Spatio-temporal PET imaging reconstruction with learned diffeomorphism

openLa Tomografia ad Emissione di Positroni (PET) è una modalità di imaging medico per ricostruire la distribuzione dell’attività metabolica, che viene utilizzata per rilevare lesioni tumorali grazie alle loro peculiari impronte metaboliche. Tuttavia, poiché richiede un lungo tempo di acquisizione, è soggetta ad artefatti da movimento e ciò porta ad una difficile individuazione dei tumori di piccole dimensioni, che sono i più importanti per una diagnosi precoce. L’algoritmo Morphed Maximum Likelihood Activity and Attenuation (M-MLAA) è stato sviluppato per affrontare il problema degli artefatti da movimento sfruttando i dati suddivisi in gate e la rete neurale SynthMorph per la registrazione di immagini, al fine di ricostruire un’immagine corretta dagli artefatti di movimento. L’obiettivo di questo progetto è l’implementazione su dati clinici dell’algoritmo M-MLAA e la valutazione delle sue prestazioni; purtroppo, ciò non è stato possibile a causa di problemi nell’implementazione dell’algoritmo Maximum Likelihood Activity and Attenuation (MLAA) sulla libreria Python Synergistic Image Reconstruction Framework (SIRF). I risultati mostrano che tali problemi potrebbero essere causati da una definizione errata della trasformata di Radon nella libreria. Nonostante ciò, l’algoritmo M-MLAA mostra buone prestazioni quando testato su dati sintetici, suggerendo che potrebbe rappresentare un promettente metodo di correzione dagli artefatti di movimento nella ricostruzione di immagini PET, consentendo di individuare lesioni tumorali in fase precoce.Positron Emission Tomography (PET) is a medical imaging modality to reconstruct the distribution of metabolic activity that is used to detect cancer lesions thanks to their peculiar metabolic fingerprints. However, since it requires long acquisition time, it is affected by motion artifacts and this leads to a difficult detection of small size tumours, that are the most important for early-stage diagnosis. The Morphed Maximum Likelihood Activity and Attenuation (M-MLAA) algorithm has been developed to assess the motion artifact problem by gaining advantage of gated data and SynthMorph image registration network to reconstruct a motion corrected image. This project’s goal is to implement the M-MLAA algorithm on clinical data and to evaluate its performance; unfortunately, this was not achieved due to problems in the implementation of the Maximum Likelihood Activity and Attenuation (MLAA) algorithm on Synergistic Image Reconstruction Framework (SIRF) Python library. The results show that those problems might be caused by an incorrect definition of the Radon transform in the library. Despite that, M-MLAA algorithm shows good performances when tested on synthetic data, suggesting that it could be a promising motion correction reconstruction method for PET images, capable of detecting early-stage cancer lesions

Altered Neurocircuitry in the Dopamine Transporter Knockout Mouse Brain

The plasma membrane transporters for the monoamine neurotransmitters dopamine, serotonin, and norepinephrine modulate the dynamics of these monoamine neurotransmitters. Thus, activity of these transporters has significant consequences for monoamine activity throughout the brain and for a number of neurological and psychiatric disorders. Gene knockout (KO) mice that reduce or eliminate expression of each of these monoamine transporters have provided a wealth of new information about the function of these proteins at molecular, physiological and behavioral levels. In the present work we use the unique properties of magnetic resonance imaging (MRI) to probe the effects of altered dopaminergic dynamics on meso-scale neuronal circuitry and overall brain morphology, since changes at these levels of organization might help to account for some of the extensive pharmacological and behavioral differences observed in dopamine transporter (DAT) KO mice. Despite the smaller size of these animals, voxel-wise statistical comparison of high resolution structural MR images indicated little morphological change as a consequence of DAT KO. Likewise, proton magnetic resonance spectra recorded in the striatum indicated no significant changes in detectable metabolite concentrations between DAT KO and wild-type (WT) mice. In contrast, alterations in the circuitry from the prefrontal cortex to the mesocortical limbic system, an important brain component intimately tied to function of mesolimbic/mesocortical dopamine reward pathways, were revealed by manganese-enhanced MRI (MEMRI). Analysis of co-registered MEMRI images taken over the 26 hours after introduction of Mn^(2+) into the prefrontal cortex indicated that DAT KO mice have a truncated Mn^(2+) distribution within this circuitry with little accumulation beyond the thalamus or contralateral to the injection site. By contrast, WT littermates exhibit Mn^(2+) transport into more posterior midbrain nuclei and contralateral mesolimbic structures at 26 hr post-injection. Thus, DAT KO mice appear, at this level of anatomic resolution, to have preserved cortico-striatal-thalamic connectivity but diminished robustness of reward-modulating circuitry distal to the thalamus. This is in contradistinction to the state of this circuitry in serotonin transporter KO mice where we observed more robust connectivity in more posterior brain regions using methods identical to those employed here

