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Yüksek frekans osilasyonların (HFO) epileptojenik alanda biyomarker olarak kullanımı
Epilepsi nöbet şeklinde kendini gösteren ve tekrarlayan nörolojik bir hastalıktır. Hastalık, beyinde bazı nöronların anormal aktivitesi sonucu ortaya çıkar. Epilepsi çocukluk çağında veya yetişkinlikte her yaşta görülebilen ve herkeste farklı semptomlar gösterebilen bir hastalıktır. Epilepsi nöbetleri genellikle kas spazmı, bilinç kaybı ve bayılma şeklinde görülür. Dolayısıyla insanların günlük yaşamlarını, yapabileceği aktiviteleri etkileyebilir. Epilepsi ömür boyu devam edebilir, ancak uygun tedavi ve ilaçlarla nöbetler kontrol altına alınabilir ve kişi normal yaşantısını sürdürebilir. Bazı hastalarda hastanın durumu uygun ise cerrahi yönteme başvurulur. Epilepsi cerrahisi ciddi bir işlemdir, bu nedenle hastalar çok dikkatli değerlendirilir. Hastanın cerrahi işleme uygunluğunu belirlemek amacıyla nörolog ve beyin cerrahlarının birlikte çalıştığı multidisipliner bir ekip tarafından değerlendirme yapılır. Epilepsi cerrahisi ile nöbet odaklarının yerine ve durumuna bağlı olarak farklı prosedürler uygulanır ve nöbetlerin azalması amaçlanır. Bu çalışmada nöbetlerden önce bir belirteç olabilecek olan yüksek frekans osilasyonlarının varlığı araştırılmıştır. Elektroensefalogram verisi; nöbet öncesi, nöbet sırası ve nöbet sonrası olarak üç ayrı sınıfa ayrılmış, sinyal işleme teknikleri kullanılarak öznitelikleri çıkartılmış, çıkarılan bu istatistiksel ve yapısal özniteliklere göre sınıflandırması yapılmıştır. Ayrıca her bir sınıf için önemli olduğu düşünülen 14 kanal belirlenmiş ve bu kanallara göre sınıflandırma çalışması yapılmıştır. HFO varlıkları belirlendikten sonra, HFO tabanlı özniteliklere göre de sınıflandırma işlemi yapılmıştır. Sınıflandırma amacıyla Bayes, K-En Yakın Komşu, Destek Vektör Makineleri, Çok Katlı Algılayıcı, Rastgele Orman Sınıflandırıcısı kullanılmıştır. Sınıflandırma sonuçlarında rastgele orman sınıflandırıcısı ile istatistiksel ve yapısal öznitelikler için %83, HFO tabanlı öznitelikler için %77,43 ve kanallar için %77,97 doğruluk oranları elde edilmiştir.
Bilgisayarlı tomografi görüntlerinden derin öğrenme tabanlı karaciğer segmentasyonu
Karaciğer kaynaklı hastalıklara bağlı yüksek ölüm oranlarının mevcut olduğu günümüzde, tıbbi görüntüleme yöntemleriyle kısa sürede doğru teşhisin konulması büyük önem taşır. Her ne kadar bu görevi radyologlar ve onkologlar gerçekleştirmekte olsa da teşhisin bilgisayar destekli tanı yöntemleri ile otomatikleştirilmesi, teşhis süresinin kısalması, uzmanlar arası yorum farklarının önlenmesi ve tedavi aşamasına hızlı geçiş açısından ciddi fayda sağlayacaktır. Bu nedenle tıbbi görüntüleme yöntemlerinden biri olan bilgisayarlı tomografi (BT) görüntüleri üzerinde çalışmalar hız kazanmakta ve özellikle abdominal(karın) BT görüntülerindeki karaciğeri diğer organlardan ayırmak (segmente etmek), ikinci aşamada karaciğerdeki lezyon tespiti ve sınıflandırılmasına zemin hazırlamaktadır. BT görüntülerinin segmentasyonu için birçok yöntem bulunmakla beraber bugün kullanımı yaygınlaşan evrişimli sinir ağı (CNN) yapıları, diğer yöntemleri yüksek başarı oranlarıyla geride bırakmaktadır. CNN yapılarının eğitilerek verilen görevi yerine getirmesi çok büyük veri setleri ve yüksek performansta donanım ve yazılım gerektirmektedir. Bu nedenle transfer öğrenme denilen önceden eğitilmiş CNN yapılarını kullanılacak görev için tekrar daha küçük boyuttaki veri setiyle eğitme yöntemi, büyük veri setleriyle olan eğitim sürelerinin uzunluğunu, öğrenmenin gerçekleşeceği kaynak yazılım ve donanımların maddi yükünü azaltacaktır. Bu tez çalışmasında, transfer öğrenme yöntemi kullanılarak ImageNet adlı geniş veri setiyle önceden eğitilmiş CNN yapıları olan VGG16, VGG19, RESNET18, RESNET50 modellerinin LiTS2017 abdominal BT görüntülerini içeren açık veri setiyle tekrar eğitilerek görüntü kesitlerindeki karaciğeri segmente etmedeki performansları karşılaştırılacaktır.
Derin öğrenme yöntemleri ile yüz görüntülerinden kronik ve genetik hastalıkların ön tanısı
Kronik hastalıklar genellikle uzun süre tedavi ya da bakım gerektiren, genetik hastalıklar ise genler aracılığı ile nesilden nesile aktarılabilen sağlık sorunlarıdır. Hemen her hastalık bireylerin yaşam kalitesini olumsuz etkilemektedir. Son yıllarda yüz özelliklerinin, yüz de değişen ve gelişen anomalilerin analizi ile hastalık teşhisi için derin öğrenme algoritmalarının etkin bir şekilde kullanılması giderek önem kazanmaktadır. Bu çalışmada derin öğrenme yöntemleri ile yüz görüntülerinden anomali tespiti ve hastalık sınıflandırma başarısı araştırılmıştır. Klasik ESA'lara kıyasla geliştirilen modellerin performansını değerlendiren bu çalışma, farklı modellerin başarılarının karşılaştırılması amaçlanmıştır. . Transfer öğrenme yöntemleri ve farklı teknikler ile her modelin hem kendi içinde ham de diğer modeller ile performans başarıları karşılaştırılmıştır. Klasik bir ESA mimarisi ve ViT modeli ile ikili hastalık başarı ve performansı karşılaştırılmıştır. ESA mimarilerinden (Resnet50 ve InceptionV3), yeni mimari modellerden görsel dönüştürücüler (ViT) ve EfficientFormer ile çoklu hastalık sınıflandırması yapılmıştır. Çalışmada dört hastalık grubu ve bir kontrol grubu olarak belirlediğimiz tüm hastalıkların ikili sınıflandırılması yapılmış ve en yüksek performans ViT modeli ile elde edilmiştir.Derin öğrenme uygulamaları, özellikle ViT modelinin küçük veri setleriyle yüz teşhisinde gösterdiği yüksek başarı oranı, yeni geliştirilen modellerin hızlı ve hibrit yaklaşımlara ihtiyaç duymaksızın etkin sonuçlar üretme yeteneğiyle dikkat çekmektedir. Bu gelişmeler, medikal alanda hekimlerin hasta yükünü azaltmanın yanı sıra insani hataların önlenmesine de önemli katkılar sağlayarak, bu teknolojilerin güvenle kullanılabileceğini göstermektedir. Ayrıca, girişimsel ve radyolojik yöntemlere ihtiyaç duyulmadan bazı hastalıkların erken tanısının konulabilmesi, sağlık sistemlerinin verimliliğini artırarak ülkelerin sağlık harcamalarında önemli tasarruflar sağlayabilecektir. Bu durum hem hasta bakım maliyetlerini azaltacak hem de kaynakların daha etkin kullanılmasına olanak tanıyacaktır.
Bilgisayarlı tomografi görüntüleme modellemesi için gate yazılımı kullanarak Monte Carlo simülasyonu
Bilgisayarlı tomografi sistemi ve Catphan phantomunun (CTP404 modeli) geliştirilmesi için Monte Carlo (MC) simülasyon çerçevesi, GATE (Tomografik Emisyon için Geant4 Uygulaması) tarafından sağlanmıştır. Proje kapsamında, biri yüksek enerjili radyasyon, diğeri ise düşük enerjili radyasyon kullanan iki simülasyon süreci çalıştırılmıştır. Oluşturulan çıktı görüntüleri detaylı bir analizden geçirilmiş ve iki simülasyon sonucu arasındaki farkı temsil etmiştir. Bu, görüntü iyileştirme teknikleri, enerji dozu ve phantom içindeki malzemeler için Hounsfield Birimleri (HU) hesaplamalarını içermektedir. Simülasyon sonuçlarının doğruluğunu doğrulamak amacıyla deneysel kurulum tekrarlanmış, PET/CT Siemens Biograph Horizon kullanılarak gerçek CT taramaları elde edilmiş ve sonuçta elde edilen DICOM görüntüleri analiz edilmiştir. MC simülasyonlarının gerçek CT görüntüleme koşullarını kopyalamadaki doğruluğunu değerlendirmek için karşılaştırmalı bir analiz yapılmıştır. Sonuçlar, simüle edilmiş ve gerçek görüntüler arasındaki benzerliği doğrulamıştır. Çalışma, CT görüntüleme simülasyonları için MC yöntemlerinin etkinliğini göstererek, tıbbi görüntüleme araştırma ve geliştirme çalışmalarını ilerletmek için doğru bir araç sağlamaktadır.
