MR

Objectives To compare Magnetic Resonance (MR) and Computed Tomography (CT) for the assessment of left (LV) and right (RV) ventricular functional parameters. Methods Seventy nine patients underwent both Cardiac CT and Cardiac MR. Images were acquired using short axis (SAX) reconstructions for CT and 2D cine b-SSFP (balanced- steady state free precession) SAX sequence for MR, and evaluated using dedicated software. Results CT and MR images showed good agreement: LV EF (Ejection Fraction) (52±14% for CT vs. 52±14% for MR; r0 0.73; p>0.05); RV EF (47±12% for CT vs. 47±12% for MR; r00.74; p>0.05); LV EDV (End Diastolic Volume) (74± 21 ml/m 2 for CT vs. 76±25 ml/m 2 for MR; r00.59; p>0.05); RV EDV (84±25 ml/m 2 for CT vs. 80±23 ml/m 2 for MR; r0 0.58; p>0.05); LV ESV (End Systolic Volume)(37±19 ml/m 2 for CT vs. 38±23 ml/m 2 for MR; r00.76; p>0.05); RV ESV (46±21 ml/m 2 for CT vs. 43±18 ml/m 2 for MR; r00.70; p>0.05). Intra- and inter-observer variability were good, and the performance of CT was maintained for different EF subgroups. Conclusions Cardiac CT provides accurate and reproducible LVand RV volume parameters compared with MR, and can be considered as a reliable alternative for patients who are not suitable to undergo MR. Key Points • Cardiac-CT is able to provide Left and Right Ventricular function. • Cardiac-CT is accurate as MR for LV and RV volume assessment. • Cardiac-CT can provide accurate evaluation of coronary arteries and LV and RV function

Dimedone Derivative {2-[(4-Hydroxy-phenylamino)- methylene]-5,5-dimethyl-cyclohexane-1,3-dione} Plays an Important Role in Breast Cancer Treatment

Purpose: To investigate the effect of 2-[(4-hydroxy-phenylamino)-methylene]-5,5-dimethyl-cyclohex (HPDH) on mammary carcinogenesis induced by 7,12-dimethylbenz(a)anthracene in female Sprague Dawley rats.Methods: Among three groups of rats (50 each) used in the study, the control group was fed standard diet alone, ibuprofen group received standard diet containing 1200 mg/kg ibuprofen while HPDH group was administered standard diet containing 1200 mg/kg HPDH. The treatment was for 10 days for all the groups. All the animals received 20 mg of DMBA intragastrically by gavage. Clinical parameters for the rats were recorded weekly. Micrometer caliper was used to measure the diameter of all the tumors at the end of the experiment and tumor volume calculated. Histological evaluation was performed using  hematoxylin and eosin (H&E) staining. High performance liquid chromatography (HPLC) was used to determine the level of HPDH and ibuprofen in the serum of the animals.Results: The data revealed a significant decrease in the number of rats with mammary tumor, number of tumors/rat and tumor volume by 54, 72 and 75 %, respectively, in HPDH group compared to control group. The ibuprofen- treated rats also showed significant decrease in the number of rats with tumor, number of tumors/rat and tumor volume by 43, 55, and 59 %, respectively. Treatment of rats with HPDH increased the latency period of tumor induction significantly (p < 0.005). Median detection period (50 % of tumors) was 92, 83 and 56 days, respectively, in HPDH, ibuprofen and control groups, respectively, after DMBA induction.Conclusion: These results demonstrate that HPDH possesses strong chemopreventive activity against mammary carcinogenesis.Keywords: Carcinogenesis, Mammary tumor, Median detection period, Tumor, Latency period, Chemopreventive activity, Ibuprofe

