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Biomedical subjects

J M Brady

Publications and source records attributed to J M Brady.

At least 19 recordsLinked to original sources

Removal of FMRI environment artifacts from EEG data using optimal basis sets.

The combination of functional magnetic resonance imaging (FMRI) and electroencephalography (EEG) has received much recent attention, since it potentially offers a new tool for neuroscientists that makes simultaneous use of the strengths of the two modalities. However, EEG data collected in such experiments suffer from two kinds of artifact. First, gradient artifacts are caused by the switching of magnetic gradients during FMRI. Second, ballistocardiographic (BCG) artifacts related to cardiac activities further contaminate the EEG data. Here we present new methods to remove both kinds of artifact. The methods are based primarily on the idea that temporal variations in the artifacts can be captured by performing temporal principal component analysis (PCA), which leads to the identification of a set of basis functions which describe the temporal variations in the artifacts. These basis functions are then fitted to, and subtracted from, EEG data to produce artifact-free results. In addition, we also describe a robust algorithm for the accurate detection of heart beat peaks from poor quality electrocardiographic (ECG) data that are collected for the purpose of BCG artifact removal. The methods are tested and are shown to give superior results to existing methods. The methods also demonstrate the feasibility of simultaneous EEG/FMRI experiments using the relatively low EEG sampling frequency of 2048 Hz.

Algorithms↗

Digital mammography: a world without film?

OBJECTIVES: eDiaMoND is a next generation Internet ("Grid") multidisciplinary research project funded by the UK e-Science Programme with the following objectives; the development of a next generation Internet enabled prototype to demonstrate the potential benefits of a national infrastructure to support digital mammography; the exploration of potential benefits for digital mammography systems, with particular emphasis being placed on selected applications, namely, screening, training, computer-aided detection and appropriate support for epidemiological studies. METHODS: EDiaMoND has worked in conjunction with selected clinical partners to enable the collection of valuable mammography information and the design of applications based upon extensive requirements gathering exercises. The clinical partners validated both the immediate needs and assisted with defining future needs of such an architecture to support the UK Health Service. RESULTS: The project has succeeded in invoking the interest of clinical partners and representatives of the UK NHS Breast Screening Programme in our vision of a world without film, albeit a long way off. The project has also succeeded in identifying the barriers to adopting this approach with the current limitations within the NHS, and has developed a blueprint for working towards this strategy. CONCLUSIONS: A UK national digital mammography archive has the potential to provide major benefits for the UK. For example, such an archive could: ensure that previous mammograms are always available, and could link up seamlessly the screening, assessment and symptomatic clinics; it could provide a huge teaching and training resource; it could be a huge resource for epidemiological studies.

Archives↗

Changes in connectivity profiles define functionally distinct regions in human medial frontal cortex.

A fundamental issue in neuroscience is the relation between structure and function. However, gross landmarks do not correspond well to microstructural borders and cytoarchitecture cannot be visualized in a living brain used for functional studies. Here, we used diffusion-weighted and functional MRI to test structure-function relations directly. Distinct neocortical regions were defined as volumes having similar connectivity profiles and borders identified where connectivity changed. Without using prior information, we found an abrupt profile change where the border between supplementary motor area (SMA) and pre-SMA is expected. Consistent with this anatomical assignment, putative SMA and pre-SMA connected to motor and prefrontal regions, respectively. Excellent spatial correlations were found between volumes defined by using connectivity alone and volumes activated during tasks designed to involve SMA or pre-SMA selectively. This finding demonstrates a strong relationship between structure and function in medial frontal cortex and offers a strategy for testing such correspondences elsewhere in the brain.

Adult↗

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

Increasing use is being made of Gd-DTPA contrast-enhanced MRI (CE-MRI) for breast cancer assessment since it provides three-dimensional (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. 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. This article is a clinical overview of the results of a technique to transform the coordinates of regions of interest (ROIs) from the 2D mammograms to the spatial reference frame of the contrast-enhanced MRI volume. An evaluation of the fusion framework is demonstrated with a series of clinical cases and a total of 14 patient examples.

Breast Neoplasms↗

Characterization and propagation of uncertainty in diffusion-weighted MR imaging.

