Pattern identification of biomedical images with time series: contrasting THz pulse imaging with DCE-MRIs

Objective We provide a survey of recent advances in biomedical image analysis and classification from emergent imaging modalities such as terahertz (THz) pulse imaging (TPI) and dynamic contrast-enhanced magnetic resonance images (DCE-MRIs) and identification of their underlining commonalities. Methods Both time and frequency domain signal pre-processing techniques are considered: noise removal, spectral analysis, principal component analysis (PCA) and wavelet transforms. Feature extraction and classification methods based on feature vectors using the above processing techniques are reviewed. A tensorial signal processing de-noising framework suitable for spatiotemporal association between features in MRI is also discussed. Validation Examples where the proposed methodologies have been successful in classifying TPIs and DCE-MRIs are discussed. Results Identifying commonalities in the structure of such heterogeneous datasets potentially leads to a unified multi-channel signal processing framework for biomedical image analysis. Conclusion The proposed complex valued classification methodology enables fusion of entire datasets from a sequence of spatial images taken at different time stamps; this is of interest from the viewpoint of inferring disease proliferation. The approach is also of interest for other emergent multi-channel biomedical imaging modalities and of relevance across the biomedical signal processing community

Augmented breast tumor classification by perfusion analysis

Magnetic resonance and computed tomography imaging aid in the diagnosis and analysis of pathologic conditions. Blood flow, or perfusion, through a region of tissue can be computed from a time series of contrast-enhanced images. Perfusion is an important set of physiological parameters that reflect angiogenesis. In cancer, heightened angiogenesis is a key process in the growth and spread of tumorous masses. An automatic classification technique using recovered perfusion may prove to be a highly accurate diagnostic tool. Such a classification system would supplement existing histopathological tests, and help physicians to choose the most optimal treatment protocol. Perfusion is obtained through deconvolution of signal intensity series and a pharmacokinetic model. However, many computational problems complicate the accurate-consistent recovery of perfusion. The high time-resolution acquisition of images decreases signal-to-noise, producing poor deconvolution solutions. The delivery of contrast agent as a function of time must also be determined or sampled before deconvolution can proceed. Some regions of the body, such as the brain, provide a nearby artery to serve as this arterial input function. Poor estimates can lead to an over or under estimation of perfusion. Breast tissue is an example of one tissue region where a clearly defined artery is not present. This proposes a new method of using recovered perfusion and spatial information in an automated classifier. This classifier grades suspected lesions as benign or malignant. This method can be integrated into a computer-aided diagnostic system to enhance the value of medical imagery

Quantitative Analysis of Dynamic Contrast-Enhanced Magnetic Resonance Breast Images: Optimization of the Time-to-Peak as a Diagnostic Indicator

Dynamic contrast-enhanced MRI (DCE-MRI) has been widely used in the diagnosis of breast cancer and as an aid in the management of this disease. Although DCE-MRI has a high sensitivity for the detection of malignant breast lesions, distinguishing malignant from benign lesions is more challenging for this method and may depend to some extent on how the images are analysed. Although clinical assessment of these images typically involves qualitative assessment by an expert, there is growing interest in the development of quantitative and automated methods to assist the expert assessment. This thesis involves the quantitative analysis of a particular empirical feature of the time evolution of the DCE-MRI signal known as the time-to-peak ( 7 ^ ) . In particular, this thesis investigates die feasibility of applying measures sensitive to 7 ^ heterogeneity as indicators for malignancy in breast DCE-MRI. Breast lesions in this study were automatically segmented by K-means clustering. Voxel- by-voxel 7\u27peak values were extracted using an empirical model. The / 1th percentile values (p = 10, 20...) of the 7’peak distribution within each lesion, as well as the fractional and absolute hot spot volumes were determined, where hot spot volume refers to the volume of tissue with 7 ^ less than a threshold value. Using the area under the receiver operating characteristic curve (AUC), these measures were tested as indicators for differentiating fibroadenomas from invasive lesions and from ductal carcinoma in situ, as well as for differentiating non-fibroadenoma benign lesions from these malignant lesions. For differentiating fibroadenomas from malignant lesions, low percentile values (p = 10) provided high diagnostic performance. At the optimal threshold (3 min), the hot spot volume provided high diagnostic performance. However, non-fibroadenoma benign lesions were quite difficult to distinguish from malignant lesions. This thesis demonstrates that quantitative analysis of the 7’peak distribution can be optimized for diagnostic performance providing indicators sensitive to intra-lesion r peak heterogeneity