Photobioreactor Technologies for High-throughput Microalgae Cultivation

The evaluation and optimisation of microalgae cultivation process for biomass, lipid and high value chemicals production requires experimental investigation of several interacting variables. This thesis addresses the development of a range of small-scale photobioreactor technologies and shows how they can be applied for rapid, early stage evaluation and scale-up of microalgae cultivation processes. In particular, the work focuses on the engineering evaluation of a novel shaken miniature photobioreactor (mPBr) and a single-use photobioreactor (SUPBr) that can be adapted for both phototrophic and heterotrophic cultivation. A prototype twin-well mPBr was initially designed and fabricated with light provided from cool white light emitting diodes (LED). This was scaled-out to a 24-well mPBr system (4 mL working volume) on a novel shaken platform. High power warm white LEDs provided a maximum light intensity of 2000 µmolm‾²s‾¹. In both systems, surface aeration (via a semipermeable membrane) and mixing were provided by orbital shaking. Real-time control of temperature, relative humidity and CO2 levels was achieved via incubator level control. Amongst the tested geometries of the mPBr, round base and pyramid base gave the best performance. The mass transfer coefficient (kLa) values in the 24-well were measured between 20 – 88 h‾¹ and visual observation of fluid hydrodynamics showed an increase in total surface area with increased shaking frequency. Negligible evaporation was observed at 90% relative humidity for light intensity of < 400 µmolm‾²s‾¹ and at 32 °C, while light intensity variation across the platform is in the range ± 20 µmolm‾²s‾¹. Evaluation of phototrophic culture kinetics of Chlorella sorokiniana in both mPBr designs showed good reproducibility between wells. The best culture performance occurred at 380 µmolm‾²s‾¹, 300 rpm and 5% CO2, where final biomass concentration and total lipid concentration achieved were 9 ± 0.2 gL‾¹ and 55% w/w respectively. The SUPBr comprised a transparent polymeric CultiBagTM operated on the illuminated rotary shaken platform described above. Mixing time values were determined over the range 40 - 220 rpm and were generally less than 40 s. Hydrodynamic studies showed three distinct flow regimes at various shaking frequencies: in-phase, transitional and out-of-phase. Under optimal flow regime, the highest cell concentrations achieved was 6.7 gL‾¹ ± 0.3. Doubling the total working volume resulted in 35 - 40% reduction in biomass concentration due to an increase in the light path length. Phototrophic scale-up criteria from mPBr to SUPBr was successfully achieved based on light–path length and kLa values. Comparison of final biomass concentrations showed similar performance of 6 ± 0.2 gL‾¹ and comparable total lipid production of 25 – 30% by weight at a light intensity of 180 ± 20 µmolm‾²s‾¹. Furthermore, application of the shaken 24-well system for heterotrophic cultivation of microalgae and scale-up to a 7.5 L stirred tank bioreactor was also shown. Cells were cultured in 24 parallel wells, shake flasks and a 7.5 L bioreactor with working volumes of 4 mL, 100 mL and 4000 mL respectively using glucose (10 gL‾¹) as the main carbon source. Constant k(L)a was chosen as scale-up criteria and the values range between 30 – 60 h‾¹. Final biomass concentrations showed good agreement in the range of 4.5 ± 0.5 gL‾¹ and total lipid production of 43 – 50% by weight for the three systems. Overall, the results show the utility of the mPBr and SUPBr technologies for the rapid evaluation and scale-up of both phototrophic and heterotrophic microalgae cultivation conditions

