Magnetic Resonance Printed in the USA.
Imaging, Vol. 9, pp. 959-%I, All rights reserved.
1991 Copyright
0730-725x/91 $3.00 + .oo 0 1991 Pergamon Press plc
l Original Contribution
EFFECTS
OF RADIATION THERAPY ON THE HUMAN NORMAL (WHITE MATTER) VISUALIZED BY MR IMAGING AMARNATH
JENA,* UDAY
BRAIN
GOURA K. RATH,~ R. RAVICHANDRAN,* P. SAHI,~ AND S. KHUSHU*
*NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences, Lucknow Marg, Delhi 110054, India, and TDepartment of Radiation Oncology, Institute Rotary Cancer Hospital, AIIMS, Ansari Nagar, New Delhi 110016, India Sequential MR imaging could provide information related to the pathological changes due to the application of external cytotoxic agents such as radiotherapy on the central nervous system. This paper describes the results of our attempt to demonstrate short-term changes associated with normal brain during and immediately following radiotherapy when the whole brain is irradiated for malignant conditions. No observable changes were found in the normal brain parenchyma in any of the patients (n = 8) in T1-, T,-, and proton-density-weighted images in the sequential scans in the first and second weeks and immediately following radiotherapy. Also, no changes were observed in the normal brain appearance at 2 mo (n = 6), up to 6 mo (n = l), and up to 15 mo (n = 1) after completion of radiotherapy.
Keywords: Radiation; Brain; Effects.
INTRODUCTION
first few weeks from the start of treatment diately following treatment.
Of the presently available noninvasive imaging methods, magnetic resonance imaging (MRI) is the suitable modality to visualize brain and associated changes due to the application of external cytotoxic agents such as radiotherapy, because of the high contrast resolution, imaging based on the molecular environment associated with intra- and extracellular water components, and no additional radiation dose to the patient during sequential imaging. Because the brain is a closed compartment, the tolerance for radiotherapy and the fraction size are crucial in the routine prescription of brain radiotherapy. The early and delayed effects of radiotherapy have been well discussed for X-ray CT and radionuclide imaging methods; however, only a few reports on the effects of radiotherapy using MR imaging in the human system are available. re3 These studies were mainly to investigate possible long-term effects in the relaxation parameters and image appearance in brain tumors and normal brain. Our present study was planned to investigate whether there are any observable changes due to radiotherapy during the
MATERIALS
AND
and imme-
METHODS
The patients with brain tumors were from the All India Institute of Medical Sciences, New Delhi, with histologically proved tumors by biopsy or surgery. Eight patients (glioma, 3; meningioma, 2; medulloblastoma, 2; and glioblastoma, 1) were studied with MR imaging in sequential scans. All patients were observed without steroid during radiotherapy. MR imaging was performed 1 day prior to the start of radiotherapy treatment, during first week, and at the end of second week in 6 patients, at the end of radiotherapy in all 8 patients, after 2-3 mo in 6 patients, after 6 mo in 1 patient, and 15 mo postradiotherapy in 1 patient. The patients received radiotherapy with cobalt-60 teletherapy (Theretron 780, M/S Therotronix, Ottawa, Canada) at Institute Rotary Cancer Hospital, New Delhi, using two parallel opposed lateral portals to the skull, calculating the dose at the midplane. The total dose delivered to the brain including boost radio-
tre, Institute of Nuclear Medicine and Allied Sciences, Lucknow Marg, Delhi 110054, India.
RECEIVED 2/8/91; ACCEPTED 6/5/91.
Address correspondence and reprint requests to Lt. Col. A. Jena, DRM, DNBE (NM), Head, NMR Research Cen959
960
Magnetic Resonance Imaging 0 Volume 9, Number
6, 1991
Fig. 1. Sequential axial T2 images (TR = 2000 msec; TE = 128 msec) of brain through the lateral ventricles in an operated patient with right sphenoidal meningioma who received total radiation dose of 65 Gy to the brain in a period of 6 weeks, showing no appreciable abnormal signal intensity after 1 mon (c) following radiotherapy.
therapy
with shrunken
fields was 60-65
in normal
brain parenchyma
Gy in 6 wk for
all patients.
