Table of contents

Raman spectroscopy is a potentially important clinical tool for real-time diagnosis of disease and in situevaluation of living tissue. The purpose of this article is to review the biological and physical basis of Raman spectroscopy of tissue, to assess the current status of the field and to explore future directions. The principles of Raman spectroscopy and the molecular level information it provides are explained. An overview of the evolution of Raman spectroscopic techniques in biology and medicine, from early investigations using visible laser excitation to present-day technology based on near-infrared laser excitation and charge-coupled device array detection, is presented. State-of-the-art Raman spectrometer systems for research laboratory and clinical settings are described. Modern methods of multivariate spectral analysis for extracting diagnostic, chemical and morphological information are reviewed. Several in-depth applications are presented to illustrate the methods of collecting, processing and analysing data, as well as the range of medical applications under study. Finally, the issues to be addressed in implementing Raman spectroscopy in various clinical applications, as well as some long-term directions for future study, are discussed.

The results of measurements using an open-ended coaxial probe of the audio/radiofrequency dielectric properties of human skin in vivo , either dry or moistened with physiological saline, are reported. Permittivity and conductivity dispersion curves were parametrized by using a newly reported dispersion function (Raicu V 1999 Dielectric properties of biological matter: model combining Debye-type and `universal' responses Phys. Rev.E 604677), and the results obtained are discussed in the light of the recent advances in this field. It is suggested that the coaxial probe reports on the properties of the superficial layer, the stratum corneum, when the skin surface is dry, whilst the signal from deeper skin layers becomes dominant after wetting the skin with conductive physiological saline.

The perturbation correction factor (p ) is defined as the deviation of the absorbed dose in the medium from that predicted by the Spencer-Attix extension of the Bragg-Gray cavity theory where the medium occupies exactly the same volume as the solid state cavity and the electron fluence energy spectrum in the cavity is identical in shape, but not necessarily in magnitude, to that in the medium. The value of (p ) has been examined for TL detectors irradiated in megavoltage electron beams (5-20 MeV) using the EGS4 Monte Carlo code. LiF and CaF₂solid state detectors simulated were standard size discs of thickness 1 mm and diameter 3.61 mm irradiated in a water phantom with their centres at d_max , or close to it. Values of (p ) for LiF ranged from 0.998±0.005 to 0.994±0.005 for electron beams with initial energies of 5 and 20 MeV respectively. For CaF₂the corresponding values were 0.956±0.006 to 0.989±0.006 for the same size cavities irradiated at the same depth. EGS4 Monte Carlo simulations demonstrate that the total electron fluence (primary electrons and -rays) in these solid state detector materials is significantly different from that in water for the same incident electron energy and depth of irradiation. Thus the Spencer-Attix assumption that the electron fluence energy spectrum in the cavity is identical in shape to that in the medium is violated. Differences in the total electron fluence give rise to electron fluence perturbation correction factors which were up to 5% less than unity for CaF₂ , indicating a strong violation in this case, but were generally less than 1% for LiF. It is the density of the cavity which perturbs the electron fluence, but it is actually the atomic number differences between the medium and cavity that are responsible for the large electron fluence perturbation correction factors for detectors irradiated close to d_maxbecause the atomic number affects the change in stopping power with energy. When correction is made for the difference between the electron fluence spectrum in the uniform water phantom and the solid state cavity, the Spencer-Attix cavity equation predicts the dose to water within 0.3% in both clinical and monoenergetic electron beams. Harder's formulation for computing the average mass collision stopping power of water to calcium fluoride, surprisingly, requires perturbation correction factors that are closer to unity than those determined using the Spencer-Attix integrals at depths close to d_max .