당뇨병 의 최소침습 진단 및 약물 치료를 위한 방법론

학위논문 (박사) -- 서울대학교 대학원 : 공과대학 협동과정 바이오엔지니어링전공, 2021. 2. 최영빈.This dissertation is focused on design, fabrication and evaluation of a strip-type tear glucose sensor and an implantable magnetic pump for minimally-invasive diagnosis and drug therapy, respectively. Management of diabetes mellitus have been painful procedures to many patients, because the diagnosis included needled finger pricking with a lancet, and the drug therapy were conducted with needled injections. There have been research efforts to minimize the pain associated with the diabetes mellitus management, but still there are unmet drawbacks. Therefore, methodologies of minimally-invasive diagnosis and drug therapy are proposed in this study. First, a strip-type tear glucose sensor was developed for concurrent tear collection and measurement with a small tear volume. Current tear glucose measurement has drawbacks such as large tear sample volume, long tear collection time, discomfort to patients, and two-step procedure that require sample transfer from tear collector to measuring instruments. To resolve these issues, a highly-accurate strip-type electrochemical sensor was modified by reducing the volume of reaction chamber to 0.4 μl. Then the modified sensor and a 3D printed lid to ensure safety to the eye were assembled. The assembled sensor, or the tear-glucose device, could collect tear fluid sample within 2 seconds, and simultaneously measure tear glucose concentration accurately without sample transfer. Through animal experiments, a high correlation between tear glucose concentration and the blood glucose concentration were determined with the tear-glucose device. The Clarke error grid analysis suggested that the blood glucose concentration estimated from the tear glucose sensor showed acceptable accuracy compared to that measured with commercially available blood glucometer. In addition, an implantable magnetic pump enabled with on-demand bolus delivery of exenatide was developed. The magnetic pump could deliver a bolus of 11.4 ± 0.3 μg of exenatide for optimal exenatide delivery regimen. This magnetic pump was designed to be actuated with a patterned magnetic field, thus could prevent unintended actuations by a single household magnet. In addition, a flexible polyurethane drug container in the magnetic pump could resolve negative pressure issues that could occur in solid drug container. The magnetic pump could deliver up to 300 times without a drug replenishment. The absence of battery and the presence of refillable drug container enabled a semi-permanent usage of the magnetic pump. The magnetic pump showed a similar pharmacokinetic profile compared to the injection therapy. When implanted in type 2 diabetic animal models, the magnetic pump showed comparable efficacy to injection therapy, in terms of body weight change, food intake, glycemic control, insulin secretion, insulin sensitivity, gastric emptying rate, beta cell proliferation and adipocyte size reduction. Through these studies, it is concluded that the strip-type tear glucose sensor and the magnetically actuated pump developed herein could be suggested as methodologies to replace invasive finger pricking and injection therapy.많은 당뇨 병 환자들이 현재 채혈을 통한 진단 방법과 주사를 통한 약물 치료를 통해 혈당을 관리하고 있다. 이런 침습적인 진단 및 투약 방식은 환자들에게 많은 고통과 트라우마 굳은 살, 가려움증 및 염증 등의 부작용을 초래하는 문제점이 있다. 이를 해결하기 위해 본 논문에서는 당뇨 병 진단 및 약물치료를 위한 최소침습 방법론 을 제안하고자 한다. 먼저 채혈 진단 방식의 대안으로 눈물 내 당 농도, 즉 누당을 측정 하는 센서를 개발하였 다 누당은 혈당과 높은 상관관계를 보이는 까닭에 많은 진단 연구가 진행되었다. 그러나 많은 양의 눈물 샘플을 필요로 하며 이를 채취하는 시간이 길어져 환자에게 불편함과 고통을 야기하는 문제점이 있었다. 또한 눈물 샘플을 채취 장치에서 측정 장치로 옮기는 과정에서 발생하는 정확도의 하락과 불편함이 문제가 되었다. 이런 문제를 해결하기 위해 높은 정확도를 가지는 전기화학 센서를 개조하여 필요 눈물 양을 0.4 μl로 줄였으며, 3D 프린트 된 lid의 장착을 통하여 전안부 접촉 시에도 손상을 야기하지 않도록 하였다. 