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1 From the Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City. Received November 15, 2000; revision requested January 10, 2001; final revision received June 4; accepted August 1. Supported in part by National Institutes of Health grant 1 RO1 CA71906-01A2.
| ABSTRACT |
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MATERIALS AND METHODS: Twenty-three patients with advanced uterine cervical cancer who were treated with RT were prospectively evaluated. Each patient underwent four dynamic magnetic resonance (MR) studies: before RT, 2 and 4 weeks after initiation of RT, and 4 weeks after completion of RT. SI and CE were calculated in all four studies of each patient.
RESULTS: Bone marrow inside the RT field showed steady and marked increase in precontrast SI and early and transient increase in CE at 2 weeks after initiation of RT followed by progressive and marked decrease in CE at 4 weeks after initiation of RT and 4 weeks after completion of RT. Bone marrow outside the RT field showed slight increase in precontrast SI and steady and moderate decrease in CE to a lesser degree without early increase as seen in bone marrow inside the RT field.
CONCLUSION: RT causes an increase in precontrast SI predominantly in bone marrow inside the RT field. However, a decrease in CE is seen in bone marrow not only inside but also outside the RT field.
Index terms: Bone marrow, effects of irradiation on, 331.47 • Magnetic resonance (MR), contrast enhancement, 331.121411, 331.12143 • Radiation, injurious effects, 331.47 • Spine, MR, 331.121411, 331.12143
| INTRODUCTION |
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The previous studies used only nonenhanced MR imaging in the evaluation of SI of the irradiated bone marrow. To our knowledge, dynamic contrast material–enhanced imaging of the irradiated bone marrow has not been reported, and the temporal changes in SI and contrast enhancement (CE) of the irradiated bone marrow have not been investigated. Furthermore, the temporal changes in SI and CE of the adjacent bone marrow, which may have been exposed to a very low scatter dose of radiation, have not been established.
The purpose of this study was to evaluate the temporal changes in SI and the degree of CE of the bone marrow in the lumbosacral vertebrae both inside and outside the RT field in a prospective patient population.
| MATERIALS AND METHODS |
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MR Imaging
Dynamic contrast-enhanced MR examinations were performed in all patients with use of a 1.5-T unit (Signa Advantage 1.5; GE Medical Systems, Milwaukee, Wis) and a body coil. Sagittal T1-weighted fast spin-echo images were obtained by using the following parameters: 150/16 (repetition time msec/echo time msec); number of signals acquired, one; 10-mm section thickness; 256 x 128 matrix; and 40 x 20-cm field of view. Sequential T1-weighted images were obtained every 3 seconds during a total of 120 seconds (40 images). A bolus injection of 0.1 mmol of an MR contrast agent (ProHance; Bracco, Milan, Italy) per kilogram of body weight was given 30 seconds after the start of image acquisition at a rate of 9 mL/sec with a power injector (Spectris; Medrad, Pittsburgh, Pa).
Data Analysis
The quantitative analysis of each MR study was performed at a computer workstation (SPARCstation 20; Sun Microsystems, Palo Alto, Calif) with original software developed at the MR Research Laboratory of our institution. The original MR images were transferred from the MR imager to the computer workstation. The region of interest (ROI) was placed on the computer display by one author (S.O.). The ROI of each vertebral body was determined by outlining the bone marrow space of each vertebra. The ROI of the intervertebral disk was also determined for use as a reference. The mean SI of the ROI was calculated at each vertebra and intervertebral disk, and a pixel-to-pixel analysis of SI was performed on each MR study. A dynamic time-SI curve of each vertebra and intervertebral disk on each study was generated.
Precontrast SI of the bone marrow of each vertebra was determined by averaging the SI values of the initial 10 images obtained before the arrival of the contrast agent (Fig 1). Similarly, precontrast SI of the intervertebral disk was obtained by averaging the SI values of the initial 10 images to use as a reference. Precontrast relative SI (rSI) of each vertebra was defined as the ratio of precontrast SI of the vertebra to that of the intervertebral disk. The temporal changes in precontrast rSI of each vertebra during the four MR studies were analyzed. The degree of CE of each vertebra was calculated by dividing the mean SI of the postcontrast final 10 images by the mean SI of the precontrast initial 10 images (SIpost/SIpre ratio) (Fig 1). The temporal changes in the ratio were analyzed on each vertebra on four MR studies.
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| RESULTS |
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Temporal Change in Precontrast rSI
The bone marrow inside the RT field showed a steady and marked increase in precontrast rSI during RT (second and third studies) and after the completion of RT (fourth study) (Fig 2). Changes inside the RT field were significant compared with the rSI on the first study. The differences between the first and second studies, the second and third studies, and the third and fourth studies were statistically significant (P < .001, respectively).
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The differences in rSI between the bone marrow inside and that outside the RT field were significant on the second (P = .006), third (P < .001), and fourth studies (P < .001).
Temporal Change in Degree of CE
The bone marrow inside the RT field showed an early and transient increase in CE at 2 weeks of RT (second study), followed by a precipitous decrease in CE below the level of the first study at 4 weeks of RT (third study). This was followed by a further gradual decrease 4 weeks after the completion of RT (fourth study) (Fig 3). The differences between the second and third studies and the third and fourth studies were statistically significant (P < .001, respectively). The difference between the first and second studies was not significant (P > .05).
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The differences in CE between the bone marrow inside and that outside the RT field were significant on the third and fourth studies (P < .001, respectively).
| DISCUSSION |
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Accordingly, the temporal changes on our second study obtained 2 weeks after the initiation of RT likely reflect acute radiation-induced changes. The changes on our third study obtained 4 weeks after the initiation of RT and fourth study obtained 4 weeks after the completion (8 weeks after the initiation) of RT mostly represent chronic radiation-induced changes.
