Bản chất của hình ảnh y sinh học (Phần 1)

1 The Nature of Biomedical Images The human body is composed of many systems, such as the cardiovascular system, the musculo-skeletal system, and the central nervous system Each system is made up of several subsystems that carry on many physiological processes For example, the visual system performs the task of focusing visual or pictorial information on to the retina, transduction of the image information into neural signals, and encoding and transmission of the neural signals to the visual cortex The visual cortex is responsible for interpretation of the image information The cardiac system performs the important task of rhythmic pumping of blood through the arterial network of the body to facilitate the delivery of nutrients, as well as pumping of blood through the pulmonary system for oxygenation of the blood itself The anatomical features of the organs related to a physiological system often demonstrate characteristics that re ect the functional aspects of its processes as well as the well-being or integrity of the system itself Physiological processes are complex phenomena, including neural or hormonal stimulation and control inputs and outputs that could be in the form of physical material or information and action that could be mechanical, electrical, or biochemical Most physiological processes are accompanied by or manifest themselves as signals that re ect their nature and activities Such signals could be of many types, including biochemical in the form of hormones or neurotransmitters, electrical in the form of potential or current, and physical in the form of pressure or temperature Diseases or defects in a physiological system cause alterations in its normal processes, leading to pathological processes that a ect the performance, health, and general well-being of the system A pathological process is typically associated with signals and anatomical features that are di erent in some respects from the corresponding normal patterns If we possess a good understanding of a system of interest, it becomes possible to observe the corresponding signals and features and assess the state of the system The task is not di cult when the signal is simple and appears at the outer surface of the body However, most systems and organs are placed well within the body and enclosed in protective layers (for good reason!) Investigating or probing such systems typically requires the use of some form of penetrating radiation or invasive procedure © 2005 by CRC Press LLC Biomedical Image Analysis 1.1 Body Temperature as an Image Most infections cause a rise in the temperature of the body, which may be sensed easily, albeit in a relative and qualitative manner, via the palm of one's hand Objective or quantitative measurement of temperature requires an instrument, such as a thermometer A single measurement f of temperature is a scalar, and represents the thermal state of the body at a particular physical location in or on the body denoted by its spatial coordinates (x y z ) and at a particular or single instant of time t If we record the temperature continuously in some form, such as a strip-chart record, we obtain a signal as a one-dimensional (1D) function of time, which may be expressed in the continuous-time or analog form as f (t) The units applicable here are o C (degrees Celsius) for the temperature variable, and s (seconds) for the temporal variable t If some means were available to measure the temperature of the body at every spatial position, we could obtain a three-dimensional (3D) distribution of temperature as f (x y z) Furthermore, if we were to perform the 3D measurement at every instant of time, we would obtain a 3D function of time as f (x y z t) this entity may also be referred to as a four-dimensional (4D) function When oral temperature, for example, is measured at discrete instants of time, it may be expressed in discrete-time form as f (nT ) or f (n), where n is the index or measurement sample number of the array of values, and T represents the uniform interval between the time instants of measurement A discrete-time signal that can take amplitude values only from a limited list of quantized levels is called a digital signal this distinction between discrete-time and digital signals is often ignored If one were to use a thermal camera and take a picture of a body, a twodimensional (2D) representation of the heat radiated from the body would be obtained Although the temperature distribution within the body (and even on the surface of the body) is a 3D entity, the picture produced by the camera is a 2D snapshot of the heat radiation eld We then have a 2D spatial function of temperature | an image | which could be represented as f (x y) The units applicable here are o C for the temperature variable itself, and mm (millimeters) for the spatial variables x and y If the image were to be sampled in space and represented on a discrete spatial grid, the corresponding data could be expressed as f (m x n y), where x and y are the sampling intervals along the horizontal and vertical axes, respectively (in spatial units such as mm) It is common practice to represent a digital image simply as f (m n), which could be interpreted as a 2D array or a matrix of values It should be noted at the outset that, while images are routinely treated as arrays, matrices, and related mathematical entities, they are almost always representative of physical or other measures of organs or of physiological pro© 2005 by CRC Press LLC The Nature of Biomedical Images cesses that impose practical limitations on the range, degrees of freedom, and other properties of the image data Examples: In intensive-care monitoring, the tympanic (ear drum) temperature is often measured using an infrared sensor Occasionally, when catheters are being used for other purposes, a temperature sensor may also be introduced into an artery or the heart to measure the core temperature of the body It then becomes possible to