Acta Oncologica

ISSN: 0284-186X (Print) 1651-226X (Online) Journal homepage: http://www.tandfonline.com/loi/ionc20

Modern Imaging Methods in Oncology Michael N. Maisey & John B. Bingham To cite this article: Michael N. Maisey & John B. Bingham (1992) Modern Imaging Methods in Oncology, Acta Oncologica, 31:8, 889-902, DOI: 10.3109/02841869209089726 To link to this article: https://doi.org/10.3109/02841869209089726

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Rcwirw in Oncologicu Vol. 5. No. 2. pp. 889-902, 1992 (in Acru Onc,ulu,qiccrVol. 31, No. 8)

MODERN IMAGING METHODS IN ONCOLOGY MICHAELN. MAISEYand JOHN B. BINCHAM

Modern imaging methods are very important in the management of patients with cancer and of their disease. It is vital that clinicians treating them understand the relevance of different imaging techniques for specific applications, so that the best choice can be made to aid diagnosis and monitor response to treatment. This review briefly covers the development and principles of the diverse imaging methods available, from the discovery of x-rays by Rontgen in 1895 to the recent techniques of magnetic resonance and positron emission tomography. The authors endeavour to point out the strengths and weaknesses of each method, using clinical examples where appropriate. Finally, future developments are discussed. It is hoped that this review will aid clinicians diagnosing and treating cancer patients to choose the most suitable imaging method for their patients from among the vast array available.

Imaging methods play a fundamental part in the modern management of disease and their use in the management of patients with cancer is as important as in any branch of clinical medicine. The effective use of imaging techniques requires a good knowledge of the physical basis for the methodology as well as the technical and other limitations. It also requires a close relationship between clinicians treating cancer and their radiological and other imaging colleagues as well as between radiologists in different disciplines. Imaging techniques are used in oncology for diseasescreening in the asymptomatic patient, diagnosis of disease in the symptomatic patient, to assess the extent of known disease (staging), to obtain information about the likely pathology and degree of malignancy and to follow the response to treatment or progressive disease. Imaging may be used to detect complications of treatment (e.g. cardiac toxicity) and of the disease (e.g. long bone fractures) and finally to establish the presence of a disease-free state or of recurrent disease. Finally, imaging may be used therapeutically and for measurement. Examples include biopsy localisation, stereotactic surgery, angiography for drug therapy and embolisation and for the volume selection of localised magnetic resonance spectroscopy. From the Division o f Radiological Sciences, United Medical and Dental Schools of Guy's and St. Thomas's Hospitals. Guy's Hospital, London Bridge. SEI 9RT. England. Correspondence to: Prof. Michael N. Maisey (address as above).

This review will consider: 1) the development and physical basis of the imaging methods, 2 ) the strength and weaknesses of the more important methods, 3) the likely development areas.

The practice of clinical medicine had to wait until 1895 for the development of the modern era of medical imaging. which has since displayed anatomy, pathological morphology and physiology in the living subject in the way anatomists and pathologists had been demonstrating during the preceding centuries.

Physical basis and development X-rays

On the 8th of November, 1895. Professor Wilhelm Konrad Rontgen ( I ) noted that '. . , certain crystals placed near a highly evacuated electric discharge tube caused luminescence and could be shielded by denser objects.' To distinguish them from other rays he called them x-rays. One month after this description the first non-invasive image, a radiograph of his wife's hand, was published. Within a short time diagnostic x-ray facilities were installed in major hospitals in Europe and North America. Subsequently, there has been steady progress in the improvement of radiology, extending the quality. scope and 889

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applications. Key advances have included the introduction of angiography by the Portugese neurosurgeon Egaz Moniz in 1927 and recently refined still further by the use of digital vascular imaging (DVI) techniques. A major limitation for deeper organs was the overlying tissue in front of and behind the organ of interest. Computerised tomography

