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Stereotaxic biopsy and positron emission tomography correlation of cerebral gliomas
Surg Neurol 1987;27:87-92
87
Stereotaxic Biopsy and Positron Emission Tomography Correlation of Cerebral Gliomas Curtis Worthington, M.D., Jane L. Tyler, M.D., and Jean-Guy Villemure, M.D. Brain Imaging Center, Montreal Neurological Institute and Hospital, Department of Neurology and Neurosurgery, McGill University, Montreal, Canada
Worthington C, Tyler JL, VillemureJ.-G. Stereotaxic biopsy and positron emission tomography correlation of cerebral gliomas. Surg Neurol 1987;27:87-92.
Computer-directed stereotaxis was used to obtain tissue diagnosis in two cases of cerebral glioma, one low grade, and the other high grade. Both lesions had a similar computed tomographic appearance. Positron emission tomography was performed in each case using [lSF]fluorodeoxyglucose. A correlation was made in each case between the metabolic activity of the tumor as measured by positron emission tomography, the radiographic appearance, and the tumor histology. KEY WORDS; Stereotaxic surgery; Positron emission tomography; Glioma; Tumor biopsy; Instrumentation; CT; Brain tumor metabolism
Certain cerebral tumors that are not amenable to bulk resection because they are deep, infiltrating, or occupy a critical anatomic location, may be diagnosed by stereotaxic biopsy. Computer-guided stereotaxis, which makes use of a number o f neuroradiological techniques, is becoming increasingly more common [4,12-15, 17,18,21,22]. Recently, it has been proposed that stereotaxic principles be applied to positron emission tomography (PET) [10,11]. The positron-emitting substance 2-[18F]fluoro-2-deoxy-D-glucose (FDG) has been used to measure glucose utilization in cerebral gliomas and thereby determine relative degrees of metabolic activity in these lesions [1,6-8,19,20]. In the cases presented here, computer-guided [computed tomography (CT) and angiography] stereotaxis was performed in conjunction with PET. In this way, a correlation was made between the radiological appearance, the metabolic activity, and the histological nature of the gliomas studied.
Address reprint requests to: Curtis Worthington, M.D., NeurologyNeurosurgery Clinic, P.A., 315 Calhoun Street, Charleston, South Carolina 29401.
© 1987 by ElsevierSciencePublishingCo., Inc.
Materials and Methods Preoperatively, patients underwent CT using a double dose delayed contrast-infused medium (Intravenous Conray-30, 4 ml/kg body wt; Mallinckrodt, Inc., St. Louis, Mo.), and F D G PET scans. Positron emission tomography studies were collected on the Therascan 3128 positron tomograph [5], a two-ring machine containing 64 bismuth germanate detectors per ring, with an image resolution of 12 mm. Regional cerebral glucose utilization was measured using an adaptation by Phelps et al [23] o f the method of Sokoloff et al [26] for human studies, incorporating a reformulation of the operational equation suggested by Brooks [3]. A 5-mCi intravenous bolus of F D G was injected, and arterial blood samples were collected throughout the study. Once equilibrium was established (at - 4 5 minutes after injection), two 14-minute static scans were done to yield six tomographic slices over the tumor volume. Typical images contained 3 - 6 million true coincidences. T o obtain functional units o f cerebral regional metabolism (LCMRGI), the plasma activity curve was numerically integrated by the Brooks operational equation to yield a simple scale factor and offset which converts observed tissue activity to glucose utilization, Stereotaxic biopsy was carried out using the lateral, orthogonal approach described by Mussen and Talairach, and modified by Olivier and Bertrand [17,18, 21,22,24,27]. T h e frame was applied to the patient's head in the operating room. A CT scan was then performed using double dose delayed infused contrast medium, with the patient in the frame and, using the stereotaxic CT imaging program, the scan was analyzed. By this method, points were chosen for biopsy within the tumor volume and the stereotaxic coordinates of those points were determined (Figures 3 and 7). The patient then underwent left carotid artery digital subtraction angiography, again with the stereotaxic frame in place. Using the stereotaxic angioimaging program, it was possible to analyze and adjust the points chosen for biopsy, so as to avoid all vascular structures (Figure 4). Using computer-assisted imaging programs, the proper coordinates were chosen and the biopsy was then performed in the operating room. 0090-3019/87/$3.50
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F i g u r e 3. Case I. Stereotaxic C T image showing the tu,o targets (A and B) chosen for biopsy. (A): x = 5.5 cms, y - 6. ~ cms, z - 4 . l eros. (B): x = 7.4cms, y = 6.3 c m l , z = - 4 . 5 cms. F i g u r e 1. Case 1. Contra.~t-enhanced C T sean showing left frontal spaceoccupying lesion.