obtain a continuous measurement of temperature, although only a few samples taken at intervals of a few minutes may be stored for subsequent analysis Figure 1.1 illustrates representations of temperature measurements as a scalar, an array, and a signal that is a function of time It is obvious that the graphical representation facilitates easier and faster comprehension of trends in the temperature than the numerical format Long-term recordings of temperature can facilitate the analysis of temperature-regulation mechanisms 15, 16] Infrared (with wavelength in the range 000;5 000 nm) or thermal sensors may also be used to capture the heat radiated or emitted from a body or a part of a body as an image Thermal imaging has been investigated as a potential tool for the detection of breast cancer A tumor is expected to be more vascularized than its neighboring tissues, and hence could be at a slightly higher temperature The skin surface near the tumor may also demonstrate a relatively high temperature Temperature di erences of the order of 2o C have been measured between surface regions near breast tumors and neighboring tissues Figure 1.2 shows thermal images of a patient with benign brocysts and a patient with breast cancer the local increase in temperature due to a tumor is evident in the latter case Thermography can help in the diagnosis of advanced cancer, but has limited success in the detection of early breast cancer 17, 18] Recent improvements in detectors and imaging techniques have created a renewed interest in the application of thermography for the detection of breast cancer 19, 20, 21, 22, 23] Infrared imaging via a telethermographic camera has been applied to the detection of varicocele, which is the most common cause of infertility in men 24, 25, 26] In normal men, the testicular temperature is about ; o C below the core body temperature In the case of varicocele, dilation of the testicular veins reduces the venous return from the scrotum, causes stagnation of blood and edema, and leads to increased testicular temperature In the experiments conducted by Merla et al 25], a cold patch was applied to the subject's scrotum, and the thermal recovery curves were analyzed The results obtained showed that the technique was successful in detecting subclinical varicocele Vlaisavljevic 26] showed that telethermography can provide better diagnostic accuracy in the detection of varicocele than contact thermography © 2005 by CRC Press LLC Biomedical Image Analysis 33.5 o C (a) Time (hours) 08 10 12 14 16 18 20 22 24 Temperature 33.5 33.3 34.5 36.2 37.3 37.5 38.0 37.8 38.0 (o C ) (b) 39 Temperature in degrees Celsius 38 37 36 35 34 33 32 10 12 14 16 Time in hours 18 20 22 24 (c) FIGURE 1.1 Measurements of the temperature of a patient presented as (a) a scalar with one temperature measurement f at a time instant t (b) an array f (n) made up of several measurements at di erent instants of time and (c) a signal f (t) or f (n) The horizontal axis of the plot represents time in hours the vertical axis gives temperature in degrees Celsius Data courtesy of Foothills Hospital, Calgary © 2005 by CRC Press LLC The Nature of Biomedical Images FIGURE 1.2 (a) (b) Body temperature as a 2D image f (x y) or f (m n) The images illustrate the distribution of surface temperature measured using an infrared camera operating in the 000 ; 000 nm wavelength range (a) Image of a patient with pronounced vascular features and benign brocysts in the breasts (b) Image of a patient with a malignant mass in the upper-outer quadrant of the left breast Images courtesy of P Hoekstra, III, Therma-Scan, Inc., Huntington Woods, MI © 2005 by CRC Press LLC Biomedical Image Analysis The thermal images shown in Figure 1.2 serve to illustrate an important distinction between two major categories of medical images: anatomical or physical images, and functional or physiological images The images illustrate the notion of body temperature as a signal or image Each point in the images in Figure 1.2 represents body temperature, which is related to the ongoing physiological or pathological processes at the corresponding location in the body A thermal image is, therefore, a functional image An ordinary photograph obtained with re ected light, on the other hand, would be a purely anatomical or physical image More sophisticated techniques that provide functional images related to circulation and various physiological processes are described in the following sections 1.2 Transillumination Transillumination, diaphanography, and diaphanoscopy involve the shining of visible light or near-infrared radiation through a part of the body, and viewing or imaging the transmitted radiation The technique has been investigated for the detection of breast cancer, the attractive feature being the use of nonionizing radiation 27] The use of near-infrared radiation appears to have more potential than visible light, due to the observation that nitrogen-rich compounds preferentially absorb (or attenuate) infrared radiation The fat and broglandular tissue in the mature breast contain much less nitrogen than malignant tissues Furthermore, the hemoglobin in blood has a high nitrogen content, and tumors are more vascularized than normal tissues For these reasons, breast cancer appears as a relatively dark region in a transilluminated image The e ectiveness of transillumination is limited by scatter and ine ective penetration of light through a large organ such as the breast Transillumination has been found to be useful in di erentiating between cystic ( uid- lled) and solid lesions however, the technique has had limited success in distinguishing malignant tumors from benign masses 18, 28, 29] 1.3 Light Microscopy Studies of the ne structure of biological cells and tissues require signi cant magni cation for visualization of the details of interest Useful magni cation © 2005 by CRC Press LLC The Nature of Biomedical Images of up to 000 may be obtained via light microscopy by the use of combinations