Physical Properties of Tissues: A Comprehensive Reference Book

Cambridge

Preface and Acknowledgements

During the process of compiling this book I have drawn on a wide literature base both within medical science and outside it. I hope that those specialists upon whose work I have drawn will feel that I have summarised their specialism with sufficient care and condensed it without trivialisation. I believe that in some areas I have been able to build usefully upon early surveys of tissue properties and that the revised compilations of data in this book have current value. It is to be hoped that the specialist in ultrasound or dielectric properties of tissue may perhaps find the information on thermal or X–ray properties valuable, and that the expert on skin or blood may learn from parallel knowledge of other body tissues. For those bioengineers, physicists or physiologists dealing with a wider range of problems the book is intended to provide a broad–ranging reference allowing immediate access to a literature base which may not be known in detail. For the clinical diagnosticians, particularly radiologists, I have compiled data on normal body tissue which forms the underlying basis of their investigations. The understanding of some aspects of physiotherapy, hyperthermia and surgery using microwaves, diathermy, ultrasound or lasers depends in part on a thorough knowledge of tissue properties. Lastly, those concerned with environmental hazards, whether these be from ultraviolet radiation, gamma radiation or microwaves, require knowledge of the relevant physical property of tissue in order that some sensible estimate of hazard may be made. It is my hope that parts of this compilation of data may prove to be a valuable resource for some or all of these groups of scientists, either as a simple data bank or as a guide into a literature.

Whilst every effort has been made in transcribing the data from the original sources, constructing the tables and cross–checking the values to validate their accuracy, it is perhaps inevitable that minor errors may still be included. The responsibility for such errors is, of course, entirely mine. The serious user of the data included in this book is strongly recommended to consult the origina¹ reference before making a final decision about its use. All measurements are fully referenced and the sources should be accessible through any academic library service.

I extend my thanks to many friends and colleagues who have given valuable guidance and help during the preparation of this book, and without whose advice the task would have been very much more laborious. The original suggestion for a book bearing this title was suggested by James Drake who was most helpful in its early stages of preparation. Sally Clift, Brian Diffey, Lindsay Grant, Dick Lerski, Francis Ring, Hazel Starritt, Ian Swain and Peter Wells have all at times made helpful comments and their input has been greatly appreciated. Martin Schönhoff helped with translation from some German texts. Lastly I wish to express my particular thanks to Stephen Lillicrap for his continual personal support, and his reassurance that the effort involved was worthwhile.

Francis Duck

Chapter 1

Introduction

In 1929 a book was published under the title The Physics of X–Ray Therapy. Its author, then only 25 years old, remarked when discussing the problems facing the radiotherapist planning a radiation treatment that, ‘for sufficiently obvious reasons, it is not easy to obtain data for the complex mass of tissues constituting the body of the patient’. W.V. Mayneord was at the time physicist to the radiotherapeutic department of the Cancer Hospital (Free) in London, and within a little over ten years would be appointed to a personal chair in Physics Applied to Medicine in the University of London. Since that time the requirement for data on the ‘complex mass of tissue’ has extended far beyond that which Professor Mayneord was discussing for ionising radiation dosimetry. Other therapies in use at that time, using ultraviolet radiation, heat, light and electricity have since evolved. New diagnostic tools using ultrasound and nuclear magnetic resonance have emerged. Laser therapy is now in widespread use. In all these areas of medicine the need for knowledge of tissue properties, particularly physical properties, remains essential so that each therapeutic and diagnostic tool may be used with maximum understanding and to greatest advantage.

This book, then, describes quantitatively the physical properties of mammalian tissues. The classical areas of physics, namely heat, light, sound, properties of matter, electricity and magnetism, are considered in turn. In each case, the properties which are used to describe the tissue are reviewed, with emphasis being placed on a thorough documentation of reported measurements of these properties. Ultrasonic rather than sonic properties are reported, and whilst information on the magnetic properties of tissue is minimal, a substantial review of some nuclear magnetic resonance properties is included. ‘Light’ is broadened to include both ultraviolet and infrared radiation. In addition the properties of mammalian tissue in relation to ionising radiation, x–radiation and gamma radiation, and charged and uncharged particles are also reviewed. Lastly, some relevant data concerning the composition of human tissue are included.