Case Reports
Case i
F i g u r e 2. Case 1. F D G - P E T s~z~n. Regions of interest (ROI) indicate glucose utikzation at (a) equal to normal brain in opposite hemisphere (c). Glucose utilization at (b) fcorresponding to posterior aspect of tumorJ is decreased. Glucose utilization values for gray matter are depressed globally. Glucose utilization units (micromoles/lO0 grams/minute) for regions of interest: (a) - I8, (b) = 17, (c) = 19.
A 38-year-old right-handed woman was admitted to the neurology service in D e c e m b e r 1978, suffering from recent onset of right hemibody, focal motor, and generalized seizures. H e r neurological examination revealed a mild right hemiparesis and a mild expressive dysphasia. Multiple CT scans p e r f o r m e d with and without contrast enhancement revealed only an ill-defined relative hypodensity in the left suprasylvian region. This lesion was believed to be most consistent with a glioma, but because of the sensitive nature of the antomical location, surgery was deferred. A decision was made to irradiate the lesion empirically, and the patient received 6,000 fads to the whole brain. The patient stabilized and was able to care for herself and her family, but continued to have right focal m o t o r seizures approximately three times per month. In August 1984, the patient was readmitted to the hospital because of a marked increase in the frequency and severity of her seizures, a progressive right hemiparesis, a dense expressive dysphasia, and a global confusional state. C o m p u t e d tomography scans revealed a space-occupying lesion of the left suprasylvian region (Figure 7). The lesion had an anterior c o m p o n e n t that was diffusely enhanced, and an area of "ringlike" enhancement surrounding a posterior region of low attenuation. Some space-occupying effect was noted with blunting of the left frontal horn and left trigone. The
Stereotaxic Biopsy and PET of Gliomas
Figure 4. Case l. Stereotaxic angiogram showing position of two targets (A and B) for biopsy. lesion was again believed to be consistent with a relatively low-grade glioma. However, in view of the patients global deterioration, radiation necrosis was considered to be a diagnostic possibility. To ascertain the relative metabolic parameters of tumor and surrounding brain in this patient, PET with FDG was performed (Figure 2). The anterior portion of the lesion, which appeared hyperdense on the CT scan, showed glucose utilization essentially equal to that of normal brain. By contrast, the posterior portion of the tumor corresponding to the hypodense region in the CT scan showed a markedly decreased metabolic activity ( - 6 0 % less), as compared to normal brain. Stereotaxic biopsy was performed thereafter (Figures 3 and 4). Tissue samples taken from the anterior, hyperdense, normometabolic region (A) revealed a mixed glioma composed of a small neoplasic oligodendrocytic population, but predominently Composed of fibrillary astrocytes. It was judged to be grade II. Samples from the posterior, hypodense, hypometabolic region (B) were entirely composed of stellate and piloid astrocytes and were judged to be astrocytoma of grade II. Case 2
A 49-year-old right-handed woman presented with a 9month history of fatigue and difficulty in concentrating,
Surg Neurol 1987;27:87-92
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a 6-week history of progressive speech difficulty, and a 2-week history of numbness and tingling in the right arm and right lip, with progressive weakness of the right arm. Examination confirmed a dense expressive dysphasia with accompanying right hemiparesis. Computed tomography revealed a space-occupying lesion of the Figure 5. Case 2. Contrast-enhanced CT scan showing space-occupying lesion of left centrum semiovale.
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left centrum semiovale (Figure 5). This lesion was enhanced in a "ringlike" fashion around a central inhomogenous region of low attenuation. There was mass effect with effacement of the left lateral ventricle. The lesion was believed to be most consistent with a glioma. In spite of therapy with dexamethasone, the patient's condition deteriorated during the first week of hospitalization. Positron emission tomography studies performed with FDG revealed a diffuse depression of glucose utilization in the hemisphere ipsilateral to the tumor. An area corresponding to the hypodense center of the lesion oh-
F i g u r e 6. Case 2. (A) FDG-PET scan. Regions of interest rereal higher than normal glucose utilization at the rim of the tumor (b) but lower than normal glucose utilization towards the crstic/necrotfi: center of the tumor (a) compared to a eontralateral region of white matter/ventricle (c). (B) Corona/ reconstruction of scan is shown. Glucose utilization units ~m#romoles/lO0 grams/minute) for regions of interest: (a) = ~, (b) - 12, (c) = 7.