of lenses However, the resolution of light microscopy is reduced by the following factors 30]: Di raction: The bending of light at edges causes blurring the image of a pinhole appears as a blurred disc known as the Airy disc Astigmatism: Due to nonuniformities in lenses, a point may appear as an ellipse Chromatic aberration: Electromagnetic (EM) waves of di erent wavelength or energy that compose the ordinarily used white light converge at di erent focal planes, thereby causing enlargement of the focal point This e ect may be corrected for by using monochromatic light See Section 3.9 for a description of confocal microscopy Spherical aberration: The rays of light arriving at the periphery of a lens are refracted more than the rays along the axis of the lens This causes the rays from the periphery and the axis not to arrive at a common focal point, thereby resulting in blurring The e ect may be reduced by using a small aperture Geometric distortion: Poorly crafted lenses may cause geometric distortion such as the pin-cushion e ect and barrel distortion Whereas the best resolution achievable by the human eye is of the order of 0:1 ; 0:2 mm, light microscopes can provide resolving power up to about 0:2 m Example: Figure 1.3 shows a rabbit ventricular myocyte in its relaxed state as seen through a light microscope at a magni cation of about 600 The experimental setup was used to study the contractility of the myocyte with the application of electrical stimuli 31] Example: Figure 1.4 shows images of three-week-old scar tissue and fortyweek-old healed tissue samples from rabbit ligaments at a magni cation of about 300 The images demonstrate the alignment patterns of the nuclei of broblasts (stained to appear as the dark objects in the images): the threeweek-old scar tissue has many broblasts that are scattered in di erent directions, whereas the forty-week-old healed sample has fewer broblasts that are well-aligned along the length of the ligament (the horizontal edge of the image) The appearance of the forty-week-old sample is closer to that of normal samples than that of the three-week-old sample Images of this nature have been found to be useful in studying the healing and remodeling processes in ligaments 32] © 2005 by CRC Press LLC Biomedical Image Analysis FIGURE 1.3 A single ventricular myocyte (of a rabbit) in its relaxed state The width (thickness) of the myocyte is approximately 15 m Image courtesy of R Clark, Department of Physiology and Biophysics, University of Calgary © 2005 by CRC Press LLC The Nature of Biomedical Images (a) FIGURE 1.4 (b) (a) Three-week-old scar tissue sample, and (b) forty-week-old healed tissue sample from rabbit medial collateral ligaments Images courtesy of C.B Frank, Department of Surgery, University of Calgary © 2005 by CRC Press LLC 10 1.4 Electron Microscopy Biomedical Image Analysis Accelerated electrons possess EM wave properties, with the wavelength h , where h is Planck's constant, m is the mass of the electron, given by = mv and v is the electron's velocity this relationship reduces to = 1p:23 V , where V is the accelerating voltage 30] At a voltage of 60 kV , an electron beam has an e ective wavelength of about 0:005 nm, and a resolving power limit of about 0:003 nm Imaging at a low kV provides high contrast but low resolution, whereas imaging at a high kV provides high resolution due to smaller wavelength but low contrast due to higher penetrating power In addition, a high-kV beam causes less damage to the specimen as the faster electrons pass through the specimen in less time than with a low-kV beam Electron microscopes can provide useful magni cation of the order of 106 , and may be used to reveal the ultrastructure of biological tissues Electron microscopy typically requires the specimen to be xed, dehydrated, dried, mounted, and coated with a metal Transmission electron microscopy: A transmission electron microscope (TEM) consists of a high-voltage electron beam generator, a series of EM lenses, a specimen holding and changing system, and a screen- lm holder, all enclosed in vacuum In TEM, the electron beam passes through the specimen, is a ected in a manner similar to light, and the resulting image is captured through a screen- lm combination or viewed via a phosphorescent viewing screen Example: Figure 1.5 shows TEM images of collagen bers (in crosssection) in rabbit ligament samples The images facilitate analysis of the diameter distribution of the bers 33] Scar samples have been observed to have an almost uniform distribution of ber diameter in the range 60 ; 70 nm, whereas normal samples have an average diameter of about 150 nm over a broader distribution Methods for the detection and analysis of circular objects are described in Sections 5.6.1, 5.6.3, and 5.8 Example: In patients with hematuria, the glomerular basement membrane of capillaries in the kidney is thinner (< 200 nm) than the normal thickness of the order of 300 nm 34] Investigation of this feature requires needle-core biopsy of the kidney and TEM imaging Figure 1.6 shows a TEM image of a capillary of a normal kidney in cross-section Figure 1.7 (a) shows an image of a sample with normal membrane thickness Figure 1.7 (b) shows an image of a sample with reduced and variable thickness Although the ranges of normal and abnormal membrane thickness have been established by several studies 34], the diagnostic decision process is subjective methods for objective and quantitative analysis are desired in this application © 2005 by CRC Press LLC The Nature of Biomedical Images (a) 45 (b) FIGURE 1.28 Two frames of the echocardiogram of a subject with normal function of the mitral valve (a) Mitral valve in the fully open position (b) Mitral valve in the closed position Images courtesy of Foothills Hospital, Calgary FIGURE 1.29 M-mode ultrasound image of a subject with normal function of the mitral valve The horizontal axis represents time The echo signature of the mitral valve lea ets as they open and close