Techniques for Analysis and Motion Correction of Arterial Spin Labelling (ASL) Data from Dementia Group Studies

This investigation examines how Arterial Spin Labelling (ASL) Magnetic Resonance Imaging can be optimised to assist in the early diagnosis of diseases which cause dementia, by considering group study analysis and control of motion artefacts. ASL can produce quantitative cerebral blood flow maps noninvasively - without a radioactive or paramagnetic contrast agent being injected. ASL studies have already shown perfusion changes which correlate with the metabolic changes measured by Positron Emission Tomography in the early stages of dementia, before structural changes are evident. But the clinical use of ASL for dementia diagnosis is not yet widespread, due to a combination of a lack of protocol consistency, lack of accepted biomarkers, and sensitivity to motion artefacts. Applying ASL to improve early diagnosis of dementia may allow emerging treatments to be administered earlier, thus with greater effect. In this project, ASL data acquired from two separate patient cohorts ( (i) Young Onset Alzheimer’s Disease (YOAD) study, acquired at Queen Square; and (ii) Incidence and RISk of dementia (IRIS) study, acquired in Rotterdam) were analysed using a pipeline optimised for each acquisition protocol, with several statistical approaches considered including support-vector machine learning. Machine learning was also applied to improve the compatibility of the two studies, and to demonstrate a novel method to disentangle perfusion changes measured by ASL from grey matter atrophy. Also in this project, retrospective motion correction techniques for specific ASL sequences were developed, based on autofocusing and exploiting parallel imaging algorithms. These were tested using a specially developed simulation of the 3D GRASE ASL protocol, which is capable of modelling motion. The parallel imaging based approach was verified by performing a specifically designed MRI experiment involving deliberate motion, then applying the algorithm to demonstrably reduce motion artefacts retrospectively

Computer assisted analysis of contrast enhanced ultrasound images for quantification in vascular diseases

Contrast enhanced ultrasound (CEUS) with microbubble contrast agents has shown great potential in imaging microvasculature, quantifying perfusion and hence detecting vascular diseases. However, most existing perfusion quantification methods based on image intensity, and are susceptible to confounding factors such as attenuation artefacts. Improving reproducibility is also a key challenge to clinical translation. Therefore, this thesis aims at developing attenuation correction and quantification techniques in CEUS with applications for detection and quantification of microvascular flow / perfusion. Firstly, a technique for automatic correction of attenuation effects in vascular imaging was developed and validated on a tissue mimicking phantom. The application of this technique to studying contrast enhancement of carotid adventitial vasa vasorum as a biomarker of radiation-induced atherosclerosis was demonstrated. The results showed great potential in reducing attenuation artefact and improve quantification in CEUS of carotid arteries. Furthermore, contrast intensity was shown to significantly increase in irradiated carotid arteries and could be a useful imaging biomarker for radiation-induced atherosclerosis. Secondly, a robust and automated tool for quantification of microbubble identification in CEUS image sequences using a temporal and spatial analysis was developed and validated on a flow phantom. The application of this technique to evaluate human musculoskeletal microcirculation with contrast enhanced ultrasound was demonstrated. The results showed an excellent accuracy and repeatability in quantifying active vascular density. It has great potential for clinical translation in the assessment of lower limb perfusion. Finally, a new bubble activity identification and quantification technique based on differential intensity projection in CEUS was developed and demonstrated with an in-vivo study, and applied to the quantification of intraplaque neovascularisation in an irradiated carotid artery of patients who were previously treated for head and neck cancer. The results showed a significantly more specific identification of bubble signals and had good agreement between the differential intensity-based technique and clinical visual assessment. This technique has potential to assist clinicians to diagnose and monitor intraplque neovascularisation.Open Acces

Local brain temperature manipulation system and physiological parameters (R2', CBF and ADC) measurements in acute stroke