Throughout the book it not the microscopic or biochemical components of tissue which are described. Rather it is, first and foremost, the large–scale properties an organ, or the tissue comprising part of an organ, which are considered. Whilst there is considerable value in the study and description of, for instance, the dielectric or ultrasonic properties of biochemical solutions or cell suspensions, it is not primarily within the scope of this book to evaluate and explain the physical properties of tissue through the investigation of its component parts. One exception to this rule is for blood, where values are reported for the whole range of haematocrit from pure plasma to packed red cells.

One constituent of tissue which has been singled out for special attention is water. About three–quarters of the total mass of soft tissue is water, and some of the physical properties of tissue are dominated by its presence. Ultrasound propagates through soft tissue with a velocity close to that of water. X–ray photons are attenuated similarly in water and tissue, and the thermal capacity and conductivity of soft tissue and water are similar. On the other hand there are some obvious situations where soft tissue properties differ substantially from those of water. Light is strongly scattered by tissue; ultrasound is absorbed strongly. The magnetic relaxation of hydrogen protons is substantially faster in soft tissue than in pure water. However, whether tissue properties are close to those of water or very different from them, water is a valuable reference point against which to compare the physical property of any tissue. In addition the properties of pure water have been widely studied and reported. Throughout this book, relevant values for water of the physical quantity under discussion have been included to allow comparison to be made easily.

Each chapter is organised in a similar way. Firstly, basic definitions are given of the quantities to be used. No values are tabulated without an associated definition. Standard units are given, together with acceptable alternatives. Simple statements of the theoretical basis of the properties under discussion are also given. Sufficient discussion is included to allow a correct interpretation of the data included in the tables, but without being tutorial in nature. Fuller texts are referenced for those whose knowledge is limited. Whilst for many physical quantities simple expressions can be used to describe the behaviour of homogeneous, linear, isotropic media, these expressions cannot usually be applied to mammalian tissue without reservation because it is an inhomogenous mixture, both physically and chemically, which may well be, in addition, non–linear and anisotropic. Considerable efforts have been made over the years to develop sound theoretical bases for the behaviour of all of the physical properties of tissue. Much progress has been made, particularly in the area of ionising radiation. For this reason only the data presented in Chapter 7, dealing with ionising radiation, is dominated by calculated rather than experimental values, although the latter are included for comparison. For other properties there is much less agreement about the theoretical basis for the prediction of tissue properties. Therefore it is largely the results of experimental investigations rather than predictions based on theory which constitute the bulk of the data included in the tables. For each quantity the limitations associated with a simple theory are identified and reference is made to relevant sources which discuss more thorough analyses.

There are few simple mathematical models which can be used to describe the physical behaviour of tissue. The simplest model assumes a linear relationship between two quantities and a property of the material is defined as the ratio between the two. Obvious examples are electrical resistivity and Young’s modulus of elasticity. For many properties it has been usual to assume a linear relationship until proved otherwise, and this assumption has from time to time caused problems. For instance, Young’s modulus is relevant only if Hooke’s Law applies: equal stress causes equal strain. In fact the extension or contraction of tissues, and in particular of soft tissue, is highly non–linear, and linear assumptions can be applied only approximately and over a narrow band of stress. Another area where linear assumptions have often been applied incorrectly is in the analysis of the temperature dependence of a physical quantity. The temperature coefficient is rarely constant over a wide temperature range and assumptions of linearity can be justified only over narrow bands of temperature.

Other properties may best be quantified on the basis of exponential laws. Attenuation of wave transmission can be quantified simply in this way as can the magnetic relaxation of nuclei. A single value of attenuation coefficient, or of relaxation time, fully describes the property of the material, provided that the assumption of an single exponential process is in fact true. In reality, relaxation, for instance, may best be described by a multi–exponential function. Again, the attenuation loss may not be exponential, as is the case with broad spectrum x–rays, and care is needed in the use of simple attenuation coefficients. It is worth adding that as scattering is usually anisotropic and may well involve multiple scattering processes, its analysis and measurement remains a substantial problem for all radiations.