A fully probabilistic framework is presented for estimating local probability density functions on parameters of interest in a model of diffusion. This technique is applied to the estimation of parameters in the diffusion tensor model, and also to a simple partial volume model of diffusion. In both cases the parameters of interest include parameters defining local fiber direction. A technique is then presented for using these density functions to estimate global connectivity (i.e., the probability of the existence of a connection through the data field, between any two distant points), allowing for the quantification of belief in tractography results. This technique is then applied to the estimation of the cortical connectivity of the human thalamus. The resulting connectivity distributions correspond well with predictions from invasive tracer methods in nonhuman primate.

Algorithms↗

Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging.

Evidence concerning anatomical connectivities in the human brain is sparse and based largely on limited post-mortem observations. Diffusion tensor imaging has previously been used to define large white-matter tracts in the living human brain, but this technique has had limited success in tracing pathways into gray matter. Here we identified specific connections between human thalamus and cortex using a novel probabilistic tractography algorithm with diffusion imaging data. Classification of thalamic gray matter based on cortical connectivity patterns revealed distinct subregions whose locations correspond to nuclei described previously in histological studies. The connections that we found between thalamus and cortex were similar to those reported for non-human primates and were reproducible between individuals. Our results provide the first quantitative demonstration of reliable inference of anatomical connectivity between human gray matter structures using diffusion data and the first connectivity-based segmentation of gray matter.

Adult↗

Detecting the brain surface in sparse MRI using boundary models.

We introduce a framework for the detection of the brain boundary (arachnoid) within sparse MRI. We use the term sparse to describe volumetric images in which the sampling resolution within the imaging plane is far higher than that of the perpendicular direction. Generic boundary detection schemes do not provide good results for such data. In the scheme we propose, the boundary is extracted using a constrained mesh surface which iteratively approximates a 3D point set consisting of detected boundary points. Boundary detection is based on a database of piecewise constant models, which represent the idealised MR intensity profile of the underlying boundary anatomy. A non-linear matching scheme is introduced to estimate the location of the boundary points using only the intensity data within each image plane. Results are shown for a number of images and are discussed in detail.

Algorithms↗

Estimation of compressed breast thickness during mammography.

To estimate radiation dose during mammography the breast thickness must be known. We present a new method for estimating the thickness of a compressed breast using only the breast image as projected onto a mammogram, calibration data such as the mAs value and image processing techniques. The method proves to be of high accuracy (+/- 0.2 cm for craniocaudal mammograms) and has the advantage over other methods of allowing retrospective estimation of thickness.

Breast↗

Mammographic image analysis.

We describe our recent progress aimed at computer analysis of mammograms. The overall aim is to provide the clinician with reliable quantitative information. We summarise a representation we have developed of the 'interesting' (non-adipose) tissue in a breast, then put the representation to work in three ways: (i) to propose a new quantitative measure to aid in diagnosing masses; (ii) to explore the possibility of reducing by half the radiation dose required for a mammogram; and (iii) recalling some of the results that can be provided by differential compression mammography, in which mammograms are taken at two slightly different compressions.

Guidelines as Topic↗

Detecting approximal dental caries with transillumination: a clinical evaluation.

Independent examinations of 300 patients were conducted to evaluate fiber optic transillumination's performance in caries detection. FOTI was used as an adjunct to clinical and radiographic examinations for caries, restoration or secondary caries of approximal surfaces in maxillary anterior permanent teeth. Clinical and radiographic examinations were significantly more effective.

Adolescent↗

Evolution of the rat kallikrein gene family: gene conversion leads to functional diversity.

Kallikrein-like simple serine proteases are encoded by closely related members of a gene family in several mammalian species. Molecular cloning and genomic Southern blot analysis after conventional and pulsed-field gel electrophoresis indicate that the rat kallikrein gene family comprises 15-20 members, probably closely linked at a single locus. Determination of the nucleotide sequences of the rGK-3, -4, and -6 genes here completes sequence data for a total of nine rat kallikrein family members. Comparison of the rat gene sequences to each other and to those of human and mouse kallikrein family genes reveals patterns of relatedness indicative of concerted evolution. Analysis of nucleotide sequence variants in kallikrein family members shows that most sequence variants are shared by multiple family members; the patterns of shared variants are complex and indicate multiple short gene conversions between family members. Sequence exchanges between family members generate novel assortments of variants in amino acid coding regions that may affect substrate specificity and thereby contribute to the diversity of enzyme activity. Furthermore, small sequence exchanges also may play a role in generating the diverse patterns of tissue-specific expression of rat family members. These analyses indicate an important role for gene conversion in the evolution of the functional diversity of these duplicated genes.