Cross-sectional tomography was first described by Kuhl & Edwards in 1963 ( 2 ) , using radioactive emission tomography. This important advance brought together mathematical techniques for image reconstruction with mechanically rotating detectors and was developed by Hounsfield (3) in 1973 into computerised x-ray transmission tomography (CT) with the first clinical applications reported by Ambrose (4). This major advance was, in spite of pessimistic predictions, in response to an early design of a potential cross-sectional imaging device which induced one leading x-ray manufacturer to write ( 5 ) 'Even if it could be made t o work as you suggest we cannot imagine a significant market for such an expensive apparatus which would d o nothing but make a radiographic cross-section of the head'. Rapid technological development has occurred mainly related to speed of acquisition of images and reconstruction times. In the body, particularly, the ability to obtain scans within the time of the breath-hold resulted in a considerable improvement in the quality of the images in the chest and abdomen. Resolution has also improved considerably since the first generation scanners, related, in part, to computer advances as well as engineering improvements. One limitation of C T has been the mechanics of rotating the heavy x-ray tube and detectors around the patient intermittently. This has been partially solved by a continuously rotating system but a novel solution has been the use of electronic beam deflection so that 50 millisecond scans are now possible (6). This has enabled examination of the cardiac chambers throughout the cardiac cycle. Iodinated contrast media are used to enhance the differences between normal and abnormal tissue, particularly important in the brain and to show vascular structures, most useful in demonstrating the mediastinal anatomy. CT is now routine for staging of many neoplastic lesions and plays an important role in follow-up. Radionuclide imaging

Shortly after the discovery of x-rays in 1895, a French physicist, Henri Bequerel placed a phosphorescent salt of uranium on a light proof envelope containing light sensitive film and noted black spots on the film inside. His conclusion, which was not entirely correct, was that these crystals emitted the x-rays described by Rontgen. He gave the task of investigating this phenomenon to his student Matya Sklodowska. With her husband Pierre Curie she

demonstrated the phenomenon of radioactivity in pitchblende which was due to the presence of a radioactive nuclide (subsequently called polonium after her country of Poland) and she later purified radium. Villard, in 1990, described the gamma rays which were emitted by some radioactive materials and which were to form the basis of medical imaging with radioactive tracers. However, the credit for laying the foundation for the use of radioactive tracers in medicine is usually ascribed to George Hevesy (7), the Hungarian chemist who, in 1913, showed that radioactive nuclides could be used as 'tracers' for stable atoms. The principle of x-ray imaging is based on the differential absorption of the x-rays due to differences in the electron density of tissue and thereby displaying normal and pathological structures, whereas imaging with radioactive tracers shows normal physiology and functional changes caused by disease. The differences in speed of development of these two imaging modalities reflect the historical emphasis on anatomy and structural pathology followed by a much later appreciation of the importance of function at both organ and cellular level. It is now increasingly recognised that function is as important as structure and that diagnostically they are complementary -most morphological abnormalities are demonstrated by using x-rays and most disorders of function by radioactive tracers. It was approximately half a century from the discovery of radioactivity before the first medical images using radionuclides were produced. Moore (8) localised a brain tumour using "lI-labelled di-iodofluorescein based on the diffusion of a radioactive tracer from the vascular space into the tumour due to breakdown of the blood-brain barrier, a concept first proposed in 1880 by the German pharmacologist Paul Erlich. As with C T it was the amalgamation of technologies developed at different times which enabled functional imaging with radionuclides to develop and become the functional partner of x-ray imaging. Key developments were: the design of a cyclotron in 1931 by Ernest Lawrence (9); the discovery and production of technetium by Segre & Seaborg in 1937 (10) and the recognition in 1964 by Harper et al. of the potential of one of its many radioisotopes 99mTc( 1 I ) ; development of the mechanical rectilinear scanner by Cassen et al. ( 12) in 1951 and later the gamma camera by Anger in 1958 (13). Radionuclide imaging provided the first opportunity to non-invasively diagnose brain tumours, liver, splenic and renal masses but it is important to note that, although radionuclide scanning is capable of diagnosing these tumours, C T and ultrasound are now used as the first diagnostic option. There is an important principle here: although a particular technique may be capable of a diagnostic application and may be used in the absence of a better method, in the longer term it will be the capacity of an individual technique to provide unique physical, chemical or functional information which will determine the

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future use. Thus, ultrasound or C T with high spatial resolution should be used to detect and display structural disorders whilst radionuclide imaging which has inherently poor anatomical resolution is more appropriate for the demonstration of function.

