Section 2 -

What Pathologists Need to Know About Imaging in the Diagnosis of Bone Lesions Michael J. Klein The University of Alabama at Birmingham School of Medicine

Unless orthopedic lesions produce widespread skeletal deformities or very large masses that produce obvious surface irregularities or fungate through the skin, they are essentially invisible without radiographic imaging studies. Attempting to interpret small bone biopsies taken out of their radiographic context is similar to driving an automobile while legally blind. There is no way to localize the disease process, to characterize its relationship with the bone, and to assess the adequacy and representativeness of the biopsy. Having pertinent radiographic data is akin to having a dissected gross specimen in hand, because the entire disease process may then be placed in its logical surrounding framework. Many advances have been made in imaging techniques beyond routine radiography. On the other hand, almost all of the known bone tumors were described prior to the advent of these techniques, so none is required in order to make a diagnosis. Moreover, none of the modern imaging techniques can give, by itself, a complete and representative picture of the entire process so well as a routine radiolgraph. Consequently, the production and availability of satisfactory routine radiographs remains the most important imaging modality for pathologists to understand and interpret biopsies of skeletal diseases. Each new imaging technique has added to our diagnostic armamentarium, but thus far every new study, regardless of its increased sensitivity, has merely been complementary to conventional radiographs. Specialized imaging studies should not be sought in place of routine radiographs. In fact, any imaging study should only be ordered when the routine radiographs or less expensive or invasive techniques cannot answer a diagnostic question about a given lesion . X-rays are electromagnetic waves having a high energy and a very short wavelength and amplitude. These physical properties enable them to penetrate matter in a manner proportionate to atomic spacing and electron density of the atoms they encounter. Radiographic images result from a combination of absorption, scatter, and transmission of the x-ray beam passing through tissues to a detector. Tissues of greater radiodensity, such as bone or calcium salts, cause less exposure of the detector, whereas tissues containing air or fat are least radiodense. Even though radiolucent tissues are poorly visualized, the contrast between radiodense and radiolucent tissues sometimes allows for their interpretation, e.g., articular cartilage or a cartilage growth plate interposed between bones. When interpreting a radiograph, a pathologist must always remember to think in three dimensions, for the fact that radiographs are two-dimensional representations of three-dimensional pathophysiology, is easily overlooked. A radiograph of a long bone appears to have two compact outer zones corresponding to the cortex and a hazy central portion corresponding to the medullary cavity. A three-dimensional construct reminds us that the x-ray beam transects two thicknesses of cortex even in those places that our mind's eye assumes is medullary. The more dense outer regions are merely those areas where the tangential beam effectively transects greater than two thicknesses of cortex. Since the medullary cavity is primarily comprised of fatty marrow in an adult long bone, any lesion confined to the medullary cavity in the shaft of a long bone is invisible on a radiograph unless it destroys greater than 40% of the bone in its path, or if is radiodense. Destruction of less than 40% of the bone may still be visualized on conventional radiographs if the area of destruction can be isolated in such a way that the x-ray beam transects a proportionately larger area of the destruction. This is the primary reason it is necessary to take orthogonal views (anteroposterior, lateral, and oblique) when producing radiographs. Bone lesions tend to follow statistically reproducible patterns of skeletal distribution and radiographic appearances. Primary bone tumors like osteosarcoma and Ewing 's sarcoma affect young individuals, whereas giant cell tumor and chondrosarcoma are usually seen in the mature skeleton. With the exception of some vascular neoplasms, primary bone tumors tend to be solitary. Metastatic carcinoma in bone seldom occurs prior to the fifth decade and is usually multifocal. Metabolic bone disease may produce focal skeletal lesions, but usually causes diffuse skeletal changes. Radiographic assessment of osseous lesions depends not only upon what the lesion does to the bone, but how the bone affects the lesion. In general, bone reacts to structural and functional abnormalities in the same way regardless of whether the lesion is traumatic, inflammatory, metabolic, or neoplastic; the variations in reaction are only in degree. Arguably, the most important attribute by which to judge the biological potential of a process radiographically is to evaluate the border between the abnormality and normal bone. In general, the more poorly defined the border, the more aggressive the biologic potential of the process. Lesions with sharp definition appear this way because osteoclastic activity, which is a slow process, proceeds at either the same rate or higher rate than lesional growth. Processes having a sclerotic border have this border because osteoblast activity, which is also a slow process, has the capacity to wall off or define the borders of the lesion. Another