A
W o r t h i n g t o n e t al
served on CT had a low rate of glucose utilization compared to normal brain (Figure 6). A "ringlike" region of higher than normal glucose utilization was observed corresponding to the hyperdense periphery of the lesion seen on CT scanning. A stereotaxic biopsy was performed. In the present stereotaxic system, the "X" axis represents the anterior-posterior dimensions of the skull; the "Y" axis represents the superior-inferior dimensions; and the "Z" axis represents the lateral dimensions, the distance from the sagittal plane. The stereotaxic CT imaging program was employed using a coronal reconstruction in the plane of the chosen "X" coordinate (Figure 7). A single "Y" coordinate was then chosen within the imaged volume and the "Z" coordinate alone was varied to obtain tissue samples from both the hypodense central core of the lesion (A) as well as the enhancing capsule (B). Using the lateral, orthogonal approach, a tissue sample could be obtained from both regions with a single twist drill hole and single biopsy needle placement. Tissue diagnosis of both regions biopsied revealed grade IV astrocytoma. The hyperdense capsule, which correlated with the region of hypermetabolism on PET, consisted principally of cells containing hyperchromatic, pleomorphic nuclei, and regions of marked endothelial proliferation. The specimen from the hypodense, hypometabolic core consisted of few active neoplastic cells with large areas of necrosis.
Discussion Differences in metabolic activity associated with primary brain tumors have been measured using FDG-PET [ 1,6-8,19,20]. It has been shown that tumor histological grade correlates positively with the degree of glucose metabolism. DiChiro et al [6-8] reported significantly lower rates of glucose utilization in low-grade gliomas (grades I and II) as compared with high-grade gliomas (grades III and IV). Patronas et al [20], who have observed differences in glucose metabolism in high-grade
Stereotaxic Biopsy and PET of Gliomas
F i g u r e 7. Case 2. Stereotaxic C T image in coronal reconstruction showing two targets (A and B) chosen for biopsy. (A): x = 7.6 cms, y = 7.7 cms, z = -2.4cms. (B):x = 7.6cms, y = 7.7cms, z = -3.6cms.
gliomas, have recently proposed FDG-PET as a prognostic indicator in malignant primary brain tumors. In the present cases, a correlation was drawn between the metabolic activity, the CT appearance, and the histological nature of the lesions present. These cases support the previous findings on the metabolic nature of gliomas as measured by PET. In case 1, a low-grade glioma, the metabolic activity as measured by PET was equal to normal brain in the more histologically active portions, and lower than normal brain in other portions. In case 2, a high-grade glioma, the metabolic activity in the histologically more malignant portions exceeded that of normal brain. The necrotic portions, as expected, showed very little metabolic activity. Patronas et al [19] considered the problem of differentiating radiation necrosis from recurrent tumor by PET. In case one described above, radiation necrosis was considered a diagnostic possibility. Based on the PET finding of a low metabolic rate, necrosis could not be ruled out. In cases of high-grade glioma, it is likely that PET can differentiate between necrosis and tumor recurrence, as Patronas et al had found. In the case of low-grade tumor this is less likely. These tumors, however, should be irradiated only after lengthy consideration of the histology indicates some degree of malignant change, and not empirically as occurred in this case. A problem arises in the interpretation of these PET studies as they relate to the histology obtained by stereotaxic biopsy. While point-to-point precision exists between the tissue analysis and the radiographic appearance because of stereotaxic localization, no such precision exists relative to PET. Regions of interest chosen for analysis must be considered only approximate in relation