Ultrasound

The modern imaging technology which has probably had the greatest impact at the lowest cost is ultrasound imaging. Donald & Brown ( 14), recognised the similarity between the foetus in utero and a submarine. and were first to use pulsed ultrasound to image the foetus in the same way that submarines were detected by sonar. This is based on the detection of the reflected ultrasonic beam from interfaces of different composition and with this technique they produced a foetal image in 1960 ( I 5). Previous authors had proposed methods of using ultrasound in both transmission mode ( 16) and reflecting mode ( 17) but it was the work of Donald & Brown that ushered in the modern era of two-dimensional real time sonography. There has been rapid technological improvement so that detailed foetal anatomy is now visible and there is now widespread application to other organs and clinical problems so that ultrasound is the method of choice for the initial examination of the solid organs of the upper abdomen and the pelvis.

Positron emission tomogruphy (PET.j

A drawback preventing the development of the full potential of radionuclide tracer imaging methods was the lack of suitable radioactive tracers for 3 key elements: oxygen, carbon and nitrogen, which form the basis of all organic compounds and many drugs. The development of the cyclotron in the 1930's and subsequent refinements have allowed the routine production of radioactive isotropes of these elements for medical uses. These radionuclides decay by the emission of positively charged electrons (positrons) which interact with an electron-releasing energy (51 I KeV) as two photons at almost 180" to each other. Useful isotopes which decay by positron emission have short half lives (oxygen 2 min, nitrogen 10 min. carbon 20 min) consequently when used clinically, the patient must be close to the site of production. Cross-sectional imaging of the distribution of these tracers and labelled biological and pharmaceutical compounds (e.g. 0,. CO?, H,O, neuroleptic drugs, amino acids, glucose) is an important extension of radionuclide imaging. The technique of positron emission tomography was first described over 15 years ago (18). Widespread clinical application is limited by the cost, and the need for close proximity to a cyclotron, though developments in cyclotron technology are extending the availability of these techniques. After many years of basic research. clinical areas are emerging where PET has been shown to affect patient

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management (19-21). These are in four major medical specialities: cardiology, e.g. the demonstration of viable but akinetic myocardium ('hibernating myocardium') by the incorporation of "fluorodeoxyglucose ( "FDG); neurology, where localised abnormalities of flow and metabolism can be shown in most cases of focal epilepsy; psychiatry, for the diagnosis of Alzheimer's and multi-infarct dementia and in oncology, e.g. using "C-labelled amino acids to diffcrentiate scar tissue from viable residual tumours after radiation or chemotherapy. These methods are also increasing our understanding of mechanisms of cerebral function in health and disease and the interactions of drugs with receptors 'in vivo'. Many more applications will enter clinical practice in the near future. Mugnetic resonance

The nuclear magnetic resonance ( N M R ) phenomenon was first described by Bloch et al. (22) and Purcell et al. (23) in 1946, and is the basis of powerful physico-chemical analytical laboratory methods. Nuclei of certain atoms with unpaired nucleons (either an odd number of neutrons or protons or both, e.g. 'H, "P, "C, "Na), when placed in a strong magnetic field will align with lines of magnetic force and can be made to absorb and emit electromagnetic radiation. These signals are characteristic of the nucleus, its concentration and chemical environment. The possibility of NMR techniques being used in medical imaging was raised by an American chemist, Paul Lauterbur (24). It was also suggested that differences in MR signal between benign and malignant tissue might be used diagnostically (25). Mansfield & Maudsley (26) and Hinshaw et al. (27) in 1977 first applied the techniques and produced cross-sectional images based on the use of magnetic field gradients in addition to the uniform magnetic field, to achieve the spatial information necessary for image production. Massive investments in the technology of superconducting magnets, radiofrequency electronics and coil design have transferred MRI from the research laboratory to become a clinical tool in routine use in many institutions. MRI is capable of producing high resolution images of soft tissues and is based on differences in the concentration and the macromolecular chemical environment of the hydrogen protons of water and fat. However, it is a poor technique for cortical bone since the few protons in its structure are too firmly anchored to move in the magnetic field and thus d o not produce a signal. MR is in principle superior to C T for soft tissue because variations of tissue characteristics of similar tissues (e.g. white and grey matter in the brain) are greater than the differences in electron density, which is the determining factor for the image contrast in CT. In general, if the detail of soft tissue anatomy is required, imaging sequences which emphasise the TI relaxation parameter of hydrogen protons are