Dose perturbation correction factors, (p ), for LiF, CaF₂and Li₂ B₄ O₇solid state detectors have been determined using the EGS4 Monte Carlo code. Each detector was simulated in the form of a disc of diameter 3.61 mm and thickness 1 mm irradiated in a clinical kilovoltage photon beam at a depth of 1 cm in a water phantom. The perturbation correction factor (p ) is defined as the deviation of the absorbed dose ratio from the average mass energy absorption coefficient ratio of water to the detector material, (_en / )_med,det , which is evaluated assuming that the photon fluence spectrum in the medium and in the detector material are identical. We define another mass energy absorption coefficient ratio, (_en / )_med,det , which is evaluated using the actual photon fluence spectrum in the medium and detector for LiF and CaF₂rather than assuming they are identical. (_en / )_med,detpredicts the average absorbed dose ratio of the medium to the detector material within 0.3%. When the difference in atomic number between the cavity and the phantom material is large then their photon fluence spectra will differ substantially resulting in a difference between (_en / )_med,detand (_en / )_med,det . The value of (p ) calculated using (_en / )_med,detis up to 27% greater than unity for a cavity of CaF₂in 50 kV x-rays. When the atomic number of the medium and detector are similar, their photon fluence spectra are similar, and the difference between (_en / )_med,detand (_en / )_med,detis small. For instance their difference for LiF is less than 2%. The average mass energy absorption coefficient ratio, (_en ( )/ )_{w ,LiF} , evaluated using the mean or representative energy, , is up to 8% different from (_en / )_{w ,LiF} . For calcium fluoride the difference between (_en / )_{w ,CaF2}and (_en ( )/ )_{w ,CaF2}is up to 42% in the energy range studied.

An analytic expression for the tumour control probability (TCP), valid for any temporal distribution of dose, is discussed. The TCP model, derived using the theory of birth-and-death stochastic processes, generalizes several results previously obtained. The TCP equation is where S (t ) is the survival probability at time tof the nclonogenic tumour cells initially present (at t= 0), and band dare, respectively, the birth and death rates of these cells. Equivalently, b= 0.693/T_potand d /bis the cell loss factorof the tumour. In this expression trefers to any time during or after the treatment; typically, one would take for tthe end of the treatment period or the expected remaining life span of the patient. This model, which provides a comprehensive framework for predicting TCP, can be used predictively, or - when clinical data are available for one particular treatment modality (e.g. fractionated radiotherapy) - to obtain TCP-equivalent regimens for other modalities (e.g. low dose-rate treatments).

Radiation therapy beams demonstrate a gradual dose fall-off at the field edges, due to factors affecting the physical penumbra and transport of radiation. Adequate target coverage requires an increase in field size larger than the target volume itself for a uniform dose to be delivered to that target volume. A method is presented for the design and fabrication of penumbra compensating filters (PCFs) which essentially sharpen the penumbra on a field-by-field basis and are used in conjunction with custom shielding blocks. We have explored the feasibility of using PCFs to reduce the field margins required for our four-field conformal prostate treatments. The penumbra compensation is designed based on a profile measured along the direction perpendicular to the blocked field edge that shows the greatest 50% to 95% isodose distance for a typical conformal prostate patient. Rigid foam material is milled and filled with a low melting point alloy material to create a filter which provides dose compensation in the field periphery of the custom shielding block. The accuracy of our methodology has been established using film dosimetry. By employing PCFs, the reduction in the rectal margin ranges from approximately 4 mm in the posterior region to 13 mm in the superior-posterior region, as compared with the shielding blocks alone. The reduction in bladder margin ranges from approximately 4 mm in the superior-anterior region to 10 mm in the superior region. Dose-volume histograms for an idealized cylindrical rectum indicate a substantial reduction in the volume treated to high doses. The calculated normal tissue complication probability values were 8.7% and 10.5% with and without PCFs included in the blocked fields respectively. The advantages of using PCFs, compared with multileaf collimator based techniques, are discussed.

We review and extend the theory of tomographic dose reconstruction for intensity modulated radiotherapy (IMRT). We derive the basis for a saturation with beam number of dose conformation, and provide an analysis which ranks particular beam orientations in terms of the contribution to the delivered dose. Preferred beam directions are found which effectively reduce the number of beams necessary to achieve a given level of dose conformation. The analysis is a new application of the tomographic projection-slice theorem to the problem of beam orientation determination. The effects of the beam front filter and the positivity constraint arising from the tomographic approach are analysed, and modifications of the beam front filter for small beam numbers are suggested. The theory is applied to simple geometric shapes in two dimensions. A Gaussian ellipse, where analytical results are obtained, and simple hard-edged convex prescribed dose shapes are examined to illustrate beam selection based on the beam overlap metric. More complex concave prescribed dose shapes which contain a sensitive organ are also analysed and for low beam numbers are found to have preferred beam directions.