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to the radiological appearance and tissue samples obtained. Standardization of PET to improve the accuracy of the technique presently is receiving much consideration. Fox e t al [10,11] have proposed a stereotaxic system for anatomic localization in PET. It is anticipated that the Olivier-Bertrand-Tipal (modified Leksell) stereotaxic system soon can be adapted for use with PET (as it has been adapted for MRI both at this institution and elsewhere) (personal communication, 1984) [ 14,18, 21]. This will allow precise, accurate correlation of PET studies and tissue sampling. It has been pointed out that contrast enhanced CT provides some indication, while being by no means totally reliable, of where stereotaxic biopsy should be performed to provide a certain diagnosis [12]. Positron emission tomography, if fully adapted to a stereotaxic system, may provide supplementary information leading to the most appropriate target for biopsy. The CT appearances in the lesions considered here were somewhat similar, being composed of a core of low attenuation surrounded by a "ringlike" enhancing capsule. Yet, the histological characteristics o f these lesions were markedly different. Certain authors have pointed out the relatively poor correlation between tumor grade and radiological appearance [16,25]. Discrepancies in tumor extent as measured by CT and PET modalities have been considered [2], as well as the discrepancies in tumor extent as measured by PET and MRI (with increasingly more frequency). In the case of an infiltrating glioma, the "physiological" extent of the tumor as measured by a parameter such as FDG-PET, may be more important than the "anatomical" extent observed in CT or other conventional radiographic methods. Positron emission tomography may have both diagnostic and prognostic significance in the evaluation of primary brain tumors because of its unique ability to measure metabolic parameters in these lesions [6-8,20]. Furthermore, if relative differences in metabolism (and, therefore, relative differences in malignancy) within a tumor mass can be measured, this may serve as a "physiological-anatomical" guide to directing therapy, including limits of surgical resection, brachytherapy, arterial chemotherapy, and immunotherapy. In summary, PET has confirmed the previously demonstrated finding that metabolic activity in gliomas is related to degree of malignancy. Some correlation could be drawn between the metabolic activity and radiological appearance of various portions of these tumors. Modern imaging techniques have allowed the development of a stereotaxic system by which tissue samples can be obtained from various portions of tumor efficiently and safely. In this way, precise areas of tumor can be analyzed histologically and correlated with CT and PET images.
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References 1. Beaney RP. Positron emission tomography in the study of human tumors. Semin Nucl Med 1984;14:324-41. 2. Bergstrom M, Collins VP, Ehrin F, Ericson K, Eriksson L, Greitz T, Halldin C, yon Hoist H, Langstr6m B, Lilja A, Lundqvist H, Nagren K. Discrepancies in brain tumor extent as shown by computed tomography and positron emission tomography using ~'SGa EDTA, 11C glucose, and 11C methionine. Comput Assist Tomogr 1983;7:1062"6. 3. Brooks R. Alternative formula for glucose utilization using labelled deoxyglucose. J Nucl Med 1982;23:538-9. 4. Bullard DE, Nashold BS Jr, Osborne D, Burger PC, Dubois P. CT-guided stereotactic biopsies using a modified frame and Gildenberg techniques. J Neurol Neurosurg Psychiatry 1984; 47:590-5. 5. Cooke BE, Evans AC, Fanthome EO, Alarie R, Sendyk AM. Performance figures and images from the Therascan 3128 positron emission tomograph. IEEE Trans Nucl Sci 1984;NS-31:640-4. 6. DiChiro G, Brooks RA, Petronas NJ, Bairamian D, Kornblith PL, Smith BH, Mansi L, Barker J. Issues in the in vivo measurement of glucose metabolism of human central nervous system tumors. Ann Neurol 1984;15(suppl):S138-46. 7. DiChiro G, Brooks RA, Sokoloff L, Patronas NJ, DeLaPaz RL, Smith BH, Kornblith PL. Glycolytic rate and histological grade of human cerebral gliomas. A study with *SF fluorodeoxyglucose and positron emission tomography. In: Heiss WD, Phelps ME, eds. Positron emission tomography of the brain. Berlin, Heidelberg, New York:Springer-Verlag, 1983:181-91. 8. DiChiro G, DeLaPaz RL, Brooks RA, Sokoloff L, Kornblith PL, Smith BH, Patronas NJ, Kufta CV, Kessler RM, Johnston CS, Manning RG, Wolf AP. Glucose utilization of cerebral gli0mas measured by 18F fluorodeoxyglucose and positron emission tomography. Neurology 1982;32:1323-9. 9. Diksic M, Jolly D. New high yield synthesis of lSF-labelled 2deoxy-2-fluoro-D-glucose. IntJ Appl Radiat Isot 1983;34:894-6. 10. Fox PT, Perlmutter JS, Raichle ME. A stereotactic method of anatomical localization for positron emission tomography. J Cornput Assist Tomogr 1985;9:141-53. 1 l. Fox PT, Perlmutter JS, Raichle ME. Stereotactic localization for positron emission tomography. XII International Symposium on Cerebral Blood Flow and Metabolism. Lund, Ronneby: Studentlitteratur, 1985:215. 12. Goodman JH. State-of-the-art stereotaxic surgery. Contemp Neurosurg 1984;6:1-6. 13. Leksell L, Jernberg B. Stereotaxis and tomography (technical note). Acta Neurochir 1980;52:1-7.