Mathematical model-based clinical decision support system algorithm design study that can support the diagnosis of celiac disease
Background: Celiac disease (CD) is one of autoimmune disorder. It is caused by consumption of gluten which is a protein found in barley, rye and wheat. Individuals with CD experience an immunity response due to damage to the lining of their small intestines after consuming gluten, causing them to experience a variety of sign and symptoms also potential long-term complications. Currently definitive diagnosis of CD is typically made by small bowel biopsy, which determines the extent of intestinal damage. Diagnosing celiac disease is difficult because some of its signs and symptoms resemble with other autoimmune diseases. Early diagnosis prevents severe progression of the disease by preventing rapid increase in intestinal permeability. In order to overcome the difficulties experienced in the diagnosis of CD and to enable patients to reach a specialist as soon as possible, it is becoming increasingly important to develop systems that can support diagnosis, with the help of developing technology. While research focuses on intestinal epithelium deformation in the field of video capsule image processing, the effect of gluten sensitivity on facial appearance is still an open research topic in the literature. When looking at the development of celiac disease in the body, it is associated with diseases that impact the skin through intestinal inflammation, immune system problems and microbiome dysbiosis. In addition, CD causes changes in skin structure and facial features because it affects the gastro-intestinal system and can cause malabsorption of nutrients. This holds promise for supporting the diagnosis of CD through face image classification by detecting observable facial features or some patterns. Although there are studies in the literature that aim to support early diagnosis using data on disease history and symptoms, there are no hybrid models that use facial images. Based on this, this thesis study was planned under two different research questions. The first research question focused on the changes on the CD face images and asked, "How effective are the transfer learning models VGG16 and MobileNetV2 in classification CD facial images to aid in the diagnosis, and do they support the early diagnosis of CD with significant performance?" It is structured in the format. The second research question asked: "Can CD Marsh (0-4) levels be determined with machine learning models using routine blood test results and demographic data performed in primary health centers?" focused on and compared the performance of deep learning models (PyTorch) and traditional machine learning algorithms. With both research questions, it is aimed to present a new perspective on the literature. Since such a data set does not currently exist, data was collected from patients diagnosed with CD followed in the gastroenterology clinic at Van Training and Research Hospital, Turkey, within the scope of ethical permission 2022/09-02. Purpose: It is obvious that it is important to examine the feasibility of designing a system that aims to ensure early diagnosis of CD, which has similar symptoms to many autoimmune diseases, and to ensure that patients are referred to a specialist as soon as possible, and to examine its effective use in the clinic. Based on this, this thesis first aims to question the ability of transfer learning with two pretrained models to classify the database containing facial images to show meaningful performance in the early diagnosis of CD. Secondly, it is aimed to prevent delays in referring celiac disease to a specialist in primary health care units due to its similar symptomatic features with other diseases. For this purpose, it is aimed to analyze a method that will support the diagnosis of the disease and the determination of Marsh levels by classifying routine blood test and demographic data with Decision Tree, Random Forest, Gradient Boosting, Naive Bayes and deep learning (Pytorch) algorithms. It is also aimed to analyze a method that will support the determination of the celiac level severity. Method: In the thesis study, two different data sets were used and interpreted by applying two methods suitable for the purpose. For the first research question, facial images of celiac patients were classified using the transfer learning method. Two different pre-trained models (VGG16 and MobileNetV2) were used. Then model with the highest classification performance was selected. For the second research question, with the aim of determining intestinal atrophy (marsh level) in celiac patients, clinical signs and symptoms were classified with deep learning (Pytorch) and traditional machine learning algorithms, and the model with the highest accuracy rate was determined. Models with high performance criteria in both stages were selected for the development of models in which hybrid data sets could be used in the future. In the dataset containing face images (DS_Face), there was a CD diagnosis and an equal number of control groups. There are 200 adult facial images. While 70% of the images diagnosed with CD in the DS_Face dataset is female and 30% are male, the distribution of the control group is 60% female and 40% male. Of the patients in the facial images diagnosed with CD, 28 were newly diagnosed and 72 were previously diagnosed. Of the previously diagnosed patients, 25 did not comply with the gluten-free diet. 47 of them are partially adhered to the diet. The second data set (DS_Marsh) was created to determine the marsh level based on routine blood test and demographic information; It consists of patient history, demographic information and blood test results of 182 people. DS_Marsh dataset; It has a distribution of 132 female and 50 male patients. In this data set, the distribution of compliance with the gluten-free diet is as follows: 72 people who do not comply and 106 people who partially comply. Results: In the DS_Face dataset, an accuracy rate of 73% was reached in the classifying of facial images of non-compliant, partially adherent, newly diagnosed patients and the control group using the pre-trained VGG16 model. Precision, F1 and recall score values were found to be 0.54, 0.52 and 0.56, respectively. Moreover, the pre-trained MobileNet.v2 model used by the Medipipe model marker had a test loss of approximately 0.44 and an accuracy rate of 85% on the test dataset with 0.80 precision, 0.81 recall and 0.80 F1 scores. As a result, in the DS_Face dataset, the MobileNet.v2 model showed a stronger performance in CD diagnosis compared to the VGG16 model. On the DS_Marsh dataset, the PyTorch model performed with 80% accuracy in determining Marsh levels. Recall, precision, and F1 scores were measured as 0.80, 0.81 and 0.70, respectively. Recall, precision, and F1 cores were achieved as 1.0, 1.0, 1.0 with the Decision Tree, Random Forest and Gradient Boosting classifiers, each of which showed full performance, 100% accuracy rate and classification capacity. The recall, precision, and F1 scores of the Naive Bayes classifier, which shows a 55% accuracy rate compared to others, are listed as 0.44, 0.67 and 0.53, respectively. Conclusion: The performances of the VGG16 Model and Mobilenet.V2 Model were compared in the DS_Face data set created to examine the first research question. Model VGG16 correctly classified almost one third of the test images. Mobilenet.V2 Model classified 85% of the test images correctly. The VGG16 model's classification performance was lower than the MobilenetV2 model due to its architectural structure and some other features mentioned below. VGG16 is a deeper network with more parameters due to its model architecture and more suitable for big dataset. MobileNetV2, on the other hand, is designed to be more efficient on small data sets with fewer parameters. This caused MobilenetV2 to perform better on the DS_Face dataset. Additionally, since MobileNetV2 was used with the Mediapipe model marker, the mediapipe model marker provided additional preprocessing and feature extraction that improved the performance of the model and contributed to higher accuracy. And finally, VGG16, a more complex model, may have overfitted, especially if the dataset is not large enough. In conclusion, the performance of facial classification models such as Mobilenet.V2 on the changes that occur on the skin and facial features of patients newly diagnosed with CD and previously diagnosed but not complying with the gluten diet provides concrete findings regarding the development of decision support models capable of supporting early diagnosis in these patients. The models used for classification in the DS_Marsh dataset created to examine the second research question, respectively, showed over 80% accuracy in Pytorch, while Decision Tree, Random Forest and Gradient Boosting showed 100% performance. System designs that will allow these routine blood test findings and demographic information to be used even in primary health care units are promising due to their contribution to the quality of life of patients, the patient load in the healthcare system, and the economy. This study, planned with two research questions to improve the patient' life quality and reduce the burden of healthcare services and expenses in the economy, emphasizes the importance of data-based methods in medical diagnoses to improve decision-making and benefit patient outcomes. In future studies, it has been concluded that the use of the Mediapipe model marker with pre-trained MobileNetV2 model and Decision Tree, Random Forest and Gradient Boosting classifiers will provide high performance in hybrid system designs that will accelerate referral to a specialist for early diagnosis by using both facial images, routine blood findings and demographic information. Keywords: Diagnosis of Celiac Disease, Face Image classification, Deep and machine learning, Transfer learning, Mediapipe (MobileNetV2),and VGG16
Surgical percutaneous guide-needle's micro electronic guider
To cut a long story short, the developed prototype could be classified as easy to use, with less radiation exposure, low cost, accurate, less time-consuming, less reliance on human individual skills, and single puncture attempt guiding device. The whole of those advantages are obtained from the results of the performed phantom study. According to those Promising initial results of phantom experiments, it could be declared that the first two stages of our working plan are done; it is necessary to move forward to perform the remaining stages. Experiments on laboratory animals and other needed invivo experiments to get more actual and detailed results about procedure time, radiation exposure dose, and accuracy in comparison to other sensor-based techniques, robotic-based techniques, and freehand conventional methods. It is also recommended to use original sensors instead of third-party used sensors to get more accurate results. In addition to modifying the mobile application, wireless connection, size, and useable materials to make it a more applicable and ergonomic device. Also, another positioning sensor, such as GPS, could be added to get more detailed results about the depth that will be an added value to the designed needle orientation system. In addition to integrated whole the newly designed system in a micro-scale device.
İmplantlarda kullanılan metal malzemelerin farklı yaşlandırma teknikleri altında incelenmesi
Kemik ve eklem bozuklukları dünya çapında milyonlarca kişiyi doğrudan etkileyen önemli bir sağlık sorunudur. Bu durum cerrahi müdahaleleri ve biyomedikal implantlara duyulan ihtiyacı artırmıştır. İmplantların yaklaşık %70-80'i metalik biyomalzemelerden imal edilmektedir. Gelişen teknoloji ve yöntemler, ortopedik uygulamalardaki araştırmaların metalik biyomalzemelerin geliştirilmesini sağlamıştır. Metalik malzemelerin performanslarını artırmak için seramik takviyeler metal matris kompozitlere dahil edilmektedir. Bu çalışmada, biyomedikal implant uygulamaları için geleneksel toz metalurjisi yöntemi kullanılarak B4C katkılı CoCrMo, Ti ve 17-4 PH matrisli kompozitler üretilmiştir. Farklı oranlardaki B4C katkısının mekanik özellikler ve korozyon direncine olan etkisi araştırılmıştır. Kompozitlerin mikroyapıları taramalı elektron mikroskobu kullanılarak incelenmiştir. Mekanik ve korozyon performansları ise sertlik, aşınma, ultrasonik elastisite modülü ölçümleri, elektriksel iletkenlik ve elektrokimyasal korozyon testleri (Potansiyodinamik Polarizasyon ve Elektrokimyasal Empedans Spektroskopisi) ile değerlendirilmiştir. Performans ölçümlerinin tutarlılığı ve güvenilirliği Weibull Analizi ile doğrulanmıştır. Bulgular, B4C ilavesinin biyomedikal alaşımların özelliklerini değiştirebileceğini ve B4C takviyeli biyomedikal implantlar için mühendislik avantajları sunabileceğini göstermiştir. B4C katkısı CoCrMo, Ti ve 17-4 PH alaşımlarının sertlik, elastisite modülü ve korozyon hızı değerlerini artırırken aşınma yüzdesi, iletkenlik ve yüzey oksit film korozyon dirençlerini düşürmüştür. CoCrMo-5B4C, Ti-5B4C ve 17-4PH-6B4C kompozitleri gösterdikleri üstün özellikleriyle biyomedikal implant uygulamalarında kullanılabilecek kompozitler olarak öne çıkmıştır. İmplant uygulamaları açısından B4C katkılı Ti kompozitleri, B4C katkılı CoCrMo ve 17-4 PH kompozitlerine göre daha üstün sonuçlar ortaya koymuştur. Ti-5B4C, yüksek aşınma direnci, düşük korozyon oranı ve insan kemiğine yaklaşan elastisite modülü değerleriyle en dengeli kompozit olarak belirlenmiştir. Bu çalışma ile Ti-B4C kompozitlerinin, gelişmiş implant teknolojilerinde, ortopedik ve diş implantlarında, omurga sabitleme cihazlarında ve diğer yük taşıyan biyomedikal uygulamalarda kullanımının uygun olduğu yapılan deneyler ile gösterilmiştir.
Medikal uygulamalar için tulyum laser sistemi tasarimi ve geliştirilmesi
The Thulium (Tm:YAP) laser is suitable for medical applications due to strongabsorption in water. In this thesis, a computer controlled Tm:YAP laser system witha power output up to 1 W and emission wavelength of 1980 nm were established.Once the laser system was stabilized, its output power, spot size, and light intensitymeasurements were performed. The thermal effects of the laser system on brain, liver,heart, and kidney tissues were macroscopically analyzed. The ablation efficiency ofthe laser system was experimentally tested on ex-vivo brain tissue. The maximumablation efficiency was obtained at a power level of 200 mW with a duration of 10seconds (69 W/cm2). The fluence effect for skin ablation was analyzed by histology onWistar rat skin tissues during a 4-day healing period. Temperature measurements bythermal camera and thermocouples were investigated to see the temperature effect ofCW and modulated mode of the Tm:YAP laser under skin and on skin surface. Thetemperature increase was faster and the temperature decrease was found slower in CWmode. The main aim of the study is to explore the welding capabilities of Tm:YAPlaser in modulated and CW modes of operation on Wistar rat skin during 21-dayhealing period. Full-thickness incisions were welded at 100 mW and 5 s (34.6 W/cm2).The results were compared to conventional suture techniques by both histology andtensile strength measurements. After day 4, full closure was obtained for both lasermodes, whereas, full closure was not observed till day 4 in suture group. In tensilestrength analysis, tensile forces found for both modulated and CW modes of operationwere significantly higher than the tensile force values found for conventional suturetechnique. Tm:YAP laser tissue welding possessed significantly stronger closure thanconventional suture technique.
