Robust Low-Dose CT Perfusion Deconvolution via Tensor Total-Variation Regularization

Acute brain diseases such as acute strokes and transit ischemic attacks are the leading causes of mortality and morbidity worldwide, responsible for 9% of total death every year. Time is brain is a widely accepted concept in acute cerebrovascular disease treatment. Efficient and accurate computational framework for hemodynamic parameters estimation can save critical time for thrombolytic therapy. Meanwhile the high level of accumulated radiation dosage due to continuous image acquisition in CT perfusion (CTP) raised concerns on patient safety and public health. However, low-radiation leads to increased noise and artifacts which require more sophisticated and time-consuming algorithms for robust estimation. In this paper, we focus on developing a robust and efficient framework to accurately estimate the perfusion parameters at low radiation dosage. Specifically, we present a tensor total-variation (TTV) technique which fuses the spatial correlation of the vascular structure and the temporal continuation of the blood signal flow. An efficient algorithm is proposed to find the solution with fast convergence and reduced computational complexity. Extensive evaluations are carried out in terms of sensitivity to noise levels, estimation accuracy, contrast preservation, and performed on digital perfusion phantom estimation, as well as in vivo clinical subjects. Our framework reduces the necessary radiation dose to only 8% of the original level and outperforms the state-of-art algorithms with peak signal-to-noise ratio improved by 32%. It reduces the oscillation in the residue functions, corrects over-estimation of cerebral blood flow (CBF) and under-estimation of mean transit time (MTT), and maintains the distinction between the deficit and normal regions

Improving low-dose blood-brain barrier permeability quantification using sparse high-dose induced prior for Patlak model

Blood-brain barrier permeability (BBBP) measurements extracted from the perfusion computed tomography (PCT) using the Patlak model can be a valuable indicator to predict hemorrhagic transformation in patients with acute stroke. Unfortunately, the standard Patlak model based PCT requires excessive radiation exposure, which raised attention on radiation safety. Minimizing radiation dose is of high value in clinical practice but can degrade the image quality due to the introduced severe noise. The purpose of this work is to construct high quality BBBP maps from low-dose PCT data by using the brain structural similarity between different individuals and the relations between the high- and low-dose maps. The proposed sparse high-dose induced (shd-Patlak) model performs by building a high-dose induced prior for the Patlak model with a set of location adaptive dictionaries, followed by an optimized estimation of BBBP map with the prior regularized Patlak model. Evaluation with the simulated low-dose clinical brain PCT datasets clearly demonstrate that the shd-Patlak model can achieve more significant gains than the standard Patlak model with improved visual quality, higher fidelity to the gold standard and more accurate details for clinical analysis. Copyright 2013 Elsevier B.V. All rights reserved

A robust deconvolution method to disentangle multiple water pools in diffusion MRI

The diffusion-weighted magnetic resonance imaging (dMRI) signal measured in vivo arises from multiple diffusion domains, including hindered and restricted water pools, free water and blood pseudo-diffusion. Not accounting for the correct number of components can bias metrics obtained from model fitting because of partial volume effects that are present in, for instance, diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI). Approaches that aim to overcome this shortcoming generally make assumptions about the number of considered components, which are not likely to hold for all voxels. The spectral analysis of the dMRI signal has been proposed to relax assumptions on the number of components. However, it currently requires a clinically challenging signal-to-noise ratio (SNR) and accounts only for two diffusion processes defined by hard thresholds. In this work, we developed a method to automatically identify the number of components in the spectral analysis, and enforced its robustness to noise, including outlier rejection and a data-driven regularization term. Furthermore, we showed how this method can be used to take into account partial volume effects in DTI and DKI fitting. The proof of concept and performance of the method were evaluated through numerical simulations and in vivo MRI data acquired at 3 T. With simulations our method reliably decomposed three diffusion components from SNR = 30. Biases in metrics derived from DTI and DKI were considerably reduced when components beyond hindered diffusion were taken into account. With the in vivo data our method determined three macro-compartments, which were consistent with hindered diffusion, free water and pseudo-diffusion. Taking free water and pseudo-diffusion into account in DKI resulted in lower mean diffusivity and higher fractional anisotropy values in both gray and white matter. In conclusion, the proposed method allows one to determine co-existing diffusion compartments without prior assumptions on their number, and to account for undesired signal contaminations within clinically achievable SNR levels