important attribute is the examination of a periosteal reaction. Under normal circumstances, the periosteum is invisible on radiographs, however, elevation or irritation of this tough but soft membrane results in bone formation that may be observed on a radiograph. While this bone may be organized in various ways, the degree of continuity of this reaction is inversely related to the speed of growth of the lesion causing it. In short, discontinuous periosteal new bone formation is a more worrisome feature than continuous periosteal new bone formation. Finally, certain types of bone lesions produce osseous or cartilage matrix contents that give rise to characteristic radiographic findings that may allow more specific identification by radiographs alone. Once the constellation of radiographic features is observed, particular special imaging studies may be performed, if necessary, to further characterize specific diagnostic features. Plane Tomography In plane tomography, the x-ray tube and the cassette (or detectors) move in opposite directions to one another with respect to the patient. Because the film and the source move, the radiograph is blurred, but the area closest to the pivot point between source and cassette moves the least and is in better focus compared to the remaining structures. By moving the apparatus closer or further from the object of study, serial slices in which the areas of interest is in relative focus are prepared. This technique is useful in evaluating overlapping details in bone such as fracture lines or edges of tumors. Since it is relatively expensive, Computerized Tomography Computerized tomography is an x-ray based technique in which a variable number of x-ray sources are coupled to their own x-ray detectors via computer. The computer calculates the difference between energy leaving the source and that reaching the detector and yields an image that is essentially a map of radiodensity. The resulting images are identical to what would be obtained by slicing the body part into thin parallel sections ranging from a millimeter to a centimeter or more in thickness, and making contact specimen x-rays of each slice. In effect, processes can be examined with surgical sensitivity without performing surgery. CT is capable of detecting very small differences in tissue density with very good resolution, so it is useful in detecting small abnormalities in bone that would be masked in a conventional radiograph. It is also very helpful in assessing localized cortical destruction which is very important diagnostically but difficult to biopsy. It is particularly useful as a localizing technique to perform closed needle biopsies on lesions; it can even assess with some accuracy whether the abnormality has been sampled. On the other hand, CT has poor contrast, and it is not as good as MRI for soft tissue evaluations. Magnetic Resonance Imaging Magnetic resonance imaging, or MRI is a technique using the radiofrequency portion of the electromagnetic spectrum rather than its x-ray counterpart. The smaller the nucleus, the less radiofrequency energy is required to induce magnetic resonance; for all practical purposes, the resonance signal measured using magnetic fields of the strength commonly used in medical applications is that of hydrogen atoms. This means that substances containing fat and free water resonate most freely in biological applications. Interpreting MRI in simple diagnostic fashion does not require that a physician need understand all the subtle physical principles of MRI any more than driving an automobile requires one to be a mechanic. What is required is a general knowledge of anatomy combined with an awareness of the typical signals generated by various tissues in MRI. Although resolution of MRI is inferior to that of CT scans, the degree of contrast is much better in MRI. Objects with little free hydrogen, such as compact bone do not give off a signal, so resolution of cortical abnormalities is poor. Although cancellous bone also gives off no signal, the medulla of the ends of bone is only 25% bone and 75% fat and marrow by volume. Since this fat gives off a strong signal, the medullary cavity appears bright. Evaluation of the extent of soft tissue masses and of the interface of tumors with normal marrow is particularly superior on MRI. Because MRI can discriminate between water, fat, and whole blood, it can sometimes reveal physiological information about a dynamic process in the same way as scintigraphy. Scintigraphy (Bone Scanning) Radioisotopic bone scanning, or bone scintigraphy, uses an injected radioactive tracer with a high affinity for osteoblastic activity. Uptake is measured with a gamma counter and areas of the skeleton with increased oseoblastic activity are identified even before radiographically demonstrable bone is formed. Because it reflects physiologic events before they become anatomic events, it is useful in assessing early alterations in bone disease. It can detect infection and avascular necrosis less than a day after the onset of the process, while radiographic changes may not develop for ten days to two weeks. It is often useful to detect responses to metabolic diseases or skeletal metastases before these appear radiogaphically. Single Photon Emission Computed Tomography (SPECT) This technique is a modification of scintigraphy in which the scanned images are examined tomographically. Thus the exact relationship between conventional radiography and CT scanning is the same as that which exists between Scintigraphy and SPECT. Scanned images are more sensitive than in