Elizabeth Berry

The interaction between Terahertz radiation and biological tissue

Terahertz (THz) radiation occupies that region of the electromagnetic (EM) spectrum between approximately 0.3 and 20 THz. Recent advances in methods of producing THz radiation have stimulated interest in studying the interaction between radiation and biological molecules and tissue. Given that the photon energies associated with this region of the spectrum are 2.0 x 10(-22) to 1.3 x 10(-20) J, an analysis of the interactions requires an understanding of the permittivity and conductivity of the medium (which describe the bulk motions of the molecules) and the possible transitions between the molecular energy levels. This paper reviews current understanding of the interactions between THz radiation and biological molecules, cells and tissues. At frequencies below approximately 6 THz. the interaction may be understood as a classical EM wave interaction (using the parameters of permittivity and conductivity), whereas at higher frequencies. transitions between different molecular vibrational and rotational energy levels become increasingly important and are more readily understood using a quantum-mechanical framework. The latter is of particular interest in using THz to probe transitions between different vibrational modes of deoxyribonucleic acid. Much additional experimental work is required in order to fully understand the interactions between THz radiation and biological molecules and tissue.

An introduction to medical imaging with coherent terahertz frequency radiation

Methods have recently been developed that make use of electromagnetic radiation at terahertz (THz) frequencies, the region of the spectrum between millimetre wavelengths and the infrared, for imaging purposes. Radiation at these wavelengths is non-ionizing and subject to far less Rayleigh scatter than visible or infrared wavelengths, making it suitable for medical applications. This paper introduces THz pulsed imaging and discusses its potential for in vivo medical applications in comparison with existing modalities.

Preliminary experience with medical applications of rapid prototyping by selective laser sintering

Rapid prototyping techniques, originally developed for building components from computer aided designs in the motor industry, are now being applied in medicine to build models of human anatomy from high resolution multiplanar imaging data such a computed tomography (CT). The established technique of stereolithography and the more recent selective laser sintering (SLS), both build up an object layer by layer. Models have applications in surgical planning, for the design of customised implants and for training. Preliminary experience of using the SLS technique for medical applications is described, addressing questions regarding image processing, data transfer and manufacture. Pilot models, built from nylon, included two skills (a child with craniosynoslosis and an adult with hypertetorism) and a normal femur which was modelled for use in a bioengineering test of an artificial hip. The dimensions of the models were found to be in good agreement with the CT data from which they were built-for the childs skull the difference between the model and the CT data was less than 1.0 +/- 0.5 mm in each direction. Our experience showed that, with care, a combination of existing software packages may be used for data conversion. Ideally, image data of high spatial resolution should be used. The pilot models generated sufficient clinical interest for the technique to be pursued in the orthopaedic field.

Catalogue of human tissue optical properties at terahertz frequencies

Recently published studies suggest thatterahertz pulsed imaging will have applications inmedicine and biology, but there iscurrently very little information about the opticalproperties of human tissue at terahertzfrequencies. Such information would be useful forpredicting the feasibility of proposedapplications, optimising acquisition protocols,providing information about variability ofhealthy tissue and supplying data for studies of theinteraction mechanisms. Research ethicscommittee approval was obtained, andmeasurements made from samples of freshlyexcised human tissue, using a broadbandterahertz pulsed imaging system comprisingfrequencies approximately 0.5 to 2.5 THz.Refractive index and linear absorptioncoefficient were found. Reproducibility wasdetermined using blood from one volunteer,which was drawn and measured on consecutivedays. Skin, adipose tissue, striatedmuscle, vein and nerve were measured (to date, from oneindividual). Water had a higher refractiveindex (2.04 ± 0.07) than any tissue.The linear absorption coefficient was higher formuscle than adipose tissue, as expectedfrom the higher hydration of muscle. As these samples camefrom a single subject, there is currentlyinsufficient statistical power to draw firmconclusions, but results suggest that in vivo clinical imaging will be feasible in certainapplications.