MR imaging was performed with a 1.5-T system (Magnetom, Siemens AG, West Germany) with standard head coil. The T,-weighted images were obtained with TR = 700 msec and TE = 17-28 msec. The T2images were obtained with TR = 2000-2500 msec with TE ranging from 28 to 328 msec. Proton-densityweighted images were made available with TR = 20002500 msec with short TE = 17-28 msec. Multiecho sequence images with TR = 2000 msec and TEs 28328 msec (16 points) were used for obtaining T,-cal-
(white matter)
after 3 days (a), after 1 wk (b), and
culated images using the commercial software (C2 and Dl) provided along with the equipment. The mean T2 values and the standard deviation in the region of interest encircling normal brain were calculated using the “statistics” program. Axial sections with 5-mm thickness and interslice distance of 2.5 mm in 256 x 256 matrix were obtained in all cases. The images of the corresponding axial planes were compared in sequential images of the same patient obtained at different time intervals with the images before starting the radiotherapy to document possible changes due to irradiation of the brain. White matter appearance in the
Fig. 2. Sequential axial T2 images (TR = 2000-2500 msec; TE = 120-128 msec) of brain in a patient with low-grade
astrocytoma who received total radiation dose of 60 Gy to the brain (a) 1 day before, (b) 1 mo after, and (c) 6 mo after radiotherapy, showing no appreciable abnormal intensity in normal brain parenchyma. However, gradual regression of the tumor mass is evident.
Radiation
therapy
of brain
visualized
contralateral side of the tumor and the areas adjacent to the lateral ventricles was observed carefully to get qualitative assessment. Two individual observers analyzed the images of sequential scans to document regional differences in image intensity in white matter. RESULTS No observable changes in the MR appearance of the normal brain parenchyma were seen in the brain images in these patients studied at 1 wk from the start and at the end of radiotherapy in the T,-, T2-, and proton-density-weighted images (Figs. 1 and 2). There was no significant change observed with radiotherapy in the mean T,and standard deviation in comparable regions of interest of the normal brain in sequential scans. The mean T,value of the normal brain was 95 + 7 msec (n = 6) before start of radiotherapy and 96 + 7 msec (n = 6) after radiotherapy. There was no change in the T2distribution in comparable regions of interest in the normal brain parenchyma. DISCUSSION The purpose of the present work was to document immediate changes, if any, in the normal brain due to administration of radiotherapy. We have looked for any possible intensity variation in the normal brain areas, and they were not observed in any of these cases. Attempts have been made to correlate the adverse effects of radiotherapy from MR images.‘s4 Grade 3-4 changes were shown to be associated with higher radiation doses, 70 Gy. We do not compare our results with those of any of the studies already reported, because we have investigated only the immediate effects following the administration of radiation. The imme-
by MR 0 A. JENA ET AL.
961
diate result of irradiation is induction of raised intracranial tension, which is expected because of edema and intra- and extracellular increase in water. Such changes, if any, have not been shown with routine SE sequences applied in our patients. Compression of ventricles may be expected as an immediate effect if the brain swelling takes place. This was not seen in our study. It may also be concluded that the radiation dose delivered per fraction is well within tolerance limits, not associated with any immediate side effects. These patients were not having any radiation sickness due to global skull irradiation. The presentation of our results is to help future planning of the study protocol in assessing early radiation damage to the normal brain, because there were no observable changes during the period of radiotherapy and up to a period of several months in these cases. REFERENCES Costine, L.C.; Konski, A.; Ekholm, S.; et al. Adverse effects of brain irradiation correlated with MR and CT imaging. ht. J. Radiat. Oncol. Biol. Phys. 15:319-330; 1988. Houdek, P.V.; Landy, H.J.; Quencer, R.M.; et al. MR characterisation of brain and brain tumor response to radiotherapy. Znt. J. Radiat. Oncol. Biol. Phys. 15:213218; 1988. Ngo, F.Q.H.; Thomas, F.J.; Weinstein, M.A.; et al. Early and delayed response of brain glioma to radiotherapy as studied by magnetic resonance imaging. In: P.S. Allen (Ed). Magnetic Resonance in Cancer. Elmsford, NY: Pergamon Press; 1985: pp. 119-120. Zimmerman, R.D.; Fleming, C.A.; Lee, B.C.P.; et al. Periventricular hyperintensity as seen by magnetic resonance: Prevalence and significance. AJNR 7:13-20; 1986.