Several other empirical and semi–empirical mathematical models have been used to quantify the observed physical behaviour of tissue. Relaxation processes, which may be observed in the alteration with frequency of quantities such as ultrasonic attenuation, dielectric constant or nuclear magnetic relaxation time, have been analysed in this way. Values from such analyses have been included in the tables of data. A commonly used, simple expression is that of a power law of the form a=bfc, f1

Following the description of theory and definitions of quantities, a brief outline giving a historical perspective of the development of the present state of knowledge is given, identifying valuable reviews and surveys which have already been published. Provided the experimental methods have not subsequently been shown to be unsound, measurements on tissues made by early workers are usually valuable reference points in a developing science, and data from these studies have sometimes been retained in the tables. On the other hand, more recent experimental methods have in some cases rendered earlier measurements redundant, and they are referenced only for their historical interest.

The bulk of each chapter consists of tables of values drawn from the literature together with some explanation and discussion. There has been some inevitable selection from the mass of available data for inclusion in the tables, although the surveys have been kept as wide as possible. When selection has been necessary, preference has generally been given to values obtained from human tissue at body temperature in vivo, provided that the measurement methods used were not substantially prejudiced by the problems of in–vivo measurement. In addition, other general preference hierarchies have been applied. Values for human tissue have been selected in preference to those from other animals, although some animal values have often been retained for comparison. Measurements at body temperature have always been preferred to those at room temperature, and values of temperature coefficients have always been included where available. More recent data have usually superseded older data. No independent value judgements have been made as to the quality of any measurement obtained from the literature: it has been assumed that, at the time of publication, the reported values were the best available. Only in the light of subsequent discussion and criticism in later publications has earlier material been set aside.

There are two other main categories of data which may be absent. The first consists of those measurements which have been published in the open literature, but which have not come to my attention. The English language literature has been searched quite thoroughly in order to compile the tables included here, but inevitably some material will have been missed. To the authors of these papers I give my sincere apologies. Of equal importance is the scientific material in journals and books published in languages other than English. Although material from these sources is cited occasionally, mostly via other references, the majority of the literature outside English language journals has not been reviewed.

The second main category of omission, for which I make no apology, consists of data contained within useful studies which have remained unpublished in individual laboratories, or at best have been included only in university theses. Such theses are cited intermittently in this book when referenced by others, but only when the material appears to be unique. Careful experimental measurements of the properties of tissue are not sufficiently plentiful to warrant leaving them only in local libraries.

The main quantitative information is presented in the tables. In addition, graphs have been included where it seemed valuable to present a qualitative and generalised indication of the variation of a particular quantity. This has usually been done to show, for instance, the variation of a tissue property with temperature or with frequency, or its overall variability. These graphs are not intended as primary reference material and should not be relied upon to provide quantitative data. They are included only to give the reader a simple overview of a particular, generally non–linear dependence, and the tables of data should always be used for detailed reference.

The tabulated tissue values should be used with some care, and attention should be given to the discussion associated with these tables. The values presented do not have the status of physical constants; indeed they are highly variable in some cases. This variability has a variety of causes. Firstly, the tissue within any particular organ may itself be variable in the physical property under discussion. The label ‘liver’, ‘spleen’ or ‘bone’ does not describe a simple standard material but refers generally to a range of materials even within one particular organ. In some cases, tissues within an organ may be more clearly specified and a narrower variability observed. For instance, cortical bone differs from trabecular bone; the properties of kidney vary between the cortex and the medulla and those of the brain between grey and white matter. Even so, natural biological variability results in considerable ranges for all the physical properties listed. When a measurement has been made on a single tissue sample, or no range of values has been reported, only the single value is included in the table. If two measurements were reported, both values are included. For three or more measurements the overall range is listed. If sufficient measurements have been made, a standard deviation may be given. Great care should be taken when using values from the tables to recognise that this natural variability is real and to include note of the variation when using the data.