Robust Algorithms for Registration of 3D Images of Human Brain

This thesis is concerned with the process of automatically aligning 3D medical images of human brain. It concentrates on rigid-body matching of Positron Emission Tomography images (PET) and Magnetic Resonance images (MR) within one patient and on non-linear matching of PET images of different patients. In recent years, mutual information has proved to be an excellent criterion for automatic registration of intra-individual images from different modalities. We propose and evaluate a method that combines a multi-resolution optimization of mutual information with an efficient segmentation of background voxels and a modified principal axes algorithm. We show that an acceleration factor of 6-7 can be achieved without loss of accuracy and that the method significantly reduces the rate of unsuccessful registrations. Emphasis was also laid on creation of an automatic registration system that could be used routinely in clinical environment. Non-linear registration tries to reduce the inter-individual variability of shape and structure between two brain images by deforming one image so that homologous regions in both images get aligned. It is an important step of many procedures in medical image processing and analysis. We present a novel algorithm for an automatic non-linear registration of PET images based on hierarchical volume subdivisions and local affine optimizations. It produces a C2-continuous deformation function and guarantees that the deformation is one-to-one. Performance of the algorithm was evaluated on more than 600 clinical PET images

A four-dimensional probabilistic atlas of the human brain

The authors describe the development of a four-dimensional atlas and reference system that includes both macroscopic and microscopic information on structure and function of the human brain in persons between the ages of 18 and 90 years. Given the presumed large but previously unquantified degree of structural and functional variance among normal persons in the human population, the basis for this atlas and reference system is probabilistic. Through the efforts of the International Consortium for Brain Mapping (ICBM), 7,000 subjects will be included in the initial phase of database and atlas development. For each subject, detailed demographic, clinical, behavioral, and imaging information is being collected. In addition, 5,800 subjects will contribute DNA for the purpose of determining genotype-phenotype-behavioral correlations. The process of developing the strategies, algorithms, data collection methods, validation approaches, database structures, and distribution of results is described in this report. Examples of applications of the approach are described for the normal brain in both adults and children as well as in patients with schizophrenia. This project should provide new insights into the relationship between microscopic and macroscopic structure and function in the human brain and should have important implications in basic neuroscience, clinical diagnostics, and cerebral disorders

Quantitation in MRI : application to ageing and epilepsy

Multi-atlas propagation and label fusion techniques have recently been developed for segmenting the human brain into multiple anatomical regions. In this thesis, I investigate possible adaptations of these current state-of-the-art methods. The aim is to study ageing on the one hand, and on the other hand temporal lobe epilepsy as an example for a neurological disease. Overall effects are a confounding factor in such anatomical analyses. Intracranial volume (ICV) is often preferred to normalize for global effects as it allows to normalize for estimated maximum brain size and is hence independent of global brain volume loss, as seen in ageing and disease. I describe systematic differences in ICV measures obtained at 1.5T versus 3T, and present an automated method of measuring intracranial volume, Reverse MNI Brain Masking (RBM), based on tissue probability maps in MNI standard space. I show that this is comparable to manual measurements and robust against field strength differences. Correct and robust segmentation of target brains which show gross abnormalities, such as ventriculomegaly, is important for the study of ageing and disease. We achieved this with incorporating tissue classification information into the image registration process. The best results in elderly subjects, patients with TLE and healthy controls were achieved using a new approach using multi-atlas propagation with enhanced registration (MAPER). I then applied MAPER to the problem of automatically distinguishing patients with TLE with (TLE-HA) and without (TLE-N) hippocampal atrophy on MRI from controls, and determine the side of seizure onset. MAPER-derived structural volumes were used for a classification step consisting of selecting a set of discriminatory structures and applying support vector machine on the structural volumes as well as morphological similarity information such as volume difference obtained with spectral analysis. Acccuracies were 91-100 %, indicating that the method might be clinically useful. Finally, I used the methods developed in the previous chapters to investigate brain regional volume changes across the human lifespan in over 500 healthy subjects between 20 to 90 years of age, using data from three different scanners (2x 1.5T, 1x 3T), using the IXI database. We were able to confirm several known changes, indicating the veracity of the method. In addition, we describe the first multi-region, whole-brain database of normal ageing