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chosen (TI weighted MR images), whereas sequences which emphasise the T2 relaxation parameters (T2 weighted images) or suppress the fat signals (e.g. short tau inversion recovery, STIR) are better for demonstrating contrast between abnormal and normal tissue. This is due to the high water content of pathological abnormalities. X-ray angiography

The routine use of angiography for the delineation of tumours and their blood supply has declined considerably since the advent of C T and ultrasound. There remain some situations where angiography is necessary to demonstrate the blood supply to tumours and the relationship of the masses to the normal vasculature, particularly musculoskeletal tumours. In addition, there has been some use of preoperative embolisation of vascular tumours to reduce their blood loss at surgery and to reduce their bulk. Occasionally intra-arterial infusion of chemotherapeutic agents is used to reduce the effects of systemic toxicity, particularly in the liver.

detection of supratentoral brain tumours, but only MR may be able to show a cervical cord tumour. There are other examples and the following section will briefly review important areas of clinical medicine where imaging methods are needed based on whether the methods used are complementary, competitive, i.e. both clinically useful but differing in accuracy, or provide unique information which is otherwise unobtainable. Neurology

For the diagnosis of brain tumours both CT and MR are useful. However, for posterior fossa tumours MRI is clearly superior (28) and should be the first choice whenever possible. These tumours are usually identifiable on C T but bone artefact decreases the sensitivity of detection. For cerebello-pontine angle tumours (particularly intracanalicular acoustic neuromas and cholesteatomas) (29) and pituitary microadenomas (30) MRI is again preferable (Fig. 1). CT remains the method of choice for the detection of intracerebral metastatic disease and many units simply

Relative merits and disadvantages of imaging methods If bone anatomy is the goal, plain radiography or C T is unsurpassed, but when functional and metabolic information is required the use of radionuclides is more appropriate. However, these basic principles ignore many practical factors which may override theoretical considerations. An appreciation of the physical and chemical basis of techniques will assist in the appropriate choice of imaging technique and in the evaluation of new developments. Examples of practical limiting factors include the risks to patients with metal implants or pacemakers when using MRI, metal artefacts and difficulties with positioning patients using CT; the observation that obesity may improve abdominal C T scans but makes ultrasound less reliable; difficulties in obtaining good ultrasound examinations when there is intervening bone or bowel, and the time taken to obtain a diagnostic scan in a moving or unco-operative patient which may make an MR or radionuclide ( R N ) scan useless even when it is theoretically the method of choice. More simply, a diagnostic facility may not be easily available, MR and PET are good examples, and even local expertise in particular techniques will have an influence. It is important to know whether a particular imaging method will provide unique, new and essential information unobtainable any other way or is it simply an improvement over other methods. RN, C T and M R brain scans, in ascending order of sensitivity, are all adequate for the

Fig. 1. Coronal T,-weighted MR image through the pituitary following intravenous contrast medium (Gd-DTPA) in a paticnt with pituitary-dependent Cushing’s disease showing a non-enhancing microadenoma in the central part of the anterior lobe of the pituitary (arrowed).

Fig. 2. a ) CT scan through the posterior fossa after intravenous iodinated contrast medium demonstrating an enhancing metastatic deposit in the left cerebellar hemisphere. b) An axial T2-weighted MR image shows the metastasis as a small high signal lesion with surrounding oedema (arrow). Incidentally, there is a small arachnoid cyst slightly deforming the brain stem (arrowed). c) Axial and coronal T , -weighted MR scans show the enhancing metastatic deposit (arrow), enhanced by i.v. injection of gadolinium-DTPA.