Imaging, Vol. 9, pp. 959-%I, All rights reserved.
1991 Copyright
0730-725x/91 $3.00 + .oo 0 1991 Pergamon Press plc
l Original Contribution
EFFECTS
OF RADIATION THERAPY ON THE HUMAN NORMAL (WHITE MATTER) VISUALIZED BY MR IMAGING AMARNATH
JENA,* UDAY
BRAIN
GOURA K. RATH,~ R. RAVICHANDRAN,* P. SAHI,~ AND S. KHUSHU*
*NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences, Lucknow Marg, Delhi 110054, India, and TDepartment of Radiation Oncology, Institute Rotary Cancer Hospital, AIIMS, Ansari Nagar, New Delhi 110016, India Sequential MR imaging could provide information related to the pathological changes due to the application of external cytotoxic agents such as radiotherapy on the central nervous system. This paper describes the results of our attempt to demonstrate short-term changes associated with normal brain during and immediately following radiotherapy when the whole brain is irradiated for malignant conditions. No observable changes were found in the normal brain parenchyma in any of the patients (n = 8) in T1-, T,-, and proton-density-weighted images in the sequential scans in the first and second weeks and immediately following radiotherapy. Also, no changes were observed in the normal brain appearance at 2 mo (n = 6), up to 6 mo (n = l), and up to 15 mo (n = 1) after completion of radiotherapy.
Keywords: Radiation; Brain; Effects.
INTRODUCTION
first few weeks from the start of treatment diately following treatment.
Of the presently available noninvasive imaging methods, magnetic resonance imaging (MRI) is the suitable modality to visualize brain and associated changes due to the application of external cytotoxic agents such as radiotherapy, because of the high contrast resolution, imaging based on the molecular environment associated with intra- and extracellular water components, and no additional radiation dose to the patient during sequential imaging. Because the brain is a closed compartment, the tolerance for radiotherapy and the fraction size are crucial in the routine prescription of brain radiotherapy. The early and delayed effects of radiotherapy have been well discussed for X-ray CT and radionuclide imaging methods; however, only a few reports on the effects of radiotherapy using MR imaging in the human system are available. re3 These studies were mainly to investigate possible long-term effects in the relaxation parameters and image appearance in brain tumors and normal brain. Our present study was planned to investigate whether there are any observable changes due to radiotherapy during the
MATERIALS
AND
and imme-
METHODS
The patients with brain tumors were from the All India Institute of Medical Sciences, New Delhi, with histologically proved tumors by biopsy or surgery. Eight patients (glioma, 3; meningioma, 2; medulloblastoma, 2; and glioblastoma, 1) were studied with MR imaging in sequential scans. All patients were observed without steroid during radiotherapy. MR imaging was performed 1 day prior to the start of radiotherapy treatment, during first week, and at the end of second week in 6 patients, at the end of radiotherapy in all 8 patients, after 2-3 mo in 6 patients, after 6 mo in 1 patient, and 15 mo postradiotherapy in 1 patient. The patients received radiotherapy with cobalt-60 teletherapy (Theretron 780, M/S Therotronix, Ottawa, Canada) at Institute Rotary Cancer Hospital, New Delhi, using two parallel opposed lateral portals to the skull, calculating the dose at the midplane. The total dose delivered to the brain including boost radio-
tre, Institute of Nuclear Medicine and Allied Sciences, Lucknow Marg, Delhi 110054, India.
RECEIVED 2/8/91; ACCEPTED 6/5/91.
Address correspondence and reprint requests to Lt. Col. A. Jena, DRM, DNBE (NM), Head, NMR Research Cen959
960
Magnetic Resonance Imaging 0 Volume 9, Number
6, 1991
Fig. 1. Sequential axial T2 images (TR = 2000 msec; TE = 128 msec) of brain through the lateral ventricles in an operated patient with right sphenoidal meningioma who received total radiation dose of 65 Gy to the brain in a period of 6 weeks, showing no appreciable abnormal signal intensity after 1 mon (c) following radiotherapy.
therapy
with shrunken
fields was 60-65
in normal
brain parenchyma
Gy in 6 wk for
all patients.