Tomosentezin diş x-ray görüntülerine uygulanmasi
Digital tomosynthesis is a method of reconstructing any number oftomographic planes, by using a set of limited angle projections,acquired as the X-ray source moves in an arc around the object.In some cases the quality of the reconstructed planes is affectedby structured noise, due to blur from planes other than thefulcrum plane. The purpose of this project is to implement theMultiple Projection Algorithm along with the out-of-plane blurremoval method that could remove the noise from the reconstructedplanes and improve their quality.For this purpose, one software phantom was used to evaluate theparameters that affect the image quality. Different groups werecreated with varying arc lenghts and projection counts . Theseimages were reconstructed with the Multiple ProjectionsReconstruction Algorithm (MPA) written in MATLAB.Blur removal method was implemented to increase image quality.Image quality was assessed by evaluation of the reconstructedplanes in terms of both visual assessment and SSIM analysis. TheMPA followed by the proposed noise removal algorithm resulted inless noisy tomosynthesis images.The algorithm was also tested with dental phantom data set. Theresults showed that the tomosynthesis image reconstruction is apromising and a low cost method to evaluate digital dental x-rayswithout excess radiation to the patient.
Development of an acqusition and image enhancement platform for digital dental imaging
With technologıcal developments in X-ray imaging, digital systems started to replace analog systems. Principle advantages of digital X-ray imaging are; it has lower cost (in the long run), is ready to be processed with a computer, could acquire 3D images and has better imaging quality even at low radiation doses. Usage of digital technology in dental imaging is also increasing rapidly. Although, dental dose levels are significantly less than other X-ray imaging techniques, its cumulative effects could be harmful in the long term. Main aim of this thesis is to set up a digital dental imaging system and to implement its image processing software. A digital dental Xray system consists of three of the shelf components; a digital intraoral X-ray sensor, a portable X-ray tube and a computer. The new digital system and its acqusition software are tested on phantom and cadaver tests. Furthermore, effects of several image enhancement techniques on low dose dental radiographic images are examined.
1940-nm tulyum fiber lazeri ile seramik braketlerin çikarilmasi
The aim of the study was to determine the proper laser paramaters for 1940-nm Thulium Fiber Laser for ceramic bracket removing. In order to assess the effectiveness of 1940-nm Thulium Fiber Laser in orthodontic ceramic bracket debonding , polycrystalline ceramic brackets were bonded to mandibular bovine teeth with adhesive agent . The samples were divided into 9 different groups , 11 in each , due to applied laser power and laser duration, debonding method used . In addition, there was a control group that had no laser application . The debonding process was performed by 1940-nm Thulium Fiber Laser in CW (continous mode ) . The efficency of the laser was investigated together with the required debonding forces and intrapulpal temperature changes . In this study, keeping intrapulpal temperature changes below the threshold value that is accepted 5.5 °C must be accepted as a must. In most of the lasing groups , the increase in intrapulpal temperature changes were observed almost below the threshold value 5.5 °C . The findings revealed that 1940-nm Thulium Fiber Laser irradiation could reduce the needed debonding force or SBS (shear bond strength ) values significantly compared to control group . Irradiation of the specimens by 1940-nm Thulium Fiber Laser caused almost more than 50 % reduction in the needed debonding force when compared to the control group. Different application methods : non-scanning and scanning were studied to assess the effects of the distinct configurations. Scanning method was tried to reduce the intrapulpal temperature rise during laser irradiation but in this study side effects of this method were faced . Different application methods did not create any remarkable differences. In the lasing groups with the energies 25 J and more , adhesive remnant has not been observed on the enamel surfaces.
Laser etching of enamel for bonding orthodontic bracket
The aim of this study is to determine the optimum laser parameters to provide the maximum bonding strength with reference to conventional bonding technique for orthodontic braces. 1940 nm Thulium Fiber Laser was used in pulse mode and in two different parameters for enamel etching procedure. In addition, there is a control group which had conventional acid etching technique.Laser etching procedure was carried out by two different approaches: Lasing without cooling and with cooling. For the first approach, according to the whitening of the enamel initiation, application time of laser irradiation was defined for each laser parameters.For the second approach, in order to prevent damage on alive tissue, water spray and air pressure cooling was applied during lasing to limit pulp temperature to maximum 5,5 °C which is the critical temperature.After the bonding of ceramic braces, they were debonded from the enamel surface using mechanical test machine. When the bonding strength of the braces were analyzed, it was observed that the mean bonding strength of both the etching without cooling group and etching with cooling group are significantly different from acid etched group (p<0.05, student t-test). SEM evaluations of etched surface with laser showed that surface morphologies were not similar with acid etching group.
Mechanics of spastic muscle and effects of treatment techniques: Assessments with intra-operative and animal experiments
Present thesis is focused on mechanics of spastic human muscles and the effects of widely used treatment methods in the context of the determinant role of epimuscular myofascial force transmission (EMFT). A novel intra-operative method was developed to measure human Gracilis (GRA) muscle isometric forces with respect to knee angle. In healthy subjects, GRA was shown to have very large operational length range. For spastic cerebral palsy patients on the other hand, GRA muscle did not show ?abnormal? mechanical characteristics: (i) Length range was not narrowed and (ii) high flexion forces were not available. Such abnormality occurred if its antagonist vastus medialis is activated simultaneously. Therefore, EMFT mechanism through inter-antagonistic interaction was suggested to determine human muscle characteristics in spasticity. Effects of treatment methods were investigated in animal experiments: (1) Muscle lengthening surgery was shown to affect (i) proximal and distal sides differentially and (ii) non-operated neighboring muscle as well. (2) Botulinum Toxin Type-A (BTX-A) administration was shown to change the mechanics of not only the injected but also non-injected muscles in conditions close to in vivo. Additional to active force reductions (i) the narrowed length range of force exertion and (ii) pronounced passive force increase contradictory to the aim were shown. EMFT mechanism was concluded to be determinant for the treatment methods as well.
Similarity and consistency analysis of functional connectivity maps
Functional connectivity (FC) refers to statistical relations of activations of dis- tinct neuronal populations without any reference to causal or anatomic connections. One of the problems in FC studies is, to interpret the resultant FC matrix and only few studies in the literature have focused on consistency and temporal variability of FC networks. In this study functional near infrared spectroscopy (fNIRS) signals were recorded from prefrontal cortex (PFC) of 12 healthy subjects during a stroop test. Mutual information was used as a metric to determine functional connectivity between PFC regions. 2D correlation based similarity measure was used as a method to analyze within-subject and inter-subject consistency of FC maps, and how they change in time. How functional integration changes during to stroop test session was also investigated, using a graph-theoretical metric "global efficiency". It was found that within-subject consistency (0.61 ± 0.09) is significantly higher (p < 0.001) than inter-subject con- sistency (0.28 ± 0.13). Within-subject consistency was not found to be task-specific. Results also revealed that there is a gradual change in FC patterns during stroop ses- sion for congruent and neutral tasks, where there is no such trend in the presence of an interference effect (incongruent task). Finally it was found that, the changes in global efficiency of the FC networks during the stroop test session exhibit a parallel trend. One of the results of these findings is that it is feasible to study consistency, inter- subject variability and temporal changes in functional connectivity during a cognitive task with fNIRS.
Auditory brain response detection using a portable EEG headset
In general terms, evoked potentials are electrical signals generated by the nervous system in response to a stimulus. Auditory evoked potentials (AEPs) are generated in response to an acoustic stimulus. Measuring the electrical response of auditory system gives many information about the status of individuals hearing. Auditory brain response (ABR) is an AEP and can be detected using EEG technology and signal processing techniques. In this thesis, an ABR detection system has been implemented. Experiment procedure was designed using auditory oddball paradigm. An acoustic stimulus has been sent to the subject and a marker about the stimulus has been sent to the recording software simultaneously while recording EEG. A low cost, wireless EEG headset was used to record EEG data under auditory stimulus from 13 subjects. Raw EEG data has been processed by using epoch extraction, event related potential (ERP) averaging, and independent component analysis (ICA) methods. Some features were extracted about the auditory stimulus. Then the extracted features were used to classify the data to understand if hearing has occurred or not under given stimulation. Results of the experiments showed that the implemented ABR detection system detected the sound and silence stimulation with 85% accuracy.
Effects of mechanical and temporal parameters on tactile psychophysical responses
Tactile feedback is becoming more important in clinical devices and engineering. Therefore, studies on basic sensory processing in the somatosensory system are essential. In this thesis, the mechanical and temporal parameters affecting the absolute tactile detection threshold of human Pacinian (P) channel were investigated. Temporal summation in P channel was found to be independent of stimulus frequency and the experimental results did not t the classical model of temporal summation. The model needs to be modeled to show the U-shaped Pacinian channel behavior. Additionally, the spatial summation property of the P channel was demonstrated on fingertip at three different contact locations and at three contactor sizes. The effects of skin mechanics on psychophysical thresholds of the P channel were studied by measuring mechanical impedance. A significant correlation was found between the thresholds and the dynamic modulus of the skin. Conventionally, somatosensory evoked potentials (SEPs) are measured on the scalp by applying electrically stimulating the peripheral nerves in the clinical setting. Here, SEPs were represented by different types of wavelet functions, which can be used in data compression. Non invasive recordings of scalp potentials were also investigated by applying strong mechanical stimulation on the fingertip. However, time-frequency analysis did not show much useful information about stimulus properties, which would be useful in understanding basic somatosensory processes. The results of this thesis may be useful in various fields such as haptics, robotics, prostheses, dermatology, and cosmetics. Specifically, spatial and temporal summation should be incorporated in the high-frequency vibrotactile feedback in prosthetic arms.
Sensitivity and specificity of the multi-channel CW-fNIRS for medical purposes
In last decades, optical imaging technology has been rapidly developed and become much popular for scientific researches. Its safe, non-invasive and portable design easily integrates fNIRS to different research areas and makes it much preferable especially for brain researchers. Since fNIRS sensitively scan neurobiological changes in the PFC during neurological and psychiatric disorders, many studies benefits from the convenience of fNIRS to extend the understanding about these disorders. This study aims to present reflections of different PFC related disorders which are schizophrenia, migraine and attention deficit & hyperactivity disorder (ADHD) on fNIRS measurements and to reveal their differences from control group via advanced signal processing application. For this purpose, collected fNIRS measurements during cognitive task were preprocessed to remove artifacts and prepared for further analysis. Pre-processed signal sets were used to create feature set for each subject with the assistance of independent component analysis. Then these feature sets were investigated by clustering algorithm to observe discrimination of experimental groups and performance of the system was reported. In some cases, proposed system presents success rates up to 82% for migraine group, 92% for schzophrenia group and 95% ADHD group.