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image the brain following a bolus of intravenous contrast medium rather than obtaining a non-enhanced scan first. In situations where CT and MR are not easily available, radioiosotope imaging with '""Tc-diethylenetriaminepentaacetic acid (DTPA) remains an acceptable screening test. Only where there is a strong suspicion of intracerebral metastatic disease with a negative C T scan is it normally necessary to utilise MR imaging. T2-weighted images usually suffice but the sensitivity of the detection of metastatic deposits may well be slightly increased by the use of the intravenous paramagnetic contrast agent, gadoliniumDTPA (31) (Fig. 2). This is handled by the brain in a similar way to iodinated contrast media in C T and shows areas of abnormal perfusion and breakdown of the bloodbrain barrier. Although MR does not normally need to be used in the diagnosis of supratentorial tumours it has considerable use for the radiotherapist for planning radiotherapy fields as the coronal and sagittal display are more suitable for planning than the axial plane of CT. As with metastatic disease, T2-weighted sequences are sensitive for the presence of primary tumour but differentiation between tumour and oedema is best shown by TI-weighted sequences after intravenous gadolinium-DTPA (32). Developments in functional brain imaging are providing unique information about cerebral perfusion and function. Abnormalities of perfusion can be demonstrated (33) using

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new radionuclide tracers such as ""Tc-hexamethylpropyleneamine oxime ( HMPAO) and 9 9 m T ~.2-ethylenediylbis-l L-cysteine diethyl ester (ECD) (34) in stroke, focal epilepsy (Fig. 3) and in the dementias. PET is more reliable and quantitative for measuring cerebral perfusion and there are some situations where PET will provide definitive clinical information; e.g. intractable focal epilepsy (35) when the site of the focus cannot be identified by electroencephalography (EEG), single photon emission computed tomography (SPECT) or MRI; using "C-labelled amino acids to differentiate scar from recurrent cerabral tumour following surgery and radiotherapy, for the early diagnosis of Huntington's disease where there is decreased glucose metabolism in the basal ganglia (36) and the differential diagnosis of dementia. MRI has made a great impact on the investigation of spinal cord disorders (Figs 4 , s ) . It has considerably decreased the need for myelography in the same way as C T did for air encephalography. Whenever possible the first investigation after plain radiography for suspected intrinsic or extrinsic cord disease should be MRI ( 3 7 ) . T, -weighted sequences, sometimes supplemented with contrast administration are usually sufficient. On the other hand, bony disorders of the spine are usually best examined by plain films and C T complemented by a radionuclide bone scan using 9'mTc-methylene diphosphonate (MDP) with occasional addition of SPECT. Bone

A combination of radiographs, C T and radionuclide bone scan is suitable for most neoplastic bone disorders. As a general principle the whole body radionuclide bone scan is pre-eminent for demonstrating active osteoblastic metastatic disease (38) (Fig. 6) but needs to be supplemented with appropriate radiographs and sometimes CT. The latter provide structural information necessary for a more specific diagnosis. Radionuclide bone scans can be used for marking a suspect site prior to percutaneous needle biopsy (39) but guidance by fluoroscopy is generally more straightforward. It is no longer necessary to obtain a routine skeletal survey for metastatic bone disease though radiographs are appropriate for symptomatic areas. particularly if imminent fracture is suspected. Despite MR providing little information about the cortex of bone it does have a high sensitivity for marrow replacement by metastatic disease due to the high fat content of marrow (Fig. 7). Consequently, in the presence of symptoms of bone pain it is a very suitable modality for the detection of lytic metastatic disease when the isotope bone scan is equivocal or negative (40).

Fi,y. 3. Radionuclide SPECT study of cerebral perfusions in a child with recurrent focal epilepsy. This slice shows a focus of increased Row in the right fronto-parietal region during a focal fit.

Cl1est The plain postero-anterior radiograph remains the mainstay ofchest evaluation. Although the lateral film occasionally

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Fig. 4. a ) M R I showing lobulated extramedullary intradural turnour in the thoracic canal which proved to be a neurofibroma. b) The outline of the tuniour is more clearly demarcated following intravenous constant medium in these T, -weighted images.

a)

b)

Fig. 5. a ) and b) In these M R images the extradural compression of the upper thoracic cord by nietastic disease to the vertebral bodies from carcinoma of the breast is shown in T,-weighted axial and sagittal planes.

