Richard I. Kitney

Interactive algorithms for the segmentation and quantitation of 3-D MRI brain scans

Interactive algorithms are an attractive approach to the accurate segmentation of 3D brain scans as they potentially improve the reliability of fully automated segmentation while avoiding the labour intensiveness and inaccuracies of manual segmentation. We present a 3D image analysis package (MIDAS) with a novel architecture enabling highly interactive segmentation algorithms to be implemented as add on modules. Interactive methods based on intensity thresholding, region growing and the constrained application of morphological operators are also presented. The methods involve the application of constraints and freedoms on the algorithms coupled with real time visualisation of the effect. This methodology has been applied to the segmentation, visualisation and measurement of the whole brain and a small irregular neuroanatomical structure, the hippocampus. We demonstrate reproducible and anatomically accurate segmentations of these structures. The efficacy of one method in measuring volume loss (atrophy) of the hippocampus in Alzheimers disease is shown and is compared to conventional methods.

Engineering modular and orthogonal genetic logic gates for robust digital-like synthetic biology

Modular and orthogonal genetic logic gates are essential for building robust biologically based digital devices to customize cell signalling in synthetic biology. Here we constructed an orthogonal AND gate in Escherichia coli using a novel hetero-regulation module from Pseudomonas syringae. The device comprises two co-activating genes hrpR and hrpS controlled by separate promoter inputs, and a σ54-dependent hrpL promoter driving the output. The hrpL promoter is activated only when both genes are expressed, generating digital-like AND integration behaviour. The AND gate is demonstrated to be modular by applying new regulated promoters to the inputs, and connecting the output to a NOT gate module to produce a combinatorial NAND gate. The circuits were assembled using a parts-based engineering approach of quantitative characterization, modelling, followed by construction and testing. The results show that new genetic logic devices can be engineered predictably from novel native orthogonal biological control elements using quantitatively in-context characterized parts.

Biomedical signal processing (in four parts)

This is the third in a series of four tutorial papers on biomedical signal processing and concerns the estimation of the power spectrum (PS) and coherence function (CF) od biomedical data. The PS is introduced and its estimation by means of the discrete Fourier transform is considered in terms of the problem of resolution in the frequency domain. The periodogram is introduced and its variance, bias and the effects of windowing and smoothing are considered. The use of the autocovariance function as a stage in power spectral estimation is described and the effects of windows in the autocorrelation domain are compared with the related effects of windows in the original time domain. The concept of coherence is introduced and the many ways in which coherence functions might be estimated are considered.

Investigation of acoustic noise on 15 MRI scanners from 0.2 T to 3 T.

Acoustic noise levels for fast MRI pulse sequences were surveyed on 14 systems with field strengths ranging from 0.2 T to 3 T. A microphone insensitive to the magnetic environment was placed close to the magnet isocenter and connected via an extension cable to a sound level meter outside the scan room. Measured noise levels varied from 82.5 ± 0.1 dB(A) for a 0.23 T system to 118.4 ± 1.3 dB(A) for a 3 T system. Further measurements on four of the closed‐bore systems surveyed showed that: 1) pulse sequence parameters (particularly FOV and TR) were more influential in determining noise level than field strength, 2) the noise level was found to vary along the z‐direction with a maximum near the bore entrance, and 3) in one of two systems tested there was a significant increase in noise with a volunteer present instead of a test object. The results underline the importance of hearing protection for patients and for staff spending extended periods in the scan room. J. Magn. Reson. Imaging 2001;13:288–293.

Breath Amplitude Modulation of Heart Rate Variability in Normal Full Term Neonates

ABSTRACT. The relationship between heart rate variability and respiration patterns was investigated using spectral analysis techniques in nine full-term infants whose ages ranged from 39-75 h. All the infants were studied during sleep, although no attempt was made to classify rapid eye movement or nonrapid eye movement states prospectively. The data obtained were examined to determine which aspects of neonatal breathing patterns are correlated with heart rate variability. Three spectral regions of heart rate variability could be identified: a very low frequency region below 0.02 Hz; a low frequency region from 0.02-0.20 Hz; and a high frequency region above 0.20 Hz. The dominant heart rate variability activity in these neonates was seen in the very low and low frequency regions, with little activity in the high frequency regions. In contrast to older infants and adults, respiration and heart rate variability were not strongly related through a high frequency region respiratory sinus arrhythmia but rather through a breath amplitude sinus arrhythmia which occurs in the low frequency region of the spectrum. The prominent very low frequency activity and the low frequency activity ascribed to breath amplitude modulation may result from autonomic nervous system mediation of chemoregulation.

Opportunities for microfluidic technologies in synthetic biology

We introduce microfluidics technologies as a key foundational technology for synthetic biology experimentation. Recent advances in the field of microfluidics are reviewed and the potential of such a technological platform to support the rapid development of synthetic biology solutions is discussed.

Synthetic biology – the state of play

Just over two years ago there was an article in Nature entitled “Five Hard Truths for Synthetic Biology”. Since then, the field has moved on considerably. A number of economic commentators have shown that synthetic biology very significant industrial potential. This paper addresses key issues in relation to the state of play regarding synthetic biology. It first considers the current background to synthetic biology, whether it is a legitimate field and how it relates to foundational biological sciences. The fact that synthetic biology is a translational field is discussed and placed in the context of the industrial translation process. An important aspect of synthetic biology is platform technology, this topic is also discussed in some detail. Finally, examples of application areas are described.

3-D visualization of arterial structures using ultrasound and Voxel modelling

SummaryIn this paper, a new type of vascular imaging system is presented which is designed for use in conjunction with percutaneous transluminal treatment techniques (balloon and laser angioplasty, atherectomy etc). Three dimensional computer models of arterial sections are reconstructed in full voxel space from data acquired using a purpose-built, catheter-mounted ultrasound probe. The system is standalone, using commercially available computer hardware and specially written software. The software is equally compatible with source data from other modalities (e.g. CT and MR), and the system can therefore be incorporated into a PACS environment.

PARTNERSHIP AND INNOVATION IN THE LIFE SCIENCES

Government support for partnering between BioPharma companies and universities is growing in the UK and some European countries but few studies have explored these partnerships. Through interviews and a survey of key institutions we explored perceptions of key informants on industry and university partnerships. Study participants identified that partnering helped them to increase innovation in RD flexibility in operational management to solve problems in establishing and running these partnerships; leadership, especially by investigators to champion and lead collaborations; developing organisational capabilities of universities; and creation of an enabling environment by governments were identified as the critical success factors for partnering. The challenges faced were identified as lack of funding for university research teams; pressure on pricing from industry partners; disagreements on IP ownership; asymmetry of industry and university capabilities in partnering; and lack of administrative support with excessive bureaucracy from universities.

Real-time heart rate variability extraction using the Kaiser window

A new method for real-time heart rate variability (HRV) detection from the R-wave signal, based on the integral pulse frequency modulation (IPFM) model and its similarity to pulse position modulation, is presented. The proposed method exerts lowpass filtering with a Kaiser window. It can also be used for off-line HRV analysis in both the time and frequency domains. Real-time bandpass filtering as a new HRV investigation method and as a by-product of the proposed algorithm is also introduced. Furthermore, the discrete time domain version of the French-Holden algorithm is developed, and it is thoroughly proved that lowpass filtering is an ideal method for detection of HRV.