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

Computer-aided detection and diagnosis of breast cancer in 2D and 3D medical imaging through multifractal analysis

This Thesis describes the research work performed in the scope of a doctoral research program and presents its conclusions and contributions. The research activities were carried on in the industry with Siemens S.A. Healthcare Sector, in integration with a research team. Siemens S.A. Healthcare Sector is one of the world biggest suppliers of products, services and complete solutions in the medical sector. The company offers a wide selection of diagnostic and therapeutic equipment and information systems. Siemens products for medical imaging and in vivo diagnostics include: ultrasound, computer tomography, mammography, digital breast tomosynthesis, magnetic resonance, equipment to angiography and coronary angiography, nuclear imaging, and many others. Siemens has a vast experience in Healthcare and at the beginning of this project it was strategically interested in solutions to improve the detection of Breast Cancer, to increase its competitiveness in the sector. The company owns several patents related with self-similarity analysis, which formed the background of this Thesis. Furthermore, Siemens intended to explore commercially the computer- aided automatic detection and diagnosis eld for portfolio integration. Therefore, with the high knowledge acquired by University of Beira Interior in this area together with this Thesis, will allow Siemens to apply the most recent scienti c progress in the detection of the breast cancer, and it is foreseeable that together we can develop a new technology with high potential. The project resulted in the submission of two invention disclosures for evaluation in Siemens A.G., two articles published in peer-reviewed journals indexed in ISI Science Citation Index, two other articles submitted in peer-reviewed journals, and several international conference papers. This work on computer-aided-diagnosis in breast led to innovative software and novel processes of research and development, for which the project received the Siemens Innovation Award in 2012. It was very rewarding to carry on such technological and innovative project in a socially sensitive area as Breast Cancer.No cancro da mama a deteção precoce e o diagnóstico correto são de extrema importância na prescrição terapêutica e caz e e ciente, que potencie o aumento da taxa de sobrevivência à doença. A teoria multifractal foi inicialmente introduzida no contexto da análise de sinal e a sua utilidade foi demonstrada na descrição de comportamentos siológicos de bio-sinais e até na deteção e predição de patologias. Nesta Tese, três métodos multifractais foram estendidos para imagens bi-dimensionais (2D) e comparados na deteção de microcalci cações em mamogramas. Um destes métodos foi também adaptado para a classi cação de massas da mama, em cortes transversais 2D obtidos por ressonância magnética (RM) de mama, em grupos de massas provavelmente benignas e com suspeição de malignidade. Um novo método de análise multifractal usando a lacunaridade tri-dimensional (3D) foi proposto para classi cação de massas da mama em imagens volumétricas 3D de RM de mama. A análise multifractal revelou diferenças na complexidade subjacente às localizações das microcalci cações em relação aos tecidos normais, permitindo uma boa exatidão da sua deteção em mamogramas. Adicionalmente, foram extraídas por análise multifractal características dos tecidos que permitiram identi car os casos tipicamente recomendados para biópsia em imagens 2D de RM de mama. A análise multifractal 3D foi e caz na classi cação de lesões mamárias benignas e malignas em imagens 3D de RM de mama. Este método foi mais exato para esta classi cação do que o método 2D ou o método padrão de análise de contraste cinético tumoral. Em conclusão, a análise multifractal fornece informação útil para deteção auxiliada por computador em mamogra a e diagnóstico auxiliado por computador em imagens 2D e 3D de RM de mama, tendo o potencial de complementar a interpretação dos radiologistas

Intraoperative Quantification of Bone Perfusion in Lower Extremity Injury Surgery