Amino Acid Sequence↗

The expression of two kallikrein gene family members in the rat kidney.

The mRNAs for two kallikrein gene family members expressed in the rat kidney have been characterized. One mRNA (PS) has previously been found in the pancreas and submaxillary gland and encodes true kallikrein. The second mRNA (K1) encodes a novel kallikrein-like enzyme expressed in the kidney and submaxillary gland that retains many of the key amino acid residues for the characteristic enzymatic cleavage specificity of kallikrein. Two oligonucleotide hybridization probes specific for the K1 mRNA demonstrate that the K1 mRNA is expressed in the kidney and submaxillary gland, but in none of the other eight tissues known to express one or more members of the rat kallikrein gene family. The K1 mRNA is the dominant kallikrein-related mRNA of the kidney, expressed at roughly 10 times the level of the true kallikrein (PS) mRNA. In the submaxillary gland the K1 mRNA is expressed at roughly one-fourth the level of true kallikrein mRNA.

Amino Acid Sequence↗

Expression of two kallikrein gene family members in the rat prostate.

We have characterized two kallikrein gene family members expressed in the prostate and submaxillary glands of rats. One mRNA (S3) is identical with the previously characterized submaxillary gland S3 mRNA that encodes an enzyme closely related to tonin. The second mRNA (P1) encodes a novel kallikrein-like enzyme that retains key amino acid residues responsible for the characteristic enzymatic cleavage specificity of kallikrein. Two P1-specific oligonucleotide probes derived from the P1 mRNA sequence were used to demonstrate the presence of P1 mRNA in the prostate and submaxillary glands and its absence in eight other rat tissues known to express one or more members of the kallikrein family. The P1-coding gene (rGK-8) was identified among genomic clones containing kallikrein family members by hybridization with a P1-specific oligonucleotide probe. The identification of the P1 gene was verified by nucleotide sequencing; the exon sequences of rGK-8 match the P1 mRNA sequence. The upstream region of rGK-8, where transcriptional regulatory elements likely reside, is very similar to that of other rat kallikrein family genes which are expressed in distinct tissue-specific patterns.

Amino Acid Sequence↗

Organization and expression of the rat kallikrein gene family.

We have cloned and characterized eight members of the kallikrein gene family from rat genomic DNA. Three of the cloned genes correspond to the previously characterized kallikrein family mRNAs PS, S2, and P1, which encode true kallikrein, tonin, and a novel kallikrein-like enzyme, respectively. In two cases, two kallikrein family genes are located on single genomic clones, suggesting close linkage of this family in the rat genome. Based on the total number of cloned genes and mRNAs, the minimum size of the rat family is 11 genes. Comparisons between the rat genes demonstrate a high degree of nucleotide sequence identity (greater than 80%) in exonic, intronic, and nearby flanking regions. This extensive sequence conservation not limited to clearly functional domains suggests that concerted evolution of this gene family has occurred. Despite the high overall sequence conservation among the rat family members, several discrete regions of high variability exist in the coding regions. We have defined the tissue-specific expression of the PS (true kallikrein), S2 (tonin), and S3 mRNAs with gene-specific oligonucleotide probes derived from these variant regions. PS is expressed in a wide range of tissues, while S2 mRNA is restricted to the submaxillary gland and S3 mRNA to the submaxillary and prostate glands. The high sequence conservation within the upstream flanking regions of these genes suggests that a small number of nucleotide differences determines the disparate transcriptional specificity of individual family members.

Amino Acid Sequence↗

Scanning electron microscopy of submandibular sialoliths: a preliminary report.

This report compares the scanning electron microscopic appearances of the structures in two sialoliths, one surgically removed, the other naturally exfoliated. The first exhibited the typical structure of a lamellated outer layer with an amorphous core. The core contained a large number of structures resembling calcified filamentous organisms. The second consisted of a similar outer lamella but the core contained crystal-lined spaces, amorphous matrix and an heterogeneous array of crystal shapes: there were no structures resembling organisms.

Humans↗