Robust point correspondence applied to two- and three-dimensional image registration

Accurate and robust correspondence calculations are very important in many medical and biological applications. Often, the correspondence calculation forms part of a rigid registration algorithm, but accurate correspondences are especially important for elastic registration algorithms and for quantifying changes over time. In this paper, a new correspondence calculation algorithm, CSM (correspondence by sensitivity to movement), is described. A robust corresponding point is calculated by determining the sensitivity of a correspondence to movement of the point being matched. If the correspondence is reliable, a perturbation in the position of this point should not result in a large movement of the correspondence. A measure of reliability is also calculated. This correspondence calculation method is independent of the registration transformation and has been incorporated into both a 2D elastic registration algorithm for warping serial sections and a 3D rigid registration algorithm for registering pre and postoperative facial range scans. These applications use different methods for calculating the registration transformation and accurate rigid and elastic alignment of images has been achieved with the CSM method. It is expected that this method will be applicable to many different applications and that good results would be achieved if it were to be inserted into other methods for calculating a registration transformation from correspondences.

Use of magnetic resonance angiography to select candidates with recently symptomatic carotid stenosis for surgery: systematic review

Abstract Objective: To determine if sufficient evidence exists to support the use of magnetic resonance angiography as a means of selecting patients with recently symptomatic high grade carotid stenosis for surgery. Design: Systematic review of published research on the diagnostic performance of magnetic resonance angiography, 1990-9. Main outcome measures: Performance characteristics of diagnostic test. Results: 126 potentially relevant articles were identified, but many articles failed to examine the performance of magnetic resonance angiography as a diagnostic test at the surgical decision thresholds used in major clinical trials on endarterectomy. 26 articles were included in a meta-analysis that showed a maximal joint sensitivity and specificity of 99% (95% confidence interval 98% to 100%) for identifying 70-99% stenosis and 90% (81% to 99%) for identifying 50-99% stenosis. Only four articles evaluated contrast enhanced magnetic resonance angiography. Conclusions: Magnetic resonance angiography is accurate for selecting patients for carotid endarterectomy at the surgical decision thresholds established in the major endarterectomy trials, but the evidence is not very robust because of the heterogeneity of the studies included. Research is needed to determine the diagnostic performance of the most recent developments in magnetic resonance angiography, including contrast enhanced techniques, as well as to assess the impact of magnetic resonance angiography on surgical decision making and outcomes. What is already known on this topic Carotid endarterectomy for recently symptomatic carotid stenosis is beneficial in patients with 70-99% stenosis as measured by conventional angiography It is not known whether the less invasive imaging technique of magnetic resonance angiography can accurately identify patients who will benefit from surgery What this study adds Magnetic resonance angiography is highly sensitive and specific in diagnosing 70-99% carotid stenosis However, the studies on which this conclusion is based are of low quality and high heterogeneity

Intra-articular primatised anti-CD4: efficacy in resistant rheumatoid knees. A study of combined arthroscopy, magnetic resonance imaging, and histology

OBJECTIVES CD4+ T cells sustain the chronic synovial inflammatory response in rheumatoid arthritis (RA). SB-210396/CE 9.1 is an anti-CD4 monoclonal antibody that has documented efficacy in RA when given intravenously. This study aimed to establish the safety and efficacy of the intra-articular administration of SB-210396/CE 9.1 compared with placebo, examining its mode of action using a combined imaging approach of arthroscopy, magnetic resonance imaging (MRI), and histology. METHODS Thirteen RA patients with active, resistant knee synovitis, were randomised to intra-articular injection of placebo (n=3), 0.4 mg (n=3) or 40 mg (n=7) of anti-CD4 after sequential dynamic gadolinium enhanced MRI, followed by same day arthroscopy and synovial membrane biopsy. Imaging and arthroscopic synovial membrane sampling were repeated at six weeks. This study used a unique region of interest (ROI) analysis mapping the MRI area analysed to the specific biopsy site identified arthroscopically, thus providing data for all three modalities at the same synovial membrane site. RESULTS 12 patients completed the study (one placebo treated patient refused further MRI). Arthroscopic improvement was observed in 0 of 2 placebo patients but in 10 of 10 patients receiving active drug (>20% in 6 of 10). Improvement in MRI was consistently observed in all patients of the 40 mg group but not in the other two groups. A reduction in SM CD4+ score was noted in the 40 mg group and in the 0.4 mg group. Strong correlations both before and after treatment, were identified between the three imaging modalities. Intra-articular delivery of SB-210396/CE 9.1 was well tolerated. CONCLUSIONS SB-210396/CE 9.1 is safe when administered by intra-articular injection. A trend toward efficacy was found by coordinated MRI, arthroscopic, and histological imaging, not seen in the placebo group. The value of ROI analysis was demonstrated.