is illustrated Image courtesy of Foothills Hospital, Calgary © 2005 by CRC Press LLC 46 Biomedical Image Analysis In spite of limitations in image quality and resolution, ultrasonography is an important medical imaging modality due to the nonionizing nature of the medium For this reason, ultrasonography is particularly useful in fetal imaging Figure 1.30 shows a B-mode ultrasound image of a fetus The outline of the head and face as well as the spinal column are clearly visible in the image Images of this nature may be used to measure the size of the head and head-to-sacrum length of the fetus Ultrasonography is useful in the detection of abnormalities in fetal development, especially distension of the stomach, hydrocephalus, and complications due to maternal (or gestational) diabetes such as the lack of development of the sacrum FIGURE 1.30 B-mode ultrasound (3:5 MHz ) image of a fetus (sagital view) Image courtesy of Foothills Hospital, Calgary Ultrasonography is also useful in tomographic imaging 83, 93], discriminating between solid masses and uid- lled cysts in the breast 53], and tissue characterization 5] © 2005 by CRC Press LLC The Nature of Biomedical Images 47 1.9 Magnetic Resonance Imaging MRI is based on the principle of nuclear magnetic resonance (NMR): the behavior of nuclei under the in uence of externally applied magnetic and EM (radio-frequency or RF) elds 4, 6, 84, 94, 95, 96] A nucleus with an odd number of protons or an odd number of neutrons has an inherent nuclear spin and exhibits a magnetic moment such a nucleus is said to be NMR-active The commonly used modes of MRI rely on hydrogen (1 H or proton), carbon (13 C ), uorine (19 F ), and phosphorus (31 P ) nuclei In the absence of an external magnetic eld, the vectors of magnetic moments of active nuclei have random orientations, resulting in no net magnetism When a strong external magnetic eld Ho is applied, some of the nuclear spins of active nuclei align with the eld (either parallel or antiparallel to the eld) The number of spins that align with the eld is a function of Ho and inversely related to the absolute temperature At the commonly used eld strength of 1:5 T (Tesla), only a relatively small fraction of spins align with the eld The axis of the magnetic eld is referred to as the z axis Parallel alignment corresponds to a lower energy state than antiparallel alignment, and hence there will be more nuclei in the former state This state of forced alignment results in a net magnetization vector (At equilibrium and 1:5 T , only about seven more spins in a million are aligned in the parallel state hence, MRI is a low-sensitivity imaging technique.) The magnetic spin vector of each active nucleus precesses about the z axis at a frequency known as the Larmor frequency, given by !o = Ho (1.4) where is the gyromagnetic ratio of the nucleus considered (for protons, = 42:57 MHz T ;1 ) From the view-point of classical mechanics and for H , this form of precession is comparable to the rotation of a spinning top's axis around the vertical MRI involves controlled perturbation of the precession of nuclear spins, and measurement of the RF signals emitted when the perturbation is stopped and the nuclei return to their previous state of equilibrium MRI is an intrinsically 3D imaging procedure The traditional CT scanner requires mechanical scanning and provides 2D cross-sectional images in a slice-by-slice manner: slices at other orientations, if required, have to be computed from a set of 2D slices covering the required volume In MRI, however, images may be obtained directly in any transversal, coronal, sagital, or oblique section by using appropriate gradients and pulse sequences Furthermore, no mechanical scanning is involved: slice selection and scanning are performed electronically by the use of magnetic eld gradients and RF pulses The main components and principles of MRI are as follows 84]: © 2005 by CRC Press LLC 48 Biomedical Image Analysis A magnet that provides a strong, uniform eld of the order of 0:5 ; T This causes some active nuclei to align in the direction of the eld (parallel or antiparallel) and precess about the axis of the eld The rate of precession is proportional to the strength of the magnetic eld Ho The stronger the magnetic eld, the more spins are aligned in the parallel state versus the antiparallel state, and the higher will be the signal-to-noise ratio (SNR) of the data acquired An RF transmitter to deliver an RF electromagnetic pulse H1 to the body being imaged The RF pulse provides the perturbation mentioned earlier: it causes the axis of precession of the net spin vector to deviate or \ ip" from the z axis In order for this to happen, the frequency of the RF eld must be the same as that of precession of the active nuclei, such that the nuclei can absorb energy from the RF eld (hence the term \resonance" in MRI) The frequency of RF-induced rotation is given by !1 = H1 : (1.5) When the RF perturbation is removed, the active nuclei return to their unperturbed states (alignment with Ho ) through various relaxation processes, emitting energy in the form of RF signals A gradient system to apply to the body a controlled space-variant and time-variant magnetic eld h(t x) = G(t) x (1.6) where x is a vector representing the spatial coordinates, G is the gradient applied, and t is time The components of G along the z direction as well as in the x and y directions (the plane x ; y is orthogonal to the z axis) are controlled individually however, the component of magnetic eld change is only in the z direction The gradient causes nuclei at di erent positions to precess at di erent frequencies, and provides for spatial coding of the signal emitted from the body The Larmor frequency at x is given by (1.7) !