scintigraphy, but actual counting time is much longer. Positron Emission Tomography In this study, the injected radionuclide emits positrons. When each positron combines with an electron, two gamma rays are emitted. The increased production of radiation increases the ratio of actual signal to background noise compared to SPECT, resulting in better resolution of images. PET images can be combined with and superimposed on CT images to yield anatomic and corresponding physiologic information. The technique requires on site preparation of radionuclides, which limits its availability and makes it very expensive. Table I. Summarized Attributes of Imaging Studies Imaging Technique Principle Chief Advantage Disadvantages Usual Appearance Routine X-rays X-rays directly used to generate a two dimensional image of bone and soft tissue. Provides the entire anatomic picture of the region of interest. Should be the screening procedure for all other imaging studies. Relatively insensitive. Requires multiple views. Air-Black Fat-Dark grey Other soft tissues- Lighter grey Bone, calcium, heavy metals- White Plane Tomography Same as in routine X-ray except that the X-ray source and detector is moved relative to a stationary patient. The pivot point between source and detector appears most focused; the remainder is blurred. Provides the entire anatomic picture, but increases the sensitivity of routine X-rays by isolating specimen planes. Expensive and becoming less generally available. Same as routine X-rays. CT Scanning A computer measures the difference between incident and absorbed X-rays in a slice of tissue of designated thickness. The image is a map of tissue density in the slice. Increases the sensitivity of X-rays by isolating thin tissue slices. Very good resolution permits fine analysis of compact bone changes. Can be used to measure tissue density precisely. Poor contrast. Soft tissues are not well visualized. Because lesional areas may be small, tissue slices may not incorporate pathology. Same as routine X-rays, but sensitivity increased. MRI Nuclei are polarized by a magnetic field. A radiofrequency signal deflects their dipole moments from the magnetic field and during the deflection causes them to give off the same radiofrequency signal. This signal is examined by a radiofrequency detector and plotted with respect to time. Very high inherent contrast demonstrates details in soft tissues not revealed by CT scan. Can distinguish between fat, muscle, fibrous tissue. Shows circulatory alterations and edema as well as the ability to delimit the true boundaries of tumor and normal tissue. Poor resolution. Bone generates no detectable signal. Tissue slices may not incorporate pathology for same reasons as in CT.   T1 Weighting Ts Weighting Fat Very bright Bright Water Dark (Hypointense) Bright (Hyperintense) Fibrous Tissue Dark Usually Dark Bone Very dark (Signal void) Very dark (Signal void) Bone Scintigraphy A radioisotope with a short half-life that localizles to areas of bone formation is injected intravenously. A gamma counter is passed over the body and localizes areas of uptake. Demonstrates physiologic changes when there is early reactive bone long before anatomic changes can be detected by X-ray or CT scanning. Examines the entire skeleton at once. Lesions that are not bordered by reactive bone may show no uptake even if the changes are visible on X-rays. Bone forming reactions demonstrate high uptake (brightness). Single Photon Emission Computed Tomography (SPECT) A radioisotope is injected as in bone scintigraphy, but the images are examined tomographically. The relationship of scintigraphy to SPECT is the same as conventional radiography to CT scanning. The ratio of counts to noise is much better than in scintigraphy because radioactive sources are not superimposed. The image quality is better than in scintigraphy. More counting is needed than in scintigraphy. Spatial resolution is sometimes worse than in scintigraphy. Same as in Bone Scintigraphy. Positron Emission Tomography (PET) The injected radioisotope emits positrons. The degradation of each positron creates two X-rays. The increased production of rays (two for each positron) results in a higher signal to noise ratio and much better resolution than in SPECT. Very high cost for system and test. Positron emitting nuclides have very short half-lives and must be produced on-site by a cyclotron. Similar to Bone Scintigraphy; can be superimposed on or even combined with CT of the same site. Reproduced in part from Klein, MJ: Radiographic Correlation in Orthopedic Pathology Adv. Anat. Pathol. Volume 12:155-179, 2005. References Gilkey, F., Sweet, D.E., and Mirra, J.: Radiologic/Pathologic Correlation of Bone Tumors. In Bone Tumors, Clinical, Radiologic, and Pathologic Correlations, 2nd Edition, Chapter 27, p 1803-1831, Ed. Mirra,J.,J.B. Lippincott Co., Philadelphia,PA, 1989. Klein, M.J. "Pathophysiology of Bone Tumors. In: Orthopaedics, Fitzgerald,RH, Kaufer,H., Malkani,AL eds.(St. Louis: Mosby, Inc), 2002, 991-1001. Klein, MJ: Radiographic Correlation in Orthopedic Pathology. Adv Anat Pathol 12:155-179, 2005 Lodwick,GS, Wilson,AJ, Farrell,C et.al.: Determining growth rates of focal lesions of bone from radiographs. Radiology 134:577, 1980. Madewell, J.E., Ragsdale, B.D., Sweet, D.E. Radiologic and Pathologic Analysis of Solitary Bone Lesions. Part I. Internal Margins. Radiol. Clin. North Am..19: 715-48, 1981. Olendorf, W., and Olendorf, W.Jr.: MRI Primer (New York: Raven Press), 1991. Webb, A: Introduction to Biomedical Imaging (Piscataway, NJ:IEEE Press-Wiley Interscience), 2003.