Locoregional High Frequency Hyperthermia And Temperature Measurement

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Locoregional High-Frequency Hyperthermia and Temperature Measurement

Author : G. Bruggmoser
Publisher : Springer Science & Business Media
ISBN 13 : 3642825303
Total Pages : 153 pages
Book Rating : 4.6/5 (428 download)

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Book Synopsis Locoregional High-Frequency Hyperthermia and Temperature Measurement by : G. Bruggmoser

Download or read book Locoregional High-Frequency Hyperthermia and Temperature Measurement written by G. Bruggmoser and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 153 pages. Available in PDF, EPUB and Kindle. Book excerpt: The present challenge in the treatment of tumors is to reduce the number of patients that still die as a result of primary tumors. Today, the percentage of such deaths remains high at 30%, even when all the common therapeutic methods, namely surgery, radiotherapy, and chemotherapy, are applied. In order to reduce this percentage, new types of radiation sources with a higher linear energy transfer have been intro duced, such as neutrons and pions. Fractionation patterns have been modified and radiosensitizers have been applied to in crease biological efficiency. Studies of the combined application of chemotherapy and radiotherapy have been made to find the best therapeutic effect. In the early 1970s biological findings confirmed the effect of hyperthermia on tumor cells. The first clinical studies on hyper thermia treatment demonstrated that it resulted in better local tumor control. Further application of this treatment modality showed that hyperthermia should be used in addition to radio therapy and chemotherapy. Despite these encouraging results, hyperthermia has not been introduced into common clinical use, due primarily to technical problems. There are a number of methods of transferring heat into tumors; however, with regard to physical conditions, an op timum method has not yet been found. One of the reasons is that up to now we have had no reliable method of obtaining thermal mapping of all parts of the human body. Such measurements are required not only for dosimetric purposes but also for the regula tion of a hyperthermic system.

Oncothermia: Principles and Practices

Author : Andras Szasz
Publisher : Springer Science & Business Media
ISBN 13 : 9048194989
Total Pages : 575 pages
Book Rating : 4.0/5 (481 download)

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Book Synopsis Oncothermia: Principles and Practices by : Andras Szasz

Download or read book Oncothermia: Principles and Practices written by Andras Szasz and published by Springer Science & Business Media. This book was released on 2010-11-23 with total page 575 pages. Available in PDF, EPUB and Kindle. Book excerpt: Oncothermia is the next generation medical innovation that delivers selective, controlled and deep energy for cancer treatment. The basic principles for oncothermia stem from oncological hyperthermia, the oldest approach to treating cancer. Nevertheless, hyperthermia has been wrought with significant controversy, mostly stemming from shortcomings of controlled energy delivery. Oncothermia has been able to overcome these insufficiencies and prove to be a controlled, safe and efficacious treatment option. This book is the first attempt to elucidate the theory and practice of oncothermia, based on rigorous mathematical and biophysical analysis, not centered on the temperature increase. It is supported by numerous in-vitro and in-vivo findings and twenty years of clinical experience. This book will help scientists, researchers and medical practitioners in understanding the scientific and conceptual underpinnings of oncothermia and will add another valuable tool in the fight against cancer. Professor Andras Szasz is the inventor of oncothermia and the Head of St Istvan University's Biotechnics Department in Hungary. He has published over 300 papers and lectured at various universities around the world. Dr. Oliver Szasz is the managing director of Oncotherm, the global manufacturer and distributor of medical devices for cancer treatment used in Europe & Asia since the late 1980s. Dr. Nora Szasz is currently a management consultant in healthcare for McKinsey & Co.

Application of Hyperthermia in the Treatment of Cancer

Author : Rolf D. Issels
Publisher : Springer
ISBN 13 : 9783540184867
Total Pages : 300 pages
Book Rating : 4.1/5 (848 download)

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Book Synopsis Application of Hyperthermia in the Treatment of Cancer by : Rolf D. Issels

Download or read book Application of Hyperthermia in the Treatment of Cancer written by Rolf D. Issels and published by Springer. This book was released on 1988-03-22 with total page 300 pages. Available in PDF, EPUB and Kindle. Book excerpt: Physicians, biologists and physicists present their recent work in the field of hyperthermia with regard to both its application and its combination with radiation and chemotherapy. Current technical possibilities, clinical management and major aspects of its use for superficial and deep-seated tumors are pointed out. The main topics discussed are: changes of metabolism and microcirculation under heat conditions, the biological interaction of heat with X-rays and several chemotherapeutic agents, and the most recent clinical data from different institutions on the combined application in the treatment of cancer.

