Neural Diversity in the Drosophila Olfactory Circuitry: A Dissertation

Different neurons and glial cells in the Drosophila olfactory circuitry have distinct functions in olfaction. The mechanisms to generate most of diverse neurons and glial cells in the olfactory circuitry remain unclear due to the incomprehensive study of cell lineages. To facilitate the analyses of cell lineages and neural diversity, two independent binary transcription systems were introduced into Drosophila to drive two different transgenes in different cells. A technique called ‘dual-expression-control MARCM’ (mosaic analysis with a repressible cell marker) was created by incorporating a GAL80-suppresible transcription factor LexA::GAD (GAL4 activation domain) into the MARCM. This technique allows the induction of UAS- and lexAop- transgenes in different patterns among the GAL80-minus cells. Dual-expression-control MARCM with a ubiquitous driver tubP-LexA::GAD and various subtype-specific GAL4s which express in antennal lobe neurons (ALNs) allowed us to characterize diverse ALNs and their lineage relationships. Genetic studies showed that ALN cell fates are determined by spatial identities rooted in their precursor cells and temporal identities based on their birth timings within the lineage, and then finalized through cell-cell interactions mediated by Notch signaling. Glial cell lineage analyses by MARCM and dual-expression-control MARCM show that diverse post-embryonic born glial cells are lineage specified and independent of neuronal lineage. Specified glial lineages expand their glial population by symmetrical division and do not further diversify glial cells. Construction of a GAL4-insensitive transcription factor LexA::VP16 (VP16 acidic activation domain) allows the independent induction of lexAop transgenes in the entire mushroom body (MB) and labeling of individual MB neurons by MARCM in the same organism. A computer algorithm is developed to perform morphometric analysis to assist the study of MB neuron diversity

Automated Deformable Mapping Methods to Relate Corresponding Lesions in 3D X-ray and 3D Ultrasound Breast Images

Mammography is the current standard imaging method for detecting breast cancer by using x-rays to produce 2D images of the breast. However, with mammography alone there is difficulty determining whether a lesion is benign or malignant and reduced sensitivity to detecting lesions in dense breasts. Ultrasound imaging used in conjunction with mammography has shown valuable contributions for lesion characterization by differentiating between solid and cystic lesions. Conventional breast ultrasound has high false positive rates; however, it has shown improved abilities to detect lesions in dense breasts. Breast ultrasound is typically performed freehand to produce anterior-to-posterior 2D images in a different geometry (supine) than mammography (upright). This difference in geometries is likely responsible for the finding that at least 10% of the time lesions found in the ultrasound images do not correspond with lesions found in mammograms. To solve this problem additional imaging techniques must be investigated to aid a radiologist in identifying corresponding lesions in the two modalities to ensure early detection of a potential cancer. This dissertation describes and validates automated deformable mapping methods to register and relate corresponding lesions between multi-modality images acquired using 3D mammography (Digital Breast Tomosynthesis (DBT) and dedicated breast Computed Tomography (bCT)) and 3D ultrasound (Automated Breast Ultrasound (ABUS)). The methodology involves the use of finite element modeling and analysis to simulate the differences in compression and breast orientation to better align lesions acquired from images from these modalities. Preliminary studies were performed using several multimodality compressible breast phantoms to determine breast lesion registrations between: i) cranio-caudal (CC) and mediolateral oblique (MLO) DBT views and ABUS, ii) simulated bCT and DBT (CC and MLO views), and iii) simulated bCT and ABUS. Distances between the centers of masses, dCOM, of corresponding lesions were used to assess the deformable mapping method. These phantom studies showed the potential to apply this technique for real breast lesions with mean dCOM registration values as low as 4.9 ± 2.4 mm for DBT (CC view) mapped to ABUS, 9.3 ± 2.8 mm for DBT (MLO view) mapped to ABUS, 4.8 ± 2.4 mm for bCT mapped to ABUS, 5.0 ± 2.2 mm for bCT mapped to DBT (CC view), and 4.7 ± 2.5 mm for bCT mapped to DBT (MLO view). All of the phantom studies showed that using external fiducial markers helped improve the registration capability of the deformable mapping algorithm. An IRB-approved proof-of-concept study was performed with patient volunteers to validate the deformable registration method on 5 patient datasets with a total of up to 7 lesions for DBT (CC and MLO views) to ABUS registration. Resulting dCOM’s using the deformable method showed statistically significant improvements over rigid registration techniques with a mean dCOM of 11.6 ± 5.3 mm for DBT (CC view) mapped to ABUS and a mean dCOM of 12.3 ± 4.8 mm for DBT (MLO view) mapped to ABUS. The present work demonstrates the potential for using deformable registration techniques to relate corresponding lesions in 3D x-ray and 3D ultrasound images. This methodology should improve a radiologists’ characterization of breast lesions which can reduce patient callbacks, misdiagnoses, additional patient dose and unnecessary biopsies. Additionally, this technique can save a radiologist time in navigating 3D image volumes and the one-to-one lesion correspondence between modalities can aid in the early detection of breast malignancies.PHDNuclear Engineering & Radiological SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/150042/1/canngree_1.pd