Accurate prediction of final lesion is critically important for clinical decision making in the management of acute ischemia stroke patients. In addition to the widely utilized perfusion and diffusion parameters, an MR derived cerebral oxygen metabolism index, which includes both cerebral blood flow (CBF) and oxygen consumption measurements using R2' (OMI_ R2'), may be a potential candidate for infarction prediction. In this study, we sought to evaluate how these MR parameters may delineate infarction in rats with ischemic injury. There is overwhelming evidence from animal studies showing that cooling may improve outcome after cerebral ischemia, while hyperthermia exacerbates neurological injury. However, how physiology parameters during ischemic injury are modulated by brain temperature is largely unknown. In this study, we first designed an MR compatible focal brain temperature manipulation system, which can regulate brain temperature, while keeping body temperature and other physiology parameters within the normal range. The relationship between T1 and temperature in brain tissue was investigated, which can be used to derive the brain temperature for the studies under hypothermic conditions. The relationship between CBF and temperature was also studied under ischemic condition. Our results showed that this device can manipulate brain temperature from 39 to the target temperature of 29 within 10 minutes and maintain it for a long period of time. Furthermore, the device allows flexible manipulation of brain temperature. A highly linear relationship between the change of T1 and change of temperature was observed. Highly linear relationships between CBF and temperature in regions with different severity of ischemic conditions were found, with the highest slope in the normal region, whiles the lowest slope in the infarct region. The possible explanation for this finding may be the breakdown of auto regulation of cerebral hemodynamic in ischemic regions. The GESSE sequence was utilized for the measurement of R2'. Multiple navigator echoes were used for motion correction. In addition, the z-shimming method was applied for B0 inhomogeneity correction. Highly consistent R2' measurements were obtained in normal rats, with a standard deviation less than 1.4Hz and 2.1Hz in subcortical and cortical areas, respectively. With 45 minutes of MCAO, the relationship between ADC, CBF, R2' and OMI_R2' right before reperfusion was studied. Elevated R2' in both the lesion and peri-lesion regions were observed. The elevated R2' in the peri-lesion region leads to a comparable OMI_R2' as that of the contralateral hemisphere, suggesting that tissue may remain viable. However, a similar behavior was also observed in the core area which will require additional investigation

Computerized Analysis of Magnetic Resonance Images to Study Cerebral Anatomy in Developing Neonates

The study of cerebral anatomy in developing neonates is of great importance for the understanding of brain development during the early period of life. This dissertation therefore focuses on three challenges in the modelling of cerebral anatomy in neonates during brain development. The methods that have been developed all use Magnetic Resonance Images (MRI) as source data. To facilitate study of vascular development in the neonatal period, a set of image analysis algorithms are developed to automatically extract and model cerebral vessel trees. The whole process consists of cerebral vessel tracking from automatically placed seed points, vessel tree generation, and vasculature registration and matching. These algorithms have been tested on clinical Time-of- Flight (TOF) MR angiographic datasets. To facilitate study of the neonatal cortex a complete cerebral cortex segmentation and reconstruction pipeline has been developed. Segmentation of the neonatal cortex is not effectively done by existing algorithms designed for the adult brain because the contrast between grey and white matter is reversed. This causes pixels containing tissue mixtures to be incorrectly labelled by conventional methods. The neonatal cortical segmentation method that has been developed is based on a novel expectation-maximization (EM) method with explicit correction for mislabelled partial volume voxels. Based on the resulting cortical segmentation, an implicit surface evolution technique is adopted for the reconstruction of the cortex in neonates. The performance of the method is investigated by performing a detailed landmark study. To facilitate study of cortical development, a cortical surface registration algorithm for aligning the cortical surface is developed. The method first inflates extracted cortical surfaces and then performs a non-rigid surface registration using free-form deformations (FFDs) to remove residual alignment. Validation experiments using data labelled by an expert observer demonstrate that the method can capture local changes and follow the growth of specific sulcus