Frontiers in European Radiology

Author : A. L. Baert
Publisher : Springer Science & Business Media
ISBN 13 : 3642773699
Total Pages : 346 pages
Book Rating : 4.6/5 (427 download)

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Book Synopsis Frontiers in European Radiology by : A. L. Baert

Download or read book Frontiers in European Radiology written by A. L. Baert and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 346 pages. Available in PDF, EPUB and Kindle. Book excerpt: Contents Abdominal and Thoracic Magnetic Resonance Angiography: Challenges, Technical Approaches and First Clinical Applications. H.U. Kauczor, R. Hausmann, W. Semmler Magnetic Resonance Spectroscopy of Skeletal Muscle. F. Tr{ber, W.A. Kaiser, G. Layer, C. Kuhl, M. Reiser Hepatic Tumors: Relaxometry and Quantitative Tissue Characterization with Magnetic Resonance Imaging. A. Steudel, F. Tr{ber, M. Reiser Liver-Specific Particulate Contrast Agents: An Overview I. Ivancev, A. Lunderquist Contrast Medium Induced Nephropathy:Animal Experiments H.S. Thomsen et al. Rheological Properties of Blood after Diagnostic Cardiac Catheterisation with Iopromide. R. Bach et al. Color Coded Doppler Sonography of the Male Urethra During Voiding: New Observations of Flow in an Aqueous Medium and Their Physical Foundations. P. H}bsch, F. Hager, E. Benes Development of a Model of Arterial Stenosis Analysis Using Digital Subtraction Angiography: A Parametric Study of Image Quality. C. Renaudin, I. Magnin, A. Amiel Arterial Calcifications in Thoracoabdominal Computer Tomography: Frequency and Correlation with Risk Factors and Cardiovascular Diseases. J. Grich et al.

Thermoradiotherapy and Thermochemotherapy

Author : M.Heinrich Seegenschmiedt
Publisher : Springer Science & Business Media
ISBN 13 : 3642578586
Total Pages : 479 pages
Book Rating : 4.6/5 (425 download)

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Book Synopsis Thermoradiotherapy and Thermochemotherapy by : M.Heinrich Seegenschmiedt

Download or read book Thermoradiotherapy and Thermochemotherapy written by M.Heinrich Seegenschmiedt and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 479 pages. Available in PDF, EPUB and Kindle. Book excerpt: Hyperthermia has been found to be of great benefit in combination with radiation therapy or chemotherapy in the management of patients with difficult and com plicated tumor problems. It has been demonstrated to increase the efficacy, of ionising radiation when used locally but also has been of help in combination with systemic chemotherapy where hyperthermia is carried out to the total body. Problems remain with regard to maximizing the effects of hyperthermia as in fluenced by blood flow, heat loss, etc. The present volume defines the current knowledge relative to hyperthermia with radiation therapy and/or chemotherapy, giving a comprehensive overview of its use in cancer management. Philadelphia/Hamburg, June 1995 L.W. BRADY H.-P. HEILMANN Preface In an attempt to overcome tumor resistance, hypoxia, or unfavorable tumor condi tions, oncological research has come to focus on gene therapy, immunotherapy, new cytotoxic agents, and increasingly sophisticated radiotherapy. Radiation research has been directed towards heavy particle therapy and modification of the radiation response by either protecting or sensitizing agents. Improved dose localization using rotational or conformal strategies has also been implemented. Recently, changes in radiation fractionation schedules have shown promise of better results. Hyperthermia in cancer therapy can be viewed similarly as another means to increase the sensitivity of tumors to radio- and chemotherapy.