assists anatomical localization of lesions it is unusual for this projection to show an abnormality that was not visible on the frontal film. Linear tomography has almost completely been replaced by CT, particularly for the detection of pulmonary metastases and for the evaluation of the mediastinum. Although paratracheal, hilar and bronchopulmonary adenopathy is usually identifiable on the PA chest film. aortic. subcarinal and retrocrural adenopathy is much niore easily detected by CT. Generally, chest CT in

oncology is used for staging of malignant disease, particularly lymphoma and carcinoma of the lung where mediastinal infiltration and adenopathy is likely to preclude surgery and for the evaluation of the effects of therapy. Assessment as to pathological involvement of nodes by tumour is dependent on size criteria as there are rarely spccific appearances of malignant nodal disease. An upper limit of 1 cm diameter is usually used as a cut-off point for a normal node but reactive nodes may enlarge beyond this

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Fig. 6. Radionuclide whole body bone scan (yymTc-methylenediphosphonate) in a patient with breast cancer showing multiple sites of increased osteoblastic activity representing the sites of metastatic bone deposits.

size and metastatic involvement may be seen in nodes much smaller than this and the likelihood of metastatic disease is greater when the nodes are multiple. It is often necessary to biopsy a suspicious node by mediastinoscopy (41). In the United States, much attention has been paid to calcification in pulmonary nodules in an attempt to distinguish benign from malignant disease using CT analysis of

the density of the nodules (42). This has not been very successful in the U K where histoplasmosis, a common cause of a calcified nodule in the USA, is very uncommon. Magnetic resonance is effective in the detection of mediastinal adenopathy and does not normally require the administration of intravenous contrast medium to distinguish blood vessels from enlarged nodes as the former are

MODERN IMAGING METHODS IN ONCOLOGY

Fig. 7. MRI showing extensive replacement throughout the thoracic spine by metastatic disease from carcinoma of the breast.

visible as flow voids. Infiltration by tumour through the chest wall is also adequately depicted by MR (43). However, the lung parenchyma is more problematical because of the time taken to acquire MR images. Resolution of lung nodules is inferior to that of C T because of the inability to obtain breath-hold images, though more modern machines with fast sequences may be able to achieve this. Abdominal and pelvic diseuse

For most clinical problems, excluding gastro-intestinal tract disease, ultrasound examination of abdomen and pelvis is outstandingly efficient in terms of cost, time, accuracy and ease of use and should be the first investigation. Liver metastases are detected with a high sensitivity using ultrasound. though the investigation is undoubtedly operator-dependent. C T and M R have a slightly increased sensitivity and in departments where there is ready access to a modern scanner, MR has been advocated as the first choice of investigation where it is essential to exclude liver metastases prior to curative surgery. For routine follow-up of liver metastases during treatment the radionuclide scan

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is cheap, reproducible and easy to review and could be more widely used for this purpose. Renal tumours are frequently detected during urography for haematuria but the appearances are usually non-specific and require further investigation with either ultrasound or CT. The latter is more effective than ultrasonography since it is easier to obtain information about spread of tumour into the renal vein and inferior vena cava, detect para-aortic adenopathy and liver and lung metastases. C T is particularly useful following nephrectomy as bowel usually fills the renal bed and makes recurrence much more difficult to identify ultrasonically. The pancreas remains problematical. Transabdominal ultrasound is effective in detecting large pancreatic masses and dilatation of the common bile duct secondary to biliary obstruction from small lesions at the level of the ampulla of Vater but views of the pancreas are frequently obscured by overlying bowel gas. Some progress has been made with small tumours of the pancreas using high resolution endoscopic ultrasound (44). MR has not yet found a role in the routine evaluation of the pancreas. mainly since images of the retroperitoneum are considerably affected by abdominal motion and there is no bowel contrast agent available commercially at present. C T is very effective in showing pancreatic enlargement though the distinction between a tumour and focal pancreatitis may be very difficult to make and percutaneous CT o r ultrasound-guided biopsy is frequently necessary. Unfortunately, by the time pancreatic neoplasms are visible by imaging methods they are frequently incurable by surgical excision. Radiology has a role in their palliation by the use of transhepatic stent insertion. Stents can also be introduced via an endoscopic route and biopsy material obtained at the same procedure. On occasion a combined endoscopic and transhepatic approach is necessary. Lymphoma, since it is effectively a systemic disease and frequently affects the mediastinum, is best evaluated with CT, particularly since distal para-aortic and pelvic adenopathy may be difficult to evaluate with ultrasound. Adenopathy is usually assessed using size criteria as there are usually no specific features and percutaneous biopsy is necessary for indeterminate cases. Multiplicity of nodes may be as important as enlargement. CT is insensitive for the detection of lymphomatous involvement of the liver and spleen which may only be identified on a microscopic level. Functional information may be derived from a gallium-67 citrate scan or by glucose ('*FDG) and amino acid ("C-methionine) metabolism using PET (45)(Fig. 8). Ultrasound is the primary investigation of the pelvis and is useful for screening for early ovarian carcinoma particularly if endovaginal sonography is used which also has the advantage of not requiring a very full bladder. Neither ultrasound nor CT is effective in the detection of early endometrial carcinoma but MR has shown promise in early reports (46).

