Biomedical subjects

Michael Brady

Publications and source records attributed to Michael Brady.

18 recordsLinked to original sources

PubMed2006

A biologically inspired algorithm for microcalcification cluster detection.

The early detection of breast cancer greatly improves prognosis. One of the earliest signs of cancer is the formation of clusters of microcalcifications. We introduce a novel method for microcalcification detection based on a biologically inspired adaptive model of contrast detection. This model is used in conjunction with image filtering based on anisotropic diffusion and curvilinear structure removal using local energy and phase congruency. An important practical issue in automatic detection methods is the selection of parameters: we show that the parameter values for our algorithm can be estimated automatically from the image. This way, the method is made robust and essentially free of parameter tuning. We report results on mammograms from two databases and show that the detection performance can be improved by first including a normalisation scheme.

Algorithms↗

PubMed2005

Extracting and visualizing physiological parameters using dynamic contrast-enhanced magnetic resonance imaging of the breast.

An analysis procedure is presented that enables the acquisition and visualization of physiologically relevant parameters using dynamic contrast-enhanced magnetic resonance imaging. The first stage of the process involves the use of a signal model that relates the measured magnetic resonance signal to the contrast agent concentration. Since the model requires knowledge of the longitudinal relaxation time T(1), a novel optimization scheme is presented which ensures a reliable measurement. Pharmacokinetic modelling of the observed contrast agent uptake is then performed to obtain physiological parameters relating to microvessel leakage permeability and volume fraction and the assumptions made in the derivation of these parameters are discussed. A simple colour representation is utilized that enables the relevant physiological information to be conveyed to the clinician in a visually efficient and meaningful manner. A second representation, based on vector maps, is also devised and it is demonstrated how this can be used for malignant tumour segmentation. Finally, the procedure is applied to 14 pre- and post-chemotherapy breast cases to demonstrate the clinical value of the technique. In particular, the apparent improved representation of tissue vascularity when compared to conventional methods and the implications for this in treatment assessment are discussed.

Algorithms↗

PubMed2005

Phase mutual information as a similarity measure for registration.

This article describes a new method for non-rigid alignment of multimodal images. Multimodal image registration is most often accomplished by modelling, in some sense, an intensity mapping between the images. Here, the alternative strategy of modelling a relationship between local image phase is introduced. This method is intrinsically image feature based, and searches for relationships between feature appearances, rather than tissue class intensity. This enables registration of modalities for which image intensity is not a simple function of tissue class, for example ultrasound. It is also demonstrated that this method performs comparably to an intensity method even when the images are related by a simple intensity transform, but that the phase method is significantly more robust to image artifacts which corrupt the ideal intensity mapping.

Algorithms↗

PubMed2005

Basal lamina visualization using color image processing and pattern recognition.

In histologic assessment, the absence of basal lamina is a useful feature for distinguishing invasive malignancy from benign and in situ lesions. As this feature is not possible to assess in routine H&E sections, pathologists have instead relied on histochemical and immunohistochemical stains to show components of the basal lamina such as laminin or type IV collagen. Standard image-processing software with the necessary image-processing toolbox (Matlab v5, Mathworks, Natick, MA) was used in a unique combination of color image processing and pattern recognition techniques to accentuate the collagenous stroma surrounding glands, which approximates basal lamina, in a series of benign, in situ, and invasive breast proliferations. Distinct differences in pattern were found between benign and invasive lesions, and also between in situ and malignant lesions, corresponding to that observed with type IV collagen immunostaining. Compared with immunostaining, this computer-generated method had a sensitivity of 0.96, specificity of 0.89, positive predictive value of 0.92, negative predictive value of 0.89, positive likelihood ratio of 9.1, and negative likelihood ratio of 0.042. Digital image processing serves as a less expensive and faster way of visualizing basal lamina and represents a useful adjunct to identify invasive malignancy in routinely stained sections. In addition, digital visualization of basal lamina is readily amenable to quantitative assessment, and the method provides a basis for the development of computer-based cancer diagnosis.

Basement Membrane↗

PubMed2005

A registration framework for the comparison of mammogram sequences.