Orthopaedic surgery is one of the most common surgical categories. In particular, lower extremity injuries sustained from trauma can be complex and life-threatening injuries that are addressed through orthopaedic trauma surgery. Timely evaluation and surgical debridement following lower extremity injury is essential, because devitalized bones and tissues will result in high surgical site infection rates. However, the current clinical judgment of what constitutes “devitalized tissue” is subjective and dependent on surgeon experience, so it is necessary to develop imaging techniques for guiding surgical debridement, in order to control infection rates and to improve patient outcome. In this thesis work, computational models of fluorescence-guided debridement in lower extremity injury surgery will be developed, by quantifying bone perfusion intraoperatively using Dynamic contrast-enhanced fluorescence imaging (DCE-FI) system. Perfusion is an important factor of tissue viability, and therefore quantifying perfusion is essential for fluorescence-guided debridement. In Chapters 3-7 of this thesis, we explore the performance of DCE-FI in quantifying perfusion from benchtop to translation: We proposed a modified fluorescent microsphere quantification technique using cryomacrotome in animal model. This technique can measure bone perfusion in periosteal and endosteal separately, and therefore to validate bone perfusion measurements obtained by DCE-FI; We developed pre-clinical rodent contaminated fracture model to correlate DCE-FI with infection risk, and compare with multi-modality scanning; Furthermore in clinical studies, we investigated first-pass kinetic parameters of DCE-FI and arterial input functions for characterization of perfusion changes during lower limb amputation surgery; We conducted the first in-human use of dynamic contrast-enhanced texture analysis for orthopaedic trauma classification, suggesting that spatiotemporal features from DCE-FI can classify bone perfusion intraoperatively with high accuracy and sensitivity; We established clinical machine learning infection risk predictive model on open fracture surgery, where pixel-scaled prediction on infection risk will be accomplished. In conclusion, pharmacokinetic and spatiotemporal patterns of dynamic contrast-enhanced imaging show great potential for quantifying bone perfusion and prognosing bone infection. The thesis work will decrease surgical site infection risk and improve successful rates of lower extremity injury surgery

A comparative evaluation for liver segmentation from spir images and a novel level set method using signed pressure force function

Thesis (Doctoral)--Izmir Institute of Technology, Electronics and Communication Engineering, Izmir, 2013Includes bibliographical references (leaves: 118-135)Text in English; Abstract: Turkish and Englishxv, 145 leavesDeveloping a robust method for liver segmentation from magnetic resonance images is a challenging task due to similar intensity values between adjacent organs, geometrically complex liver structure and injection of contrast media, which causes all tissues to have different gray level values. Several artifacts of pulsation and motion, and partial volume effects also increase difficulties for automatic liver segmentation from magnetic resonance images. In this thesis, we present an overview about liver segmentation methods in magnetic resonance images and show comparative results of seven different liver segmentation approaches chosen from deterministic (K-means based), probabilistic (Gaussian model based), supervised neural network (multilayer perceptron based) and deformable model based (level set) segmentation methods. The results of qualitative and quantitative analysis using sensitivity, specificity and accuracy metrics show that the multilayer perceptron based approach and a level set based approach which uses a distance regularization term and signed pressure force function are reasonable methods for liver segmentation from spectral pre-saturation inversion recovery images. However, the multilayer perceptron based segmentation method requires a higher computational cost. The distance regularization term based automatic level set method is very sensitive to chosen variance of Gaussian function. Our proposed level set based method that uses a novel signed pressure force function, which can control the direction and velocity of the evolving active contour, is faster and solves several problems of other applied methods such as sensitivity to initial contour or variance parameter of the Gaussian kernel in edge stopping functions without using any regularization term

Intensity and Compactness Enabled Saliency Estimation for Leakage Detection in Diabetic and Malarial Retinopathy

Leakage in retinal angiography currently is a key feature for confirming the activities of lesions in the management of a wide range of retinal diseases, such as diabetic maculopathy and paediatric malarial retinopathy. This paper proposes a new saliency-based method for the detection of leakage in fluorescein angiography. A superpixel approach is firstly employed to divide the image into meaningful patches (or superpixels) at different levels. Two saliency cues, intensity and compactness, are then proposed for the estimation of the saliency map of each individual superpixel at each level. The saliency maps at different levels over the same cues are fused using an averaging operator. The two saliency maps over different cues are fused using a pixel-wise multiplication operator. Leaking regions are finally detected by thresholding the saliency map followed by a graph-cut segmentation. The proposed method has been validated using the only two publicly available datasets: one for malarial retinopathy and the other for diabetic retinopathy. The experimental results show that it outperforms one of the latest competitors and performs as well as a human expert for leakage detection and outperforms several state-of-the-art methods for saliency detection