MR imaging was performed with a 1.5-T system (Magnetom, Siemens AG, West Germany) with standard head coil. The T,-weighted images were obtained with TR = 700 msec and TE = 17-28 msec. The T2images were obtained with TR = 2000-2500 msec with TE ranging from 28 to 328 msec. Proton-densityweighted images were made available with TR = 20002500 msec with short TE = 17-28 msec. Multiecho sequence images with TR = 2000 msec and TEs 28328 msec (16 points) were used for obtaining T,-cal-
(white matter)
after 3 days (a), after 1 wk (b), and
culated images using the commercial software (C2 and Dl) provided along with the equipment. The mean T2 values and the standard deviation in the region of interest encircling normal brain were calculated using the “statistics” program. Axial sections with 5-mm thickness and interslice distance of 2.5 mm in 256 x 256 matrix were obtained in all cases. The images of the corresponding axial planes were compared in sequential images of the same patient obtained at different time intervals with the images before starting the radiotherapy to document possible changes due to irradiation of the brain. White matter appearance in the
Fig. 2. Sequential axial T2 images (TR = 2000-2500 msec; TE = 120-128 msec) of brain in a patient with low-grade
astrocytoma who received total radiation dose of 60 Gy to the brain (a) 1 day before, (b) 1 mo after, and (c) 6 mo after radiotherapy, showing no appreciable abnormal intensity in normal brain parenchyma. However, gradual regression of the tumor mass is evident.
Radiation
therapy
of brain
visualized
contralateral side of the tumor and the areas adjacent to the lateral ventricles was observed carefully to get qualitative assessment. Two individual observers analyzed the images of sequential scans to document regional differences in image intensity in white matter. RESULTS No observable changes in the MR appearance of the normal brain parenchyma were seen in the brain images in these patients studied at 1 wk from the start and at the end of radiotherapy in the T,-, T2-, and proton-density-weighted images (Figs. 1 and 2). There was no significant change observed with radiotherapy in the mean T,and standard deviation in comparable regions of interest of the normal brain in sequential scans. The mean T,value of the normal brain was 95 + 7 msec (n = 6) before start of radiotherapy and 96 + 7 msec (n = 6) after radiotherapy. There was no change in the T2distribution in comparable regions of interest in the normal brain parenchyma. DISCUSSION The purpose of the present work was to document immediate changes, if any, in the normal brain due to administration of radiotherapy. We have looked for any possible intensity variation in the normal brain areas, and they were not observed in any of these cases. Attempts have been made to correlate the adverse effects of radiotherapy from MR images.‘s4 Grade 3-4 changes were shown to be associated with higher radiation doses, 70 Gy. We do not compare our results with those of any of the studies already reported, because we have investigated only the immediate effects following the administration of radiation. The imme-
by MR 0 A. JENA ET AL.
961
diate result of irradiation is induction of raised intracranial tension, which is expected because of edema and intra- and extracellular increase in water. Such changes, if any, have not been shown with routine SE sequences applied in our patients. Compression of ventricles may be expected as an immediate effect if the brain swelling takes place. This was not seen in our study. It may also be concluded that the radiation dose delivered per fraction is well within tolerance limits, not associated with any immediate side effects. These patients were not having any radiation sickness due to global skull irradiation. The presentation of our results is to help future planning of the study protocol in assessing early radiation damage to the normal brain, because there were no observable changes during the period of radiotherapy and up to a period of several months in these cases. REFERENCES Costine, L.C.; Konski, A.; Ekholm, S.; et al. Adverse effects of brain irradiation correlated with MR and CT imaging. ht. J. Radiat. Oncol. Biol. Phys. 15:319-330; 1988. Houdek, P.V.; Landy, H.J.; Quencer, R.M.; et al. MR characterisation of brain and brain tumor response to radiotherapy. Znt. J. Radiat. Oncol. Biol. Phys. 15:213218; 1988. Ngo, F.Q.H.; Thomas, F.J.; Weinstein, M.A.; et al. Early and delayed response of brain glioma to radiotherapy as studied by magnetic resonance imaging. In: P.S. Allen (Ed). Magnetic Resonance in Cancer. Elmsford, NY: Pergamon Press; 1985: pp. 119-120. Zimmerman, R.D.; Fleming, C.A.; Lee, B.C.P.; et al. Periventricular hyperintensity as seen by magnetic resonance: Prevalence and significance. AJNR 7:13-20; 1986.