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14. Leksell L, Leksell D, SchwebelJ. Stereotaxis and nuclear magnetic resonance. J Neurol Neurosurg Psychiatry 1985;48:14-8. 15. Lunsford LD. Innovations in stereotactic technique coupled with computerized tomography. Contemp Neurosurg 1982;4:1-6. 16. MarksJE, Gado M. Serial computed tomography of primary brain tumors following surgery, irradiation, and chemotherapy. Radiology 1977;125:119-25. 17. Olivier A, Bertrand G. Stereotaxic device for percutaneous twistdrill insertion of depth electrodes and for brain biopsy (technical note). J Neurosurg 1982;56:307-8. 18. Olivier A, Bertrand G, Peters T. Stereotactic systems and procedures for depth electrode placement: technical aspects. Appl Neurophysiol 1983;46:37-40. 19. Patronas NJ, DiChiro G, Brooks RA, DeLaPaz RL, Kornblith PL, Smith BH, Rizzoli HV, Kessler RM, Manning RG, Channing M, Wolf AP, O'Connor CM. Work in progress: ~SFfluorodeoxyglucose and positron emission tomography in the evaluation of radiation necrosis of the brain. Radiology 1982;144:885-9. 20. Patronas NJ, DiChiro G, Kufta C, Bairamian D, Kornblith PL, Simon R, Larson SM. Prediction of survival in glioma patients by means of positron emission tomography. J Neurosurg 1985;62:816-22. 2 l. Peters TM, Olivier A. CT aided stereotaxy for depth electrode implantation and biopsy. Can J Neurol Sci 1983;10:166-9. 22. Peters TM, Olivier A, Bertrand G. The role of computed tomographic and digital radiographic techniques in stereotactic procedures for electrode implantation and mapping, and lesion localization. Appl Neurophysiol 1983;46:200-5. 23. Phelps ME, Huang SC, Hoffman EJ, Selin C, Sokoloff L, Kuhl DE. Tomographic measurement of local cerebral glucose metabolic rate in humans with lSF-fluoro-2-deoxy-D-glucose; validation of method. Ann Neurol 1979;6:371-88. 24. Picard C, Olivier A, Bertrand G. The first human stereotaxic apparatus. The contribution of Aubrey Mussen to the field of stereotaxis. J Neurosurg 1983;59:673-6. 25. Silverman C, Marks JE. Prognostic significance of contrast enhancement in low-grade astrocytomas of the adult cerebrum. Radiology 1981;139:211-3. 26. SokoloffL, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada D, Shinohara M. The *4C-deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure and normal values in the conscious and anesthetized albino rat. J Neurochem 28:897-916. 27. Talairach J, David M, Tournoux P, Corredor H, Kvasina T. Atlas d'anatomie st6r6otaxique. Paris:Masson, 1957.
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Stereotaxic Biopsy and Positron Emission Tomography Correlation of Cerebral Gliomas Curtis Worthington, M.D., Jane L. Tyler, M.D., and Jean-Guy Villemure, M.D. Brain Imaging Center, Montreal Neurological Institute and Hospital, Department of Neurology and Neurosurgery, McGill University, Montreal, Canada
Worthington C, Tyler JL, VillemureJ.-G. Stereotaxic biopsy and positron emission tomography correlation of cerebral gliomas. Surg Neurol 1987;27:87-92.
Computer-directed stereotaxis was used to obtain tissue diagnosis in two cases of cerebral glioma, one low grade, and the other high grade. Both lesions had a similar computed tomographic appearance. Positron emission tomography was performed in each case using [lSF]fluorodeoxyglucose. A correlation was made in each case between the metabolic activity of the tumor as measured by positron emission tomography, the radiographic appearance, and the tumor histology. KEY WORDS; Stereotaxic surgery; Positron emission tomography; Glioma; Tumor biopsy; Instrumentation; CT; Brain tumor metabolism
Certain cerebral tumors that are not amenable to bulk resection because they are deep, infiltrating, or occupy a critical anatomic location, may be diagnosed by stereotaxic biopsy. Computer-guided stereotaxis, which makes use of a number o f neuroradiological techniques, is becoming increasingly more common [4,12-15, 17,18,21,22]. Recently, it has been proposed that stereotaxic principles be applied to positron emission tomography (PET) [10,11]. The positron-emitting substance 2-[18F]fluoro-2-deoxy-D-glucose (FDG) has been used to measure glucose utilization in cerebral gliomas and thereby determine relative degrees of metabolic activity in these lesions [1,6-8,19,20]. In the cases presented here, computer-guided [computed tomography (CT) and angiography] stereotaxis was performed in conjunction with PET. In this way, a correlation was made between the radiological appearance, the metabolic activity, and the histological nature of the gliomas studied.