개조된 센서와 lid의 결합으로 구성된 tear-glucose device는 전안부에 접촉한 지 2 초 이내에 필요한 양의 샘플을 채취할 수 있었으며 채취와 동시에 누당 농도를 측정하였다. 동물 모델에 적용한 결과, tear-glucose device를 통해 혈당과 누당 간의 높은 상관관계를 확인할 수 있었다. 또한 Clarke error grid analysis결과, 개발된 tear-glucose device를 통해 계산된 혈당값이 이미 상용화된 혈당 측정기 대비 준수한 정확도를 보였음을 확인할 수 있었다. 다음으로 주사 약물 치료의 대안으로 이식형 약물전달 디바이스를 개발하였다. 현재 개발된 당뇨 병 관리용 이식형 약물전달 디바이스의 경우, 약물치료 regimen을 최적화하지 못하여 tachyphylaxis를 야기하거나 디바이스의 크기, 수명, 안전성에 문제가 있는 경우가 있었다. 이러한 문제를 해결하기 위해 패턴화된 자기력 구동 이식형 약물전달 펌프를 개발하였다. 본 펌프는 on-demand bolus 전달 방식을 통해 최적화된 약물치료 regimen을 구현하고, 배터리 대신 자기력 구동 방식을 사용해 디바이스의 크기, 수명 문제를 해결하고, 패턴화된 자기력을 사용함으로 안전성 문제를 해결하였다. 또한 폴리우레탄 약물저장소를 사용하여 고체 약물저장소에서 나타나는 음압으로 인한 방출 문제를 해결하였다. 본 펌프를 평가한 결과, 11.4 ± 0.3 μg의 exenatide를 약물 충전 없이 300 회 방출시킬 수 있었다. 동물 모델에서 평가한 결과 약력학 및 약동학에서 기존 주사 약물치료와 유사한 효과를 보였다. 본 연구를 통해 개발된 누당 측정 센서와, 자기력 구동 이식형 약물전달 펌프는 기존 사용되는 혈당측정기와 주사 약물치료 방법론과 유사한 효용성을 보이는 것을 확인하였다. 따라서 이는 침습적인 당뇨 병 의 진단 및 약물치료 방식의 대안으로 제시될 수 있을 것이라 기대 한다.Abstract ……………………………………………………………………… i Contents …………………………………………………………………… iv List of Tables ……………………………………………………………… vii List of Figures …………………………………………………………… viii Chapter 1. Introduction …………………………………………………… 1 1.1. Current management methodologies for diabetes mellitus……………. 1 1.2. Tear-based methodologies of minimally-invasive diagnosis for diabetes mellitus ……………………………………………………………………… 3 1.3. Implantable drug delivery device for minimally-invasive drug therapy for diabetes mellitus………………………………………………………………5 1.4. Current limitations and research aims ………………………………… 7 Chapter 2. Strip-type tear glucose sensor for concurrent tear collection and glucose measurement ………………………………………………… 9 2.1. Device design …………………………………………………………… 9 2.2. Methods ……………………………………………………………… 11 2.2.1. Lid ……………………………………………………………… 11 2.2.2. Strip-type glucose sensor ………………………………………… 14 2.2.3. In vitro evaluation ……………………………………………… 15 2.2.4. In vivo evaluation ……………………………………………… 17 2.2.5. Statistical analysis ……………………………………………… 18 2.3. Results ……………………………………………………………… 18 2.3.1. Tear-glucose device ……………………………………………… 18 2.3.2. In vitro performance evaluation ………………………………… 20 2.3.3. In vivo performance evaluation ………………………………… 20 2.3.4. In vivo safety evaluation ………………………………………… 26 2.4. Discussions …………………………………………………………… 28 Chapter 3. Implantable magnetic pump for bolus delivery of exenatide 33 3.1. Device design ………………………………………………………… 33 3.2. Methods ……………………………………………………………… 35 3.2.1. Materials ………………………………………………………… 35 3.2.2. Magnetic pump fabrication ……………………………………… 35 3.2.3. Magnetic design principles ……………………………………… 38 3.2.4. High-performance liquid chromatography measurements ……… 38 3.2.5. In vitro performance test ………………………………………… 38 3.2.6. Accelerated depletion test ……………………………………… 39 3.2.7. Stability evaluation of exenatide ………………………………… 39 3.2.8. Animal study …………………………………………………… 40 3.2.9. Glucose tolerance test …………………………………………… 43 3.2.10. Paracetamol absorption test …………………………………… 43 3.2.11. Histology and immunohistochemistry ………………………… 43 3.2.12. Statistical analysis ……………………………………………… 44 3.3. Results ………………………………………………………………… 45 3.3.1. Pump design and working principles …………………………… 45 3.3.2. In vitro performance test ………………………………………… 52 3.3.3. In vivo pharmacokinetic tests …………………………………… 57 3.3.4. In vivo pharmacodynamic tests ………………………………… 62 3.3.5. Effects on the pancreatic islets and adipose tissues ……………… 70 3.3.6. Biocompatibility assessment …………………………………… 77 3.4. Discussions …………………………………………………………… 82 Chapter 4. Conclusion and perspective ………………………………… 86 References ………………………………………………………………… 89 Abstracts in Korean ……………………………………………………… 97 Acknowledgment……………………………………………………… 100Docto

