Nenreradiologv
Neuroradiology 16, 49~-494 (I 978)
© by Springer-Verlag1978
The Contrast-Enhanced CT Scan and the Radionuclide Brain Scan: Parallel Mechanisms of Action in the Detection of Supratentorial Astrocytomas A. R. Butler 3 , A. M. Passalaqua 2 , A. Berenstein 1 , and I. I. Kricheff l Departments of Radiology, Sections of NeuroradiologyI and Nuclear Medicine2, New York University Medical Center and Hartford Hospital3, Hartford, Connecticut, USA
Summary. The preoperative contrast-enhanced CT scan and the radionuclide brain scan of 70 patients with surgically verified supratentorial astrocytomaswere evaluated and compared. The results indicate parallel mechanisms of action of contrast enhancement and radionuclide uptake. These diagnostic modalities apparently mirror the integrity of the blood-brain barrier (BBB) and therefore are useful in assessing the degree of malignancy of supratentorial gliomas. However, lesions with an intact BBB will be missed with RN imaging. These lesions and/or the associated mass effect will be detected with contrast-enhanced computed tomography. Our findings firmly establish contrast-enhanced CT as the primary investigative tool in the suspectedbrain tumor.
Since the publication of the first clinical results of computed tomography (CT) in 1973, investigators have emphasized the importance of contrast enhancement in the detection of brain tumors. Some have empirically stated that contrast enhancement was secondary to intravascular iodine, while others have ascribed contrast enhancement to the extravascular accumulation of contrast material [ 1 , 5 , 12]. Hatam et al. presented the first clinical investigation of contrast enhancement response with time [7]. They concluded that extravascular iodine was partly responsible for tumor enhancement. Gado et al. were the first investigators to determine experimentally that contrast enhancement was partially secondary to the extravascular accumulation of iodine [6]. They also emphasized the similarity in the mechanisms of contrast enhancement and the abnormal accumulation of radioisotopes in brain lesions. There is significant evidence which suggests that the extravascular accumulation of radioisotope through a focal defect in the blood-brain barrier (BBB) is primarily
responsible for the positive radionuclide brain scan [2, 4, 8, 14]. It is the purpose of this investigation to evaluate the apparent parallel mechanisms of contrast-enhanced CT and RN uptake in a large group of supratentorial astrocytomas and to examine the roles of these diagnostic modalities in assessing the degree of malignancy of these tumors.
Materials and Methods All patients with histologically confirmed supratentorial astrocytomas during the past 3 years were collected from the neuropathology files. Those patients who had high-resolution preoperative pre- and postcontrast CT and RN brain scans within a maximal interval of 4 weeks were included in the evaluation. Seventy patients met these criteria and formed the basis for this study. High-resolution CT scans were usually performed with a 13-mm collimator. The contrast-enhanced scan was performed immediately following the noncontrast study. The pre- and postcontrast CT scans were evaluated by direct viewingof the cathode ray tube (CRT), photographs, and the 160 x 160 digital printout. When contrast enhancement was observed, a margin-free region of enhancement of at least 25 picture elements was identified on the computer printout and a mean of this region of interest was calculated. An attempt was made to locate the identical region of interest on the noncontrast scan. This area was evaluated in a similar fashion. The mean of the contrast-enhanced region of interest was divided by the mean of the noncontrast region of interest. The resultant factor was designated the index of contrast enhancement (ICE). The intensity of contrast enhancement was evaluated according to the following scale: slight enhancement was equivalent to an ICE between. 1.1 and 1.59; moderate enhancement represented an index factor of 1.60 to 2.50; marked enhancement indicated an ICE which was greater than 2.50, Static radionuclide brain scans were obtained with the gamma camera 1 h after the IV administration of 15 mCi of 99mTc-pertechnetate. The intensity of the positive scans was graded from slight to marked by visually comparing the activity in the tumor with that of the superior sagittal sinus (SSS), Slight uptake was faintly seen, moderate uptake was well defined, but of less intensity than the SSS. Marked radionuclide uptake represented an intensity equal to or greater than the SSS.