In this paper, we present a two-stage algorithm for mammogram registration, the geometrical alignment of mammogram sequences. The rationale behind this paper stems from the intrinsic difficulties in comparing mammogram sequences. Mammogram comparison is a valuable tool in national breast screening programs as well as in frequent monitoring and hormone replacement therapy (HRT). The method presented in this paper aims to improve mammogram comparison by estimating the underlying geometric transformation for any mammogram sequence. It takes into consideration the various temporal changes that may occur between successive scans of the same woman and is designed to overcome the inconsistencies of mammogram image formation.

Algorithms↗

PubMed2004

A mammographic image analysis method to detect and measure changes in breast density.

We present an image analysis method that can detect and measure breast density from digitised mammograms. We present initial results on applying our method to characterise breast changes, in particular, changes due to Hormone Replacement Therapy (HRT). It has been established that long-term use of certain hormone replacement therapies can increase the risk of breast cancer, a fact that encourages the notion that objective measures of tissue density can be an important development in breast cancer image analysis. A set of 59 temporal pairs of mammograms of patients undergoing HRT (two images per patient) were used. The clinician's assessment of density changes constituted the ground truth for evaluating the proposed quantitative measures of density change. The measures we developed are based on the Standard Mammogram Form (SMF) representation of interesting tissue and their performance (agreement with the expert's description) is also compared to the "interactive thresholding" method that has been used in the past to characterise mammographic density. The results clearly indicate that present methods for measuring mammographic density fail to characterise temporal changes while the proposed measures have the potential to aid the radiologist in assessing temporal density changes both on a global and a local basis.

Algorithms↗

PubMed2004

Clinical validation of the paediatric pain profile.

The Paediatric Pain Profile (PPP) is a 20-item behaviour rating scale designed to assess pain in children with severe neurological disability. We assessed the validity and reliability of the scale in 140 children (76 females, mean age 9 years 11 months, SD 4 years 7 months; range 1 to 18 years), unable to communicate through speech or augmentative communication. Parents used the PPP to rate retrospectively their child's behaviour when 'at their best' and when in pain. To assess interrater reliability, two raters concurrently observed and individually rated each child's behaviour. To assess construct validity and responsiveness of the scale, behaviour of 41 children was rated before and for four hours after administration of an 'as required' analgesic. Behaviour of 30 children was rated before surgery and for five days after. Children had significantly higher scores when reported to have pain than 'at their best' and scores increased in line with global evaluations of pain. Internal consistency ranged from 0.75 to 0.89 (Cronbach's alpha) and interrater reliability from 0.74 to 0.89 (intraclass correlation). Sensitivity (1.00) and specificity (0.91) were optimized at a cut-off of 14/60. PPP score was significantly greater before administration of the analgesic than after (paired-sample t-tests, p<0.001). Though there was no significant difference in mean pre- and postoperative scores, highest PPP score occurred in the first 24 hours after surgery in 14 (47%) children. Results suggest that the PPP is reliable and valid and has potential for use both clinically and in intervention research.

Adolescent↗

PubMed2003

Selective abolition of pancreatic RNase binding to its inhibitor protein.

We have modified RNase inhibitor (RI) protein so that it no longer detectably binds pancreatic RNases but retains near-native affinity for human angiogenin (ANG). The K(i) value for RNase A is increased by a factor of >10(8), from 36 fM to >4 microM, and the selectivity factor for ANG is now >10(9). This dramatic change was achieved by remodeling the human RI loop segment Cys-408 -Leu-409 -Gly-410, which makes minor interactions with pancreatic RNase but does not contact ANG. The modifications selected were designed to sterically hinder docking of the undesired ligand. Three of the variants tested (C408W, G410W, and C408W/G410W) bind RNase A with almost the same avidity as WT RI. However, combination of the 408/410 double Trp replacement with deletion of the intervening residue, Leu-409, was sufficient to abolish inhibition of RNase A and human pancreatic RNase. The K(i) value for ANG with the deletion variant is 1.1 fM, only 2-fold higher than with WT RI. This variant may have potential utility both as an anticancer drug targeting ANG and as a tool for the investigation of the biological function of ANG. More generally, these findings demonstrate that a protein-protein interaction can be effectively and specifically disrupted by redesigning an interface region that makes no major energetic contribution to complex stability. This finding, in turn, may have implications for the development of small molecules that modulate protein-protein interactions.