Evde tedavi için mobil bir idrar analiz sistemi
Urinalysis is a remarkable diagnostic technique and an essential part of physical examination used frequently in kidney and urinary tract diseases. Urine reagent strips which are widely used in urinalysis are impregnated with a number of colored reagent blocks or pads separated from each other by narrow bands. The reagents in each block react with specific components of urine in such a way that the block changes color if the component is present, and the color change produced is proportional to the concentration of the component being tested for. Recent analysis of test strips is perfomed via refractometric devices of the corresponding test strips. In this thesis, a mobile urine strip analyzer called BUSA which can be controlled via both GUIs of MATLAB and Android operation system was designed by using Parallax's color sensor, TCS3200-DB. The fundemental idea behind this design was to form a database which included color data of control solutions of CombiScan 500, 40 patients analyzed by CombiScan 500 in Yeditepe University Hospital and prepared solutions of known pH and glucose amount. 15 patients analyzed by CombiScan 500 were compared to BUSA. Specificity of the results of the comparison for bilirubin, urobilinogen, glucose, protein, blood, nitrite and leukocyte was 1 and for ketone was 0.933. Sensitivty of the results of the comparison for glucose, protein and blood was 1, 0.2 and 1 respectively. pH and specific gravity were analyzed via Blant Altman method which means and standard deviations were 0.133, 0.5156 and 0.0017, 0.0059 respectively. In conclusion, BUSA is succesful at measuring pH and specific gravity of urine and negativeness of bilirubin, urobilinogen, ketone, glucose, protein, blood, nitrite and leukocytes. In addition, BUSA is successful at detecting positiveness of glucose and blood, except protein.
Detection and assessment of cardiac patent foramen ovale
Arterial microemboli are gas filled structures which are formed in intravascular and extravascular environment. They are characterized in spherical or ellipsoid forms which would cause diseases in a broad range from stroke to migraine. Cardiac Patent Foramen Ovale (CPFO) is considered as a congenital defect through both atria as a permeable shunt with a prevalence frequency of 25-30\% in asymptomatic population. Decompression Sickness (DCS) is a fatal disease during hyperbaric and hypobaric activities due to unestimated effects of microemboli. CPFO aperture combined with DCS is a clinical problem where bubble analysis is managed manually by special and trained cardiologists. Even this problem was considered recently by different groups within sound, image and video forms, an automated tool is considered as a challenge due to algorithmic and mechanical constraints related to noise, monitoring and probe localization. We aimed to develop a spatio-temporal methodology for clinicians which would not carry out long lasting videos where the number and the size of microemboli alter dynamically. In this thesis, developed methods are classified into two groups; qualitative and quantitative assessments. These approaches were tested initially in a simulation environment with artificial microemboli. Furthermore, microemboli and CPFO were monitored in subjects through videos using two modalities: contrast Trans Esophageal Echocardiography and contrast Trans Thoracic Echocardiography. Even our procedures would get accurate findings within videos, it is important to note that low resolution, high speckle noise, shadowing would introduce false alarms. Consequently, we conclude that this routine would standardize CPFO analysis and offer better adjustment for bubble detection.
An fmri based method for characterizing superficial layer contamination in fnirs signals
ABSTRACT AN FMRI BASED METHOD FOR CHARACTERIZING SUPERFICIAL LAYER CONTAMINATION IN FNIRS SIGNALS Functional near infrared spectroscopy (fNIRS) is a method for monitoring cerebral hemodynamics with a wide range of clinical applications. fNIRS signals are contaminated with systemic physiological interferences from both the brain and superficial tissues, resulting in a poor estimation of the task related neuronal activation. In this study, we introduce an extended superficial signal regression (ESSR) method for cancelling physiology-based systemic interference in fNIRS signals. We apply and validate our method on the optically weighted BOLD signals, which are obtained by projecting the fMRI image onto optical measurement space by use of the optical forward problem. The performance of ESSR method in removing physiological artifacts is compared to i) a global signal regression (GSR) method and ii) a superficial signal regression (SSR) method. The retrieved signals from each method are compared with the neural signals that represent the "ground truth" brain activation cleaned from cerebral systemic fluctuations. We report significant improvements in the recovery of task induced neural activation with the ESSR method when compared to the other two methods with higher spatial localization, lower inter-trial variability, and higher contrast-to-noise (CNR) improvement. Our findings suggest that, during a cognitive task i) superficial scalp contribution to fNIRS signals varies significantly among different regions on the forehead and ii) using an average scalp measurement together with a local measure of superficial hemodynamics better accounts for the total systemic interference. We conclude that maximizing the overlap between the optical pathlength of superficial and deeper penetration measurements is of crucial importance for accurate recovery of the evoked hemodynamic response in fNIRS recordings. Keywords: Hemodynamic response, systemic interference, functional near infrared spectroscopy, magnetic resonance imaging, physiological artifact removal.
1940 nm tulyum fiber laserin oral doku için cerrahi araç olarak in vitro incelenmesi
Lasers of diff erent wavelengths are being used in oral surgery for making incisions and excisions with minimal bleeding and pain. Thulium fi bre laser, with its 1940 nm emission, is well absorbed by water, making it a promising tool for oral soft tissue surgery. This study was conducted to investigate the potential of Tm: fi bre laser as an incisional and excisional oral surgical tool. Both 1940 nm Tm: fi bre and 980 nm diode laser were used on ovine tongues in this study for comparative purposes. Both lasers were applied in contact to the tissue, which was completely submerged in saline solution, via a 600 um fibre. The incisions were made by moving the fi bre tip manually at diff erent speeds (0.5, 0.75 and 1 mm/s) and with making single, three or five passes, using three diff erent power settings (2.5,3 and 3.5W for Tm:fi bre and 12,14 and 16W for diode laser). The samples were stained with H&E for microscopic evaluation of depth of ablation and extent of coagulation, and ablation efficiencies were calculated. Deeper ablations, as well as larger coagulations were obtained with both lasers by using higher power settings. However, making more passes at constant power yielded deeper ablations without signi cantly larger coagulation zones. Furthermore, increasing the speed caused shallower ablation and narrowed coagulation zones. Microscopically, a narrow vacuolization and a large coagulation zone were observed for 1940 nm Tm: fibre laser, whereas the coagulation zone produced by 980 nm diode laser was larger and no vacuolization was evident.
Network security vulnerabilities and personal privacy issues in healthcare information systems: A case study in a private hospital
Healthcare industry has become widely dependent on information technology and internet; as it moves from paper to electronic records. Despite the benefits of electronic system, good quality may not be totally achieved unless its risks to security are mitigated. Working in collaboration with a 150 bed private hospital in Turkey; this study aims to present a secure healthcare network infrastructure while presenting the security vulnerabilities in the current hospital information systems. The regulation criteria in Turkey and counterparts in USA and EU are compared according to their privacy approach and a list of items for common security controls from different industries is proposed as a best practice. The study shows that the hospital is not compliant with known healthcare standards like HIPAA or ISO 80001. Management's attitude against privacy and security shows that the responsibility is totally to IT and Biomedical Engineering Departments. Since explaining the threats and corresponding vulnerabilities in the system may cause the hospital be prone to cyber-attacks, the name of the hospital is secluded. As hospitals are adopting electronic transactions, consideration must be given to protect public electronic health records in terms of personal privacy aspects. Healthcare industry in Turkey should benefit from best practices in other industries and applications in other countries. This study can lead the pathway for policy makers in healthcare organizations and regulation authorities to implement a more secure environment for every citizen.
Time-frequency and time-scale analysis of non-stationary biomedical signals
Fourier transform (FT), which assumes that the analyzed signal is stationary, is not entirely appropriate to analyze biomedical signals since they are in non-stationary nature. To overcome this drawback, FT can be applied over short-windows of time within which the signal can be considered to be stationary. However, this short-time Fourier transform is hampered with a serious time-frequency (TF) trade-off dilemma. Recently, a number of different TF analysis techniques has been developed that provide improved TF resolution. In this dissertation, we consider two strongly non-stationary biomedical signals, lung sound and blood-flow signals, and propose novel and effective systems for the detection of crackles from the former and emboli from the latter. The crackle detection system uses the dual tree complex wavelet transform (DTCWT) for denoising and time-frequency/scale analysis with various windows/wavelets for feature extraction. The emboli detection system processes forward and reverse flow signals using FT, discrete wavelet transform (DWT), and DTCWT. Dimensionality of the extracted coefficients is reduced using Principal Component Analysis, and the new features are used for predicting whether a signal is emboli, speckle or artifact. Since the dyadic TF tiling of classical DWT is not appropriate for processing embolic signals, and since the discrete wavelet packet transform (DWPT) can adaptively decompose the TF axis, we also propose a directional complex DWPT for mapping directional information while processing quadrature signals (QSs). This method has significantly less computational complexity than the existing methods. To overcome the poor frequency resolution, severe frequency aliasing and lack of shift-invariance drawbacks of the DWT, we also propose a novel directional complex DWT. It consists of filter-banks with rational sampling factors and can be applied directly to QSs.
Antibacterial photodynamic therapy with indocyanine green and near-infrared light
Increase in antibiotic-resistance is a worldwide health problem, which may result in septicemia and subsequent death in recent years. Some of these deaths are caused by nosocomial, burn or chronic wound infections. Photodynamic therapy can be an alternative technique in treatment of infections. This research aimed to investigate the bactericidal effect of photodynamic therapy with indocyanine green and near-infrared light in vitro and in vivo. First, the effect of indocyanine green and 809-nm laser light was examined on wild type and resistant strains of Staphylococcus aureus and Pseudomonas aeruginosa in vitro. Indocyanine green concentration and laser dose were initially optimized for wild type strains. After determining most effective concentrations with specified light dose, they were applied on resistant strains. This method was totally efficient to kill these strains and optimum doses varied with different strains. Later, this method was examined on rat excisional and abrasion wound models. Wounds were infected by resistant strains of S. aureus and P. aeruginosa. Optimum parameters could not be found for excisional wounds because of bleeding, but infected abrasion wounds could be successfully treated. Around 90\% reduction in bacterial burden was observed. Applied energy dose did not cause any thermal damage on healthy tissue. This study showed that indocyanine green together with near-infrared light might be a promising antibacterial method to eliminate infections in clinics and accelerate wound healing process.