Magnetic Nanoparticles in Human Health and Medicine

Author : Costica Caizer
Publisher : John Wiley & Sons
ISBN 13 : 1119754747
Total Pages : 512 pages
Book Rating : 4.1/5 (197 download)

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Book Synopsis Magnetic Nanoparticles in Human Health and Medicine by : Costica Caizer

Download or read book Magnetic Nanoparticles in Human Health and Medicine written by Costica Caizer and published by John Wiley & Sons. This book was released on 2021-09-08 with total page 512 pages. Available in PDF, EPUB and Kindle. Book excerpt: Magnetic Nanoparticles in Human Health and Medicine Explores the application of magnetic nanoparticles in drug delivery, magnetic resonance imaging, and alternative cancer therapy Magnetic Nanoparticles in Human Health and Medicine addresses recent progress in improving diagnosis by magnetic resonance imaging (MRI) and using non-invasive and non-toxic magnetic nanoparticles for targeted drug delivery and magnetic hyperthermia. Focusing on cancer diagnosis and alternative therapy, the book covers both fundamental principles and advanced theoretical and experimental research on the magnetic properties, biocompatibilization, biofunctionalization, and application of magnetic nanoparticles in nanobiotechnology and nanomedicine. Chapters written by a panel of international specialists in the field of magnetic nanoparticles and their applications in biomedicine cover magnetic hyperthermia (MHT), MRI contrast agents, biomedical imaging, modeling and simulation, nanobiotechnology, toxicity issues, and more. Readers are provided with accurate information on the use of magnetic nanoparticles in diagnosis, drug delivery, and alternative cancer therapeutics—featuring discussion of current problems, proposed solutions, and future research directions. Topics include current applications of magnetic iron oxide nanoparticles in nanomedicine and alternative cancer therapy: drug delivery, magnetic resonance imaging, superparamagnetic hyperthermia as alternative cancer therapy, magnetic hyperthermia in clinical trials, and simulating the physics of magnetic particle heating for cancer therapy. This comprehensive volume: Covers both general research on magnetic nanoparticles in medicine and specific applications in cancer therapeutics Discusses the use of magnetic nanoparticles in alternative cancer therapy by magnetic and superparamagnetic hyperthermia Explores targeted medication delivery using magnetic nanoparticles as a future replacement of conventional techniques Reviews the use of MRI with magnetic nanoparticles to increase the diagnostic accuracy of medical imaging Magnetic Nanoparticles in Human Health and Medicine is a valuable resource for researchers in the fields of nanomagnetism, magnetic nanoparticles, nanobiomaterials, nanobioengineering, biopharmaceuticals nanobiotechnologies, nanomedicine, and biopharmaceuticals, particularly those focused on alternative cancer diagnosis and therapeutics.

Interventional Radiation Therapy

Author : Rolf Sauer
Publisher : Springer Science & Business Media
ISBN 13 : 3642841635
Total Pages : 541 pages
Book Rating : 4.6/5 (428 download)

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Book Synopsis Interventional Radiation Therapy by : Rolf Sauer

Download or read book Interventional Radiation Therapy written by Rolf Sauer and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 541 pages. Available in PDF, EPUB and Kindle. Book excerpt: With contributions by numerous experts

Hyperthermia and the Therapy of Malignant Tumors

Author : Christian Streffer
Publisher : Springer Science & Business Media
ISBN 13 : 3642829554
Total Pages : 371 pages
Book Rating : 4.6/5 (428 download)

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Book Synopsis Hyperthermia and the Therapy of Malignant Tumors by : Christian Streffer