SI Changes
The temporal changes in precontrast SI confirm the results of previous studies and are consistent with the proposed causes of SI change. Fatty replacement of the irradiated bone marrow can be demonstrated as increased SI on T1-weighted images due to the shortened T1 relaxation time of the increased fatty content in the bone marrow (1,3,4). Stevens et al (3) reported that this change appeared 3–6 weeks after the initiation of RT. Yankelevitz et al (4) reported that it appeared as early as 2 weeks after the initiation of RT. Our results suggest that the gradual increase in precontrast SI can be seen in the bone marrow inside the RT field as early as 2 weeks after the initiation of RT at a low dose.
Stevens et al (3) reported that this early radiation-induced change was detectable on STIR images but not on T1-weighted images during the first 2 weeks of RT. They speculated that the abnormality detected on STIR images during the early phase of RT probably reflected cellular edema, hemorrhage, and the early influx of nonirradiated cells and did not represent fatty replacement of the bone marrow. In our study, the increase in CE in the bone marrow inside the RT field was demonstrated on the second study and seemed to occur along with these radiation-induced changes.
Acute Changes in Irradiated Bone Marrow
During the acute phase of the radiation-induced changes, our study using quantitative assessment was sensitive in showing the early increase in precontrast SI on the second study. Our study also showed the transient increase in CE on the second study, which was observed only inside the RT field. We speculate that this increase in CE may relate to dilatation of the sinusoids seen in the acute phase (6). The importance of this finding should be determined with further studies.
Acute hemorrhage within the bone marrow is common in the acute phase (6). Therefore, slightly increased precontrast SI on T1-weighted images on the second study may suggest hemorrhage. Another explanation for the early SI increase would be that fatty replacement does indeed occur very early in the course of RT. This interpretation correlates with the well-documented extreme radiosensitivity of hematopoietic cells to low doses of radiation. The incremental increase in SI during RT on sequential studies in our series suggests that subtle fatty replacement of the bone marrow may occur very early and gradually increase during the course of RT.
Chronic Changes in Irradiated Bone Marrow
During the chronic phase (third and forth studies), our data showed that precontrast SI of the bone marrow inside the RT field was significantly increased, which most likely represents well-known fatty replacement caused by the depletion of highly radiosensitive hematopoietic cells (3). There was a significant difference between the incremental increase in SI of the bone marrow inside and that outside the RT field. The slope of SI of the bone marrow inside the RT field was steep during RT. This finding suggests that the bone marrow exposed to high doses of radiation is depleted and subsequently undergoes fatty infiltration at a steady level while RT is ongoing. After the completion of RT, the slope of SI became gradual, which may be related to the degree of fatty saturation of the bone marrow. If most of the bone marrow has already undergone fatty replacement, imaging findings would be expected to stabilize gradually. This may be consistent with the chronic phase of the radiation-induced changes. Without histologic correlation, it is difficult to fully explain the cause of the SI changes.
The increase in SI during the chronic phase was also associated with a progressive and significant decrease in CE on the third and fourth studies. This decrease in CE of the bone marrow may reflect chronic microvascular changes including arteriolocapillary occlusion and fibrosis. We speculate that the simultaneous increase in precontrast SI and the decrease in CE of the bone marrow inside the RT field may reflect the combined phenomena of decreased cellularity (hematopoietic cell), decreased vascularity and microcirculation, and increased fatty content.
Acute and Chronic Changes in Nonirradiated Bone Marrow
Most previous studies reported that the radiation-induced changes were generally limited to the bone marrow inside the RT field. Only a few studies reported SI changes of the bone marrow outside the RT field, and there are conflicting interpretations of these findings. Kauczor et al (5) reported that increased SI on T1-weighted images could be seen in the bone marrow of the spine outside the RT field. They speculated that the vertebrae might have received a very low scatter dose of radiation, which might be responsible for increased SI. Blomlie et al (7) reported that radiation-induced changes in the presumed "nonirradiated" vertebrae were observed on T1-weighted images in 58% of patients with pelvic RT and on STIR images in 48%. These changes were more apparent in the lumbar spine than in the pelvic and proximal femoral bones. They concluded, however, that the direct effect of RT seemed unlikely because the radiation dose at a distance of 3 cm outside the RT field is only 5%.
In agreement with the findings of these previous studies (5,7), the results of our study confirmed the small but measurable increase in SI in the bone marrow outside the RT field. The observation suggests that a low scatter dose of radiation may have a measurable effect on the bone marrow. Although its precise nature remains undetermined, the change is measurable with the quantitative analysis used in our study.
In contrast to the subtle precontrast SI changes, marked temporal changes in CE were observed in this study. The significant progressive decrease in CE may be suggestive of microvascular damage in response to very low doses of radiation. The cause of the discrepancy in the degree of changes between precontrast SI and the degree of CE remains unknown. However, our observations suggest that very low doses of radiation outside the RT field may have a much lesser effect on hematopoietic cells and subsequent fatty replacement than on microvascularity. Our dynamic contrast-enhanced MR imaging may thus be a more sensitive technique than nonenhanced T1-weighted imaging to detect the changes in bone marrow microvascularity in response to very low doses of radiation.
In summary, our quantitative data suggest that RT causes an increase in precontrast SI predominantly in the bone marrow inside the RT field and a decrease in CE in the bone marrow both inside and outside the RT field. Although our study requires further confirmation, MR findings in this study appear to reflect established histologic events. Dynamic contrast-enhanced imaging seems to be a sensitive technique in the assessment of changes in the bone marrow exposed to very low doses of scatter radiation.
| ACKNOWLEDGMENTS |
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