Biyobozunur nanofiberlerin biyokimyasal modfikasyonu
Providing the cells from conventional sources have many disadvantages like; difficulty of finding a suitable donor, rejection of the tissue by the body and immune system related problems. In this context, in order to fabricate desired tissue cultures, many efforts are going on development of various cell scaffold materials, surfaces and biochemicals. Although our knowledge on this subject increases in time, more studies are needed to be done. In the purpose of this thesis, histidine and fetuin immobilized Poly-$\epsilon$-caprolactone (PCL) membranes and nanofiber meshes were prepared to enhance biocompatibility. PCL nanofiber meshes were produced via electrospinning and PCL membranes by solvent casting method. For the surface modification in the first step, hexamethylenediamine (HMDA) was used to introduce amino groups onto the PCL surfaces. Histidine, and fetuin immobilization on amino groups of the surface carried out by using cyanamide and N-hydroxysuccinimide (NHS). Fourier Transform Infrared Spectroscopy (FTIR), X-ray Photoelectron Spectroscopy (XPS) and Scanning Electron Microscopy (SEM) were used for the characterization of modifications. The effects of surface modification on cell proliferation were studied by using L929 fibroblast-like cells. MTT assay and cell cultures studies have shown that histidine modified PCL nanofiber meshes have shown higher cell proliferation percentage than histidine modified PCL membranes and control groups within increasing histidine content. According to the results it was shown that PCL biocompatibility can be enhanced with such simple amino acid histidine and it is possible to use these surfaces in many different tissue engineering applications.
Investigation of oscillatory mechanisms and thalamo-cortical circuitry of the visual system by simultaneous EEG-FMRI
Neural oscillation is an indispensable phenomena in the functioning of the cortical networks. Evoked neural oscillations triggered by external rhythmic stimulation mimic spontaneous ongoing oscillations, thus could shed light on the intrinsic specialization and tuning of the cortical networks. In this thesis, flickering light stimulation is used to constitute steady state for a wide range of temporal frequencies (6-46 Hz) during simultaneous electroencephalography (EEG) and blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) scans of 40 healthy volunteers. Firstly, thalamo-cortical loop of the visual system is the subject of interest. Our finding about high correlation between the frequency response characteristics of the lateral geniculate nucleus (LGN) and the primary visual cortex (V1) supports the oscillatory tuning property of the thalamo-cortical interactions. Secondly, contribution of oscillations in the modeling of hemodynamic response is discussed based on the sensitivity of BOLD components (phasic and tonic) to temporal frequency. Our results show that, tonic BOLD component is decreasing more sharply than phasic component with increasing frequencies pointing higher dependency of tonic BOLD response to the stimulation frequency. Finally, EEG informed fMRI analysis is conducted for the sake of testing resonance phenomena. The correlation maps between the BOLD responses and the steady state visually evoked potential (SSVEP) amplitudes show significant correlation for the beta and gamma bands but not for alpha band. This result supports the view that the global amplitude maximum of the SSVEP in the alpha band is due to the synchronization without synaptic activity (BOLD) increase.
Photothermal ablation of liver tissue with 1940-nm thulium fiber laser: Ablation efficiency and temperature measurements
The purpose of this study was to investigate the effectiveness of 1940-nm Thulium fiber laser for liver surgery. This was done by determining the ablation efficiency of different working modes and power settings of 1940-nm Thulium fiber laser on liver tissue, in addition to utilizing a real time temperature monitoring to provide the necessary feedback for adjusting laser parameters to minimize the collateral thermal damage to adjacent tissues. Thulium fiber laser was delivered to lamb liver tissue samples via 400 $\mu$m flat-cut bare-ended tip fiber in contact mode. Continuous-wave and pulsed modes were used, each at 4 different laser power values (200, 400, 600, and 800 mW) and exposure times. Exposure times were chosen to give the same total applied energy of 4J for comparison purposes. A total of 64 laser applications were performed in order to study 8 laser parameter combinations with each parameter combination repeated 8 times. Following laser irradiation, tissues were processed and stained with H\&E for macroscopic evaluation of ablation and total altered areas, and ablation efficiencies were calculated. Temperature of the nearby tissue was measured using a K-type thermocouple that was inserted at a distance of 1 mm from the fiber, and rate of temperature change was calculated. A strong correlation between the rate of temperature change and ablation area was depicted. Larger ablation and total altered areas were obtained for higher power values for both continuous-wave and pulsed modes, while ablation efficiencies were not significantly different. Continuous mode yielded higher ablation and total altered areas, and higher ablations efficiencies than pulsed mode. Histological evaluation revealed a narrow vacuolization zone and negligible carbonization for higher power values.
Ablation efficiency and thermal damage of infrared lasers on ex vivo lamb brain tissues
The objective of this investigation is to guide to select the most sufficient infrared laser for the neurosurgery. For this reason, 1940-nm thulium fiber laser, 1470- nm diode laser, 1070-nm ytterbium fiber laser and 980-nm diode laser were operated with the ex vivo lamb brain tissues. Combination of some parameters such as brain tissue (subcortical and cortical tissues), laser output power, energy density, mode of operation (continuous and pulsed-modulated modes) and exposure time were applied. Pre-dosimetry study was conducted to determine coagulation and carbonization onset times for the lamb brain tissues. In this way, safe operation zone could be described for the dosimetry study. In the dosimetry study, both tissues were exposed to some energy densities (2J-4J) and power levels which are 200mW-400mW-600mW-800 mW and 0.5W-1W-1.5W-2W for 1940-nm and 1470-nm laser applications, respectively. The last two laser emitted light to both brain tissues with some power levels (1W- 2W-3W-4W) and energy densities (20J-40J). After each laser application, coagulation and ablation diameters were calculated under a light microscope. It was aimed to find suitable laser parameter so as to perform the greatest ablation efficiency which is determined as ablation diameter over coagulated diameter. Consequently, 1940-nm and 1470-nm lasers created ablated and coagulated areas while the other two lasers made only coagulated areas. Ablation efficiencies were calculated for 1940-nm and 1470-nm lasers. It was found that the former and the latter can be used as a subcortical and cortical tissue ablator, respectively.
Protein adsorption on amino acid conjugated self assembled molecules
In this thesis, novel amino acid (conjugated histidine, leucine, serine, tryptophan) conjugated self-assembled molecules (SAMs) were synthesized and used to modify model metallic [Gold, (Au)] and inorganic [Silicon Oxide, (SiO2)] surfaces to investigate protein adsorption. In the first step, Au and SiO2 surfaces were cleaned and modification of surfaces were carried out with 3-mercaptopropanoyl and 3 - (trimethoxysilyl) propane functional groups conjugated amino acids (for Au; histidine, leucine, serine, tryptophan, for SiO2; histidine and leucine), respectively. Syntheses of amino acid conjugated SAMs were characterized with 1H-Nuclear Magnetic Resonance (1H-NMR) Spectroscopy. Au and SiO2 surfaces modified with amino acid conjugated SAMs were characterized water contact angle measurements. We aimed to manipulate and change the adsorption of the proteins (Albumin, Fibrinogen and Immunoglobulin G) on these surfaces using amino acid conjugated SAMs. Protein adsorption was investigated in situ by using Quartz Crystal Microbalance (QCM) biosensors. According to results, target proteins have shown different affinity to the amino acid conjugated Au and SiO2 coated crystals depending the type of the amino acids and concentration. For instance, according to comparison of Histidine modified SiO2 and Au surfaces, properties of surfaces have shown a clear difference and effect on protein adsorption. In addition, according to comparison of Leucine modified SiO2 and Au surfaces, properties of surfaces have shown a clear effect on protein adsorption as having the same surface chemistry. Consequently, it has been observed that these controlled chemistry on the surfaces of materials have a great potential to manipulate protein adsorption for biomedical applications.
A hybrid biological/in silico neural network based brain-machine interface
Brain-machine interfaces (BMIs) aim to improve the lives of individuals with neurological disease or injury, by opening new information transfer channels between brain tissue and prosthetic actuators. In a majority of the BMI work, the data acquired from the motor cortex neurons are decoded into user's intended prosthetic actions by some "optimized" input-output mathematical model. Although this approach is quite sound, the information processing principles used are fundamentally different from those of natural neural circuits. In this thesis, we propose a novel, neurally-inspired design approach; the BMI controller consists of spiking model neurons and receives simulated synaptic inputs from extracellularly recorded neurons. The controller therefore forms a hybrid biological/in silico neural network with the neuronal circuits of the user's brain. In order to fulfill the challenging real-time requirements of the present design approach, we first developed the Bioinspired Model Development Environment (BMDE). The BMDE, implemented on a hard real-time system, significantly facilitates BMI model development processes with powerful online data visualization tools while satisfying the strict timing constraints of the proposed design approach. Using the BMDE, we realized a novel, adaptive BMI controller which consists of in silico striatal medium spiny neurons, each receiving simulated synaptic inputs from extracellularly recorded motor cortex neurons. By implementing a reward-modulated spike timing-dependent plasticity rule and a winner-takes-all mechanism, the BMI controller, based on real-time closed-loop simulations, achieves perfect target reach accuracy for a two target reaching task in one dimensional space. Using this design approach and the BMDE, new generation BMI controllers that better mimic brain circuits can be developed. Moreover, by investigating the interactions between biological and in silico neural networks during neuroprosthetic control tryouts new neuroscientific insights concerning motor control and learning can be obtained.
Nonlinear state and parameter estimation of the hemodynamic model using fMRI bold signal
The joint estimation of the parameters and the states of the hemodynamic model from the blood oxygen level dependent (BOLD) signal is a challenging problem. In the functional magnetic resonance imaging (fMRI) literature, quite interestingly, many proposed algorithms work only as a filtering method. In the fMRI state estimation literature, extended Kalman filter (EKF) is asserted to be not robust and worse than standard particle filters (PF). We compared EKF with PF and observed that the contrary is true. We also implemented particle filter that approximates the proposal function by the extended Kalman filter. We compared Gaussian type approximated estimation techniques like extended Kalman filter (EKF), unscented Kalman filter (UKF), cubature Kalman filter (CKF) as well as stochastic inference techniques like standard particle filters (PF) and auxiliary particle filter (APF). Filtering makes the estimation of the hidden states and the parameters less reliable compared with the algorithms that use smoothing. We improved the EKF performance by adding smoother. The joint state and parameter estimation is improved substantially by performing the iterative EKS (IEKS) algorithm. We compared IEKS performance with the square-root cubature Kalman smoother (SCKS) algorithm. We show that its accuracy for the state and the parameter estimation is better and much faster than iterative SCKS. SCKS was found to be a better estimator than the dynamic expectation maximization (DEM), EKF, local linearization filter (LLF) and PF methods. We show in this thesis that IEKS is a better estimator than iterative SCKS under different process and measurement noise conditions.
An MR safe nitinol guidewire design for intravascular applications
Magnetic resonance imaging (MRI) o ers excellent soft tissue contrast and radiation free imaging. Conventional guidewires employ long metallic materials for versatility and mechanical characteristics, and are subject to RF-induced heating, therefore are inappropriate for use in MR. This work describes the design and testing of a metallic guidewire that is intrinsically MR-safe with preserved mechanical performance. The MR-safe guidewire was constructed using nitinol rod segments less than a quarter wavelength of RF transmission at 1.5 T within the body to eliminate standing wave formation, hence RF heating. The insulated nitinol segments were connected by short nitinol tubes for a sti ness-matched guidewire core. Mechanical integrity was tested in vitro according to ISO standards. RF-safety was evaluated in vitro according to ASTM standards, and in vivo in swine in a 1.5T MR system. Tests were performed on the prototype and a commercially available guidewire (Glidewire, Terumo, Japan) for comparison. Mechanical tests demonstrated that the segmented-core guidewire behaves similarly to its comparator. In vitro and in vivo RF heating tests con rmed that RF heating is under 2◦C as required by US Food and Drug Administration. The feasibility of an intrinsically safe passive metallic MRI guidewire design is demonstrated. The prototype exhibits negligible heating at high ip angles in conformance with FDA guidance documents (<2◦C), yet mechanically resembles a highperformance conventional metallic guidewire. This may represent a signi cant advance once applied to clinical MRI catheterization.