Voxel-wise comparisons of cellular microstructure and diffusion-MRI in mouse hippocampus using 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND)

A key challenge in medical imaging is determining a precise correspondence between image properties and tissue microstructure. This comparison is hindered by disparate scales and resolutions between medical imaging and histology. We present a new technique, 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND), for registering medical images with 3D histology to overcome these limitations. Ex vivo 120 × 120 × 200 μm resolution diffusion-MRI (dMRI) data was acquired at 7 T from adult C57Bl/6 mouse hippocampus. Tissue was then optically cleared using CLARITY and stained with cellular markers and confocal microscopy used to produce high-resolution images of the 3D-tissue microstructure. For each sample, a dense array of hippocampal landmarks was used to drive registration between upsampled dMRI data and the corresponding confocal images. The cell population in each MRI voxel was determined within hippocampal subregions and compared to MRI-derived metrics. 3D-BOND provided robust voxel-wise, cellular correlates of dMRI data. CA1 pyramidal and dentate gyrus granular layers had significantly different mean diffusivity (p > 0.001), which was related to microstructural features. Overall, mean and radial diffusivity correlated with cell and axon density and fractional anisotropy with astrocyte density, while apparent fibre density correlated negatively with axon density. Astrocytes, axons and blood vessels correlated to tensor orientation

Improved quantification of perfusion in patients with cerebrovascular disease.

In recent years measurements of cerebral perfusion using bolus-tracking MRI have become common clinical practice in the diagnosis and management of patients with stroke and cerebrovascular disease. An active area of research is the development of methods to identify brain tissue that is at risk of irreversible damage, but amenable to salvage using reperfusion treatments, such as thrombolysis. However, the specificity and sensitivity of these methods are limited by the inaccuracies in the perfusion data. Accurate measurements of perfusion are difficult to obtain, especially in patients with cerebrovascular diseases. In particular, if the bolus of MR contrast is delayed and/or dispersed due to cerebral arterial abnormalities, perfusion is likely to be underestimated using the standard analysis techniques. The potential for such underestimation is often overlooked when using the perfusion maps to assess stroke patients. Since thrombolysis can increase the risk of haemorrhage, a misidentification of 'at-risk' tissue has potentially dangerous clinical implications. This thesis presents several methodologies which aim to improve the accuracy and interpretation of the analysed bolus-tracking data. Two novel data analysis techniques are proposed, which enable the identification of brain regions where delay and dispersion of the bolus are likely to bias the perfusion measurements. In this way true hypoperfusion can be distinguished from erroneously low perfusion estimates. The size of the perfusion measurement errors are investigated in vivo, and a parameterised characterisation of the bolus delay and dispersion is obtained. Such information is valuable for the interpretation of in vivo data, and for further investigation into the effects of abnormal vasculature on perfusion estimates. Finally, methodology is presented to minimise the perfusion measurement errors prevalent in patients with cerebrovascular diseases. The in vivo application of this method highlights the dangers of interpreting perfusion values independently of the bolus delay and dispersion

