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INTRODUCTION TO MEDICAL IMAGING
Consider the task of detecting a breast tumour using an imaging system. Identify the characteristics of the tumour which might make it detectable and the circumstances which might prevent its detection or cause it to be misdiagnosed.
The task of detecting a breast tumour using an imaging system has well been described with certain characteristics of the tumour which might make it detectable. However, certain properties such as spatial resolution, tissue contrast, equipment operational mode, tumour size, tumour density and the personnel experience have been considered as circumstances which might prevent the tumour's detection or cause it to be misdiagnosed. Nevertheless, a combination of any of the available modalities like Mammography, Ultrasound, Nuclear Medicine [Nmed] and Magnetic Resonance Imaging [MRI] may demonstrate the best result in the task of detecting a breast tumour.
Breast tumour may succinctly be defined, as the presence of malignant lesion, cyst or calcification in breast tissue. Naturally, the complexity of breast tissue has made it bungling for physicians to examine by palpation alone whether a lump in the breast is malignant or benign. Sabel and Aichinger (1996) opined that breasts can be examined by a variety of physical methods, but ideally, the method of investigation should have high specificity and sensitivity. This calls for the application of complex imaging modalities.
Imaging modality options have been more extensive in recent time particularly in the area of breast screening. Current options include; X-rays mammography, Nuclear Medicine (NMed), Ultrasound, Magnetic Resonance Imaging (MRI) and a host of hybrid modalities (Pope, 1998). However, Jones (1982) suggests that modality options available for breast tumour should rely upon detecting differences between tumour and normal breast tissues, any alterations in breast architecture and any changes that occur in physiology or vascular morphology due to tumour growth. More importantly, it should not take up excessive amounts of manpower, money or time, and it should be non-invasive and harmless.
Over the years, mammography has proved to be the most effective method of breast screening (Hurley and Kaldor 1992 in Sabel and Aichinger 1996 p316). A low energy X-ray, its clinical value has been acknowledged at different time in research history. This value depends critically on its spatial resolution and its ability to create contrast that brings the different effects which the various disease processes have on breast structure (Jones 1982). To boost breast screening activities, the addition of ultrasound became imperative. Generally, ultrasound systems employ piezoelectric transducers to emit short pulses of (mechanical) energy into the breast with appropriate instrumentation to measure the characteristics of the reflected or transmitted pulses (Dendy et al 1999). In ultrasound system, the optimal imaging frequency depends on the type of investigation and the size of the breast; typical frequencies range from 2MHz - 10MHz which are below those associated with any apparent biological hazard and consequently may be used on asymptomatic patients over long periods of time. However, improved technology has brought about Magnetic Resonance Imaging [MRI] and Nuclear Medicine [NMed] into breast screening arena.
Obviously, MRI utilizes the interaction between the magnetism of atomic nuclei and radio waves to portray the structure of breast tissues mainly according to their hydrogen content. This basis of MRI image formation suggests its ability to separate components within one tissue type with a certain degree of variation in image content because of differential intra-tissue distribution of water and or fat. While Nuclear Medicine [NMed] relies upon the selective uptake of radioactive compounds by breast tissues with external counting techniques used to measure the distribution of radionuclide.
This exercise is primarily concerned about the task of detecting a breast tumour using any of the above mentioned modalities. Thus, to understand the way in which the different modalities are deployed in details, a brief knowledge of breast anatomy and physiology is essential.
DETECTABLE CHARACTERISTICS OF THE BREAST TUMOUR
Wikipedia Encyclopaedia (www.thefreedictionary.com) refers to female breast as the upper ventral region of human torso that contains the fibrous, glandular and adipose tissue in lobes and lobules (milk sacs) which are surrounded with fat. The upper outer aspect is thicker than other sectors of the breast and most tumours occur at the upper parts. However, as the woman ages, and following pregnancy or menopause, the fibrous and glandular tissue is replaced by fat (IPEMed 2005, Report 89).