Base Sequence↗

PubMed2003

Velocity estimation in ultrasound images: a block matching approach.

In this paper, we focus on velocity estimation in ultrasound images sequences. Ultrasound images present many difficulties in image processing because of the typically high level of noise found in them. Recently, Cohen and Dinstein have derived a new similarity measure, according to a simplified image formation model of ultrasound images, optimal in the maximum likelihood sense. This similarity measure is better for ultrasound images than others such as the sum-of-square differences or normalised cross-correlation because it takes into account the fact that the noise in an ultrasound image is multiplicative Rayleigh noise, and that displayed ultrasound images are log-compressed. In this work we investigate the use of this similarity measure in a block matching method. The underlying framework of the method is Singh's algorithm. New improvements are made both on the similarity measure and the Singh algorithm to provide better velocity estimates. A global optimisation scheme for algorithm parameter estimation is also proposed. We show that this optimisation makes an improvement of approximately 35% in comparison to the result obtained with the worst parameter set. Results on clinically acquired cardiac and breast ultrasound sequences, demonstrate the robustness of the method.

Algorithms↗

PubMed2003

Fusion of contrast-enhanced breast MR and mammographic imaging data.

Increasing use is being made of Gd-DTPA contrast-enhanced magnetic resonance imaging for breast cancer assessment since it provides 3D functional information via pharmacokinetic interaction between contrast agent and tumour vascularity, and because it is applicable to women of all ages as well as patients with post-operative scarring. Contrast-enhanced MRI (CE-MRI) is complementary to conventional X-ray mammography, since it is a relatively low-resolution functional counterpart of a comparatively high-resolution 2D structural representation. However, despite the additional information provided by MRI, mammography is still an extremely important diagnostic imaging modality, particularly for several common conditions such as ductal carcinoma in situ (DCIS) where it has been shown that there is a strong correlation between microcalcification clusters and malignancy. Pathological indicators such as calcifications and fine spiculations are not visible in CE-MRI and therefore there is clinical and diagnostic value in fusing the high-resolution structural information available from mammography with the functional data acquired from MRI imaging. This paper presents a novel data fusion technique whereby medial-lateral oblique (MLO) and cranial-caudal (CC) mammograms (2D data) are registered to 3D contrast-enhanced MRI volumes. We utilise a combination of pharmacokinetic modelling, projection geometry, wavelet-based landmark detection and thin-plate spline non-rigid 'warping' to transform the coordinates of regions of interest (ROIs) from the 2D mammograms to the spatial reference frame of the contrast-enhanced MRI volume. Of key importance is the use of a flexible wavelet-based feature extraction technique that enables feature correspondences to be robustly determined between the very different image characteristics of X-ray mammography and MRI. An evaluation of the fusion framework is demonstrated with a series of clinical cases and a total of 14 patient examples.

Adult↗

PubMed2003

Clinical use of a simultaneous HPLC assay for indinavir, saquinavir, ritonavir, and nelfinavir in children and adults.

Protease inhibitor (PI) monitoring may improve the care of human immunodeficiency virus (HIV)-infected patients; however, pediatric data are limited. A high-performance liquid chromatographic (HPLC) assay developed for the simultaneous determination of indinavir, ritonavir, saquinavir, and nelfinavir in 0.2 mL of plasma was used to quantify PI concentrations in HIV patients. The reliability, sensitivity, and specificity of the assay were first verified in stored adult samples. Later, blood collected prospectively from patients aged 2.9 to 42 years of age (10 adults aged 24 to 42 and 15 children aged 2.9 to 18 years) was tested. Nondetectable (below 25-50 ng/mL) concentrations (ND) were found in 33% of adult samples and 24% of pediatric samples. Four patients taking from 13.7 to 28 mg/kg/d of ritonavir (mean of 21.3) had concentrations ranging from ND to 11.4 microg/mL, quite different from predicted values. Correctable, important clinical problems including drug-drug interactions, drug administration problems, and confirmed noncompliance were identified and corrected using modern therapeutic drug monitoring (TDM) techniques. Routine PI monitoring and interpretation (TDM) could improve the care of adult and pediatric HIV patients; especially in patients who do not respond as expected to treatment, develop viral resistance or toxicity, and have questionable compliance.