3D reconstruction from 2D projections obtained along a single circular source trajectory is most commonly done using an algorithm due to Feldkamp, Davis and Kress. In this paper we propose an alternative approach based on a cone-beam to parallel-beam rebinning step, a corresponding rebinning step into a rectangular virtual detector plane and a filtered backprojection. This approach yields an improved image quality reflected by a decreased low-intensity drop which is well known for 3D reconstruction from projection data obtained along circular trajectories. At the same time the computational complexity is lower than in Feldkamp's original approach.

Based on this idea, a hybrid 3D cone-beam reconstruction method is formulated that enlarges the reconstruction volume in its dimension along the rotation axis of the cone-beam CT system. This enlargement is achieved by applying different reconstruction conditions for each voxel. An optimal ratio between the reconstructible and irradiated volume of the scanned object is achieved.

The personal radiant exposure distribution of solar erythemal UV in tree shade for an upright posture was measured, with measurements over the whole summer for a total of 17 trees. For each tree, the personal radiant exposure distribution was measured for both the morning and afternoon periods. The exposure ratios averaged over all the trees and over the morning and afternoon periods ranged from 0.16 to 0.49 for the different anatomical sites. A numerical model was employed to estimate the UV radiant exposure to humans in tree shade over the entire summer. The body sites with the higher exposure ratios in the tree shade were the vertex of the head, shoulders and forearms with radiant exposures over the summer of 1300 MED to the vertex of the head and 1100 MED to the shoulders and forearms. These radiant exposures in the shade are substantially higher than the ambient erythemal UV measured in full sun on a horizontal plane over a full summer at a more temperate northern hemisphere latitude. The average radiant exposures per day to each anatomical site for a complete day in the tree shade ranged from 4.6 to 14.6 MED. This research has provided new data that is essential to quantify human UV exposure during outdoor activities.

Point kernels have been generated and applied for calculation of scatter dose distributions around monoenergetic point sources for photon energies ranging from 28 to 662 keV. Three different approaches for dose calculations have been compared: a single-kernel superposition method, a single-kernel superposition method where the point kernels are approximated as isotropic and a novel `successive-scattering' superposition method for improved modelling of the dose from multiply scattered photons. An extended version of the EGS4 Monte Carlo code was used for generating the kernels and for benchmarking the absorbed dose distributions calculated with the superposition methods. It is shown that dose calculation by superposition at and below 100 keV can be simplified by using isotropic point kernels. Compared to the assumption of full in-scattering made by algorithms currently in clinical use, the single-kernel superposition method improves dose calculations in a half-phantom consisting of air and water. Further improvements are obtained using the successive-scattering superposition method, which reduces the overestimates of dose close to the phantom surface usually associated with kernel superposition methods at brachytherapy photon energies. It is also shown that scatter dose point kernels can be parametrized to biexponential functions, making them suitable for use with an effective implementation of the collapsed cone superposition algorithm.

The classical Sievert integral method is a valuable tool for dose rate calculations around brachytherapy sources, combining simplicity with reasonable computational times. However, its accuracy in predicting dose rate anisotropy around ¹⁹² Ir brachytherapy sources has been repeatedly put into question. In this work, we used a primary and scatter separation technique to improve an existing modification of the Sievert integral (Williamson's isotropic scatter model) that determines dose rate anisotropy around commercially available ¹⁹² Ir brachytherapy sources. The proposed Sievert formalism provides increased accuracy while maintaining the simplicity and computational time efficiency of the Sievert integral method. To describe transmission within the materials encountered, the formalism makes use of narrow beam attenuation coefficients which can be directly and easily calculated from the initially emitted ¹⁹² Ir spectrum. The other numerical parameters required for its implementation, once calculated with the aid of our home-made Monte Carlo simulation code, can be used for any ¹⁹² Ir source design. Calculations of dose rate and anisotropy functions with the proposed Sievert expression, around commonly used ¹⁹² Ir high dose rate sources and other ¹⁹² Ir elongated source designs, are in good agreement with corresponding accurate Monte Carlo results which have been reported by our group and other authors.