Download or read book Hyperthermia and the Therapy of Malignant Tumors written by Christian Streffer and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 371 pages. Available in PDF, EPUB and Kindle. Book excerpt: Tumour therapy depends essentially on being able to destroy the clonogenic activity of tumour cells while keeping the damage to the normal tissue low. Clinical experience shows that tumour response varies greatly even if tumours with the same localisation, clinical, and histopathological staging are compared. Some tumours appear to be resistant to conventional radiotherapy (X-rays, y-rays or fast electrons) or chemotherapy. In these cases new therapy modalities are necessary. Combined therapy modalities seem to have advan tages for some resistant tumours; one possibility of such a treatment is to combine radiotherapy or chemotherapy with hyperthermia. This means that the local tumour, the tumour region or even the whole body of the patient has to be heated to temperatures between 40° to 45° C (in case of whole body hyperthermia to 42° C maximal) for a certain time (usually 30-60 min are adequate). Hyperthermia has a long tradition in medicine as a treatment modality for various diseases. Inscriptions of the old Egyptians and texts of the Greeks have pointed out its importance. Usually whole body hyperthermia has been used by the induction of fever. Local hyperthermia began around 1900 when Westermark treated unre sectable cervix carcinomas with hot water in a metallic coil. By the beginning of this century an increase of radiation effects was hy pothesised with hypothermia and later observed. However, only in the 1960s and 1970s were systematic investigations started which showed radiosensitisation and chemosensitisation by hyperthermia in cells and tissues including tumours.

Laser-induced Interstitial Thermotherapy

Author : Gerhard J. Müller
Publisher : SPIE Press
ISBN 13 : 9780819418593
Total Pages : 572 pages
Book Rating : 4.4/5 (185 download)

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Book Synopsis Laser-induced Interstitial Thermotherapy by : Gerhard J. Müller

Download or read book Laser-induced Interstitial Thermotherapy written by Gerhard J. Müller and published by SPIE Press. This book was released on 1995 with total page 572 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Interstitial, Endocavitary and Perfusional Hyperthermia

Author : Michel Gautherie
Publisher : Springer Science & Business Media
ISBN 13 : 3642746403
Total Pages : 239 pages
Book Rating : 4.6/5 (427 download)

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Book Synopsis Interstitial, Endocavitary and Perfusional Hyperthermia by : Michel Gautherie

Download or read book Interstitial, Endocavitary and Perfusional Hyperthermia written by Michel Gautherie and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 239 pages. Available in PDF, EPUB and Kindle. Book excerpt: "Internal" hyperthermia is a type of thermotherapy by which heat is sup plied to tumor tissue in situ. There are three different techniques for pro viding internal hyperthermia: (1) interstitial hyperthermia using implanted needle probes, (2) intracavitary hyperthermia using probes introduced into natural body cavities, and (3) perfusional hyperthermia by means of ex tracorporal blood heating. Compared with external hyperthermia, internal hyperthermia has been preferentially accepted by oncologists because it can be more easily combined with other forms of treatment, e. g., interstitial thermotherapy with brachytherapy, or perfusional hyperthermia with che motherapy. Various types of equipment for interstitial and intracavitary thermotherapy have been developed and used quite extensively in clinical trials, generally in combination with radiation therapy. There are four different methods for producing interstitial or intracavitary hyperthermia, each related to different types of heating. Most studies have been performed using radiofrequency electrodes (resistive heating) or coaxial microwave antennas (radiative heating). Recently, however, "hot source" techniques that rely on thermal conduction and blood flow convection for heat transport have found clinical application. These techniques include ferromagnetic implants activated by hot water or by electrical means. In the near future, new methods for in terstitial or intraluminal heating based upon advanced ultrasonic and laser technologies will be developed.

Methods of External Hyperthermic Heating

Author : Michel Gautherie
Publisher : Springer Science & Business Media
ISBN 13 : 3642746330
Total Pages : 367 pages
Book Rating : 4.6/5 (427 download)

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Book Synopsis Methods of External Hyperthermic Heating by : Michel Gautherie

Download or read book Methods of External Hyperthermic Heating written by Michel Gautherie and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 367 pages. Available in PDF, EPUB and Kindle. Book excerpt: The development of equipment capable of producing and monitoring safe, effective and predictable hyperthermia treatments represents a major challenge. The main problem associated with any heating technique is the need to adjust and control the distribution of absorbed power in the tissue during treatment. Power distribution is considered adequate only when tumor tissue can be maintained at the required hyperthermic levels while, at the same time, healthy tissue is not overheated. This problem is particularly crucial when external heating devices are used to produce hyperthermia. Ex ternal hyperthermia refers to those methods which supply heat to tumor tissue in an external, noninvasive manner, as opposed to internal hyperther mia by which heat is supplied to tumor tissue in situ. Until recently, most of the technical developments and clinical trials of ther motherapy for superficial and deep tumors have been based on elec tromagnetic systems. Presently, there is increasing interest in the use of ultra sound to accomplish these goals. Electromagnetic techniques of external thermotherapy include radiative, capacitive, and, to a lesser extent, inductive procedures. Recent designs for radiative applicators have incorporated microstrip structures. These have the advantage of being compact and lightweight compared with dielectrically loaded waveguide applicators.