Address reprint requests to: Curtis Worthington, M.D., NeurologyNeurosurgery Clinic, P.A., 315 Calhoun Street, Charleston, South Carolina 29401.
© 1987 by ElsevierSciencePublishingCo., Inc.
Materials and Methods Preoperatively, patients underwent CT using a double dose delayed contrast-infused medium (Intravenous Conray-30, 4 ml/kg body wt; Mallinckrodt, Inc., St. Louis, Mo.), and F D G PET scans. Positron emission tomography studies were collected on the Therascan 3128 positron tomograph [5], a two-ring machine containing 64 bismuth germanate detectors per ring, with an image resolution of 12 mm. Regional cerebral glucose utilization was measured using an adaptation by Phelps et al [23] o f the method of Sokoloff et al [26] for human studies, incorporating a reformulation of the operational equation suggested by Brooks [3]. A 5-mCi intravenous bolus of F D G was injected, and arterial blood samples were collected throughout the study. Once equilibrium was established (at - 4 5 minutes after injection), two 14-minute static scans were done to yield six tomographic slices over the tumor volume. Typical images contained 3 - 6 million true coincidences. T o obtain functional units o f cerebral regional metabolism (LCMRGI), the plasma activity curve was numerically integrated by the Brooks operational equation to yield a simple scale factor and offset which converts observed tissue activity to glucose utilization, Stereotaxic biopsy was carried out using the lateral, orthogonal approach described by Mussen and Talairach, and modified by Olivier and Bertrand [17,18, 21,22,24,27]. T h e frame was applied to the patient's head in the operating room. A CT scan was then performed using double dose delayed infused contrast medium, with the patient in the frame and, using the stereotaxic CT imaging program, the scan was analyzed. By this method, points were chosen for biopsy within the tumor volume and the stereotaxic coordinates of those points were determined (Figures 3 and 7). The patient then underwent left carotid artery digital subtraction angiography, again with the stereotaxic frame in place. Using the stereotaxic angioimaging program, it was possible to analyze and adjust the points chosen for biopsy, so as to avoid all vascular structures (Figure 4). Using computer-assisted imaging programs, the proper coordinates were chosen and the biopsy was then performed in the operating room. 0090-3019/87/$3.50
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F i g u r e 3. Case I. Stereotaxic C T image showing the tu,o targets (A and B) chosen for biopsy. (A): x = 5.5 cms, y - 6. ~ cms, z - 4 . l eros. (B): x = 7.4cms, y = 6.3 c m l , z = - 4 . 5 cms. F i g u r e 1. Case 1. Contra.~t-enhanced C T sean showing left frontal spaceoccupying lesion.
Case Reports
Case i
F i g u r e 2. Case 1. F D G - P E T s~z~n. Regions of interest (ROI) indicate glucose utikzation at (a) equal to normal brain in opposite hemisphere (c). Glucose utilization at (b) fcorresponding to posterior aspect of tumorJ is decreased. Glucose utilization values for gray matter are depressed globally. Glucose utilization units (micromoles/lO0 grams/minute) for regions of interest: (a) - I8, (b) = 17, (c) = 19.