The aim of this work is to analyse the equivalence of two classes of radiation therapy. One class of therapy is characteristic of Gamma Knife type irradiations and is defined by pencil beam concentric irradiation converging on multiple centres throughout the patient's body. The other class of treatment is characteristic of accelerator based, beam intensity modulated type irradiation defined by a rotation of wide beams around a single centre. We focus our attention on deriving formulae that relate treatments in these two classes and characterize conditions under which they are valid.

Photon beams of 4, 6 and 15 MV from Varian Clinac 2100C and 2300C/D accelerators were simulated using the EGS4/BEAM code system. The accelerators were modelled as a combination of component modules (CMs) consisting of a target, primary collimator, exit window, flattening filter, monitor chamber, secondary collimator, ring collimator, photon jaws and protection window. A full phase space file was scored directly above the upper photon jaws and analysed using beam data processing software, BEAMDP, to derive the beam characteristics, such as planar fluence, angular distribution, energy spectrum and the fractional contributions of each individual CM. A multiple-source model has been further developed to reconstruct the original phase space. Separate sources were created with accurate source intensity, energy, fluence and angular distributions for the target, primary collimator and flattening filter. Good agreement (within 2%) between the Monte Carlo calculations with the source model and those with the original phase space was achieved in the dose distributions for field sizes of 4 cm × 4 cm to 40 cm × 40 cm at source surface distances (SSDs) of 80-120 cm. The dose distributions in lung and bone heterogeneous phantoms have also been found to be in good agreement (within 2%) for 4, 6 and 15 MV photon beams for various field sizes between the Monte Carlo calculations with the source model and those with the original phase space.

The multileaf collimator (MLC) hardware constraints are usually neglected in the process of intensity-modulated beam optimization. Consequently, it is not always possible to deliver planned beam modulation using dynamic MLC. Beam optimization is significantly diminished if the results must be approximated due to limitations imposed by the delivery device. To overcome this problem, an inverse beam optimization method which incorporates the hardware constraints has been developed. The hardware constraints, including the leaf velocity, the dose rate and the minimum required gap between opposing and adjacent leaves, were considered. An iterative search for feasible modulation was conducted alternately in the dosimetric space and the MLC position-time space. The optimization algorithm was designed for a unidirectional leaf trajectory and a constant dose rate. A scheme to reduce tongue-and-groove underdosage during optimization was also implemented. Comparisons were made between the solutions produced by this method and conventional optimization disregarding the hardware restrictions. The beam profiles generated by the conventional method were modified to satisfy the hardware specifications. The results indicate that inclusion of MLC constraints during optimization can improve the degree of conformity that is deliverable.

The concept of equivalent uniform dose (EUD) was introduced to provide a method of reporting radiotherapy dose distributions which takes account of the nonlinearity of tissue dose-response, whilst not attempting to make predictions of absolute outcome. The purpose of this investigation was to determine the level of sensitivity of EUD to model parameters for significant variations in dose distribution and consequently the reliability of the factor as a dose-indicator, and to compare EUD with the more familiar index, tumour control probability (TCP). EUD and TCP, derived from the linear-quadratic formalism, were investigated for a test tissue being irradiated non-uniformly. Variations in the parameters of the model (tissue cell characteristics, dose heterogeneity, fractionation parameters) indicated the sensitivity of EUD and TCP to them. For time independent factors - cell density, cell radiosensitivity, radiosensitivity heterogeneity (population averaged) and ratio / - EUD was found to vary insignificantly in comparison with TCP, though this is a function of the actual form of the dose distribution under consideration. For fractionated treatments where the mean dose per fraction is varying (due to dosimetric/positioning errors for example), both EUD and TCP showed little variation with the degree of dose non-uniformity. For other time-dependent factors, fractionation rate and cell repopulation times, TCP again showed significant variation relative to EUD. The relative insensitivity of EUD implies that this index will be useful for dose evaluation when parameters are not known with accuracy, for the intercomparison of dose control studies and as a radiobiologically based optimization objective. However, given confidence in model parameters, the sensitivity of TCP would make it a more reliable tool for indicating potentially successful and unsuccessful irradiation strategies. It is suggested that both parameters be used in conjunction, with EUD and TCP results viewed with an appreciation of the characteristics of each model.