Adolescent↗

PubMed2003

Clinical use of a simultaneous HPLC assay for indinavir, saquinavir, ritonavir and nelfinavir in children and adults.

PROTEASE INHIBITOR TDM: This study examines the importance of therapeutic drug monitoring (TDM) of protease inhibitors (PI) in adults and children infected with the human immunodeficiency virus (HIV). Pediatric patients were included because information in this population is limited. A high performance liquid chromatographic (HPLC) assay measured indinavir, saquinavir, ritonavir and nelfinavir simultaneously in 0.2 mL of plasma. Initially, the reliability, sensitivity and specificity of the assay were verified in stored samples of plasma from adult patients who had been receiving PIs. Non-detectable concentrations (ND) were <25-50 ng/mL. In 96 out of 293 stored samples from adult patients, selected randomly, concentrations of PIs were ND. In a second prospective study of 10 adults (9 mothers and one father, aged 24-42 years) and 15 children (2.9-18 years) ND levels of PI were observed frequently (27% or 4 out of 15 pediatric subjects). In the latter study, drug-drug interactions, dosing errors, noncompliance and other important problems were identified and corrected. Routine monitoring and interpretation of PI concentrations (TDM) may improve the management of adult and pediatric patients infected with HIV, especially in those who fail to respond, develop adverse effects or viral resistance, or lack compliance.

Adult↗

PubMed2003

MammoGrid: large-scale distributed mammogram analysis.

Breast cancer as a medical condition and mammograms as images exhibit many dimensions of variability across the population. Similarly, the way diagnostic systems are used and maintained by clinicians varies between imaging centres and breast screening programmes, and so does the appearance of the mammograms generated. A distributed database that reflects the spread of pathologies across the population is an invaluable tool for the epidemiologist and the understanding of the variation in image acquisition protocols is essential to a radiologist in a screening programme. Exploiting emerging grid technology, the aim of the MammoGrid [1] project is to develop a Europe-wide database of mammograms that will be used to investigate a set of important healthcare applications and to explore the potential of the grid to support effective co-working between healthcare professionals.

Breast Neoplasms↗

PubMed2002

Virological and immunological effects of short-course antiretroviral therapy in primary HIV infection.

BACKGROUND: National and international guidelines call for the treatment of primary HIV infection (PHI) with combination antiretroviral therapy, although the ideal timing and duration of this intervention is unknown. Recent immunological studies of antiretroviral therapy on small numbers of patients with PHI have reported preservation of HIV-specific CD4 T-helper responses, ordinarily lost in the absence of intervention. We sought to investigate whether a short course of antiretroviral therapy (SCART) at PHI was sufficient to preserve HIV-specific cellular immunity. METHODS: Forty-five subjects with confirmed PHI were offered SCART at diagnosis. HIV specific cellular immune responses and virological parameters were assessed at monthly intervals. RESULTS: Thirty-seven of the subjects chose SCART at PHI, and achieved a plasma viral load < 50 RNA copies/ml by a median of 10 weeks (range, 4-32 weeks). Two of the 45 individuals had evidence of genotypic HIV drug resistance at baseline, and none developed new mutations following therapy. All patients who received SCART at PHI showed preservation of HIV-specific CD4 T-helper responses up to 64 weeks off SCART. CONCLUSION: SCART at PHI was safe, did not induce the development of drug resistance, and appeared sufficient to preserve HIV-specific CD4 T-helper responses. However, PHI is highly heterogeneous, and a large-scale randomized trial of SCART at PHI is now needed.