It is usual for experimentalists to report estimates of errors as an assessment of the precision of the experiment. Judgements about absolute accuracy are often not made when reporting the results of a particular set of measurements. This knowledge comes more often from the comparison of measurements of the same quantity using different techniques. Some quantities, such as density or ultrasonic velocity, should be capable of measurement with both high precision and a high degree of accuracy. Other measurements may have poor precision or be inaccurate for a variety of unrecognised reasons, or have causes whose effects cannot easily be quantified. NMR relaxation time measurement in vivo may well fall into this category at present. True variability of tissue can be assessed properly only if the measurements are in the first category, in which the overall percentage error in measurement is much less than the percentage variation in tissue. For quantities in the second category, incorrect conclusions about tissue variability can arise. It is recommended that those using particular values from the tables for serious research refer to the original references for a full discussion of measurement errors.

In addition to the natural variability within any organ, other factors can result in an overall spread of the data. Particular factors are discussed alongside each of the physical properties listed, and their importance judged and quantified as far as possible. Ageing of the tissue causes alterations in some properties, and where values are available the question of ageing is addressed. Fetal or immature tissue may also differ from adult tissue, in particular in the case of the fetus because of its relatively high water content. Of importance too is the relevance to human tissue of measurements carried out on animal tissues. Generally many more measurements have been made on animal tissues and where possible comparisons are made. Sex differences may or may not occur, depending usually on the importance of differences in tissue composition between the sexes.

For many measurements simple empirical equations have been reported which have been suggested for use as a quantitative summary of the observed variation of a particular tissue property with some other factor. For instance, both ultrasonic velocity and thermal conductivity have been related quantitatively to the partial constituent parts of tissue, water, lipid and protein. Similarly, empirical relationships relating the properties of blood to its percentage red blood cell concentration have also been reported. When such empirical equations have been reported they have been included in the text and reference may be made to the tabulations giving percentage constituents of tissues, to enable the prediction of properties for selected tissues (Chapter 9). As noted earlier, water dominates many tissue properties. In addition the presence of fat also has a strong influence, significantly lowering the density, thermal conductivity, ultrasonic velocity and linear x–ray attenuation, and modifying nuclear magnetic relaxation. The amount of protein, especially collagen, also affects the tissue and this is seen especially in its mechanical properties.

Most of the measurements included are for normal tissues. For some physical properties, particularly those associated with clinical diagnosis, a large quantity of experimental data has also been reported in the literature relating pathology to these quantities. Examples are linear X–ray attenuation coefficient, ultrasonic attenuation and NMR relaxation time. This material has not been included in detail. However, some values have been tabulated for pathological tissues which are intended primarily for illustrative rather than reference purposes.

A final factor which may cause the physical properties of tissue to alter is death. It is clearly much easier to make careful experimental measurements on a prepared excised tissue sample in vitro in the laboratory than to make the same measurement on a living animal or human subject. However, it may be that these measurements bear little relation to the living state if important alterations in the physical property to be measured occur between the times of death and measurement. Furthermore, fixation of the tissue may preserve it biologically but substantially alter it physically. The question of the value and relevance of in–vitro measurements to the in–vivo state is discussed in each chapter.

In addition to biological factors, changes in some physical factors result in alterations in physical properties. The frequency and temperature dependence of many properties has already been mentioned. The geometric direction of measurement may also be important for some properties if the tissue is anisotropic. Many tissues, such as cortical bone, tendon and muscle have an organised structure which results in anisotropy of some physical properties. Examples are the strength of bone, the resistivity of muscle and the NMR relaxation of tendon. If such anisotropy exists but is not recognised, the measured variability of a property will increase. Lastly, the range of linearity for any property needs to be known and the implications for measurement outside this range recognised. In some cases, in the propagation of ultrasound through tissue, for instance, the non–linear property of the tissue may be quantified using a suitable