Optical properties of tissue measured using terahertz pulsed imaging.

The first demonstrations of terahertz imaging in biomedicine were made several years ago, but few data are available on the optical properties of human tissue at terahertz frequencies. A catalogue of these properties has been established to estimate variability and determine the practicality of proposed medical applications in terms of penetration depth, image contrast and reflection at boundaries. A pulsed terahertz imaging system with a useful bandwidth 0.5-2.5 THz was used. Local ethical committee approval was obtained. Transmission measurements were made through tissue slices of thickness 0.08 to 1 mm, including tooth enamel and dentine, cortical bone, skin, adipose tissue and striated muscle. The mean and standard deviation for refractive index and linear attenuation coefficient, both broadband and as a function of frequency, were calculated. The measurements were used in simple models of the transmission, reflection and propagation of terahertz radiation in potential medical applications. Refractive indices ranged from 1.5 ± 0.5 for adipose tissue to 3.06 ± 0.09 for tooth enamel. Significant differences (P < 0.05) were found between the broadband refractive indices of a number of tissues. Terahertz radiation is strongly absorbed in tissue so reflection imaging, which has lower penetration requirements than transmission, shows promise for dental or dermatological applications.

Risk perception and safety issues.

This session on ‘Risk perception and safety issues’ was a companion to the session ‘Biological effects’. Where the latter was concerned with studies designed to determine any genotoxic effects from exposure of human cells to terahertz frequency radiation, here the topic of safety was considered in somewhat broader terms. International guidelines in relation to the heating effects of electromagnetic radiation were of interest, together with the methods for the assessment of risk and a consideration of the perception of risk, especially among non-scientists. A number of bodies have an interest in this field, but because the terahertz band has not until recently been widely used, the expertise tends to lie in adjacent wavelengths. The most relevant body is the International Commission on NonIonizing Radiation Protection (ICNIRP), which has its website at www.icnirp.org. It has published guidelines covering the terahertz band over both its optical and electromagnetic field regions [1, 2], which meet at 1 mm (300 GHz), and copies are available for download from the website. Other relevant organisations include the World Health Organisation [3], which offers a summary on the public perception of risk [4] and the two US organisations whose standards documents provide the basis for the international guidelines. The Institute of Electrical and Electronics Engineers publishes the IEEE Standard for Safety Levels with Respect to Human Exposure to Radio Frequency Electromagnetic Fields, 3 kHz to 300 GHz [5] and the Laser Institute of America is responsible for the American National Standard for the Safe Use of Lasers [6]. The websites for these organisations are respectively www.ieee.org and www.laserinstitute.org. Further resources are the International EMF Project’s database of standards [7] and the list of national organisations for non-ionizing radiation protection [8].

Bayesian fused classification of medical images

In many applications in computer vision and signal processing, it is necessary to assimilate data from multiple sources. This is a particularly important issue in medical imaging, where information on a patient may be available from a number of different modalities. As a result, there has been much recent research interest in this area. The authors suggest an additional Bayesian method which generates a segmented classification concurrently with improving reconstructions of a set of registered images. A synthetic example is used to demonstrate the subjectives and benefits of this proposed approach. Two medical applications, one fusing computed tomography (CT) and single photon emission computed tomography (SPECT) brain scans, and the other magnetic resonance (MR) images at two different resolutions, are considered.