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A.R. Butler et al.: The Contrast-Enhanced CT Scan and RN Brain Scan
Table 1. Results of contrast-enhanced computed tomography compared with radionuclide brain scanning Diagnosis
Gliomas (Grades I and II) Gliomas (Grades III and IV)
Contrast enhancement
Isotope scanning
Number
Positive Negative F a l s e negative
Number
Positive Negative False negative
24 46
5 46
24 46
5 45
19 0
0 0
19 1
19 1
Table 2. Comparison of the intensity of the contrast-enhanced CT scan and the radionuclide brain scan Diagnosis
Gliomas (Grades I and ii) Gliomas (Grades III and IV)
Number
24 46
Contrast enhancement
Radionuclide brain scan
Negative Slight Moderate Marked
NegativeSlight
ModerateMarked
19 0
19 1
4 16
5 0
Results The results are summarized in Tables 1 and 2. There were 24 low-grade astrocytomas (Kernohan's Grades I and II) and there was contrast enhancement in five. In four of these tumors the intensity of radionuclide uptake was judged moderate and in the remaining case the intensity of uptake was slight. In 19 low-grade astrocytomas there was no contrast enhancement and there was no accumulation of radioisotope. The majority of the nonenhancing low-grade gliomas were seen as parenchymal lucencies on the pre- and postcontrast CT scans. The remainder were seen as mixtures of increased and decreased density. In addition to the parenchymal abnormalities, the associated mass effect and ventricular size were clearly demonstrated. There was contrast enhancement in all 46 of the highgrade gliomas (Kemohan's Grades III and IV). The intensity of enhancement was marked in 21 cases and moderate in 24 cases. Tumor mass was clearly separable from surrounding edema. The radionuclide brain scan was positive in 45 of the 46 cases. RN imaging failed t o detect a paramidline lesion in the inferior aspect of the right frontal lobe. The uptake of radionuclide was marked in 29 cases and moderate in 16 cases. Slight accumulation of iodine or radioactive tracer was not seen in any of the high-grade gliomas. Moderate and marked accumulation of contrast material was uniformly seen in the high-grade astrocytoma. Moderate accumulation of radioisotope was encountered in a relatively large number of highgrade gliomas, but also in four low-grade gliomas. Marked intensity of RN uptake was always seen in the high-grade glioma.
0 24
0 21
1 0
0 29
intracranial tumors with contrast-enhanced CT and RN brain scanning [2, 4, 8, 14]. There is debate regarding the extent of the contribution of intravascular tracer, but tissue vascularity probably plays a role, particularly during the early phase of imaging [4, 8, 13]. The capillaries in normal brain are different from nonneural capillaries in that their junctions are fused and this prevents the free exchange of substances between the intravascular and extravascular compartments [8, 14]. These 'tight junctions' form the structural basis for the concept of the blood-brain barrier. The lack of capillary junctional fenestrations normally prevents the extravascular accumulation of iodine and radioactive tracer. However, in astrocytomas, these endothelial junctions are frequently patent and become progressively so as the malignancy of the tumor increases [9, 10]. This continuum in capillary abnormalities allows a progressive increase in the extravascular accumulation of these diagnostic agents [14]. In low-grade gliomas the capillary endothelial cells are close to normal and junctional gaps are not present [9, I0]. These minor alterations in the BBB may not allow or may significantly retard the extravascular accumulation of contrast media or radioisotope. The evaluation of 24 low-grade gliomas with contrast-enhanced CT and RN brain scanning clearly reflected these neuropathologic observations. There was no contrast enhancement and no RN uptake in 19 of the low-grade astrocytomas, in all of these cases the RN brain scan was normal. Delayed RN imaging ( 2 4 h) was obtained in some of these lesions and was always normal. All of these nonenhancing lesions were seen with CT as either parenchymal lucencies or as a combination of increased and decreased density on the pre- and postcontrast CT brain scans (Fig. la and
b). Discussion The extravascular accumulation of iodine and radioactive tracer is largely responsible for the detection of
In the five enhancing low-grade gliomas there was slight accumulation of iodine (Fig. 2a). The minimal contrast enhancement probably reflected minor alterations in capillary permeability [14]. The RN brain scan was
A. R. Butler et al.: The Contrast-Enhanced CT Scan and RN Brain Scan
Fig. la and b. Low-grade astrocytoma fight frontal lobe. a Noncontrast-enhanced scan. Area of decreased absorption in the right frontal area. Contralateral ventricular displacement, b Contrast-enhanced scan. No contrast enhancement
Fig. 2a and b. Low-grade astrocytoma right frontoparietal area. a Contrast-enhanced scan. Slight and ill-defined linear streaks of contrast enhancement (arrows). b Right lateral static radionuclide brain scan (1 h). Focal area of minimal increased activity (arrow).