A 38-year-old right-handed woman was admitted to the neurology service in D e c e m b e r 1978, suffering from recent onset of right hemibody, focal motor, and generalized seizures. H e r neurological examination revealed a mild right hemiparesis and a mild expressive dysphasia. Multiple CT scans p e r f o r m e d with and without contrast enhancement revealed only an ill-defined relative hypodensity in the left suprasylvian region. This lesion was believed to be most consistent with a glioma, but because of the sensitive nature of the antomical location, surgery was deferred. A decision was made to irradiate the lesion empirically, and the patient received 6,000 fads to the whole brain. The patient stabilized and was able to care for herself and her family, but continued to have right focal m o t o r seizures approximately three times per month. In August 1984, the patient was readmitted to the hospital because of a marked increase in the frequency and severity of her seizures, a progressive right hemiparesis, a dense expressive dysphasia, and a global confusional state. C o m p u t e d tomography scans revealed a space-occupying lesion of the left suprasylvian region (Figure 7). The lesion had an anterior c o m p o n e n t that was diffusely enhanced, and an area of "ringlike" enhancement surrounding a posterior region of low attenuation. Some space-occupying effect was noted with blunting of the left frontal horn and left trigone. The
Stereotaxic Biopsy and PET of Gliomas
Figure 4. Case l. Stereotaxic angiogram showing position of two targets (A and B) for biopsy. lesion was again believed to be consistent with a relatively low-grade glioma. However, in view of the patients global deterioration, radiation necrosis was considered to be a diagnostic possibility. To ascertain the relative metabolic parameters of tumor and surrounding brain in this patient, PET with FDG was performed (Figure 2). The anterior portion of the lesion, which appeared hyperdense on the CT scan, showed glucose utilization essentially equal to that of normal brain. By contrast, the posterior portion of the tumor corresponding to the hypodense region in the CT scan showed a markedly decreased metabolic activity ( - 6 0 % less), as compared to normal brain. Stereotaxic biopsy was performed thereafter (Figures 3 and 4). Tissue samples taken from the anterior, hyperdense, normometabolic region (A) revealed a mixed glioma composed of a small neoplasic oligodendrocytic population, but predominently Composed of fibrillary astrocytes. It was judged to be grade II. Samples from the posterior, hypodense, hypometabolic region (B) were entirely composed of stellate and piloid astrocytes and were judged to be astrocytoma of grade II. Case 2
A 49-year-old right-handed woman presented with a 9month history of fatigue and difficulty in concentrating,
Surg Neurol 1987;27:87-92
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a 6-week history of progressive speech difficulty, and a 2-week history of numbness and tingling in the right arm and right lip, with progressive weakness of the right arm. Examination confirmed a dense expressive dysphasia with accompanying right hemiparesis. Computed tomography revealed a space-occupying lesion of the Figure 5. Case 2. Contrast-enhanced CT scan showing space-occupying lesion of left centrum semiovale.
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Surg Neurol 1987;27:87-92
left centrum semiovale (Figure 5). This lesion was enhanced in a "ringlike" fashion around a central inhomogenous region of low attenuation. There was mass effect with effacement of the left lateral ventricle. The lesion was believed to be most consistent with a glioma. In spite of therapy with dexamethasone, the patient's condition deteriorated during the first week of hospitalization. Positron emission tomography studies performed with FDG revealed a diffuse depression of glucose utilization in the hemisphere ipsilateral to the tumor. An area corresponding to the hypodense center of the lesion oh-
F i g u r e 6. Case 2. (A) FDG-PET scan. Regions of interest rereal higher than normal glucose utilization at the rim of the tumor (b) but lower than normal glucose utilization towards the crstic/necrotfi: center of the tumor (a) compared to a eontralateral region of white matter/ventricle (c). (B) Corona/ reconstruction of scan is shown. Glucose utilization units ~m#romoles/lO0 grams/minute) for regions of interest: (a) = ~, (b) - 12, (c) = 7.
A
W o r t h i n g t o n e t al
served on CT had a low rate of glucose utilization compared to normal brain (Figure 6). A "ringlike" region of higher than normal glucose utilization was observed corresponding to the hyperdense periphery of the lesion seen on CT scanning. A stereotaxic biopsy was performed. In the present stereotaxic system, the "X" axis represents the anterior-posterior dimensions of the skull; the "Y" axis represents the superior-inferior dimensions; and the "Z" axis represents the lateral dimensions, the distance from the sagittal plane. The stereotaxic CT imaging program was employed using a coronal reconstruction in the plane of the chosen "X" coordinate (Figure 7). A single "Y" coordinate was then chosen within the imaged volume and the "Z" coordinate alone was varied to obtain tissue samples from both the hypodense central core of the lesion (A) as well as the enhancing capsule (B). Using the lateral, orthogonal approach, a tissue sample could be obtained from both regions with a single twist drill hole and single biopsy needle placement. Tissue diagnosis of both regions biopsied revealed grade IV astrocytoma. The hyperdense capsule, which correlated with the region of hypermetabolism on PET, consisted principally of cells containing hyperchromatic, pleomorphic nuclei, and regions of marked endothelial proliferation. The specimen from the hypodense, hypometabolic core consisted of few active neoplastic cells with large areas of necrosis.