(x) = (Ho + G x): Nuclei at speci c positions or planes in the body may be excited selectively by applying RF pulses of speci c frequencies The combination of the gradient elds and the RF pulses applied is called the pulse sequence An RF detector system to detect the RF signals emitted from the body The RF signal measured outside the body represents the sum of the RF signals emitted by active nuclei from a certain part or slice of the body, as determined by the pulse sequence The spectral spread of the RF signal due to the application of gradients provides information on the location of the corresponding source nuclei © 2005 by CRC Press LLC The Nature of Biomedical Images 49 A computing and imaging system to reconstruct images from the measured data, as well as process and display the images Depending upon the pulse sequence applied, the RF signal sensed may be formulated as the 2D or 3D Fourier transform of the image to be reconstructed 4, 84, 94, 95] The data measured correspond to samples of the 2D Fourier transform of a sectional image at points on concentric squares or circles 4] The Fourier or backprojection methods of image reconstruction from projections (described in Chapter 9) may then be used to obtain the image (The Fourier method is the most commonly used method for reconstruction of MR images.) Various pulse sequences may be used to measure di erent parameters of the tissues in the body being imaged The image obtained is a function of the nuclear spin density in space and the corresponding parameters of the relaxation processes involved Longitudinal magnetization refers to the component of the magnetization vector along the direction of the external magnetic eld The process by which longitudinal magnetization returns to its state of equilibrium (that is, realignment with the external magnetic eld) after an excitation pulse is referred to as longitudinal relaxation The time constant of longitudinal relaxation is labeled as T1 A 90o RF pulse causes the net magnetization vector to be oriented in the plane perpendicular to the external magnetic eld: this is known as transverse magnetization When the excitation is removed, the a ected nuclei return to their states of equilibrium, emitting a signal, known as the free-induction decay (FID) signal, at the Larmor frequency The decay time constant of transverse magnetization is labeled as T2 Values of T1 for various types of tissues range from 200 ms to 000 ms T2 values range from 80 ms to 180 ms Several other parameters may be measured by using di erent MRI pulse sequences: the resulting images may have di erent appearances and clinical applications MRI is suitable for functional imaging The increased supply of oxygen (or oxygenated blood) to certain regions of the brain due to related stimuli may be recorded on MR images The di erence between the prestimulus and post-stimulus images may then be used to analyze the functional aspects of speci c regions of the brain Examples: Figure 1.31 shows a sagital MR image of a patient's knee, illustrating the bones and cartilages that form the knee joint Images of this type assist in the detection of bruised bones, bleeding inside the distal end of the femur, torn cartilages, and ruptured ligaments Figures 1.32 (a){(c) illustrate the sagital, coronal, and transversal (crosssectional) views of the MR image of a patient's head The images show the details of the structure of the brain MRI is useful in functional imaging of the brain © 2005 by CRC Press LLC 50 FIGURE 1.31 Biomedical Image Analysis Sagital section of the MR image of a patient's knee Image courtesy of Foothills Hospital, Calgary © 2005 by CRC Press LLC The Nature of Biomedical Images (a) (b) (c) FIGURE 1.32 (a) Sagital, (b) coronal, and (c) transversal (cross-sectional) MR images of a patient's head Images courtesy of Foothills Hospital, Calgary 51 © 2005 by CRC Press LLC 52 Physiological system (patient) Image data acquisition Biomedical images Transducers Imaging system Probing signal or radiation Analog-todigital conversion Picture archival and communication system (PACS) Computer-aided diagnosis and therapy Physician or medical specialist FIGURE 1.33 Analysis of regions or objects; feature extraction Image or pattern analysis Computer-aided diagnosis and therapy based upon biomedical image analysis © 2005 by CRC Press LLC Detection of regions or objects Filtering and image enhancement Image processing Biomedical Image Analysis Pattern recognition, classification, and diagnostic decision The Nature of Biomedical Images 1.10 Objectives of Biomedical Image Analysis 53 The representation of biomedical images in electronic form facilitates computer processing and analysis of the data Figure 1.33 illustrates the typical steps and processes involved in computer-aided diagnosis (CAD) and therapy based upon biomedical images analysis The human{instrument system: The components of a human{instrument system 97, 98, 99, 100, 101, 102] and some related notions are described in the following paragraphs The subject (or patient): It is important always to bear in mind that the main purpose of biomedical imaging and image analysis is to provide a certain bene t to the subject or patient All systems and procedures should be designed so as not to cause undue inconvenience to the subject, and not to cause any harm or danger In applying invasive or risky procedures, it is extremely important to perform a risk{bene t analysis and determine if the anticipated bene ts of the procedure are worth placing the subject at the risks involved Transducers: lms, scintillation detectors, uorescent screens, solidstate detectors, piezoelectric crystals, X-ray generators, ultrasound generators, EM coils, electrodes, sensors Signal-conditioning equipment: PMTs, ampli ers, lters Display equipment: oscilloscopes, strip-chart or paper recorders, computer monitors, printers Recording, data processing, and transmission equipment: lms, analogto-digital converters (ADCs), digital-to-analog converters (DACs), digital tapes, compact disks (CDs), diskettes, computers, telemetry systems, picture archival and communication systems (PACS) Control devices: power supply stabilizers and isolation equipment, patient intervention systems