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Fig. 8. This patient was suspected of a brain infarct or tumour after an abnormal C T scan. a) The "FDG scan showed hypometabolism at the site of the lesion which is consistent with either infarct or low-grade glioma. b) A scan using "C-methionine showed markedly increased uptake due to either increased protein synthesis or blood- brain barrier breakdown. Administration of 5 g of phenylalanine prior to a repeat "C-methionine study saturates active uptake mechanisms, but not passive. c) The repeat study showed very little methionine uptake at the lesion site, confirming tumour. The tumour was found to be a low-grade astrocytoma. (With thanks to Peter Conti, Johns Hopkins Medical Institution, Baltimore, USA).

Transabdominal ultrasound will show enlargement of the prostate in both benign and malignant disease but it is difficult to distinguish between them using morphological appearances alone. If an endorectal probe is used, small hypoechoic areas within the prostate can be identified and biopsied at the same examination so that malignant nodules within the prostate can be separated from other causes of reduced echoes (47). Recent work with endorectal coils in MR suggests that it may be possible to identify malignant involvement based on signal change rather than recourse to biopsy (48).

ultrasound for the distinction of solid from cystic masses (52).

The uptake of I3'I remains a very specific and sensitive imaging method for metastatic thyroid cancer after thyroid ablation. This radionuclide is also widely used for treatment of hyperthyroidism and thyroid cancer. Anatomical delineation with C T or MRI may be needed for appropriate surgical management, particularly for tumour debulking prior to radio-iodine therapy. Recently medullary cell thyroid cancer has been shown to accumulate injected 99mTc(V)dimercaptosuccinic acid (DMSA) (53) and imaging with this radiopharmaceutical in conjunction with MRI or C T often provides information for the effective Endocrine disease management of patients with this tumour (Fig. 9). A n There is general agreement that the first imaging investiimmense amount of effort has gone into the investigation gation of adrenal disease is C T (49) although ultrasound of radiolabelled monoclonal antibodies for imaging neohas been claimed to be as accurate. Radionuclide scans are plastic masses. However, in spite of this there is probably complementary investigations providing functional inforno situation when monoclonal antibody imaging can be mation about a mass: '231-meta-iodobenzylguanidine regarded as essential t o the best management of a particu( MIBG) for phaeochromocytomas and 75Se-cholesterol for lar cancer. Further development of engineered antibody cortical tumours. Similarly, there is some agreement about fragments may alter this situation in the future. other endocrine organs; ultrasound being the primary investigation for parathyroid disease (50), followed by 201Breast thallium/""Tc-0, subtraction scan for equivocal cases. In some centres C T is used first (51) although MRI may A combination of clinical examination and mammograprove in due course to be the best but it is not widely used phy is sufficient for the management of most breast lesions at present. but ultrasound examination of the breast using a high The thyroid gland was the first organ to be scanned with resolution probe is helpful for the distinction between radionuclides and the initial examination of thyroid discystic and solid masses in the breast. There is considerable 04 by ease remains imaging with Iz31 or 9 9 m T ~ - followed interest in the role of Doppler ultrasound for distinguish-

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FIg. 9. Surgical removal of a recurrent medullary thyroid carcinoma was facilitated after the a ) TI weighted MR scan showed the lesion (arrowed) in relation to the other body structures. b) The recurrence of the turnour had been shown by accumulation of tracer in the

9')n'Tc-(V)DMSA scan. (Used with permission from The Lancet)

ing between benign and malignant masses in the breast as judged by differences in blood flow characteristics. Although real time ultrasound imaging is sensitive for the detection of mass lesions in the breast its specificity is not as high as mammography since microcalcification without a mass may be the only indication of malignancy. Since microcalcification is not visible ultrasonically the use of ultrasound as a screening test for the detection of carcinoma is inappropriate. Sofi rissue nroplcrsiu