Methods for cleaning the BOLD fMRI signal

Available online 9 December 2016 http://www.sciencedirect.com/science/article/pii/S1053811916307418?via%3Dihubhttp://www.sciencedirect.com/science/article/pii/S1053811916307418?via%3DihubBlood oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI) has rapidly become a popular technique for the investigation of brain function in healthy individuals, patients as well as in animal studies. However, the BOLD signal arises from a complex mixture of neuronal, metabolic and vascular processes, being therefore an indirect measure of neuronal activity, which is further severely corrupted by multiple non-neuronal fluctuations of instrumental, physiological or subject-specific origin. This review aims to provide a comprehensive summary of existing methods for cleaning the BOLD fMRI signal. The description is given from a methodological point of view, focusing on the operation of the different techniques in addition to pointing out the advantages and limitations in their application. Since motion-related and physiological noise fluctuations are two of the main noise components of the signal, techniques targeting their removal are primarily addressed, including both data-driven approaches and using external recordings. Data-driven approaches, which are less specific in the assumed model and can simultaneously reduce multiple noise fluctuations, are mainly based on data decomposition techniques such as principal and independent component analysis. Importantly, the usefulness of strategies that benefit from the information available in the phase component of the signal, or in multiple signal echoes is also highlighted. The use of global signal regression for denoising is also addressed. Finally, practical recommendations regarding the optimization of the preprocessing pipeline for the purpose of denoising and future venues of research are indicated. Through the review, we summarize the importance of signal denoising as an essential step in the analysis pipeline of task-based and resting state fMRI studies.This work was supported by the Spanish Ministry of Economy and Competitiveness [Grant PSI 2013–42343 Neuroimagen Multimodal], the Severo Ochoa Programme for Centres/Units of Excellence in R & D [SEV-2015-490], and the research and writing of the paper were supported by the NIMH and NINDS Intramural Research Programs (ZICMH002888) of the NIH/HHS

Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 140

This bibliography lists 306 reports, articles, and other documents introduced into the NASA scientific and technical information system in March 1975

Retrospective Motion Correction in Magnetic Resonance Imaging of the Brain

Magnetic Resonance Imaging (MRI) is a tremendously useful diagnostic imaging modality that provides outstanding soft tissue contrast. However, subject motion is a significant unsolved problem; motion during image acquisition can cause blurring and distortions in the image, limiting its diagnostic utility. Current techniques for addressing head motion include optical tracking which can be impractical in clinical settings due to challenges associated with camera cross-calibration and marker fixation. Another category of techniques is MRI navigators, which use specially acquired MRI data to track the motion of the head. This thesis presents two techniques for motion correction in MRI: the first is spherical navigator echoes (SNAVs), which are rapidly acquired k-space navigators. The second is a deep convolutional neural network trained to predict an artefact-free image from motion-corrupted data. Prior to this thesis, SNAVs had been demonstrated for motion measurement but not motion correction, and they required the acquisition of a 26s baseline scan during which the subject could not move. In this work, a novel baseline approach is developed where the acquisition is reduced to 2.6s. Spherical navigators were interleaved into a spoiled gradient echo sequence (SPGR) on a stand-alone MRI system and a turbo-FLASH sequence (tfl) on a hybrid PET/MRI system to enable motion measurement throughout image acquisition. The SNAV motion measurements were then used to retrospectively correct the image data. While MRI navigator methods, particularly SNAVs that can be acquired very rapidly, are useful for motion correction, they do require pulse sequence modifications. A deep learning technique may be a more general solution. In this thesis, a conditional generative adversarial network (cGAN) is trained to perform motion correction on image data with simulated motion artefacts. We simulate motion in previously acquired brain images and use the image pairs (corrupted + original) to train the cGAN. MR image data was qualitatively and quantitatively improved following correction using the SNAV motion estimates. This was also true for the simultaneously acquired MR and PET data on the hybrid system. Motion corrected images were more similar than the uncorrected to the no-motion reference images. The deep learning approach was also successful for motion correction. The trained cGAN was evaluated on 5 subjects; and artefact suppression was observed in all images

Development of an optimised non-invasive MRI method to measure renal perfusion in patients with impaired renal function

Arterial Spin Labelling (ASL) is a unique Magnetic Resonance Imaging (MRI) approach for quantifying tissue perfusion non-invasively. More than two decades of technical developments established ASL as a valuable tool in neuroimaging, having more recently began its translation to the clinic. ASL holds great potential for the assessment of kidney disease given that it does not require contrast agents which are typically contraindicated for patients with impaired renal function. However, renal ASL applications remain limited and the technique has yet to be incorporated into clinical practice. The sensitivity of ASL to patient movement, which severely corrupts the renal perfusion estimates, is arguably one of the greatest factors hindering a wide adoption of this technique. This thesis begins with an overview of the main concepts addressed in this work (kidney physiology, MRI and ASL) and a thorough literature review of previous renal ASL work. The problem of patient movement is then addressed at all levels of the ASL framework by combining a motion-insensitive ASL acquisition scheme with a specifically tailored image processing pipeline. The feasibility of this technique to provide repeatable renal perfusion measurements is demonstrated in the first paediatric cohort with impaired renal function to undergo renal ASL. Finally, the critical findings of this thesis are summarised and prospective future research directions are outlined