Fig. 3a and b. High-grade astroeytoma fight temporoparietal area. a Contrast-enhanced scan. Marked intensity of contrast enhancement, b Left lateral radionuclide brain scan. Marked intensity of radionuclide uptake in the left frontal area
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positive in these lesions with an intensity subjectively evaluated as slight in one case (Fig. 2b), and moderate in the remaining four. The most important point in these observations is the strong correlation between the presence of contrast enhancement and RN uptake in these tumors. The evaluation of the intensity of accumulation of these tracers was different and one would not expect a definitive one-to-one correlation. The parallel mechanisms of contrast enhancement and RN uptake were clearly seen in this series of highgrade gliomas. The intensity of enhancement was moderate in 24 cases and marked in 21 cases. Radionuclide imaging was positive in 45/46 high-grade gliomas. The single lesion which was not detected on the RN brain scan was a deep paramidline lesion in the fight frontal lobe. The detection rate for lesions in this area is less than that for tumors which are more superficially located. The intensity of uptake in the positive RN brain scans was moderate in 16 cases and marked in 29 cases. Marked accumulation of iodine and radiopharmaceutical was always encountered in the high-grade astrocytoma (Fig. 3a and b). The:~subjective~ appraisal of moderate uptake of radioisotope can be seen in the high-grade as well as the low-grade glioma. Despite obvious disparities in evaluating the intensity of radionuclide and iodine accumulation, there was a close similarity in the intensity of accumulation of these diagnostic agents. This was particularly so in relatively superficial lesions. The correlation was less in tumors near the midline, as these lesions tended to be relatively less intense on the RN brain scan. This apparent difference can possibly be explained by the fact that the energy of the radiation decreases rapidly with distance, and therefore midline lesions may appear less intense on the RN brain scan. Secondly, the parallel hole collimator which is used in the gamma camera is more advantageous in the detection of relatively superficial lesions. The temporal relationship of contrast enhancement and RN uptake seen in sequential CT and RN brain scanning affords highly corroborative evidence of the parallel mechanisms of these two diagnostic rnodalities. Nonenhanced lesions which are not detected on the RN brain scan will simultaneously accumulate iodine and isotope on subsequent scans. Additionally, sequential CT and RN brain scanning reveals that lesions which initially accumulate radioisotope and iodine to a slight degree will avidly accumulate these diagnostic agents as the degree of malignancy of the tumor increases. Contrast enhancement in supratentorial astrocytomas is highly correlated with microscopic vascularity and necrosis [3]. Isolated increases in pleomorphism and cellularity are not associated with contrast enhancement [3]. In this series a positive radionuclide brain scan was also not seen with isolated increments in cellularity and pleomorphism. The absence of contrast enhancement and radionuclide uptake was singularly seen in the low-grade astrocytoma. The contrast-enhanced low-grade gliomas clearly accumulated contrast media less intensely than in the high-
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grade gliomas, OlWioualy, in a larger series there may be some overlap. B u t it appears that the intensity o f contrast enhancement reflects qualitative abnormalities in the BBB and can therefore be useful in assessing the degree o f malignancy o f these tumors [3]. Radionuclide imaging was falsely negative in 19 lowgrade astrocytomas. The RN brain scan is often normal in the low-grade glioma [11, 15]. tn brain tumors the RN brain scan evaluates the integrity o f the BBB and possibly intrinsic vascularity. Contrast-enhanced CT monitors these pathophysiologic parameters and in addition CT uniquely evaluates pathologic anatomy.