The major objectives of biomedical instrumentation 97, 98, 99, 100, 101, 102] in the context of imaging and image analysis are: Information gathering | measurement of phenomena to interpret an organ, a process, or a system Screening | investigating a large asymptomatic population for the incidence of a certain disease (with the aim of early detection) Diagnosis | detection or rmation of malfunction, pathology, or abnormality © 2005 2005 by by CRC CRC Press PressLLC LLC © 54 Biomedical Image Analysis Monitoring | obtaining periodic information about a system Therapy and control | modi cation of the behavior of a system based upon the outcome of the activities listed above to ensure a speci c result Evaluation | objective analysis to determine the ability to meet functional requirements, obtain proof of performance, perform quality control, or quantify the e ect of treatment Invasive versus noninvasive procedures: Image acquisition procedures may be categorized as invasive or noninvasive procedures Invasive procedures involve the placement of devices or materials inside the body, such as the insertion of endoscopes, catheter-tip sensors, and X-ray contrast media Noninvasive procedures are desirable in order to minimize risk to the subject Note that making measurements or imaging with X rays, ultrasound, etc could strictly be classi ed as invasive procedures because they involve penetration of the body with externally administered radiation, even though the radiation is invisible and there is no visible puncturing or invasion of the body Active versus passive procedures: Image acquisition procedures may be categorized as active or passive procedures Active data acquisition procedures require external stimuli to be applied to the subject, or require the subject to perform a certain activity to stimulate the system of interest in order to elicit the desired response For example, in SPECT investigations of myocardial ischemia, the patient performs vigorous exercise on a treadmill An ischemic zone is better delineated in SPECT images taken when the cardiac system is under stress than when at rest While such a procedure may appear to be innocuous, it does carry risks in certain situations for some subjects: stressing an unwell system beyond a certain limit may cause pain in the extreme situation, the procedure may cause irreparable damage or death The investigator should be aware of such risks, factor them in a risk{bene t analysis, and be prepared to manage adverse reactions Passive procedures not require the subject to perform any activity Acquiring an image of a subject using re ected natural light (with no ash from the camera) or thermal emission could be categorized as a passive and noncontact procedure Most organizations require ethical approval by specialized committees for experimental procedures involving human or animal subjects, with the aim of minimizing the risk and discomfort to the subject and maximizing the bene ts to both the subject and the investigator © 2005 by CRC Press LLC The Nature of Biomedical Images 55 1.11 Computer-aided Diagnosis Radiologists, physicians, cardiologists, neuroscientists, pathologists, and other health-care professionals are highly trained and skilled practitioners Why then would we want to suggest the use of computers for the analysis of biomedical images? The following paragraphs provide some arguments in favor of the application of computers to process and analyze biomedical images Humans are highly skilled and fast in the analysis of visual patterns, but are slow (usually) in arithmetic operations with large numbers of values A single 64 64-pixel SPECT image contains a total of 096 pixels a high-resolution mammogram may contain as many as 000 000 = 20 106 pixels If images need to be processed to remove noise or extract a parameter, it would not be practical for a person to perform such computation Computers can perform millions of arithmetic operations per second It should be noted, however, that the recognition of objects and patterns in images using mathematical procedures typically requires huge numbers of operations that could lead to slow responses in such tasks from low-level computers A trained human observer, on the other hand, can usually recognize an object or a pattern in an instant Humans could be a ected by fatigue, boredom, and environmental factors, and are susceptible to committing errors Working with large numbers of images in one sitting, such as in breast cancer screening, poses practical di culties A human observer could be distracted by other events in the surrounding areas and may miss uncommon signs present in some images Computers, being inanimate but mathematically accurate and consistent machines, can be designed to perform computationally speci c and repetitive tasks Analysis by humans is usually subjective and qualitative When comparative analysis is required between an image of a subject and another or a reference pattern, a human observer would typically provide a qualitative response Speci c or objective comparison | for example, the comparison of the volume of two regions to the accuracy of the order of even a milliliter | would require the use of a computer The derivation of quantitative or numerical features from images would certainly demand the use of computers Analysis by humans is subject to interobserver as well as intraobserver variations (with time) Given that most analyses performed by humans are based upon qualitative judgment, they are liable to vary with time for a given observer, or from one observer to another The former could be due to lack of diligence or due to inconsistent application of © 2005 by CRC Press LLC 56 Biomedical Image Analysis knowledge, and the latter due to variations in training and the level of understanding or competence Computers can apply a given procedure repeatedly and whenever recalled in a consistent manner Furthermore, it is possible to encode the knowledge (to be more speci c, the logical processes) of