The determination of the extent of soft tissue neoplasms and their relationship to the neurovascular bundle has, until recently. been performed using CT. It is apparent that the high contrast resolution and the multiplanar capability of MR make it the more appropriate choice for most problems. However, although MR is sensitive for the detection of tumours it is relatively tissue non-specific (Fig. 10) and as elsewhere in the body, particularly insensitive for the presence of calcification. Metastatic disease is well shown by M R and is suited to areas where C T is technically difficult, such as the brachial plexus, and the coronal plane is particularly suited to examination of this area (Fig. 1 I ) . Ultrasound is not commonly used for the initial evaluation of soft tissue tuniours. but may be of value for distinguishing benign cystic structures, such as Baker's cysts adjacent to the knee from solid tumours.

This review, which could not be comprehensive, has attempted to define some of the areas of oncology whcrc new imaging technologies have made an impact on diagnosis and assessment of disease and where there is some degree of consensus on how they should be applied. Future developments The rapid development of imaging methods that has been seen from 1895 to the present time shows no sign of slowing down and new methods will be introduced into clinical medicine and made more widely available. One development which will affect all ongoing studies and may make the greatest contribution without being a new imaging technique in itself will be digital data acquisition. Picture archiving and communication systems ( PACS) will enable image processing techniques to be applied which will improve both the diagnostic content and the communication to clinicians (54). and will make radiographs and all other images accessible on the wards, in clinics and in the operating theatre. Closely allied to this will be better image display, particularly three-dimensional, from CT, MR and SPECT. Routine application of these images to some orthopaedic and neurosurgical problems is already accepted and will be used increasingly for evaluating complex angiographic images. The greater ease of image manipulation and processing will also encourage wider application of image fusion

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Fig. 10. A large myxoid liposarcoma of the right thigh is shown in the coronal plane using a ) a STIR sequence and in the axial plane with TI-weighting b) before and c ) after i.v. contrast medium (arrow).

whereby data representing different functions or measured parameters can be displayed as a single new image, e.g. bone scans and radiographs, PET receptor mapping with MR scans, and metabolic images of cancer with CT scans. MR techniques have been developed which may also have a role in clinical medicine, especially with increasing emphasis on the avoidance of ionising radiation. These include imaging with nuclei other than protons (e.g. '7Na), blood flow imaging ( 5 5 ) (Fig. 12), both anatomical

C)

Fig. I / . Brachial plexus involvement from metastatic brcast ciircinorna is seen in the coronal plane with a ) STIR. b) T,-weighted sequences and c ) in the sagittal plane (arrowed).

(pseudo angiography) and quantitative flow measurements which have already reached the stage of early clinical application. The unique information available from an M R investigation is magnetic resonance spectroscopy ( M R S ) ( 5 6 , 57) which can provide non-invasive biochemical analysis of "P and ' H compounds and pH measurements from localised volumes of tissue. However, the techniques are difficult and widespread clinical application remains remote.

MODERN IMAGING METHODS IN ONCOLOGY

a)

90 I

b)

Fig. IZ. These images of the head were constructed froni I mm thick slices acquired by a 3-dimensional flow compensated field echo pulse sequence. a ) 40 slices were used to produce image. which shows the artery and vein structure of a normal volunteer. b) 60 slices were used for the image; a 9-year-old patient with a large arteriovenous malformation in the right parietal lobe. (Used with permission from The Lancet).

After many years’ development PET imaging is entering the area of routine clinical diagnosis and patient manage ment. I t is expected that PET will become increasingly important especially in the drug control of psychiatric disorders and in the monitoring of cancer treatment. The dissemination of these techniques will be slow because they are among the most difficult to perform and the most expensive to establish. In the past there has been a plethora of available investigations which have often been uncritically accepted and have rarely been introduced in a planned and rational way. The challenge for the future is to use the methods available selectively to improve patient carc and for the health service to introduce them in a planned and controlled way. Those involved in imaging should provide advice for appropriate pathways of investigation and the clinicians must indicate clearly what questions are to be answered by the imaging services.

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