We describe a new method to convert CT numbers into mass density and elemental weights of tissues required as input for dose calculations with Monte Carlo codes such as EGS4. As a first step, we calculate the CT numbers for 71 human tissues. To reduce the effort for the necessary fits of the CT numbers to mass density and elemental weights, we establish four sections on the CT number scale, each confined by selected tissues. Within each section, the mass density and elemental weights of the selected tissues are interpolated. For this purpose, functional relationships between the CT number and each of the tissue parameters, valid for media which are composed of only two components in varying proportions, are derived. Compared with conventional data fits, no loss of accuracy is accepted when using the interpolation functions. Assuming plausible values for the deviations of calculated and measured CT numbers, the mass density can be determined with an accuracy better than 0.04 g cm^-3 . The weights of phosphorus and calcium can be determined with maximum uncertainties of 1 or 2.3 percentage points (pp) respectively. Similar values can be achieved for hydrogen (0.8 pp) and nitrogen (3 pp). For carbon and oxygen weights, errors up to 14 pp can occur. The influence of the elemental weights on the results of Monte Carlo dose calculations is investigated and discussed.

A method of producing CaSO₄ :Dy thermoluminescent mini-dosimeters was reported in 1986 by B W Wessels for determination of the in vivoabsorbed dose in radioimmunotherapy, a field in which absorbed dose gradients are important. These dosimeters, which undergo dissolution when used in a liquid environment, showed a sensitivity loss of up to 30% after 4 days of immersion in our tests. Moreover, several studies have shown that biocompatibility problems can occur during in vivostudies in animals.

This paper describes the production and testing of a new type of thermoluminescent mini-dosimeter obtained by microextrusion of a mixture of LiF:Mg,Cu,P polypropylene and plastic adjuvants. These dosimeters, in the form of long 400 µm diameter filaments, can be cut to the desired length. The production process allows an LiF:Mg,Cu,P load of up to 50%.

Results obtained in external irradiation indicate that these new miniature LiF:Mg,Cu,P dosimeters have good sensitivity (about 1.6 times that of CaSO₄ :Dy mini-TLDs), homogeneous response within a production batch (mean ±4%), response stability in water (0.7% of variation in sensitivity after 2 weeks of immersion) and stability in aqueous solutions at different pH.

LiF:Mg,Cu,P mini-dosimeters appear to be highly promising for internal dosimetry, and evaluation is in progress in animals.

High standards of treatment verification are necessary where complex new delivery techniques, such as intensity modulated radiation therapy using dynamic multileaf collimation, are being developed. This paper describes the use of a fluoroscopic electronic portal imaging device (EPID) to provide real-time qualitative verification of leaf position during delivery of a dynamic MLC prescription in addition to off-line quantitative verification. A custom-built circuit triggers the EPID to capture a series of snap-shot images at equally spaced dose points during a dynamic MLC prescription. Real-time verification is achieved by overlaying a template of expected leaf positions onto the images as they are acquired. Quantitative off-line verification is achieved using a maximum gradient edge detection algorithm to measure individual leaf positions for comparison with required leaf positions. Investigations have been undertaken to optimize image acquisition and assess the edge detection algorithm for variations in machine dose rate, leaf velocity and beam attenuation. On-line verification enables the operator to monitor the progress of a dynamic delivery and has been used for independent confirmation of accurate dynamic delivery during intensity modulated treatments. Off-line verification allows measurement of leaf position with a precision of 1 mm although image acquisition times must be less than or equal to 140 ms to ensure coincidence of the maximum gradient in the image with the 50% dose level.

A cone-beam computed tomography (CT) system utilizing a proton beam has been developed and tested. The cone beam is produced by scattering a 160 MeV proton beam with a modifier that results in a signal in the detector system, which decreases monotonically with depth in the medium. The detector system consists of a Gd₂ O₂ S:Tb intensifying screen viewed by a cooled CCD camera. The Feldkamp-Davis-Kress cone-beam reconstruction algorithm is applied to the projection data to obtain the CT voxel data representing proton stopping power. The system described is capable of reconstructing data over a 16 × 16 × 16 cm³volume into 512 × 512 × 512 voxels. A spatial and contrast resolution phantom was scanned to determine the performance of the system. Spatial resolution is significantly degraded by multiple Coulomb scattering effects. Comparison of the reconstructed proton CT values with x-ray CT derived proton stopping powers shows that there may be some advantage to obtaining stopping powers directly with proton CT. The system described suggests a possible practical method of obtaining this measurement in vivo .