Registration of medical images for applications in minimally invasive procedures

Il punto di partenza di questa tesi \ue8 l'analisi dei metodi allo stato dell'arte di registrazione delle immagini mediche per verificare se sono adatti ad essere utilizzati per assistere il medico durante una procedura minimamente invasiva , ad esempio una procedura percutanea eseguita manualmente o un intervento teleoperato eseguito per mezzo di un robot . La prima conclusione \ue8 che, anche se ci sono tanti lavori dedicati allo sviluppo di algoritmi di registrazione da applicare nel contesto medico, la maggior parte di essi non sono stati progettati per essere utilizzati nello scenario della sala operatoria (OR) anche perch\ue9, rispetto ad altre applicazioni , OR richiede anche la validazione, prestazioni in tempo reale e la presenza di altri strumenti . Gli algoritmi allo stato dell'arte sono basati su un iterazione in tre fasi : ottimizzazione - trasformazione - valutazione della somiglianza delle immagini registrate. In questa tesi, studiamo la fattibilit\ue0 dell'approccio in tre fasi per applicazioni OR, mostrando i limiti che tale approccio incontra nelle applicazioni che stiamo considerando. Verr\ue0 dimostrato come un metodo semplice si potrebbe utilizzare nella OR. Abbiamo poi sviluppato una teoria che \ue8 adatta a registrare grandi insiemi di dati non strutturati estratti da immagini mediche, tenendo conto dei vincoli della OR . Vista l'impossibilit\ue0 di lavorare con dati medici di tipo DICOM, verr\ue0 impiegato un metodo per registrare dataset composti da insiemi di punti non strutturati. Gli algoritmi proposti sono progettati per trovare la corrispondenza spaziale in forma chiusa tenendo conto del tipo di dati, il vincolo del tempo e la presenza di rumore e /o piccole deformazioni. La teoria e gli algoritmi che abbiamo sviluppato sono derivati dalla teoria delle forme proposta da Kendall (Kendall's shapes) e utilizza un descrittore globale della forma per calcolare le corrispondenze e la distanza tra le strutture coinvolte . Poich\ue9 la registrazione \ue8 solo una componente nelle applicazioni mediche, l' ultima parte della tesi \ue8 dedicata ad alcune applicazioni pratiche in OR che possono beneficiare della procedura di registrazione .The registration of medical images is necessary to establish spatial correspondences across two or more images. Registration is rarely the end-goal, but instead, the results of image registration are used in other tasks. The starting point of this thesis is to analyze which methods at the state of the art of image registration are suitable to be used in assisting a physician during a minimally invasive procedure, such as a percutaneous procedure performed manually or a teleoperated intervention performed by the means of a robot. The first conclusion is that, even if much previous work has been devoted to develop registration algorithms to be applied in the medical context, most of them are not designed to be used in the operating room scenario (OR) because, compared to other applications, the OR requires also a strong validation, real-time performance and the presence of other instruments. Almost all of these algorithms are based on a three phase iteration: optimize-transform-evaluate similarity. In this thesis, we study the feasibility of this three steps approach in the OR, showing the limits that such approach encounter in the applications we are considering. We investigate how could a simple method be realizable and what are the assumptions for such a method to work. We then develop a theory that is suitable to register large sets of unstructured data extracted from medical images keeping into account the constraints of the OR. The use of the whole radiologic information is not feasible in the OR context, therefore the method we are introducing registers processed dataset extracted from the original medical images. The framework we propose is designed to find the spatial correspondence in closed form keeping into account the type of the data, the real-time constraint and the presence of noise and/or small deformations. The theory and algorithms we have developed are in the framework of the shape theory proposed by Kendall (Kendall's shapes) and uses a global descriptor of the shape to compute the correspondences and the distance between shapes. Since the registration is only a component of a medical application, the last part of the thesis is dedicated to some practical applications in the OR that can benefit from the registration procedure

Advanced Image Acquisition, Processing Techniques and Applications

"Advanced Image Acquisition, Processing Techniques and Applications" is the first book of a series that provides image processing principles and practical software implementation on a broad range of applications. The book integrates material from leading researchers on Applied Digital Image Acquisition and Processing. An important feature of the book is its emphasis on software tools and scientific computing in order to enhance results and arrive at problem solution