Hyperthermia in Cancer Therapy

Author : F. Kristian Storm
Publisher :
ISBN 13 :
Total Pages : 600 pages
Book Rating : 4.3/5 (91 download)

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Book Synopsis Hyperthermia in Cancer Therapy by : F. Kristian Storm

Download or read book Hyperthermia in Cancer Therapy written by F. Kristian Storm and published by . This book was released on 1983 with total page 600 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Biological Basis of Oncologic Thermotherapy

Author : Michel Gautherie
Publisher : Springer Science & Business Media
ISBN 13 : 3642749399
Total Pages : 466 pages
Book Rating : 4.6/5 (427 download)

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Book Synopsis Biological Basis of Oncologic Thermotherapy by : Michel Gautherie

Download or read book Biological Basis of Oncologic Thermotherapy written by Michel Gautherie and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 466 pages. Available in PDF, EPUB and Kindle. Book excerpt: Studies on the effects of hyperthermia have aroused great interest in recent years. On the one hand, it has been demonstrated. that hyperthermia may be a useful treatment modality for tumors, in combination with ionizing radia tion or cytotoxic drugs. On the other hand, it is of great scientific interest to study the effects of increased temperature on biological systems. Although hyperthermia has been used in the treatment of cancer for cen turies, its therapeutic success was doubtful. However, since it has been shown that radiation-induced cell killirtg can be remarkably enhanced by hyperthermia, many investigations have been performed with cells in vitro, tumors in situ, and normal tissues. From these studies it has been concluded that many biological phenomena and their characteristics which are found in tumors may be conducive to the use of hyperthermia in cancer therapy. Many researchers are studying the cell-killing mechanisms of heat and fac tors that modify cell thermosensitivity. A very fascinating biological phenomenon is the general observation that living cells can enhance their thermoresistance within hours of heat treatment. The development of such thermotolerance is apparently a universal process, and its mechanism is of general scientific interest. Metabolic and physiological processes are changed during and after hyperthermic treatment. These changes exert a strong feedback on the thermo sensitivity of cells and tissues, and also in fluence the heating characteristics of tissues, especially in tumors.

Peritoneal Tumors and Metastases

Author : Beate Rau
Publisher : Springer Nature
ISBN 13 : 3030626407
Total Pages : 407 pages
Book Rating : 4.0/5 (36 download)

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Book Synopsis Peritoneal Tumors and Metastases by : Beate Rau

Download or read book Peritoneal Tumors and Metastases written by Beate Rau and published by Springer Nature. This book was released on 2021-05-13 with total page 407 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides surgeons and oncologists with a well-founded and detailed overview of the available treatment options for peritoneal malignancy and differential selection of the appropriate forms of therapy. Systemic chemotherapy options are also considered, as are surgical cytoreduction (CRS) and all forms of intraperitoneal chemotherapy (IPC) especially hyperthermic IPC (HIPEC), and immunotherapy, including specific procedures such as PIPAC. Subsequent chapters address perioperative care, complications and recurrences, as well as psycho-oncological, palliative medical and nursing care. The process of parietal and visceral peritonectomy in the large and small intestine is additionally illustrated by three video clips accessible online. Covering a broad range of aspects, including peritoneal metastasis and intraperitoneal chemotherapy, the book offers a valuable tool for surgeons, oncologists and anesthesiologists alike.