many experts into a single computational procedure, and thereby enable a computer with the collective \intelligence" of several human experts in an area of interest One of the important points to note in the discussion above is that quantitative analysis becomes possible by the application of computers to biomedical images The logic of medical or clinical diagnosis via image analysis could then be objectively encoded and consistently applied in routine or repetitive tasks However, it should be emphasized at this stage that the end-goal of biomedical image analysis should be computer-aided diagnosis and not automated diagnosis A physician or medical specialist typically uses a signi cant amount of information in addition to images, including the general physical appearance and mental state of the patient, family history, and socio-economic factors a ecting the patient, many of which are not amenable to quanti cation and logical rule-based processes Biomedical images are, at best, indirect indicators of the state of the patient many cases may lack a direct or unique image-to-pathology relationship The results of image analysis need to be integrated with other clinical signs, symptoms, and information by a physician or medical specialist Above all, the intuition of the medical specialist plays an important role in arriving at the nal diagnosis For these reasons, and keeping in mind the realms of practice of various licensed and regulated professions, liability, and legal factors, the nal diagnostic decision is best left to the physician or medical specialist It could be expected that quantitative and objective analysis facilitated by the application of computers to biomedical image analysis will lead to a more accurate diagnostic decision by the physician On the importance of quantitative analysis: \When you can measure what you are speaking about, and express it in numbers, you know something about it but when you cannot measure it, when you cannot express it in numbers, your knowledge is of a meagre and unsatisfactory kind: it may be the beginning of knowledge, but you have scarcely, in your thoughts, advanced to the stage of science." { Lord Kelvin (William Thomson, 1824 { 1907) 103] On assumptions made in quantitative analysis: \Things not in general run around with their measure stamped on them like the capacity of a freight car it requires a certain amount of investigation to discover what their measures are What most experimenters take for granted before they begin their © 2005 by CRC Press LLC The Nature of Biomedical Images 57 experiments is in nitely more interesting than any results to which their experiments lead." { Norbert Wiener (1894 { 1964) 1.12 Remarks We have taken a general look at the nature of biomedical images in this chapter, and seen a few images illustrated for the purpose of gaining familiarity with their appearance and typical features Speci c details of the characteristics of several types of biomedical images and their processing or analysis are described in subsequent chapters, along with more examples We have also stated the objectives of biomedical imaging and image analysis Some practical di culties that arise in biomedical investigations based upon imaging were discussed in order to draw attention to the relevant practical issues The suitability and desirability of the application of computers for biomedical image analysis were discussed, with emphasis on objective and quantitative analysis toward the end-goal of CAD The following chapters provide the descriptions of several image processing and analysis techniques for various biomedical applications 1.13 Study Questions and Problems Give three reasons for the application of computers in medicine for computeraided diagnosis List the relative advantages and disadvantages of X-ray, ultrasound, CT, MR, and nuclear medicine imaging for two clinical applications Indicate where each method is inappropriate or inapplicable Discuss the factors a ecting the choice of X-ray, ultrasound, CT, MR, and nuclear medicine imaging procedures for clinical applications Describe a few sources of artifact in X-ray, ultrasound, CT, MR, and nuclear medicine imaging Discuss the sources and the nature of random, periodic, structured, and physiological artifacts in medical images Describe the di erence between anatomical (physical) and functional (physiological) imaging Give examples Distinguish between active and passive medical imaging procedures give examples © 2005 by CRC Press LLC 58 Biomedical Image Analysis Distinguish between invasive and noninvasive medical imaging procedures give examples Discuss factors that a ect the resolution in various medical imaging modalities, including X-ray, ultrasound, CT, MR, and nuclear medicine imaging 1.14 Laboratory Exercises and Projects Visit a few medical imaging facilities in your local hospital or health sciences center View the procedures related to the acquisition of a few medical images, including X-ray, ultrasound, MR, CT, and SPECT images Respect the priority, privacy, and dentiality of patients Discuss the imaging protocols and parameters with a medical physicist and the technologists Develop an understanding of the relationship between the imaging system parameters, image quality, and radiation exposure to the patient Request a radiologist to explain how he or she interprets the images Obtain information on the di erences between normal and abnormal (disease) patterns in each mode of imaging Collect a few sample images for use in image processing experiments, after obtaining the necessary permissions and ensuring that you carry no patient identi cation out of the facility Most medical imaging facilities use phantoms or test objects for quality control of imaging systems If a phantom is not available, prepare one by attaching strips of di erent thickness and di erent metals to a plastic or plexiglass sheet With the help of a quali ed technologist, obtain X-ray images of a phantom at widely di erent kV