Mechanics of the Developing Brain: From Smooth-walled Tube to the Folded Cortex

Over the course of human development, the brain undergoes dramatic physical changes to achieve its final, convoluted shape. However, the forces underlying every cinch, bulge, and fold remain poorly understood. This doctoral research focuses on the mechanical processes responsible for early (embryonic) and late (preterm) brain development. First, we examine early brain development in the chicken embryo, which is similar to human at these stages. Research has primarily focused on molecular signals to describe morphogenesis, but mechanical analysis can also provide important insights. Using a combination of experiments and finite element modeling, we find that actomyosin contraction is responsible for initial segmentation of the forebrain. By considering mechanical forces from the internal and external environment, we propose a role for mechanical feedback in maintaining these segments during subsequent inflation and bending. Next, we extend our analysis to division of right and left cerebral hemispheres. In this case, we discover that morphogen signals and mechanical feedback act synergistically to shape the hemispheres. In human, cerebral hemispheres go on to form complex folds through a mechanical process that involves rapid expansion of the cortical surface. However, the spatiotemporal dynamics of cortical growth remain unknown in human. Here, we develop a novel strain energy minimization approach to measure regional growth in complex surfaces. By considering brain surfaces of preterm subjects, reconstructed from magnetic resonance imaging (MRI), this analysis reveals distinct patterns of cortical growth that evolve over the third trimester. This information provides a comprehensive view of cortical growth and folding, connecting what is known about patterns of development at the cellular and folding scales. Abnormal brain morphogenesis can lead to serious structural defects and neurological disorders such as epilepsy and autism. By integrating mechanics, biology, and neuroimaging, we gain a more complete understanding of brain development. By studying physical changes from the simple, microscopic embryo to the macroscopic, folded cortex, we gain insight into relevant biological and physical mechanisms across developmental stages

Image Registration Workshop Proceedings

Automatic image registration has often been considered as a preliminary step for higher-level processing, such as object recognition or data fusion. But with the unprecedented amounts of data which are being and will continue to be generated by newly developed sensors, the very topic of automatic image registration has become and important research topic. This workshop presents a collection of very high quality work which has been grouped in four main areas: (1) theoretical aspects of image registration; (2) applications to satellite imagery; (3) applications to medical imagery; and (4) image registration for computer vision research

Towards 3D facial morphometry:facial image analysis applications in anesthesiology and 3D spectral nonrigid registration

In anesthesiology, the detection and anticipation of difficult tracheal intubation is crucial for patient safety. When undergoing general anesthesia, a patient who is unexpectedly difficult to intubate risks potential life-threatening complications with poor clinical outcomes, ranging from severe harm to brain damage or death. Conversely, in cases of suspected difficulty, specific equipment and personnel will be called upon to increase safety and the chances of successful intubation. Research in anesthesiology has associated a certain number of morphological features of the face and neck with higher risk of difficult intubation. Detecting and analyzing these and other potential features, thus allowing the prediction of difficulty of tracheal intubation in a robust, objective, and automatic way, may therefore improve the patients' safety. In this thesis, we first present a method to automatically classify images of the mouth cavity according to the visibility of certain oropharyngeal structures. This method is then integrated into a novel and completely automatic method, based on frontal and profile images of the patient's face, to predict the difficulty of intubation. We also provide a new database of three dimensional (3D) facial scans and present the initial steps towards a complete 3D model of the face suitable for facial morphometry applications, which include difficult tracheal intubation prediction. In order to develop and test our proposed method, we collected a large database of multimodal recordings of over 2700 patients undergoing general anesthesia. In the first part of this thesis, using two dimensional (2D) facial image analysis methods, we automatically extract morphological and appearance-based features from these images. These are used to train a classifier, which learns to discriminate between patients as being easy or difficult to intubate. We validate our approach on two different scenarios, one of them being close to a real-world clinical scenario, using 966 patients, and demonstrate that the proposed method achieves performance comparable to medical diagnosis-based predictions by experienced anesthesiologists. In the second part of this thesis, we focus on the development of a new 3D statistical model of the face to overcome some of the limitations of 2D methods. We first present EPFL3DFace, a new database of 3D facial expression scans, containing 120 subjects, performing 35 different facial expressions. Then, we develop a nonrigid alignment method to register the scans and allow for statistical analysis. Our proposed method is based on spectral geometry processing and makes use of an implicit representation of the scans in order to be robust to noise or holes in the surfaces. It presents the significant advantage of reducing the number of free parameters to optimize for in the alignment process by two orders of magnitude. We apply our proposed method on the data collected and discuss qualitative results. At its current level of performance, our fully automatic method to predict difficult intubation already has the potential to reduce the cost, and increase the availability of such predictions, by not relying on qualified anesthesiologists with years of medical training. Further data collection, in order to increase the number of patients who are difficult to intubate, as well as extracting morphological features from a 3D representation of the face are key elements to further improve the performance