Research efforts revealed a number of diseases that affect the female breast but the most prevalent are cystic disease, fibroadenomas and cancer which account for more than 90% of the lesions observed (Haagensen 1971 in Jones 1982, p464). Gowing 1968 in Jones (1982 p465) describes Cystic disease features as characteristically spherical in shape with a smooth surface and developed as a result of dilatation of ducts, while fibroadenoma is a solid lump caused by proliferation of connective tissue stroma and atypical multiplication of ducts. But cancer may be identified by the presence of a mass which is frequently hard, irregular and as a malignant tumour, relatively fixed. This is in contrast to cyst and fibroadenoma, which are mobile in the surrounding breast tissue. Gowing 1968 in Jones (1982 p465) further observed that, cancer may invade the overlying skin, thereby causing the thickening or dimpling of the skin, or retraction of the nipple. Thus, the morphology of a malignant lesion depends upon many factors including tumour type and vascular supply, as well as its size and location within the breast (IPEMed. 2005, Report 89).
Evans et al 2002 in IPEMed(2005 p99) opined that, an accurate representation of the shape of the calcifications should be regarded as an important aid to diagnosis. Calcifications composed of calcium hydroxapatite or tricalcium phosphate, oftentimes irregularly shaped and present in clusters. Also soft tissue masses if cancerous are usually irregularly shaped and often infiltrate into the surrounding tissues with fine spicules. Masses have approximately the same density as glandular tissue and are denser than adipose tissue (IPEMed 2005, Report 89). The above defined diseases are benign tumour that frequently occurs, especially in younger women. Generally, lesions of the breast are indicated by masses, calcifications or distortions of breast architecture and a positive diagnosis will depend not only on their presence in the radiographic image but also on their number, size, shape and configuration. Apart from the above mentioned anatomical and the breast morphology, a number of other machine dependent circumstances might prevent the detection of breast tumour.
CIRCUMSTANCES WHICH MIGHT PREVENT TUMOUR DETECTION
Contrast Resolution; Whenever we talk about image quality, we are expressly referring to imaging modality contrast resolution. Resolution in this context is the ability of an imaging system to display two closely associated small structures as distinct objects (Allisy-Roberts and Williams 2008). The better the ability of a modality to resolve tissues in space, the better it is for the patient with regard to the patient's degree of diagnosis and management. The effectiveness of any modality depends on its image quality and this in turn depends on modality contrast resolution. Therefore, a comparison of some imaging modalities would suffice the rip of tumour detection.
Taking X-ray principle into consideration, contrast resolution in mammography is formed on the basis of its differential attenuation coefficient. This attenuation is 1.53cm-1 in dense tissue such as in dense breast, and 0.92cm-1 in material like air and fluid due to their low density (Burke et al 1982). In this regards, conventional mammography tends to demonstrate poorly as a result of the high attenuation from the dense breast. The plausible explanation is that in imaging systems like film screening with limited contrast, the normal mammary parenchyma can easily obscure tumour masses. In a similar fashion, subtle calcium deposits can also be obscured by the structured noise of the surrounding dense breast tissue (Green and Oestmann 1999). This is not to say that, conventional mammography could not demonstrate positive lesion with good and dedicated mammographic equipment that offers spatial resolution between 15 to 30 line pairs per millimetre. This resolution level is required to permit analysis of the morphology of masses, and the detection and analysis of microcalcifications that may be as small as 200 to 300µm in diameter. However, the introduction of digital mammography has brought about greater improvement in the use of mammography, such as in dose reduction and the use of dual energy, which has improved detection of calcifications without interference from overlying soft tissue structures. Since mammography relies on attenuation coefficient alone for its contrast resolution, it has however, suffered a setback in the area of contrast reversal which MRI has demonstrated in a better way (Westbrook and Kaut 1994).