Development of a computer controlled fabrication system for interventional magnetic resonance imaging device production
Magnetic Resonance Imaging (MRI) is a promising candidate against X-Ray fluoroscopy for interventional cardiovascular procedures due to its ionizing radiation free mechanism and superior soft tissue contrast. However, Interventıonal MRI fıeld lacks of dedicated clinical grade MRI safe and visible devices. Aim of this thesis study is to design and develop a Computer Numerical Control (CNC) based 4-axis conductive ink dispenser system for developing low profile "active" interventional devices for cardiovascular procedures under MRI. The proposed 4 axis CNC controlled dispenser system allows to form three dimensional receiver antenna configurations automatically onto non-planar catheter shaft surfaces. The developed system decreases the process time and increases the repeatability significantly compared to alternative lithography based techniques also used for low profile active device development. The validation and calibration test results showed that the motion control system works within tolerance of 3.1µm and the dispenser unit works with more than % 90 accuracy during several trials. As a part of this thesis study, a resonator marker on a 6 Fr catheter shaft was designed and formed based on former Electromagnetic (EM) simulation results. The resonator marker is basically an LC tank circuit incorporating a solenoid coil and a capacitor. It is used to visualize the distal tip of a 6Fr catheter under 1.5T MR systems. The impedance and resonant frequency of resonant marker were measured with a vector network analyzer and necessary modifications were made via copper electroplating until the resonant marker is tuned to 63.66 MHz. The visibility and RF induced heating tests were performed successfully for prototype marker device under MRI.
Design of a collimator for breast-specific gamma imaging and assessment of NEC rate for a pet scanner using Monte Carlo simulations and response surface methodology
This thesis is composed of two studies that demonstrate the implementation of Monte Carlo (MC) simulations and response surface methodology (RSM) to specific problems in planar and tomographic nuclear medicine imaging. In the first study, the collimator of a planar small field-of-view continuous crystal breast specific gamma camera is optimized by maximizing the lesion contrast-to-noise ratio (CNR) with respect to hole diameter, septal thickness and hole length. This study demonstrated that the pairwise interaction effects of the collimator parameters play a key role in determining the set of optimal parameter. As a result of optimization, a considerable improvement of up to 73% in CNR with respect to the reference collimators is achieved. Moreover, the critical region for detectability shifted towards the direction of smaller lesion diameter and lower tumor-to-background ratio. Another conclusion of the study is that the optimizer adapts itself to the spatial resolution/sensitivity trade-off as the lesion depth changes. Based on these findings, we conclude that the advantages obtained with this approach may lead to an advancement in collimator design. Whereas, the second study is involved with the positron emission tomography (PET) camera performance based on the noise-equivalent-count rate (NECR). In this part, the effect of lower energy threshold (LET) and coincidence time window (CTW) on NECR is investigated over a range of activities. Our findings showed that both LET and CTW showed significant linear and quadratic effects. Moreover, the evidence of presence of interaction among parameters makes this approach superior in comparison to conventional one-variable-at-a-time assessment techniques. Through an in-depth literature review, the proposed approach is also shown to be useful for a range of cameras for both human and animal use, as well as organ-specific and time-of-flight PET scanners.
SOD1 A4V mutation increases Nav1.3 channel excitability on xenopus laevis oocyte
Amyotrophic lateral sclerosis (ALS) is a lethal, paralytic disease caused by degeneration of motor neurons in the spinal cord, brain stem and motor cortex. Mutations in the gene encoding copper/zinc superoxide dismutase (SOD1) are present in 20 % of familial ALS and 2 % of all ALS cases. The most common SOD1 gene mutation in North America is a missense mutation substituting valine for alanine (A4V). In this study, sodium channel currents in oocytes expressing either wild type or mutant (A4V) SOD1 protein were analyzed. In this study elicited on Xenopus Laevis oocyte, it is demonstrated that the A4V mutation confers a propensity to hyperexcitability on a voltage dependent sodium channel (Nav) mediated by heightened total Na+ conductance and a hyperpolarizing shift in the voltage dependence of Nav 1.3 activation. To estimate the impact of these channel effects on excitability in an intact neuron, these changes were simulated in the program NEURON; this shows that the changes induced by mutant SOD1 increase the spontaneous firing frequency of the simulated neuron. These findings are consistent with the view that excessive excitability of neurons is one component in the pathogenesis of this disease.
Design and application of compartmentalized platforms for neurobiological research
Design And Application of Compartmentalized Platforms for Neurobiological Research Conventional culture systems remain inadequate for comprehensive understanding of injury and regeneration in peripheral neurons that extend axons over long distances and through varying extracellular microenvironments. Therefore, a highly tailorable in vitro system, that allows studying in different in vitro models that mimics axonal injury, regeneration and nerve transplants is required. This dissertation presents the development and application of novel compartmentalized in vitro cell culture platforms, where cell bodies are cultured on one side and axons are allowed to grow to the other side through microchannels that connect the two fluidically isolated compartments. These devices enable the manipulation of local environments and a more complete understanding of axonal degeneration and localized and site of action of toxic, neuroprotective, and neurotropic effects of agents in peripheral axons. First, regenerative effects of members of the glial cell-line derived nerve growth factor (GDNF) family of ligands (GFLs) were investigated in a microfluidic physical injury model and GDNF was most potent in promoting axon outgrowth after axotomy. Next, the first high throughput compartmentalized microfluidic platform (HTCMP) is developed, which is an innovative model for in vitro assays in drug screening, where distal axonal degeneration can be modeled by manipulating compartments independently. HTCMP is tested and implemented in drug screening, in order to identify therapeutic candidates for axonal protection from Paclitaxel induced peripheral neuropathy (PIPN). Flucinolone Acetonide (FA) is identified as a neuroprotective compound in vitro and validated in vivo that it demonstrates axonal protection from PIPN as well as relieving neuropathic pain. FA can be co- or pre administered before the injury to peripheral axons takes place, so that PIPN may be prevented. Finally, compartmentalized microfluidic platforms that mimics the isolated in vivo environment, are used in an in vitro model of stem cell replacement therapy for nerve injuries, and it is demonstrated that that the axons of mESC (mouse embryonic stem cell) derived motor neurons are myelinated by mESC derived oligodendrocytes. Keywords: compartmentalized microfluidic culture platform, chemotherapy induced peripheral neuropathy, Paclitaxel, GDNF, Flucinolone Acetonide, high throughput drug screening, myelination; embryonic stem cells (ESCs); mouse ESCs derived motor neurons; mouse ESCs derived oligodendrocytes.
Reliability improvement of computer aided diagnostic system using mutual information
Computer aided diagnosis (CAD) is one of the most important topic in recent years since the systems are able to provide a second reliable opinion to physicians and early diagnosis with these systems are possible. In this study we aim to construct a system for the detection of Alzheimer's disease (AD) using PET images from a database. The CAD system includes a database consisting of a 3D PET image for every query. Via using a similarity metric namely mutual information(MI), every query compares to all other query in database. According to their similarity results, a decision index is calculated. The decision index demonstrate presence or absence of AD. The system was developed and evaluated using two different databases extracted from Alzheimer's disease Neuroimaging Initiative (ADNI) database. All normal and Alzheimer's images are stored and ordered in database. First database consists of 259 normal and 138 AD patient whereas second database consists of 102 normal and 95 AD patient. Main difference of two database is registration. Images in second database are warped with talairach atlas. CAD performance was evaluated using Receiver Operating Characteristic analysis. For every query, a decision index was calculated. According to our results we observed that accuracy and speed of the CAD system is affected by certain parameters. The method proposed in the article is adequate to distinguish the disease. The mutual information method is very simple, applicable and fast enough to use in clinic area.
Image denoising and image enhancement on the applications of confocal laser scanning microscopy
Confocal laser scanning microscopy (CLSM) is a developing optical imaging device enabling non-invasive examination of live biological tissues with laser light in realtime. CLSM provides optical sectioning of samples. Image can get corrupted with noise of different levels due to out-of-focus light back-scattered above and below the focal plane. Construction of the CLSM setup is established and several images are captured. This work attempts to analyze the effects of different denoising and contrast enhancement techniques by using real CLSM images with the help of different image quality metrics. Additive white Gaussian noise (AWGN) is used as a noise model. A reliable method for estimating the standard deviation of AWGN in a single image is also performed on real CLSM images. Wavelet transform is the most effective candidate for noise suppression since it is capable of preserving energy conservation during inverse transformation. A denoising algorithm is developed to make it applicable on CLSM. An important issue that affects the performance of 2D-DWT is the selection of components employed in the algorithm along with their parameter selection. This study examines the effect of employing different combinations of 2D-DWT components and tuning parameter values on different image quality assessments. Design of Experiments (DOE) is presented as a systematic approach to catch the best combination of these parameter values. Analysis of variance (ANOVA) is used to inspect the main effect and interaction effects of the treated parameters. Computational results verified the efficacy of the proposed algorithm and the methodical approach for the image denoising of CLSM images. After denoising, several histogram equalization methods are put into practice for contrast enhancement. The comparison of methods that give better enhancement result is provided with the means of different quantative measures for better visualization.
Determination of biomarkers for mild cognitive impairment in parkinson's disease using magnetic resonance spectroscopic imaging
Parkinson's disease (PD) patients could be categorized as PD with cognitively normal (PD-CN), PD with mild cognitive impairment (PD-MCI), and PD with dementia (PDD). There is a need for finding noninvasive biomarkers for the early diagnosis of PD-MCI. Proton magnetic resonance spectroscopic imaging (1H-MRSI) is a non-invasive MR technique that provides spectroscopic information about metabolic activity of the brain. 19 patients with PD-MCI and 21 patients with PD-CN were included in this study and neuropsychological tests were performed. Multi-voxel 1H-MRSI data were acquired in all patients. An MRSI data analysis tool was developed to create 1H MR spectroscopic peak parameter maps out of raw MRSI data and overlay them onto reference T2-weighted MR images. FMRIB Software Library (FSL) tool was used to register metabolite maps overlaid onto T2-weighted MR images to an MNI152 brain atlas. A Mann-Whitney rank-sum test was applied to compare the differences of metabolic parameters and neuropsychological test scores between PD-MCI and PD-CN. A Friedman test was used to analyze the MR spectroscopic metabolite ratio variations in different brain regions of PD-MCI and PD-CN. Spearman rank correlation coefficient was used to find correlations of neuropsychological test scores and MRS metabolite ratios. There were no significant differences in MRS metabolite ratios in different brain regions of PD-MCI and PD-CN after accounting for multiple comparisons. However, frontal lobe and cerebral white matter showed trends for metabolic differences. Neuropsychological test scores were correlated with several spectroscopic parameters. The results of this study might enable a definition of a biomarker for PD-MCI diagnosis in the future, when combined with possible other MR based biomarkers.