Adult↗

PubMed2002

Improved optimization for the robust and accurate linear registration and motion correction of brain images.

Linear registration and motion correction are important components of structural and functional brain image analysis. Most modern methods optimize some intensity-based cost function to determine the best registration. To date, little attention has been focused on the optimization method itself, even though the success of most registration methods hinges on the quality of this optimization. This paper examines the optimization process in detail and demonstrates that the commonly used multiresolution local optimization methods can, and do, get trapped in local minima. To address this problem, two approaches are taken: (1) to apodize the cost function and (2) to employ a novel hybrid global-local optimization method. This new optimization method is specifically designed for registering whole brain images. It substantially reduces the likelihood of producing misregistrations due to being trapped by local minima. The increased robustness of the method, compared to other commonly used methods, is demonstrated by a consistency test. In addition, the accuracy of the registration is demonstrated by a series of experiments with motion correction. These motion correction experiments also investigate how the results are affected by different cost functions and interpolation methods.

Acoustic Stimulation↗

PubMed2002

Estimation of the partial volume effect in MRI.

The partial volume effect (PVE) arises in volumetric images when more than one tissue type occurs in a voxel. In such cases, the voxel intensity depends not only on the imaging sequence and tissue properties, but also on the proportions of each tissue type present in the voxel. We have demonstrated in previous work that ignoring this effect by establishing binary voxel-based segmentations introduces significant errors in quantitative measurements, such as estimations of the volumes of brain structures. In this paper, we provide a statistical estimation framework to quantify PVE and to propagate voxel-based estimates in order to compute global magnitudes, such as volume, with associated estimates of uncertainty. Validation is performed on ground truth synthetic images and MRI phantoms, and a clinical study is reported. Results show that the method allows for robust morphometric studies and provides resolution unattainable to date.

Brain↗

PubMed2002

A CAD system for the 3D location of lesions in mammograms.

A CAD system for estimating the 3D (three-dimensional) positions of lesions found in two mammographic views is described. The system is an extension of our previous method [Comput. Vis. Image Understand. 83 (2001) 38] which finds corresponding 2D positions in different mammographic views. The method calculates curved epipolar lines by developing a simulation of breast deformation into stereo camera geometry. Using such curved epipolar lines, not only can we determine point correspondences, but can estimate the 3D location of a lesion. In this paper, we first explain the underlying principles and system organisation. The correctness of the 3D positions calculated by the system is examined using a set of breast lesions, which appear both in mammograms and in MRI data. The experimental results demonstrate the clinical promise of the CAD system.

Algorithms↗

PubMed2002

Segmentation of ultrasound B-mode images with intensity inhomogeneity correction.

Displayed ultrasound (US) B-mode images often exhibit tissue intensity inhomogeneities dominated by nonuniform beam attenuation within the body. This is a major problem for intensity-based, automatic segmentation of video-intensity images because conventional threshold-based or intensity-statistic-based approaches do not work well in the presence of such image distortions. Time gain compensation (TGC) is typically used in standard US machines in an attempt to overcome this. However this compensation method is position-dependent which means that different tissues in the same TGC time-range (or corresponding depth range) will be, incorrectly, compensated by the same amount. Compensation should really be tissue-type dependent but automating this step is difficult. The main contribution of this paper is to develop a method for simultaneous estimation of video-intensity inhomogeities and segmentation of US image tissue regions. The method uses a combination of the maximum a posteriori (MAP) and Markov random field (MRF) methods to estimate the US image distortion field assuming it follows a multiplicative model while at the same time labeling image regions based on the corrected intensity statistics. The MAP step is used to estimate the intensity model parameters while the MRF step provides a novel way of incorporating the distributions of image tissue classes as a spatial smoothness constraint. We explain how this multiplicative model can be related to the ultrasonic physics of image formation to justify our approach. Experiments are presented on synthetic images and a gelatin phantom to evaluate quantitatively the accuracy of the method. We also discuss qualitatively the application of the method to clinical breast and cardiac US images. Limitations of the method and potential clinical applications are outlined in the conclusion.

Algorithms↗