The ability of MRI to perform contrast reversal is due to the fact that it images are based on information about the freedom of hydrogen molecules in the breast tissue. In MRI the signal intensity depends significantly on tissue water content, tissue type and Radiofrequency (RF) pulse sequence which in turn determine its contrast resolution properties (Pope 1998). Resolution is largely affected by a number of factors, such as the uniformity of it fields and the size of the gradient fields, the proton density, and the T1 and T2 relaxation. This is because the greater the number of hydrogen protons, the larger the signal. Since the breast tissue is made of fibrous, glandular and adipose tissue which contains over 70% of hydrogen, then it is obvious that higher signal would probably come from the breast tissue. However, inside the tissue, the principle of relaxation works in such a way that the ease with which the adjacent atoms can absorb the surplus energy provided by RF, depends on the exact nature of the tissue and this provides a way of distinguishing one type of tissue from another. The above principle made MRI images susceptible to contrast manipulation which is of greater advantage over mammography.
Mode of Operations. Radiographically, mammography relies critically on its anatomical mode of operation to be able to shown some considerable small numbers of breast cancers prior to any clinical signs or symptoms and this has led to its use in screening women for occult disease (Olestericher et al 2005). Breast compression is essential in mammography because it reduces absorbed dose and image blur and also increases image contrast (IPEMed. 2005, Report 89). Dose reduction is due to increased penetration of the x-ray photons through thinner tissue sections and geometric blur is as a result of breast being held firmly in place and closer to the receptor. Obviously, reduced scattered radiation leaving the bottom of the breast and softer x-ray reaching the receptor would increase the mammography contrast. Nevertheless, many factors influence the detection of breast tumour with mammography; these are: breast architecture (Jones 1982), calcifications and spicules of fibrous tissue (Sabel and Aichinger 1995), breast parenchyma density (Ciatto et al 2004), age (Buist et al 2004), use of hormone therapy (Connor et al 2004) and fat (IPEMed. 2005, Report 89). One of the critical limitations of mammography is in the investigation of dense breast tissues. Film-screen mammography is frequently unsatisfactory, even with photo-timed exposures. This is because there is often an insufficient contrast to differentiate tumours from the dense breast parenchyma (Green and Oestmann 1999). The introduction of MRI would go a long way to resolve this mammography shortcoming.
On comparison basis, MRI imaging uses both physiological based imaging techniques and tumour vascularity, to demonstrate benign in normal breast. However adipose tissue has been acknowledged to have shown the highest signal intensity because of its short T1-relaxation time. The other breast tissue types have similarly low signal intensity on T1-weighted images. T2-weighted spine echo sequences (e.g TR=1600ms, TE=70ms) which is resulted by delaying the application of gradient fields by about 30ms are oftentimes normally adopted in breast screening (Kaiser and Zeitler 1985, Heywang et al 1986). Here tissues with long values of T2 specifically watery tissues and tumour like cysts are favoured and appear brighter. However, proton-density-weighted images depend little on T1 or T2 but highlight the density of mobile protons and hence water content of the breast tissue. Thus, in MRI the signal intensity depends significantly on tissue water content and cysts appear much brighter than fat in order to enable MRI to demonstrate both cyst and dense breast parenchyma positively (Sabel and Aichinger 1995).
Size of the tumour
Green and Oestmann (1992) wrote that, in patient with suspected breast cancer, mammography images need to have adequate signal-to-noise (SNR) to help define the tiniest possible microcalcifications. Therefore mammography especially in digital storage phosphor images, the higher the SNR, the better its lesion positive demonstration. Therefore, adequate SNR helps to define the maximum number of individual microcalcifications and clusters that can be identified within the spatial resolution constraints of mammography modality. However, Jones (1982) in Sabel and Aichinger (1995 p335) pointed out, that for mammography to demonstrate calcification positively based on the radiographic system adopted, the lower limit of the diameter of the calcification must be within the range of 100-300µm. In addition, when the breast is glandular, it is more difficult to image its architecture using mammography than when the breast contains large amounts of fat (Oestreicher et al 2005). Therefore, the quality of a mammogram depends upon the overall resolution of the imaging system, the radiographic technique as well as the size and type of breast being examined.