Fabrication and characterization of sharkskin mimicked chitosan-graphene oxide nanocomposite membranes
Bu tezde,temel polimer kitosan ve katk maddesi grafen oksit(GO) olan köpekbalığı derisi taklit edilmiş polimerik membranların üretimleri ve karakterizasyonlar gerçekleştirilerek biyobozunurluk, biyouyumluluk ve arttırılmış esneklik gibi biyolojik, kimyasal ve mekanik özellikleri geliştirilmiş membranların elde edilmesi amaçlanmıştır. Antibakteriyel özellik gösterdiği bilinen köpekbalığı derisi mikro desen yüzeyinin, yine ayn özelliğe sahip olan kitosan ile taklit edilebileceği hipotezi öne sürülmüş ve doğrulanmıştır. Köpekbalığı yüzey yapısın taklit edebilmek için yumuşak litografi yöntemi seçilmiştir. Polidimetilsiloksan(PDMS), negatif kalıpların üretimi için kullanılmıştır. Devamında, saflaştırılmış kitosan seyreltik asetik asit (% 2 v/v) solüsyonu ile çözünerek kitosan çözeltisi hazırlanmıştır. Kitosan/GO nanokompozitleri hazırlamak için farklı miktarlarda GO(%0.1 w/w, %0.2 w/w, %0.3 w/w) içeren kitosan çözeltileleri, grafen oksitin ultra-homojenize edilmesinden sonra kitosan solüsyonuna eklenmesiyle elde edilmiştir. Bu kitosan/GO çözeltileri köpekbalığı derisi negatif kalıplar üzerine dökülmüştür. Kopma uzaması ve çekme dayan m n içeren mekanik karakterizasyonlar düz kitosan membranlar ile gerçekle3tirilmi3tir. Taramal elektron mikroskobu (SEM) morfolojik karakterizasyon için kullanılırken, Raman Spektroskopisi, X-Ray Fotoelektron Spek- troskopisi(XPS), Su temas açısı ve şişme testi ile kimyasal karakterizasyon düz ve köpekbalığı taklidi olan membranlarda gerçekleştirilmiştir. Sonuçlar, biyobozunur doğal polimer kullanılarak köpekbalığı derisinin mikro desenlerinin taklit edilebileceği hipotezin doğrulanmıştır. Ek olarak, köpek balığı derisini taklit eden kitosan/GO nanokompozit membranların uygun taklit kalitesine sahip olduğu gözlemlenmiştir. Ayrıca, kitosana GO eklenmesi polimerin kimyasal ve mekanik özelliklerinde kayda değer iyileşmeler sağlamıştır.
Detailed analysis of voxel based morphometry
Voxel Based Morphometry, VBM, is one of the most widely used brain morphometry methods which aims to reveal the structural differences between the brain MR images of different populations. It is a whole brain and fully automatic approach in which all the images are registered onto a common template and then segmented into grey matter, white matter and cerebrospinal fluid. After an optional modulation step (regaining the original volume which is shrinked or enlarged during the registration), smoothing takes place in order to make the data more normally distributed and to diminish the inexact nature of the nonlinear registration. Finally, voxel-wise statistical operations are performed between the groups of the images. As revealed in several studies, changes in these steps and changes in their parameters might influence the resulting statistics. Although some short guidelines exist for conducting the processing stages, this thesis tries to explain each main step and gathers the discussions in the literature to make the VBM users aware of some pitfalls and limitations of VBM; and also gives brief descriptions about the other brain morphometry methods to give a view for where VBM stands at. In this thesis, the effect of modulation and masking strategy at the statistical stage were studied and concluded that not using the modulation and using average-based masking for the statistical part increased the detection power of VBM. Additionally, within the scope of this thesis, three clinical applications of VBM are performed and presented: Comparisons of the brain images of mathematicians, SSPE patients, and solvent abusers vs healthy controls.
Laser brain surgery with near infrared lasers: Investigation of the optimal parameters by real-time temperature monitoring
The thermal damage of the surrounding tissue can be an unwanted result of continuous-wave laser irradiation. In order to propose an effective way alternative to conventional surgical techniques, photothermal damage must be taken under control by a detailed dose study. Real-time temperature monitoring can be also an effective way to get rid of these side effects. The aim of this study was to overcome the side effects of photothermal interactions with a better establishment of experiments for investigating the photothermal effects of lasers and to specify optimal laser parameters in order to propose lasers in clinical use. In the present study, ablation/vaporization capability of three different infrared lasers operating at 980-nm, 1070-nm and 1940-nm were investigated through comparative experiments. All studies were performed ex vivo followed by in vivo with real-time temperature monitoring and male Wistar rats were used as an animal model. Animals were sacrificed immediately after the stereotaxic surgery for histological examinations. Sections were stained with Cresyl Fast Violet in order to measure the thermally altered areas. The relation between laser parameters, temperature changes and ablation efficiency were determined. The correlations between rate of temperature change and ablation efficiency were calculated. In conclusion, this comparative study showed that the change in temperature in the tissue during laser irradiation, even though the laser source is different in terms of wavelength, can be a good indicator for the characteristics of lesion created by the laser.
Ortopedik uygulamalar için polikaprolakton-kitosan nanolif kaplı Ti-mikroalaşımlı AZ31 Mg alaşımının biyobozunurluk özelliklerinin araştırılması
Bu tez çalışmasında, ortopedik implant uygulamaları için AZ31 Mg alaşımının Ti mikro alaşımlandırma (ağr. %0,1 Ti, AZ31Ti) ile kontrollü biyobozunur özelliğinin geliştirilmesi çalışılmıştır. Çalışma kapsamında, AZ31 ve AZ31Ti alaşımlarının mikroyapı, sertlik ve çekme dayanımları karşılaştırılmıştır. Kaplanmamış ve elektro-eğirme yöntemi ile nanofiber kaplanmış alaşımların biyouyumluluk ve hücre tutunma testinin yanı sıra yapay vücut sıvısı (SBF) içinde in-vitro korozyon dayanımları araştırılmıştır. Fiber oluşumu için polikaprolakton (PCL) ve kitosan (CS) kullanılmıştır (PCL/CS). Ayrıca, PCL/CS karışımına karanfil özütlü enkapsüle gümüş nanopartikül (eAgNP) ilave edilerek ayrı bir kaplama karışımı (PCL/CS-eAgNP) hazırlanmıştır. AZ31Ti yüzeylerine elektro-eğirme yöntemiyle PCL/CS ve PCL/CS-eAgNP olmak üzere iki farklı nanofiber kaplama yapılmıştır. Biyouyumluluk testi için MC3T3-E1 (CRL-2593) osteoblast hücreleri model olarak kullanılmıştır. Malzeme karakterizasyon analizleri; Optik Mikroskop (OP), Taramalı Elektron Mikroskobu (SEM), Alan Emisyonlu Taramalı Elektron Mikroskobu (FE-SEM), X-Işınları Difraksiyonu (XRD), Fouirer Dönüşümlü Kızılötesi Spektroskopisi (FTIR), temas açısı ölçümleri ile yapılmıştır. OP görüntüleri ve SEM mikroyapı sonuçları; AZ31 ile kıyaslandığında, Ti mikro alaşımlamayla ortalama tane büyüklüğü ve şekillerinde belirgin bir farklılık olmadığını göstermiştir. XRD analizleri, AZ31 ve AZ31Ti alaşımlarının difraksiyon kırınımlarının benzerlik gösterdiğini ve Ti mikro alaşımlamanın AZ31 alaşımının kristal yapısının değiştirmediğini göstermiştir. Ti mikro alaşımlamayla hadde numunelerin sertlik değerlerinde ve mekanik özelliklerinde kayda değer bir değişiklik olmadığı gözlemlenmesine rağmen SEM analizleri, korozyon kaybı sonuçlarını teyit ederek en fazla korozyona uğrayan alaşımın AZ31 alaşımı oluğunu göstermiştir. FESEM görüntüleri, PCL/CS ve PCL/CS-eAgNP kaplamaların ortalama fiber çapları arasında anlamlı bir fark bulunmadığını ve her iki kaplama için de ~55 nm olduğunu göstermiştir. PCL/CS kaplı numunenin temas açısı 123° ve PCL/CS-eAgNP kaplı numunenin ise 118° olarak ölçülmüş ve eAgNP ile kaplamanın ıslatma özelliğinin çok da değişmediği, PCL/CS nanofiber kaplı AZ31Ti alaşımının korozyon kaybı, kaplanmamış AZ31Ti numunesine oldukça yakın olduğu için kaplamanın korozyon kontrolünde beklenen performansı gösteremediği sonucuna varılmıştır. XTT hücre proliferasyon testine göre absorbans sonuçları; PCL/CS kaplanmış numunelerin kaplanmamış alaşım grubuna kıyasla daha iyi biyouyumluluğa sahip olmasına karşın PCL/CS-eAgNP kaplı numunelerin en zayıf biyouyumluluğa sahip olduğunu göstermiştir. Hücre kültürü çalışmaları sonrasında numunelerin SEM görüntülerinde, kaplanmamış numune, zayıf hücre yapışması sergilerken, hücreler, karakteristik kaplama morfolojisi nedeniyle PCL/CS nanofiber kaplı numune üzerinde düzleşmekte ve genişlemekte olduğu gözlemlenmiştir. Anahtar Kelimeler: AZ31 Alaşımı, Biyouyumluluk, Biyobozunma, Elektro-eğirme Yöntemi, Ti mikro alaşımlandırma
Nanopartikül katılmış pan nanofiberler ile güçlendirilmiş termoplastik kompozitlerin üretimi, X-ışını ve elektromanyetik dalgaların soğurulması
Teknolojik gelişmelerin artmasıyla birlikte radyasyon kavramı oldukça ciddi bir sorun haline gelmiştir. Bu sorunları çözmek için ileri fonksiyonel malzeme ihtiyaçları ve bu ihtiyaçlar doğrultusunda yapılan çalışmalar hızlı bir şekilde artmaktadır. Havacılık, otomotiv, medikal sektörü ve savunma sanayii gibi çalışma sahalarında ileri fonksiyonel malzemeler gün geçtikçe önemini arttırmaktadır. Radyasyon ve X-Işınlarına maruz kalımının etkilerini en aza indirmek amacıyla kalkanlama malzemeleri kullanılmaktadır. Kullanılan bu kalkanlama malzemeleri teknolojik çalışmalarla birlike daha fonksiyonel bir biçimde tasarlanması, hafifliği ve esnekliği ön plana çıkaracak şekilde olması için çalışmalar yapılmaktadır. Savunma sanayii'nde ise radar kesit alanı düşürülmesi, hafif ve dayanıklı alternatif ileri fonksiyonel malzeme arayışları her geçen gün artmaktadır. Bu yüksek lisans tez çalışmasında Poliakrilonitril (PAN) polimerinin içerisine %1Ag, %1SiC ve %0.5Ag+ %0.5SiC nanopartikülleri katılarak nanopartikül katkılı PAN nanofiberleri üretilmiştir. Üretilen PAN nanofiberleri Elium 188 ® termoplastik matris reçinesi içerisine el yatırma yöntemiyle yerleştirerek Elium+PAN tabakalı termoplastik nanokompozitleri üretilmiştir. Üretilen Elium+PAN tabakalı termoplastik nanokompozitlerinin Taramalı Elektron Mikroskop (SEM) görüntüleri alınmıştır. X-Işını kırınım analizi (XRD), Termaogravimetrik (TGA), Fourier dönüşümlü infrared spektroskopi (FTIR) karakterizasyon testleri, X-Işınları azalım testleri ve EMI testleri yapılarak X-ışınlarını ve elektromanyetik dalgaları soğurma özellikleri araştırılmıştır. Elium+PAN tabakalı termoplastik nanokompozitleri 200 mA, 100 mSec ve 20 mAs değerlerini sabit tutarak 40 kV, 60 kV, 80 kV ve 100 kV doz değerlerinde 100 cm mesafeden ölçümler yapılarak X-Işınları azalım testleri gerçekleştirilmiştir. Nanokompozitlerin X-Bandında (8.2-12.4 GHz) aralığında EMI testleri gerçekleştirilmiştir. Yapılan testler sonucunda Elium+PAN/%0.5Ag+%0.5SiC tabakalı termoplastik nanokompoziti 40 kV, 60 kV, 80 kV ve 100 kV doz değerlerinde en iyi zayıflatma katsayısına ulaştığı görülmüştür. Tabakalı termoplastik nanokompozitlerin içerisindeki nanopartikül miktarının eser miktarda olmasına rağmen bulunan değerler gelecek çalışmalar için önem arz etmektedir.