Discussion Differences in metabolic activity associated with primary brain tumors have been measured using FDG-PET [ 1,6-8,19,20]. It has been shown that tumor histological grade correlates positively with the degree of glucose metabolism. DiChiro et al [6-8] reported significantly lower rates of glucose utilization in low-grade gliomas (grades I and II) as compared with high-grade gliomas (grades III and IV). Patronas et al [20], who have observed differences in glucose metabolism in high-grade
Stereotaxic Biopsy and PET of Gliomas
F i g u r e 7. Case 2. Stereotaxic C T image in coronal reconstruction showing two targets (A and B) chosen for biopsy. (A): x = 7.6 cms, y = 7.7 cms, z = -2.4cms. (B):x = 7.6cms, y = 7.7cms, z = -3.6cms.
gliomas, have recently proposed FDG-PET as a prognostic indicator in malignant primary brain tumors. In the present cases, a correlation was drawn between the metabolic activity, the CT appearance, and the histological nature of the lesions present. These cases support the previous findings on the metabolic nature of gliomas as measured by PET. In case 1, a low-grade glioma, the metabolic activity as measured by PET was equal to normal brain in the more histologically active portions, and lower than normal brain in other portions. In case 2, a high-grade glioma, the metabolic activity in the histologically more malignant portions exceeded that of normal brain. The necrotic portions, as expected, showed very little metabolic activity. Patronas et al [19] considered the problem of differentiating radiation necrosis from recurrent tumor by PET. In case one described above, radiation necrosis was considered a diagnostic possibility. Based on the PET finding of a low metabolic rate, necrosis could not be ruled out. In cases of high-grade glioma, it is likely that PET can differentiate between necrosis and tumor recurrence, as Patronas et al had found. In the case of low-grade tumor this is less likely. These tumors, however, should be irradiated only after lengthy consideration of the histology indicates some degree of malignant change, and not empirically as occurred in this case. A problem arises in the interpretation of these PET studies as they relate to the histology obtained by stereotaxic biopsy. While point-to-point precision exists between the tissue analysis and the radiographic appearance because of stereotaxic localization, no such precision exists relative to PET. Regions of interest chosen for analysis must be considered only approximate in relation
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to the radiological appearance and tissue samples obtained. Standardization of PET to improve the accuracy of the technique presently is receiving much consideration. Fox e t al [10,11] have proposed a stereotaxic system for anatomic localization in PET. It is anticipated that the Olivier-Bertrand-Tipal (modified Leksell) stereotaxic system soon can be adapted for use with PET (as it has been adapted for MRI both at this institution and elsewhere) (personal communication, 1984) [ 14,18, 21]. This will allow precise, accurate correlation of PET studies and tissue sampling. It has been pointed out that contrast enhanced CT provides some indication, while being by no means totally reliable, of where stereotaxic biopsy should be performed to provide a certain diagnosis [12]. Positron emission tomography, if fully adapted to a stereotaxic system, may provide supplementary information leading to the most appropriate target for biopsy. The CT appearances in the lesions considered here were somewhat similar, being composed of a core of low attenuation surrounded by a "ringlike" enhancing capsule. Yet, the histological characteristics o f these lesions were markedly different. Certain authors have pointed out the relatively poor correlation between tumor grade and radiological appearance [16,25]. Discrepancies in tumor extent as measured by CT and PET modalities have been considered [2], as well as the discrepancies in tumor extent as measured by PET and MRI (with increasingly more frequency). In the case of an infiltrating glioma, the "physiological" extent of the tumor as measured by a parameter such as FDG-PET, may be more important than the "anatomical" extent observed in CT or other conventional radiographic methods. Positron emission tomography may have both diagnostic and prognostic significance in the evaluation of primary brain tumors because of its unique ability to measure metabolic parameters in these lesions [6-8,20]. Furthermore, if relative differences in metabolism (and, therefore, relative differences in malignancy) within a tumor mass can be measured, this may serve as a "physiological-anatomical" guide to directing therapy, including limits of surgical resection, brachytherapy, arterial chemotherapy, and immunotherapy. In summary, PET has confirmed the previously demonstrated finding that metabolic activity in gliomas is related to degree of malignancy. Some correlation could be drawn between the metabolic activity and radiological appearance of various portions of these tumors. Modern imaging techniques have allowed the development of a stereotaxic system by which tissue samples can be obtained from various portions of tumor efficiently and safely. In this way, precise areas of tumor can be analyzed histologically and correlated with CT and PET images.
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