If fat and water had formed the basis of MRI image formation, then, the assertion that MRI processed the ability to separate components within one tissue type with certain degree of variation in image content because of its differential intra-tissue water and fat distribution hold sway as modality of the future. This is the good contrast resolution the imaging professional is waiting for. Base on the aforementioned characteristic, MRI could be adjudged as the modality for old women breast screening as fibrous and glandular tissue must have been replaced by fat. Also in young female dense breast, cysts may equally be demonstrated. However, with the introduction of contrast agent specifically gadolinium has made the demonstration of calcifications possible. Contrast agents MRI, unlike other modalities are being measured based on the contrast agent effect and not the agent (Pope 1998). However, a major deficiency of Gd-DTPA enhanced MRI is that the tumour is often isointense with fat in T1-weighted images. Since the breast contains considerable amounts of adipose tissue, a hyperintense enhancing mass can be obscured by the surrounding hyperintense fat. Thus a complex procedure like fat subtraction imaging techniques need be applied in order to resolve the problem (Gilles et al 1993 in Sabel and Aichinger 1995).
To justify the above position, the work of Brem et al (2009) is being reviewed in part here to allow for adequate comparison between mammography and MRI in relation to their detection of invasive lobular carcinoma. Located in the lobular epithelium area of the breast tissue, invasive lobular carcinoma is very subtle at the earlier stage and may not show any desmoplastic response. In Brem et al (2009) study, 28 cases of biopsy-proved were detected in the 26 women in the study group ranging in age between 46 and 82 years old with mean age of 62.8 years. On mammography examination, it was reported that 22 of 28 demonstrate abnormalities which include, 13 asymmetric densities, 4 architectural distortions and 5 spiculated masses. 6 negative were recorded out rightly. However, only 12 patients participated in the MRI screening and 10 of the 12 showed positive (Brem et al 2009).
Furthermore, the results of the study showed that MRI has the greater sensitivity (83%) for detecting invasive lobular carcinoma over mammography (79%). Brem et al (2009) maintained that the high sensitivity observed in MRI were due to the fact that the MRI uses physiological based imaging techniques and tumour vascularity, whereas mammography uses anatomic techniques of imaging. Although there was no mention made by the authors as whether digital mammography could improve its sensitivity, the assertion raises question as to the spatial resolution and contrast of mammography, because given the principles previously stated by which mammography operates - specifically in areas of breast architecture, vascularity and age, it is not unexpected that it would be able to demonstrate invasive lobular carcinoma more than MRI. For instance, the six incidences of invasive lobular carcinomas that were unseen on mammography were detected by MRI. Then, one may wonder the justifications in the continue application of mammography on the account of cost of screening viz-a-viz the associated health risk in terms of radiation dose and possible cancer thereof. Thus this brings to fore the continue search for better and radiation free alternatives to mammography and the quest for emphasising MRI.
Having analyzed both the characteristics of tumour and some salient properties that may probably make its detention tricky, one has come to the conclusion that, for good results to be achieved in breast screening, it may be that a combination of imaging modalities will be superior to any single screening technique. This is because of the nature of the breast and the morphology of the tumour, it has been extremely difficult to design an all round modality for breast screening. Nevertheless, Magnetic resonance imaging (MRI) as new breast imaging technique as it is, gaining popularity. With the use of gadolinium-DTPA as an intravenous contrast agent, breast MRI has been shown to be capable of detecting early breast cancer with 83% and above sensitivity. The enhancement of the breast lesion reflects local tissue changes in blood flow, capillary permeability, and extracellular volume. The high associated cost and inadequate specificity may impair the use of MRI as a screening method for the general population. However, it may be an appropriate screening tool for high-risk populations because of the associated health hazards due to ionizing radiation that may affect the glandular tissues while using mammography. The use of inappropriate radiofrequency coil, the predisposition to burn injuries due to absorption of heat generated by the magnetic field in MRI, the claustrophobic effect, noisy examination and its inability to accommodate patients with metallic implants and pacemakers have added to its clinical limitations.