Conclusion
The strong correlation between the presence or absence and the intensity o f contrast enhancement and RN uptake demonstrated in this series o f astrocytomas offers significant corroborative evidence that the mechanisms o f contrast enhancement and radionuclide uptake are identical. Contrast-enhanced CT and RN brain imaging mirror the integrity of the BBB and therefore can be useful in assessing the degree of malignancy of supratentorial astrocytomas. However, in the presence o f an intact BBB (low-grade glioma), the RN brain scan will be normal. In these cases there will be no accumulation o f contrast media, b u t the parenchymal abnormality and/or the associated mass effect will be seen with CT. These findings establish contrast-enhanced CT as the primary investigative tool in the diagnostic evaluation o f the suspected brain tumor.
Acknowledgments. The authors wish to thank Ms. Christine M. Volzo for her help in the preparation of this paper. The work was supported in part by the National Brain Tumor Study Group Grant #NO1 CM 67059. References 1. Ambrose, J.: Computerized X-ray scanning of the brain. J. Neurosurg. 40,679-695 (1974) 2. Bakay, L.: Basic aspects of brain tumor localization by radioactive substances. A review of current concepts. J. Neurosurg. 27, 239-245 (1967)
3. Butler, A. R., Horii, S. C., Kricheff, I. I., et al.: Contrast enhancement in astrocytomas: A statistical analysis of the parameters of malignancy and the positive contrast enhancement CT scan. Presented at the Sixty-Third Scientific Assembly and Annual Meeting of the Radiologieal Society of North America, Chicago, II1., 1977 4. Crocker, E. F., Zimmerman, R. A., Phelps, M. E., Kuhl, D. E.: The effect of steroids on the extravaseular distribution of radiographic contrast material and teehnetinm pertechnetate in brain tumors as determined by computed tomography. Radiology 119,471-474 (1976) 5. Ethier, R., Sherwin, A., Taylor, S.: Computerized angiotomography. The use of 100 cc. Hypaque-M60%. Clinical and experimental results. Presented at the First International Symposium on Computerized Axial Tomography, Montreal 1974 6. Gado, M. H., Phelps, M. E., Coleman, R. E.: An extravascular component of contrast enhancement in cranial computed tomography. Parts I and II. Radiology 117,589-597 (1975) 7. Hatam, A., Bergvall, R., Lewander, S., et al.: Contrast medium enhancement with time in computer tomography differential diagnosis of intracranial lesions. Acta Radiol. [Diagn.] (Stockh.) 346, 63-81 (1975) 8. Holman, B. L.: The blood brain barrier: Anatomy and physiology. Prog. Nucl. Med. 1,236-248 (1972) 9. Long, D. M.: Capillary ultrastructure and the blood-brain barrier in human malignant brain tumors. J. Neurosurg. 32, 127-144 (1970) 10. Long, D. M.: Capillary ultrastructure and the blood brain barrier. Human brain tumors. 6th Int. Congr. of Neuropathology, Pads, pp. 995-996 1970 11. Moreno, J. B., Deland, F. H.: Brain scanning in the diagnosis of astrocytomas of the brain. J. Nucl. Med. 12, 107-111 (1971) 12. New, P. F. J., Scott, W. R., Schnur, J. A., et al.: Computerized axial tomography with the EMI scanner. Radiology 110,109-123 (1974) 13. Penning, L., Front, D., Bechar, K., et al.: Factors governing the uptake of pertechnetate by human brain tumors. A scintigraphic study. Brain 96,225-234 (1973) 14. Shuttleworth, E. C.: Barrier phenomena in brain tumors. Prog. Exp. Tumor Res. 17, 279~290 (1972) 15. Witcofski, R. L., Maynard, C. D., Roper, T. J.: A comparative analysis of the accuracy of the technetium-99m pertechnetate brain scan. Follow-up of 1000 patients. J. Nucl. Med. 8,187-196 (1967)
A. R. Butler, MD Department of Radiology Hartford Hospital Hartford, CT 06115, USA