Knee meniscus is a hydrated tissue; it is a fibrocartilage of the knee joint composed primarily of water. We present results of interferometric surface monitoring by which we measure physical properties of human knee meniscal cartilage. The physical response of biological tissue to a short laser pulse is primarily thermomechanical. When the pulse is shorter than characteristic times (thermal diffusion time and acoustic relaxation time) stresses build and propagate as acoustic waves in the tissue. The tissue responds to the laser-induced stress by thermoelastic expansion. Solving the thermoelastic wave equation numerically predicts the correct laser-induced expansion. By comparing theory with experimental data, we can obtain the longitudinal speed of sound, the effective optical penetration depth and the Grüneisen coefficient. This study yields information about the laser-tissue interaction and determines properties of the meniscus samples that could be used as diagnostic parameters.

The use of thermographic techniques has increased as infrared detector technology has evolved and improved. For laser-tissue interactions, thermal cameras have been used to monitor the thermal response of tissue to pulsed and continuous wave irradiation. It is important to note that the temperature indicated by the thermal camera may not be equal to the actual surface temperature. It is crucial to understand the limitations of using thermal cameras to measure temperature during laser irradiation of tissue.

The goal of this study was to demonstrate the potential difference between measured and actual surface temperatures in a quantitative fashion using a 1D finite difference model. Three ablation models and one cryogen spray cooling simulation were adapted from the literature, and predictions of radiometric temperature measurements were calculated. In general, (a) steep superficial temperature gradients, with a surface peak, resulted in an underestimation of the actual surface temperature, (b) steep superficial temperature gradients, with a subsurface peak, resulted in an overestimation, and (c) small gradients led to a relatively accurate temperature estimate.

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A printed error has been discovered in table 1, p 793 of the above paper. The printed kparameter values were exactly a factor of 100 too small. The Cvalues remain unchanged. The table caption, modified for clarity, and the corrected table are shown below. It is emphasized that these corrections have no effect on other results presented in that paper.

Table 1.Best fit parameters of equation (16) to the 1D distributions shown in figure 7 (x ⩾ 0 and normalized for y-intercept of 1).

This is the second edition of perhaps the definitive textbook on physics for diagnostic radiology. It is a revision of the first edition, which appeared just over 10 years ago. It is therefore interesting to reflect upon the substantial developments made in radiology in the intervening period. These technological changes have precipitated this revision. The text of various chapters has been updated to reflect this.

Guest authors have been drafted in to update key chapters; this includes K Goldstone for chapter 6 on Radiation Measurement and Doses to the Patient, Dr T Whittingham for chapter 13 on Ultrasound and Dr Jackson and Dr Moore for chapter 14 on Magnetic Resonance Imaging. These new chapters complement the rest of the book and are written in a clear and concise manner.

The strength of this textbook remains in the clarity of the descriptions of the fundamental physics. It is therefore a book ideally suited for radiologists in training. However, the breadth and depth of the textual explanations of the underlying physics make the book ideal as an introductory text for both physicists and radiographers.

The strength of this textbook remains in the clarity of the descriptions of the fundamental physics. It is therefore a book ideally suited for radiologists in training. However, the breadth and depth of the textual explanations of the underlying physics make the book ideal as an introductory text for both physicists and radiographers.

Whilst the layout of the book is logical, its contents reflect the training syllabus for Part 1 of the Physics of the Royal College of Radiologists' fellowship examination. A major component of this syllabus is the European and United Kingdom radiation protection legislation. Thus introductions to the various directives of the European Commission and the UK regulatory framework are described in some detail. The book is up to date in respect of referring to the latest basic safety standards and medical exposures directives. Unfortunately, the book will become dated rather quickly, as UK legislation to meet these directives is planned in the year 2000.

This is a book which can be recommended with confidence to radiologists in training, medical physicists and radiographers. It is an excellent textbook and well worth the investment.