Microwave Applications

Author : Horst Groll
Publisher : Springer Science & Business Media
ISBN 13 : 3642831575
Total Pages : 124 pages
Book Rating : 4.6/5 (428 download)

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Book Synopsis Microwave Applications by : Horst Groll

Download or read book Microwave Applications written by Horst Groll and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 124 pages. Available in PDF, EPUB and Kindle. Book excerpt: In opto-electronics and microwave technology, new research results are translated into technological developments and applications at a breathtaking pace. This congress and trade fair, held bienniallys since 1973, covers a broad spectrum of latest advances in laser technology, opto-electronics, and for the first time, microwave technology. The fundamental physical principles are explained in basic-level seminars, panel lectures provide an overview of major spezialized fields, and the latest results are described in individual lectures. This volume deals with the 12 papers presented at the Microwave Congress.

Thermotherapy for Neoplasia, Inflammation, and Pain

Author : M. Kosaka
Publisher : Springer Science & Business Media
ISBN 13 : 4431670351
Total Pages : 556 pages
Book Rating : 4.4/5 (316 download)

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Book Synopsis Thermotherapy for Neoplasia, Inflammation, and Pain by : M. Kosaka

Download or read book Thermotherapy for Neoplasia, Inflammation, and Pain written by M. Kosaka and published by Springer Science & Business Media. This book was released on 2013-04-17 with total page 556 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a comprehensive overview of the multitude of different forms of thermotherapy in connection with aspects of thermal physiology and cell biology. The aim is to elucidate the scientific background of therapeutic actions and to promote effective new applications at the beginning of the 21st century. Significant to these purposes is cooperation between experts in the fields of thermal biology, hyper thermic oncology, rheumatology, and balneology, as represented by the editors. Emphasis has been placed on a balanced choice of contributions, in the hope that this will enable the reader to draw helpful connections between the principles and prac tice of thermotherapy. It is apparent that a wealth of published data exists concerning thermotherapy on the one hand and thermal physiology on the other. However, in the former field empirical aspects of therapeutic usefulness prevail, while in the latter, aspects of basic science are in the foreground. Accordingly, the sources where published data may be found are quite different and as a consequence many findings of potential mutual interest published in medical journals have gone unnoticed by readers of physio logical journals, and vice versa. It is hoped that this book will bridge the gap and encourage researchers' efforts to integrate the available knowledge to attain optimal coordination of clinical and theoretical aspects.

Breast Cancer

Author : Sam Brünner
Publisher : Springer Science & Business Media
ISBN 13 : 3642829643
Total Pages : 141 pages
Book Rating : 4.6/5 (428 download)

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Book Synopsis Breast Cancer by : Sam Brünner

Download or read book Breast Cancer written by Sam Brünner and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 141 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Third International Copenhagen Symposium on Detection of Breast Cancer afforded a further opportunity for scientists from all over the world to come together and present important papers con cerning breast cancer and early diagnostic procedures. The Sympo sium was an opportunity to learn from extensive screening proce dures carried out at outstanding centers in the United States, Sweden, the Netherlands, and England. Furthermore, the Sympo sium dealt with new modalities such as ultrasonography, magnifi cation techniques, and magnetic resonance; and very important contributions concerning self-examination, fine needle aspiration biopsy, and radiation risks were presented. A whole section was also dedicated to the highly important cooperation between radiologist, surgeon, and pathologist. It is our sincere hope that a study of the different aspects of breast cancer presented in this volume will encourage the reader to join in the struggle against this dreadful dis ease. December 1986 S. Brunner B. Langfeldt Contents B. Nielsen Image Quality in Mammography: Physical and Technical Limitations . 1 S. A. Feig, B. M. Galkin, and H. D. Muir Clinical Considerations in Selection of Dedicated Mammography Units . . . . . . . . . . . . . . . . . . . . 15 . . . E. A. Sickles The Role of Magnification Technique in Modern Mammography . . . . . . . . . . . . . . . . . . . . . . . . . . 19 B. M. Galkin, S. A. Feig, P. Frasca, H. D. Muir, and R. Z. Soriano Imaging Capabilities and Dose Considerations of Different Mammographic Units . . . . . . . . . . . . . . . . . . 25 . . . E. A. Sickles Computed Tomography Scanning, Transillumination, and Magnetic Resonance Imaging of the Breast . . . . . . . . . . . 31 A. G. Haus Recent Trends in Screen-Film Mammography: Technical Factors and Radiation Dose . . . . . . . . . .