Comparative analysis of OSEM parameters for cardiac SPECT imaging across multiple camera brands: A monte carlo study
Background and Objective: To examine the effect of ordered subset expec- tation maximization (OSEM) parameters on the quantitative image quality of cardiac SPECT images in two different frequently used SPECT cameras and determine the op- timal settings for producing images of best diagnostic quality. Another objective was to assess if different cameras produced a significant change in optimal parameters and levels of detectability. Methods: The optimization of OSEM iterative reconstruction algorithm was carried out by comparing image quality metrics, namely, contrast-to- noise ratio (CNR) and defect contrast across 12 OSEM subset-iteration combinations to find the best choice for cardiac perfusion SPECT images. Eight frames were re- constructed using the SIMIND Monte Carlo Simulation package. An activity of 370 MBq (10mCi) and projection acquisition interval of 20 seconds per projection were used. Attenuation (AC) and scatter corrections (SC) were performed in this study for all images. Results: The 16-2 subset-iteration combination yielded the highest CNR and defect contrast values for both cameras. The difference between CNR values for two cameras was found to be around 5% only. Conclusions: Monte Carlo simulations can be useful to investigate how quantitative image quality behaves with respect to reconstruction parameters and correction algorithms in a controlled environment. The found optimum is similar to values reported in previous findings. In this study, the use of different camera brands did not affect the optimum. The quantitative detectability measures were also very similar.
Assessment of the human brain metabolism in vivo using magnetic resonance spectroscopic editing techniques at 3T
Proton MR spectroscopic imaging (1H-MRSI) is a metabolic MRI technique that could be added to the brain imaging protocols for a detailed investigation of the brain metabolism. Neurodegenerative diseases and brain tumors manifest changes in glutamate/glutamine (Glu/Gln) complex (Glx) and myo-inositol (mI) peaks in 1H-MRSI. These metabolites could not be separated with routine 1H-MRSI techniques, so there is a need for MR spectral editing techniques. J-resolved point resolved spectroscopy (PRESS) and echo time (TE)-averaged PRESS are MR spectral editing techniques, which allow for separation of the Glu, Gln, mI, and glutathione (GSH) metabolites. In this thesis, Monte Carlo simulations were used to optimize the number of TEs to reduce the acquisition time of 2D J-resolved PRESS for a detailed investigation of Glu and GSH metabolites with TE-averaged PRESS and accelerate the data acquisition with compressed sensing. A Wilcoxon signed-rank test was used to detect any significant differences in metabolite to creatine (Cr) and Glu/Gln ratios and signal-to-noise ratios between multi-voxel 35 ms PRESS and optimized TE-averaged PRESS. Mean metabolite to Cr ratios were compared between full and compressed sensing accelerated optimized TE-averaged PRESS data using Bland Altman statistical test. This study indicated that optimized TE-averaged PRESS successfully and separately quantified the peaks of Glu at 2.35 ppm, and compressed sensing reconstruction could be applied for further reduction of scan time of optimized TE-averaged PRESS.
Frequency-dependent dynamics of intrinsic connectivity networks
Despite converging evidence of hierarchical organization in the cerebral cortex, with sensory-motor and association regions at opposite ends, the mechanism of such hierarchical interactions remains elusive. This organization was primarily investigated regarding the spatiotemporal dynamics of intrinsic connectivity networks (ICNs). However, more effort is needed to investigate network dynamics in the frequency domain. We aimed to examine the integrative role of brain regions in the frequency domain with graph metrics. Phase-based connectivity estimation was performed in three frequency bands (0.011-0.038, 0.0433-0.071, and 0.076-0.103 Hz) in the BOLD signal during rest. We applied modularity analysis to connectivity matrices and investigated those areas, which we called integrative regions, that showed frequency-domain flexibility. Inte- grative regions, mostly belonging to attention networks, were densely connected to higher-order cognitive ICNs in lower frequency bands but to sensory-motor ICNs in higher frequency bands. We compared the normalized participation coefficient values of integrative and core regions with respect to their relation to higher-order cognition using a permutation-based t-test for multiple linear regression. Regression parameters of integrative regions in relation to three cognitive scores in executive functions, and working memory were significantly larger than those of core regions (Pfdr < 0.05) for salience ventral attention network. Parameters of integrative regions in relation to intelligence scores were significantly larger than those with core regions (Pfdr < 0.05) in dorsal attention network. Results indicate their essential role at an intermediate level in behavior and emphasize the importance of frequency-band analysis of brain networks.
The effect of surface functionalization on cell behavior
Bone-on-a-chip platforms that replicate the native bone microenvironment are indispensable for research of complex physiological conditions. Polydimethylsiloxane (PDMS) has widespread use for these platforms and needs biochemical modification to derive suitable biocompatibility and bioactivity for bone research. In this study, PDMS surfaces were coated with Hydroxyapatite (HA) using immobilization and biomineralization techniques with the aid of small molecules, namely Aspartic Acid (AA), Glutamic Acid (Glu), and Citric Acid (CA). The effectiveness of biomineralization and immobilization techniques and the impact of small molecules on HA deposition on PDMS surfaces were investigated by chemical and morphological analysis of the surfaces, besides in vitro cell culture studies. Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) and X-ray Photoelectron Spectroscopy (XPS) spectra confirmed that the small molecule modification on both PDMS and onto nHA particles was achieved successfully. X-ray Diffraction (XRD) patterns showed characteristic peaks of HA deposited by either biomineralization or immobilization on PDMS surfaces, which were also observed with scanning electron microscopy (SEM). The interaction of human fetal human osteoblasts cells (hFOB 1.19) with HA-deposited PDMS surfaces was evaluated with in vitro cell culture studies, which revealed increased cell viability across all groups, with HA deposited on AAPDMS surfaces being the most stimulating group. Overall, it is further worthy of study on the effect of small molecules on HA deposition to the PDMS substrates, especially for those mimicking chemical and morphological features of the bone surface
3D printing of f-MWCNT incorporated plga/ha scaffolds for bone regeneration
3D printing is an effective technology due to production of objects quickly and precisely by controlling over their shape and size. In the study, poly(lactide-co- glycolide) (PLGA) and its nanocomposites with 5 wt.% hydroxyapatite (HA) and with 0.5, 1 and 2 wt.% carboxyl functionalized multi-walled carbon nanotube (MWCNT) were prepared by 3D printing technique, Fused Deposition Modelling(FDM). The print- ing parameters were optimized based on rheological studies. Accordningly, all ink com- positions exhibited a shear thinning behaviour. The inclusion of MWCNTs reduced filament size, which was related to hydrogen bonding between functional groups of the components. This increased the ultimate porosity from 42% to 60% with improved shape fidelity. The chemical structure was examined by XRD and FTIR. The surface bioactivity of the scaffolds was tested by water contact angle (WCA) measurement and stimulated body fluid (SBF). A universal testing machine was used for the compressive characteristics of biomaterials. Finally, biocompatibility was confirmed by in vitro cell analysis. The higher surface hydrophilicity was achieved by incorporating MWCNTs. In addition, degradation outcomes indicated that the HA and MWCNT made the mi- crostructure more stable. The compressive modulus for PLGA/HA/CNT2 scaffold was reported to be 548.5 MPa which within the range appropriate for cancellous bone re- placement. Cell culture results suggested that the nanocomposites scaffolds facilitated the cellular response, likely via MWCNT alignment during nozzle passage. Alizarin red staining revealed a significant raise in mineralization degree of MC3T3-E1 on 3D porous scaffolds with MWCNTs. The findings imply that the generated 3D printed PLGA/HA/CNT scaffold hold potential for effective bone treatment.
Kornea rejenerasyonuna yönelik amniyotik membran temelli stratejiler
Human amniotic membrane (HAM), obtained from the inmost layer of the placenta, has been utilized in tissue engineering and regenerative medicine applications for many years in various forms such as intact HAM, decellularized, micronized or extract form. Amniotic membrane extract (AME) is an extract form of HAM and known to contain a plethora of cytokines and growth factors, making it a highly attractive option for topical applications. In the first part of thesis, the effects of AME concentration on corneal keratocytes and the effects of using AME with eye drops on cell viability were investigated. It has been observed that the combined use of 50 μg/mL AME and eye drops increases corneal keratocyte cell proliferation. In the second part of thesis, AME was blended with Wharton's jelly mesenchymal stem cells derived-exosomes (WJ-MSC-Exos) and the effects of their combined use on the proliferation of corneal keratocytes as well as their ability to promote in vitro cell migration, wound healing, and their impact on cellular morphology were evaluated. Although WJ-MSC-Exos and AME have been used separately for wound healing research, their combined synergistic effects have not been studied extensively. Our findings indicated that the presence of both exosomes (3x105 Exo/mL) and AME (50 μg/mL) synergistically enhance the proliferation of corneal keratocytes. Overall, all these findings demonstrate that HAM can be utilized towards corneal regeneration through various strategies, or in combination with helpful solutions such as exosomes and eye drops. Keywords: Wharton's Jelly Mesenchymal Stem Cells Derived Exosomes, Amniotic Membrane Extract, Corneal Keratocytes, Eye Drops, in vitro corneal wound healing.