p and mAs settings Study the contrast, noise, and detail visibility in the resulting images Digitize the images for use in image processing experiments Visit a medical (clinical or pathology) laboratory View several samples and specimens through microscopes Respect the priority, privacy, and dentiality of patients Request a technologist or pathologist to explain how he or she interprets the images Obtain information on the di erences between normal and abnormal (disease) patterns in di erent types of samples and tests Collect a few sample images for use in image processing experiments, after obtaining the necessary permissions and ensuring that you carry no patient identi cation out of the laboratory Interview physicians, radiologists, pathologists, medical physicists, and medical technologists to nd areas where they need and would like to use computing technology, digital image processing, computer vision, pattern recognition, and pattern classi cation methods to help in their work Volunteer to assist them in their work! Develop projects for your course of study or research © 2005 by CRC Press LLC The Nature of Biomedical Images 59 in biomedical image analysis Request a specialist in the relevant area to collaborate with you in the project Prepare a set of test images by collecting at least ten images that contain the following features: a collection of small objects, a collection of large objects, directional (oriented) features, ne texture, coarse texture, geometrical shapes, human faces, smooth features, sharp edges Scan a few photos from your family photo album Limit synthesized images to one or two in the collection Limit images borrowed from Web sites to two in the collection Use the images in the exercises provided at the end of each chapter For a selection of test images from those that have been used in this book, visit www.enel.ucalgary.ca/People/Ranga/enel697 © 2005 by CRC Press LLC [...]... imaging, only the desired cross-sectional plane of the body is irradiated using a nely collimated ray of X-ray photons (see Figure 1.19), instead of irradiating the entire body with a 3D beam of X rays as in ordinary radiography (Figure 1.9) The fundamental radiographic equation for CT is the same as Equation 1.2 Ray integrals are measured at many positions and angles around the body, scanning the body in... Department of Pathology and Laboratory Medicine, University of Calgary © 2005 by CRC Press LLC The Nature of Biomedical Images (a) (b) FIGURE 1.7 © 2005 by CRC Press LLC 13 TEM images of kidney biopsy samples at a magni cation of approximately 8 000 (a) The sample shows normal capillary membrane thickness (b) The sample shows reduced and varying membrane thickness Images courtesy of H Benediktsson,... Nature of Biomedical Images 15 1.5 X-ray Imaging The medical diagnostic potential of X rays was realized soon after their discovery by Roentgen in 1895 (See Robb 38] for a review of the history of X-ray imaging.) In the simplest form of X-ray imaging or radiography, a 2D projection (shadow or silhouette) of a 3D body is produced on lm by irradiating the body with X-ray photons 4, 3, 5, 6] This mode of... systems use an initial exposure of the order of 5 ms to estimate the penetration of the X rays through the body being imaged, and then determine the required exposure Beam hardening: The X rays used in radiographic imaging are typically not monoenergetic that is, they possess X-ray photons over a certain band of frequencies or EM energy levels As the X rays propagate through a body, the lower-energy... screen- lm mammography However, xeromammography results in a higher dose to the subject, and has not been in much use since the 1980s A typical mammographic imaging system is shown schematically in Figure 1.15 Mammography requires high X-ray beam quality (a narrow-band or nearly monochromatic beam), which is controlled by the tube target material (molybdenum) and beam ltration with molybdenum E ective... cation of approximately 30 000 (a) Normal and (b) scar tissue Images courtesy of C.B Frank, Department of Surgery, University of Calgary © 2005 by CRC Press LLC 12 FIGURE 1.6 Biomedical Image Analysis TEM image of a kidney biopsy sample at a magni cation of approximately 3 500 The image shows the complete cross-section of a capillary with normal membrane thickness Image courtesy of H Benediktsson, Department... R.M Rangayyan and A Kantzas, \Image reconstruction", Wiley Encyclopedia of Electrical and Electronics Engineering, Supplement 1, Editor: John G Webster, Wiley, New York, NY, pp 249{268, 2000 c This material is used by permission of John Wiley & Sons, Inc Figure 1.20 depicts some of the scanning procedures employed: Figure 1.20 (a) shows the translate-rotate scanning geometry for parallel-ray projections... grid artifact Image courtesy of L.J Hahn, Foothills Hospital, Calgary See also Figure 1.14 © 2005 by CRC Press LLC 24 FIGURE 1.14 Biomedical Image Analysis X-ray image of the American College of Radiology (ACR) phantom for mammography The pixel-value range 117 210] has been linearly stretched to the display range 0 255] to show the details Image courtesy of S Bright, Sunnybrook & Women's College Health... 2005 by CRC Press LLC The Nature of Biomedical Images 25 such early breast cancer is generally not amenable to detection by physical examination and breast self-examination The primary role of an imaging technique is thus the detection of lesions in the breast 29] Currently, the most e ective method for the detection of early breast cancer is X-ray mammography Other modalities, such as ultrasonography,... the energy gained by an electron when a potential of 1 V is applied to it The kV p measure relates to the highest possible X-ray photon energy that may be achieved at the voltage used Low-energy X-ray photons are absorbed at or near the skin surface, and do not contribute to the image In order to prevent such unwanted radiation, a lter is used at the X-ray source to absorb low-energy X rays Typical lter