A thermodynamic analysis of forced convection through porous media using pore scale modeling

The flow thorough porous media is analyzed from a thermodynamic perspective, with a particular focus on the entropy generation inside the porous media, using a pore scale modeling approach. A single representative elementary volume was utilized to reduce the CPU time. Periodic boundary conditions were employed for the vertical boundaries, by re-injecting the velocity and temperature profiles from the outlet to the inlet and iterating. The entropy generation was determined for both circular and square cross-sectional configurations, and the effects of different Reynolds numbers, assuming Darcy and Forchheimer regimes, were also taken into account. Three porosities were evaluated and discussed for each cross-sectional configuration, and streamlines, isothermal lines and the local entropy generation rate contours were determined and compared. The local entropy generation rate contours indicated that the highest entropy generation regions were close to the inlet for low Reynolds flows and near the central cylinder for high Reynolds flows. Increasing Reynolds number from 100 to 200 reveals disturbances in the dimensionless volume averaged entropy generation rate trend that may be due to a change in the fluid flow regime. According to Bejan number evaluation for both cross-section configurations, it is demonstrated that is mainly provoked by the heat transfer irreversibility. A performance evaluation criterion parameter was calculated for different case-studies. By this parameter, conditions for obtaining the least entropy generation and the highest Nusselt number could be achieved simultaneously. Indeed, this parameter utilizes both the first and the second laws of thermodynamics to present the best case-study. According to the performance evaluation criterion, it is indicated that the square cross-section configuration with o=0.64 exhibits better thermal performance for low Reynolds number flows. A comparison between the equal porosity cases for two different cross-sectional configurations indicated that the square cross-section demonstrated a higher performance evaluation criterion than the circular cross-section, for a variety of different Reynolds numbers

Initial validation of a virtual-reality learning environment for prostate biopsies: realism matters!

: Introduction-objectives: A virtual-reality learning environment dedicated to prostate biopsies was designed to overcome the limitations of current classical teaching methods. The aim of this study was to validate reliability, face, content and construct of the simulator. Materials and methods: The simulator is composed of a) a laptop computer, b) a haptic device with a stylus that mimics the ultrasound probe, c) a clinical case database including three dimensional (3D) ultrasound volumes and patient data and d) a learning environment with a set of progressive exercises including a randomized 12-core biopsy procedure. Both visual (3D biopsy mapping) and numerical (score) feedback are given to the user. The simulator evaluation was conducted in an academic urology department on 7 experts and 14 novices who each performed a virtual biopsy procedure and completed a face and content validity questionnaire. Results: The overall realism of the biopsy procedure was rated at a median of 9/10 by non-experts (7.1-9.8). Experts rated the usefulness of the simulator for the initial training of urologists at 8.2/10 (7.9-8.3), but reported the range of motion and force feedback as significantly less realistic than novices (p=0.01 and 0.03 respectively). Pearson's r correlation coefficient between correctly placed biopsies on the right and left side of the prostate for each user was 0.79 (p<0.001). The 7 experts had a median score of 64% (59-73), and the 14 novices a median score of 52% (43-67), without reaching statistical significance (p=0,19). Conclusion: The newly designed virtual reality learning environment proved its versatility and its reliability, face and content were validated. Demonstrating the construct validity will require improvements to the realism and scoring system used