preliminary clinical evaluation of the ASTRA4D algorithm

Objectives. To propose and evaluate a four-dimensional (4D) algorithm for joint motion elimination and spatiotemporal noise reduction in low-dose dynamic myocardial computed tomography perfusion (CTP). Methods. Thirty patients with suspected or confirmed coronary artery disease were prospectively included und underwent dynamic contrast-enhanced 320-row CTP. The presented deformable image registration method ASTRA4D identifies a low-dimensional linear model of contrast propagation (by principal component analysis, PCA) of the ex-ante temporally smoothed time-intensity curves (by local polynomial regression). Quantitative (standard deviation, signal-to-noise ratio (SNR), temporal variation, volumetric deformation) and qualitative (motion, contrast, contour sharpness; 1, poor; 5, excellent) measures of CTP quality were assessed for the original and motion-compensated volumes (without and with temporal filtering, PCA/ASTRA4D). Following visual myocardial perfusion deficit detection by two readers, diagnostic accuracy was evaluated using 1.5T magnetic resonance (MR) myocardial perfusion imaging as the reference standard in 15 patients. Results. Registration using ASTRA4D was successful in all 30 patients and resulted in comparison with the benchmark PCA in significantly (p<0.001) reduced noise over time (-83%, 178.5 vs 29.9) and spatially (-34%, 21.4 vs 14.1) as well as improved SNR (+47%, 3.6 vs 5.3) and subjective image quality (motion, contrast, contour sharpness: +1.0, +1.0, +0.5). ASTRA4D resulted in significantly improved per-segment sensitivity of 91% (58/64) and similar specificity of 96% (429/446) compared with PCA (52%, 33/64; 98%, 435/446; p=0.011) and the original sequence (45%, 29/64; 98%, 438/446; p=0.003) in the visual detection of perfusion deficits. Conclusions. The proposed functional approach to temporal denoising and morphologic alignment was shown to improve quality metrics and sensitivity of 4D CTP in the detection of myocardial ischemia.Zielsetzung. Die Entwicklung und Bewertung einer Methode zur simultanen Rauschreduktion und Bewegungskorrektur für niedrig dosierte dynamische CT Myokardperfusion. Methoden. Dreißig prospektiv eingeschlossene Patienten mit vermuteter oder bestätigter koronarer Herzkrankheit wurden einer dynamischen CT Myokardperfusionsuntersuchung unterzogen. Die präsentierte Registrierungsmethode ASTRA4D ermittelt ein niedrigdimensionales Modell des Kontrastmittelflusses (mittels einer Hauptkomponentenanalyse, PCA) der vorab zeitlich geglätteten Intensitätskurven (mittels lokaler polynomialer Regression). Quantitative (Standardabweichung, Signal-Rausch-Verhältnis (SNR), zeitliche Schwankung, räumliche Verformung) und qualitative (Bewegung, Kontrast, Kantenschärfe; 1, schlecht; 5, ausgezeichnet) Kennzahlen der unbearbeiteten und bewegungskorrigierten Perfusionsdatensätze (ohne und mit zeitlicher Glättung PCA/ASTRA4D) wurden ermittelt. Nach visueller Beurteilung von myokardialen Perfusionsdefiziten durch zwei Radiologen wurde die diagnostische Genauigkeit im Verhältnis zu 1.5T Magnetresonanztomographie in 15 Patienten ermittelt. Resultate. Bewegungskorrektur mit ASTRA4D war in allen 30 Patienten erfolgreich und resultierte im Vergleich mit der PCA Methode in signifikant (p<0.001) verringerter zeitlicher Schwankung (-83%, 178.5 gegenüber 29.9) und räumlichem Rauschen (-34%, 21.4 gegenüber 14.1) sowie verbesserter SNR (+47%, 3.6 gegenüber 5.3) und subjektiven Qualitätskriterien (Bewegung, Kontrast, Kantenschärfe: +1.0, +1.0, +0.5). ASTRA4D resultierte in signifikant verbesserter segmentweiser Sensitivität 91% (58/64) und ähnlicher Spezifizität 96% (429/446) verglichen mit der PCA Methode (52%, 33/64; 98%, 435/446; p=0.011) und dem unbearbeiteten Perfusionsdatensatz (45%, 29/64; 98%, 438/446; p=0.003) in der visuellen Beurteilung von myokardialen Perfusionsdefiziten. Schlussfolgerungen. Der vorgeschlagene funktionale Ansatz zur simultanen Rauschreduktion und Bewegungskorrektur verbesserte Qualitätskriterien und Sensitivität von dynamischer CT Perfusion in der visuellen Erkennung von Myokardischämie

Cerebellum and neurodegenerative diseases: Beyond conventional magnetic resonance imaging

The cerebellum plays a key role in movement control and in cognition and cerebellar involvement is described in several neurodegenerative diseases. While conventional magnetic resonance imaging (MRI) is widely used for brain and cerebellar morphologic evaluation, advanced MRI techniques allow the investigation of cerebellar microstructural and functional characteristics. Volumetry, voxel-based morphometry, diffusion MRI based fiber tractography, resting state and task related functional MRI, perfusion, and proton MR spectroscopy are among the most common techniques applied to the study of cerebellum. In the present review, after providing a brief description of each technique's advantages and limitations, we focus on their application to the study of cerebellar injury in major neurodegenerative diseases, such as multiple sclerosis, Parkinson's and Alzheimer's disease and hereditary ataxia. A brief introduction to the pathological substrate of cerebellar involvement is provided for each disease, followed by the review of MRI studies exploring structural and functional cerebellar abnormalities and by a discussion of the clinical relevance of MRI measures of cerebellar damage in terms of both clinical status and cognitive performance